ORI/IRB Standard Operating Procedures (SOPs)

Approved By: ORI Director, Nonmedical IRB Chair, Medical IRB Chair

Date First Effective: May 15, 2005

Last Revision Date: February 15, 2019

Revision #12

OBJECTIVE

To describe policies and procedures for determining the types of activities that qualify as human research or clinical investigations and therefore require prior Institutional Review Board (IRB) review and approval

GENERAL DESCRIPTION

In accordance with federal and institutional regulations and prior to project implementation, the IRB must approve any undertaking in which a University of Kentucky (UK) faculty, staff, or student conducts human research. The UK policy document entitled “When Do Activities Involving Human Subjects Need Institutional Review Board (IRB) Review and Approval?” outlines what types of activities are human subjects research or clinical investigations and therefore require IRB review and approval.

Definitions 

Department of Health and Human Services (HHS)/Common Rule

Research:  A systematic investigation, including research development, testing, and evaluation, designed to develop or contribute to generalizable knowledge [45 CFR 46.102(l)]. Activities that meet this definition constitute research, whether or not they are conducted or supported under a program which is considered research for other purposes. For example, some demonstration and service programs may include research activities. Also, if a study involves human subjects (in accordance with the human subject definition below) and is being done for the purpose of completing an academic degree program (e.g., thesis, capstone, dissertation, etc.), it is considered by the university to meet the definition of research, whether designed to contribute to generalizable knowledge or not.

Human Subject is a living individual about whom an investigator (whether professional or student) conducting research: (1) Obtains information or biospecimens through intervention or interaction with the individual, and uses, studies, or analyzes the information or biospecimens; or (2) Obtains, uses, studies, analyzes, or generates identifiable private information or identifiable biospecimens. 

Intervention includes both physical procedures by which information or biospecimens are gathered (e.g., venipuncture) and manipulations of the subject or the subject’s environment that are performed for research purposes. 

Interaction includes communication or interpersonal contact between investigator and subject. 

Private information includes information about behavior that occurs in a context in which an individual can reasonably expect that no observation or recording is taking place, and information that has been provided for specific purposes by an individual will not be made public (e.g., a medical record).

Food and Drug Administration (FDA)

Clinical investigation involves use of a test article (i.e., drug, device, food substance, or biologic), one or more human subjects, meets requirements for prior submission to the FDA (involves drugs or medical devices other than the use of FDA approved drugs or medical devices in the course of medical practice), or results are intended to be part of an application for research or a marketing permit.

If the activities involve use of an FDA regulated test article (i.e., drug, device, food substance, or biologic under the purview of the FDA), UK applies the FDA definitions of “human subjects.” 

Human subject (FDA) is an individual who is or becomes a participant in research either as a recipient of a test article or as a control or as an individual on whose specimen a device is used. A subject may be either a healthy individual or a patient [21 CFR 56.102(e)] (Drug, Food, Biologic).

Human subject (FDA for medical devices) is a human who participates in an investigation, either as an individual on whom or on whose specimen an investigational device is used or as a control. A subject may be in normal health or may have a medical condition or disease [21 CFR 812.3(p)] (Medical Devices). This definition includes the use of tissue specimens even if they are unidentified. 

If the research involves any of the following, FDA regulations 21 CFR 50 & 56 apply and require IRB approval prior to implementation: 

• Any use of a drug in research other than the use of an FDA approved drug in the course of medical practice;
• Any use of a medical device in studies where the purpose is to determine the safety or effectiveness of the device; or
• Data will be submitted to or held for inspection by FDA as part of a marketing permit. 

University of Kentucky

The definition of human subject typically means only “living individuals”; however, at UK, research involving fetal tissue requires IRB review. Other exceptions involving collection of human specimens in FDA regulated device research may apply. 

In cases where the definition of “research” or “human subject” is different from above, UK IRB applies institutional oversight based on the applicable sponsor or agency specific definitions 
(e.g., See the Department of Defense/IRB/ORI Coordination SOP).

A principal investigator may be a UK employee, UK student, or in rare cases may be an employee at a site with which UK has signed an IRB Memorandum of Understanding, IRB Authorization or Individual Investigator Agreement. 

For the purpose of evaluating whether an activity meets the definition of research, the following activities have been excluded: 

• Scholarly and journalistic activities (e.g., oral history, journalism, biography, literary criticism, legal research, and historical scholarship), including the collection and use of information, that focus directly on the specific individuals about whom the information is collected. 

  (Please note: For scholarly and journalistic activities to be considered to not meet the definition of research, they must be conducted solely for the primary intent of the activity in question. For example, an oral history project being done solely for the purpose of collecting oral history interviews for archiving in a repository to be made available to the public for future use and historic preservation would not be considered research. However, a project that is designed to contribute to generalizable knowledge that happens to involve the use of oral histories and is being conducted for both purposes (i.e., contributing to generalizable knowledge and collecting oral history interviews), whether or not the interviews will be deposited into an archive, may still meet the definition of research and require IRB review.)

• Public health surveillance activities, including the collection and testing of information or biospecimens, conducted, supported, requested, ordered, required, or authorized by a public health authority. Such activities are limited to those necessary to allow a public health authority to identify, monitor, assess, or investigate potential public health signals, onsets of disease outbreaks, or conditions of public health importance (including trends, signals, risk factors, patterns in disease, or increases in injuries from using consumer products). Such activities include those associated with providing timely situational awareness and priority setting during the course of an event or crisis that threatens public health (including natural or manmade disasters).
   
• Collection and analysis of information, biospecimens, or records by or for a criminal justice agency for activities authorized by law or court order solely for criminal justice or criminal investigative purposes.
   
• Authorized operational activities (as determined by each agency) in support of intelligence, homeland security, defense, or other national security missions.

RESPONSIBILITY

Execution of SOP: Principal Investigator (PI)/Study Personnel, Office of Research Integrity (ORI) Staff, IRB Members, IRB Chairs.

PROCEDURES 

Human Subject Research Determinations

1. It is the responsibility of each investigator to seek IRB review and approval prior to initiation of any research involving human subjects or before conducting any clinical investigation.
2. The investigator is responsible for making a preliminary decision regarding whether his/her activities meet either (a) the U.S. Department of Health and Human Services (HHS) definitions of both “research” and “human subjects” and/or (b) the FDA definitions of both “clinical investigation” and “human subjects.” The document titled “When Do Activities Involving Human Subjects Need Institutional Review Board (IRB) Review and Approval?” is available to guide the investigator in making this decision. However, only the IRB or its official designee(s) can make an official determination.
3. The investigator may contact ORI staff, the IRB Chair/Vice Chairs, or IRB members for advice on the applicability of the federal regulations and UK policy.
4. In cases where it is not clear whether the study requires IRB review and/or to receive an official determination, the ORI or IRB may ask the investigator to submit a Not Human Research (NHR) determination request form to the IRB/ORI detailing the proposed project/research. The Director or IRB Chair or their designees review the request and make the final determination whether the activities meet the federal definitions using, as a guide, such documents as (but not limited to), “When Do Activities Involving Human Subjects Need Institutional Review Board Review and Approval?” and “UK Guide for Determining When Protocols Involving Coded Private Information or Biological Specimens Meet the Federal Definition of Human Research,” and applicable federal policy/regulation(s).  
5. The ORI communicates the decision of the IRB or the ORI to the investigator. If the investigator has concerns regarding the decision, he/she may submit a written appeal to the ORI that includes justification for the concerns. The appeal and justification are reviewed by the IRB or its official designee(s) and the official decision provided to the investigator by the ORI. The appeal determination is final.

References

21 CFR 56.102

45 CFR 46.102

Approved By: ORI Director, Nonmedical IRB Chair, Medical IRB Chair

Date First Effective: May 10, 2005

Last Revision Date: February 15, 2019

Revision #9

OBJECTIVE

To define policies and procedures for appointing Institutional Review Board (IRB) members 

GENERAL DESCRIPTION 

Each IRB at the University of Kentucky (UK) has a minimum of five voting members sufficiently qualified through experience and expertise to promote respect for its advice and counsel in safeguarding the rights and welfare of human subjects. The membership includes regular members who have designated alternates with qualifications comparable to the regular member. Additionally, in accord with OHRP policy, a regular member of any of the UK IRBs may serve as an alternate for any comparably qualified member on any other UK IRB. Consultants and ex officio members provide guidance and input regarding IRB operations and protocol review. 

IRB membership complies with federal requirements outlined in 45 CFR 46.107, 46.108(a)(2) and 21 CFR 56.107 to ensure appropriate diversity of the members through consideration of multiple professions/disciplines, ethnicities and cultural backgrounds, gender, and sensitivity to such issues as community attitudes and representation of the general perspectives of human subjects. In addition, the IRB includes members who can determine the acceptability of proposed research in terms of institutional commitments and regulations, applicable law, and standards of professional conduct and practice. If the IRB regularly reviews research involving a vulnerable category of subjects, the IRB membership includes individuals who are knowledgeable about and experienced in working with those subjects. 

Each IRB includes at least one member with each of the following primary affiliations: nonscientific, scientific, and nonaffiliated (i.e., not affiliated with UK and not part of the immediate family of a person affiliated with UK), and (on IRB committees that review FDA regulated studies) a physician. 

In addition, the IRB invites individuals with competence in special areas to assist in the review of issues which require expertise beyond or in addition to that available on the IRB. 

RESPONSIBILITY 

Execution of SOP:  Office of Research Integrity (ORI) Staff, ORI Director, Vice President for Research (VPR), IRB, IRB Chairs 

PROCEDURES 

Appointment Procedures/Terms of Membership 

1. The VPR appoints members to standing University research committees and, as authorized by the Provost and President, appoints Chairs, Vice Chairs, and members to the IRB. Approximately once a year upon request, the ORI submits recommendations for membership to the VPR. The ORI designated staff is responsible for soliciting recommendations from a variety of sources for either non-tenure track faculty/staff or individuals in a tenured position (preferable), preparing the recommendations for submission to the VPR, and ensuring that the membership meets federal requirements. Other UK administrative units may also submit nominations for membership on the IRB.
2. The ORI designated staff provides IRB Chairs and the ORI Director with a copy of the recommendations sent to the VPR.
3. Appointments for IRB Chairs, Vice Chairs, and IRB members (including alternates) are for staggered three-year terms beginning the fall of each academic year. UK has no limit on the number of terms IRB Chairs, Vice Chairs, members, and alternates may serve on the IRB. The VPR automatically reappoints ex officio members each year. See the Quality Improvement Program Administrative Assessment Review SOP for procedures for periodically evaluating the performance of IRB Chairs, Vice Chairs, and members.
4. Individuals under consideration for appointment as an IRB Chair must meet the following requirements: completion of human research protections training; experience as a voting IRB member (or comparable experience); display of adequate knowledge of ethical principles, professional standards, federal regulations, and other applicable law through IRB meeting attendance and participation; and demonstration of professional competence necessary to review specific research activities.
5. IRB Chairs, Vice Chairs, members, and alternates are responsible for providing the ORI with curriculum vitae to document each member’s expertise, degrees, and/or license number. The ORI maintains vitae for each member throughout his/her term on the IRB and periodically requests updates, as appropriate.
6. Individuals under consideration for appointment as voting IRB members must not have competing business interests or hold research business positions at the University of Kentucky. In addition, individuals who are responsible for business development do not carry out day-to-day operations of the review process.
7. Alternate IRB members replace regular IRB members who are unable to attend convened meetings of the IRB. Alternate members have qualifications comparable to the applicable regular members and may be an alternate for more than one IRB member. Designated ORI staff maintain a list of alternate members on the official IRB membership list. Terms of appointment, length of service, and duties are identical to those for regular IRB members. Regular members on any IRB can serve as alternate members for comparably qualified members on any other IRB.
8. Alternates attending a meeting or conducting protocol review have all the authority of regular IRB members and receive the same training and protocol review application materials as the regular members. If the regular member and the alternate member substituting for that meeting attend the same convened meeting, only one individual may vote.
9. Ex officio members are non-voting members who serve as liaisons to ensure coordination among other research administrative units. Examples include but are not limited to the Investigational Drug Service (IDS) representative, ORI Director, Radiation Safety Officer (RSO), Legal Counsel, and Institutional Biosafety Officer.
10. ORI staff recruit ad hoc and cultural consultants with competence in special areas to assist in the review of issues that require expertise beyond or in addition to that available on the IRB. Ad hoc or cultural consultants may provide comments or recommendations in writing to the IRB prior to the meeting or attend the convened meeting to participate in the review. These ad hoc and cultural consultants do not vote with the IRB and do not count toward a quorum at a convened meeting. See the Initial Full Review SOP for procedures for contacting consultants.
11. When the IRB reviews research that involves prisoners, a majority of the IRB (exclusive of the prisoner representative) must not have any association with the prison involved, apart from their relationship on the IRB.
12. For IRB review of research on prisoners, at least one voting member at the IRB meeting must be a prisoner or a prisoner representative with appropriate background and experience to serve in that capacity.
13. For IRB review of research supported by the National Institute on Disability and Rehabilitation Research, the IRB membership includes at least one person primarily concerned with the welfare of children with disabilities or individuals with mental disabilities when the study purposefully requires their inclusion as research participants.

Filling Appointments Due to Resignations During the Year

1. Designated ORI staff solicit recommendations from a variety of sources, recruit potential members, and make recommendations for replacement of members who resign during the year. The VPR makes all final appointments as authorized by the Provost and President.

OHRP/FDA IRB Registration/IRB Membership Roster 

1. The ORI designated staff member completes the OHRP/FDA IRB registration forms in accordance with OHRP and FDA registration requirements and updates the registration in a timely manner.
2. The ORI-designated staff member maintains a list of all IRB members and denotes in which scientific capacity each member serves.
3. ORI staff use the membership list to determine who may attend IRB meetings and count toward the quorum. It includes a list of regular members and designated alternates and indicates the scientific status and area(s) of expertise of all members.
4. To meet OHRP/FDA registration requirements and in order to hold convened meetings, the scientist and nonscientist member designations are as follows:
   • Nonscientist: members who have had little or no scientific or medical training or who do not currently hold positions that involve scientific research or clinical practice (e.g., administrative positions).
   • Scientist: members who are physicians or who hold Ph.D., Pharm.D., or other advanced degrees who are actively engaged in research in the physical, educational, social, behavioral, or biological sciences and disciplines and/or hold regular faculty appointments.

REFERENCES

21 CFR 56.107

21 CFR 56.115(a)(5) & 56.106

45 CFR 46.103(b)(3) & 115(a)(5)

45 CFR 46.107

45 CFR 46.108(a)(2)

45 CFR 46 Subpart E

U.S. Department of Health and Human Services (HHS) Registration of an IRB

Approved By: ORI Director, Nonmedical IRB Chair, Medical IRB Chair

Date First Effective: May 31, 2005

Last Revision Date: June 21, 2013

Revision #6

OBJECTIVE 

To describe policies and procedures for identifying and managing Institutional Review Board (IRB) member and ad hoc or cultural consultant conflict of interest in any type of review (e.g., initial, continuation, modification, noncompliance, unanticipated problem/adverse event, protocol violation, exemption certification)

GENERAL DESCRIPTION 

In the environment of research, openness and honesty are indicators of integrity and responsibility. These are characteristics that promote quality research and can only strengthen the research process. This policy helps ensure that personal and financial interests do not compromise the rights and welfare of human research subjects. The IRB eliminates all IRB members’ and consultants’ (e.g., ad hoc or cultural) conflicts of interest prior to conducting IRB reviews. 

Definitions

A conflict of interest involves any situation in which an IRB member or consultant has any significant personal or financial interest in the proposed research or clinical investigation.

 Significant personal interest includes but is not limited to:

• An interest that the IRB member or consultant believes conflicts with his/her ability to objectively review a protocol including interests of the individual or immediate family member (spouse and dependent children) involved in the design, conduct, or reporting of the research protocol.

Examples of a conflicting interest are if the IRB member or consultant is any of the following:

• Principal investigator (PI);
• Co-investigator;
• Study personnel receiving funding from the study, as listed in the study budget;
• A supervisory role over the PI of the study (e.g., graduate advisor);
• Family member of PI. 

Significant financial interest is anything of monetary value, including, but not limited to:

• Salary or other payments for services (e.g., consulting fees or honoraria);
• Equity interests (e.g., stocks, stock options, or other ownership interests);
• A proprietary interest in the research such as a patent, trademark, copyright, or licensing agreements including royalties from such rights;
• A financial interest in the sponsor, product or service being tested;
• A position as an executive director or director of the agency or company sponsoring the research regardless of the amount of compensation;
• Any compensation that could be affected by the outcome of the research regardless of the amount of compensation.

Significant financial interest does NOT include: 

• Salary, royalties, or other remuneration from the University;
• Income from seminars, lectures, or teaching engagements sponsored by public or non-profit entities;
• Income from service on advisory committees or review panels for public or non-profit entities;
• An equity or financial interest that when aggregated for the IRB member or consultant and the IRB member’s or consultant’s spouse and dependent children meets both of the following tests: does not exceed $5,000 in value as determined through reference to public prices or other reasonable measures of fair market value and does not represent more than a 5% ownership interest in any single entity;
• Salary, royalties or other payments that when aggregated for IRB member or consultant and the IRB member’s or consultant’s spouse and dependent children over the next 12 months are not expected to exceed $5,000. 

RESPONSIBILITY 

Execution of SOP:  Office of Research Integrity (ORI) Staff, IRB Chair, IRB Member, Ad Hoc or Cultural Consultant

PROCEDURES 

1. Each year, ORI staff send a Conflict of Interest Statement to all IRB members. Each IRB member completes and returns a signed statement to the ORI.
2. No regular or alternate member may participate in review of any research project in which the member has a conflict of interest, except to provide information as requested. Such review includes initial, continuation, exempt, modification, unanticipated problems involving risk to participants or others, protocol violation, and noncompliance reviews using expedited or convened procedures.
3. It is the responsibility of each voting member or alternate member of the IRB to disclose any conflict of interest when conducting a review and to excuse him or herself from deliberations and voting.
4. The procedure for excusing an IRB member, including the IRB Chair, from deliberating/voting on all full review protocols for which there is a conflict of interest is detailed in the Conduct of IRB Meetings SOP. ORI staff document all conflict of interest disclosures in the IRB meeting minutes.
5. A consultant may not participate in the review of any research project in which the consultant has a conflict of interest. Such review includes initial, continuation, exempt, modification, unanticipated problems involving risk to participants or others, protocol violation, and noncompliance reviews using expedited or convened procedures.
6. ORI staff confirm that no conflict of interest exists when contacting an individual to serve as a consultant. Once ORI staff have this confirmation, they distribute the combined confidentiality/conflict of interest agreement to the consultant. (See Conflict of Interest Statement and Confidentiality Agreement for IRB Consultant.) 

REFERENCES 

38 CFR 16.107(e)

21 CFR 46.103, 107

21 CFR 56.107

21 CFR 54 (as reference)

42 CFR 50 Subpart F

OHRP May 2004 Financial Relationships and Interests in Research Involving Human Subjects: Guidance for Human Subject Protection

Approved By: ORI Director, Nonmedical IRB Chair, Medical IRB Chair

Date First Effective: June 30, 2005

Last Revision Date: May 9, 2019

Revision #8

OBJECTIVE 

To describe the institution's programs for ensuring that all Institutional Review Board (IRB) members and Office of Research Integrity (ORI) staff are appropriately educated about the regulatory requirements and ethical considerations for the protection of human subjects involved in research 

GENERAL DESCRIPTION 

The foundation for the effective implementation of all facets of the University of Kentucky (UK) human research protection program (HRPP) and for efforts to promote compliance with HRPP requirements lies in a comprehensive, mandatory education program for all applicable personnel, including IRB members and research support staff in the ORI. UK has a multifaceted human subjects’ protection education program which is designed to provide essential training on ethics and regulations of research and local IRB policies/procedures as explained below.

RESPONSIBILITY

Execution of SOP: IRB members and ORI staff. 

PROCEDURES 

Initial Education for IRB Members

Following appointment to membership on the IRB and prior to serving as reviewers, IRB members, ex officio members, and alternate members receive the following training:

1. The ORI provides an orientation session for each new member.

2. ORI staff provide new IRB members with training materials which includes the “University of Kentucky IRB Member Orientation Module” and access to online training tutorials.

   The ORI Education staff assign an experienced IRB member or designee to serve as a mentor to inexperienced new IRB members. The mentor guides the new member in his/her reviews of protocols, IRB policies procedures, and operations. 

3. Prior to serving as an expedited reviewer, an IRB member must complete Expedited training and observe at least one convened meeting. An online course and ongoing support from designated ORI staff are available, as needed, to educate reviewers on applying expedited categories, criteria for approval, and general responsibilities as an expedited reviewer.
4. Prior to serving as an exempt reviewer, designated ORI staff provide training to educate first-time reviewers on applying the exempt categories and general responsibilities as an exempt reviewer.
5. The University requires all IRB members to be trained in the protection of human subjects. Members may meet this requirement by successful completion of Collaborative Institutional Training Initiative (CITI) Human Subject Protection (HSP) online training.
6. In addition to the above training, members have access to the following educational materials from the ORI website including the University of Kentucky IRB Survival Handbook, ORI/IRB SOPs, UK IRB guidance, policies, educational materials, and IRB forms.

Continuing Education of IRB Members 

ORI staff offer the following continuing education opportunities to current members of the IRB:

1. IRB Members E-mail Lists: The ORI maintains e-mail distribution lists which are used on an ongoing basis to send IRB members a variety of materials such as pertinent articles, regulatory updates, web references to resource materials or government reports, or communication about a specific protocol review.
2. Presentations: Upon request or as appropriate, the ORI presents training on selected topics at IRB meetings or IRB in-service programs. ORI invites specialists in a specific area to address the IRB as needed. ORI subscribes to and makes available applicable webinar presentations.
3. Dissemination of Articles or Educational Materials Collected at Professional Meetings or from Scientific Literature: Periodically, ORI staff include copies of these materials with the IRB agenda. Also, the ORI sends correspondence to IRB members periodically informing them that materials are available upon request.
4. ORI staff review and update information in the IRB Survival Handbook, as necessary.
5. Every three (3) years, IRB members must become re-certified in human subjects’ protection training. The CITI on-line human subjects protection training program offers a continuing education program which satisfies this requirement. Other options are also available (e.g. attendance at the Regional Human Subject Protection Conference, PRIM&R conferences, etc.)
6. As available, UK provides funds for the IRB Chairs or select members to attend a national IRB meeting.
7. Once a year, ORI co-sponsors a regional Human Subject Protection Conference. UK pays for IRB members’ registrations.

Initial Education for New ORI Staff

1. The ORI Research Education Specialist and supervisory staff establish and implement a training plan for each new ORI staff member, which includes hands-on training by designated experienced staff members.
2. Other internal training documents that may be disseminated to new staff include but are not limited to ORI Staff Manual including ORI Customer Service Standards.
3. New ORI staff members review existing ORI/IRB standard operating procedures.
4. UK requires that all ORI staff be trained in the protection of human subjects. ORI staff fulfill this requirement with successful completion of the CITI on-line initial HSP training program.

Continuing Education of ORI Staff 

1. The ORI Director holds staff meetings approximately two (2) times a month. New federal initiatives and interpretations of federal regulations and/or discussion of ethical issues occur on an ongoing basis at these meetings. The ORI Director or Research Education staff periodically provides training on selected topics. Also, experts in specific areas provide training on specific topics (e.g., gene therapy, occupational health safety) at staff meetings. Periodically, ORI staff members present posters or give presentations on selected issues/topics/conferences at staff meetings.
2. The ORI encourages and periodically requires its staff members (professional and clerical) to attend University, city, state, national, or regional IRB teleconferences, workshops, lectures or webinars.
3. ORI staff have access to the educational materials distributed to IRB members. Staff also receive copies of selected compliance information/material distributed by the ORI Director or senior staff (e.g., OHRP publications such as the Engagement Memo, copies of innovative materials used by other IRBs/institutions, FDA and OHRP correspondence, training materials developed by external groups, PRIM&R Board educational e-mails).
4. The ORI subscribes to automated news feeds and shares applicable publications with staff.  
5. If during the year, designated ORI staff revise Standard Operating Procedures (SOPs) or add information to an SOP, and the SOP is subsequently approved/signed by the Director of ORI (and when applicable, other individuals; e.g., SOPs for coordination between units), ORI staff are notified by the designated ORI staff person upon implementation of the approved/signed revised SOP. For additional details, see the Generation, Use, and Revision of Standard Operating Procedures SOP. Also, internal training documents are disseminated to ORI staff as deemed necessary to ensure procedural consistency.
6. Every three (3) years, ORI staff must become re-certified in human subjects’ protection training. The CITI on-line human subjects protection training program offers a continuing education program to satisfy this requirement. Other options are available (e.g. attendance at the Regional Human Subject Protection Conference, PRIM&R conferences, etc.).

REFERENCES 

Generation, Use, and Revision of Standard Operating Procedures SOP

Approved By: ORI Director, Nonmedical IRB Chair, Medical IRB Chair

Date First Effective: June 19, 2005

Last Revision Date: October 22, 2010

Revision #8

OBJECTIVE   

To describe the policies and procedures for developing, reviewing, revising, and distributing standard operating procedures (SOPs) for the Institutional Review Board (IRB) and Office of Research Integrity (ORI).  

GENERAL DESCRIPTION 

The University of Kentucky (UK) IRB and the ORI maintain standard operating procedures to ensure effective functioning of the UK human research protection program. The ORI documents when procedures are initiated, revised, and disseminated to staff, IRB members, investigators, and study personnel as well as the procedures for staff training regarding SOPs and maintenance of training records.

RESPONSIBILITY

Execution of SOP: ORI Director, ORI Staff, ORI Quality Improvement Program (QIP) Coordinator, Research Education Specialist (RES), Principal Investigator (PI)/Study Personnel, Vice President for Research (VPR).

PROCEDURES 

Procedure for Writing Standard Operating Procedures 

1. The ORI Director, with advice from ORI staff, IRB Chairs, Vice Chairs, IRB members and/or investigators determines when a new SOP needs to be established. Designated ORI staff are responsible for writing SOPs.
2. Any ORI staff member may draft an SOP based on his/her specialization. All SOPs are in compliance with federal, state, and institutional regulations.
3. ORI staff consult with the IRB Chairs and/or IRB members on IRB related issues in developing the SOPs.
4. As appropriate, the ORI staff distribute copies of newly drafted SOPs to designated IRB Chairs, IRB members, and/or ORI staff for review.
5. If the SOP involves coordination with another University administrative office, the ORI Director, or ORI staff cooperate with the administrative unit involved in drafting the SOP and route the SOP to the appropriate individual representing that office for approval and signature.
6. The ORI staff ensures that each SOP designates the date on which it originally became effective as well as the most recent revision date, which serves as the currently effective date for the SOP. The most recent revision date indicates that this version is currently in effect.
7. Each SOP contains a revision number, which indicates how many times since its origination ORI staff have revised an SOP. These dates are also available on the ORI website.
8. The ORI Director, IRB Chairs, and any appropriate coordinating officials sign and date each SOP. The Executive Chair of the Medical IRB signs on behalf of the Medical IRBs. 

Dissemination of Standard Operating Procedures

1. The RES or designee monitors the SOPs and disseminates new SOPs to all ORI staff members and to the IRB Chairs, Vice Chairs, or members if the SOP involves their activities.
2. The RES also circulates an SOP Tracking Form to applicable ORI staff for their signature to document circulation and review of new SOPs.
3. ORI staff and/or IRB Chairs or designees are responsible for reviewing the new SOP, signing the attached SOP Tracking Form, and returning it to the RES within a reasonable amount of time.
4. The ORI maintains the most recent versions of all approved SOPs on the ORI website. ORI staff provide information on the availability of the SOPs through a variety of educational initiatives [e.g., the Institutional Review Board (IRB) Survival Handbook].
5. According to the ORI guidance document, “A Principal Investigator’s Guide to Responsibilities, Qualifications, Records, and Documentation of Human Subjects Research,” PIs are responsible for reviewing and complying with ethical codes, IRB guidance documents, and ORI/IRB SOPs relevant to them, to professional practice, and to other applicable regulatory requirements.

Revisions to Standard Operating Procedures

1. The ORI Director, with advice from ORI staff, IRB Chairs, Vice Chairs, and/or IRB members, determines when to revise an existing SOP. In most cases, the RES revises the SOP.  The RES may make minor administrative corrections without revising an SOP (e.g. typographical or grammatical errors).  ORI staff may draft revisions to an SOP based on his/her specialization. All SOP revisions are in compliance with federal, state, and institutional regulations.
2. In revising SOPs, ORI staff may consult with IRB Chairs and/or IRB members on IRB related issues.
3. As appropriate, the RES circulates copies of newly revised SOPs to IRB Chairs, IRB members, and/or ORI staff for review.
4. If the revised SOP involves coordination with another University administrative office, the RES routes the SOP to the appropriate individual representing that office for review, approval, and signature.
5. The revised SOP becomes effective when signed by the ORI Director or designee, IRB Chairs, and coordinating official(s) on the date indicated.
6. The RES places an updated copy of a revised SOP in the SOP binder he/she maintains. The designated ORI staff member also posts the updated SOP to the ORI website and advises ORI staff and/or IRB members of the revisions.
7. The RES informs ORI staff of all changes in the SOPs that are relevant to their job functions via individual meetings, presentations at staff meetings and if applicable through published announcements.
8. The RES informs IRB members of all changes in SOPs that are relevant to their responsibilities and provides this information via direct mailings, presentations and/or the ORI website.
9. If an SOP impacts investigators/study personnel, the RES or designee provides this information to them through the ORI website and disseminates changes through a variety of educational initiatives (e.g., listserve announcements, newsletters, presentations).
10. The ORI Director or designee informs institutional officials of all changes in the SOPs when appropriate.

Temporary Addendums for Transitional Periods or Emergency Situations

1. The ORI Director or designee has the authority to implement temporary contingency procedures that may veer from designated SOPs in emergency situations or during transitional periods.
2. The ORI Director or designee will document temporary contingency procedures and the period in which they are in effect via an SOP addendum to the applicable SOP. The addendum will be signed and dated by the ORI Director. 

Review of Standard Operating Procedures 

1. The RES, QIP Coordinator, or designee conducts a periodic review, once a year, or according to workload or need, of the continuing suitability of the SOPs.
2. ORI staff may review SOPs at any time for accuracy/applicability. The IRB/ORI staff obtain information necessary to update procedures through monitoring of sources including, but not limited to, the U.S. Food & Drug Administration website, Department of Health & Human Services, and the Office for Human Research Protections listserv.
3. If significant or applicable changes to procedures become necessary, the ORI Director, or RES revise the SOP in question as soon as possible, and the RES distributes the revisions to  the IRB, ORI staff, and appropriate individuals representing coordinating administrative offices in a timely manner following the procedures outlined above.  (See the section onRevisions to Standard Operating Procedure.)

Suspension or Deletion of a SOP

1. Upon consulting with IRB Chairs, the ORI Director has authority to suspend or delete an 

   SOP in such circumstances as major policy deliberation, changes in institutional administration, or reorganization of departments, offices or divisions with which the ORI and IRB have coordination relationships or joint procedures. 

2. When an SOP is suspended or becomes obsolete, the RES deletes the SOP, informs appropriate staff and/or IRB members, and ensures that ORI staff remove the SOP from the ORI website and database and archive it, as appropriate.

Record Keeping

1. The RES maintains copies of all current SOPs in both hard copy and electronic form. The designated ORI staff person archives copies of all previous editions of the SOPs in the SOP binder.
2. The RES or designee maintains copies of all original and subsequent revisions of all SOPs indefinitely.

REFERENCES

Not applicable

Approved By: ORI Director, Nonmedical IRB Chair, Medical IRB Chair

Date First Effective: July 24, 2006

Last Revision Date: February 20, 2024

Revision #6

Non-AAHRPP Accredited IRB’s

1. UK may agree to defer responsibility for IRB review to a non-AAHRPP accredited institution’s IRB for research that is not greater than minimal risk. To defer responsibility, the non-UK IRB must have an OHRP-approved FWA and OHRP-registered IRB. Under the terms of the FWA, an institution guarantees that it complies with the federal regulations governing human subjects research and follows a statement of ethical principles for protecting the rights and welfare of human subjects in research. Additionally, UK requires the institution to submit documentation to the Reliance Team of the policies and procedures that cover Initial Review, Continuing Review, Adverse Event/Unanticipated Problem/Protocol Violation Review, Reporting of Serious/ Continuing Non-Compliance,  Unanticipated Problems involving risks to subjects or others, and suspension or termination of research.
2. Assurance of compliance with the applicable laws and regulations is further documented through the completion of a written reliance agreement. UK investigators comply with UK’s standard operating procedures (SOPs) as previously outlined above when relying on an external IRB.

Other HRPP Requirements

1. Ancillary reviews such as biosafety or radiation safety review are conducted by the Relying Institution, To ensure the Reviewing IRB/HRPP is appropriately informed of these reviews, UK requires the completion of a Reliance Communication Plan. The Reliance Communication Plan also documents circumstances when the external IRB must consider additional regulatory requirements such as those of the Department of Defense (DoD) and Department of Justice (DOJ).
2. UK investigators are informed of ancillary reviews and the requirements for communicating the outcomes to the Reviewing IRB in the UK Investigator’s Reliance Toolkit.

REFERENCES

21 CFR 50

21 CFR 56

45 CFR 46.114

AAHRPP Standard I-9

FDA Cooperative Research Guidance FDA Non-Local IRB Review Guidance OHRP Engagement Memo

OHRP Terms of the Federal wide Assurance of Protection for Human Subjects

ATTACHMENTS

Template Communication Plan for SMART IRB

IRB Reliance Request/Registration Form

Reliance Agreement Signature Assurances

Overall Principal Investigator/Lead Study Team Guidance and Checklist

Relying Investigator Guidance and Checklist

Potential Relying Site SMART IRB Point of Contact Survey

Approved By: ORI Director, Nonmedical IRB Chair, Medical IRB Chair

Date First Effective: May 24, 2005

Last Revision Date: May 9, 2019

Revision #14

OBJECTIVE

To describe the policy and procedures for initial full review by the Institutional Review Board (IRB)

GENERAL DESCRIPTION

The IRB conducts initial review for non-exempt research at convened meetings unless the research is eligible for expedited initial review. See the procedures for conducting a convened meeting, the definition of quorum, and the requirements for conducting a full review meeting in the Conduct of IRB Meeting SOP. Investigators must submit studies that do not meet the federally mandated criteria for exempt or expedited initial review for full review. (See Exempt and Expedited Initial Review SOPs.) The IRB only approves research that meets the federal criteria for approval as specified in 45 CFR 46.111 and 21 CFR 56.111. Also, during initial full review, the IRB reviews the informed consent process and documentation as specified in the Informed Consent SOP. The IRB Chairs or designated IRB Members document determinations by completing the applicable Reviewer Checklist/Signature Page. 

RESPONSIBILITY 

Execution of SOP:  IRB Chairs, IRB Members, Principal Investigator (PI)/Study Personnel, Office of Research Integrity (ORI) Staff, ORI Research Compliance Officer (RCO), ORI Research Privacy Specialist (RPS). 

PROCEDURES

Submission and Screening

1. The PI or designee completes an IRB application for IRB review of a research protocol for initial full review and submits it to the ORI.
2. The electronic submission system schedules the IRB application on the agenda for the next available meeting. Each medical IRB meets approximately once every three weeks whereas the non-medical IRB meets monthly. Protocols are scheduled for review on a "first-come, first-serve" basis, limiting the number of reviews as appropriate in order to permit adequate time for discussion and deliberation of agenda items. The electronic submission system sends a request for the PI or designee to attend the meeting unless the IRB waives the requirement to attend.
3. In cases where an investigator transfers identifiable primary research data from another institution which does not meet criteria for exempt or expedited review mechanisms, ORI staff typically schedule the initial review on the agenda as “Full Review Without a Timeslot.” The PI does not attend the meeting unless otherwise indicated by the IRB.
4. ORI staff screen the application to ensure accuracy and completeness. ORI staff note screening findings and provide these comments to the IRB Chair to be discussed at the convened meeting.
5. If UK is the reviewing IRB for a reliance study, ORI staff add a Reliance Team Member as a consultant in E-IRB to ensure that all reliance obligations are satisfied according to the reliance agreements, communication plans and/or local context forms.
6. ORI staff ensure coordination with other university committee reviews as outlined in the applicable standard operating procedures and/or to ensure compliance with pertinent federal requirements. Examples of screening include, but are not limited to, the items listed below.
   • If the investigator checks “cancer” as an attribute in the IRB application, ORI staff notify the Markey Cancer Center Protocol Review and Monitoring Committee (PRMC) following the procedures outlined in the Markey Cancer Center/IRB/ORI SOP.
   • If the investigator checks items on the IRB application that indicate Institutional Biosafety Committee (IBC) approval is necessary, the investigator must include IBC provisional approval materials as an additional document. ORI staff do not schedule the application for review and return the application to the PI if these materials are missing. The Institutional Biosafety Officer has the authority to make the final decision as to whether the project requires IBC approval.
   • Using the information provided in the application, ORI staff screen to determine whether the PI addressed off-site issues following procedures outlined in the IRB Reliance SOP.
   • If research involves prisoners, ORI staff assign the protocol to a prisoner representative for review.
   • If the PI is a registered nurse (RN), ORI staff assign the protocol to a committee with an RN serving as an IRB member who will attend and vote on the protocol at the convened meeting.
   • If the U.S. Department of Education has funded the research and/or the proposed research involves surveying children in public schools, ORI staff inform the IRB of specific U.S. Department of Education requirements.
   • If the research is supported by other federal agencies, which have specific requirements, such as the U.S. Department of Defense (DoD) or U.S. Department of Energy (DOE), ORI staff inform the IRB of specific agency requirements for the review and conduct of the research.
   • If the investigator indicates in the IRB submission that the research involves an investigational new drug (IND) or investigational device exemption (IDE), ORI staff confirm the validity of the IND or IDE number by ensuring that the investigator has uploaded a copy (containing the number) of the detailed protocol from the sponsor and/or verification statement from the sponsor or the Food and Drug Administration (FDA).
   • ORI staff screen the IRB submission to determine whether the investigator is also serving as the sponsor in accordance with FDA regulations. If so, ORI staff verify that the PI has completed the Collaborative Institutional Training Initiative (CITI) Sponsor-Investigator training.
   • If the research involves vulnerable subjects and/or sensitive types of research/procedures, ORI staff add an appropriate vulnerable population reviewer to provide feedback in addition to the primary reviewer.
   • If the investigator has selected “yes” to the Research Financial Interest Disclosure Question, indicating he/she has a significant financial interest, ORI staff and the IRB follow procedures outlined in the Investigator Conflict of Interest/OSPA/IRB/ORI Coordination SOP.
7. ORI staff also screen the protocol to determine whether additional expertise is necessary to conduct the review. If so, ORI staff may ask an ad hoc or cultural consultant who has appropriate expertise in the discipline to participate in the review. The ORI maintains a list of potential cultural consultants qualified by cultural and/or linguistic knowledge or training to assist the IRB, as appropriate, and may contact IRB members, UK faculty, or department chairs for advice in identifying consultants.
8. The PI may also recommend cultural consultants provided they are not directly involved in the study. These consultants may review consent forms, provide verifications of translations, and provide guidance on the impact of the research on subjects and the impact of the culture on the research to be conducted.
9. ORI staff ensure that ad hoc or cultural consultants do not have a conflict of interest in accordance with the IRB Member and Consultant Conflict of Interest SOP.
10. All ad hoc or cultural consultants have access to the same information in IRB as voting IRB members.
11. ORI staff assign a primary reviewer based on the IRB member’s educational background and expertise. RN IRB members serve as primary reviewers for protocols in which the PI is an RN. If no IRB member has the appropriate expertise, ORI staff ask an ad hoc or cultural consultant to serve as primary reviewer.
12. An ORI Research Privacy Specialist (RPS) screens all initial Medical IRB submissions to determine whether a protocol falls under regulations of the Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule and/or the Family Educational Rights to Privacy Act (FERPA). The Nonmedical IRB staff conduct the same screening for all initial Nonmedical IRB submissions. The Nonmedical IRB staff assign any protocol regulated by the Privacy Rule and/or by FERPA to an RPS, who provides recommendations for each protocol to ensure compliance with the Privacy Rule and/or with FERPA. See the HIPAA in Research SOP for additional information regarding HIPAA review procedures.

Submission of Applications to the IRB and Primary Reviewer Responsibilities

1. Approximately five to ten days prior to each convened meeting, ORI staff make the IRB submission available to attending/voting and selected ex officio IRB members for review and send PIs requests to attend, unless the requirement is waived. The available materials include all sections of the IRB application and uploaded attachments.
2. The primary reviewer is responsible for:
   • Conducting an in-depth review;
   • Determining whether the project involves an HHS approved protocol (e.g., NIH cooperative group trial) and, if so, comparing the “Risks” and “Alternatives” sections of the HHS approved sample informed consent document with the UK proposed form to ensure that the HHS and UK sections of the consent are consistent;
   • Informing the full IRB of any discrepancies in the application materials; and
   • Reviewing the financial disclosure form and alerting the IRB if a “yes” disclosure is made.
3. All IRB members review all information on the agenda in advance of the meeting (including those protocols for which the IRB member is not the primary reviewer) to be familiar with the protocol, to be prepared to discuss the protocol at the meeting, and to be prepared to determine whether the research meets the regulatory criteria for approval.

Ad hoc or cultural consultants may provide comments or recommendations in writing to the IRB prior to the meeting or attend the convened meeting to participate in the review. In cases where the consultant participates in the meeting, the minutes of the meeting document the information provided by the consultant. (See Minutes of IRB Meetings SOP.)

IRB Review

1. A majority of the voting IRB members (or their designated alternates), including at least one member whose primary concerns are in nonscientific areas, must be present in order to conduct a convened meeting. For the Medical IRB, a licensed physician must be present. In order for the IRB to approve the proposed research, the protocol must receive the approval of a simple majority of those members present at the meeting. (See The Conduct of IRB Meetings SOP.)
2. When the IRB reviews research that involves categories of human subjects vulnerable to coercion or undue influence, ORI staff ensure that adequate representation or consultation is present for discussions of research involving vulnerable human subjects. (See Protection of Vulnerable Subjects SOP and Membership of IRB SOP.)
3. All IRB members attending the meeting are able to review the IRB submission prior to the convened meeting, have the opportunity to discuss each research protocol during the convened meeting, and participate in the determination of whether the research meets the regulatory criteria for approval.
4. The IRB reviews each initial full review application with the PI or co-investigator present during the convened IRB meeting unless the ORI or IRB waives the requirement. After the PI leaves the meeting, the IRB reviews the application and discusses any controverted issues and their resolution prior to voting.
5. During discussion, the IRB members raise only those issues that the committee determines do not meet the federal criteria for approval as specified in 45 CFR 46.111 or 21 CFR 56.111. In addition, the IRB determines whether the risk level selected by the PI is appropriate. Also, the IRB considers whether the PI’s preliminary assessment of federally mandated specific findings requirements (e.g., request for waiver of informed consent) is acceptable with respect to federal requirements.
6. For research involving a drug or device where the PI or the sponsor has not obtained an IND or IDE, the committee determines what action(s) is needed (whether the PI needs to obtain an IND/IDE or whether PI needs to contact the FDA for guidance). (See Medical Device Clinical Investigations, Compassionate Use, and Treatment IDE SOP and Expanded Access Program (EAP) for Drugs SOP.)
7. In conducting the initial review of the proposed research, the IRB utilizes the Criteria for IRB Approval: Reviewer Checklist.
8. A member or consultant with a conflict of interest must leave the room during the vote and only participate in the review by providing information in accordance with the IRB Member and Consultant Conflict of Interest SOP.

Review Outcome(s) 

1. An IRB member makes a motion, another member seconds the motion, and then the convened IRB votes for, against, or abstains from one of the following five actions:
   • APPROVED (Vote for a #1): IRB approval - A vote for a #1 indicates that the IRB has concluded that the research and consent/assent forms meet the federal criteria for approval. IRB approval verifies that the IRB agrees with the assessment of the protocol and/or specific findings as described by the PI in the application. ORI staff process the submission for approval, generating an approval letter, according to the guidelines in the ORI Customer Service Standards, as well as an informed consent/assent document (if applicable) with the affixed "IRB Approval" validation stamp, which includes the valid date of IRB approval. If the IRB approves a HIPAA Waiver of Authorization Request, a separate approval letter is generated. (See Mandated Reporting to External Agencies SOP.)
   • MINOR REVISIONS and/or ADDITIONAL INFORMATION REQUIRED (Vote for a #2): A vote of #2 indicates that the IRB has approved the protocol pending submission of minor revisions and that the IRB has given the individual chairing the meeting (and/or other IRB member with appropriate expertise or qualifications) the authority to approve the minor revisions. ORI staff generate a letter/comments requesting revisions and return the submission to the investigator, according to the guidelines in the ORI Customer Service Standards, describing the revisions requested by the IRB.
     The PI responds to the IRB’s suggested revisions, making relevant changes in the IRB application and re-submits to the ORI. ORI staff assign the response to the IRB Chair or member who chaired the meeting for further review. The Chair or designee may defer the response to a convened meeting for review by the full committee, request additional information, or approve the protocol.
   • TABLED (Vote for a #3): A vote of #3 indicates that the IRB withholds approval pending submission of major revisions/additional information. ORI staff generate a letter and return the submission to the investigator, outlining the reasons for tabling the protocol  and includes a description of the revisions or clarifications requested. For some studies, the IRB may appoint one or more members of the IRB to discuss the reasons with the investigator. If the vote is for a #3, ORI staff schedule the PI’s response to the requested revisions for review by the full committee; the IRB does not require the PI to attend.
   • TABLED (Vote for a #4):  If the vote is for a #4, the IRB follows the same procedure as for a vote of #3, except the PI needs to attend the future IRB meeting at which the IRB reviews his/her response to discuss or answer IRB concerns or questions. ORI staff notify the PI of the request for him/her to attend that future IRB meeting.
   • DISAPPROVED (Vote for a #5): If the vote is for a #5, ORI staff generate a letter describing the reasons for disapproving the protocol. Disapproval of a protocol usually occurs when the IRB determines that the risk of the procedures outweighs any benefit to be gained or if the proposed research does not meet the federal criteria for IRB approval.
2. The PI and/or study staff have 90 days from the date of the convened IRB meeting to submit requested revisions. If more time is needed, the PI must request an extension from ORI staff.  While ORI may grant an extension, the PI must complete and submit all requested revisions to the IRB within 9 months of the date of the convened meeting.  If revisions are not received within this timeframe, ORI may withdraw the protocol, and the PI must submit a new application for initial review.
3. During the convened meeting, the IRB determines the approval period, as appropriate to the degree of risk but not less frequently than once per year for research retaining full board review status. The IRB may set a shorter approval period for high risk protocols or protocols with high risk/low potential benefit ratios. Research determined by the convened board to be minimal risk and meets one or more expedited categories is subject to the procedures outlined in the Continuation Review SOP.
4. When a protocol receives final approval, the ORI assigns the start of the approval period as the date of the convened IRB meeting. If a protocol initially received a vote #2 (the IRB requested minor revisions) and the PI completed the revisions, the approval period starts from the meeting date of the convened IRB during which the IRB initially reviewed the protocol. Should there be serious concerns or a lack of significant information (vote #3 or vote #4) which requires the convened IRB to complete its review and issue approval of the study at a subsequent meeting, the approval period starts with the date of the subsequent convened IRB meeting.
5. Before issuing the IRB approval letter, ORI staff confirm that all of the applicable Institutional Biosafety Committee, Radiation Safety Committee, Radioactive Drug Research Committee, and Research Conflict of Interest Committee, approvals are in place. If applicable approvals are not in place, ORI staff notify the investigator in writing, requesting the appropriate information. When the investigator submits the information, ORI staff may put it on an agenda for review by the IRB, if appropriate. ORI staff only issue the IRB approval letter after obtaining appropriate documentation.
6. Before issuing approval, ORI staff also ensure that all study personnel have completed the required human subject protection training. If the PI and study personnel have not completed training, ORI staff notify the PI. All study personnel must complete required training before the IRB can issue approval.
7. If the PI is serving as the sponsor in accord with FDA regulations, ORI staff ensure that the PI has completed the Sponsor-Investigator on-line training, or equivalent training as approved by the ORI Director or the IRB Chair or their designee before issuing approval.
8. Before issuing approval, ORI staff verify that any pending IND or IDE has been approved by the FDA or has passed the 30-calendar day FDA clearance period. If the IND or IDE submission is pending acknowledgment of receipt by the FDA, or the 30-calendar day clearance period has not passed, the ORI stipulates in the IRB approval letter that research must not commence until IND or IDE is in place. The PI provides ORI with FDA correspondence confirming that the IND or IDE is in place or the 30-calendar day period has passed, prior to initiating the research.
9. If the research involves prisoners, ORI staff check to determine whether the PI submitted the protocol for funding to an HHS agency. If this is the case and the protocol involves prisoners, ORI staff, with input from the PI, prepare and submit a prisoner certification report to the Office for Human Research Protection (OHRP) in accordance with OHRP requirements and the Mandated Reporting to External Agencies SOP.
10. Once the IRB approves a protocol, ORI staff send an approval letter to the PI, which includes the approval period, a reminder to use only the approved consent/assent form, and a reminder that the IRB must approve any changes to the protocol prior to initiation of the changes.
11. Upon request, ORI staff also send the PI a funding agency Certification of Approval form. (See the Mandated Reporting to External Agencies SOP.)
12. At IRB approval, it is the PI’s responsibility to request an Extent of Compliance Statement if the protocol falls under the International Conference on Harmonisation guidance related to Good Clinical Practice. The ORI maintains a statement of compliance signed by the IRB Chair and provides that statement upon request.
13. If the PI has concerns regarding the IRB decision/recommendations for changes in the study, he/she may submit a written appeal that includes a justification for changing the IRB decision.  The convened IRB reviews the appeal in conjunction with a separate party (e.g., chair/vice chair from a different committee, consultant, etc.) to assist in adjudicating the appeal. The appeal determination is final.                        

REFERENCES

21 CFR 50.25

21 CFR 56.111

21 CFR 312

21 CFR 812 

21 CFR 50 Subpart D

45 CFR 46.108

45 CFR 46.111

45 CFR 46.116 

45 CFR 46.117 

45 CFR 46 Subpart B 

45 CFR 46 Subpart C

45 CFR 46 Subpart D

Approved By: ORI Director, Nonmedical IRB Chair, Medical IRB Chair

Date First Effective: May 10, 2005

Last Revision Date: February 15, 2019

Revision #11

OBJECTIVE 

To describe the policies and procedures for conducting expedited initial review

GENERAL DESCRIPTION

The Institutional Review Board (IRB) uses an expedited review process to review studies that meet the categories adopted by the Department of Health and Human Services (HHS) or the Food and Drug Administration (FDA) that involve no greater than “minimal risk.” The expedited applicability criteria, including the definition of “minimal risk” and federally mandated categories are attached. Expedited review procedures allow the IRB to review and approve studies that meet the criteria in the attached document without convening a meeting of the full IRB. The IRB Chair and/or one or more experienced reviewers from among the IRB membership (regular and alternate members) conducts expedited initial review. 

Expedited reviewers only approve research that meets the federal criteria for approval as specified in 45 CFR 46.111 and 21 CFR 56.111. Also, expedited reviewers ensure that the study’s informed consent process and documentation meet the requirements as specified in 45 CFR 46.116 and 21 CFR 50.25 unless the IRB waives the requirements in accord with federal regulations. (See Informed Consent SOP.)

Expedited reviewers exercise all the authority of the IRB except that the reviewers may not disapprove the research. The IRB only disapproves a research activity in accordance with non-expedited procedures set forth in the HHS and FDA regulations. 

The IRB agenda for convened meetings advises the IRB of research studies approved using expedited review procedures. Any member can request to review an IRB expedited study submission.

RESPONSIBILITY

Execution of SOP: IRB Chair, IRB Members, Office of Research Integrity (ORI) Staff, Research Privacy Specialist (RPS), ORI Research Compliance Officer (RCO), Principal Investigator (PI)/Study Personnel 

PROCEDURES

Assigning Reviewers

1. IRB members who have completed orientation including expedited training and attended at least one convened meeting are eligible to conduct expedited review.
2. ORI staff make initial IRB reviewer assignments based on the member’s familiarity with IRB issues and his/her experience and expertise. For Medical expedited review assignments, ORI staff assign the submission to one experienced member for review. For Nonmedical expedited review assignments, ORI staff assign the submission to the Chair or designated member.
3. Expedited reviewers notify ORI staff if they are unable to conduct an expedited review during the assigned time period or have a conflict of interest on any protocol as outlined in the IRB Member and Consultant Conflict of Interest SOP. Another reviewer is selected by ORI staff.

Submission and Screening

1. The PI makes a preliminary determination that a protocol is eligible for expedited review based on the criteria in the attached document. The IRB makes the final determination regarding whether a protocol is eligible for expedited review.
2. Upon receipt of the application, ORI staff screen it for accuracy and make a preliminary determination whether the application meets the criteria for expedited review, including minimal risk, and identify the research categories. If the application does not meet the criteria for expedited review, ORI notifies the PI and changes the submission type to “Full”.
3. ORI staff follow the screening procedures outlined in the Initial Full Review SOP (e.g., screening for: coordination with other University review committees; vulnerable subjects or federally mandated specific findings; waiver of informed consent or documentation requests; completion of mandatory training requirements; or need of additional expertise or prisoner representative review). See the Initial Full Review SOP for a detailed description of ORI staff procedures.
4. ORI staff note, during the screening process, whether the submission involves areas of research requiring federally mandated specific findings.
5. ORI staff screen for Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule and/or Family Educational Rights and Privacy Act (FERPA) concerns. If the PI includes a HIPAA form, checks “HIPAA” in the application, or if there are any HIPAA or FERPA concerns, ORI staff assign an ORI Research Privacy Specialist (RPS) as an additional reviewer. The RPS reviews the application and provides feedback via comments to the PI, ORI staff, and expedited reviewer.
6. ORI staff provide screening comments to the PI. The PI and/or study staff have 60 days from that date to respond to screening comments. If more time is needed, the PI must request an extension from ORI staff.  Also, the PI may request that the protocol be sent to the IRB without responding to screening comments. If the PI has not made a request or responded within this timeframe, ORI may withdraw the protocol, and the PI must submit a new application for initial review.
7. After screening the application, ORI staff assign a primary reviewer to the application. For Nonmedical protocols, the Chair or designated member is the reviewer. Additional reviewers are added as needed for necessary expertise. The reviewer(s) receive notification by email that a protocol has been assigned for to their review.

IRB Expedited Review Process

Expedited reviewers conduct expedited reviews outside of a convened meeting in accordance with 45 CFR 46.110. If an expedited reviewer is not available or has a conflict of interest, ORI staff contact another reviewer to conduct the review. 

ORI staff assign Medical IRB protocols to a single primary expedited reviewer and Nonmedical IRB protocols to the Chair or designated member as the primary reviewer. Assigned reviewers have access to all IRB protocol materials provided by the PI. If a reviewer is unable to complete his/her review within approximately ten (10) business days, ORI staff send the reviewer up to two reminders. If the expedited reviewer still does not respond, ORI staff reassign the protocol. 

The primary expedited reviewer, with input from other assigned reviewers as applicable, provides feedback for any clarification needed and documents the issues discussed on the Expedited Reviewer Signature Page. The expedited reviewer utilizes the Criteria for IRB Approval: Reviewer Checklist to document that the research meets the federal criteria for IRB approval. The expedited reviewer makes determinations for specific findings using the information from the IRB application and records his/her determinations on the Expedited Reviewer Signature Page. The reviewer documents any issues pertaining to specific findings (e.g., requests for a waiver of informed consent or documentation of informed consent, and/or Subpart B, C, D findings) in the materials submitted by the PI and the expedited reviewer’s final approval of the application. 

Review Outcomes

1. Both Medical and Nonmedical primary expedited reviewers make the final determination as to whether research activities meet the expedited review criteria outlined in the attached document.
2. The primary reviewer determines whether the research meets the federal criteria for approval as outlined in 45 CFR 46.111 and 21 CFR 56.111.
3. Primary expedited reviewers ensure that the investigator describes the informed consent process and how to obtain documentation of informed consent, as specified in 45 CFR 46.116 and 117 and 21 CFR 50.25 unless the primary expedited reviewer waives the requirements in accord with federal regulations. (See Informed Consent SOP.)  
4. Expedited reviewers only raise controverted issues or request changes that they have determined do not meet the federal criteria for approval or UK IRB policies.
5. The primary expedited reviewer documents on the Expedited Reviewer Signature Page his/her determinations regarding expedited eligibility, applicable expedited category (or categories), rationale for conducting continuation review (if applicable), and whether the research meets the federal criteria for approval.
6. The primary expedited reviewer makes one of the following three determinations:
   • APPROVED: IRB approval indicates that the IRB reviewer(s) concluded the research and consent forms meet the federal criteria for approval. An approval determination verifies the IRB agrees with the assessment of the protocol and/or specific findings as described by the PI in the application. ORI staff process the determination, and the PI is provided with an approval letter and, when applicable, stamped informed consent/assent documents. Upon request, ORI staff send the PI a funding agency Certification of Approval form.
   • REVISIONS and/or ADDITIONAL INFORMATION REQUIRED: The IRB reviewer(s) withhold approval pending submission of revisions/additional information. ORI staff return the protocol to the PI to address concerns/questions provided by the reviewer(s). The PI responds and re-submits the application to the ORI within 90 days of receiving the requested revisions. ORI staff assign the PI’s response to the primary expedited reviewer who made the initial determination. Barring extenuating circumstances or a granted extension, if a PI does not respond to requested revisions in the 90-day time-period, the application is administratively withdrawn, and a new protocol submission is required.
   • FULL REVIEW REQUIRED: The primary expedited reviewer may determine the protocol requires full review by the IRB at a convened meeting.
7. The PI and/or study staff have 90 days from the date of initial notification that the IRB has     requested revisions to submit the revisions. If more time is needed, the PI must request an extension from ORI staff.  Barring extenuating circumstances, extensions may not exceed 9 months of the date of the initial revision notification.  If revisions are not received within this timeframe, ORI may withdraw the protocol, and the PI must submit a new application for initial review.
8. The primary expedited reviewer can determine that the research is eligible for a less stringent mechanism of review (i.e., the project is eligible for exemption or the activities do not fall under the purview of the IRB). If the protocol is determined to be eligible for exemption, ORI staff change the protocol review type. If the activities do not fall under the purview of the IRB, the IRB handles the review using procedures outlined in the Determination of Activities That Need IRB Review SOP.
9. The ORI procedures for notifying the PI of the review outcome, obtaining follow-up correspondence, and issuing approval letters outlined in the Initial Full Review SOP which also applies to expedited review. See Initial Full Review SOP for details.
10. The date the primary expedited reviewer signs off for final approval of the study is the date the approval period starts. The primary expedited reviewer must document rationale for requiring an annual continuation review, if applicable. Otherwise, the protocol requires an annual administrative review. See Continuation Review SOP for details.
11. If the PI has concerns regarding the primary expedited reviewer’s decision/recommendations, he/she may submit his/her concerns via a written appeal. The PI sends the request to the ORI. The appropriate primary expedited reviewer or the convened IRB reviews the appeal in conjunction with a separate party (e.g., chair/vice chair from a different committee, consultant, etc.) to assist in adjudicating the appeal. The appeal determination is final.

FDA-Regulated or Expedited studies approved prior to implementation of the Revised Common Rule (approved prior to January 21, 2019)

FDA-regulated studies and protocols that were IRB approved prior to the implementation of the Revised Common Rule, the FDA or previous Common Rule regulations will apply. No action is required on the part of the investigator as these studies will be “grandfathered in” the previous regulations. Investigators are still expected to submit modification requests and annual continuing reviews. See Modification, Deviations, and Exceptions SOP and Continuation Review SOP. For more information regarding the regulations applicable to these studies, please see archived Expedited SOP Revision #10. 

REFERENCES

21 CFR 56.102(i)

21 CFR 56.110

45 CFR 46.108(b)

45 CFR 46.110 

45 CFR 46.115

63 FR 60364-60367

Approved By: ORI Director, Nonmedical IRB Chair, Medical IRB Chair

Date First Effective: May 10, 2005

Last Revision Date: May 21, 2023

Revision #10

OBJECTIVE

To describe the policies and procedures for the exempt review process

GENERAL DESCRIPTION

Research procedures that meet the categories set forth in 45 CFR 46.104(d); 21 CFR 56.104(d) may qualify for exemption. An Institutional Review Board (IRB) member reviews and provides a determination for all exemptions claimed for research conducted at the University of Kentucky (UK) or by employees or agents of UK facilities. Research activities are exempt from the human research protection regulations when the only involvement of human subjects falls within one or more of the exempt categories. The categories are as follows:

1. Research, conducted in established or commonly accepted educational settings, that specifically involves normal educational practices that are not likely to adversely impact students’ opportunity to learn required educational content or the assessment of educators who provide instruction. This includes most research on regular and special education instruction strategies, and research on the effectiveness of or the comparison among instructional techniques, curricula, or classroom management methods. 
   
   This category does not apply to Food and Drug Administration (FDA) regulated research.
2. Research that only includes interactions involving educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures, or observation of public behavior (including visual or auditory recording) if at least one of the following criteria is met:
   
   (i) The information obtained is recorded by the investigator in such a manner that the identity of the human subjects cannot readily be ascertained, directly or through identifiers linked to the subjects;
   
   (ii) Any disclosure of the human subjects' responses outside the research would not reasonably place the subjects at risk of criminal or civil liability or be damaging to the subjects' financial standing, employability, educational advancement, or reputation; or
   
   (iii) The information obtained is recorded by the investigator in such a manner that the identity of the human subjects can readily be ascertained, directly or through identifiers linked to the subjects, and an IRB conducts a limited IRB review to make the determination required by 45 CFR 46.111(a)(7).
   
   The first two criteria of this category (i and ii) may not be applied to research with minors when involving surveys and/or interviews. They may only be applied to research with minors when involving educational tests or the observation of public behavior and the investigators do not participate in those activities. The third criteria of this exemption (iii) may not be applied to research with minors.
3. (i)  Research involving benign behavioral interventions in conjunction with the collection of information from an adult subject through verbal or written responses (including data entry) or audiovisual recording if the subject prospectively agrees to the intervention and information collection and at least one of the following criteria is met:
   (A) The information obtained is recorded by the investigator in such a manner that the identity of the human subjects cannot readily be ascertained, directly or through identifiers linked to the subjects;
   (B) Any disclosure of the human subjects' responses outside the research would not reasonably place the subjects at risk of criminal or civil liability or be damaging to the subjects' financial standing, employability, educational advancement, or reputation; or
   (C) The information obtained is recorded by the investigator in such a manner that the identity of the human subjects can readily be ascertained, directly or through identifiers linked to the subjects, and an IRB conducts a limited IRB review to make the determination required by 45 CFR 46.111(a)(7).
   
   (ii) For the purpose of this provision, benign behavioral interventions are brief in duration, harmless, painless, not physically invasive, not likely to have a significant adverse lasting impact on the subjects, and the investigator has no reason to think the subjects will find the interventions offensive or embarrassing. UK defines brief duration for an intervention (not including data collection, unless intertwined) as lasting no longer than a few minutes to a few hours on a single day. Provided all such criteria are met, examples of such benign behavioral interventions would include having the subjects play an online game, having them solve puzzles under various noise conditions, or having them decide how to allocate a nominal amount of received cash between themselves and someone else. 
   
   (iii) If the research involves deceiving the subjects regarding the nature or purposes of the research, this exemption is not applicable unless the subject authorizes the deception through a prospective agreement to participate in research in circumstances in which the subject is informed that he or she will be unaware of or misled regarding the nature or purposes of the research.
   
   Research involving minors is not eligible for this category of exemption.
   
   This category does not apply to FDA regulated research.
4. Secondary research for which consent is not required: Secondary research uses of identifiable private information or identifiable biospecimens that have been or will be collected for a non-related primary or initial activity, if at least one of the following criteria is met:
   
   (i) The identifiable private information or identifiable biospecimens are publicly available;
   
   (ii) Information, which may include information about biospecimens, is recorded by the investigator in such a manner that the identity of the human subjects cannot readily be ascertained directly or through identifiers linked to the subjects, the investigator does not contact the subjects, and the investigator will not re-identify subjects;
   
   (iii) The research involves only information collection and analysis involving the investigator's use of identifiable health information when that use is regulated under 45 CFR parts 160 and 164, subparts A and E, for the purposes of “health care operations” or “research” as those terms are defined at 45 CFR 164.501 or for “public health activities and purposes” as described under 45 CFR 164.512(b); or
   
   (iv) The research is conducted by, or on behalf of, a Federal department or agency using government-generated or government-collected information obtained for non-research activities, if the research generates identifiable private information that is or will be maintained on information technology that is subject to and in compliance with section 208(b) of the E-Government Act of 2002, 44 U.S.C. 3501 note, if all of the identifiable private information collected, used, or generated as part of the activity will be maintained in systems of records subject to the Privacy Act of 1974, 5 U.S.C. 552a, and, if applicable, the information used in the research was collected subject to the Paperwork Reduction Act of 1995, 44 U.S.C. 3501 et seq. 
   Note: This fourth criteria is unlikely to be used. If you feel that it is applicable, please contact the Office of Research Integrity (ORI) for Assistance.
   
   This category may not be applied to research involving primary collection from subjects; collection must be performed for a non-related purpose. Collection can be either prospective or retrospective.
   
   This category does not apply to FDA regulated research.
5. Research and demonstration projects that are conducted or supported by a Federal department or agency, or otherwise subject to the approval of department or agency heads (or the approval of the heads of bureaus or other subordinate agencies that have been delegated authority to conduct the research and demonstration projects), and that are designed to study, evaluate, improve, or otherwise examine public benefit or service programs, including procedures for obtaining benefits or services under those programs, possible changes in or alternatives to those programs or procedures, or possible changes in methods or levels of payment for benefits or services under those programs. Such projects include, but are not limited to, internal studies by Federal employees, and studies under contracts or consulting arrangements, cooperative agreements, or grants. Exempt projects also include waivers of otherwise mandatory requirements using authorities such as sections 1115 and 1115A of the Social Security Act, as amended.
   
   (i) Each Federal department or agency conducting or supporting the research and demonstration projects must establish, on a publicly accessible Federal website or in such other manner as the department or agency head may determine, a list of the research and demonstration projects that the Federal department or agency conducts or supports under this provision. The research or demonstration project must be published on this list prior to commencing the research involving human subjects.
6. Taste and food quality evaluation and consumer acceptance studies:
   
   (i) If wholesome foods without additives are consumed; or
   
   (ii) If a food is consumed that contains a food ingredient at or below the level and for a use found to be safe, or agricultural chemical or environmental contaminant at or below the level found to be safe, by the FDA or approved by the Environmental Protection Agency or the Food Safety and Inspection Service of the U.S. Department of Agriculture.
7. Storage or maintenance for secondary research for which broad consent is required: Storage or maintenance of identifiable private information or identifiable biospecimens for potential secondary research use if an IRB conducts a limited IRB review and makes the determinations required by 45 CFR 46.111(a)(8). 
   
   Research category 7 is not an option at the University of Kentucky at this time.
8. Secondary research for which broad consent is required. Research involving the use of identifiable private information or identifiable biospecimens for secondary research use, if the following criteria are met:
   
   (i) Broad consent for the storage, maintenance, and secondary research use of the identifiable private information or identifiable biospecimens was obtained in accordance with 45 CFR 46.116(a)(1) through (4), (a)(6), and (d);
   
   (ii) Documentation of informed consent or waiver of documentation of consent was obtained in accordance with 45 CFR 46.117;
   
   (iii) An IRB conducts a limited IRB review and makes the determination required by 45 CFR 46.111(a)(7) and makes the determination that the research to be conducted is within the scope of the broad consent referenced in paragraph (d)(8)(i) of this section; and 
   
   (iv) The investigator does not include returning individual research results to subjects as part of the study plan. This provision does not prevent an investigator from abiding by any legal requirements to return individual research results. 
   
   Research category 8 is not an option at the University of Kentucky at this time.

The UK IRB reviews research in categories that are exempt from the federal human research requirements to determine whether an exemption is appropriate.

RESPONSIBILITY

Execution of SOP: IRB Members, Office of Research Integrity (ORI) Staff, ORI Research Privacy Specialist (RPS), and Principal Investigator (PI)/Study Personnel

PROCEDURES

Assigning Reviewers

1. ORI staff currently assigned as alternate IRB members are the primary reviewers tasked with making exemption determinations and conducting limited IRB review, if required. These ORI staff may assign submissions to the IRB Chair or another IRB member to assist with or conduct the exemption review as needed or if specific expertise is required. ORI staff members who have a conflict of interest related to a specific application, as outlined in the IRB Member and Consultant Conflict of Interest SOP, assign the application to another reviewer.
2. IRB Chairs and other IRB members assigned as reviewers of exempt protocols are responsible for notifying ORI staff if they are not able/available to conduct the review. An assigned reviewer is also responsible for notifying ORI staff if they have a conflict of interest as outlined in the IRB Member and Consultant Conflict of Interest SOP. 

Submission and Screening

1. The PI makes a preliminary determination that a protocol is eligible for exempt review based on an assessment of the protocol, establishing that it is eligible for one or more of the exemption categories specified in the federal regulations. The IRB member makes the final determination regarding whether a protocol is eligible for exemption.
2. The PI submits an exempt IRB application.
3. Upon receipt of the application, designated ORI staff screen the application for completeness and accuracy. The designated ORI staff member reviews the PI’s exempt category selection for appropriateness. The designated ORI staff member either assigns themselves  as the reviewer or provides screening comments to another IRB member. The comments include recommendations for the appropriate exempt category(ies) and justification for the chosen category(ies). If it is clear to the designated ORI staff member the application does not meet the criteria for exempt review, the designated ORI staff member contacts the PI and recommends that they consider withdrawing the exempt application and resubmitting as either an expedited or full review application.
4. ORI staff contact the PI during the application screening process to request any additional information needed for a thorough review.
5. ORI staff also screen for Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule and/or Family Educational Rights to Privacy Act (FERPA) concerns. If there is a HIPAA or FERPA concern, ORI staff forward the application to the ORI Research Privacy Specialist (RPS) or designee for review. The RPS or designee reviews the application and submits comments and the IRB reviewer takes them into consideration and makes the final determination.

IRB Exempt Review

1. The IRB reviewer is responsible for reviewing the application upon receipt to determine whether all of the proposed research procedures fit one or more of the exemption categories specified in the federal regulations. The reviewer ensures that the research meets ethical principles and standards for protecting research subjects. If required by the exempt category(ies), the reviewer performs and documents the determinations of a limited IRB review, applying the criteria at 45 CFR 46.111(a)(7).
2. The IRB reviewer ensures the research does not include any of the following:
   • Targeted enrollment of prisoners as they are excluded from the exemption categories (however, research aimed at involving a broader subject population that only incidentally includes prisoners may be allowed);
   • Survey or interview procedures which include children as subjects (exemption category #2 only);
   • The administration of educational tests to children and/or observation of public behavior involving children where the investigator directly participates in the activities being administered and/or observed (exemption category #2 only);
   • FDA-regulated research (exemption categories #1-5).
3. The IRB reviewer may contact the PI for any clarification needed and documents the issues discussed with the PI.
4. If the IRB reviewer is unable to respond within approximately ten (10) days, ORI staff send up to two (2) reminders. If the reviewer is still unable to respond, ORI staff forward the protocol to another reviewer.

Review Outcome(s)

1. The IRB reviewer makes one of the following recommendations:
   • APPROVED: IRB approval indicates that the IRB reviewer(s) concluded the research and consent forms meet the federal criteria for approval. An approval determination verifies the IRB agrees with the assessment of the protocol and/or specific findings as described by the PI in the application. ORI staff process the determination and the PI is provided with an approval letter and, when applicable, stamped informed consent/assent documents.
   • REVISIONS and/or ADDITIONAL INFORMATION REQUIRED: The IRB reviewer(s) withhold approval pending submission of revisions/additional information. ORI staff return the protocol to the PI to address concerns/questions provided by the reviewer(s). The PI responds and re-submits the application to the ORI within 90 days of receiving the requested revisions. ORI staff assign the PI’s response to the IRB reviewer who made the initial determination. Barring extenuating circumstances, if a PI does not respond to requested revisions in the 90-day time-period, the application is administratively withdrawn, and a new protocol submission is required.
   • EXPEDITED or FULL REVIEW REQUIRED: The IRB reviewer may determine the protocol requires expedited or full review by the IRB.
2. The PI and/or study staff have 90 days from the date of initial notification that the IRB has requested revisions to submit the revisions. If more time is needed, the PI must request an extension from ORI staff.  While ORI may grant an extension, the PI must complete and submit all requested revisions to the IRB within 9 months of the date of the initial revision notification.  If revisions are not received within this timeframe, ORI may withdraw the protocol, and the PI must submit a new application for initial review.
3. The IRB reviewer can also recommend that the activities do not fall under IRB purview. In these cases, the IRB handles the review using procedures outlined in the Determination of Activities that Need IRB Review SOP.
4. ORI staff forward the IRB reviewer’s recommendation to the PI in accordance with ORI Customer Service Standards.
5. The PI is responsible for submitting any requested revisions.
6. ORI staff approve directive requested revisions made in response to the IRB’s review as an administrative change.  This includes, for example:
   • addition of a letter of support from a non-UK research site;
   • addition or minor modifications to recruitment materials, advertisements;
   • changes to study duration or schedule, (e.g., extending end date of study, adding an additional semester of the same data collection activities);
   • minor changes to study population in non-therapeutic studies (e.g., raising inclusion criteria from age 20 to 30);
   • small changes to incentives (e.g., $25 instead of $15 gift card); and
   • minor changes to data collection instruments in non-limited review protocols.
     
     Minor changes are limited to directive revisions such as grammatical edits, new dates, expanding a Likert scale, clarifying an item, or adding questions that would not change the subject matter or overall time commitment.  Revisions that are substantive, ambiguous, open-ended, or involve sensitive topics are not minor.
7. For substantive requested revisions, the IRB reviewer determines whether the revisions are sufficient for an exempt determination and, if so, ORI staff issue an exemption certification to the PI.
8. If the reviewer determines the revisions are inappropriate or insufficient, they may request that the PI make further revisions. This review and revision process continues until the research is either approved or the IRB reviewer determines the study is not eligible for exemption.
9. If the IRB reviewer determines that the study is not eligible for an exemption, the PI may submit the research proposal as an expedited study if the study meets the criteria for expedited review. If the study does not meet the criteria for expedited review, the PI submits a full review application.
10. If the PI has concerns regarding the IRB decision/recommendations for changes in the study, they may submit the concerns via a written appeal, including a justification for changing the IRB decision. The PI sends the request to the ORI. The reviewer and/or the IRB Chair/Vice Chair or the full convened IRB reviews the appeal in conjunction with a separate party (e.g., chair/vice chair from a different committee, consultant, etc.) to assist in adjudicating the appeal. The appeal determination is final.
11. IRB records for all exempt determinations include the citation of the specific category(ies), justifying the exemption.
12. When the IRB has certified a research study as exempt, the IRB does not require continuation or annual administrative reviews. The exemption approval is in effect for a six-year period. Approximately three months prior to the end of the six-year period, the ORI notifies the PI that the exemption will expire and that they must submit a new exemption application if the project is to continue. 

Exempt studies certified prior to implementation of the Revised Common Rule (approved prior to January 21, 2019)

For studies receiving an exempt determination prior to the implementation of the Revised Common Rule, the previous regulations will apply. No action is required on the part of the investigator as these studies will be “grandfathered in” under the previous regulations. Investigators are still expected to submit modification requests that may affect the exempt determination. For information regarding the regulations applicable to these studies, please see archived Exempt Review SOP Revision #8. 

REFERENCES

45 CFR 46.104(d)

21 CFR 56.104(d)

Approved By: ORI Director, Nonmedical IRB Chair, Medical IRB Chair

Date First Effective: May 17, 2005

Last Revision Date: February 15, 2019

Revision #11

OBJECTIVE

To describe the policies and procedures for conducting continuation review (CR) and annual administrative review (AAR)

GENERAL DESCRIPTION

The Institutional Review Board (IRB) conducts substantive and meaningful CR for research requiring review by the convened board at intervals appropriate to the degree of risk, but not less than once per year. The research protocol must satisfy the criteria set forth in 45 CFR 46.111 and 21 CFR 56.111 for the IRB to approve the protocol for continuation. 

In accord with federal requirements, the IRB approval period for research requiring convened board review can extend no longer than one (1) year after the start of the approval period. The PI may not continue research activities after expiration of IRB approval; continuation is a violation of federal requirements specified in 45 CFR 46.103(a) and 21 CFR 56.103(a). If the IRB approval expires, the PI must cease all research activities and may not enroll new subjects in the study. However, if the IRB determines there is an overriding safety concern and/or ethical issue or that it is in the best interests of the individual subjects to continue participating in the research activities, the IRB may permit the subjects to continue in the study for the time required to complete the CR process. 

Research originally reviewed and approved by the convened board continues to undergo CR review until:

1. The research is permanently closed to the enrollment of new subjects, all subjects have completed all research-related interventions, and the research remains active only for long-term follow-up of subjects; OR
2. Study personnel have enrolled no subjects at UK and no additional risks have been identified either at UK or at any site if the research involves a multi-site study; OR
3. The only remaining research activities are limited to data analysis; OR
4. The research involves the study of drugs and/or medical devices AND does not require an Investigational New Drug (IND) (21 CFR Part 312) and/or an Investigational Device Exemption (IDE) (21 CFR Part 812) and/or the device is approved for marketing and being used in accordance with the approved labeling. The IRB must also have determined and documented at a convened meeting that the research is not greater than minimal risk and no additional risks have been identified.

Once the research meets one of these requirements, the study will have either a CR or AAR reviewed by a single IRB member, usually a Vice Chair. 

Research originally reviewed and approved under expedited review procedures undergoes expedited CR if: 

• It was approved under the Old Common Rule (i.e., prior to January 21, 2019);
• It is FDA-regulated, regardless of when it was approved; or
• It was approved under the Revised Common Rule (i.e., on or after January 21, 2019) and the IRB has documented justification for requiring substantive and meaningful CR.

Expedited review studies subject to CR are approved for a period of no longer than one (1) year and may not continue after expiration without undergoing subsequent CR.

Unless there is documented IRB justification for requiring an expedited CR, the following research at UK undergoes an annual administrative review (AAR):

• Research originally reviewed and approved by expedited review procedures under the Revised Common Rule (i.e., on or after January 21, 2019); or
• Non-FDA-regulated research originally reviewed and approved by the convened board under the Revised Common Rule that reaches a point where it no longer requires review by the full board (e.g., becomes closed to enrollment, never enrolled subjects, current activities limited to data analysis). 

Studies subject to AAR are approved for a period of no longer than one (1) year and may not continue after expiration without undergoing subsequent AAR. 

RESPONSIBILITY 

Execution of the SOP: Office of Research Integrity (ORI) Staff, IRB Members, IRB Chair, IRB Vice Chair, ORI Research Privacy Specialist (RPS), Principal Investigator (PI)/Study Personnel

PROCEDURES 

CR and AAR Requests, Submissions, and Screening

1. The PI is sent either a CR or AAR request and subsequent reminders before the IRB approval period expires (e.g., approximately 90 days, 60 days, and 30 days prior to expiration). The PI is responsible for responding to the requests in a timely manner.
2. The PI must submit a CR or an AAR for a study until it is eligible for closure. See the Study Closure SOP for details on circumstances in which a PI may close a study.
3. If UK is the reviewing IRB for a reliance study, ORI staff add the Reliance team as a consultant for the review to ensure that all reliance obligations are satisfied according to the reliance agreements, communication plans and/or local context forms.
4. If the CR is submitted for review by the convened board, ORI staff screen the submission to determine whether the study is eligible for expedited review procedures.
5. ORI staff also screen the application to ensure compliance with select federal requirements, such as prisoner representative review if applicable.
6. ORI staff assign ad hoc and cultural consultants regarding issues related to the addition of subject populations for which the IRB does not have the appropriate expertise, using the procedures outlined in the Initial Full Review SOP.
7. The ORI may request additional information or materials from the PI if the application is not complete. (If the PI does not respond, ORI staff contact the PI and/or research staff for additional information/materials.) 

Full CR Procedures 

1. The Medical and Nonmedical IRBs conduct continuing review of research at regularly scheduled convened meetings.
2. The Vice Chair or designee serves as the primary reviewer for convened review (full CRs). If the Vice Chair has a conflict of interest (e.g., is study personnel on the protocol), is unavailable, or does not have the appropriate expertise to review the CR, ORI staff send the CR to the Chair, another Vice Chair, a voting member of the IRB, or a consultant with the appropriate expertise. 
3. The primary reviewer and the IRB members scheduled to attend the meeting have access to the IRB application approximately 5-10 days prior to the convened meeting.
4. IRB members review information on the agenda in advance of the meeting (including protocols for which the member is not the primary reviewer) to be prepared to discuss the protocol at the meeting and determine whether the research meets the regulatory criteria for approval. Unless otherwise noted, the IRB agrees with ORI screening comments/revisions.
5. IRB members are responsible for evaluating the information communicated to the subject during the consent process as outlined in the Informed Consent SOP. The IRB reviews the informed consent/assent/HIPAA document(s) to ensure accuracy and completeness.
6. The IRB ensures the PI provides any significant new findings that might relate to subjects’ willingness to continue participation in accordance with regulations.
7. When the IRB reviews research that involves categories of individuals vulnerable to coercion or undue influence, ORI staff ensure adequate representation or consultation is present for discussion of research involving vulnerable human subjects. (See Protection of Vulnerable Subjects SOP and Membership of IRB SOP.)
8. ORI staff conduct the convened meeting in accord with the Conduct of IRB Meetings SOP. IRB members who have a conflict of interest follow procedures outlined in both the Conduct of IRB Meetings and IRB Member and Consultant Conflict of Interest SOPs.
9. Primary reviewers provide recommendations to the IRB at the convened meeting on issues they determine do not meet the federal criteria for approval, are controverted, or need additional information.
10. If the primary reviewer is unable to attend the meeting, ORI staff provide the reviewer’s comments or recommendations for presentation to the IRB at the convened meeting.
11. The convened IRB assesses the CR materials using the federal criteria for approval (i.e., 45 CFR 46.111 and 21 CFR 56.111).
12. At the meeting, the IRB reviews the CR materials and any controverted issues and their resolution prior to voting. During discussion, the IRB members only raise controverted issues they determine do not meet the federal criteria for approval as specified in 45 CFR 46.111 and21 CFR 56.111. IRB approval verifies the IRB agrees with the assessment of the protocol and/or specific findings as described by the PI in the CR.  
13. The convened IRB makes the final determination on the outcome of the review. The primary reviewer or designated IRB member documents the IRB’s determinations on the IRB Continuation Review: Primary Reviewer Checklist. 

Expedited CR – Protocols Subject to the Old Common Rule (Approved before January 21, 2019) and FDA-regulated Protocols Subject to the Revised Common Rule (Approved on or after January 21, 2019) 

1. The Medical and Nonmedical Vice Chairs or designees serve as the expedited reviewer for expedited CRs. If the expedited reviewer has a conflict of interest (e.g., is study personnel on the protocol), is unavailable, or does not have the appropriate expertise to review the CR, ORI staff send the CR to the Chair, another Vice Chair, or a voting member of the IRB.
2. ORI staff assign the Vice Chair as the primary reviewer, giving the Vice Chair access to all information and materials for the CR submission, including:
   • A completed CR report that includes, when applicable: the number of subjects enrolled (including gender and minority status) and subjects withdrawn from the study;
   • A written summary and assessment of both unanticipated problems and available information regarding adverse events since the last IRB review; recent literature; complaints about the research; and any new significant findings (i.e., new findings and implications for subject participation) described;
   • A copy of the currently approved sponsor protocol for externally funded research (including any prior IRB approved modifications) and/or research description (summary which addresses all elements of criteria for approval); and if applicable:
   • A cover memo if it contains pertinent information to review the protocol;
   • Attachments (e.g., updates/changes, explanations)
   • Summary data and safety monitoring reports;
   • A clean and highlighted copy of the consent/assent form for which the investigator is seeking IRB approval, if requesting changes. If no changes are being made, only a clean copy of the consent/assent necessary;
   • Copies of signed consent forms and HIPAA Authorizations for the two most recently enrolled subjects, if applicable;
   • IRB Continuation Review: Primary Reviewer Checklist;
   • ORI staff recommendations, including HIPAA comments, if applicable.
3. If the expedited reviewer determines full review is necessary, he/she documents this requirement in the Reviewer’s Recommendations section of the IRB Continuation Review: Primary Reviewer Checklist. The expedited reviewer may also raise controverted issues he/she determines do not meet federal criteria and/or may request additional information. Upon receipt of the reviewer’s recommendation, ORI staff follow convened CR procedures.
4. When informed consent/assent is applicable, the expedited reviewer reviews the informed consent/assent process and document(s) submitted for re-approval to ensure accuracy and completeness.
5. ORI staff serve as intermediaries between the PI and the IRB expedited reviewer. However, the expedited reviewer may contact the PI directly for clarification. The reviewer documents any issues discussed with the PI in the CR materials.
6. The expedited reviewer documents in the CR materials any determinations pertaining to specific findings as mandated by federal regulations not previously addressed by the IRB. Expedited reviewer approval of the CR materials documents that the reviewer agrees with the PI’s assessment of the specific findings.
7. The expedited reviewer ensures that the PI provides any significant new findings that might relate to subjects’ willingness to continue participation in accordance with the regulations. The reviewer uses the IRB Continuation Review: Primary Reviewer Checklist as a prompt.
8. The expedited reviewer applies the same criteria for approval as outlined above for full review (i.e., applies 45 CFR 46.111 and 21 CFR 56.111, and informed consent regulatory criteria), and completes the IRB Continuation Review Primary Reviewer Checklist as documentation of his/her determination.
9. Expedited CR protocols are listed on the IRB agenda to advise members of the expedited CR reviews.

Expedited AAR Procedures – Expedited non-FDA-regulated Protocols Subject to the Revised Common Rule (Approved on or after January 21, 2019)

1. All Medical and Nonmedical expedited research protocols not regulated by the FDA, approved on or after January 21, 2019, requires an AAR unless there is documented IRB justification to require a CR. (FDA-regulated research and expedited studies with documented IRB justification to require a CR follow the Expedited Continuation Review procedures (#1-9) listed above.)
2. ORI staff assign the AAR submission to the Vice Chair or designee as the primary reviewer, giving the Vice Chair access to all information and materials including:
   • An update on the status of the research;
   • A written summary and assessment of both unanticipated problems and available information regarding adverse events since the last IRB review;
   • A copy of the consent/assent form for which the investigator is seeking IRB approval, if applicable (highlighted and clean versions if changes are being made);
   • Copies of signed consent forms and HIPAA Authorizations for the two most recently enrolled subjects, if applicable;
   • IRB Continuation Review: Primary Reviewer Checklist;
   • ORI staff recommendations, including HIPAA comments, if applicable.
3. The expedited reviewer determines: if the AAR is approved; if more information is required prior to approval; if the submission needs to undergo an expedited CR; or if the submission should undergo a CR by the convened board. If the reviewer determines that either an expedited or full board CR is necessary, he/she documents the justification for the determination in the Reviewer’s Recommendations section of the IRB Continuation Review: Primary Reviewer Checklist. Upon receipt of the expedited reviewer’s recommendation, ORI staff implement appropriate CR or AAR procedures (i.e., expedited or full CR).
4. AARs are listed on the IRB agenda to advise members of the expedited AARs reviews.

Approval Expiration 

1. If a PI fails to submit a CR or AAR or the IRB has not completed review by the end of the approval period, ORI notifies the PI that approval has expired. ORI staff inform the PI that research must cease and no new subject enrollment may occur. ORI staff also inform the PI that he/she should, if appropriate, notify subjects that the study approval has expired and, if applicable, it is his/her responsibility to notify the funding agency of the expiration of the IRB approval.
2. The PI may ask the IRB for permission to allow subjects currently participating to continue due to an overriding safety concern, ethical issues, or because it is in the best interest of the individual subjects. The IRB makes the determination when appropriate. The ORI or IRB notifies the PI of that determination.
3. If protocol approval has expired and the PI wants to re-activate or re-submit the study, the ORI requests either a document that verifies no research activities have occurred since the expiration (i.e., recruitment or enrollment of new subjects, interaction, intervention, or data collection from currently enrolled subjects, or data analysis) or a written summary of events that occurred from the PI during the expiration.
4. If the PI submits the CR/AAR materials/revisions after the end of approval period, the IRB requires a new initial review application along with the CR/AAR documents.
5. When CR/AAR and approval of a research study does not occur prior to the end of the approval period, the IRB does not report the expiration as a suspension of approval under Food and Drug Administration (FDA) or U.S. Department of Health and Human Services (HHS) regulations.

Review Outcome(s) 

1. For Full CR, an IRB member makes a motion, the motion is seconded, and the IRB members then vote for, against, or abstain from one of the following five actions:
   • APPROVED (Vote for a #1): IRB approval - A vote of #1 indicates the IRB concluded that the research and, if applicable, consent/assent forms meet the federal criteria for approval. The IRB’s approval vote verifies that the IRB members agree with the information/materials submitted for continuation of the protocol and/or specific findings described in the CR report by the PI.
   • REVISIONS and/or ADDITIONAL INFORMATION REQUIRED (Vote for a #2): A vote of # 2 indicates the IRB has approved the protocol pending submission of minor revisions and that the IRB has given the individual chairing the meeting (and/or other IRB member with appropriate expertise or qualifications) the authority to approve the minor revisions which do not involve substantive issues.
   • TABLED - Vote for a #3: A vote of #3 indicates the IRB withholds approval pending submission of major revisions/additional information. The requested revisions list the reasons for tabling. For some studies, the IRB may appoint one or more members of the IRB to discuss the reasons with the investigator. If the vote is for a #3, ORI staff schedule the PI’s response to the requested revisions for review by the full committee. The IRB does not require the PI to attend the future IRB meeting.
   • TABLED – Vote for a #4: A vote of #4 follows the same procedure as a vote of #3 except the PI needs to attend the future IRB meeting at which the IRB reviews his/her response to discuss or answer IRB concerns or questions. ORI staff notify the PI of the request for him/her to attend the future IRB meeting.
   • DISAPPROVED (Vote for a #5): A vote of #5 indicates the IRB disapproves the protocol. ORI staff send the investigator a letter describing the reasons for disapproving the protocol. This outcome usually occurs when the IRB determines the risk of the procedures outweighs any benefit or if the research does not meet the federal criteria.
2. The IRB determines during the convened meeting the approval period as appropriate to the degree of risk in the research, but not less frequently than once per year. The IRB may set a shorter approval period (i.e., for CR to occur more often than annually) for high risk protocols or protocols with a high risk/low potential benefit ratio. No approval period extends beyond one (1) year. When a protocol receives final approval, ORI staff document the approval period in the approval letter to the investigator. For Full CR, ORI staff include the approval period in the meeting minutes.
3. For expedited CRs, the reviewer may make the following determinations: 1) approved; 2) revisions and/or additional information required; 3) review by the full committee required. The reviewer exercises all the authority of the IRB except he/she may not disapprove the CR. Only the convened IRB may disapprove the submission.
4. For convened review, Full CRs, the date of the start of the approval period is the date of the convened meeting. When the outcome of the IRB vote is for a #2 (approved pending submission of minor revisions), ORI staff issue approval after the IRB Chair or the individual chairing the meeting reviews and approves the PI’s response. The approval period begins on the date on which the convened IRB reviewed the protocol and voted for a #2. For Expedited CR/AAR, the date of the start of the approval period is the date the expedited reviewer approves the CR/AAR.
5. For convened review, expedited AARs, the reviewer may make the following determinations: 1) approved; 2) revisions and/or additional information required; 3) expedited CR required; 4) CR review by the committee required. The reviewer exercises all the authority of the IRB except he/she may not disapprove the AAR. Only the convened IRB may disapprove the submission.
6. If the approval expires before approval of the CR/AAR, the reviewer can make a determination to allow subjects currently participating to continue in accord with procedures described in the section on approval expirations.
7. Upon request, ORI staff also send the PI a funding agency Certification of Approval form. (See the Mandated Reporting to External Agencies SOP.)
8. If the PI has concerns regarding the IRB decision/recommendations for changes in the study, he/she submits a written appeal that includes a justification for changing the IRB decision. The PI sends the appeal to the ORI. The applicable reviewer or convened IRB reviews the appeal. The appeal determination is final. 

REFERENCES

21 CFR 56.108(a)(1)&(2)

21 CFR 56.109(f)

21 CFR 56.110

21 CFR 56.111

21 CFR 56.115(a)(3)&(7)

45 CFR 46.108

45 CFR 46.109(f)

45 CFR 46.111 

45 CFR 46.115(a)(3)&(7)

45 CFR 160

45 CFR 164

Approved By: ORI Director, Nonmedical IRB Chair, Medical IRB Chair

Date First Effective: May 15, 2005

Last Revision Date: May 14, 2023

Revision #11

OBJECTIVE

To describe the policies and procedures for reviewing a modification to a previously approved protocol

GENERAL DESCRIPTION

Investigators may not initiate any changes in research procedures or consent/assent form(s) without prior IRB review and approval, except where necessary to eliminate apparent immediate hazards to the subject. Examples of modifications that require IRB review include but are not limited to changes in: 

• Study personnel;
• Advertising materials (flyers, radio spots, etc.);
• Research procedures;
• Subject populations (e.g., age range);
• Location where research will be conducted;
• Consent/assent forms;
• Recruitment procedures; or
• Date for completion of study.

If the investigator makes and implements protocol changes without prior IRB approval in order to eliminate apparent hazards to the subject(s), the investigator must immediately report the changes to the IRB. The IRB will review the changes and make a determination as to whether the changes are consistent with the subject’s continued welfare (See Protocol Violations SOP).

Investigators must promptly notify the IRB in writing of any change in protocol status, such as suspension, discontinuation or completion of a study. (See the Continuation Review SOP and the Study Closure SOP for procedures on reporting an activity status change to the IRB.) Change in status includes any suspension or pause in research activities due to test article availability lasting longer than two weeks.

Definition

Modifications are defined as changes that impact the overall protocol.

RESPONSIBILITY

Execution of SOP: Principal Investigators (PI)/Study Personnel (SP), IRB Chair, IRB, Office of Research Integrity (ORI) Staff, ORI Research Privacy Specialist

PROCEDURES

Submission of Modifications

1. The PI is responsible for submitting a modification request (MR) to the ORI prior to the implementation of any change.
2. The PI updates/alters the sections of the IRB application as applicable. 

3. An MR must include all approved documents unless the document is being updated as part of the MR. In this case, the PI deletes the currently approved version of the document and attaches the updated document along with a highlighted/tracked changes version of the updated document.

   Please note: Modifications can be requested within a continuation review (CR) submission. A PI cannot submit a separate MR and CR simultaneously. 

Screening of Submissions

1. ORI staff screen the MR for completeness and accuracy. ORI staff request additional information from the PI as necessary.
2. If UK is the reviewing IRB for a reliance study, ORI staff contact the Reliance Team to determine if the proposed changes conflict with the reliance agreement/communication plan and/or local context form.
3. ORI staff determine if the modification involves use of a medical device under FDA jurisdiction (i.e., collecting safety or efficacy data), if the requested changes reference an instrument, apparatus, reagent, machine, implement and/or device. If so, ORI staff screen the application to ensure the PI has provided all relevant materials (e.g., device labeling, indications, risk justification), and included FDA language in the informed consent and HIPAA authorization.  
4. ORI staff consult applicable sources to determine if the modification involves use of or testing of products under FDA jurisdiction (i.e., use beyond the course of medical practice) if the requested change references a drug, biologic, therapeutic dietary supplement, substance affecting structure or function of the body, and/or product intended to diagnose, cure, mitigate, treat, or prevent disease. If so, ORI staff ensure the PI has provided all relevant materials (e.g., product labeling, investigator brochure) and included FDA language in the informed consent and HIPAA authorization.
5. ORI staff ensure relevant materials are available for IRB review as needed if the modification adds vulnerable populations or requires documentation of specific regulatory findings.
6. ORI staff may also secure additional review (i.e., prisoner representative) depending on the nature of the requested change, if applicable. The IRB reviewer in such cases is responsible for applying the relevant regulatory requirements or ethical principles.
7. ORI staff screen changes to consent/assent forms for apparent issues (e.g., absence of ORI’s toll-free number, use of incorrect/unapproved versions). ORI staff alert the IRB reviewer of any omissions or inconsistencies. The IRB has final authority for requiring consent/assent changes.
8. ORI staff screen changes to study personnel (SP) to ensure that all new SP have completed the required human subject protection training. If SP have not completed the required training, ORI staff inform the PI that the request cannot be approved by the IRB until the required training has been completed. ORI staff ask the PI whether they wish to remove the SP in question from the MR. Alternately, the PI may choose to wait for approval until the SP in question complete the training. In that case, ORI staff assigns the MR to the IRB after SP training is complete.
9. ORI staff select the IRB Chair or other IRB member as the primary reviewer.
10. ORI staff screen for compliance with HIPAA regulatory requirements. ORI staff assign the MR to the Research Privacy Specialist (RPS) to review the submission in accordance with the HIPAA in Research SOP when applicable. 

Administrative Review Procedures

1. ORI staff may approve an MR submission as an administrative change if the request only involves adding study personnel, without removing or replacing other personnel, or making any other changes to the protocol, since the IRB made the initial determination that the number of staff listed on the study is adequate and the credentials and/or described qualifications are representative of the appropriate expertise needed to conduct the study.
2. For exempt review protocols, ORI staff approve an MR submission as an administrative change if the edit that is clear and straightforward.  This includes, for example:
   • adding study personnel, without removing or replacing other personnel, since the IRB made the initial determination that the number of staff listed on the study is adequate and the credentials and/or described qualifications are representative of the appropriate expertise needed to conduct the study;
   • directive requested revisions made in response to the IRB’s review;
   • addition of a letter of support from a non-UK research site (if site addition was reviewed by reliance);
   • addition or minor modifications to recruitment materials, advertisements;
   • changes to study duration or schedule, (e.g., extending end date of study, adding an additional semester of the same data collection activities);
   • minor changes to study population in non-therapeutic studies (e.g., raising inclusion criteria from age 20 to 30);
   • small changes to incentives (e.g., $25 instead of $15 gift card); and
   • minor changes to data collection instruments in non-limited review protocols.

Minor changes are limited to directive revisions such as grammatical edits, new dates, expanding a Likert scale, clarifying an item, or adding questions that would not change the subject matter or overall time commitment.  Revisions that are substantive, ambiguous, open-ended, or involve sensitive topics are not minor. 

Expedited Review Procedures 

1. The IRB Chair or designated IRB member conducts an MR review using expedited procedures if the requested changes are minor. A minor change is one which makes no substantial alteration in:
   • The level of risk to subjects;
   • The research design or methodology;
   • The subject population;
   • Qualifications of the research team;
   • The facilities available to support the safe conduct of the research; or
   • Any other factor that would warrant review of the proposed changes by the convened IRB
2. The IRB Chair or designated IRB member reviews the MR undergoing expedited review using standard expedited review procedures. The expedited reviewer exercises all the authority of the IRB except the reviewer cannot disapprove the research or research activity. The listing of the expedited review on an agenda for the convened IRB serves to advise the IRB of the expedited review.
3. The IRB Chair or designated IRB member is responsible for reviewing the proposed modification to determine whether the modified research continues to fulfill the criteria for IRB approval, and documents their determination on the Modification Reviewer Signature Page. 

Full Review Procedures

1. ORI staff place an MR on an agenda for a convened meeting, following procedures outlined in the Initial Full Review SOP, when the MR involves more than just minor changes, an IRB Chair or designated IRB member recommends full review, or the sponsor or PI specifically request full review procedures.
2. ORI staff invite the PI to attend the meeting if the IRB requires that they attend. The full IRB reviews the MR, following procedures outlined in the Initial Full Review SOP, and applies the federal criteria for approval as applicable to the request.
3. Approximately 5-10 days prior to the meeting, ORI staff close the agenda. The MR and the protocol materials affected by the proposed modification become available to the full board for review.
4. The IRB Chair or designated IRB member who serve as the primary reviewer reports recommendations to the IRB at the convened meeting. The IRB Chair or designated IRB member makes recommendations on issues they determine do not meet the federal criteria for approval, involve controverted issues, or need additional information. If the IRB Chair or designated IRB member is unable to attend the meeting, written comments or recommendations are provided to the IRB at the convened meeting.
5. The convened IRB reviews and votes on the MR consistent with procedure outlined in the Initial Full Review SOP. The IRB Chair or designated IRB member documents the IRB determination on the Modification Reviewer Signature Page. 

Review Outcome(s)

1. ORI staff notify the PI of the IRB’s decision following the procedures in the Initial Full and Initial Expedited Review SOP.
2. The end date of the protocol approval period remains the same as that assigned during initial or continuation review when the IRB approves a modification.
3. If the PI has concerns regarding the IRB decision/recommendations for changes in the study, they may submit their concerns via a written appeal that includes justification for changing the IRB decision. The PI sends the request to the ORI. The expedited reviewer, IRB Chair, or convened IRB review the appeal. The appeal determination is final. 

REFERENCES

21 CFR 56.110(b)(2)

45 CFR 46.110(b)(2)

45 CFR 46.111

21 CFR 56.111

21 CFR 312

21 CFR 812

Approved By: ORI Director, Nonmedical IRB Chair, Medical IRB Chair

Date First Effective: May 15, 2005

Last Revision Date: March 15, 2019

Revision #10

Previously a part of SOP C2.0300 Modification – IRB Review of Changes 

OBJECTIVE

To describe the policies and procedures for requesting IRB review of a one-time deviation from the currently approved protocol or one-time exception to the currently approved enrollment criteria prior to implementation.

GENERAL DESCRIPTION

Investigators must obtain prospective IRB approval for deviations from the IRB approved protocol or research procedures, except where necessary to eliminate apparent immediate hazards to the subject. Investigators are responsible for obtaining both IRB approval and if applicable, sponsor approval prior to implementing a deviation/exception.  Investigators are responsible for compliance with sponsor or local policies prohibiting protocol exceptions (i.e., National Cancer Institute). 

Definitions

Exceptions or deviations are one-time changes that impact individual subjects and do not change the overall protocol. Investigators may not implement these changes without prior IRB review and approval except where necessary to eliminate apparent hazards to the subject(s).

The IRB considers the enrollment of a research subject in a protocol who either fails to meet current IRB approved protocol inclusion criteria or who falls under protocol exclusion criteria to be a protocol exception.

The IRB considers a departure from the current IRB approved procedures that impact an individual subject to be a protocol deviation.

If the investigator makes and implements protocol changes (i.e., exceptions or deviations) without prior IRB approval in order to eliminate apparent hazards to the subject(s), the investigator must immediately report the changes to the IRB. The IRB will review the changes and make a determination as to whether the changes are consistent with the subject’s continued welfare (See Protocol Violations SOP).

RESPONSIBILITY

Execution of SOP: Principal Investigators (PI)/Study Personnel (SP), IRB Chair, IRB, Office of Research Integrity (ORI) Staff, ORI Research Privacy Specialist

PROCEDURES

Submission of Deviations and Exceptions

1. The PI is responsible for submitting a deviation/exception request to the study sponsor, as applicable, and the IRB prior to the implementation of any change.
2. The PI answers all questions on the Deviation or Exception Form.
3. The PI includes additional documentation to be considered for approval, when applicable. 

Screening of Submissions

1. ORI staff screen the deviation/exception for completeness and accuracy. ORI staff request additional information from the PI as necessary.
2. If UK is the reviewing IRB for a reliance study, ORI staff contact the Reliance Team to determine if the proposed deviation or exception conflicts with the reliance agreement/communication plan and/or local context form.
3. ORI staff ensure relevant materials are available for IRB review as needed if the deviation/exception adds vulnerable populations or requires documentation of specific regulatory findings.
4. ORI staff may also secure additional review (i.e., prisoner representative) depending on the nature of the requested change. The reviewer in such cases is responsible for applying the applicable regulatory requirements or ethical principles.
5. ORI staff select the IRB Chair or other IRB member as the primary reviewer.
6. ORI staff screen for compliance with HIPAA regulatory requirements. ORI staff assign the deviation/exception to the Research Privacy Specialist (RPS) to review the submission in accordance with the HIPAA in Research SOP when applicable. 

Expedited Review Procedures 

1. The IRB Chair or other IRB member conducts a deviation or exception request review using expedited procedures if the requested changes are minor. A minor change is one which makes no substantial alteration in:
   • The level of risk to subjects;
   • The research design or methodology;
   • The subject population;
   • Qualifications of the research team;
   • The facilities available to support the safe conduct of the research; or
   • Any other factor that would warrant review of the proposed changes by the convened IRB
2. The IRB Chair or designated IRB member reviews the deviation or exception undergoing expedited review using standard expedited review procedures. The expedited reviewer exercises all the authority of the IRB except the reviewer cannot disapprove the research. The listing of the item on an agenda for the convened IRB serves to advise the IRB of the expedited review. 
    
3. The IRB Chair or designated IRB member is responsible for reviewing the proposed deviation or exception request, determining whether the research continues to fulfill the criteria for IRB approval, and documenting his/her determinations on the Protocol Deviation/Exception Signature Page. 

Full Review Procedures

1. ORI staff place the deviation or exception request on an agenda for a convened meeting, following procedures outlined in the Initial Full Review SOP when the request involves substantial deviations or exceptions, an IRB Chair or designated IRB member recommends full review, or the sponsor or PI specifically request full review procedures.
2. ORI staff invite the PI to attend the meeting if the IRB requires that he/she attend. The convened IRB reviews the deviation or exception request following procedures outlined in the Initial Full Review SOP and applies the federal criteria for approval as applicable to the request.
3. Approximately 5-10 days prior to the meeting, ORI staff close the agenda. The deviation or exception request becomes available to the full board for review.
4. The IRB Chair or designated IRB member who serves as the primary reviewer reports recommendations to the IRB at the convened meeting. The IRB Chair or designated IRB member makes recommendations on issues he/she determines do not meet the federal criteria for approval, involve controverted issues, or need additional information. If the IRB Chair or designated IRB member is unable to attend the meeting, written comments or recommendations are provided to the IRB at the convened meeting.
5. The convened IRB reviews and votes on the deviation or exception request consistent with procedure outlined in the Initial Full Review SOP. The IRB chair or designated IRB member documents the IRB determination on the Protocol Deviation/Exception Signature Page. 

Review Outcome(s)

1. ORI staff notify the PI of the IRB’s decision following the procedures in the Initial Full and Initial Expedited Review SOP.
2. The end date of the protocol approval period remains the same as that assigned during initial or continuation review when the IRB approves a deviation or exception request.
3. If the PI has concerns regarding the IRB decision/recommendations for changes in the study, he/she may submit his/her concerns via a written appeal that includes justification for changing the IRB decision. The PI sends the request to the ORI. The expedited reviewer, IRB Chair, or convened IRB review the appeal. The appeal determination is final.

REFERENCES

21 CFR 56.110(b)(2)

45 CFR 46.110(b)(2)

45 CFR 46.111

21 CFR 56.111

21 CFR 312

21 CFR 812

Approved By: ORI Director, Nonmedical IRB Chair, Medical IRB Chair

Date First Effective: May 30, 2005

Last Revision Date: February 12, 2025

Revision #11

OBJECTIVE

To describe the policies and procedures for prompt investigator reporting of unanticipated problems or adverse events, investigator reporting of problems/adverse events that do not meet the prompt reporting requirements, and the procedures for Institutional Review Board (IRB) review of investigator reports for University of Kentucky (UK) studies  

GENERAL DESCRIPTION

Regulatory guidance provided in 45 CFR 46.108(a)(4) and 21 CFR 56.108(b) requires the IRB to have written procedures for ensuring prompt reporting to the IRB, appropriate University officials, and applicable regulatory agencies of any unanticipated problems involving risks to human subjects or others. In response to the regulatory obligation, the UK IRB utilizes a three-category reporting system to facilitate review of reports and determinations about whether the problem/event raises new concerns about 1) risks to subjects or others; 2) the risk/benefit ratio; 3) the approved informed consent document; and the 4) need for re-consent.

The UK reporting categories are as follows:

1. Prompt Reporting to the IRB of an unanticipated problem involving risks to subjects or others or all internal research-related deaths and external unanticipated research-related deaths (including anticipated death occurring more frequently than expected);
2. Non-Prompt Reporting to the IRB of anticipated problems/anticipated serious adverse events or unrelated deaths (required by sponsor but not by UK);
3. Continuation Review Reporting to the IRB includes a written summary of both unanticipated problems and available information regarding adverse events since the last IRB review. The summary must include the PI’s assessment of whether the problems/adverse events warrant changes to the protocol, consent process, or risk/benefit ratio. For multisite studies, the written summary should describe external events determined to be unanticipated problems involving risks to subjects. 

The policy on prompt reporting, non-prompt reporting, and continuation review reporting of problems/events is the basis for the SOP. The policy details the IRB requirements for reporting, including adverse events and unanticipated problems involving risks to research subjects and others. In addition to the three categories, there are two broad types of reports, internal and external. 

Definitions

An internal event/problem is one that occurs with research subjects enrolled in a project approved by the UK IRB and directed by an investigator employed by the University or one whose project is under the purview of the UK IRB. 

An external event/problem is one that occurs with research subjects enrolled in multi-center research projects that do not fall under the purview of the UK IRB. 

See UK IRB Policy on Unanticipated Problem and Safety Reporting for additional definitions.

RESPONSIBILITY

Execution of SOP: IRB Chair, IRB, Office of Research Integrity (ORI) Staff, Principal Investigator (PI)/Study Personnel 

PROCEDURES

UK Reporting Requirements for Prompt Reporting of Problems/Adverse Events 

1. The PI reports unanticipated problems involving risks to subjects or others and internal research-related deaths using the UK Internal or External Prompt Reporting Form. Unanticipated problems involving risks to subjects or others are problems/adverse events which are unexpected AND related to the study procedures AND suggest that the research places subjects or others at a greater risk of harm (including physical, psychological, economic, or social harm) than was previously known or recognized. For multi-site studies, the PI reports external events determined to be unanticipated problems involving risks to subjects or others AND unanticipated research-related deaths using the UK External Prompt Reporting Form.
2. The PI reports unanticipated life-threatening events and unanticipated adverse device effects (UADE) within seven (7) calendar days of his/her receipt of the information and all other unanticipated problems involving risks to subjects or others within 14 calendar days of his/her receipt of the information. Institutional policy requires the investigator to provide follow-up reports on life-threatening events within 14 calendar days of his/her receipt of the information.
3. The PI reports deaths meeting prompt reporting criteria using the appropriate UK Internal/External Prompt Reporting Form immediately upon investigator receipt of the information (i.e., within 48 hours).
4. The IRB may request more stringent requirements for reporting events for individual research studies if the respective committee determines it to be necessary.

Submissions/Screening and Review of Internal Problems/Events: Prompt Report

1. The PI makes the preliminary determination if the event meets the criteria for an IRB reportable internal problem/event in accordance with the UK Policy on Unanticipated Problem and Safety Reporting.
2. The PI completes the UK Internal Prompt Reporting Form and submits the form to the ORI in the time period outlined in the IRB Policy on Unanticipated Problem and Safety Reporting.
3. If the PI recognizes the problem/event involves risks to subjects or others and the information is not already in the consent/assent document(s), he/she submits a revised consent/assent form(s) as well as a highlighted version of the document(s) for review and approval by the IRB.
4. ORI staff screen the report to determine whether it is complete and place the report on an IRB agenda.
5. Staff assign the report(s) and related material(s) to the IRB Chair or designee who serves as the primary reviewer.
6. The primary reviewer may review related material(s) including but not limited to: the complete or relevant portions of the IRB application; documents revised as a result of the problem/event; or documents which provide additional assessments or summary information. The individual serving as primary reviewer receives, at a minimum, the completed UK Prompt Reporting Form.
7. After reviewing the materials, the primary reviewer makes comments in the protocol in the electronic system for review by the convened IRB.
8. The IRB reviews internal events and problems at a convened IRB meeting using initial full review procedures.
9. If the study is federally funded (e.g., by the U.S. Department of Health and Human Services), or is regulated by the Food and Drug Administration (FDA), additional IRB reporting requirements may be in effect. (See the Mandated Reporting to External Agencies SOP.)

Review Outcome(s)

1. For all problems/events submitted under the IRB’s prompt reporting policy, the IRB determines whether the problem/event meets the UK definition of unanticipated problem involving risks to subjects or others. If the unanticipated problem/event involves risks to subjects or others, the IRB follows the established reporting policy. (See Mandated Reporting to External Agencies SOP.) The IRB actions may include but are not limited to:
   • Acknowledgment/acceptance without further recommendation;
   • A request for further clarification from the investigator;
   • Changes in the protocol (e.g., additional test or visits to detect similar events in a timely fashion);
   • Changes in the consent/assent form(s);
   • A requirement to inform subjects already enrolled or to re-consent (e.g., when the information may relate to the subject’s willingness to continue to take part in the research);
   • A change in frequency of continuation review;
   • Further inquiry into other protocols utilizing the particular drug, device, or procedure in question;
   • Suspension or termination of the study; or
   • Request for quality improvement review; or
   • Other actions deemed appropriate by the IRB.
2. If the IRB acknowledges/accepts the internal problem/event without recommendation, ORI staff generate a letter and send it to the PI indicating the review outcome.
3. If the committee requests clarification(s), additional information, or revisions, ORI staff notify the PI of the need for additional information and/or changes.
4. The PI responds to IRB requests for information or revisions and sends the response to the ORI. ORI staff assign investigator responses to the IRB Chair for further review. The IRB Chair may forward the response to the entire IRB for additional review, request additional information, or acknowledge/accept the response without recommendation.
5. If the PI has concerns regarding the IRB’s decision/recommendation for changes in the study, he/she may submit an appeal that includes justification for changing the IRB decision. The PI sends the request to the ORI. The IRB Chair or the convened IRB reviews the appeal. The IRB determination of the review of the appeal is final.

Submissions/Screening and Review of External Problems/Events: Prompt Report

1. The PI makes a preliminary determination whether the external event meets the criteria for an unanticipated problem involving risks to subjects or others in accord with the UK IRB Policy on Unanticipated Problem and Safety Reporting.
2. The PI completes the UK External Prompt Reporting Form and submits it to the ORI in the time period outlined in the UK IRB Policy on Unanticipated Problem and Safety Reporting.
3. ORI staff screen the External Prompt Reporting Form for completeness.
4. ORI staff assign the External Prompt Reporting Form(s), any attached external reports of problems/events, and related material(s) to the IRB Chair or designee. The IRB Chair or designee serves as an expedited reviewer using expedited review procedures. The expedited reviewer may receive related material(s) including but not limited to documents revised as a result of the problem/event and/or documents which provide additional assessments or summary information.
5. If the expedited reviewer determines the unanticipated event is an unanticipated problem involving risks to subjects or others, he/she completes the External Prompt Reporting Form. ORI staff schedule review of the unanticipated event(s) by the convened IRB.
6. If the expedited reviewer determines the event is not an unanticipated problem involving risks to subjects or others, he/she documents his/her review by signing the original report and list any concerns/recommendations.
7. ORI staff includes the external problem/event on the IRB agenda for a convened meeting. Any IRB member may request to review the entire IRB file (paper) or access in the electronic system and the expedited reviewer’s recommendations.

Review Outcomes

1. The IRB actions may include but are not limited to:
   • Acknowledgment/acceptance without further recommendation;
   • A request for further clarification from the investigator;
   • Changes in the protocol (e.g., additional tests or visits to detect similar events in a timely fashion);
   • Changes in the consent/assent form(s);
   • A requirement to inform subjects already enrolled or to re-consent (e.g., when the information may relate to the subject’s willingness to continue to take part in the research);
   • A change in frequency of continuation review;
   • Further inquiry into other protocols utilizing the particular drug, device, or procedure in question;
   • Recommendation for full review;
   • Request for quality improvement program review; or
   • Other actions deemed appropriate by the IRB.
2. If the IRB acknowledges/accepts the external unanticipated problem/event without recommendation, ORI staff send a letter to the PI indicating the review outcome.
3. If the reviewer requests clarification(s), additional information, or revisions, ORI staff notify the PI of the need for additional information and/or changes.
4. The PI responds to requests for information or revisions and submits the response to the ORI. ORI staff assign responses to the IRB Chair or designee for further review. The IRB Chair or designee may request additional information, recommend full review, or acknowledge/accept the response without recommendation.
5. The IRB Chair or designee reviews any replies from the investigators on behalf of the committee unless the IRB Chair or designee determines the reply needs further review by the convened IRB. The IRB Chair or designee documents acknowledgment/acceptance of the report, and ORI staff notify the PI in writing in a timely manner.
6. If the PI has concerns regarding the IRB decision/recommendation for changes in the study, he/she may submit an appeal that includes justification for changing the IRB decision. The PI sends the request to the ORI. The IRB Chair, designee, or the convened IRB reviews the appeal. The IRB determination of the review of the appeal is final. 

Reporting of Problems/Events that Do Not Meet Prompt Reporting Requirements (Non-Prompt Reporting)to the IRB (required by Sponsors, not required by the UK IRB)

1. If the sponsor requires IRB documentation of submission of reports of events, which do not meet the UK IRB’s prompt reporting requirements to the IRB, the PI may submit these events to the IRB using the IRB Cover Form for Non-Prompt Reporting of Problems/Adverse Events.
   1. ORI staff assign the Non-Prompt Report and its attachments to the IRB Chair or designee.
   2. If the IRB Chair or designee determines the PI should report the problem(s)/event(s) per the prompt reporting requirements, he/she documents this on the Non-Prompt Report materials. ORI staff notify the PI of the requirement to submit the Internal/External Prompt Reporting Form.
2. ORI staff sends a letter from the IRB acknowledging the materials received although the problem(s)/event(s) does not meet the UK IRB’s prompt reporting requirements.

Continuation/Annual Administrative Review Reporting of Problems and/or Adverse Events

1. The PI submits a written summary of both unanticipated problems and available information regarding adverse events since initial or the latest continuing IRB review at Continuation/Annual Administrative Review. For multisite studies, the written summary should describe external events determined to be unanticipated problems involving risks to subjects or others. The summary must include the PI’s assessment of whether the problems/adverse events warrant changes to the protocol, consent process/documents, or risk/benefit ratio. (For policies and procedures for conducting continuation review, see the Continuation and Annual Administrative Review SOP.)

References

21 CFR 56.108(b)

45 CFR 46.108(a)(4)

Approved By: ORI Director, Nonmedical IRB Chair, Medical IRB Chair

Date First Effective: July 8, 2005

Last Revision Date: May 9, 2019

Revision #6

OBJECTIVE

To describe the policies and procedures for reviewing a protocol violation

GENERAL DESCRIPTION

Federal regulations require the Institutional Review Board (IRB) to review proposed changes in any research activity and to ensure that the investigator does not initiate such changes in approved research without IRB review and approval except when necessary to eliminate apparent immediate hazards/risks to the subject [45 CFR 46.108(a)(3)(iii) and 21 CFR 56.108(a)(4)].

Research activity includes all aspects of the conduct of the research study (e.g., recruitment methods, consent process, procedures used to protect privacy and confidentiality, etc.) and all of the information outlined in the IRB application/protocol reviewed and approved by the IRB. 

Definitions

A protocol violation is any exception or deviation involving a single subject that is not approved by the IRB prior to its initiation or implementation. These protocol violations may be major or minor violations. (See Modification, Deviation and Exception SOP for definitions of exception and deviation.)

A major violation is one that may impact subject safety, make a substantial alteration to risks to subjects, or any factor determined by the IRB Chair or an IRB member to warrant a review of the violation by the convened IRB. Examples of major violations may include, but are not limited to:

• Failure to obtain informed consent (i.e., there is no documentation of informed consent, or informed consent is obtained after initiation of study procedures);
• Enrollment of a subject who did not meet all inclusion/exclusion criteria;
• Performing a study procedure not approved by the IRB;
• Failure to report serious unanticipated problems/adverse events involving risks to subjects to the IRB and (if applicable), the sponsor;
• Failure to perform a required lab test that, in the opinion of the PI, may affect subject safety or data integrity;
• Drug/study medication dispensing or dosing error;
• Study visit conducted outside of required time frame that, in the opinion of the PI or IRB, may affect subject safety;
• Failure to follow the safety monitoring plan. 

A minor violation is a violation that does not impact subject safety or does not substantially alter risks to subjects. Examples of minor violations may include, but are not limited to:

• Implementation of unapproved recruitment procedures;
• Missing signed and dated consent form;
• Missing pages of executed consent form;
• Inappropriate documentation of informed consent, including:
  • Missing subject signature;
  • Missing investigator signature;
  • Copy not given to the person signing the form;
  • Someone other than the subject dated the consent form;
  • Individual obtaining informed consent not listed on IRB approved study personnel list.
• Use of invalid consent form (i.e., paper consent form without IRB approval stamp or outdated/expired consent form);
• Failure to follow the approved study procedure that, in the opinion of the PI, does not affect subject safety or data integrity;
  • Study procedure conducted out of sequence;
  • Omitting an approved portion of the protocol;
  • Failure to perform a required lab test;
  • Missing lab results;
  • Enrollment of ineligible subject (e.g., subject’s age was 6 months above age limit);
  • Study visit conducted outside of required timeframe.
• Over-enrollment.

RESPONSIBILITY 

Execution of SOP: Principal Investigator (PI)/Study Personnel, IRB Chair, IRB, Office of Research Integrity (ORI) Research Compliance Officer (RCO), ORI Staff

PROCEDURES

Submission of Protocol Violations

1. The PI submits all protocol violations that occur during the course of a study to the IRB immediately upon discovering them and/or within fourteen (14) calendar days of the occurrence. The PI or designee completes and submits the IRB Protocol Violation Report with required attachments to the ORI.
2. The PI also reports all protocol violations to the sponsor, if applicable, following the sponsor’s requirements. 

Screening of Submissions

1. ORI staff screen the IRB Protocol Violation Report for completeness and accuracy. If the submission is incomplete or inaccurate, ORI staff either return it to the PI or continue to process the submission but request additional information from the PI, which they forward to the IRB.
2. If UK is the reviewing IRB for a reliance study, ORI staff contact the Reliance Team to determine if the reliance agreement/communication plan stipulates reporting requirements for the protocol violation.
3. ORI staff screen submitted protocol violations to determine whether the violations involve vulnerable populations or require documentation of specific regulatory findings. If either of the above applies, ORI staff advise the IRB of any regulatory requirements the IRB should address in conducting the review. The IRB is responsible for applying the regulatory requirements.
4. ORI staff screen submitted protocol violations for HIPAA concerns and follow the procedures outlined in the HIPAA in Research SOP regarding noncompliance. Investigators working in a UK covered entity must comply with the UK Medical Center’s HIPAA policies and procedures.    

Determining Mechanism of Review (i.e., Expedited vs. Convened)

1. ORI staff send the IRB Protocol Violation Report, including any applicable attachments, to the IRB Chair. If the IRB Chair is not available, ORI staff may send the report to another member of the IRB.
2. The IRB Chair or IRB member makes a determination regarding whether the violation is major or minor and whether to review the violation using convened or expedited review procedures, respectively. If the violation is minor, the IRB Chair or IRB member conducts the review using expedited procedures.
3. If the sponsor or the PI specifically requests convened review procedures for a protocol violation which the IRB Chair has determined to be minor, ORI staff place the protocol report on an agenda for full review following procedures in the Initial Full Review SOP.

Expedited/Full Review Procedures 

1. The IRB Chair or a designated IRB member conducts expedited review using standard expedited review procedures. (See Expedited Initial Review SOP)
2. If the protocol violation report undergoes full review, the IRB Chair or designated IRB member has the option to invite the investigator to attend the meeting to answer any questions or concerns that the IRB may have regarding the protocol violation.
3. ORI staff notify the PI in writing if he/she must attend an IRB meeting. ORI staff schedule the submission for review and provide the IRB Protocol Violation Report to the IRB. The full IRB reviews the protocol violation using procedures outlined in the Initial Full Review SOP.
4. If the IRB determines that the violation is reportable to external agencies, ORI staff notify the ORI Research Compliance Officer (RCO). The ORI RCO or designee prepares a report to the applicable federal agency and maintains records as outlined in the Mandated Reporting to External Agencies SOP. 

Review Outcome(s)

1. The IRB/ORI staff handle the review and outcome of review as outlined in the Modification--IRB Review of Changes SOP and Deviation and Exceptions--IRB Review of Changes SOP and/or, if applicable, the Termination or Suspension of Research by the IRB SOP.
2. The convened IRB may, if appropriate, make a determination that the protocol violation(s) constitute “serious” or “continuing noncompliance,” or an “unanticipated problem involving risks to subjects or others” as defined in the Noncompliance SOP.
3. If the PI has concerns regarding the IRB’s decision, he/she may submit an appeal that includes justification for changing the IRB decision. The PI sends the request to the ORI. The IRB Chair or the convened IRB reviews the appeal. The IRB determination of the review of the appeal is final. 

REFERENCES

21 CFR 56.108(a)(4)

45 CFR 46.108(a)(3)(iii)

Approved By: ORI Director, Nonmedical IRB Chair, Medical IRB Chair

Date First Effective: June 10, 2005

Last Revision Date: July 18, 2011

Revision #4

OBJECTIVE

To describe Institutional Review Board (IRB) policy and procedures for conducting reviews of Health Insurance Portability and Accountability Act (HIPAA) research authorization forms, waiver of authorization requests, de-identification forms, and coordination with the University of Kentucky’s HIPAA Privacy Officer

GENERAL DESCRIPTION 

The IRB reviews HIPAA research de-identification, research authorization, and research waiver of authorization requests for any investigator obtaining protected health information (PHI) from a UK covered entity (CE) department.  Although federal regulations do not require IRBs to review authorization forms or de-identification requests, UK made a decision to review authorization forms and de-identification requests as a service to its researchers and to assist them in complying with the HIPAA Privacy Rule.  All other HIPAA research issues such as preparatory work, decedent research, limited data sets, public health activities, business associate agreements, privacy notice, and accounting of disclosures fall under the jurisdiction of UK’s Privacy Officer.

Definitions

Protected health information is defined as any of the 18 identifiers listed in the HIPAA Privacy Regulations in combination with health information that is created or maintained by a UK covered entity (CE) department that relates to the past, present, or future physical or mental health or conditions of an individual.

A UK covered entity department is defined as any department that provides services that meets the definition of health care provider, health plan, or health care clearinghouse and bills patients/subjects electronically.  UK legal counsel determined which UK departments fall within UK’s CE. 

A business associate agreement is defined as a contract where a person or entity performs certain functions or activities that involve the use and/or disclosure of PHI.

Options for Obtaining Protected Health Information

An investigator has the following six options for obtaining PHI from the University of Kentucky (UK) for research purposes:   

• De-identified Information - health information that cannot be linked to an individual;
• Authorization - a document signed by the subject that gives the researcher permission to use/disclose PHI collected during the research study for defined purposes;  
• Waiver of Authorization - a request to forgo the authorization requirement based on the fact that the disclosure of PHI is a minimal risk to the subject and the research can not practically be done without access to/use of PHI;
• Limited Data Set - a subset of identifiers that contain the following elements: city, state, zip code, date of birth, death, or date of service;
• Preparatory Work - PHI reviewed for the purpose of designing a research study or identifying potential subjects. PHI cannot be removed from the CE during the review; or
• Decedent Research - research where PHI is collected from a subject(s) that is deceased prior to the initiation of the study.

RESPONSIBILITY 

Execution of SOP: IRB Chair, IRB Members, Principal Investigators (PI)/Research Staff, ORI Staff, Research Privacy Specialist (RPS), UK Privacy Officer, Research Compliance Officer (RCO) 

PROCEDURES 

General Procedures 

1. Investigators working in a UK CE department comply with the UK Medical Center’s HIPAA educational requirements.
2. IRB members do not review any research authorizations, waiver of authorization, or de-identification requests in which they have a conflict of interest. (See IRB Member and Consultant Conflict of Interest SOP for additional information.)
3. UK does not conduct the HIPAA privacy review for other institutions for which UK IRB serves as the IRB of record. 

Research Authorization Review Procedures

1. The PI makes a preliminary assessment to determine whether his/her protocol needs a research authorization form.  A PI may call the ORI if he/she needs assistance in determining the HIPAA review type.
2. The PI submits his/her IRB application (i.e., exempt, expedited, or full) and authorization form to the ORI.  The PI uses the IRB’s Model Authorization Form, which includes all federally and institutionally mandated criteria.
3. If the investigator includes a HIPAA Authorization Form in the IRB submission or checks “HIPAA” in the application, or if there are any HIPAA concerns, ORI staff forward the IRB application to the ORI Research Privacy Specialist for review.
4. The RPS reviews protocols forwarded by ORI staff and determines whether the study is regulated by the HIPAA Privacy Rule and if an authorization form is appropriate for the study.  The RPS reviews the authorization form to ensure that all federally and institutionally mandated criteria are in the document and submits written recommendations to ORI staff.  ORI staff forward the RPS’s comments to the appropriate IRB Committee and/or IRB reviewer.
5. The IRB reviews research authorization forms at convened meetings of the IRB, as outlined in the Initial Full, Expedited, Exempt and Continuation Review SOPs.  IRB members use the ORI HIPAA Authorization Form Checklist and comments from the RPS to assist them with their authorization review.  The IRB and/or IRB reviewer make the final determination as to whether the study is regulated by the HIPAA Privacy Rule and whether the investigator must revise the authorization form.
6. The IRB may review authorizations during initial full review, expedited review, or continuation review.  The IRB requests revisions of any authorization form that does not contain all the federally and institutionally mandated criteria for authorization forms.
7. The ORI sends requests for revisions to the authorization form to the PI, who in turn makes the necessary corrections and resubmits the revised document to ORI.  The IRB reviews revisions to the authorization form and determines whether all the federally and institutionally mandated criteria for authorization forms are satisfied.
8. Once the IRB determines the HIPAA Authorization Form meets the federal regulations and institutional requirements, no further IRB review is necessary unless the investigator makes subsequent changes to the authorization form.  The PI obtains IRB review prior to implementing changes in the authorization form.
9. The PI takes the IRB reviewed authorization form signed by the subject to Medical Records (or data source) to obtain PHI.
10. The IRB does not review authorization forms for research activities conducted at sites outside of UK’s CE.
11. The IRB does not review authorizations under the following circumstances:
    • PHI that was created or received either before or after the compliance date (April 14, 2003) may continue to be used and disclosed for research purposes, if any one of the following was obtained prior to the compliance date:
      • An authorization or other express legal permission from the subject to use or disclose PHI for the research; or
      • The informed consent of the subject to participate in the research; or
      • A waiver of informed consent by the IRB in accordance with the federal regulations pertaining to human subject research protection commonly known as the Common Rule or in accordance with an exception under the FDA’s human subject protection regulations.
    • If the PI obtains a waiver of informed consent prior to the compliance date, but subsequently seeks informed consent after the compliance date, he/she must obtain the subject’s authorization at the time he/she obtains the new informed consent. It is the PI’s responsibility to submit a copy of the authorization form for IRB review.
12. The ORI maintains copies of all versions of the PI’s research authorization form for a period of no less than six (6) years after the study closure. (See Recordkeeping SOP.)
13. The ORI/IRB revises the IRB’s Model Authorization Form as appropriate.

Research Waiver of Authorization Request Review Procedures

1. The PI makes a preliminary assessment to determine whether his/her proposal needs a HIPAA research waiver of authorization.  A PI may call the ORI if he/she needs assistance in determining the HIPAA review type.
2. The PI submits his/her IRB application (i.e., exempt, expedited, or full) and research waiver of authorizations requests to the ORI.  A PI submits a waiver request using the ORI’s HIPAA Waiver of Authorization Request Form, which includes all federally and institutionally mandated criteria.
3. If the PI includes a HIPAA Waiver of Authorization Request Form in the IRB submission or checks “HIPAA” in the application or if there are any HIPAA concerns, ORI staff forward the IRB application to the RPS for review.
4. The RPS reviews protocols forwarded by ORI staff and determines whether the study is regulated by the HIPAA Privacy Rule and if a research waiver of authorization request is appropriate for the study.  The RPS reviews the waiver to ensure that all federally and institutionally mandated criteria are in the document and submits written recommendations to ORI staff.
5. ORI staff forward the RPS’s comments to the appropriate IRB and/or IRB reviewer.
6. The IRB reviews Research Waiver of Authorization Request Forms at convened IRB meetings, as outlined in the Initial Full, Expedited, Exempt, Continuation Review, and Modification SOPs. IRB members use the ORI HIPAA Waiver of Authorization Form Checklist and comments from the RPS to assist them with their HIPAA review.  The IRB and/or IRB Reviewer make the final determination as to whether the study is regulated by the HIPAA Privacy Rule and whether the investigator must revise the HIPAA form.
7. The IRB may review the waiver of authorization request during initial full review, expedited review, continuation review, or exemption review.  The IRB requests revisions of any waiver of authorization request that does not adequately address the questions/issues in the ORI’s HIPAA Waiver of Authorization Request Form.
8. The ORI sends requests for revisions to the PI, who in turn makes the necessary corrections and resubmits the revised form to the ORI.  The IRB reviews revisions to the HIPAA Waiver of Authorization Request Form and determines whether all the federally and institutionally mandated criteria for waiver of authorization are satisfied.
9. Once the IRB reviews the waiver, the IRB Chair or Designee signs the waiver of authorization approval letter and forwards the document to the ORI.  The ORI sends the letter to the PI.
10. Once the IRB determines the contents of the HIPAA Authorization Form meet the federal regulations and institutional requirements, the waiver of authorization request, no further IRB review is necessary unless the PI makes subsequent changes to the HIPAA form.  It is the PI’s responsibility to obtain IRB approval prior to implementing changes in the Waiver of Authorization Request Form.
11. The PI takes the Waiver of Authorization Approval letter to Medical Records (or data source) to obtain PHI.
12. The IRB does not review a research waiver of authorizations for research activities conducted at sites outside of UK’s CE.
13. The IRB does not require a research waiver of authorizations under the following circumstances:
    • A PI may use and disclose for research purposes PHI that was created or received either before or after the compliance date (April 14, 2003) if a waiver of informed consent was reviewed by the IRB in accordance with the federal regulations and obtained prior to the compliance date.
    • If the PI obtains a waiver of informed consent prior to the compliance date, but subsequently seeks informed consent after the Compliance Date, he/she must obtain the subject’s authorization at the time he/she obtains the new informed consent.
14. The ORI maintain copies of all versions of the PI’s HIPAA Waiver of Authorization Request Forms for a period of no less than six (6) years after the study is closed.  (See Recordkeeping SOP)
15. The ORI/IRB revises the HIPAA Waiver of Authorization Request Form as appropriate. 

Research De-identification Review Procedures 

1. The PI makes a preliminary assessment to determine whether his/her protocol meets the criteria for de-identification.  A PI may call the ORI if he/she needs assistance in determining the HIPAA review type.
2. The PI submits his/her IRB application (i.e., exempt, expedited, or full) and research de-identification requests to the ORI, using the ORI HIPAA De-identification Certification Form.
3. If the PI includes a HIPAA De-identification Certification Form in the IRB submission or if there are any HIPAA concerns, ORI staff forward the IRB application to the ORI RPS for review.
4. The RPS reviews protocols forwarded by ORI staff and determines whether de-identification is appropriate for the study and submits written recommendations to ORI staff.
5. ORI staff forward the RPS’s comments to the appropriate IRB and/or IRB reviewer.  
6. The IRB reviews research de-identification requests at convened IRB meetings, as outlined in the Initial Full Review, Expedited Initial Review, Exempt Review, Continuation Review, and Modification, Deviations, and Exceptions—IRB Review of Changes SOPs.  IRB members may use comments from the RPS to assist them with their HIPAA review.  The IRB makes a final determination as to whether the study meets the criteria for de-identification.  The IRB notifies the PI if the study does not meet the criteria for de-identification.
7. If the IRB denies the de-identification request, ORI staff or the RPS notify the PI and provide assistance in determining the appropriate HIPAA review type.
8. A PI in the CE submits a HIPAA De-identification Certification Form to Medical Records (or data source) to obtain PHI. A PI not in the CE submits a HIPAA De-identification Certification Form and a Business Associate Agreement to Medical Records to obtain PHI.
9. The IRB does not review research de-identification requests for research activities conducted at sites outside of UK’s CE.
10. The ORI/IRB revises the HIPAA De-identification Certification Form as appropriate.

Research Databases/Repositories Review Procedures

1. Since the HIPAA Privacy Rule does not give clear guidance on databases and repositories, the IRB follows the NIH’s Research Repositories, Databases, and the HIPAA Privacy Rule guidance document when reviewing HIPAA database/repositories issues.
2. The PI submits an IRB application (initial full or expedited) and the applicable HIPAA form to establish or remove PHI or specimens with identifiers from a research database or repository.
3. The database/repository does not fall under the Privacy Rule if the PI:
   • De-identifies all data/specimens collected for the database/repository; or
   • Obtains self reported health information from the subject and does not add the health information to a designated record set.  For the purposes of this policy, a designated record set is defined as a group of records maintained by or for a covered entity that includes (1) medical and billing records about individuals maintained by or for a covered health care provider; (2) enrollment, payment, claims adjudication, and case or medical management record systems maintained by or for a health plan; or (3) used, in whole or in part, by or for the covered entity to make decisions about individuals.
4. PIs, IRB members, ORI staff, and the RPS follow the authorization, waiver of authorization, and de-identification procedures previously outlined in this document.
5. The IRB does not require a PI to comply with the HIPAA requirements if the research database or repository was established before April 14, 2003 and the following conditions are met:
   • The information/specimens in the database are de-identified (e.g., all 18 identifiers listed in the HIPAA Privacy are removed); or
   • Subjects signed a consent form; or
   • The IRB waived informed consent.

HIPAA Compliance Procedures for Investigators Working in the Covered Entity 

1. Investigators working in a UK CE must comply with the UK Medical Center’s HIPAA policies and procedures.
2. Any significant noncompliance HIPAA issue, such as a breach or complaint, involving research will be reviewed in conjunction with the UK Privacy Officer.
   • If the UK Privacy Officer receives a HIPAA research complaint or an alleged HIPAA research noncompliance issue, the Privacy Officer will immediately (i.e., within approximately 2 working days) notify the ORI RPS or ORI’s Research Compliance Officer (RCO).  The Privacy Officer may confer with the RPS or the RCO to assess whether the complaint/alleged noncompliance issue falls under the purview of the IRB or both the IRB and UK Corporate Compliance.
   • If the ORI RCO receives a HIPAA research complaint or report of an alleged HIPAA research noncompliance issue, the RCO or RPS will immediately (i.e., within approximately 2 working days) notify the UK Privacy Officer.  The RCO or the RPS may confer with the Privacy Officer to assess whether the complaint/alleged noncompliance issue falls under the purview of the IRB or both the IRB and UK Corporate Compliance.
   • If the complaint/alleged noncompliance issue falls under IRB purview, the ORI will initiate an inquiry following ORI/IRB standard operating procedures.  (See the Subject Complaints/Concerns and Noncompliance SOPs)  The IRB determines whether the incident meets requirements for reporting to the federal regulatory agencies.  In making the determination, IRB follows the procedures for reporting. (See the Mandated Reporting to External Agencies SOP)
   • After the IRB has completed its review of the complaint/alleged noncompliance issue, the ORI RCO or RPS provides the UK Privacy Officer with a copy of the final deliberations if the allegation involves both research and a violation of the HIPAA regulations.  If ORI staff determine the incident to be reportable to a federal regulatory agency, the RCO sends a copy of the federal report to the UK Privacy Officer.  (See the Mandated Reporting to External Agencies SOP)
   • If the complaint/alleged noncompliance falls under UK Corporate Compliance purview, the Privacy Officer will initiate an investigation.  After the Privacy Officer has completed its review of the complaint/alleged noncompliance, the Privacy Officer provides the ORI with a copy of the final deliberations if the allegation involves both research and a violation of the HIPAA regulations.  If the Privacy Officer determines the incident to be reportable to a federal regulatory agency, the Privacy Officer sends a copy of the federal report to the ORI. 

REFERENCES

45 CFR 164.512 

45 CFR 164.532

45 CFR 164.530 

45 CFR 164.508

45 CFR 164.514

NIH’s Research Repositories, Databases, and the HIPAA Privacy Rule  

NIH’s Privacy Boards and the HIPAA Privacy Rule

Approved By: ORI Director, Nonmedical IRB Chair, Medical IRB Chair

Date First Effective: May 31, 2005

Last Revision Date: August 19, 2009

Revision #4

OBJECTIVE 

To provide guidance in handling concerns, complaints, or questions received regarding a research study involving human subjects 

GENERAL DESCRIPTION

The right of research subjects to lodge a concern (e.g., allegation), complaint, or question and to be assured that the concern, complaint, or question is taken seriously and resolved in a timely manner is of prime importance. The Research Compliance Officer (RCO) or designee in the Office of Research Integrity (ORI) is responsible for investigating concerns, complaints, and questions from subjects and any improprieties involving investigators or their staff. The RCO or designee handles these issues in a timely manner, assuring protection of human subjects, and the IRB holds any violators accountable to the applicable regulation. A research subject (past, current, or prospective), a designated spokesperson, family member, or anyone with a concern about a human research study may raise concerns, complaints, or questions about a research project by telephone, in writing, or in person to the RCO or designee. Each IRB approved informed consent document includes a toll free telephone number to reach the RCO or designee; the toll free telephone number is also listed on the ORI and University websites. 

RESPONSIBILITY 

Execution of SOP:  Research Compliance Officer (RCO), ORI Staff, IRB Chair, Principal Investigator (PI)/Study Personnel 

PROCEDURES

Concerns/Complaints/Questions

1. A research subject or anyone with a concern, complaint, or question regarding a research study involving human subjects may raise the concern, complaint, or question with the ORI. Upon receipt of a concern (e.g., allegation), complaint, or question, the RCO or designee gathers the following information from the complainant as appropriate:
   • Subject’s (or complainant’s) name, address, and phone number (This information is NOT MANDATORY, and an individual may report an incident anonymously; however, the RCO or designee advises the individual that a thorough review may not be possible, and that, without this information, follow-up responses to the individual are not feasible.);
   • Study protocol title (or acronym) and the name of the PI;
   • Date(s) of the incident, and;
   • An explanation of the concern, complaint, or question.
2. The RCO or designee assures the individual (or complainant) that he/she will inquire into the circumstances and that the IRB/ORI will take appropriate measures to address the issue. Furthermore, the RCO or designee informs the individual that a response to him or her will be forthcoming as rapidly as possible provided that contact information is given (e.g., if possible, within 2 to 3 weeks if the issue is a complaint). The RCO or designee also explains to the individual the limits to confidentiality.
3. The RCO or designee handles the concern, complaint, or question in a confidential manner to the extent allowed by law. The ORI limits access to information concerning the contact to employees with responsibilities that require knowledge of the concern, complaint, or question.
4. The RCO or designee conveys the information regarding the concern, complaint, or question to the PI of the study at issue, the ORI Director, and the IRB Chair in a timely manner.
5. The RCO or designee promptly investigates the concern, complaint, or question; evaluates the alleged impropriety on a case-by-case basis; and makes every effort to correct the issue(s) at the administrative level.
6. If the alleged impropriety involves potential harm to subjects or others, the RCO or designee notifies the IRB for immediate action pending formal inquiry. The RCO or designee reports concerns, complaints, or questions involving serious issues immediately to the IRB Chair, the ORI Director, the Vice President for Research (VPR), and, if appropriate, Legal Counsel.
7. The RCO or designee manages the inquiry, preparing related correspondence, and maintaining documentation of the review for up to six years from completion of the inquiry or close out of the IRB file, whichever is longer.
8. The IRB Chair or his/her designee, in collaboration with the RCO or designee, ensures appropriate response to each concern, complaint, or question and reports the action(s) taken to the IRB. If the complaint, concern, or question is of a minor nature such as a payment issue, the IRB Chair, the RCO, or designee may resolve the issue without bringing it forth for an IRB committee vote. The IRB Chair, the RCO, or designee refers major issues such as failure to obtain signed informed consent from potential subjects (if required) to the IRB committee, and the IRB votes on any actions the IRB takes. All actions taken are by the IRB, are appropriate for the circumstances, and the final course of action is dependent on the nature, severity, and seriousness of the findings.
9. Depending on the nature of the event or circumstances, the IRB may take the following actions but is not limited to:
   • Further inquiry;
   • Administrative action;
   • Details and recommendations forwarded to the appropriate committee chairs (e.g., IRB, Radiation and/or Safety Committees) for consideration in their committees;
   • Details and recommendations forwarded to the appropriate department chair for action as appropriate;
   • Details and recommendations forwarded to the VPR, Veterans Affairs Medical Center Research and Development Office/Committee, and/or University Legal Counsel for action;
   • Details and recommendations forwarded to the appropriate officials at affiliated institutions for notification, action, and/or follow-up, if applicable, and;
   • Other actions as deemed appropriate.
10. The ORI and IRB monitor any concerns, complaints, or questions that an individual may lodge for issues of noncompliance. The RCO or designee brings issues involving noncompliance to the attention of the IRB Chair, the IRB, and the ORI Director. (See the Noncompliance SOP.) 

REFERENCES 

45 CFR 46.116(a)

21 CFR 50.25(a)

Approved By: ORI Director, Nonmedical IRB Chair, Medical IRB Chair

Date First Effective: May 15, 2005

Last Revision Date: September 4, 2014

Revision #10

OBJECTIVE

To describe the policies and procedures the Institutional Review Board (IRB) and the Office of Research Integrity (ORI) follow for handling allegations of noncompliance

GENERAL DESCRIPTION

The ethical conduct of research is a shared responsibility. It requires cooperation, collaboration, and trust among the institution, investigators and their research staff, the participants who enroll in research, IRB members, and ORI staff. The primary responsibility of the IRB is to ensure protection of the rights and welfare of research subjects. In performing that responsibility, the IRB addresses allegations of noncompliance with IRB requirements and/or federal regulations governing the conduct of human research. ORI staff, IRB members, or IRB consultants do not participate in alleged noncompliance reviews if they have a conflict of interest. (See the IRB Member and Consultant Conflict of Interest SOP.)

Definitions

Noncompliance is defined as conducting research in a manner that disregards or violates federal regulations or institutional policies and procedures applicable to human research. Noncompliance with IRB policies and/or federal requirements may involve a range of issues from relatively minor, administrative, or technical violations to more serious violations which pose risk to subjects and/or violations of their rights and welfare. 

Continuing noncompliance is a persistent failure to adhere to the laws, regulations, or policies governing human research.

Serious noncomplianceis a failure to adhere to the laws, regulations, or policies governing human research that may reasonably be regarded as:

(1) Involving substantive harm, or a genuine risk of substantive harm, to the safety, rights, or welfare of human research subjects, research staff, or others; or 

(2) Substantively compromising the effectiveness of a facility’s human research protection or human research oversight programs.

RESPONSIBILITY

Execution of SOP:  Office of Research Integrity (ORI) Staff, IRB Chair, IRB Members, ORI Research Compliance Officer (RCO), ORI Director, Principal Investigator (PI)/Study Personnel 

PROCEDURES

Submission and Screening of Allegations of Noncompliance

1. Anyone may submit allegations of noncompliance or continuing noncompliance involving human subjects research to the ORI verbally or in writing. ORI staff or the IRB may also identify concerns during the review process.  The ORI/IRB maintains confidentiality regarding the identity of the person submitting the allegation to the extent possible.
2. The RCO or designee (e.g., ORI staff) screens the allegation/concern of noncompliance to determine whether the protocol(s) affected is supported by federal funds.
3. The RCO or designee also determines whether the protocol has issues pertinent to other research review committees, i.e., Institutional Biosafety Committee, Markey Cancer Center, Center on Aging, Radiation Safety Committee, Radioactive Drug Research Committee, Office of Sponsored Projects Administration, and Investigational Drug Service.
4. If the RCO or designee finds any issues pertinent to these research review committees, he/she coordinates with these units as outlined in the IRB/ORI coordination SOP, if appropriate. 

Assessment of Allegations

1. The RCO or designee reviews allegations/concerns to determine whether the facts justify the allegation (i.e., there are supporting documents or statements).
2. If the RCO or designee deems an allegation/concern unsubstantiated (i.e., finds no supporting documents or statements), he/she consults with the IRB Chair or his/her designee and, if appropriate, the ORI Director. The IRB Chair, ORI Director, or designee may decide no additional action is needed, further inquiry is necessary, or the issue should be presented to a convened IRB.
3. If the RCO or designee determines that an allegation/concern is substantiated but the concerns are minor or administrative issues, the RCO or designee (e.g., ORI staff) manages the concern through communications with the PI or the complainant (e.g., timely reward payment). The RCO or designee reports the minor issue to the IRB Chair, designee, and/or ORI Director. The IRB Chair, ORI Director, or designee may determine that the noncompliance does not meet serious or continuing noncompliance and no additional action is needed, or determine further inquiry is necessary, or determine the issue should be presented to a convened IRB.
4. If the RCO or designee determines the allegation/concern may be substantiated and may involve an unanticipated problem or serious or continuing noncompliance, he/she forwards applicable materials to the IRB Chair or designee with a copy to the ORI Director as appropriate.
5. At the completion of the assessment, when appropriate, the RCO or designee communicates (by phone, email, or letter), the IRB Chair’s or designee’s decision to the complainant (if the identity of the person is known) and, if applicable, to the individual against whom the allegation/concern was raised (respondent). 

Initiating an Inquiry into More Serious Violations

1. If the allegation/concern involves more serious issues than administrative or minor concerns, the convened IRB, the IRB Chair or designee decides whether to initiate an inquiry. The convened IRB or IRB Chair bases the decision on the seriousness and/or the frequency of violations and/or disregard for the federal regulations or the institutional policies and procedures applicable to human subjects research.
2. If the RCO (or designee), IRB Chair, or convened IRB determines that an allegation/concern is substantiated and suggests that subjects are at immediate risk, the IRB Chair, in consultation with the ORI Director or designee, considers whether to immediately suspend IRB approval in accord with the Termination and Suspension SOP.
3. If the convened IRB or the IRB Chair or designee decides to initiate an inquiry to determine the validity of the allegations/concerns, ORI staff notify the complainant or individual/IRB that identified the concern. If the allegation/issue involves a co-investigator or a research assistant, ORI staff may also contact that individual. The RCO or designee or the IRB Chair notify the PI via telephone and/or e-mail. RCO or designee or IRB Chair sends written follow-up correspondence.
4. The IRB may appoint one or more voting member(s) or RCO or designee (e.g., the IRB Chair or his/her representative) to gather information pertaining to the nature of the allegation/concern, the procedures approved in the IRB protocol, and the procedures followed in conducting the study.
5. The IRB representative interviews the complainant or, in cases where the complainant requests anonymity, the individual who received the original allegation/concern interviews the complainant. In some cases, the complainant may have already submitted a written complaint. Either the IRB representative or the RCO or designee may request additional information from the complainant.
6. The convened IRB, the IRB Chair, or a designated IRB representative (e.g. RCO or designee) interviews the respondent and gives him/her the opportunity to comment on the allegation/concern and provide information. The respondent may submit a written rebuttal to the complaint. Either the IRB or the RCO may request additional information from the respondent.
7. Depending on the nature of the allegation/concern and the information collected during the interviews, the convened IRB or its representative may interview other individuals. In addition, in conducting the review, the convened IRB or its representative may examine research data, both published and unpublished; informed consent/assent forms; medical records; inclusion/exclusion criteria; the applicable approved IRB protocol; and any other pertinent information.
8. When appropriate, the IRB member(s) conducting the inquiry prepares, with the assistance of an assigned ORI staff member, a summary report for the convened IRB. The report may consist of a summary of the allegations/concerns, interview summaries, and copies of pertinent information or correspondence. The report may or may not include recommendations for IRB action. (In some cases, the IRB representative simply provides the IRB with a summary of the allegations/issues, the interview summaries, and copies of pertinent information without an accompanying written report from the review team.) 

Review Procedures for Potential Serious or Continuing Noncompliance

1. The ORI advises the IRB regarding the applicable University and federal regulations, assists the IRB in documenting the review, answers questions about the review process, maintains the records as required by state and federal laws, and serves as a liaison with the funding agency or agencies.
2. The IRB reviews the material presented by the review team at a convened meeting at which a quorum is present. The materials provided include the summary report of the noncompliance, the protocol if applicable and the informed consent document if applicable.  The convened IRB determines whether to request additional information or whether to interview additional witnesses. The IRB may give the respondent the opportunity to meet with the convened IRB before it takes final action. 

Review Outcomes/IRB Actions

1. The convened IRB makes the determination whether the allegation/concern is substantiated, and if so, whether the noncompliance is serious or continuing based on the materials compiled during the inquiry. If the noncompliance is serious or continuing and the research federally funded, the IRB, with the assistance of the RCO or designee, reports the incident(s) to the applicable agency following procedures outlined in the Mandated Reporting to External Agencies SOP.
2. The convened IRB may take a variety of actions, depending on the outcome of the review, including, but not limited to, the following:
   • Approve continuation of research without changes;
   • Request formal educational intervention;
   • Request minor or major changes in the research procedures and /or consent documents;
   • Modify the continuing review schedule;
   • Require monitoring of research;
   • Require monitoring of the consent process;
   • Suspend or terminate IRB approval/disapprove continuation of the study;
   • Require inspections of other active protocols of the investigator (See Quality Improvement Program Directed On-Site Review SOP);
   • Disqualify the investigator from conducting research involving human subjects at the University;
   • Determine that the investigator may not use the data collected for publication;
   • Require that the investigator contact subjects previously enrolled in the study and provide them with additional information and/or re-consent them;
   • Request that the investigator inform publishers and editors if he/she has submitted or published manuscripts emanating from the research; and/or
   • The RCO, ORI Director, IRB Chair or designee communicates (phone call, email, or letter) the IRB decision to the person raising the allegation (if the identity of the person is known) and to the respondent.
3. The IRB informs the following individuals of the allegation/issue, the review process, and the findings of the review, if appropriate, depending upon the outcome of the review, the external sponsor, or the requirements of the applicable regulatory agency:
   • Investigator;
   • Complainant;
   • The department chair;
   • Dean or unit director;
   • Vice President for Research;
   • Office for Human Research Protections and/or the Food and Drug Administration (See Mandated Reporting to External Agencies SOP);
   • Sponsor, if appropriate;
   • Other administrative personnel as appropriate (See applicable IRB/ORI coordination SOPs).
4. The PI submits concerns in writing to the IRB within thirty days of the date the IRB issues the final decision. The IRB limits concerns to a review of the procedures employed to reach the decision (i.e., claims that the process was faulty in a way that creates a considerable risk that the outcome was incorrect) or grievances against sanctions imposed as a result of a finding of noncompliance. The PI specifies the nature of any claimed procedural error or the perceived unfairness of sanctions issued.
5. The IRB may resolve questions or concerns raised by a PI regarding the outcome of a specific IRB noncompliance review through direct communication with the PI. If not resolved, the convened IRB reviews the appeal in conjunction with a separate party (e.g., chair/vice chair from a different committee, consultant, etc.) to assist in adjudicating the appeal. The appeal determination final.  

REFERENCES

21 CFR 56.123

45 CFR 46.112

Approved By: ORI Director, Nonmedical IRB Chair, Medical IRB Chair

Date First Effective: May 15, 2005

Last Revision Date: September 4, 2014

Revision #10

OBJECTIVE 

To describe policies and procedures for suspending or terminating research approved by the Institutional Review Board (IRB)

GENERAL DESCRIPTION 

The convened IRB has the authority to suspend or terminate approval of research that is not being conducted in accordance with the IRB approval, that has been associated with serious or continuing noncompliance, or that has been associated with substantive harm to the rights and welfare of human subjects.  Any suspension or termination of approval shall include a statement of the reason for the IRB action. 

The IRB Chair or designee has the authority to request that the IRB suspend approval when the continuation of the research may adversely affect the rights and welfare of research subjects or when the IRB needs additional information to ensure that the rights and welfare of subjects are protected and there is insufficient time to have the convened IRB review the situation. 

The IRB reports the suspension or termination promptly to the investigator and appropriate institutional official(s).  If the research is funded by an extramural agency, federal regulations dictate whether the funding agency must be informed that IRB approval has been suspended or terminated.  Principal investigators (PIs) are responsible for informing the funding agency of any suspension or termination of funded research. 

Reporting to federal regulatory agencies is not required if the PI voluntarily closes down a study to new subject accrual or temporarily halts the research procedures.  The IRB, IRB Chair, Office of Research Integrity (ORI), or administrative officials may recommend voluntary closure to the PI, but the PI makes the decision whether closure is appropriate.  However, if the IRB or IRB Chair requires suspension or termination, then the incident is reportable under the Mandated Reporting to External Agencies SOP

Definitions

A suspension of IRB approved research is a temporary interruption in the enrollment of new subjects, activities involving previously enrolled subjects, or other research activities.

A termination of IRB approval refers to a permanent halt in the enrollment of new subjects, activities involving previously enrolled subjects, or other research activities.

RESPONSIBILITY

Execution of SOP: IRB, IRB Chair, Office of Research Integrity Staff, Principal Investigator/Study Personnel

PROCEDURES

Suspension of IRB Approval 

1. The convened IRB determines and documents in the minutes the reasons for suspending the research and any information needed from the PI and/or corrective actions or events that need to take place for the IRB to consider a withdrawal of the suspension.
2. If the IRB Chair or designee suspends IRB approval, the IRB Chair documents the reason for suspension and notifies the PI in writing or requests that ORI staff prepare the correspondence.  ORI staff inform the IRB, and the IRB discusses the suspension at a convened meeting.
3. If UK is the reviewing IRB for a reliance study, ORI staff informs the Reliance Team who notifies the relying institution according to the reliance agreement, communication plan, or local context form.
4. When a suspension involves the withdrawal of current subjects from a research protocol, the IRB considers alternatives that protect subjects currently enrolled to ensure that harm is not incurred from such withdrawal.  Such considerations may include possible transfer of subjects to another investigator, arrangement of clinical care outside the research, continuation of some research activities under the supervision of an independent monitor, permitting follow-up of subjects for safety reasons, or requiring reporting of adverse events or outcomes to the IRB and the sponsor.
5. ORI staff notify the PI in writing of the suspension.  The correspondence may include, but is not limited to, the following:
   • An explanation of the extent of the suspension in terms of enrollment, recruitment, interventions, interactions, and data analysis;
   • The reasons for the suspension, an explanation of the reasons for the decision, and an offer to the investigator to respond to the convened IRB in writing;
   • A request for a description of any procedures needed to protect the rights and welfare of current subjects if the suspension involves currently enrolled subjects;
   • A description of whether follow-up of subjects for safety reasons is permitted or required.
6. The PI notifies enrolled subjects of any suspended research protocol, and the PI considers the appropriate procedures for withdrawal of enrolled subjects, taking into account their rights and welfare. (See Principal Investigator Responsibilities Guidance Document.)
7. The IRB determines which institutional officials to notify of the suspension and whether to report the suspension to an external agency.  (See Mandated IRB Reporting to External Agencies SOP.)  Also, ORI staff send copies of suspension correspondence to other UK administrative units in accordance with the coordination SOPs (e.g., Institutional Biosafety Committee, Markey Cancer Center, Radiation Safety Committee, Investigational Drug Service, and the Office of Sponsored Projects Administration).

Termination of IRB Approval 

1. The convened IRB determines and documents in the minutes the reasons for terminating the research.
2. When a termination involves the withdrawal of current subjects from a research protocol, the IRB considers alternatives that protect subjects currently enrolled to ensure that harm is not incurred from such withdrawal.  Such considerations may include possible transfer of subjects to another investigator, arrangement of clinical care outside the research, continuation of some research activities under the supervision of an independent monitor, permitting follow-up of subjects for safety reasons, or requiring reporting of adverse events or outcomes to the IRB and the sponsor.
3. ORI staff notify the PI of the termination.  The notification may include, but is not limited to, the following:
   • An explanation of the extent of the termination in terms of enrollment, recruitment, interventions, interactions, and data analysis;
   • The reasons for the termination, an explanation of the reasons for the decision, and an offer to the investigator to respond to the convened IRB in writing;
   • A request for a description of any procedures that need to be followed to protect the rights and welfare of current subjects if the termination involves currently enrolled subjects;
   • A description of whether follow-up of subjects for safety reasons is permitted or required;
   • An explanation that any request for the IRB to reconsider the termination must be made within 30 days from date of the notification.
4. The PI notifies enrolled subjects of any termination of a research protocol, and the PI considers the appropriate procedures for withdrawal of enrolled subjects, taking into account their rights and welfare. (See Principal Investigator Responsibilities Guidance Document)
5. The IRB determines which institutional official to notify of the termination and whether a report to an external agency is required (See Mandated Reporting to External Agencies SOP).  Also, ORI staff send copies of the termination notification to other administrative units in accordance with the coordination SOPs (e.g., Institutional Biosafety Committee, Markey Cancer Center, Radiation Safety Committee, Investigational Drug Service, and the Office of Sponsored Projects Administration).
6. If UK is the reviewing IRB for a reliance study, ORI staff informs the Reliance Team who notifies the relying institution according to the reliance agreement, communication plan, or local context form.

Reporting and Recordkeeping of Suspension or Termination

1. See the Mandated Reporting to External Agencies SOP for a description of policies and procedures regarding reporting and recordkeeping of UK studies.

REFERENCES

21 CFR 56.113

45 CFR 46.113

Approved By: ORI Director, Nonmedical IRB Chair, Medical IRB Chair

Date First Effective: July 12, 2005

Last Revision Date: May 9, 2019

Revision #6

OBJECTIVE

To describe policies and procedures for the preparation, scheduling, and conduct of convened meetings of the Institutional Review Board (IRB)

GENERAL DESCRIPTION

The University of Kentucky IRB conducts convened meetings in accordance with applicable federal requirements for full review (i.e., 21 CFR 56.108, 45 CFR 46.108) 

RESPONSIBILITY

Execution of SOP: IRB Chair, IRB Members, Office of Research Integrity (ORI) Staff; Principal Investigator (PI)/Study Personnel

PROCEDURES

Preparation and Distribution of the Agenda 

1. ORI staff develop, maintain, and revise the IRB meeting schedule, as appropriate. The meetng dates are available on the ORI website or by request. ORI staff coordinate meeting rooms and catering arrangements after confirming the meeting dates.
2. ORI staff create an agenda approximately five (5) to ten (10) days before a meeting. ORI staff review the agenda for accuracy and completeness before making it available to members of the appropriate IRB.
3. If special circumstances exist, ORI staff prepare an addendum to the agenda and make it available to IRB members prior to the meeting.
4. ORI staff make the agenda and related materials available to other appropriate individuals (e.g., Investigational Drug Service Director, HIPAA Privacy Specialist, Radiation Safety Officer).
5. ORI staff notify PIs of appointment times for initial full review protocols.
6. The agenda serves as a guideline for the conduct of the meeting. The agenda for the meeting may include additional discussion items at the discretion of the IRB Chair, ORI staff, or IRB members.

Quorum Requirements

1. A majority (e.g., IRB members = 11; majority = 6) of the IRB members must be present.
2. At least one member whose primary concerns are in nonscientific areas is present at the convened meeting.
3. A licensed physician member must be present when the IRB reviews FDA-regulated research.
4. Alternate members may attend in place of absent regular members in order to meet quorum requirements. (See Membership of IRB SOP)
5. The IRB does not consider ad hoc and cultural consultants to establish a quorum.
6. Members excuse themselves from the meeting during a vote when they have a conflict of interest. In such cases, they do not count towards the number necessary to constitute a vote or majority. If quorum is lost during a meeting (e.g., loss of a majority through excused members with conflicting interests or early departure or absence of a non-scientist member, etc.), the IRB does not take further protocol actions that require a vote unless quorum is restored.

Review of Protocols

1. The IRB Chair, Vice Chair, or any voting IRB member may chair the convened meeting.
2. For initial full review, the IRB requires that PIs attend the convened meeting. The IRB, IRB Chair, or ORI staff may grant permission for the co-investigator or knowledgeable party to attend in place of the PI. The IRB, IRB Chair/Vice Chair, or ORI staff may also waive this attendance requirement.
3. For other types of review, IRB members, the IRB Chair, or ORI staff may also invite or require the PI to attend, when deemed appropriate.
4. ORI staff or the IRB Chair may grant permission for attendance by observers upon request. Faculty make requests on behalf of student observers to the ORI. Upon receipt of any request, ORI staff or the IRB Chair use discretion to grant permission for attendance to selected meetings by observers. ORI staff or the IRB Chair make meeting selections based on availability and agenda suitability. ORI staff obtain a statement of confidentiality from observers who have permission to attend. ORI does not provide observers with copies of application materials.
5. IRB members do not participate in the review of any component of a project in which the member has a conflict of interest, except to provide information requested by the IRB. (See IRB Member and Consultant Conflict of Interest SOP)
6. For discussion of review outcomes and controverted issues, see Initial Full Review, Continuation Review, Protocol Violations, Modification, Deviations and Exceptions-IRB Review of Changes, and Noncompliance SOPs.
7. ORI staff are responsible for preparing meeting minutes. (See Minutes of IRB Meeting SOP.)

Tele/Videoconference Participation

1. The IRB may conduct convened meetings by telephone or video conferencing as long as IRB member(s) have been provided with prior access to all of the materials to be reviewed at the meeting, a quorum as defined above is present, and discussion occurs in real time.
2. Members participating via tele/videoconferencing count as part of the quorum and may vote. "Telephone polling" (where ORI staff or others contact IRB members individually by telephone) does not qualify as a convened meeting. To allow for appropriate discussion, all members must be connected and able to participate simultaneously for a tele/videoconference to take place.

Voting

1. IRB members may not vote by proxy (i.e., members not present at the convened meeting or participating in the tele/videoconference call may not vote on an issue discussed during a convened meeting). However, members can provide written comments for IRB consideration.
2. Voting at a convened meeting takes place under the following conditions:
   • A majority of the members for the specific IRB must be present (or connected via speakerphone/video) for all reviews/actions voted on at a convened meeting;
   • A passing vote must consist of a majority of members present (or connected via speakerphone/video) voting in favor of the motion;
   • An individual who is not listed on the active IRB membership roster may not vote with the IRB;
   • Ex-officio members of the IRB may not participate in the vote;
   • Ad hoc and cultural consultants may not participate in the vote;
   • At least one non-scientist member must always be present for the vote;
   • A physician must be present to vote on FDA regulated research.
3. If the outcome of the IRB vote is a “2” (approved pending submission of minor revisions), the IRB Chair or the individual chairing the meeting may review and approve the PI’s response on behalf of the IRB under an expedited review procedure. 

REFERENCES 

21 CFR 56.108

21 CFR 56.109

45 CFR 46.107

45 CFR 46.108

Approved By: ORI Director, Nonmedical IRB Chair, Medical IRB Chair

Date First Effective: October 15, 2005

Last Revision Date: September 10, 2021

Revision #13

OBJECTIVE

To describe policies and procedures for obtaining and documenting informed consent/assent and for reviewing and requesting a waiver of informed consent or a waiver of signatures for non-exempt human research

GENERAL DESCRIPTION 

Informed Consent/Assent Permission: Process and Documentation 

A major requirement of research involving human subjects is that investigators must obtain an informed consent of prospective subjects before they include these subjects in research. Informed consent is an ongoing educational process that takes place between the investigator and prospective subject, allowing the investigator and the participant to exchange information and ask questions. In most cases, federal regulations require informed consent and signatures documenting the process. In certain circumstances, the federal regulations allow a waiver of the signature requirement. 

The consent document is not a substitute for discussion between investigators and research subjects. To ensure an effective informed consent process, the Institutional Review Board (IRB) and investigators comply with all applicable federal regulations (e.g., 21 CFR 50, 45 CFR 46.116, 117). These regulations mandate the inclusion of a concise and focused presentation of the key information most likely to assist a prospective subject or Legally Authorized Representative (LAR) in understanding the reasons why one might or might not want to participate in the research. Additionally, the regulations mandate the inclusion of nine basic informed consent elements. Nine additional elements may be required, depending on the nature of the research. IRB policy also specifies the information to include in the consent process. The informed consent template outlines basic elements and the additional elements of informed consent. The investigator should only include the additional elements, as applicable. The basic elements of informed consent must be included unless the IRB has approved a waiver or alteration of informed consent. The investigator may use a short form if approved by the IRB in accord with applicable federal requirements.

Definitions

Assent is defined as the affirmative agreement of a child or an individual with impaired consent capacity to participate in research. Mere failure to object should not, absent affirmative agreement, be construed as assent.

Permission is defined as the agreement of parent(s) or guardian to the participation of their child or ward in research or clinical investigation. Permission includes the element of consent set forth in federal regulations and outlined in the informed consent template included in the IRB expedited and full review applications.

In Kentucky, the terms child or children refer to all individuals under 18 years of age unless the individual(s) is legally emancipated. (See section Emancipated Individuals for details of Kentucky state law.)  Individuals under 18 years of age who are not emancipated meet the federal definition for “child” [e.g., U.S. Department of Health and Human Services (HHS), Food and Drug Administration (FDA), and U.S. Department of Education].

Legally Authorized Representative (LAR) is an individual who has the authority to make research participation decisions on behalf of another. In accord with state law and federal regulation, individuals who can serve as legally authorized representatives are as follows: 

1. Permission and/or authorization by a legally authorized representative for children: Consistent with Kentucky health care decision statutes for choosing an LAR for children, the following responsible parties in the order of priority listed shall be authorized to make research participation decisions on behalf of the child: (a) the judicially appointed guardian of the person, if the guardian has been appointed and if the decisions to be made under the consent are within the scope of the guardianship; (b) the parent of the child.
2. Permission and/or authorization by a legally authorized representative for individuals with impaired consent capacity: Consistent with Kentucky health care decision statutes for choosing a legally authorized representative for adult subjects unable to consent, one of the following responsible parties, in the following order of priority (if no individual in a prior class is reasonably available, willing, and competent to act), is authorized to make research participation decisions on behalf of the person: (a) the judicially appointed guardian of the person, if the guardian has been appointed and if the decisions to be made under the consent are within the scope of the guardianship; (b) the attorney-in-fact named in a durable power of attorney, if the durable power of attorney specifically includes authority for the decisions to be made under the consent; (c) the spouse of the person; (d) an adult child of the person, or if the person has more than one (1) child, the majority of the adult children who are reasonably available for consultation; (e) the parents of the person; (f) the nearest living relative, or if more than one of the same relation, a majority of the nearest living relatives. 
   
   Consent by a LAR should involve all the same considerations that informed consent from a competent subject involves. 

In Kentucky, a guardian is an individual who may serve as a LAR as defined above and meet the federal definitions for a guardian.

Waiver of Informed Consent Process

The IRB has the authority to approve a consent procedure that does not include, or which alters some or all of the federally mandated elements of informed consent provided the approved procedure meets applicable federal regulations. A summary of applicable waivers of federal regulations and University requirements is as follows:

1. FDA-regulated or HHS-funded studies: to waive informed consent requirements, the IRB must find and document that the study meets the requirements in 45 CFR 46.116(c)(d).
2. Non-FDA or HHS-funded or regulated studies involving planned emergency research: the University of Kentucky (UK) does not accept proposals that require a waiver of informed consent for planned emergency research for non-FDA/HHS regulated research.
3. FDA regulated and/or HHS-funded planned emergency research: the IRB approves exceptions for informed consent requirements if the study meets all of the requirements specified in 21 CFR Subpart B 50.24.
4. Single subject emergency use of an FDA-regulated test article: the UK policy is more stringent than the FDA requirements outlined in 21 CFR 50.23. UK requires investigators to consult with the IRB Chair or designee before using the test article in a single subject without informed consent. The IRB may allow an exception to consultation, consistent with 21 CFR 50.23.
5. Waiver of parental or guardian permission in FDA-regulated and HHS-funded studies: when consent of parents or guardians is not a reasonable requirement because it poses additional risk to the potential subject or the parents’ interest may not adequately reflect the child’s interest (e.g., neglected or abused children), the IRB may waive parental or guardian permission in accord with 45 CFR 46 Subpart D and 46.408(c) and Subpart A 46.116.                                                                                           

Waiver of Signatures

Federal regulations permit an IRB to waive the signature requirements for obtaining informed consent under special circumstances.

1. FDA-regulated studies: IRB may waive the signature requirement for some or all of the subjects if the study meets the conditions listed in 21 CFR 56.109(c).
2. Non-FDA-regulated studies: the IRB may waive the requirement to obtain a signed consent form for some or all of the subjects if the study meets the requirements in 45 CFR 46.117(c)(1). 

RESPONSIBILITY

Execution of SOP: Principal Investigator (PI)/Study Personnel, Office of Research Integrity (ORI) Staff, IRB, UK Legal Counsel, Quality Improvement Program (QIP) Coordinator 

PROCEDURES 

Informed Consent Process and Documentation 

1. The PI submits a proposed informed consent procedure and written form in his/her IRB application prior to initiation of research, except in situations such as research proposals that meet exempt criteria (although informed consent(s) may be included). The PI indicates in the IRB application the study personnel who will participate in the informed consent process or individuals the PI will authorize to obtain informed consent on his/her behalf.
2. The UK IRB informed consent template is available on the ORI website. Investigators use this template as a guide. The consent template contains the nine (9) basic and nine (9) additional elements of informed consent as well as additional IRB requirements for UK research involving human subjects. See Additional Elements Where Appropriate below.
3. At a minimum, the proposed consent process and form must begin with key information and include the following nine (9) federally required elements and additional elements where appropriate:
   • Key Information: a concise and focused presentation of the key information that is most likely to assist a prospective subject or legally authorized representative in understanding the reasons why one might or might not want to participate in the research.
   • Research statement: a statement that the study involves research, an explanation of the purpose of the research, an explanation of the expected duration of participation, a description of the procedures involved, and identification of any procedures which will be experimental.
   • Reasonably foreseeable risks or discomforts: a statement that describes foreseeable risks or discomforts associated with the research, the likelihood of their occurrence, and the ramifications associated with the risks (e.g., decreased blood count may result in the need for a blood transfusion).
   • Reasonably expected benefits to subjects or others: a statement that describes benefits to subjects or others that may reasonably be expected from the research including no benefit, if this is applicable. Payment for participation in a research project is not considered a benefit.
   • Appropriate alternatives: a statement that describes with enough detail any alternative procedures or course of treatment that may benefit the subject. If no alternatives exist, the consent form must state that there are no alternatives except not to participate.
   • Extent of confidentiality: a statement that describes the extent to which the investigator/study personnel will maintain or not maintain confidentiality of records identifying the subject (e.g., law requires reporting child abuse, etc.) and describes how the research team will protect subjects’ private records during and after the conclusion of proposed research studies. Any research that is subject to audit or inspection must identify who will have access to the subject’s record (e.g., FDA, National Institutes of Health (NIH), UK, Government Accounting Office, sponsors, or contract research organizations).
   • Compensation or treatment for injury: for studies with greater than minimal risk, a statement explaining any compensation and an explanation of any medical treatments available if injury occurs or where the subject may obtain further information. The IRB informed consent template contains standard statements in accordance with UK policy.
   • Contact information: a statement that describes contact information details, including telephone numbers, and whom to contact for the following situations: questions about the research (e.g., investigator and other team members), questions about subjects’ rights, comments, suggestions, or input (e.g., the ORI), and in the event of a research-related injury (depending on the nature of the research, the PI or a physician on the research team).
   • Voluntary participation statement: a statement that describes clearly that participation in the research is voluntary, refusal to participate will involve no penalty or loss of benefits to which the subject is otherwise entitled, the subject may discontinue participation at any time without penalty or loss of benefits to which the subject is otherwise entitled.
   • Collection of private information or identifiable biospecimens for future use: a statement that identifiers might be removed from the identifiable private information or identifiable biospecimens and that, after such removal, the information or biospecimens could be used for future research studies or distributed to another investigator for future research studies without additional informed consent from the subject or the legally authorized representative; OR a statement that the subject’s information or biospecimens collected as part of the research, even if identifiers are removed, will not be used or distributed for future research studies.
   • Additional elements where appropriate: The IRB requires the additional elements unless the item(s) does not apply given the nature of the research or the proposed procedures (e.g., subjects will not receive remuneration for participation).
     • Unforeseeable risks to subjects, embryos, or fetuses: a statement warning subjects that some risks are currently not known or foreseeable, when applicable;
     • Investigator-initiated termination of participation: a statement that describes the instances in which an investigator may terminate a subject’s participation (e.g., subject noncompliance, subject not benefiting from research, etc);
     • Additional costs: a statement that describes any additional costs a subject may encounter such as transportation, time away from work, parking, health costs, etc.;
     • Early withdrawal/procedures for termination: a statement that describes a subject’s right to withdraw from the study and any procedures that may be necessary after an early withdrawal for subject’s safety;
     • Significant new findings: a statement that subjects will be told of any new findings which may affect willingness to continue in the research;
     • Approximate number of subjects: a statement that explains the approximate number of subjects to be enrolled in the study, nationwide and locally;
     • Biospecimens for commercial profit: a statement that the subject’s biospecimens (even if identifiers are removed) may be used for commercial profit and whether the subject will or will not share in this commercial profit.
     • Return of individual research results: a statement regarding whether clinically relevant research results, including individual research results, will be disclosed to subjects, and if so, under what conditions.
     • Whole genome sequencing: for research involving biospecimens, a statement regarding whether the research will (if known) or might include whole genome sequencing (i.e., sequencing of a human germline or somatic specimen with the intent to generate the genome or exome sequence of that specimen).
4. If the research involves vulnerable populations or sensitive issues, the investigator addresses additional regulatory and/or institutional requirements. The investigator may consult the IRB Survival Handbook or ORI staff for guidance. The vulnerable populations and sensitive issues include, but are not limited to:
   • Research involving the participation of children;
   • Research involving DNA banking, genetic research, or gene therapy;
   • Research activities directed toward fetuses and/or neonates;
   • Research involving economically or educationally disadvantaged persons;
   • Research involving prisoners;
   • Research involving individuals with impaired decision-making capacity.
5. If UK is the reviewing IRB for a reliance study, ORI staff contacts the Reliance Team to determine if the Reliance Agreement, communication plan, or local context form indicates that additional language be added to the consent document (e.g., local injury language, state reporting requirements, etc.).
6. The investigator also must address the following issues, if applicable to the proposed research:
   • HHS/NIH-sponsored multicenter clinical trial: the investigator must include a copy of the HHS/NIH-approved sample informed consent document in the application. The investigator must justify any deletion or substantive modification of information concerning risks or alternative procedures contained in the sample informed consent document, and the IRB must approve these deletions or modifications. For trials sponsored by the National Cancer Institute (NCI), investigators must provide copies of such IRB-approved changes, with their justifications to the appropriate Cooperative Group headquarters;
   • Investigational drugs, devices, or biologics: In the IRB approved consent form, the investigator must inform the subject in the purpose that the study includes evaluation of both safety and effectiveness of the test article and state the test article is investigational, and, if applicable, not approved by the FDA;
   • Applicable FDA-regulated clinical trials: In the IRB approved consent form, the investigator must inform the subject that the clinical trial will be entered into a national clinical trial registry data bank; the consent form must also be posted on a publicly available federal website (clinicaltrials.gov or a docket folder on regulations.gov).
   • Early withdrawal from FDA-regulated clinical trials: In the IRB approved consent form, the investigator informs the subject that data collected to the point of withdrawal, remains part of the study database and may not be removed. The investigator informs the subject if the protocol includes continued follow-up activities such as accessing medical or confidential records to collect clinical outcome information after withdrawal from the interventional portion of a trial. In an IRB approved consent form, the investigator obtains the subject’s consent for this limited participation; otherwise, the researcher does not conduct follow-up activities to collect clinical outcome information.
   • The process of dose escalation;
   • The possibility of risk for an unborn child, a man or woman’s ability to procreate, or a woman’s ability to conceive or carry a child;
   • Additional requirements as specified in the IRB full and expedited review; applications/informed consent template.
7. If the research involves establishing a specimen/tissue repository or registry, the PI must address the applicable issues outlined in the “Sample Repository/Registry/Bank Consent” template.
8. The IRB assesses the PI’s description of the informed consent process to ensure that the process meets the general requirements of informed consent (i.e., consent be obtained from the subject or subject’s legally authorized representative; be in language understandable to the subject; be obtained under circumstances that provide the subject with the opportunity to consider whether or not to participate and that minimize coercive influences; does not include language through which the subject is made to waive his/her legal rights or releases the investigator, sponsor, or institution from liability for negligence). The IRB uses the Criteria for IRB Approval: Reviewer Checklist in conducting this assessment.
9. The IRB determines whether disclosure of any investigator conflict of interest is warranted in the informed consent process and document.
10. The IRB reviews the proposed informed consent document(s) to ensure that all applicable federal and UK requirements are met.
11. When the IRB approves a study, the consent document is stamped with an approval date. Investigators may only enroll subjects using informed consent/assent forms which have a valid “IRB approval” stamp unless circumstances do not accommodate use of version containing an IRB stamp (e.g., use of an electronic system).
12. The investigator is responsible for ensuring that informed consent is obtained from each research subject or his/her LAR after the subject or the subject’s LAR has had an adequate opportunity to read the form and prior to subject participation in any part of the study, using the process and form approved by the IRB.
13. The subject or the subject’s LAR sign and date the informed consent document at the time of consent. Only individuals authorized (in the IRB approved protocol) to obtain informed consent adds their name on the line entitled “Name of [authorized] person obtaining consent from the subject.” The subject or LAR signing on the subject’s behalf receives a copy of the signed form.

Use of the Short Form Written Consent Document

1. The PI may request to use a short form written consent document and process as required by 45 CFR 46.116) up to five times in the same language, to enroll non-English speaking subjects.
2. The IRB reviews the request and may approve the short form process if the study meets all of the requirements outlined in 45 CFR 46.117(b), and as applicable, 21 CFR 50.27(b).
3. When the IRB approves use of the short form written consent:
   • The IRB approves the English informed consent which provides the oral content presented to the subject or the subject’s LAR, and the translated short form which embodies the basic and appropriate elements of informed consent.
   • The PI ensures there is a witness, independent of the study team, to the oral presentation.
   • For participants who do not speak English, the PI ensures an interpreter is available to translate the oral presentation of the IRB approved English version of the consent form.  If the interpreter is present in-person or video conference, he/she may also serve as the witness.
   • The subject or the subject’s LAR signs and dates the short form.
   • The witness signs and date the short form.
   • The witness and study personnel obtaining consent sign and date the English version of the consent form.
   • The study personnel obtaining consent gives a copy of the short form consent and the English consent form to the subject or the subject’s LAR.  

University of Kentucky Research Involving Individuals with Impaired Consent Capacity

1. The PI completes the IRB application and after obtaining IRB approval implements the research in accordance with the requirements for assessing consent capacity specified in the UK Impaired Consent Capacity Policy. See this policy and the IRB application for details on the procedure.
2. In conducting the review, the IRB uses the recommendations for assessing consent capacity as a guide to ensure additional safeguards are in place. (See Impaired Consent Capacity Policy for details.)

Assent

1. The PI develops processes and forms consistent with guidance provided in a number of IRB policies including but not limited to: UK Impaired Consent Capacity Policy; UK IRB Policy on Children in Research; Assent Form Template;and requirements found in the IRB application related to assent.
2. The PI includes in the IRB application a description of the process/ procedure for obtaining and documenting assent when research includes:
   • Children and/or;
   • Individuals with impaired consent capacity.
3. The IRB reviews the proposed process and, if applicable, the assent form to ensure compliance with IRB guidance and federal requirements.

Emancipated Individuals

1. Under Kentucky state law, absent a court order, there are no classes of individuals under the age of 18 who are named as emancipated for all purposes. Consequently, if the PI would like to enroll some or all prospective subjects as emancipated, the PI consults with UK legal counsel when preparing the IRB application and prior to submitting the application to the IRB. He/she includes legal counsel’s recommendations in the IRB application.
2. Under Kentucky state law, in general, individuals under the age of 18 who are living on their own, have borne a child, or are married are viewed as emancipated and are able to consent to participate in some research studies. Legal counsel reviews the studies on a case-by-case basis to determine whether the subjects are legally emancipated. If pregnant individuals under the age of 18 are neither married nor living on their own (i.e., living at home under the care of their parents or some other adult), they are not legally emancipated, and both parental permission and subject assent are needed.
3. When conducting the study, given the variety of living situations that an individual may find him or herself living in, investigators may need to make decisions on a subject-by-subject basis regarding the applicable state statutory requirements. If there are questions relating to whether an individual meets the state statutory requirements to be emancipated, the investigator consults UK legal counsel.
4. If a child or a class of subjects is deemed to be emancipated, 45 CFR 46 Subpart D and 21 CFR 50 Subpart D do not apply, and the subject may provide informed consent as an adult.

Obtaining Informed Consent outside the State of Kentucky

1. If the PI conducts the research outside the state of Kentucky and the research involves children, a LAR, or a guardian, the investigator follows the requirements of the state/country in which he/she conducts the research. The PI also determines which individuals meet the federal definitions for child/children, LAR, or guardian in the location outside the state of Kentucky.
2. The PI identifies the state law(s) applicable to the determination of legally authorized representative and contacts UK legal counsel for review and determination prior to approval by the IRB. If the PI is unable to identify applicable state law(s), the PI contacts UK legal counsel for assistance prior to approval by the IRB.

Non-English Speaking Subjects

1. Investigators deliver all information regarding informed consent/assent to potential subjects or their LAR in the subject’s native language(s) or one that the subject understands. The investigator provides the IRB and prospective subjects a translated version of the consent/assent form(s).
2. ORI staff identifies a cultural consultant to review the study and informed consent/assent document(s) for accuracy and cultural appropriateness. If ORI staff are unable to identify an individual to serve as a cultural consultant, the investigator provides a cultural consultant for review of the accuracy of the informed consent form(s) and evaluation of cultural appropriateness.
3. ORI staff ensure the consultant does not have a conflict of interest. (See IRB Member and Consultant Conflict of Interest SOP)
4. The IRB may use expedited review procedures in approving such documents if the IRB has already approved the English language consent/assent document(s), and the cultural consultant attests to the accuracy of the translation. 

Competent English-Speaking Subjects with Reading or Visual Impairment

1. Investigator, designated study personnel, or subject’s family member reads the IRB approved consent document to the blind or illiterate potential subject or their LAR in the presence of an impartial third-party witness.
2. The investigator allows ample time for the document to be read and the subject or LAR to consider participation.  
3. The investigator may enroll a qualifying potential subject who retains the ability to understand the concepts of the study and evaluate the risk and benefit of being in the study when it is explained verbally.
4. The potential subject makes the decision and indicates approval or disapproval to study entry.
5. The subject makes his/her mark or the LAR signs to document consent.
6. The impartial third party witnesses the entire consent process and signs the consent document.

Research that Requires Monitoring of Informed Consent/Assent Process and Procedures

1. The IRB determines which research requires monitoring of the informed consent/assent process and the procedure and frequency with which such monitoring occurs based on the degree of risk to subjects, the need for protection of vulnerable subjects, or concerns related to an incident of noncompliance.
2. A designated IRB member(s), the QIP Coordinator (see QIP Directed On-Site Review SOP), or other designee(s) (as determined by the IRB) monitors the informed consent/assent process. The monitoring involves direct observation, interviews of subjects, surveys of subjects, or other means as deemed appropriate by the IRB for the circumstances.

Recordkeeping

1. For studies conducted at a UK hospital or clinic, the PI scans a copy of the signed consent form or, if applicable, assent form into the electronic medical record unless the IRB waives the requirement. The PI must also keep the original signed consent/assent document(s), or an accurate reproduction(s), securely throughout the record retention period in accord with the IRB-approved protocol.
2. For studies conducted in other settings (i.e., not conducted in UK hospital/clinic), the PI keeps original signed informed consent/assent document(s), or an accurate reproduction(s), in accord with the ORI/IRB Recordkeeping SOP and study procedures as approved by the IRB.
3. For FDA-regulated research, the study personnel obtaining informed consent, document in the subject's case history, that the subject provided consent prior to participation.
4. The IRB documents its review as delineated in the applicable procedures for a particular review mechanism (e.g., initial full review, expedited review, modification review, etc.) and the ORI/IRB Recordkeeping SOP.
   Waiver of Informed Consent
5. The PI makes a preliminary decision to seek a waiver of informed consent and submits a justification for the request in the IRB application.
   • The IRB may waive the requirements or alter elements if it finds and documents:
     • The research involves no more than minimal risk to the subjects;
     • The research will not adversely affect the rights and welfare of subjects;
     • The investigator could not practicably conduct the research without the waiver or alteration; and
     • Whenever appropriate, study personnel provide subjects additional pertinent information after participation.
6. The IRB may also waive the requirement to obtain informed consent or alter some of the elements if the IRB finds and documents that:
   • The research or demonstration project is to be conducted by or is subject to approval of state or local government officials and is designed to study, evaluate or examine public benefit of service programs, procedures, methods or levels of payment; AND
   • The investigator could not practicably conduct the research without the waiver or alteration.
7. If the IRB reviews the protocol at a convened meeting, ORI staff document the waiver of informed consent approval in the IRB meeting minutes.
8. If the protocol is eligible for expedited review, the expedited reviewer documents whether the study meets each of the criteria on the Expedited Reviewer Signature Page.

Waiver of Informed Consent for FDA-regulated Planned Emergency Research 

1. The PI completes the IRB application following the procedures outlined in the Initial Full Review SOP. The ORI staff screen the application using procedures outlined in the Initial Full Review SOP. ORI staff ask the PI to address any additional issues in accordance with 21 CFR 50.24 not included in the standard IRB application, such as plans for public disclosure in communities prior to initiation.
2. At the convened meeting, ORI staff provide the IRB Chair or designee with a copy of 21 CFR 50.24. The individual chairing the meeting goes through each regulatory requirement. The IRB discusses whether the research meets each requirement and raises any applicable controverted issues. The outcomes of the review are the same as those listed in the Initial Full Review SOP. ORI staff record the discussion in the minutes, following the procedures in the Minutes of IRB Meetings SOP.

Exception from Informed Consent Requirement for Use of FDA-Regulated Test Articles in a Single Subject

1. The PI must obtain informed consent, even in an emergency use situation, unless the study meets certain conditions. (See Emergency Use SOP)

Waiver of Parental or Guardian Permission for Research Involving Children 

1. The PI makes a preliminary decision to seek a waiver of parental or guardian permission for participation of children in accord with 45 CFR Subpart D 46.408 (c) or 45 CFR 46.116(c)(d). The PI includes justification for the waiver and a description of a substituted appropriate mechanism for protecting children who participate in the research.
2. The IRB approves the request provided the study meets the conditions outlined in 45 CFR Subpart D 46.408(c) or 45 CFR 46.116(f)(3).
3. If the IRB reviews the research at a convened meeting, ORI staff record the discussion on each criterion in the minutes.
4. If the IRB reviews the study using expedited procedures, the expedited reviewer documents whether the research meets the criteria on the Expedited Reviewer Signature Page.

Waiver of Signatures for FDA-Regulated Research

1. The PI makes an initial request to waive the signature requirements for obtaining informed consent, as specified in the IRB application.
2. The IRB waives the signature requirement to obtain a signed informed consent form if the research presents no more than minimal risk and involves no procedures for which the IRB normally requires written consent.
3. When the IRB waives the signature requirement, the IRB has the authority to require the investigator to provide subjects with a written statement regarding the research and reviews a written description of the information that the PI will give to the subjects.
4. If the IRB reviews the request at a convened meeting, ORI staff include the discussion on each of the criteria in the IRB minutes.
5. If the IRB reviews the study using expedited procedures, the expedited reviewer documents whether the research meets each of the criteria on the Expedited Reviewer Signature Page.

Waiver of Signatures for Non-FDA-regulated Studies

1. The PI makes an initial request to waive the signature requirements for obtaining informed consent, as specified in the IRB application.
2. The IRB may waive the signature requirements to obtain a signed informed consent form if:
   • The only record linking the subject and the research would be the consent document and the principal risk would be potential harm resulting from a breach of confidentiality. Study personnel must ask each subject whether he/she wants to sign the informed consent document; or
   • The research presents no more than minimal risk to subjects and involves no procedures for which written consent is normally required (i.e., a cover letter or a phone script); or
   • If the subjects or legally authorized representatives are members of a distinct cultural group or community in which signing forms is not the norm, that the research presents no more than minimal risk of harm to subjects and provided there is an appropriate alternative mechanism for documenting that informed consent was obtained.
3. When the IRB waives the signature requirement, the IRB has the authority to require the investigator to provide subjects with a written statement regarding the research and reviews a written description of the information that subjects will receive.
4. When the IRB reviews the request at a convened meeting, ORI staff include the discussion on each of the criteria in the meeting minutes.
5. When the IRB reviews the protocol using expedited procedures, the expedited reviewer documents whether the research meets each of the criteria on the Expedited Reviewer Signature Page. 

Exception from Informed Consent Requirement for Screening, Recruiting, or Determining Eligibility of Potential Research Subjects 

1. The PI must obtain informed consent when screening, recruiting, or determining eligibility, unless the study meets certain conditions. An IRB approves a research proposal in which an investigator obtains information or biospecimens for the purpose of screening, recruiting, or determining eligibility of prospective subjects without informed consent of the prospective subject or the subject’s legally authorized representative, if either of the following conditions are met:
   • the investigator obtains information through oral or written communication with the prospective subject or legally authorized representative, or
   • The investigator obtains identifiable private information or identifiable biospecimens by accessing records previously collected or stored identifiable specimens.

Studies approved prior to implementation of the Revised Common Rule (approved prior to January 21, 2019)

For those studies receiving approval prior to the implementation of the Revised Common Rule, the previous regulations apply. No action is required on the part of the investigator as these studies are “grandfathered in” under the previous regulations and do not need to update consent forms to comply with the Revised Common Rule. For more information regarding the regulations applicable to these studies, please see archived Informed Consent SOP Revision #11. 

REFERENCES

21 CFR 50.20

21 CFR 50.23

21 CFR 50.24

21 CFR 50.25

21 CFR 50.27

21 CFR 56.109 (b),(c) 

45 CFR 46.111

45 CFR 46.116

45 CFR 46.117

34 CFR 97 [Department of Education Subpart D]

Approved By: ORI Director, Nonmedical IRB Chair, Medical IRB Chair

Date First Effective: June 27, 2005

Last Revision Date: February 15, 2019

Revision #9

OBJECTIVE

To describe policies and procedures for reviewing research involving vulnerable subjects

GENERAL DESCRIPTION

The University of Kentucky (UK) Institutional Review Board (IRB) gives special consideration to protecting the welfare of vulnerable subjects such as children, prisoners, fetuses/neonates, individuals with impaired decision-making capacity, and/or economically or educationally disadvantaged persons. The IRB also recognizes that additional populations such as students may qualify as vulnerable populations and need safeguards in place for their protection during study participation. 

RESPONSIBILITY

Execution of SOP:  Principal Investigator (PI)/Study Personnel, IRB, Office of Research Integrity (ORI) Staff 

PROCEDURES

Screening and Educational Guidance 

1. The PI identifies the categories of vulnerable subjects (e.g., individuals with impaired decision-making capacity, fetuses/neonates, economically or educationally disadvantaged persons, children, prisoners, and students) involved in the research in the IRB application.
2. When research on vulnerable subjects is conducted outside the state of Kentucky, the PI identifies the state law(s) applicable to the determination of legally authorized representative and contacts UK legal counsel for review and determination prior to approval by the IRB. If the PI is unable to identify applicable state law(s), the PI contacts UK legal counsel for assistance prior to approval by the IRB.
3. The investigator also provides specific information in the IRB initial review application which focuses on ethical and regulatory issues pertaining to conduct of research involving vulnerable subjects.
4. ORI staff conduct a preliminary screening of an IRB application upon receipt.
5. IRB membership includes representation with expertise in selected vulnerable populations routinely reviewed by the IRB, such as children or prisoners. ORI staff screen the application to ensure that designated representatives review research involving prisoners, children, or if the application requires consultation for other issues. Depending upon the type of review, designated representatives either attend the convened meeting or provide comments prior to the meeting.
6. The ORI, IRB Chair, or designee requests a consultant review if additional expertise is needed. (See Initial Full Review, Expedited Initial Review, Continuing Review, or Modification, Deviations, and Exceptions IRB Review of Changes SOPs)

Protocol Review Process

1. The IRB reviews the IRB application to determine whether the protocol includes enrollment of vulnerable subjects and whether appropriate safeguards are in place.
2. As applicable, the IRB considers the following elements when reviewing research involving vulnerable subjects:
   • Inclusion/exclusion criteria;
   • Selection or exclusion of certain groups based on perceived limitations (i.e., targeting prisoners as research subjects because they are a readily available “captive” population);
   • Knowledge of applicable or local context/laws that bear on the decision-making process (i.e., emancipated individuals, legally authorized representatives, age of majority for research consent).
3. The IRB follows applicable federal and state regulations and IRB policy to assist in reviewing and approving proposed research that involves vulnerable subjects such as:
   • Pregnant Women, Human Fetuses and Neonates (45 CFR 46, Subpart B);
   • Research Involving Prisoners (45 CFR 46, Subpart C) Prisoner representatives review IRB applications involving prisoners. Under the Kentucky Administrative Regulations applicable to county jails (not federal prisons), inmates may not participate in medical research (i.e., drug, device, biologic clinical trials);   
   • Research Involving Children (45 CFR 46, Subpart D, 21 CFR 50, Subpart D and 34 CFR 97, Subpart D) – (See guidance in IRB Policy on Children in Research and the Informed Consent SOP).
   • Research Involving Individuals with Impaired Decision-Making Capacity – (See guidance in the UK Impaired Decision-Making Capacity Policy, and the Informed Consent SOP);
     • Research involving economically or educationally disadvantaged persons;
     • Research involving UK students – (See the IRB Guidance for Enrolling University Students as Subjects);
     • Research involving K-12 students – (See the IRB Guidance for Enrolling K-12 Students as Subjects).
4. The IRB considers each of the specific findings discussed in the IRB application forms for research involving vulnerable subjects as documented by IRB approval. IRB approval also documents that the IRB members acknowledge and agree with the preliminary description of safeguards and the risk assessment of the protocol as described in the application by the PI. ORI staff document discussions of controverted issues at convened meetings in the meeting minutes.
5. Specific findings are either documented by ORI staff in the meeting minutes (i.e., for protocols reviewed by the convened board) or by exempt/expedited reviewers in their determinations in accord with applicable IRB/ORI SOPs. The IRB does not reapply the categories during subsequent reviews unless changes to the protocol warrant such review.
6. The IRB requires more frequent review (i.e., issue an approval period shorter than 12-months) for protocols involving vulnerable populations based on the nature of the research and the level of risk.

References

45 CFR 46 Subpart B 

45 CFR 46 Subpart C 

45 CFR 46 Subpart D 

21 CFR 50 Subpart D

34 CFR 97 Subpart D

Approved By: ORI Director, Nonmedical IRB Chair, Medical IRB Chair

Date First Effective: October 15, 2005

Last Revision Date: August 6, 2020

Revision #10

OBJECTIVE

To describe the procedures for Institutional Review Board (IRB) review of medical device clinical investigations including those exempt from, or subject to Investigational Device Exemption (IDE) regulations (i.e., Full IDE, Abbreviated IDE and Treatment IDE) and compassionate use of an investigational device.

GENERAL DESCRIPTION

The Food and Drug Administration (FDA) IDE regulation [21 CFR 312] describes three types of device studies: 1) exempt studies, 2) significant risk (SR) and 3) nonsignificant risk (NSR) studies. For studies that do not meet the criteria for exemption from IDE requirements, the sponsor and the IRB categorize the device investigation as either SR or NSR. The sponsor makes the initial determination of risk. The principal investigator (PI) submits the proposed study to a convened IRB for formal determination of the appropriate category.

Unless the study is exempt from IDE requirements, an SR device study must be conducted under an FDA approved IDE and an NSR device study may be conducted under an abbreviated IDE with the IRB acting as surrogate for the FDA. An exemption from the IDE requirement is not an exemption from the requirement for prospective IRB review or informed consent. In the event of any question regarding need for an IDE, the IRB may request that the PI consult FDA and provide documentation of FDA’s response. FDA is the final arbiter as to whether a device study is exempt, SR, or NSR.

Each PI who uses an investigational medical device is responsible for control of the devices received in accordance with regulatory requirements. PIs develop and submit a plan for control, storage, and accountability of the device to the IRB. During review of the research protocol, the IRB evaluates these plans and PI responsibilities regarding the investigational devices. The investigator is responsible for implementing the plan as approved by the IRB. Post IRB-approval monitoring to evaluate whether the investigator meets these responsibilities falls under the Quality Improvement Program (QIP). (See the Quality Improvement Program Directed On-Site Review SOP for details.)

FDA’s expanded access program provides a pathway for patients with a serious or life-threatening disease or condition to access an investigational medical device through compassionate use, treatment IDE, and emergency use.

FDA’s compassionate use provision allows access for patients who do not meet the requirements for inclusion in a clinical investigation but for whom the treating physician believes the device may provide a benefit in treating and/or diagnosing a serious disease or condition, for which there is no comparable or satisfactory alternative. A physician or sponsor of an IDE may submit a IDE supplement to FDA requesting compassionate use or if there is no IDE for the device, the physician or sponsor may submit a compassionate use request to FDA. The provision is typically approved for individual patients but may be approved to treat a small group of patients. For compassionate use, the IRB chair or designee documents concurrence with the use, ensures FDA concurrence, and receives and reviews safety reports if applicable.

FDA’s treatment use provision of the IDE facilitates availability of promising new devices to patients with life-threatening or serious diseases for whom no comparable or satisfactory alternative exists.  Standard IDE regulations for conduct and review apply to the Treatment IDE as data is collected on the device’s safety and effectiveness. A treating physician who uses a device under a Treatment IDE is responsible for complying with all applicable IDE responsibilities.

FDA’s emergency use provisions are described in the Emergency Use SOP which outlines procedures for emergency use of a device in an immediately life-threatening situation in which no standard acceptable treatment is available.

If a protocol involving a medical device is subject to review under more than one department or agency’s regulations, the protocol must meet the requirements of each set of regulations.

Definitions

A medical device is defined as any health care product that does not achieve its primary intended purposes by chemical action or by being metabolized. 

An investigational device is a medical device which is the subject of a clinical study designed to evaluate the effectiveness and/or safety of the device. The device is still in the developmental stage and is not considered to be in commercial distribution.

An investigational use is a clinical evaluation of a legally marketed device for a new intended use or a new indication for use.

A subject, as defined in device regulations [21 CFR 312.3], is a human who participates in an investigation, either as an individual on whom or on whose specimen an investigational device is used or as a control. A subject may be in normal health or may have a medical condition or disease.

A significant risk (SR) device study is a study of a device that presents a potential for serious risk to the health, safety, or welfare of a participant and (1) is intended as an implant; or (2) is used in supporting or sustaining human life; or (3) is of substantial importance in diagnosing, curing, mitigating, or treating disease, or otherwise prevents impairment of human health; or (4) otherwise presents a potential for serious risk to the health, safety, or welfare of a participant.

A nonsignificant risk (NSR) device study is one that does not meet the definition for an SR study. 

An Investigational Device Exemption (IDE) permits a device, which otherwise would be required to comply with a performance standard or to have premarket approval, to be shipped lawfully for the purpose of conducting investigations of that device. An approved IDE exempts a device from specific Food and Drug Administration (FDA) requirements as laid out under 21 CFR 812. An approved IDE means that the IRB (and FDA for SR devices) has approved the sponsor’s study application and that the study meets all the requirements under 21 CFR 812.

Expanded access is a potential pathway for patients with a serious or life-threatening disease or condition to access an investigational medical device that has not been approved or cleared by the FDA for treatment outside of clinical trials when no comparable or satisfactory alternative therapy options are available

Compassionate use is expanded access involving use of an investigational device to treat or diagnose an individual patient or a small group of patients with a serious disease or condition when there are no available alternative options.

A Treatment IDE is expanded access use of an investigational device to treat or diagnose a group of patients with a serious or immediately life-threatening disease or condition when the device is also being studied for the same use under an approved Investigational Device Exemption. 

RESPONSIBILITY

Execution of SOP: IRB Members, Office of Research Integrity (ORI) Staff, FDA, Principal Investigator (PI)/Study Personnel, Study Sponsor

PROCEDURES

1. An investigator conducting research that involves collection of safety or efficacy data on a medical device completes the applicable device section of the IRB application and includes reference to FDA in informed consent documents. The IRB reviews the information and documentation provided by the investigator to determine whether the study is subject to or exempt from IDE requirements.

Studies Exempt from IDE Requirements

1. The PI is responsible for consulting FDA guidance or contacting FDA to determine if the device meets specific criteria to be exempt from IDE requirements.
2. If the PI considers the device study to be exempt from IDE requirements, he/she references the exemption category to the IRB documentation from FDA or sufficient justification to support the exemption category (e.g., in-vitro diagnostic device that meets the exemption criteria in 21 CFR 812.2 (c)(3)).

Studies Subject to Full or Abbreviated IDE Requirements: Significant vs. Nonsignificant Risk Determination

1. If the study is being conducted under a valid IDE, the PI includes in the IRB application, the IDE number, name of IDE holder/sponsor, and sponsor protocol imprinted with number or written communication from FDA or the sponsor documenting the IDE number.
2. If the study is not being conducted under a valid IDE at time of IRB submission, the PI includes in the IRB application the sponsor’s initial assessment of the risk (SR or NSR), and the rationale used in making the risk determination. The PI includes FDA correspondence or documentation if available.
3. The convened IRB makes its own determination of the risk category (SR or NSR). The convened IRB may review reports of prior investigations conducted with the device, the proposed investigational plan, a description of subject selection criteria, monitoring procedures, and any other information the IRB deems necessary to make its decision.
4. The IRB may request that the PI consult with the FDA as appropriate. If FDA provides a determination, it is considered final and the IRB does not duplicate the effort.
5. If the IRB determines that a protocol submitted for approval involves an SR device, which has been deemed NSR by the sponsor, the IRB notifies the investigator and where appropriate, the sponsor (i.e., investigator is sponsor).
6. If the IRB determines that a study involves the use of an SR device, the PI must obtain an IDE and IRB approval before the study begins and must conduct the study in accordance with IDE requirements.
7. If the IRB determines that the study is NSR, there is no requirement for submission of an IDE application to the FDA. The PI conducts the study in accordance with FDA abbreviated IDE requirements.
8. After making the risk determination, the IRB conducts the review of the study using the same criteria it would use in considering approval of any full review application. (See Initial Full Review SOP.) The IRB considers the risks and benefits of the medical device compared to the risks and benefits of alternate devices or procedures as listed in the IRB application.
9. The IRB may approve or disapprove the proposed research based on local context and its responsibilities to protect human subjects in research.
10. ORI staff document the SR/NSR determination in the meeting minutes and may include the SR/NSR determination in correspondence sent to the PI. (See Minutes of IRB Meetings SOP.)
11. In a study of an investigational device in which an unanticipated problem/adverse event to subjects or others occurs, the investigator submits a report of the problem or adverse event occurring during the investigation to the IRB and sponsor. (See Unanticipated/ Anticipated Problem/Adverse Event Reporting SOP.)

IRB Evaluation of PI’s Plan to Control Device

1. During review of the research proposal, the IRB evaluates the information provided by the PI which describes qualifications or training required to use or administer the device (if applicable) and plans for control of the investigational device(s) including policies and procedures for storage, dispensing, and accountability.
2. If the IRB determines the PI’s plans are inadequate, the IRB may request changes and/or additional information.
3. The Quality Improvement Program (QIP) may conduct periodic reviews of protocols involving use of an investigational device.
4. Where applicable, the QIP staff provides the IRB with a follow-up evaluation of whether the PI meets investigator responsibilities for control, storage, dispensing, and accountability of the device.  (See the QIP Directed On-Site Review SOP for details.)

Compassionate Use of an Investigational Device (individual patient or small group) 

1. Before using the device, the PI or treating physician submits the following information to the ORI:
   • A completed device section of the IRB application with the "COMPASSIONATE USE IDE" checkbox marked;
   • Documentation of sponsor’s authorization and FDA’s concurrence with use (e.g., compassionate use IDE supplement approval letter from FDA);
   • A description of patient(s) condition, treatment, and monitoring plan;
   • An independent assessment from an uninvolved physician, if available; and
   • A copy of the informed consent/authorization form.
2. ORI staff screen the IRB submission and verify the submission includes authorization from the sponsor and approval from FDA.
3. ORI staff forward the materials to the IRB Chair, Vice Chair, or appropriate physician member of the IRB.
4. The IRB chair or his/her designee reviews the submission for concurrence with the compassionate use.
5. The PI or treating physician obtains informed consent/authorization from the patient or legally authorized representative.
6. At the conclusion of treatment, the physician or PI reports a written summary of the results of the expanded access use to the IDE sponsor or the FDA and any safety related information or problems encountered with use of the device, to the IRB and IDE sponsor or FDA (as applicable). 

Treatment Use of an Investigational Device

1. If the study is being conducted under a Treatment IDE, the PI completes the applicable device section of the IRB application, including the Treatment IDE number, name of Treatment IDE holder/sponsor, and sponsor protocol imprinted with number or written communication from FDA or the sponsor documenting the Treatment IDE number.
2. ORI staff screen the IRB submission following procedures described in the Initial Full Review SOP.
3. The convened IRB reviews the protocol using the same procedures as outlined above for a Full IDE. 

REFERENCES

21 CFR 812

21 CFR 56

21 CFR 50

21 CFR 812.66 

21 CFR 56.108(a)(1)

21 CFR 812.2(b)

21 CFR 812.2(c)(3)

21 CFR 812.36

Quality Improvement Program Directed On-Site Review SOP

Approved By: ORI Director, Nonmedical IRB Chair, Medical IRB Chair

Date First Effective: July 24, 2006

Last Revision Date: May 9, 2019

Revision #4

OBJECTIVE

To describe the process for Institutional Review Board (IRB) review of a humanitarian use device (HUD) including clinical, emergency, compassionate, and investigational use 

GENERAL DESCRIPTION

The University of Kentucky (UK) Medical IRBs may approve the following situations involving HUDs: 

• Clinical use of a HUD as a legally marketed device; OR  
• Emergency or compassionate use of a HUD based on a healthcare provider/principal investigator (PI) request that meets IRB criteria; OR
• Investigational use for research purposes either consistent with approved labeling or off-label.  

Definitions

A Humanitarian Use Device is a medical device intended to benefit patients in the treatment or diagnosis of a disease or condition that affects or is manifested in fewer than 8,000 individuals in the United States per year.

The term Use refers to use of a HUD according to its approved labeling and indications.

The term Investigational Use refers to research involving a HUD.

A Humanitarian Device Exemption (HDE) is a Food and Drug Administration (FDA) marketing application that is similar to a premarket approval application but is exempt from the effectiveness requirements of the medical device law, provided the device meets safety conditions and will not expose patients to significant or unreasonable risk. An HDE approval is based on safety and probable benefit.

An Investigational Device Exemption (IDE) refers to the regulations under 21 CFR 812. An approved IDE means that the IRB (and FDA for significant risk devices) has approved the sponsor’s study application, and the proposed use meets all the requirements of 21 CFR 812.

RESPONSIBILITY 

Execution of SOP:  IRB, IRB Chair, IRB Vice Chair, IRB Members, Office of Research Integrity (ORI) Staff, Principal Investigator (PI)/Study Personnel, Healthcare Providers 

PROCEDURES 

HUD Clinical Use for Treatment or Diagnosis Consistent with Approved Labeling 

Before use of the HUD, the responsible healthcare provider submits an IRB application to the ORI in accord with the Initial Full Review SOP for review and approval by the IRB.

1. The convened Medical IRB reviews clinical use of a HUD, using all standard full review criteria and procedures.
2. The IRB approves the clinical use of the HUD device consistent with the scope of the FDA-approved labeling for groups of patients who meet the clinical criteria.
3. The IRB may choose to require informed consent or allow use of a modified clinical consent that is consistent with or combined with the approved labeling and/or patient information packet.
4. When the healthcare provider submits Continuation Review (CR) materials, the Medical IRB conducts continuing review using standard criteria and procedures. The IRB may use expedited review procedures for continuing review.
5. The healthcare provider submits a report to FDA and to the IRB whenever a HUD may have caused or contributed to a death or serious injury or has malfunctioned and would be likely to cause or contribute to a death or serious injury if the malfunction were to recur (21 CFR 814.126(a)).
6. The healthcare provider labels and stores the HUD in a secure manner to ensure appropriate accountability and traceability and to clearly display any use limitations or restrictions designated by the IRB or HDE holder.

HUD Emergency Use for Both Off-Label or Approved Label Use

1. The healthcare provider submits an emergency use request directly to the IRB Chair in accord with the Emergency Use SOP. However, if the immediate use of the HUD is, in the healthcare provider’s opinion, required to preserve the life of the patient and time is not sufficient to obtain assessment by the IRB chair or designee, the healthcare provider submits a report in writing within five (5) working days following the use as described in #2 below.
2. The Medical convened IRB, IRB Chair, Vice Chair, or medically qualified IRB member assesses the request to determine whether it meets the following regulatory requirements for emergency use of a HUD in a single subject:
   • The patient has a life-threatening condition; OR
   • The patient has a serious medical condition that can reasonably be expected to benefit from the use of the HUD; AND
   • This is the best acceptable treatment alternative for the patient; AND
   • Alternative treatments pose greater risks for the patient or are deemed to provide less benefit than the HUD.
3. The healthcare provider obtains informed consent from the patient or the patient's legally authorized representative using the IRB-approved consent form or modified clinical consent that is consistent with or combined with the approved labeling and/or patient information packet.
4. If the healthcare provider proposes to administer the HUD in emergency use situations without informed consent, the request to the IRB Chair includes a statement certifying in writing that the proposed use meets all of the conditions listed in 21 CFR 50.23. If possible, this statement should include an assessment from an independent physician who is qualified in the appropriate medical specialty. However, if the immediate use of the HUD without informed consent is, in the healthcare provider’s opinion, required to preserve the life of the patient and time is not sufficient to obtain the independent determination by a qualified physician, the independent evaluation must be included in writing in the report provided within five (5) working days as described in #5 below.
5. Within five (5) working days following the emergency use, the healthcare provider submits written notification of the use to the IRB including identification of the patient involved, the date of use, and the outcome of the administration. The convened IRB reviews the report consistent with procedures in the Emergency Use SOP.
6. If the healthcare provider fails to submit a request involving emergency use of an HUD to the IRB for review and confirmation prior to initiation, the IRB retrospectively reviews the information pertaining to the situation to determine if the administration met the regulatory definition of HUD use and whether failure to comply with this SOP meets the IRB definition of noncompliance. (See the Noncompliance SOP)
7. If the healthcare provider administering the emergency use HUD is not listed on the IRB approved HUD protocol, he/she identifies and informs the principal healthcare provider on the protocol within five (5) working days of the emergency use.
8. For emergency use of a HUD, the healthcare provider assumes the responsibilities of the HDE holder, monitors the patient, and reports the use of the HUD (including any safety-related information) to the HDE holder or FDA.
9. The healthcare provider submits a report to the HDE holder or FDA and to the IRB whenever a HUD may have caused or contributed to a death or serious injury or has malfunctioned and would be likely to cause or contribute to a death or serious injury if the malfunction were to recur (21 CFR 814.126(a)).

HUD Off-Label Clinical Use for Treatment or Diagnosis

1. FDA determines safety and probable benefit for use of a HUD within its approved indications.
2. If a healthcare provider proposes clinical use of a HUD outside of the approved indications, he/she contacts the HDE holder to determine if any requirements or restrictions exist that prohibit off-label use.
3. Before use of the HUD, the healthcare provider proposing the off-label clinical use protocol submits an IRB application to the ORI in accord with the Initial Full Review SOP for review and approval by the IRB.  
4. The healthcare provider includes the following with the Medical IRB submission:
   1. HDE holder documentation allowing off-label clinical use (if available) or attestation that use does not violate existing restrictions or limitations;
   2. Justification for off-label clinical use;
   3. Circumstances which necessitate treatment using the HUD;
   4. A discussion of why alternative treatments are unsatisfactory; and
   5. Assurances and information about patient protection measures.
5. In the title of the application, the healthcare provider includes the words “Off-label Use HUD”. The convened Medical IRB reviews the off-label clinical use using all standard full review criteria and procedures.
6. The healthcare provider obtains informed consent from the patient or the patient's legally authorized representative using the IRB-approved consent form or modified clinical consent that is consistent with or combined with the approved labeling and/or patient information packet.
7. When the healthcare provider submits Continuation Review (CR) materials, the Medical IRB conducts continuing review using standard criteria and procedures. The IRB may use expedited review procedures for continuing review.
8. The healthcare provider submits a report to FDA and to the IRB whenever a HUD may have caused or contributed to a death or serious injury or has malfunctioned and would be likely to cause or contribute to a death or serious injury if the malfunction were to recur (21 CFR 814.126(a)).
9. The healthcare provider labels and stores the HUD in a secure manner to ensure appropriate accountability and traceability and to clearly display any use limitations or restrictions designated by the IRB or HDE holder.

Off-Label Single-Subject Compassionate Use 

1. A healthcare provider with an IRB approved HUD protocol may request a protocol exception for a single-subject compassionate use in accord with the Deviations and Exceptions SOP.
2. The healthcare provider includes the following in the exception request:
   • HDE holder documentation allowing off-label compassionate use (if available) or attestation that use does not violate existing restrictions or limitations;
   • Justification for off-label clinical use;
   • A description of the patient's non-emergent condition and the circumstances necessitating treatment with the device;
   • A discussion of why alternative treatments are unsatisfactory; and
   • Assurances and information about patient protection measures.
3. The IRB Chair, other IRB member, or convened IRB conducts the review in accord with the Deviations and Exceptions SOP.
4. The healthcare provider monitors the patient and submits a follow-up report including any safety-related information to the HDE holder or FDA and IRB.
5. The healthcare provider submits a report to the HDE holder or FDA and to the IRB whenever a HUD may have caused or contributed to a death or serious injury or has malfunctioned and would be likely to cause or contribute to a death or serious injury if the malfunction were to recur (21 CFR 814.126(a)).

HUD Investigational Use Consistent with Labeling

1. The IRB may, at its discretion, approve a PI's application for the investigational use of a HUD to collect safety and effectiveness data consistent with the scope of the FDA-approved labeling.
2. The PI conducting an investigation of a HUD according to its approved labeling and indication must obtain IRB approval and informed consent consistent with all FDA-regulated clinical studies. Hospital consents are not sufficient for investigational use.
3. The PI submits an IRB application to the ORI and the IRB reviews and approves the study in accord with the Initial Full Review SOP.

HUD Off-Label Investigational Use

1. The IRB may, at its discretion, approve a PI's application for the investigational use of a HUD beyond its approved labeling when the proposed use is in compliance with 21 CFR 812 requiring an IDE, if there is significant risk.
2. The PI submits an IRB application to the ORI and the IRB reviews and approves the study in accord with the Initial Full Review SOP and the Medical Device SOP.
3. The ORI and IRB follow procedures outlined in the Medical Device SOP for IRB review of significant risk and non-significant risk investigational device use. (See Medical Device SOP)
4. If the HUD carries significant risk, the PI may conduct the study following FDA approval of an IDE application.
5. The PI obtains informed consent consistent with all FDA-regulated clinical studies. Hospital consents are not sufficient for investigational use.

REFERENCES

21 CFR 812

21 CFR 814

21 CFR 50.23

FDA HUD Designation based on 21^st Century Cures Act

Approved By: ORI Director, Nonmedical IRB Chair, Medical IRB Chair

Date First Effective: July 24, 2006

Last Revision Date: May 9, 2019

Revision #8

OBJECTIVE

To describe the procedure for the emergency use of a Food and Drug Administration (FDA) regulated investigational drug, biologic, or device in a single subject 

GENERAL DESCRIPTION

The need for an investigational drug, biologic, or device may arise in an emergency situation that does not allow time for submission of an investigational new drug (IND) application or investigational device exemption (IDE) in accordance with federal regulations. FDA provides guidance for clinicians or investigators regarding an Emergency Use IND or IDE.

Although the FDA may exempt the requirement for prior review and approval by the IRB in emergency use cases [21 CFR 56.104(c)], University of Kentucky (UK) Institutional Review Board (IRB) policy requires review and confirmation that use of the article meets FDA criteria by the IRB Chair, Vice Chair, or physician member in these situations. In accord with FDA regulations, investigators who administer an investigational treatment, in an emergency situation, without IRB approval, must submit a report of the use to the IRB within five (5) working days.

In addition, any subsequent use of the test article in another subject must first receive full IRB review. The FDA acknowledges, however, that it would be inappropriate to deny emergency treatment to a second individual if the only obstacle is that the IRB has not had sufficient time to convene a meeting to review the issue.

In activities regulated by 45 CFR 46, an investigator may not use data related to emergency care (i.e., single patient administration) as a prospectively planned systematic investigation designed to contribute to generalizable knowledge. Investigators may not aggregate such data with research data, even if the emergency protocol is identical to that of a research protocol subsequently approved by the IRB, nor may the investigator include the outcome of such care in any report of a research activity. 

If the activity involves emergency use of an FDA regulated test article in a life-threatening situation, the activity is research under FDA regulations, and the patient is a subject under FDA regulations. The FDA may require data from an emergency use of a test article in a life-threatening situation to be reported in a marketing application. 

If use is for a life-threatening or serious disease but time is sufficient to obtain IRB approval, follow procedures in the Expanded Access Program (EAP) for Drugs SOP or the Compassionate Use or Treatment IDE section of the Medical Device SOP.

Definitions

Emergency Use is defined as the use of a test article (e.g., investigational drug, biologic, or device) in a human subject in a life-threatening situation in which no standard acceptable treatment is available and in which there is not sufficient time to obtain IRB approval.

Life-threatening, for the purposes of 21 CFR 56.102(d), includes the scope of both life-threatening and severely debilitating, as defined below.

• Life-threatening means diseases or conditions where the likelihood of death is high unless the course of the disease is interrupted. Life-threatening situations include diseases or conditions with potentially fatal outcomes, where the end point of clinical trial analysis is survival. The criteria for life-threatening do not require the condition to be immediately life-threatening or to immediately result in death. Rather, the subject must be in a life-threatening situation requiring intervention before review at a convened meeting of the IRB is feasible.
• Severely debilitating means diseases or conditions that cause major irreversible morbidity. Examples of severely debilitating conditions include blindness, loss of arm, leg, hand or foot, loss of hearing, paralysis, or stroke. 

RESPONSIBILITY

Execution of SOP: Office of Research Integrity (ORI) Staff, IRB, IRB Chair, IRB Vice Chair, Physician IRB Member, Principal Investigator (PI)/Study Personnel 

PROCEDURES

1. Before administering the test article, the PI submits the following information directly to the IRB Chair for review and confirmation for emergency use of a test article in a single subject:
   • Written memorandum, email, or telephone call summary of explanation that justifies administration of the test article (e.g., life-threatening situation, no standard acceptable treatment available, and not sufficient time to obtain IRB approval);
   • Copy of the informed consent form; and
   • Completed IRB application, if possible, but the IRB Chair may accept a post administration application. The PI must include the words "EMERGENCY USE" and the name of the test article in the title.
2. However, if the immediate use of the test article is, in the healthcare provider’s opinion, required to preserve the life of the patient and time is not sufficient to obtain assessment by the IRB chair or designee, the PI submits a report in writing within five (5) working days following the emergency use as described below.
3. If the PI proposes to administer the test article in an emergency use situation without informed consent, the request to the IRB Chair should include a statement certifying in writing that all of the conditions listed in 21 CFR 50.23 are met. These conditions are as follows:
   • The subject is confronted by a life-threatening situation necessitating the use of the test article;
   • Informed consent cannot be obtained because of an inability to communicate with or obtain legally effective consent from the subject;
   • Time is insufficient to obtain consent from the subject’s legal representative; and
   • There is no alternative method of approved or generally recognized therapy available that will provide an equal or greater likelihood of saving the subject’s life.
     
     If possible, this statement should include an evaluation by a physician who is not participating in the clinical investigation. However, if the immediate use of the test article without informed consent is, in the investigator’s opinion, required to preserve the life of the subject and time is not sufficient to obtain the independent determination by a nonparticipating physician, the independent evaluation must be included in writing in the five (5) working days report described below.
4. If the IRB Chair is not available, the PI should submit the information listed in item 1 and, if applicable, item 2 to the ORI.
5. In the event a PI submits an emergency use request to the ORI, ORI staff forward the materials to the IRB Chair, Vice Chair, or physician member, as available.
6. If time is not sufficient to obtain approval by the convened IRB, the IRB Chair, Vice Chair, or physician member assesses the request to determine whether it meets the regulatory requirements for emergency use and responds to the PI in writing. The IRB Chair, Vice Chair, or physician member may determine that the PI can proceed or may withhold confirmation. (See Emergency Use Checklist: Guidance for IRB Chair, Vice Chair, or Physician Member)
7. The IRB Chair, Vice Chair, or physician member forwards the request and his/her response to the ORI and ORI staff process the request.
8. Within five (5) working days of the emergency use, the PI must submit a report to the IRB regarding the emergency use of the test article. That report is to include:
   • A brief description of the life-threatening situation;
   • Justification for use of the test article;
   • Signed consent form or justification for administration without informed consent;
   • Statement of review and evaluation of the situation by a physician who is not participating in the clinical investigation (if administered without informed consent); and
   • A description of the outcome of administration.
9. At a convened IRB meeting, ORI staff inform the IRB that the IRB Chair, Vice Chair, or physician member assessed a request for emergency use using the regulatory definition, and the committee verifies the following criteria to approve the emergency use:
   • The subject was confronted by a life-threatening situation necessitating the use of the investigational drug, biologic, or device;
   • No alternative method of approved or generally recognized therapy was available that provided an equal or greater likelihood of saving the subject’s life; and
   • Time was not sufficient to obtain IRB approval.
10. If an investigator fails to submit a request involving emergency use of an investigational test article to the IRB for review and confirmation prior to initiation, the IRB retrospectively reviews the situation to determine if the test article administration met the regulatory definition and whether failure to comply with this SOP meets the IRB definition of noncompliance. (See the Noncompliance SOP) 

REFERENCES

21 CFR 56.102(d)

21 CFR 56.104(c)

21 CFR 50.23

Approved By: ORI Director, Nonmedical IRB Chair, Medical IRB Chair

Date First Effective: July 24, 2006

Last Revision Date: August 5, 2020

Revision #4

OBJECTIVE

To describe the procedures for utilizing the Food and Drug Administration (FDA) Expanded Access Program (EAP) including individual patient and intermediate or large population treatment investigational new drug (IND) applications

GENERAL DESCRIPTION

Definitions

Expanded Access (sometimes called Compassionate Use) is a mechanism to facilitate availability of investigational drugs (as early in the drug development process as possible) for patients with serious or immediately life-threatening diseases or conditions for which there are no satisfactory alternative treatments.

For the purpose of expanded access to investigational drugs for treatment use, immediately life-threatening disease or condition means a stage of disease in which there is reasonable likelihood that death will occur within a matter of months or in which premature death is likely without early treatment.  A serious disease or condition means a disease or condition associated with morbidity that has substantial impact on day-to-day functioning. Short-lived and self- limiting morbidity will usually not be sufficient, but the morbidity need not be irreversible, provided it is persistent or recurrent.

A treatment IND is a large scale expanded access program typically following resolution of phase III or during phase II where sufficient safety data is available.

Emergency Use is defined as the use of a test article (e.g., investigational drug, biologic, or device) in a human subject in a life-threatening situation in which no standard acceptable treatment is available and in which there is not sufficient time to obtain IRB approval. See the Emergency Use: Single Subject SOP.

General Requirements

The FDA will permit an investigational drug to be used under the EAP for the treatment of a serious or life-threatening disease or condition When all of the following apply: 

• There is no comparable or satisfactory alternative therapy to diagnose, monitor, or treat the disease or condition;
• Patient enrollment in a clinical trial is not possible;
• Potential patient benefit justifies the potential risks of treatment; and
• Providing the investigational medical product will not interfere with investigational trials that could support a medical product’s development or marketing approval for the treatment indication.

Expanded access requires prospective review by the IRB and informed consent/authorization from the patient or Legally Authorized Representative (LAR).

The FDA describes three distinct categories of EAP based on the number of people who need access and the level of risk. An expanded access IND submission is required for each type of expanded access.

1. Individual patient IND, including emergency use IND (21 CFR 312.310) commonly held by the treating physician or investigator for treatment of an individual patient.
2. Intermediate population treatment IND (21 CFR 312.315) commonly held by the sponsor (manufacturer) for use in a population smaller than a typical treatment IND or treatment protocol. The investigational drug for intermediate population treatment INDs may be in active development or may be an FDA approved drug that is unavailable or in limited supply.
3. Large population treatment IND or treatment protocol (21 CFR 312.320) commonly held by the sponsor for widespread treatment use. For a large population treatment IND, the sponsor must be pursuing marketing approval.

Before submitting an individual patient IND to the FDA, a physician or PI must confirm that the manufacturer will provide the drug. If a manufacturer has an existing EAP IND available, the PI may coordinate access to the drug through the manufacturer’s approved IND rather than filing a separate individual patient IND.

FDA developed Form 3926 specifically for physicians requesting an expanded access IND for an individual patient.  The form includes an option to request FDA waive the requirement review by the convened IRB, permitting expedited review.

FDA policy specifies that "the provision for emergency use would rarely apply to a treatment protocol or treatment IND because these are planned uses of the test article and sufficient time is available to obtain IRB review and approval." In rare cases in which emergency use does apply for individual patients, administration takes place according to emergency use federal regulations (21 CFR 56.104) following procedures in the Emergency Use: Single Subject SOP.

 The FDA identifies special considerations when a patient is to be treated under an EAP:

• Drug Development: In considering EAP use, individual needs must be balanced against societal needs. The FDA stipulates that expanded access use should not compromise enrollment or interfere with active clinical investigations that could support approval of the drug.
• Informed Consent/HIPAA Authorization: Informed consent is especially important in expanded access use situations because the subjects are desperately ill and particularly vulnerable. They will receive medications which have not been proven either safe or effective in a clinical setting. Both the setting and their desperation may work against their ability to make an informed assessment of the risk involved. Therefore, the PI must ensure that potential subjects are fully aware of the risks involved in participation.
• Charging for Treatment INDs: The FDA permits charging for the drug, agent, or biologic when used in an EAP when regulatory criteria are met. Therefore, the IRB must pay particular attention to EAPs in which the subjects will be charged for the cost of the drugs. If subjects will be charged for use of the test article, economically disadvantaged persons may inadvertently be excluded from participation. Charging for participation may preclude economically disadvantaged persons as a class from receiving access to test articles. The IRB must balance this interest against the possibility that it will not be available for treatment use until it receives full FDA approval unless the sponsor can charge for the drug.
• Regulatory Responsibilities: Per the FDA, a licensed physician under whose immediate direction an investigational drug is administered for expanded access use is considered an investigator assuming all applicable regulatory responsibilities. An individual who submits an IND for expanded access use is considered a sponsor-investigator, and assume applicable responsibilities for sponsors and investigators (21 CFR 312.305 (c)).  

RESPONSIBILITY

Execution of SOP: IRB Chair, IRB Vice Chair, IRB Members, Office of Research Integrity (ORI) Staff, Principal Investigator (PI)/Study Personnel, Physician

PROCEDURES

Individual Patient IND

1. The physician or PI submits the following individual patient expanded access:
   • a completed IRB application with the phrase "INDIVIDUAL PATIENT IND" in the title;
   • a copy of the FDA Form 3926 (for individual patient requests);
   • an individual patient IND approval letter from the FDA;
   • an investigator’s brochure, if applicable;
   • a description of patient situation and treatment plan adequate to assess whether risks have been minimized and are reasonable in relation to anticipated benefits; and
   • a copy of the informed consent/authorization form which includes the statement indicating that although the primary use of the drug is for treatment, the drug is investigational, and FDA has not determined it is safe or effective for the condition of treatment.
2. ORI staff screen the IRB submission and verify the IND number according to procedures described in the Initial Full Review SOP.
3. If the IND was requested using the Form 1571 or the waiver option on Form 3926 was not checked, the ORI schedule the submission for convened review as outlined in the Initial Full Review SOP.
4. If the IND was requested using Form 3926 and the waiver option was checked, the ORI send for review by the IRB Chair or designee as outlined in the Initial Expedited Review SOP.
5. At the conclusion of treatment, the physician or PI reports a written summary of the results of the expanded access use to the IND sponsor or the FDA and any safety related information or problems encountered to the IRB and IND sponsor or FDA (as applicable).

Central IRB Approval

1. In cases where the expanded access protocol has received central IRB approval, UK may defer responsibility for IRB review of the individual patient use to the central IRB where appropriate agreements and required approvals are obtained consistent with the IRB Reliance SOP. 

Individual Patient IND in an Emergency Situation

1. In rare cases in which an emergency requires that the patient be treated before a written IND submission can be made, the PI obtains authorization for individual use from the FDA by telephone or electronic communication with subsequent submission of IND paperwork (21 CFR 312.310).
2. The PI follows procedures described in the Emergency Use SOP, submitting emergency use information directly to the IRB Chair.
3. The IRB Chair, ORI staff, and the convened IRB follow review procedures as described in the Emergency Use SOP.

Intermediate or Large Population Treatment IND

1. The PI follows procedures described in the Initial Full Review SOP with the following additions and provisions:  
   • inclusion of the phrase "TREATMENT IND" in the title;
   • documentation of FDA treatment IND approval (i.e., correspondence from the FDA or commercial sponsor, IND number printed on sponsor protocol); and
   • related materials including the treatment protocol, investigator’s brochure, informed consent/authorization form, and potential investigational drug costs.
2. ORI staff screen the IRB submission following procedures described in the Initial Full Review SOP.
3. The convened IRB reviews the protocol as outlined in the Initial Full Review SOP and according to federal regulations.
4. At the conclusion of treatment, the physician or PI reports a written summary of the results of the expanded access use (including any safety related information) to the IND sponsor or the FDA and submits a copy to the IRB.

REFERENCES

21 CFR 312.300

Form FDA 3926 Instructions

Approved By: ORI Director, Nonmedical IRB Chair, Medical IRB Chair

Date First Effective: October 15, 2005

Last Revision Date: July 18, 2012

Revision #5

OBJECTIVE

To describe Institutional Review Board (IRB) review of data and safety monitoring plan(s) (DSMP) to ensure adequate protection is in place for subjects

GENERAL DESCRIPTION 

Investigators develop data and safety monitoring plans as a mechanism for assuring the safety of human subjects and human research data, the validity of data, and the appropriate termination of studies. The IRB requires review and approval of data and safety monitoring plans for greater than minimal risk research, or clinical investigations funded by the National Institutes of Health (NIH) or regulated by the Food and Drug Administration (FDA). 

RESPONSIBILITY 

Execution of SOP:  Principal Investigator (PI)/Study Personnel, IRB

PROCEDURES 

1. At initial review, investigators conducting greater than minimal risk research, or NIH funded/FDA regulated clinical investigations include a description of the proposed data and safety monitoring plan in the IRB application.
2. During initial review, the IRB reviews the general description of the DSMP to determine that adequate protections for human subjects are in place. (See the Initial Full Review SOP)
3. The IRB recognizes that the elements of a monitoring plan may vary depending on the potential risks, complexity, and nature of the trial.  The IRB reviews several elements of the DSMP, which may include but are not limited to:
   • Plans for monitoring the progress of trials and the safety of subjects;
   • Plans for assuring compliance with requirements regarding the reporting of adverse events;
   • Plans for review or analysis of cumulative safety data to determine whether harm is occurring;
   • Plans for assuring that any action resulting in a temporary or permanent suspension of a clinical trial is reported to the appropriate agencies;
   • Plans for assuring data accuracy and protocol compliance;
   • Plans for assuring communication among multi-center sites adequately protect the subjects (for multicenter studies where the lead PI is employed by UK or UK is the coordinating institution).
4. The IRB may request additional information regarding the DSMP at initial review.
5. After reviewing the plan, the IRB may determine that a formal DSMP is not necessary or that the study may require an independent individual or independent body (e.g., Data and Safety Monitoring Board [DSMB]) for monitoring. For example, in studies of small numbers of subjects, toxicity may more readily become apparent through close monitoring of individual subjects while in larger studies risk may better be addressed through statistical comparisons of treatment groups.
6. If an external sponsor or funding agency has the responsibility for data and safety monitoring, the Office of Sponsored Projects Development (OSPA) administrator negotiates the provision of data and safety monitoring plans and reports (both routine and urgent) by the sponsor to the PI in the funding agreement or contract.
7. If the IRB (or an external entity) determines the DSMP of an investigator-initiated protocol must include a Data and Safety Monitoring Board (DSMB), the IRB evaluates the DSMB for membership, charter, and DSMB responsibilities, all of which include, but are not limited to, the following:
   • DSMB Membership
     • Multidisciplinary representation from relevant specialties. (This may include experts such as bioethicists, biostatisticians and basic scientists.);
     • Membership limited to individuals free of apparent significant conflicts of interest, whether financial, intellectual, professional, or regulatory in nature;
     • Size appropriate to the type of study.
   • DSMB Charter
     • Detailed presentation of the membership composition, including qualifications and experience;
     • Roles and responsibilities of the DSMB and, if relevant;
     • Authority of the DSMB (e.g., advisory to the sponsor, PI);
     • Timing and purpose of DSMB meetings;
     • Procedures for maintaining confidentiality;
     • Format, content, and frequency of DSMB reports;
     • Specific data to be monitored and statistical procedures, including monitoring guidelines, to monitor the identified primary, secondary, and safety outcome variables;
     • Decision rules and actions to be taken upon specific events, outcomes or end points; and
     • Plans for changing frequency of interim analysis as well as procedures for recommending protocol changes.
   • DSMB Responsibilities
     • Initial review of the proposed research to assure quality study conduct;
     • Procedures to review and assure quality of study conduct including data management and quality control procedures;
     • Evaluation of the quality of ongoing study conduct by reviewing the study accrual, compliance with eligibility, subject adherence to study requirements, and accuracy and completeness of data;
     • Consideration of factors external to the study when relevant information becomes available, such as scientific or therapeutic developments that may have an impact on the safety of the subjects or the ethics of the study;
     • Recommendations of  early termination based on efficacy results;
     • Recommendations of termination due to unfavorable benefit-to-risk or inability to answer study questions;
     • Recommendations for continuation of ongoing studies;
     • Consideration of overall picture, primary and secondary analysis;
     • Modification of sample sizes based on ongoing assessment of event rates; and
     • Review of final results.
8. The PI submits documentation evidencing DSMP or DSMB activities (i.e., summary report, meeting minutes) to the IRB prior to continuation review if provided to the PI by the sponsor or prepared by the PI, as described in the DSMP.  The IRB reviews DSMP or DSMB materials received prior to continuation review as a modification request. (See Modification, Deviations, and Exceptions--IRB Review of Changes SOP)
9. The PI is responsible for acquiring evidence that DSMB activities have occurred if the sponsor has not been providing the documentation. At the time of continuation review of the study, the PI submits documentation representing DSMP or DSMB activities (i.e., summary report, meeting minutes) not previously submitted to the IRB.
10. At continuation review, the IRB reassesses the risk category and determines whether the PI should provide additional information in the informed consent document based on the information provided in the DSMP or DSMB materials. 

REFERENCES

NIH Policy for Data and Safety Monitoring

Approved By: ORI Director, Nonmedical IRB Chair, Medical IRB Chair

Date First Effective: July 24, 2006

Last Revision Date: March 23, 2023

Revision #8

Quality Assurance/Improvement Findings

1. At a minimum, the MCC Pediatric Oncology group reviews NCI CIRB pediatric protocols on a yearly basis and the MCC CRO reviews adult NCI CIRB protocols on a yearly basis at continuation review. The MCC Pediatric Oncology group and the MCC CRO review confirms the following:
   • the most current informed consent form was used;
   • the UK required HIPAA authorization or Waiver of Authorization form was used; and
   • the UK required informed consent form language was retained in the consent document. (See NCI CIRB Review SOP for UK specific local context informed consent language and HIPAA authorization language to be added to the NCI CIRB informed consent template).
   • the regulatory file for the study is maintained in accord with UK and sponsor policy. In addition, MCC CRO staff verifies these regulatory elements (listed above) during its quarterly auditing process. The MCC CRO staff notifies the NCI CIRB when a regulatory deficiency has been cited on an audit that occurred during the time that the NCI CIRB was responsible for study review.
2. The MCC CRO, and the MCC Pediatric Oncology group sends written reports of the findings to the RCO following review by the DSMC as outlined in the MCC DSMC SOP’s. The DSMC Chair forwards a copy of the final audit report to the RCO. The RCO forwards the report to the IRB Chair and/or ORI Director. More immediate contact with the RCO is used when necessary.

REFERENCES

21 CFR 50.25

21 CFR 56.111

45 CFR 46.108

45 CFR 46.111

45 CFR 46.116

45 CFR 46.117

45 CFR 46 Subparts C

ATTACHMENTS

University of Kentucky (UK) specific informed consent language to be added to the National Cancer Institute, Central Institutional Review Board (NCI CIRB) informed consent template

University of Kentucky (UK) specific assent language to be added to the National Cancer Institute, Central Institutional Review Board (NCI CIRB) informed consent template for pediatric protocols (assent for subjects age 12-17 years of age)

University of Kentucky (UK) specific informed consent language to be added to the National Cancer Institute, Central Institutional Review Board (NCI CIRB) informed consent template (Signed)

University of Kentucky (UK) specific assent language to be added to the National Cancer Institute, Central Institutional Review Board (NCI CIRB) informed consent template for pediatric protocols (assent for subjects age 12-17 years of age) (Signed)

University of Kentucky Pediatric Hematology/Oncology template

Approved By: ORI Director, Nonmedical IRB Chair, Medical IRB Chair

Date First Effective: June 30, 2005

Last Revision Date: May 9, 2019

Revision #7

OBJECTIVE 

To describe policies and procedures for completing the minutes of the convened meetings of the University of Kentucky (UK) Institutional Review Board (IRB) 

GENERAL DESCRIPTION 

The federal policies for the protection of human subjects [45 CFR 46.115 (a)(2)] require that "Minutes of IRB meetings, shall be in sufficient detail to show attendance at the meetings; actions taken by the IRB; the vote on these actions including the number of members voting for, against, and abstaining; the basis for requiring changes in or disapproving research; and a written summary of the discussion of controverted issues and their resolution." (Office for Human Research Protections) 

Good minutes enable a reader who was not present at the meeting to determine exactly how and with what justification the IRB arrived at its decisions. They also provide the IRB with sufficient detail to help reconstruct its discussions at a later date, if necessary. Comprehensive minutes also demonstrate respect for human subjects of research. Meeting minutes do not have to contain information provided in protocols the IRB has previously approved. This process assumes that if IRB members do not discuss a particular issue, the IRB deems the issue acceptable. 

RESPONSIBILITY 

Execution of SOP: Office of Research Integrity (ORI) Staff, IRB

PROCEDURES

Minutes Preparation

1. The ORI staff member attending the convened IRB meeting drafts detailed notes to document IRB discussions and determinations. ORI staff use the ORI minutes template as a guide in drafting minutes. Examples of the types of information included in the minutes are as follows:
   • The location of the meeting and the time the IRB convened the meeting and adjourned;
   • Documentation of attendance to include:
     • Initial and continued presence of a majority of members (i.e., quorum), including at least one non-scientist (See Conduct of Meeting SOP for definition of a quorum.);
     • Whether an alternate is voting and for whom he/she is voting;
     • When a member leaves the room or leaves the meeting;
     • That a licensed physician was present for review of all FDA protocols.
   • Minutes on the review of each protocol include the following:
     • The name(s) of IRB member(s) excused from the meeting due to a conflict of interest during the discussion and vote of the study;
     • Separate deliberations for each action taken by the IRB;
     • A summary of the discussion of any controverted issues and their resolutions;
     • The vote on these actions, including the number of voting “for,” “opposed,” or “abstaining”;
     • In order to document the continued existence of a quorum, ORI staff record votes in the minutes using the following format: # (e.g., 1, 2, 3, 4, or 5)/Total = 15; VOTE:  For = 14, Opposed = 0, Abstained = 1;
     • The IRB’s determination on frequency of continuation review (based on the degree of risk or the risk/benefit ratio);
     • Name of the investigator and others attending the meeting;
     • The basis for requiring changes in the research;
     • The level of risk determined by the IRB (at initial review; on all other reviews, the minutes only list level of risk if it has changed).
2. When the IRB disapproves a protocol, ORI staff document the basis for the disapproval in the minutes and document discussion of the controverted issues.
3. ORI staff write IRB meeting minutes impersonally and do not attribute opinions expressed by IRB members. Typically, the minutes only identify members by name when they recuse themselves from a particular review due to conflict of interest or leave the meeting for any reason.
4. The IRB considers written comments and/or information provided by ad hoc or cultural consultants in the review process. Ad hoc or cultural consultants may provide comments or recommendations in writing to the IRB prior to the meeting or attend the convened meeting to participate in the review. IRB staff maintain documentation of written comments or reports in the protocol submission. In cases where the consultant participates in the meeting, the minutes of the meeting document the information provided by the consultant.

Alternates

1. IRB meeting minutes document when an alternate IRB member replaces a voting IRB member and for whom the alternate is substituting.
2. When an alternate substitutes for a primary member, the alternate member is provided access to and reviews the same material that the primary reviewer received or would have received. 

Specific Findings

1.  When the IRB makes specific findings at convened meetings, ORI staff document these findings in the minutes of the meeting and include protocol-specific information justifying each finding. Examples of specific findings include, but are not limited to:
   • Alteration or Waiver of the Informed Consent Process in Non-FDA Requested Research: When the convened IRB reviews a procedure that alters or waives the requirements of informed consent, the minutes document the IRB’s determinations required by the federal regulations (45 CFR 46.116).
   • Waiver of Signatures: When the convened IRB reviews a procedure which waives the requirements for obtaining a signed informed consent document, the minutes document that the IRB made the findings in accordance with federal regulations (45 CFR 46.117, 21 CFR 56.109).
   • Research Involving Deception: When the convened IRB reviews research involving deception, the minutes document that the IRB made the findings in accordance with 45 CFR 46.116.
   • Research Involving Prisoners: When the IRB reviews research involving prisoners, the minutes indicate that the research meets the findings required by 45 CFR 46.305(a) and represents one of the categories of research permissible under Health and Human Services (HHS) regulations required by 45 CFR 46.306(a).
     • At least one member of the IRB is a prisoner or a prisoner representative with appropriate background and experience to serve in that capacity.
     • In cases where more than one IRB reviews a particular research project, only one IRB need satisfy this requirement.
   • Research Involving Children: When the IRB reviews research involving children, the minutes document that the IRB made the findings in accordance with IRB policy and federal regulations (45 CFR 46 Subpart D, 46.404-46.407 and 21 CFR Subpart D, 50.50-50.55).
   • Wards of the State or Other Agency: When the IRB reviews research involving children who are wards of the state or any other agency, institution, or entity, the minutes document that the IRB made the findings in accordance with federal regulations (45 CFR 46.409 and 21 CFR 50.56).
   • Research Involving Pregnant Women, Human Fetuses and Neonates: When the IRB reviews research involving pregnant women, human fetuses and neonates, the minutes document that the IRB made the findings in accordance with federal regulations (45 CFR 46 Subpart B).
   • Research Involving Individuals with Impaired Decision-Making Capacity or with Economically or Educationally Disadvantaged Persons: When the IRB reviews research involving individuals who are determined to be cognitively impaired and/or lack consent capacity, the minutes document that the IRB made the findings in accordance with federal regulations (45 CFR 46.111(b), 21 CFR 56.111(b)) and local policy.
   • Investigational New Devices: The minutes document the IRB’s determination of significant (SR) or nonsignificant risk (NSR) for Investigational New Devices and the rationale for that decision, in accordance with federal regulations ((21 CFR 812.3(m)).

Department of Health and Human Services (HHS) Approved Sample Consent Documents (e.g., NIH-Supported Multi-Center Clinical Trials) 

1. When the IRB reviews HHS-approved informed consent documents (e.g., NIH-supported multi-center clinical trials), the minutes include justification for any instance in which the IRB requested or approved the investigator’s deletions or substantive modifications of information concerning risks or alternative procedures contained in the HHS-approved sample informed consent document.

Tele/Videoconference Participation 

1. At a meeting in which IRB members participate via tele/videoconference, meeting minutes document that the IRB member:
   • Was provided access to all pertinent material prior to the meeting; and
   • Can actively and equally participate in the discussion of all protocols. 

Distribution of Minutes

1. ORI staff complete a draft of the IRB meeting minutes according to the ORI Customer Service Standards.
2. ORI staff disseminate the minutes as part of the IRB agenda for the meeting at which the minutes are scheduled to be approved.
3. Each IRB member present during the convened meeting reviews the minutes and forwards any necessary revisions to the appropriate ORI staff member. The IRB approves the minutes at a subsequent convened meeting. The IRB delegates to ORI staff the authority to correct administrative errors in meeting minutes as appropriate.
4. ORI staff provide access to approved minutes, as appropriate, to the Vice President for Research (VPR) and others as deemed appropriate by the ORI/IRB.

Record Keeping 

1. ORI staff maintain an electronic copy of minutes in a secure ORI directory. 

REFERENCES

45 CFR 46.107

45 CFR 46.108

45 CFR 46.111

45 CFR 46.115 (a)(2)

45 CFR 46.116

45 CFR 46.117

45 CFR 46 Subpart B

45 CFR 46.305(a)

45 CFR 46.306(a)

45 CFR 46.409

21 CFR 812.3(m)

21 CFR 50.23

21 CFR 50.24

21 CFR 50.56

21 CFR 56.109

21 CFR 56.111(b)

21 CFR 812.3(m)

Approved By: ORI Director, Nonmedical IRB Chair, Medical IRB Chair

Date First Effective: June 28, 2005

Last Revision Date: May 2, 2019

Revision #5

OBJECTIVE 

To describe the policies and procedures for the Office of Research Integrity (ORI)/Institutional Review Board (IRB) with respect to inspections by external regulatory agencies 

GENERAL DESCRIPTION

IRB and ORI records are subject to regulation and inspection by governmental agencies [e.g., the Food and Drug Administration (FDA) or the Office for Human Research Protections (OHRP)].  

RESPONSIBILITY

Execution of SOP: ORI Staff, IRB Chair, Vice President for Research (VPR), ORI Director, ORI Quality Improvement Program (QIP) Coordinator 

PROCEDURES

Upon Notice of Inspection

1. ORI staff/IRB Chair(s) ask all inspectors to identify themselves by name and title and to show appropriate identification. Inspectors must inform ORI staff/IRB Chair(s) what agency they represent and state the reason for the inspection. If an inspector is unable to provide identification, IRB Chair(s)/ORI staff will request that he/she return with the appropriate identification. Inspectors with the FDA must present a Form 482 upon arrival.
2. After the inspector has identified her/himself, UK personnel notify the ORI Director of the inspection. In instances when the ORI Director is not available, ORI staff offer to assist but inform the inspector that the supervisor is not present in the office. ORI staff then suggest that while they will do their best to help, the inspection should be rescheduled for a time when the ORI Director is available as the ORI Director might be better equipped to answer questions. If the ORI Director is not present and the inspector decides to stay and conduct the inspection, ORI staff must immediately contact the IRB Chair(s), ORI QIP Coordinator, and the VPR. 

During Inspection

1. The ORI Director or designee and a designated ORI staff member are available to the inspector throughout the inspection.
2. The ORI Director or designee, the designated ORI staff member, the Chair of the appropriate IRB (Medical or Nonmedical), if available, and the VPR, if available, may meet with the inspector at the beginning of the inspection.
3. ORI staff and the IRB Chair answer all questions posed by the inspector accurately, honestly, and succinctly and answer only the questions asked.
4. The inspector has the right to visually observe and inspect all facilities and records of the ORI/IRB.
5. If the inspector requests copies of IRB records or access to submissions, ORI staff comply with the requests and keep a list of the records the inspector has received or accessed. For paper files, the inspector may ask to duplicate these records at a UK facility or ask an ORI staff member to duplicate the records. If the inspector decides to use duplicating equipment outside the ORI offices, an ORI employee must travel with the inspector to verify the documents copied.
6. At the conclusion of the inspection, the ORI Director or designee, designated ORI staff member, the IRB Chair, if available, and the VPR, if available, may attend the exit interview. If an inspector identifies deficiencies, he/she may leave a copy of the findings with ORI staff, documenting the results of the inspection. If the inspector does not identify any problems during the inspection, the ORI Director/IRB Chair receives a letter following the inspection from agency headquarters confirming the outcome.

Following the Inspection

1. The ORI QIP Coordinator or designee maintains a record of everything reviewed by the inspector following the inspection, along with copies of any correspondence provided at the conclusion of or received after the inspection.
2. The QIP Coordinator or designee forwards copies of correspondence received from the inspector to the ORI Director, IRB, and the VPR. The VPR, IRB, and ORI staff discuss any corrective action and prepare and implement a response plan as appropriate.
3. The ORI/IRB submits a written response regarding the inspection to the appropriate authority, if required. The ORI Director and, if appropriate, the VPR and/or IRB Chair approve any written response. 

REFERENCES

Not applicable

Approved By: ORI Director, Nonmedical IRB Chair, Medical IRB Chair

Date First Effective: July 8, 2005

Last Revision Date: May 14, 2023

Revision #10

OBJECTIVE 

To describe policies and procedures for ensuring prompt Institutional Review Board (IRB)/Office of Research Integrity (ORI) reporting of events to institutional official(s), sponsor(s), coordinating center(s), and the appropriate federal regulatory agency as required in federal regulations

GENERAL DESCRIPTION 

University of Kentucky (UK) policy requires compliance with all applicable accreditation, local, state, and federal reporting requirements in the conduct of research involving human subjects. The IRB/ORI notifies appropriate officials when research falls under the purview of a federal regulatory agency and one or more of the following occurs:

• Unanticipated problems involving risks to subjects or others;
• Serious or continuing noncompliance with the regulations or requirements of the IRB;
• Suspension or termination of IRB approval for research due to noncompliance;
• Department of Health and Human Services (HHS) submitted or funded studies that are not otherwise approvable under 45 CFR 46 Subpart B, which include pregnant women, fetuses and neonates;
• HHS submitted or funded studies which include prisoners;
• Food and Drug Administration (FDA) regulated, HHS, or U.S. Department of Education submitted or funded studies which include children and are not otherwise approvable under applicable subparts;
• Certification of IRB approval;
• Exceptions to informed consent in emergency medical research;
• Regulatory agency requests for a report; and/or
• Inquiries or sanctions from government oversight agencies.

Reporting to regulatory federal agencies is not required if the principal investigator (PI) voluntarily closes down a study to new subject accrual or temporarily halts the research procedures. The IRB, IRB Chair, ORI, or administrative officials may recommend voluntary closure to the PI, but the PI makes the decision whether closure is appropriate. However, if the IRB or IRB Chair requires suspension or termination, the incident may be reportable under this policy.

Approval expiration as outlined in the Continuation Review SOP are not reportable under provisions of the SOP.

If the study is a reliance study in which UK reviews or UK cedes to another institution, ORI staff contact the Reliance Team to determine if the reliance agreement or communication plan stipulates reporting requirements for any of the scenarios listed below.

Definitions

Unanticipated Problem Involving Risks: See UK Policy on Unanticipated Problem and Safety Reporting.

Serious Noncompliance: See Noncompliance SOP.

Continuing Noncompliance: See Noncompliance SOP.

RESPONSIBILITY 

Execution of SOP: IRB Chair, IRB, ORI Staff, ORI Director, Vice President for Research (VPR), ORI Research Compliance Officer (RCO), Quality Improvement Program (QIP) Coordinator, Principal Investigator (PI)/Study Personnel 

PROCEDURES  

Unanticipated Problems Involving Risks to Subjects 

1. When the convened IRB determines that an unanticipated problem involving risks to the subject or others occurred on a research protocol, the ORI RCO or designee prepares a report within fifteen (15) days from the date the IRB conducts the final review of the unanticipated problem. The report includes the title of the research protocol and/or grant proposal; name of the PI on the protocol; IRB number assigned to the research protocol; the number (project identifier) of any applicable federal award(s) (grant, contract, or cooperative agreement); the nature of the event; the findings of UK or the IRB; and actions taken by the PI, UK, and/or the IRB to address the issue. The ORI Director, in consultation with the IRB Chair, finalizes the report, which the ORI RCO sends to the federal agency with a copy to the IRB Chair, VPR, PI, and other University administrators as determined by the IRB. (See also Unanticipated/ Anticipated Problem/Adverse Event Reporting SOP)
2. When research is regulated by the FDA, the IRB requires the PI to report to the sponsor, who must report to the FDA with a copy provided to the IRB. If the PI is also the sponsor, the IRB requires that the PI report to the FDA. The IRB may choose to prepare and send the report directly to the FDA.
3. If HHS conducts or funds the research, the ORI RCO sends the report to OHRP.
4. If an agency other than HHS, that is subject to the “Common Rule”, conducts or funds the research, the ORI RCO sends the report to the agency as required by the agency and OHRP.
5. The ORI RCO provides a copy of the federal report(s) and any final IRB actions to ORI staff, who are responsible for including the report(s) in the IRB study record.

Serious or Continuing Noncompliance 

1. When the convened IRB determines that serious or continuing noncompliance occurred on a research protocol, the ORI RCO or designee prepares a report within fifteen (15) days from the date the IRB conducts the final review of the serious and/or continuing noncompliance. The report includes the title of the research protocol and/or grant proposal; name of the PI on the protocol; IRB number assigned to the research protocol; the number (project identifier) of any applicable federal award(s) (grant, contract, or cooperative agreement); the nature of the event; the findings of UK or the IRB; and actions taken by the PI, UK, and/or the IRB to address the issue. The ORI Director, in consultation with the IRB Chair, finalizes the report. The ORI RCO sends the report to the federal agency with a copy to the IRB Chair, VPR, PI, and other University administrators as determined by the IRB. (See also Noncompliance SOP)
2. When research is FDA regulated, the IRB requires the PI to report to the sponsor, who must report to the FDA with a copy provided to the IRB. If the PI is also the sponsor, the IRB requires the PI to report to the FDA. The IRB may choose to prepare and send the report directly to the FDA.
3. If HHS conducts or funds the research, the ORI RCO sends the report to OHRP.
4. If an agency other than HHS, that is subject to the “Common Rule,” conducts or funds the research, the ORI RCO sends the report to the agency as required by the agency and OHRP.
5. The ORI RCO maintains all correspondence relating to the serious or continuing noncompliance. The ORI RCO provides a copy of the federal report(s) and any final IRB actions to ORI staff, who are responsible for including the report(s) in the IRB study record.

Suspension or Termination of Research 

1. When the IRB suspends or terminates approval of a research protocol, the ORI RCO or designee prepares a report to the applicable federal agency within fifteen (15) days from the date the IRB conducts the final review of the suspension or termination. The report includes the title of the research protocol and/or grant proposal; name of the PI on the protocol; IRB number assigned to the research protocol; the number (project identifier) of any applicable federal award(s) (grant, contract, or cooperative agreement); the nature of the event; the findings of UK or the IRB; and actions taken by the PI, UK, and/or the IRB to address the issue. The ORI Director, who may consult with the IRB Chair, finalizes the report, which the ORI RCO sends to the federal agency with a copy to the IRB Chair, VPR, PI, and other University administrators as determined by the IRB.
2. When research is FDA regulated, the IRB requires the PI to report to the sponsor, who must report to the FDA with a copy provided to the IRB. If the PI is also the sponsor, the IRB requires the PI to report to the FDA. The IRB may choose to prepare and send the report directly to the FDA.
3. If HHS conducts or funds the research, the ORI RCO sends the report to OHRP.
4. If an agency other than HHS, that is subject to the “Common Rule”, conducts or funds the research, the ORI RCO sends the report to the agency as required by the agency and OHRP.
5. The ORI RCO maintains all correspondence relating to the suspension or termination. The ORI RCO provides a copy of the federal report(s) and any final IRB actions to ORI staff, who are responsible for including the report(s) in the IRB study record.

Pregnant Women, Fetuses and Neonates 

1. Upon receipt of an IRB application or request, ORI staff screen protocols for any inclusion of pregnant women, fetuses or neonates in research submitted to or funded by HHS.
2. If the IRB finds that the research is not otherwise approvable for pregnant women, nonviable neonates or neonates of uncertain viability under 45 CFR 46 Subpart B and the research presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of pregnant women, fetuses or neonates, ORI staff, with input from the IRB and the PI, prepare a report to HHS based on the current guidance from OHRP. The IRB, in consultation with the ORI Director, approves the report, which ORI staff send to OHRP per OHRP guidance within fifteen (15) days of IRB approval of the report, with a copy provided to the VPR and PI.
3. ORI staff maintain copies of all correspondence.
4. If the OHRP disagrees with the IRB findings of the research involving pregnant women, fetuses, nonviable neonates, or neonates of uncertain viability, ORI staff share the information from OHRP with the IRB and the PI. 

Prisoners

1. ORI staff screen protocols for any inclusion of prisoners in research.
2. ORI staff notify the PI of HHS reporting requirements if the protocol involves prisoners.
3. With input from the IRB and/or the PI, ORI staff prepare a report to HHS based on the current guidance from OHRP on research which includes prisoners. ORI staff approve the report and send it to OHRP within fifteen (15) days of IRB approval of the report.
4. ORI staff ensure a copy of all correspondence is included in the IRB study record.
5. If OHRP disagrees with the IRB classification of the research involving prisoners, ORI staff share the information from OHRP with the IRB and PI.

Children 

1. ORI staff screen protocols submitted to/funded by HHS or the U.S. Department of Education or those regulated by FDA for any inclusion of children in research.
2. If the IRB finds that the research is not otherwise approvable but presents an opportunity to understand, prevent, or alleviate serious problems affecting the health or welfare of children under the applicable FDA, HHS, or U.S. Department of Education subpart, ORI staff, with input from the IRB and the PI, prepare a report to HHS based on the current guidance from the applicable agency. The IRB, in consultation with the ORI Director, approves the report and sends it through the VPR with a copy to the PI within fifteen (15) days of IRB approval of the report. ORI staff submit a copy to the institutional official of the applicable federal agency (e.g., Secretary of HHS through OHRP, Secretary of U.S. Department of Education, or Commissioner of FDA) based on current guidance from the agency.
3. ORI staff include all correspondence in the IRB study record.
4. If the applicable federal agency disagrees with the IRB findings of the research involving children, ORI staff share the information from the agency with the IRB and the PI.

Certification of IRB Approval 

1. When a funding agency requires certification of IRB approval, the PI contacts ORI to request that ORI staff prepare the certification document or indicates in the IRB application that the sponsor requires certification of IRB approval. The PI is responsible for requesting ORI documentation of IRB approval in accordance with funding agency requirements.
2. The PI may provide ORI staff with a copy of the agency certification form. ORI staff prepare the required agency form(s) and obtains the signature of either the UK authorized organizational representative for sponsored research or an authorized IRB member.
3. ORI staff retain a copy of the certification form in the IRB protocol record and forward the original certification form to the investigator.
4. The PI transmits the certification of IRB approval to the funding agency within the time period specified by the agency and provides the Office of Sponsored Projects Administration (OSPA) with a copy.
5. To prepare a certification form for grants/contracts that fund more than one IRB protocol, the PI provides ORI with a list of pertinent IRB protocol numbers. ORI staff verify the IRB numbers and IRB approval prior to preparing and issuing the certification document. The PI transmits the certification to the agency and provides OSPA with a copy.

Exception to Informed Consent in Emergency Medical Research 

1. When the IRB approves an exception from the general informed consent requirements for emergency research under FDA and HHS regulations, the PI provides the sponsor with a copy of the information publicly disclosed prior to the initiation and at the completion of the study. The PI is responsible for maintaining a copy of the report.
2. When the IRB does not approve an exception from the general informed consent requirements for emergency research under FDA and HHS requirements, ORI staff, with input from the IRB, prepare a report of the reasons why the IRB did not approve the exception. The IRB Chair, in consultation with the ORI Director, approves the report. ORI staff submit the report to the sponsor and the PI within fifteen (15) days of approval.
3. ORI staff include a copy of the report in the IRB study record. (See Informed Consent SOP)

Agency-Requested Reports

1. A federal agency may periodically ask the IRB or UK for a specific report on a variety of issues (e.g., alleged noncompliance submitted to a federal agency). ORI staff are responsible for informing the ORI Director of any inquiries from a government oversight office such as OHRP, FDA, or other agencies. The ORI Director or designee reviews the request and designates an ORI staff member to assist the IRB/UK with preparation of the report (e.g., the ORI RCO oversees noncompliance report preparation.)
2. The designated ORI staff member prepares the report in accordance with the agency’s request relative to content and timing.
3. The VPR or designee, in consultation with the ORI Director, approves the report. The ORI Director and/or IRB Chair or VPR determines who receives a copy of the report depending on the nature of the request.

Association for the Accreditation of Human Research Protection Programs, Inc. (AAHRPP) Reporting Requirements

1. In order to report to AAHRPP within 48 hours as required, ORI staff, researchers, and/or the IRB inform the ORI Director of any of the reportable events listed below. The ORI Quality Improvement Program (QIP) Coordinator or designee prepares a report, the ORI Director reviews the report, and the VPR approves the report. ORI staff submit reports as follows:
   • Within 24 hours of being notified or becoming aware of any negative actions taken by a government oversight office including but not limited to OHRP Determination Letters, FDA Warning Letters, and FDA restrictions placed on IRBs or Investigators.
   • Within 24 hours of being notified or becoming aware of any lawsuits (i.e., litigation, arbitration, or settlements initiated) related to human subjects research protections.
   • Within 24 hours of being notified or becoming aware of any press coverage (including not but limited to radio, TV, newspaper, online publications) of a negative nature regarding the UK HRPP.
     
     If it is unclear whether a particular item is reportable to AAHRPP, the QIP Coordinator or designee contacts the AAHRPP office for further advice.
2. The QIP Coordinator prepares the AAHRPP annual report. The QIP Coordinator or designee tracks information for inclusion in the annual report including but not limited to substantive organizational changes, changes in resources, program scope, and/or ORI policies and procedures. The ORI RCO or designee tracks noncompliance incidents, suggestions, concerns, and/or complaints received by ORI and makes recommendations to the ORI Director for inclusion in the AAHRPP annual report. The ORI Director reviews the report, and the VPR approves it.

Reports: IRB Determination of UK Officials to Receive a Copy of Reports

1. The IRB/ORI staff or the VPR determine appropriate institutional officials within UK who will receive a copy of a report on a case-by-case basis when the IRB/ORI staff send any of the federally mandated reports discussed in this SOP to a federal agency. These determinations are in accordance with applicable federal requirements and in accordance with the policies outlined in the HIPAA in Research SOP.
   
   Examples of institutional officials who may receive copies of a report include but are not limited to the following:
   • Vice President for Research (VPR);
   • Dean of the College;
   • Associate Dean of the College;
   • Department Chair;
   • Legal Counsel;
   • Director of the Office of Sponsored Projects Administration (OSPA);
   • UK Privacy Officer;
   • Other University administrators as determined by the IRB /ORI Director.

REFERENCES

45 CFR 46 Subpart B 

45 CFR 46 Subpart C 

45 CFR 46 Subpart D 

21 CFR 50 Subpart D

OHRP Guidance on the Involvement of Prisoners in Research

OHRP Guidance on the HHS 45 CFR 46.407 Review Process for Children Involved as Subjects in Research 

AAHRPP Accreditation Procedures

Approved By: ORI Director, Nonmedical IRB Chair, Medical IRB Chair

Date First Effective: June 30, 2005

Last Revision Date: May 21, 2023

Revision #11

OBJECTIVE 

To describe the policies and procedures followed to close a study.

GENERAL DESCRIPTION 

The principal investigator (PI) and/or the Institutional Review Board (IRB) may close approved protocols under certain circumstances. Generally, the PI is responsible for promptly closing out an IRB approved study if any of the following conditions exist:

1. All research/clinical investigation activities including data analysis and reporting are complete;
2. The PI never initiated the study;
3. Accrual for the study is finished, all data collection is complete and the only remaining activity is analysis of the data and:
   (i) Data are de-identified; or
   (ii) Data with identifiers for studies subject to the Revised Common Rule (approved on or after January 21, 2019) are encrypted; or
   (iii) For FDA regulated studies, there are no outstanding data queries or other investigator/site responsibilities in the trial (confirm with external study sponsor);
4. The PI plans to leave the University and intends to continue the research activities at another institution;
5. The study has been open for a period of three (3) or more years and the PI has enrolled no subjects in the study, collected no data from records, and/or collected/received no specimens.

The PI submits a closure request to the Office of Research Integrity (ORI). The status of study activities dictates the process by which closure is completed: 

1. Study Closure (executed by ORI staff as an administrative function) or
2. Final Review (executed by the IRB). 

The PI cannot close an active IRB approval if:

1. Interaction or intervention with currently enrolled subjects is still occurring;
2. Data is being collected from currently enrolled subjects and/or samples. 

Please note: If the PI is transferring from UK to another institution, the study should not be closed at UK until there is an active IRB approved protocol at the institution to which the PI is transferring.

The ORI may notify a PI that IRB approval or active IRB status has expired or that the IRB has inactivated IRB approval due to non-response from the PI to IRB requests. The IRB may suspend or terminate IRB approval. (See the Termination or Suspension of Research by the IRB SOP)

If a study has been open for a period of three (3) or more years and the PI has not enrolled subjects or acquired any specimens or recorded information for the study, the IRB may request the PI close the study, unless there are extenuating circumstances for keeping the project open (e.g., the study is about a rarely seen condition). 

Procedures for closing a study fall into three categories:

• Final review (FR);
• Study Closure due to
  • Non-response to requests for continuation or final review (See Continuation Review SOP);
  • Non-response to IRB requests for revisions (a vote of 2, 3, or 4);
• Study Closure due to study never being initiated (i.e., non-enrollment, no data collection from records, and/or no specimens having been obtained).

Regardless of the category for study closure, the expiration date for IRB approval falls on the date the protocol is closed. 

RESPONSIBILITY 

Execution of SOP:  Principal Investigator (PI)/Study Personnel, Office of Research Integrity (ORI) Staff, IRB Chair, IRB Vice Chair, IRB Members 

PROCEDURES 
Submission Process

1. Approximately three (3) months prior to the IRB approval end date, the researcher is prompted by email to initiate either a Continuation Review (CR), Annual Administrative Review (AAR), or Study Closure/Final Review depending on the review type of the research (i.e., expedited or full) and the anticipated research end date previously provided by the PI.
2. If the study qualifies for closure, the PI submits either a Final Review (FR) or Study Closure request.

Final Review

1. The PI is required to submit a Final Review (FR) if the study qualifies for closure and any of the following apply:
   • The research is FDA regulated;
   • Subjects have been enrolled since the last CR/AAR [or initial review (IR) if the study has not yet undergone a CR/AAR];
   • There have been unanticipated problems, noncompliance concerns, subject concerns, and/or protocol violations not previously reported to the IRB;
   • There are other regulations impacting the research that require it;
   • A sponsor that requires it.
2. Regardless of initial protocol process type (full or expedited review), protocols undergo expedited review procedures for FR unless the IRB reviewer determines the circumstances surrounding the request for closure require full review. ORI staff screen the FR submission and an IRB Chair, Vice Chair, or designee conducts the review.
3. Review outcomes may include:
   • Request for revisions and/or additional information;
   • Full review at a convened meeting;
   • Request that the PI attend the convened IRB meeting at which the FR is scheduled for full review;
   • Closure;
   • Denial of the FR and submission of a continuation review (CR) is required.
4. Once the ORI or IRB issues approval for closure, the protocol status is set to inactive and approval is terminated.

Study Closure

1. The PI may submit a study closure request to the ORI during an approval period based on Study Closure eligibility. Upon receipt, ORI staff verify the conditions for Study Closure are met.
2. Sometimes it is unclear whether the PI has enrolled subjects or if other conditions for Study Closure are met. In such cases, ORI staff may return the Study Closure submission and request additional information. If the conditions for Study Closure are not met, the request is denied by the ORI and the PI is instructed by ORI staff to complete either an FR, CR, or AAR.
3. If the study is a reliance study in which UK reviews or UK cedes to another institution, ORI staff contact the Reliance Team to determine if the study should remain open until all reliance obligations are satisfied.
4. If the conditions for Administrative Study Closure are met, ORI staff process the request and prepare a Study Closure letter and send it to the PI.

Closure Due to Non-Response

1. If the PI fails to respond to the IRB’s request for additional information/revisions at initial review within a specified period of time (e.g., approximately three (3) months) without providing communication outlining extenuating circumstances, the submission is administratively withdrawn. The PI must create a new submission to have the proposed study reviewed by the IRB again.
2. If the PI fails to submit a CR, AAR, or FR or fails to submit requested information related to one of those, ORI generates a notification letter stating that the protocol IRB approval is terminated and sends it to the PI. (See the Continuation and Annual Administrative Review SOP.)
3. Administrative closures for non-response are not reportable events, since the protocol approval is already expired, and there is no withdrawal of IRB approval.

Closure Due to Non-Enrollment

1. If the PI reports to the IRB at CR that they have never enrolled subjects into the study, has never collected any data from records, and/or has never received any biospecimens and the study has been open for a period of three (3) or more years, the IRB may request that the PI submit a study closure request.
2. If there are extenuating circumstances for keeping a study open, the PI submits a CR or AAR as applicable (see the Continuation and Annual Administrative Review SOP) with justification that the study be kept open. If the IRB agrees there are extenuating circumstances and the criteria for IRB approval for continuation are met, ORI staff generate a CR/AAR approval letter.
3. If the IRB determines the extenuating circumstances do not justify leaving the study open, ORI staff direct the PI to submit a study closure request.

Study Closure When PI is Leaving the Institution

1. When a PI leaves UK, they must:
   • Close his/her protocol(s) or
   • Submit a modification request to transfer the protocol(s) to another PI who will then take responsibility for the research.
2. Appropriate changes must be made to consent/assent forms, advertisements, etc., and submitted to the IRB for review as part of the modification request if a PI transfers a protocol to another investigator. Additionally, the new PI must submit a completed Signature Assurance Statement.
3. If the PI fails to transfer the protocol to another PI, no study personnel have access to perform study closure, or extenuating circumstances warrant closure, ORI staff may administratively close the protocol before the end of the approval period in response to the request of or approval by the department chairperson or equivalent.
4. Administrative closures for failure to transfer are not reportable events, since the closure is in response to a request.

Reactivating IRB Approval

1. A PI may re-initiate research previously inactivated by the IRB by submitting a new IRB application for the project. The research in such cases is treated like a new initial review submission and managed accordingly by the ORI and IRB.

Document Retention and Destruction

1. The PI maintains signed documents, (e.g., signed consents/assents) and IRB records for at least six (6) years after study closure, taking measures to prevent accidental or premature destruction of these documents. Investigators store records consistent with the plan approved by the IRB in a secured manner to prevent breaches of confidentiality.
2. For research under the authority of FDA or other regulatory agency, the PI retains signed documents and IRB records for the period specified in the applicable regulations if the requirements are longer than six (6) years after study closure. For multi-site studies, the PI consults the study sponsor regarding retention requirements but must maintain records for a minimum of six years after study closure.
3. The PI ensures that retained records are accessible for inspection and/or copying by authorized representatives of institutional or regulatory agencies. 

REFERENCES 
Not applicable

Approved By: ORI Director, Nonmedical IRB Chair, Medical IRB Chair

Date First Effective: July 12, 2005

Last Revision Date: May 9, 2019

Revision #7

OBJECTIVE

To describe policies and procedures for the University of Kentucky (UK) Institutional Review Board (IRB)/Office of Research Integrity (ORI) record keeping

GENERAL DESCRIPTION

The ORI maintains IRB records in accord with applicable regulatory and institutional requirements. 

RESPONSIBILITY

Execution of the SOP: ORI Staff, IRB Members, IRB Chair, ORI Research Compliance Officer (RCO), ORI Director, ORI Associate Director, Principal Investigator (PI)/Study Personnel 

PROCEDURES

Storage of and Access to Records

1. ORI staff secure all active IRB records in the ORI and limit access to the IRB Chair, IRB members, ORI Director, ORI staff, Vice President for Research (VPR), and officials of federal and state regulatory agencies, the Office for Human Research Protections (OHRP), the Food and Drug Administration (FDA), and accrediting bodies. ORI staff may grant UK employees with administrative appointments access to the records on an as-needed basis for official UK business. Investigators or their authorized study personnel have reasonable access to files related to their research activities. ORI staff limit all other access to IRB records to those who have legitimate need for them, as determined by the ORI Director, RCO, and/or UK Legal Counsel when submitted through state open records statutes.
2. Administrative requests for access (e.g., Dean, Associate Dean, Department Chair, Corporate Compliance Officer) must be in writing and contain the following information:
   • The name of the person requesting the information;
   • The information requested;
   • The reason for the request;
   • Assurance of confidentiality.
3. When the ORI receives a request for IRB records of studies initiated on paper, ORI staff check to see whether the request is from a PI or his/her authorized personnel. If the person requesting the record is listed as current study personnel on the protocol, ORI staff may copy pertinent parts of the paper record for that person to pick up or ORI staff may fax, mail, or e-mail the record.
4. If the authorized individual requests a substantial amount of material, ORI staff allow access to the record and a copy machine in the ORI for use by the person requesting the material.
5. If the person requesting the record is not listed as current study personnel, the ORI Director/RCO or his/her designee makes a determination as to whether the request is from appropriate accreditation bodies, University officials, administrators, or regulatory agencies that should have access before authorizing the release of any records. Unless the individual provides an acceptable reason for not informing the PI of the request, ORI staff inform the PI that ORI has received a request for access to the applicable protocol.
6. The ORI maintains protocol records for a minimum of six years (as determined by the ORI Director/RCO) after a study is closed. This storage requirement applies even if the study never enrolled a single subject. ORI staff destroy protocol records for studies that have been closed for six (6) years unless the ORI Director/RCO waives the requirement for a specific study.
7. In addition to protocol files, the ORI maintains the following information and records. ORI staff organize and store records in files, binders, or electronically as appropriate. Such records include but are not limited to the following categories:
   • Standard operating procedures;
   • IRB membership rosters;
   • Meeting minutes, which include documentation of convened IRB meetings;
   • Federalwide Assurance;
   • Computerized research protocol tracking system;
   • Other IRB correspondence;
   • Agendas for IRB meetings, which include all items to be reviewed and documentation of expedited and exempt reviews;
   • Alleged noncompliance case records;
   • Mandated reports;
   • Resumes of currently active IRB members;
   • Electronic records documenting completion of mandatory IRB training for study personnel, IRB members, and ORI staff.
8. ORI staff maintain records that are not part of specific protocol files such as meeting minutes, agendas, standard operating procedures, and membership rosters and periodically, destroy them as appropriate and determined by the ORI Director/RCO.
9. The ORI also maintains communications to and from the IRB in the ORI office and keeps any relevant communication related to a specific research protocol in the protocol record. 

Protocol Records

1. ORI staff maintain a separate record for every research application. The IRB protocol record includes (when applicable) but is not limited to:
   • Full Review Protocol
     • Initial IRB application;
     • Scientific evaluations of the proposed research, if any;
     • Study drug information (i.e., investigator’s brochure, monograph, labeling);
     • Study device information (i.e., prior investigation, operations manual, labeling);
     • Data Safety and Monitoring Board reports, if any;
     • Results of Quality Improvement Program (QIP) reviews, if any;
     • Signed Signature Assurance;
     • IRB approved informed consent document and assent document with the approval date stamp;
     • Documentation of all IRB review and approval actions, modifications, and all relevant correspondence to and from the investigator, including initial, continuation, modification, deviation, and exception review;
     • Documentation of type of review;
     • Documentation of study close-out;
     • Specific findings (federal and institutional requirements);
     • Continuation/final review materials;
     • Significant new findings provided to human subjects, if any;
     • Reports of unanticipated problems/adverse events involving risks to subjects or others;
     • Reports of protocol violations;
     • All relevant correspondence to and from the investigator and any other correspondence related to the protocol;
     • IRB Authorization Agreements;
     • Any existing contractual agreements for off-site research;
     • Applications for funding/sponsorship;
     • Advertising or recruiting materials;
     • Protocol amendments or modifications;
     • Instrument to be used for data collection;
     • Department of Health and Human Services (HHS)/National Institutes of Health (NIH) approved sample informed consent form and protocol;
     • Copy of the package insert, drug monograph, or FDA approved label for drug or device studies using the FDA approved medication/device for approved medical indication;
     • Sponsor’s grant, contract, or device proposal if the protocol does not involve the administration of drugs;
     • Human subject protection training for principal investigators and study personnel;
     • Health Insurance Portability and Accountability Act (HIPAA) forms;
     • Institutional Biosafety Committee correspondence, provisional approval and/or approval letters;
     • Other committee approvals/correspondence;
     • Mandated reports;
     • Criteria for IRB Approval: Reviewer Checklist;
     • IRB Continuation Review: Primary Reviewer Checklist(s);
     • Other reviewer signature page(s) (e.g., Prisoner Advocate Reviewer Signature Page, Consultant Signature Page).

• Expedited Review Protocol
  • All of the items listed above under full review protocol, as applicable to individual studies;
  • Documentation and determinations required by the regulations and protocol-specific findings justifying those determinations, including that the study is eligible for expedited review and identification of the applicable expedited review category(ies);
  • Description of action taken by the primary expedited reviewer.
• Exempt Review Protocol
  • Initial application for exempt review;
  • Signed Signature Assurance;
  • Items listed under full review protocol, as applicable to individual studies;
  • Documentation and determinations required by the regulations and protocol specific findings justifying the determinations, including documentation of exempt eligibility and specifying appropriate exemption category(ies);
  • Description of action taken by the exempt reviewer.

ORI Database

1. The ORI maintains a computerized tracking system. Examples of data included in the computerized system include the following, when applicable:
   • IRB number which identifies the protocol as full, expedited, or exempt;
   • The IRB which provides review and ORI staff who manage the review;
   • Current status (active/inactive);
   • QIP status;
   • Protocol type (medical/nonmedical);
   • Title of the research project (protocol);
   • Protocol process type (full, expedited, exempt);
   • Approval stage (pre-approved, approved, suspended, terminated);
   • IRB to which the protocol is assigned;
   • Designation as a Subject Use and Research Ethics Committee protocol;
   • Risk category;
   • Dates of research period (initial approval date and anticipated ending date);
   • Approval period;
   • Names of the PI, co-investigators, study coordinators, and other study personnel as appropriate;
   • Number and age level of subjects;
   • Subject demographics;
   • Enrollment status (open or closed to accrual);
   • Research attributes (e.g., cancer, genetic research);
   • Drug information;
   • Other committee approvals (e.g., Institutional Biosafety Committee);
   • Funding source and type;
   • Research sites (if other than UK campus);
   • Date of initial approval;
   • Date of most recent approval;
   • Date of most recent continuation approval;
   • Prior notice of end of current approval period;
   • Submission and review dates for each protocol event (initial review, continuation review, final review, modification review, extension review, unanticipated problem review);
   • Other information, such as meeting dates;
   • Comment section.
2. UK Research Information Services (RIS) maintains the ORI computerized tracking system and performs a backup of this system on a regular basis. Only ORI staff members and RIS staff have passwords for the ORI system. RIS maintains documentation of backups and passwords.

Electronic submission system

1. Beginning in January 2018, the ORI maintains an online database and submission system.
2. For each protocol submission, the system maintains all study documents and information outlined above.
3. UK RIS maintains the electronic system. Only ORI and RIS staff members have administrative access to the system. Access for investigators, research staff, and IRB members is appropriately limited.

REFERENCES

45 CFR 46.115

21 CFR 56.115

Approved By: ORI Director, Nonmedical IRB Chair, Medical IRB Chair

Date First Effective: June 28, 2005

Last Revision Date: May 28, 2024

Revision #9

OBJECTIVE

To describe policies and procedures for the Quality Assurance/Improvement Program (QA/QIP) component of the University of Kentucky (UK) Office of Research Integrity (ORI).

GENERAL DESCRIPTION 

The ORI/Institutional Review Board (IRB) QA/QIP serves to improve human research protections at UK. Two of the primary quality assurance/improvement activities are directed (aka “for cause”) reviews and routine post-approval monitoring (aka “Wellness Checks”).

Directed “For Cause” Reviews

The ORI QA/QIP conducts directed for cause reviews at the request of the IRB, the Vice President for Research (VPR), or ORI Director due to unusual circumstances, significant risks to subjects, routine failure on the part of an investigator to comply with federal and/or institutional requirements, and/or allegations or concerns about the conduct of the study. The IRB, VPR, or the ORI Director may also request periodic reviews to evaluate whether investigators meet their responsibilities within specific areas of research (e.g., investigators conducting research using an investigational device). If appropriate, directed reviews also encompass elements of informed consent evaluation, as described in the QA/QIP Administrative Assessment Review SOP. The IRB may request measures to monitor the consent process to determine whether procedures for administration of informed consent are proper. If the IRB deems it necessary, the QA/QIP may review IRB records to determine accuracy and consistency with the investigator’s research records and to verify that the investigator made no material changes to the protocol. 

The QA/QIP shares findings pertaining to the review with the principal investigator (PI)/research staff and reports these findings to the IRB that requested the review. To maintain confidentiality, the QA/QIP does not record research subjects’ protected health information in the report disseminated to the IRB.

In reviewing the results of a directed review, the IRB determines if any deficiencies warrant suspension or termination of the research. If the IRB determination is suspension, the IRB develops a plan for follow-up, which may require a quality assurance/improvement review (QA/QIR) or monitoring of the informed consent process. (See Noncompliance SOP and Termination or Suspension of Research by the IRB SOP)

The ORI develops educational programs for investigators, their research staff, ORI staff, and IRB members based on the results of the QA/QIP reviews. When the IRB receives reports of findings from QA/QIP reviews, the IRB determines whether to report the findings to the Food and Drug Administration (FDA), the Office for Human Research Protections (OHRP), the study sponsor, the VPR, the Reviewing/Relying IRB(s) when applicable, or other internal departmental faculty/staff. (See Mandated Reporting to External Agencies SOP)

If the QA/QIP conducts a directed review on a protocol that falls under the purview of a unit with which the ORI has written and approved joint standard operating procedures (e.g., the Institutional Biosafety Committee or Markey Cancer Center), the QA/QIP provides the appropriate unit representative with a copy of the resulting final report. 

Routine post-approval monitoring (“Wellness Checks”)

The ORI QA/QIP conducts Wellness Checks to assist investigators with the conduct of human subjects research protocols at UK and educate them about human subjects protections in general, as needed. Unlike protocols undergoing Directed Review, Wellness Checks are not selected by the IRB. In addition, Wellness Checks are not protocols that have been “flagged” or “reported” for any reason such as participant complaints. Wellness Checks are selected by the QA/QIP using a combination of a risk-based approach (e.g., risk level designated on the protocol, involvement of vulnerable populations, studies with no additional oversight or support, etc.), specified approval time frames (e.g., approximately 6 months after initial IRB approval), and topics of interest (e.g., device studies, survey/interview topic, investigator initiated and/or student-led research, international studies, etc.). Wellness Checks involve 50% medical protocols and 50% nonmedical protocols and can be conducted on any study that undergoes IRB Review.

RESPONSIBILITY 

Execution of SOP: ORI QA/QIP, ORI Director, VPR, IRB Chair/Designated IRB Member, IRB, PI/Study Personnel

PROCEDURES

Directed Reviews

1. If the IRB, VPR, or ORI Director requests a directed review for an investigator and does not identify a specific protocol, the QA/QIP may use the following criteria to identify protocol(s) for inspection: federal, state, or industry-funded projects; currently approved and active for two years; level of risk to subjects; or subjects currently enrolled in the study.
2. For directed reviews that provide post-IRB approval evaluations to determine whether the PI is meeting responsibilities in a specific area of research (e.g., research using an investigational device), the QA/QIP runs a report to identify all protocols in the targeted area of research.
3. Once the QA/QIP determines which protocol(s) will undergo review, he/she notifies the PI of the upcoming directed QA/QI review. After sending initial notification, the QA/QIP communicates with the PI and/or the study personnel to schedule the date(s) for the review at the earliest time possible.
4. The QA/QIP conducts an entrance and exit interview with the PI as part of the review. The IRB Chair and/or an IRB member may participate in these interviews. At the PI’s discretion, select IRB-approved study personnel may also attend.
5. Prior to the entrance interview, the QA/QIP review the initial review meeting minutes (if applicable), IRB records, protocol documentation/materials, and other resources to become familiar with the protocol(s) and to identify potential issues to address during the QA/QIR review process.
6. The entrance interview precedes the QA/QIP’s review of the PI’s research records. The QA/QIP and/or participating IRB Chair/member may use this time to explain the goals of the QA/QIP and the impetus behind the directed review. It also provides the PI/study personnel with an opportunity to explain what the protocol entails, to respond to the issues that instigated the directed review, and to answer any questions arising from the QA/QIP’s preceding review of the IRB protocol records.
7. The records reviewed by the QA/QIP and/or participating IRB Chair/member may consist of but are not limited to the following:
   • Protocol Binder/Regulatory Documentation – (in hard copy and/or electronic format) The QA/QIP reviews materials and notes whether the records retained meet applicable federal, International Conference on Harmonization /Good Clinical Practice, and IRB guidelines;
   • IRB Documentation – The QA/QIP compares the PI’s records with the IRB’s records. Review of IRB documentation affords the opportunity to determine whether the PI made material changes prior to IRB approval;
   • Consent/Assent Forms – The QA/QIP examines consent/assent forms used to enroll participants to ensure that they received and (if applicable) signed the appropriate form(s) for their respective study and that approved study personnel and the participants properly signed and dated the forms as/when required;

   • Participant Binders/Files/Case Report Forms (CRFs) –The QA/QIP reviews all participants’ records for the review. In cases where the study has enrolled a large number of participants, the QA/QIP randomly selects a portion of the available binders/files for review. The QA/QIP determines whether the subjects met the inclusion/exclusion criteria for their respective study, whether the PI/study personnel recorded and documented items properly, if all data collection materials are present and properly completed;

     Medical Records –the QA/QIP may review medical records to verify the information in the CRFs;

For assistance/clarification during the record review, the QA/QIP may contact the PI directly or, if applicable, inquire with the PI’s study personnel, or wait until the exit interview to obtain clarification.

8. The QA/QIP and/or participating IRB Chair/member may also request a tour of the facilities to verify control, storage, and accountability of investigational new test articles, confirm availability of related research equipment, and/or to verify secure storage of research records.
9. The IRB may request observation/monitoring of the consent process as part of the directed review using procedures that include but are not limited to:
   • Surveying research participants enrolled in the study about the informed consent process and their experience as a research participant;
   • Witnessing administration of the informed consent process to potential participants by the QA/QIP and/or participating IRB member. The IRB determines the frequency of consent process monitoring on a case-by-case basis; examples of determining factors include the level of risk of the research, enrollment activity, funding agency/source, and targeted subject population.
10. The QA/QIP and/or participating IRB Chair/member conducts the exit interview after the QA/QIP completes the review of the research records and may request clarification regarding the protocol or research procedures at that time. The QA/QIP and/or participating IRB Chair/member provide(s) the investigator with a verbal summary of the findings and explains the remaining procedures for conclusion of the review.
11. The QA/QIP writes a report outlining the findings of the directed review following the exit interview. If the IRB Chair/member participated in the directed review, the QA/QIP may give the IRB Chair/member the opportunity to review and edit the report prior to sending it to the PI.
12. Once the QA/QIP review report is complete, the QA/QIP sends it to the PI with a requested response date determined on a case-by-case basis. Typically, the PI has two weeks to submit his/her response to the recommendations and/or provide comments on the written report.
13. Upon receipt of the PI’s response (if any), the QA/QIP schedules a review with the appropriate IRB at a convened meeting.
14. For any QA/QIP findings related to the protection of human research participants reviewed by the full committee, the IRB members vote for one of the following actions:
    • Acknowledged/Approved – No further action is required. Per the guidelines in the ORI Customer Service Standards, the PI is notified of the outcome of IRB review.
    • Revisions/additional information requested – The IRB withholds acknowledgement/approval of the report pending submission of revisions/additional information. The IRB may give the individual chairing the meeting the authority to approve non-substantial revisions/additional information or require review of substantial revisions/additional information at a subsequent convened meeting. If the IRB request necessitates further QA/QIP review, the QA/QIP acts accordingly and processes any additional findings/information for review based on the IRB’s determination at the convened meeting (either gives them to the individual who chaired the IRB meeting or assigns them to a convened IRB meeting for review). If the IRB request necessitates a response from the PI (see the ORI Customer Service Standards), the QA/QIP or other ORI staff sends the PI a letter describing the IRB’s request. When the PI responds to the IRB’s request in writing, the ORI processes the response based on the IRB’s determination at the convened meeting (either gives it to the individual who chaired the IRB meeting or assigns it to a convened IRB meeting for review). If the individual who chaired the meeting is the IRB’s designated reviewer, he/she may decide to forward the response to the entire IRB for additional review, request additional information, or acknowledge/approve the response.
    • Suspension or termination of the research - (See Termination or Suspension of Research by the IRB SOP.) Per the guidelines in the ORI Customer Service Standards, the QA/QIP or other ORI staff sends the PI a letter describing the outcome of the IRB review.
15. ORI staff save documentation for protocol-specific directed reviews in the corresponding IRB records and maintain QA/QIP documentation in the IRB records for a minimum of six years after study closure. (See IRB/ORI Recordkeeping SOP.) The QA/QIP maintains a separate restricted-access file containing documentation on all QA/QI activity.

Reliance protocols: Directed Reviews when UK is the Reviewing IRB

1. The QA/QIP notifies the Relying Sites of the pending Directed Review as needed to comply with the signed Reliance Agreement(s) applicable SOPs/Communications Plan as well as to obtain the most recent study documents (i.e., data collection, consent forms, enrollment logs, etc.).
2. In addition to the documentation described under #7 of Directed Reviews section above, the QA/QIP reviews the Reliance Agreement(s), Communications Plan(s), and/or the Local Context Form(s) (when applicable) for all Relying Sites and ensures that the UK PI has distributed the most recent study materials to the Relying Site(s).
3. The QA/QIP informs the Relying Site(s) of the results of the Directed Review if the IRB votes to Suspend or Terminate the research or if the Reliance Agreement/Communications Plan requires this information.

Reliance protocols: Directed Reviews when UK is the Relying IRB

1. If the Reviewing IRB asks for a Directed Review of UK as a Relying Site for a specific protocol, the QA/QIP follows the same procedures as the “Reliance protocols: Directed Reviews when UK is the Reviewing IRB” section above.
2. The QA/QIP requests the most recent study documents (i.e., protocol, data collection implements, stamped consent forms, etc.) from the Reviewing IRB.
3. In addition to the documentation described under #7 of the Directed Reviews section above, the QA/QIP reviews the Reliance Agreement and Communications Plan.
4. The QA/QIP informs the Reviewing Site of the results of the Directed Review unless  the IRB votes to Suspend or Terminate the research or if the Reliance Agreement/Communications Plan requires this information.

Routine post-approval monitoring (“Wellness Checks”)

1. The QA/QIP conducts Wellness Checks to ensure that PIs are meeting their responsibilities, following the research protocol as approved by the IRB, and to assist and educate PIs/study teams in doing so as needed.
2. The QA/QIP identifies studies for Wellness Checks primarily using a risk-based approach and may run reports to identify protocols in targeted areas of interest (e.g., vulnerable populations, research topic, risk level of the research, approved within specified date ranges, non-sponsored protocols, student PI, etc.). The IRB is not involved in selecting protocols for Wellness Checks.
3. Once the QA/QIP determines which protocol(s) will undergo a Wellness Check, each PI is notified of the upcoming QA/QI review and provided with a list of available dates to select from. If the PI is a student, the faculty advisor on the protocol is included in the notification. The QA/QIP and PIs then communicate to schedule the date(s) and location/format for the review at the earliest time possible. At the PI’s discretion, select IRB-approved study personnel may also attend. Faculty advisors are expected to participate in Wellness Checks when the PI is a student.
4. The QA/QIP reviews the initial review meeting minutes (if applicable), IRB records, protocol documentation/materials, and other resources prior to the Wellness Check to become familiar with the protocol(s) and identify potential issues to address during the review.
5. The Wellness Check is initiated with an entrance interview. The QA/QIP typically use this time to do introductions and explain the goals of the QA/QIP and the impetus behind Wellness Checks in general. It also provides the PI/study personnel with an opportunity to explain what the protocol entails, provide an update on its status, to answer any questions arising from the QA/QIP’s preceding review of the IRB protocol records, and to ask questions of the QA/QIP.
6. The QA/QIP reviews the research records following the entrance interview. The PI and study personnel are not present for this portion of the Wellness Check. The records reviewed during this process consist of (but are not limited to) the following:
   • Protocol Binder/Regulatory Documentation – (in hard copy and/or electronic format) The QA/QIP reviews materials and notes whether the records retained meet applicable federal, International Conference on Harmonization/Good Clinical Practice, and IRB guidelines;
   • IRB Documentation – The QA/QIP compares the PI’s records with the IRB’s records. Review of IRB documentation affords the opportunity to determine whether the PI made material changes prior to IRB approval;
   • Consent/Assent Forms – The QA/QIP examines consent/assent forms used to enroll participants to ensure that they received and (if applicable) signed the appropriate form(s) for their respective study and that approved study personnel and the participants properly signed and dated the forms as/when required;
   • Participant Binders/Files/Case Report Forms (CRFs) –The QA/QIP typically reviews all participants’ records for the Wellness Check. In cases where the study has enrolled a large number of participants, the QA/QIP randomly selects a portion of the available binders/files for review. The QA/QIP determines whether participants met the inclusion/exclusion criteria for their respective study, whether the PI/study personnel recorded and documented items properly, if all data collection materials are present and properly completed, etc.;
   • Medical Records –the QA/QIP may review medical records to verify the information in the CRFs.

For assistance/clarification during the record review, the QA/QIP may either contact the PI directly (or, if applicable, inquire with the PI’s study personnel) or wait until the exit interview to obtain clarification.

7. The QA/QIP conducts the exit interview following the review of the research records and may request clarification regarding the protocol or research procedures at that time. The QA/QIP provides the investigator with a verbal summary of the findings and any areas of concern. The QA/QIP also explains the next steps following the Wellness Check and any required actions (e.g., submission of a Modification Request, Protocol Violation report, etc.).
8. The QA/QIP may also request a tour of the facilities to verify control, storage, and accountability of investigational new test articles, confirm availability of related research equipment, and/or to verify secure storage of research records.
9. The QA/QIP writes a report outlining the findings of the Wellness Check following the exit interview. Once the QA/QIP review report is complete, the QA/QIP sends it to the PI with a requested response date determined on a case-by-case basis. Typically, the PI has two weeks to submit a response to the written report.
10. The Wellness Check report is not provided to the IRB unless significant concerns and/or issues related to the protection of human research participants are noted during the review.
11. If significant concerns were noted during the Wellness Check and the report is provided to the IRB, the PI’s response (if any) is also provided to the IRB. The QA/QIP then coordinates with ORI staff to have the written report and all associated information scheduled for review by the relevant IRB at a convened meeting. The IRB then reviews the report and findings following the procedures described for Directed Reviews.

Reliance protocols: Routine post-approval monitoring (“Wellness Checks”) when UK is the Reviewing IRB

1. If a protocol is selected for which UK is the Reviewing IRB, the QA/QIP notifies the Relying Site(s) HRPP of the pending Wellness Check to comply with the signed Reliance Agreement(s) and/or Communications Plan, to obtain the most recent study documents (i.e., data collection, consent forms, enrollment logs, etc.). The QA/QIP may also request the Relying Site(s) HRPP to conduct their own post-approval monitoring of their site depending on UK findings.
2. In addition to the documentation described under #6 of the Wellness Checks section above, the QA/QIP reviews the Reliance Agreement(s), Communications Plan(s), and/or the Local Context Form(s) for all Relying Sites and ensures that the UK PI has distributed the most recent study materials to the Relying Site(s).
3. The Relying Site(s) is/are not informed of the results of the Wellness Check unless the Reliance Agreement(s) or Communications Plan specifies the Sites will receive the reports. If the report contains significant concerns (as defined in the Protocol Violation Review SOP as a Major Violation) that were noted during the visit, then both UK’s IRB and the Relying Site(s) will receive the report/findings.

Reliance protocols: Routine post-approval monitoring (“Wellness Checks”) when UK is the Relying IRB

1. In addition to the criteria for selecting protocols, the QA/QIP consults with the UK ORI Reliance Manager when selecting a protocol for which UK is a Relying Site.
2. The QA/QIP requests the most recent study documents (i.e., protocol, data collection implements, stamped consent forms, etc.) from the Reviewing IRB.
3. In addition to the documentation described under #6 of the Wellness Checks section above, the QA/QIP reviews the Reliance Agreement and Communications Plan.
4. The QA/QIP informs the Reviewing Site of the results of the Wellness Check only if the Reliance Agreement or Communications Plan specifies that requirement. If the report contains significant concerns (as defined in the Protocol Violation Review SOP as a Major Violation) noted during visit, the Reviewing IRB and UK’s IRB will receive the report/findings.

REFERENCES

Not applicable

Approved By: ORI Director, Nonmedical IRB Chair, Medical IRB Chair

Date First Effective: June 28, 2005

Last Revision Date: August 9, 2019

Revision #6

OBJECTIVE

To describe the policies and procedures for the principal investigator (PI) self-assessment review component of the University of Kentucky’s Quality Assurance/Improvement Program (QA/QIP) 

GENERAL DESCRIPTION 

The Office of Research Integrity (ORI)/Institutional Review Board (IRB) Quality Assurance/ Improvement Program serves to improve human research protections at the University of Kentucky (UK). One of the three primary quality assurance/improvement activities is the PI self-assessment review. The self-assessment component of the QA/QIP provides an opportunity to educate research staff and PIs on federal, state, and University expectations; assist researchers in assessing their own programs; and assist in identifying areas on which additional educational programs may need to focus.

The ORI provides a web-based self-assessment form that PIs and/or research staff complete. The ORI disseminates information about the web-based self-assessment form via listserv messages, the ORI website, and other forums as they become available. The form includes questions and information pertaining to federal regulations governing human research protections, local IRB policies and procedures, and International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) guidelines.

The PI or his/her research staff perform self-assessment reviews voluntarily; however, the IRB, IRB Chair or ORI Director may also direct the PI to perform a self-assessment review. If a PI declines a direct invitation to conduct a self-assessment review with reasonable justification, at the discretion of the IRB, IRB Chair, or ORI Director, the QA/QIP may conduct or assist the investigator/research staff with a directed on-site QA/QI review.

The self-assessment form utilizes a database, maintained by the QA/QIP, to generate reports which ORI staff run on an as-needed basis. The QA/QIP analyzes the reports. If the findings reveal significant deficiencies in the protection of human subjects in research, or the IRB directs a PI to perform a self-assessment, the QA/QIP notifies the IRB and coordinating offices of the results of the PI self-assessment review.

In cases where the ORI reports findings from QA/QI reviews to the IRB, the IRB determines whether to report the findings to the Food and Drug Administration (FDA), Office for Human Research Protections (OHRP), the study sponsor, the Vice President for Research (VPR), or other internal departmental faculty/staff.

To support efforts for continuous improvement in compliance, the QA/QIP may conduct a follow-up review at the IRB’s or ORI Director’s discretion on any protocol for which a PI has completed a self-assessment form.

The web-based self-assessment form utilizes standard security features in order to protect and maintain confidentiality of the information provided by the PI/research staff. ORI staff make every effort to prevent unauthorized individuals from gaining access to any information provided. The ORI limits access to the data to the PI/designated research staff, the QA/QIP, and select ORI staff via a password security system. The results from any self-assessment review are kept confidential to the extent allowed by law. 

RESPONSIBILITY 

Execution of SOP: ORI QA/QIP, ORI Director, IRB Chair/designated IRB Member, IRB, Principal Investigator (PI)/Study Personnel 

PROCEDURES

1. The PI/research staff contacts the QA/QIP for information on how to access the web-based self-assessment form, or if a directed self-assessment, the QA/QIP directs the PI to the web based assessment form.
2. The PI/research staff completes a section of the web-based self-assessment review and is able to save responses without having to complete the review in its entirety. The PI/research staff can return to the saved review at any time utilizing the password security system. Up until submission of the completed review, the PI/research staff is able to change his/her responses within previously saved sections.
3. Once complete, the user submits the generated form. Responses are final once the PI/research staff submits the completed form, as the data are then static (locked) for reporting purposes.
4. After submission to the ORI database, the QA/QIP verifies information provided in specific sections of the form by comparing the user's responses to the ORI's IRB records. The QA/QIP investigates discrepancies and, if applicable, contacts appropriate parties for additional information. The QA/QIP may also analyze the data to determine whether significant deficiencies in human research protections exist and/or what topics may be useful for future educational programs.
5. The QA/QIP acknowledges completion and receipt of the self-assessment form by sending electronic correspondence to the PI and, if appropriate, designated research staff. If applicable, the QA/QIP requests clarification of discrepancies at that time. The correspondence also indicates that the PI/research staff can return to the web-based self-assessment form and retrieve the completed self-assessment form using the password security system. Upon retrieval, the PI/research staff can view regulatory background information and suggestions for corrective actions for applicable items.
6. If the analysis of a submitted self-assessment form suggests that significant deficiencies in human research protections exist, the QA/QIP may share the findings with the ORI Director. If deemed appropriate by the QA/QIP and/or ORI Director, the QA/QIP forwards a report to the IRB Chair for review. The QA/QIP notifies the PI regarding this decision and what the outcome may entail.
7. The IRB Chair may decide to forward the response to the entire IRB for additional review or acknowledge with no further action requested.
8. For any QA/QI findings requiring review by the full committee, the IRB members vote for one of the following actions:
   • Approved – No further action is required. Per the guidelines in the ORI Customer Service Standards, the QA/QIP sends the PI a letter describing the outcome of the IRB review.
   • Revisions/additional information requested - The IRB withholds approval pending submission of revisions/additional information. The IRB may give the individual chairing the meeting the authority to approve the revisions/additional information or require review of the revisions/additional information at a convened meeting. If the IRB request necessitates further QA/QI review, the QA/QIP acts accordingly and processes any additional findings/information for review based on the IRB’s determination at the convened meeting (either given to the individual who chaired the IRB meeting or assigned to a convened IRB meeting for review). If the IRB request necessitates a response from the PI, per the guidelines in the ORI Customer Service Standards, the QA/QIP sends the PI a letter describing the IRB’s request.
     
     When the PI responds to the IRB’s request, the ORI processes the response based on the IRB’s determination at the convened meeting (either given to the individual who chaired the IRB meeting or assigned to a convened IRB meeting for review). If the individual who chaired the meeting is the IRB’s designated reviewer, he/she may decide to forward the response to the entire IRB for additional review, request additional information, or approve.
   • Suspension or termination of the research - (See the Termination or Suspension of Research by the IRB SOP.) Per the guidelines in the ORI Customer Service Standards, the QA/QIP sends the PI a letter describing the outcome of IRB review.
9. For directed self-assessments, ORI staff store documentation resulting from PI reviews in the corresponding IRB records and retain QA/QI review documentation in the IRB records for a minimum of six (6) years after study closure. (See IRB/ORI Recordkeeping SOP.) The QA/QIP maintains a separate QA/QI review file containing documentation on all QA/QI activity.

REFERENCES

Not applicable

Approved By: ORI Director, Nonmedical IRB Chair, Medical IRB Chair

Date First Effective: June 28, 2005

Last Revision Date: August 9, 2019

Revision #11

OBJECTIVE

To describe policies and procedures for the administrative assessment component of the University of Kentucky (UK) Quality Assurance/Improvement Program (QA/QIP)

GENERAL DESCRIPTION 

The Office of Research Integrity (ORI)/Institutional Review Board (IRB) QA/QIP serves to improve human research protections at UK. One of the primary quality assurance/improvement activities is the administrative assessment review.

The ORI QA/QIP conducts administrative assessment reviews at his/her discretion or at the request of the ORI Director and/or the Vice President for Research (VPR). These reviews measure the effectiveness and/or efficiency of the ORI/IRB procedures for protection of human subjects in research. Examples of areas in which the QA/QIP may periodically conduct a thorough examination of the IRB records, the ORI files/submissions, and/or other materials to evaluate performance include, but are not limited to:

• IRB member performance;
• Proper use of expedited and exemption categories;
• Timeliness of ORI staff responses to investigators/study personnel and/or of IRB review;
• Volume of the ORI’s outreach activity for investigators and research subjects (i.e., web page “visitors” report);
• Major versus minor revisions at initial review;
• Appropriate consideration and documentation for protecting vulnerable or potentially vulnerable populations;
• Timeliness of continuation review of approved research;
• Documentation for and approval of waivers of informed consent and/or alteration of elements of informed consent;
• Inclusion of all the elements of informed consent as required by the UK IRB;
• IRB consideration for data and safety monitoring;
• Completeness of IRB minutes;
• Quality of UK’s human research protection program (HRPP) and IRB system as measured by accreditation assessment tools.

Any performance evaluation topic described under this SOP may be incorporated into a directed on-site review at the discretion of the ORI Director, the QA/QIP, the VPR, and/or the IRB Chair. The QA/QIP shares the results of an administrative assessment with the ORI Director. The results may impact current practices and may require additional educational activities for ORI staff and IRB members.

In addition, the QA/QIP coordinates the Human Research Protection Program Evaluation. This assessment focuses on maintenance of applicable documentation representing current policy and procedures, utilization of the Association for the Accreditation of Human Research Protection Programs, Inc. (AAHRPP) Self-Evaluation Instrument, and evaluation of current human research protection practices to ensure appropriate fulfillment of accreditation and HRPP standards. The program assessment serves to determine whether the institution’s HRPP is effective in achieving its intended outcomes and provides the opportunity to develop improvement plans as deemed necessary. 

RESPONSIBILITY 

Execution of SOP:  ORI QA/QIP, ORI Director, ORI Staff, ORI Professional Associate (PA), VPR, IRB 

PROCEDURES

Administrative Assessment

1. An administrative assessment may require selection of specific protocols for examination of a variety of topics including, but not limited to: review type, funding source, off-site research, event types, special research categories, specific IRB committee, and/or assigned ORI staff. Generally, the QA/QIP chooses protocols that meet the criteria for the particular administrative assessment randomly; however, the QA/QIP, ORI Director, and/or VPR have the discretion to identify specific studies for assessment. If identifying specific protocols is not necessary for the administrative assessment conducted (e.g., review of meeting minutes, review of a committee’s workload, evaluation of the performance of IRB members), the QA/QIP obtains and reviews other related materials.
2. After identifying the protocols and/or related materials for examination, the QA/QIP or designee conducts an in-depth review of either the IRB records for each identified protocol or related materials. This may entail review of the ORI computerized tracking system, electronic or physical IRB records maintained by ORI, and/or the IRB meeting minutes. The QA/QIP may conduct a comparison to verify that the events listed in the ORI computerized tracking system are in alignment.
3. The QA/QIP shares the results of the review with the ORI Director. Based on results, the ORI Director or designee takes measures to strengthen applicable areas of the HRPP.
4. The QA/QIP or designee educates ORI staff and/or the IRB in areas in need of strengthening as identified by analysis of the results, as appropriate (e.g., QA/QI presentation at an IRB meeting, staff meeting, in-service presentations, etc.). The QA/QIP informs the IRB and the VPR of specific findings only if the findings reveal significant or numerous deficiencies in protection of human subjects in research.
5. If significant deficiencies necessitate reporting to the IRB and the VPR, the IRB determines whether to report the findings to the FDA, OHRP, or the study sponsor, and/or other applicable internal departmental faculty/staff. (See Mandated Reporting SOP)
6. To support continuous improvement when policy or procedure change as a result of QA/QI review findings, the QA/QIP may perform a follow-up QA/QI review to determine whether the processes are effective.

Assessment of Expedited Review 

1. If the QA/QIP conducts an assessment for protocols reviewed using expedited procedures, he/she verifies conformance with policies and procedures, which may include but are not limited to:
   • Assignment to appropriate expedited reviewer;
   • Notification of IRB members of expedited reviews;
   • Review of protocols using expedited procedures according to the eligibility requirements for expedited review;
   • Documentation for the basis of allowing expedited review;
   • Performance of expedited reviewer;
   • Timely processing of applications by ORI staff and/or the IRB reviewer.

Assessment of Exempt Review

1. If the QA/QIP conducts an assessment for protocols reviewed for exemption certification, he/she verifies conformance with policies and procedures which may include, but are not limited to:
   • Appropriate category of exempted research chosen;
   • Assignment to appropriate exempt reviewer;
   • Documentation for the basis (allowable category) of making the exempt determination;
   • Timely processing of applications by ORI staff and/or IRB.

Assessment of Risks and Benefits

1. If the QA/QIP conducts an assessment of the IRB’s determination of risk versus potential benefit for a protocol, including designation of minimal risk when appropriate, he/she verifies documentation in the research records which includes, but is not limited to:
   • Documentation in the meeting minutes or IRB records of the IRB’s evaluation of risks of the research;
   • Provisions for safety monitoring;
   • Determination that risks to participants are minimized by using procedures that are consistent with sound research design and do not unnecessarily expose subjects to risk, and whenever appropriate, by using procedures already being performed on the subjects for diagnostic or treatment purposes;
   • Determination of the level of risk;
   • Determination of the risk level of investigational device, if applicable;
   • Appropriate disclosure of risks and benefits in the informed consent process. 

Elements of Informed Consent Evaluation 

1. When the QA/QIP conducts a review to evaluate appropriate inclusion of the elements of informed consent, he/she verifies adherence to the required elements of informed consent according to UK IRB policy using the Consent/Assent Checklist as a guide. Protocols selected for directed on-site review may include this informed consent evaluation.
2. The nature of the research dictates whether additional elements of informed consent are necessary, but for required additional elements which have been excluded (e.g., significant new findings statement), the QA/QIP confirms the IRB records contain appropriate documentation of the IRB’s determination.
3. Upon completion of the informed consent evaluation, the QA/QIP shares the results with the ORI Director and, if appropriate, the IRB Chair(s).
4. If the informed consent evaluation identifies deficiencies, the ORI Director, designated ORI staff, and/or IRB Chair(s) provide follow-up training to IRB members, and/or education to researchers on best practices.

Assessment for Appropriate Representation and Expertise for Vulnerable Population Protocol Reviews

1. If the QA/QIP conducts an assessment for appropriate representation and expertise for full review research involving vulnerable populations (e.g., children, prisoners), he/she verifies the appropriate IRB representative(s) was/were either present at the convened meeting or available via teleconference at the convened meeting. If research involving vulnerable populations is eligible for expedited review, the QA/QIP verifies the Expedited Reviewer had appropriate expertise or a consultant review was obtained.
2. The QA/QIP or ORI Director may decide to focus an assessment on a specific vulnerable population during a particular time period.

Evaluation of IRB Member Performance

1.  Approximately once each academic year, the QA/QIP or designee sends the ORI PAs and IRB members an IRB Performance Questionnaire to assess representation of appropriate knowledge, skills, and abilities respective to the roles of the IRB member and IRB Chair. Questions intend to collect information including, but not limited to:
   • IRB Member participation/service;
     • Individual members’ ability to apply knowledge of the federal regulations and ethical principles that serve as guidelines for responsible research and whether additional training is necessary to facilitate appropriate reviews;
     • Committee competence in relation to appropriate review (e.g., expertise, representation); and
     • IRB Chairperson leadership (e.g., efficiency and promotion of discussion).
2. The ORI PAs evaluate the IRB Chair, IRB Vice Chair, and IRB members serving on the PA’s assigned committee in a confidential survey.
3. The QA/QIP and/or the ORI Associate Director analyze the responses and notify the ORI Director if any of the responses appear to reveal issues with membership qualifications. If the results identify problems with membership qualifications, the ORI Director or Associate Director discusses the issues with the VPR. The VPR may direct the ORI Director or ORI Associate Director to ask an IRB member to resign and to appoint an appropriate replacement. (See the Membership of the IRB SOP)
4. The QA/QIP provides aggregated evaluation responses (to maintain anonymity of responders) to the IRB members. 

Human Research Protection Program Evaluation

1. UK’s HRPP is assessed at least once every five (5) years. The QA/QIP, with input from the ORI Director and/or designee, conducts the assessment using the AAHRPP Evaluation Instrument and feedback from AAHRPP.
2. ORI staff, the IRB, investigators, other administrative units, and the VPR may participate in the assessment process.
3. Throughout the course of the assessment, the ORI Director, QA/QIP, and/or designees may determine the need for revisions to current HRPP policies, procedures, and/or practices in order to ensure appropriate fulfillment of accreditation standards. Based on the nature of the revisions to the HRPP, the Research Education Specialist (RES), the ORI Director, the QA/QIP, and/or designee develop appropriate education plans for ORI staff, IRB members, investigators, and other affected units, if applicable.
4. The QA/QIP and/or designee(s) incorporates the outcome of this ongoing evaluation in the AAHRPP re-accreditation application (or AAHRPP Annual Report, if applicable).

REFERENCES 

Not applicable

Approved By: ORI Director, Nonmedical IRB Chair, Medical IRB Chair

Date First Effective: March 1, 2005

Last Revision Date: February 15, 2017

Revision #5

3. If the complaint/alleged noncompliance falls under IRB purview, the ORI initiates an inquiry following standard ORI/IRB operating procedures. The IRB is also responsible for determining whether the incident meets requirements for reporting to the federal regulatory agencies. In making the determination, the IRB follows standard ORI/IRB operating procedures for reporting. (See the Mandated Reporting to External Agencies SOP)
4. After the IRB has completed its review of the complaint/alleged noncompliance, the ORI RCO is responsible for providing the BSO with a copy of the final deliberations. If the IRB determines that the incident is reportable to a federal regulatory agency, the RCO is responsible for sending a copy of the federal report to the BSO.
5. If the complaint/alleged noncompliance falls under IBC purview, the BSO initiates an inquiry following standard IBC operating procedures. After the IBC has completed its review of the complaint/alleged noncompliance, the BSO is responsible for providing the ORI with a copy of the final deliberations. If the IBC determines the incident is reportable to a federal regulatory agency, the BSO is responsible for sending a copy of the federal report to ORI.

Quality Assurance/Improvement Findings

1. If the ORI Quality Assurance/Improvement Program conducts a directed or routine Quality Improvement Review (QIR) of an IBC protocol, the Quality Assurance/Improvement Program team is responsible for providing the BSO with a copy of the findings of the directed or routine QIR.
2. If the BSO or any IBC personnel audits or inspects an IBC protocol, the BSO is responsible for providing the ORI Quality Assurance/Improvement Program with a copy of the report. The ORI Quality Assurance/Improvement Program team is responsible for sending the report to the IRB to determine whether additional IRB action is necessary.

Joint Policy/Procedures

1. The ORI Director or his/her designee, when appropriate, is responsible for initiating efforts to establish joint IRB/IBC policy, procedures, and submission forms.
2. The IBC, ORI staff, the IRB, or University of Kentucky researchers or administrators may submit suggestions or recommendations for the joint policy/procedure/form initiatives to the ORI Director.
3. The ORI Director and the BSO must approve any revision to existing joint policies or forms.

REFERENCES

Not applicable

Approved By: ORI Director, Nonmedical IRB Chair, Medical IRB Chair

Date First Effective: July 24, 2006

Last Revision Date: May 9, 2019

Revision #7

OBJECTIVE

To describe the procedures for coordination between the University of Kentucky (UK) Investigational Drug Service (IDS), the Institutional Review Board (IRB), and the Office of Research Integrity (ORI) to ensure the safe and efficient conduct of clinical drug trials

GENERAL DESCRIPTION

UK is committed to ensuring the rights and welfare of human subjects involved in research using investigational drugs, agents, and/or biologics, including gene therapy medications and recombinant DNA (r-DNA). UK has established procedures to ensure that the use of any investigational drug is in compliance with institutional policies for the protection of human subjects as well as UK Pharmacy Department policies governing routine drug distribution, federal regulations, The Joint Commission (TJC) and sponsor policies. The IDS, a unit within the UK Department of Pharmacy, supports clinical drug studies by ensuring consistent handling of these products with regard to procurement, storage, dispensing, inventory control, and disposal. The UK IRB and the IDS have established procedures to coordinate the review and approval of clinical investigations involving investigational drugs in accordance with applicable law, governing regulations, and institutional policy.

Definitions

The term investigational drug or agent refers to any pharmaceutical forms of a new drug/agent or biologic used in a clinical investigation. The terms include products that are not generally recognized as safe and effective for any use under the conditions prescribed, recommended, or suggested by the Food and Drug Administration (FDA) or products already approved by the FDA as safe and effective that are being studied for new indications.

RESPONSIBILITY 

Execution of SOP:  IRB, IDS Director, IDS Staff, ORI Staff, ORI Research Compliance Officer (RCO), Principal Investigator (PI)/Study Personnel, UK Pharmacy and Therapeutics Committee, Institutional Biosafety Committee (IBC) 

PROCEDURES 

1. UK policy requires that the IRB review and approve all investigational drug use involving human subjects prior to initiation of the study regardless of whether investigators conduct investigational drug studies on an inpatient or an outpatient basis.
2. The IDS Director or designee serves as an ex-officio member of the UK Medical IRBs and provides review and oversight of research involving investigational drugs—inpatient and outpatient.
3. The IDS Director supplies the IBC, principal investigator (PI), and the study coordinator(s) with information on investigational drug protocols, particularly gene therapy protocols, as needed to ensure the safety and welfare of human subjects.
4. The IDS complies with existing Department of Pharmacy procedures and additional requirements established for dispensing investigational drugs. These procedures include verification of IRB protocol approval and informed consent, record keeping, preparation or packaging of final product, labeling of dispensed product, and disposal of unused or partially used medication.
5. IDS audits of compliance with investigational drug procedures are consistent with the requirements of TJC, the UK Pharmacy and Therapeutics Committee, and other regulatory agencies as they relate to dispensing investigational drugs.

Inpatient Investigational Drug Research

1. UK policy requires that all inpatient investigational drug investigations use the services of the IDS for storage, control, and dispensing of the drug in question unless the PI requests an exception during the protocol review process and the IDS agrees to the exception.
2. The PI prepares and submits an application and detailed sponsor protocol to the IRB for review. The ORI forwards electronic copies of medical IRB agendas to the IDS Director or designee for review.
3. IDS staff review the protocol and drug information forms to ascertain compliance with investigational drug regulations, UK policy, and the proposed mechanisms for storing, manufacturing, dispensing, and administering the drug in question. This review also takes into consideration the ability of the IDS to meet protocol requirements based on resources, personnel time, and drug/drug delivery system availability.
4. The IDS offers the PI necessary assistance to establish and maintain compliance with UK policies for drug storage, manufacturing, dispensing, and administration to hospitalized patients.
5. In the event of any concerns with the protocol, IDS staff submit concerns along with recommendations of possible alternatives to the PI for clarification or reassessment and to the IRB/ORI.
6. In the event that any concerns remain unresolved between the IDS and the PI, IDS staff forward the complete documentation to the Pharmacy and Therapeutics Committee for review and adjudication before making a final determination.
7. Once the IRB review is complete, the PI must provide a copy of the approval letter to the IDS before the IDS pharmacist will dispense an investigational drug.
8. The IDS does not dispense investigational drugs for a clinical drug trial without documentation of IRB approval.
9. The IDS maintains a copy of the research protocol in a secure area and keeps the IRB letter of approval on file.
10. The PI is responsible for providing the IDS a copy of any amendments to the protocol made during the course of the study when applicable to storage, control, and dispensing of the study drug.
11. The PI or designee provides training to personnel administering investigational drugs on the objectives of the research protocol and specific information about the drug.
12. The IDS assists the PI in staff orientation. All study personnel must administer investigational drugs under the general direction of the PI who is a medical professional (physician or dentist).
13. With the cooperation of the PI, the IDS prepares necessary drug information monographs for appropriate personnel and makes these documents available to all nurses, physicians, and pharmacists throughout the UK Hospital/Chandler Medical Center.
14. Prior to the initiation of the study, the IDS arranges with the PI to receive, store, label, dispense, maintain inventory, and audit all investigational drugs used in the conduct of the protocol in accordance with UK policy, FDA regulations, and National Institutes of Health (NIH) guidelines.
15. The IDS only dispenses investigational drugs upon pharmacist’s receipt of an authorized physician’s order (prescription) containing all information required by Department of Pharmacy policy.
16. The IDS does not dispense investigational drugs without required information unless the PI negotiates an exception and modification process in cases of critical care studies.
17. The PI or designee is responsible for obtaining and documenting informed consent from the subject or legally authorized representative prior to administering investigational drugs. The PI or designee provides to the IDS verbal or written confirmation of the completed informed consent process including documentation as required.
18. The IDS pharmacist prepares and dispenses the investigational drug in accordance with the protocol, established Department of Pharmacy manufacturing guidelines, and the Pharmacists’ Drug Information Form. The label must contain the statement “For Investigational Use Only.”
19. The IDS completes final reconciliation of investigational drug accountability logs upon notification of a study closure by the protocol sponsor or PI and arranges a close-out audit by the protocol study monitor.

Outpatient Investigational Drug Research

1. The IDS offers its services to investigators conducting clinical outpatient investigational drug studies. However, such investigators have the option to not use the IDS for storage, control, and dispensing of the drug in question.
2. The IDS handles outpatient investigational drug studies which do choose to rely on the services of the IDS according to the Inpatient Investigational Drug Research procedures outlined above.
3. Investigators who choose not to use the services of the IDS for outpatient investigational drug studies must complete and submit a Use of Investigational New Drug Form with the IRB application.
4. The IRB reviews and approves the plan for control of the investigational drug or biologic under study as described in the IRB application during a convened meeting unless the study is eligible for expedited review.
5. The IDS pharmacist conducts an annual audit of the policy and procedures for storage and dispensing of investigational drugs by researchers not using the IDS to assure that storage and dispensing comply with federal, state, and institutional regulations and standards.
6. The IDS notifies the PI in advance of the audit.
7. The IDS pharmacist uses a standard IDS audit form to aid in verifying adherence to applicable laws and regulations for use and accountability of investigational drugs.
8. Upon completion of the audit, the IDS prepares and sends a memorandum to the PI describing the audit results and suggestions for improvement, if any.
9. If a subsequent audit finds that the PI did not comply with the original suggestions for improvement, the IDS notifies the PI and reports the audit findings to the IRB.

Emergency Use and Single Patient Clearance

1. Physicians who wish to use an investigational drug under an emergency use protocol and single patient clearance must apply to the IRB Chair for clearance to proceed with the emergency use. (See ORI/IRB Emergency Use SOP)
2. The physician must have documented clearance from the IRB Chair to use investigational drugs under this system.
3. The IRB Chair reviews the protocol for emergency use, determines whether the emergency use request fits within the criteria of 21 CFR 50.23 and, if it does, provides a copy of a single patient clearance letter to the investigator.
4. The PI forwards a copy of the IRB clearance letter to the IDS for single patient use. The IDS will not dispense an investigational drug without this clearance.
5. If there is insufficient time to obtain clearance from the IRB chair or designee and the immediate use of the investigational drug is, in the healthcare provider’s opinion, required to preserve the life of the patient, the IDS may dispense the investigational drug. The investigator must submit the emergency use report to the IRB for review within five (5) working days from the date of emergency use. (See ORI/IRB Emergency Use SOP)

Complaints and Alleged Noncompliance

1. If the IDS receives a complaint from a subject, subject’s family member, staff, or researcher concerning alleged noncompliance or issues with subject’s rights and welfare of human subjects, the IDS immediately (within two days) notifies the ORI RCO. The IDS may confer with the ORI RCO to assess whether the complaint/alleged noncompliance falls under the purview of the IRB, IDS, or both.
2. If the ORI RCO receives a complaint or alleged noncompliance pertinent to IDS and the complaint or alleged noncompliance is applicable to IDS policies and procedures, the ORI RCO immediately (within two days) notifies the IDS. The ORI RCO may confer with the IDS to assess whether the complaint/alleged noncompliance falls under the purview of the IRB, IDS, or both.
3. If the complaint/alleged noncompliance falls under IRB purview, the ORI initiates an inquiry following ORI/IRB standard operating procedures. The IRB is also responsible for determining whether the incident meets requirements for reporting to any federal regulatory agencies. In making the determination, the IRB follows standard operating procedures for reporting. (See Mandated Reporting to External Agencies SOP)
4. After review of the complaint/alleged noncompliance is complete, the ORI RCO is responsible for providing the IDS with a copy of the final determination, if applicable to the IDS. If the IRB determines that the incident falls under the requirements for reporting to a federal regulatory agency and is applicable to the IDS, the ORI RCO is responsible for sending a copy of the federal report to the IDS.

REFERENCES 

Not applicable

Approved By: ORI Director, Nonmedical IRB Chair, Medical IRB Chair

Date First Effective: May 31, 2005

Last Revision Date: March 11, 2021

Revision #7

OBJECTIVE 

To describe the procedures for coordination between the Institutional Review Board (IRB)/Office of Research Integrity (ORI) and the Markey Cancer Center (MCC) on protocols to be conducted at the University of Kentucky (UK) MCC and the UK MCC at Lexington Clinic (MCCLC).

GENERAL DESCRIPTION

The MCC, MCCLC, and the IRB are committed to ensuring the protection of human subjects involved in clinical research. They have enacted a number of coordination activities in significant areas including protocol review; complaints and alleged noncompliance; quality assurance/improvement findings.

RESPONSIBILITY 

Execution of SOP: MCC Staff, MCC Director/CEO, MCC Associate Director for Clinical Research or designee, IRB Members, ORI Staff, ORI Quality Improvement Program (QIP) Coordinator, ORI Research Compliance Officer (RCO), Principal Investigator (PI)/Study Personnel, Protocol Review and Monitoring Committee (PRMC), Data and Safety Monitoring Committee (DSMC), Lexington Clinic Director/CEO.

Definitions 

National Cancer Institute (NCI) and the Markey Cancer Center define clinical trial as a type of research study that tests how well new medical approaches work in people. These studies test new methods of screening prevention, diagnosis, or treatment of a disease. Examples include therapeutic and prevention intervention or non-intervention trials (e.g., patient records, epidemiologic/observation, screening, early detection diagnostic studies).

An unacceptable audit finding as defined by the NCI Guidelines for Auditing Clinical Trials includes multiple major deficiencies, a single major flagrant deficiency, or an excessive number of lesser deficiencies. 

PROCEDURES

Protocol Review Procedures

1. Investigators submit proposed cancer clinical trials to the IRB in accord with IRB policies and procedures.
2. ORI staff screen IRB applications to determine whether the study involves cancer research and, if so, the PRMC is notified.
3. The PRMC is responsible for determining whether a study meets the NCI definition of a clinical trial and for issuing documentation to the investigator which either confirms that PRMC approval has been obtained or that PRMC review is not required.
4. ORI staff process the IRB application for review and the IRB proceeds with review in accord with ORI/IRB Initial Review SOPs, independent of the PRMC review.

Complaints and Alleged Noncompliance

1. Research subjects, family members, or others may report any serious complaint concerning subject rights and welfare or make allegations of investigator noncompliance in a cancer clinical trial to the ORI Research Compliance Officer (ORI RCO) following IRB standard operating procedures.
2. The ORI RCO handles the complaint, concern, or allegation in accord with standard ORI/IRB operating procedures.
3. At the completion of the IRB review of the complaint, concern, or alleged noncompliance regarding a cancer clinical trial, the ORI RCO provides the MCC Associate Director for Clinical Research with a copy of the final IRB deliberation and any federal reports submitted as a result of the allegation. The MCC Associate Director for Clinical Research disseminates the copy of the final deliberation and/or federal report to the Director of the MCC and MCC DSMC in accord with standard MCC operating procedures.
4. If the MCC receives a complaint, concern, or allegation from a subject, subject family member, staff, or researcher concerning alleged noncompliance or issues with subject rights and welfare of human subjects involving a cancer clinical trial, the MCC Associate Director for Clinical Research or designee informs the ORI RCO immediately (within two days). The MCC may confer with the ORI RCO to assess whether the complaint/alleged noncompliance falls under the purview of the IRB, MCC, or both.

Quality Assurance/Improvement Findings

1. If the ORI QIP Coordinator conducts a directed or routine Quality Improvement Review of a cancer clinical trial, the QIP Coordinator provides the MCC Associate Director for Clinical Research a copy of the final report within 15 working days of final review. The MCC Associate Director for Clinical Research disseminates a copy to the MCC DSMC and appropriate personnel in accord with standard MCC operating procedures.
2. If during a routine or “for cause” audit the MCC Audit Committee identifies either: 1) evidence that research subjects have been placed at significant risk of harm or the welfare of subjects has been jeopardized and that the finding has not previously been reported to the ORI RCO/IRB; or 2) there is evidence of an unacceptable audit finding, the MCC Audit Committee Chair notifies the MCC Associate Director for Clinical Research and the ORI RCO within 24 hours of identification of the issue. If the MCC DSMC suspends or terminates a study, the Chair of the MCC DSMC notifies the ORI RCO within two working days of suspension or termination of a study.
3. The MCC DSMC Chair forwards an electronic copy of all “for cause” audit reports and any routine audit reports found unacceptable by the DSMC (including the corrective action plan for the findings) to the ORI RCO within 15 working days of final review by the MCC DSMC. The MCC DSMC Chair forwards an electronic copy of the suspension or termination report to the ORI RCO within 15 working days of final review by the MCC DSMC. The ORI RCO forwards the report to the IRB and/or the ORI Director in accord with ORI standard operating procedures.

Procedures for MCCLC Research

1. Investigators submit proposed cancer clinical trial to the IRB in accord with IRB policies and procedures. Investigators indicate within the IRB applications that the proposed research will take place at MCC at Lexington Clinic.
2. ORI reliance staff are assigned as consultants for further determinations regarding offsite/reliance requirements per the IRB Reliance SOP and/or Offsite Research Guidance.
3. ORI staff process the IRB application for review and the IRB proceeds with review in accord with ORI/IRB Initial Review SOPs, independent of the PRMC review. 

REFERENCES

Unanticipated Problem/Adverse Event SOP

Termination and Suspension of Research by the IRB SOP

Mandated Reporting to External Agencies SOP

NCI Guidelines for Auditing Clinical Trials 

IRB Reliance SOP

Offsite Research Guidance

Approved By: ORI Director, Nonmedical IRB Chair, Medical IRB Chair

Date First Effective: March 1, 2005

Last Revision Date: May 9, 2019

Revision #3

OBJECTIVE 

To describe the procedures for coordination between the Institutional Review Board (IRB)/ Office of Research Integrity (ORI) and the Radiation Safety Officer (RSO) on full review protocols to be conducted involving the administration of radiation

GENERAL DESCRIPTION

Both the RSO and the IRB are committed to ensuring the protection of human subjects involved in research. A number of coordination activities in significant areas have been enacted, including joint committee membership, protocol review complaints and alleged noncompliance, quality assurance/improvement findings, and joint policy/procedures.

RESPONSIBILITY 

Execution of SOP: RSO or designee, IRB, ORI Staff, ORI Quality Improvement Program (QIP) Coordinator, ORI Research Compliance Officer (RCO); Principal Investigator (PI)/Study Personnel 

PROCEDURES

Joint Committee Membership

1. The RSO serves as an ex-officio non-voting member of the Medical IRB.
2. The ORI Director is an ex-officio member of the Committee on Safety and Environmental Health, of which Radiation Safety is a subcommittee. The ORI Director serves as the primary liaison in the development of joint RSO-IRB policies and procedures.

Protocol Review Procedures

1. When a PI proposes research that falls under the purview of the RSO, the PI contacts the RSO to request review of the laboratory prior to submitting the protocol to the IRB. The PI submits the protocol to the ORI/IRB and indicates the date of RSO review. This RSO laboratory infrastructure approval is not protocol specific but authorizes the laboratory to conduct research involving radiation. If the PI is unsure whether the research falls under RSO purview, he/she contacts the RSO for clarification.
2. Upon receipt of a complete initial submission that falls under the RSO’s purview, ORI staff schedule the protocol for review at a convened Medical IRB meeting. ORI staff forward all full review medical protocols that include research procedures involving radiation to the RSO for review. The IRB reviews new protocols that include research procedures involving radiation but withholds final approval until the RSO has reviewed the protocol.
3. ORI staff provide the RSO and IRB members with agenda notices following ORI standard operating procedures for disseminating information prior to the IRB meeting.
4. ORI staff forward any modification requests that add research procedures involving radiation to the RSO for review and comments before IRB review and approval.
5. The RSO or his/her designee provides the IRB with radiation safety expertise, assesses the adequacy of the information in the informed consent form pertaining to radiation risks, and advises the IRB regarding whether radiation safety review is needed. The RSO may attend the IRB meeting or provide comments prior to the meeting.

Complaints and Alleged Noncompliance

1. If the RSO receives a complaint from a subject, subject family member, staff, or researcher concerning alleged noncompliance or subject rights and welfare, the RSO immediately (i.e., within 2 days) notifies the ORI RCO. The RSO confers with the ORI RCO to assess whether the complaint/alleged noncompliance falls under the purview of the IRB, Radiation Safety, or both.
2. If the ORI RCO receives a complaint or alleged noncompliance involving issues pertinent to radiation safety, he/she immediately (within 2 days) notifies the RSO. The ORI RCO confers with the RSO to assess whether the complaint/alleged noncompliance falls under the purview of the IRB, Radiation Safety, or both.
3. If the complaint/alleged noncompliance falls under IRB purview, the ORI initiates an inquiry following ORI/IRB standard operating procedures. The IRB also determines whether the incident meets requirements for reporting to federal regulatory agencies. In making the determination, the IRB follows the ORI/IRB standard operating procedures for reporting.
4. If the complaint/alleged noncompliance involves issues pertinent to radiation safety, the ORI RCO provides the RSO with a copy of the final IRB determination. If the IRB determines that the incident is reportable to a federal regulatory agency, the ORI RCO sends a copy of the federal report to the RSO.
5. If the complaint/alleged noncompliance falls under RSO purview, the RSO initiates an inquiry. After the RSO completes the review of the complaint/alleged noncompliance, the RSO provides the ORI with a copy of the final determination. If the RSO determines that the incident is reportable to a federal regulatory agency, the RSO sends a copy of the federal report to the ORI.

Quality Assurance/Improvement Findings

1. If the ORI QIP Coordinator conducts a directed or routine Quality Improvement Review of an IRB protocol and finds issues pertinent to radiation safety, the ORI QIP Coordinator provides the RSO with a copy of the QIP review findings.
2. If the RSO audits or inspects a radiation safety protocol/investigator and finds issues pertinent to the IRB process, the RSO provides the ORI QIP Coordinator with a copy of the report.  The ORI QIP Coordinator sends the report to the IRB. The IRB determines whether IRB action is necessary.

Joint Policy/Procedures

1. The ORI Director, when appropriate, initiates efforts to establish joint IRB/RSO policies, procedures, and submission forms. The RSO, ORI staff, the IRB, or University researchers or administrators may submit suggestions or recommendations for joint policies/procedures/forms initiatives to the ORI Director.

REFERENCES

Not Applicable

Approved By: ORI Director, Nonmedical IRB Chair, Medical IRB Chair

Date First Effective: June 17, 2005

Last Revision Date: April 30, 2019

Revision #10

OBJECTIVE 

To describe procedures for coordination between the Office of Sponsored Projects Administration (OSPA), the Institutional Review Board (IRB), and the Office of Research Integrity (ORI) in administering sponsored research agreements at the University of Kentucky (UK)

GENERAL DESCRIPTION

OSPA, the IRB, and ORI are committed to ensuring the protection of human subjects involved in sponsored research. OSPA and the IRB/ORI coordinate activities in significant areas of sponsored research including: proposal submission; negotiation of award agreements; negotiation of clinical trial agreements (CTAs); subaward agreements for off-site research; establishing accounts; IRB fees; coordination of complying with the NIH Genomic Data Sharing (GDS) Policy; terminations and lapses of approval.

Definitions

Sponsors are the agencies, institutions, companies, organizations, foundations, or other grantors responsible for funding a research study. The term sponsor is understood to include any intermediaries, such as contract research organizations or coordinating centers, acting as agents of the sponsor in carrying out the responsibilities above. All research falling under these types of agreements are considered sponsored projects. 

RESPONSIBILITY 

Execution of SOP: OSPA Research Administrators (RA), OSPA College Grant Officers (CGO), OSPA Director, OSPA Subaward Administrators (SA), OSPA Conflict of Interest Administrator (COIA) , OSPA Administrative Staff (AA), ORI Staff, ORI Director, ORI Research Compliance Officer (RCO), ORI Off-Site Research Coordinator, Principal Investigator (PI), Study Personnel 

PROCEDURES

Proposal Submission

1. Before OSPA submits a proposal to an extramural sponsor, the PI completes the UK electronic Internal Approval Form (eIAF) clearly indicating the involvement of human subjects, if applicable, and submits it to OSPA.
2. The eIAF includes questions designed to verify whether the project involves human subjects and whether the PI has obtained IRB approval.
3. The CGO screens each proposal and the associated eIAF. When appropriate, the CGO advises the PI of sponsor requirements for submission of the certification of IRB approval and/or completion of mandatory human research training. The CGO refers the PI to the ORI in cases where the PI requires additional clarification or assistance with human research protections.
4. OSPA submits certifications of IRB approval or mandatory education requirements to the agency in accordance with agency requirements. ORI staff prepare agency certifications for the PI upon request. The OSPA Director signs the agency certifications.
5. When the OSPA RA receives the IRB protocol number, OSPA staff enter it into the OSPA electronic database. OSPA identifies all sponsored proposals involving human subjects and/or clinical trials in the electronic database so that RAs or the OSPA Director may generate reports of all research involving human subjects or of all clinical trials.
6. Initial IRB review and continuation review submissions prompts the PI to provide information identifying the sponsor and, if funded, the OSPA account number.
7. The CGO ensures that investigators, as defined in the Administrative Regulations 7:2 (AR 7:2), have completed an annual financial conflict of interest disclosure prior to the submission of a proposal to an external funding agency. The COIA reviews financial disclosures and determines whether an investigator has or could potentially have a financial conflict of interest with their sponsored research. Once a proposal is funded, the OSPA RA confirms that all investigators included on the proposal have completed a financial disclosure and the Financial Conflict of Interest training information, and confirms with the COIA that there is no financial conflict of interest on the project. Should an investigator have a financial conflict of interest on the project, the conflict of interest is managed according to University procedures outlined in AR 7:2.

Negotiation of Award Agreements

1. OSPA provides investigators with up-to-date information on institutional policy in negotiating the terms of sponsored research agreements to ensure compliance with applicable law, university policy, and good business practice. OSPA publishes information resources on the OSPA web site, including regulatory resources, sample research study agreements, and specific information on clinical trial agreements.
2. Once UK receives an extramural award, the OSPA RA reviews the proposed research agreement and negotiates acceptable terms between the sponsor and the institution. For projects including human subjects research, the agreement includes provisions for human research protections in compliance with all applicable laws, institutional policies for ethical conduct of research, and the written research protocol. The PI receives a copy of the completed agreement from OSPA.
3. The OSPA Director’s signature signifies acceptance of a research agreement for which the RA has obtained appropriate administrative approvals and/or a completed eIAF.
4. The OSPA RA negotiates the terms of the research agreement to allow for publication of the research results in accordance with sponsor and university policies and acknowledging the roles of the PI and sponsor. 

Negotiation of Clinical Trial Agreements

1. Additional award negotiation procedures beyond those outlined above apply to a sponsored research project designated as a clinical trial.
2. The PI or Study Personnel provide the OSPA RA with a copy of the proposed agreement and a sponsor contact as early in the process as possible.
3. The OSPA RA screens the terms of the CTA for specific provisions related to IRB or Health Insurance Portability and Accountability Act (HIPAA) issues which need coordination with the IRB. Types of issues that may require IRB/OSPA coordination include additional university/sponsor certifications or requirements related to human research protections, applicable federal assurances, and sponsor access to protected health information. Specific examples include, but are not limited to, the following:
   • Provisions for study-related reporting and notifications;
   • Coverage of subject injury and medical care;
   • Rights/permissions to subject samples and prior medical records; and
   • Use of participant data in future sponsor reviews.
4. When appropriate, the OSPA RA notifies ORI staff and provides a copy of the contract language in question. ORI staff advise the OSPA RA on pertinent existing regulatory and institutional policy, provide requested documentation or certifications, or refer the request to the IRB for review, as appropriate. ORI staff act as a liaison between the IRB and the OSPA RA and respond to OSPA RA requests on a case-by-case basis. The OSPA RA ensures that the resulting provisions incorporated into the CTA comply with the guidance obtained from the IRB/ORI.
5. The OSPA RA notifies ORI staff if any provisions in the contract language differ from the IRB informed consent template applicable policies (e.g., provisions for coverage of subject injury and medical care). Also, ORI staff notify the OSPA RA if the IRB makes any changes in the consent form that differ from the IRB informed consent template applicable policies. In these cases, the ORI staff and the OSPA RA review the informed consent document and the contract language for consistency. If the informed consent document needs changes, ORI staff forward required changes to the PI and the IRB for review and approval.
6. The OSPA RA obtains a copy of the IRB approval letter from the PI or the ORI and places it in the file. The RA maintains a checklist of documents required to complete a clinical trial file, including the following:
   • A copy of the research protocol (becomes a part of the CTA by attachment);
     • The fully signed agreement;
     • The Internal Approval Form; and
     • The IRB approval letter.
7. When applicable, given the nature of the research, the OSPA RA includes a clear statement in the CTA that addresses medical care for research subjects with a research-related injury.
8. The OSPA RA includes provisions in the CTA for reporting to the sponsor any deviations from the research protocol necessary to protect the safety, rights, or welfare of patients enrolled in the clinical trial and any serious or adverse reactions resulting from participation in the study.
9. Once the OSPA RA has all required documentation, he/she establishes the account.
10. If all other documentation is complete prior to receiving certification of IRB approval, the OSPA RA may establish an account with restrictions preventing research subject enrollment and prospective subject contact. See Establishing Accounts below.
11. In studies in which sponsors are responsible for monitoring the progress of the research to be conducted, the OSPA RA includes written provisions in the agreement for the sponsor to promptly report (i.e. within 30 days) any information, during and after the study, that may affect research oversight of a protocol by the IRB, affect the safety of human subjects or their willingness to participate, and/or influence the conduct of the study, as required by the Food and Drug Administration.
12. If UK receives such information from the sponsor, including evidence of serious or continuing noncompliance or evidence of scientific misconduct, OSPA staff report it to the IRB and the ORI.
13. During the study, the OSPA RA notifies ORI staff of applicable post-approval CTA amendments that may affect the informed consent. ORI staff notify the OSPA RA regarding applicable protocol amendments that may affect the CTA.

OSPA/ORI Coordination: IRB Fees 

1. The OSPA RA screens the industry-sponsored clinical trial budget to ensure the PI has included the IRB review charge. UK policy requires a one-time $3,000 charge for IRB review unless the OSPA Director waives the requirement.
2. After the OSPA RA acquires a fully signed CTA, he/she forwards to the ORI the information needed to prepare the invoice for this fee. Required information includes the following:
   • Name, address, phone, and fax number of contact person;
   • Sponsor protocol number;
   • IRB protocol number;
   • PI name; and
   • Protocol title.
3. The OSPA RA includes the e-mail sent to the ORI in OSPA’s files.
4. ORI staff prepare the invoice and send it to the sponsor. ORI staff include the UK tax number on each invoice with the payee designated as the University of Kentucky Research Foundation.
5. If appropriate, ORI staff send a second reminder to the sponsor if the sponsor does not respond.
6. ORI staff immediately deposit any checks received into the established account.
7. ORI staff also forward the original notification email with cover email confirming receipt of the check to the OSPA Director and RA.

Establishing Accounts

1. Before establishing a new account, the OSPA RA reviews the electronic file for accuracy and completeness and verifies the PI has obtained IRB approval.
2. Many sponsors will not issue an award for sponsored research involving human subjects without IRB approval, and OSPA will not typically establish an account without it.  However, if all other documents are complete except the certification of IRB approval, the OSPA RA may forward a form to the PI and his/her chair for signature. Upon receipt of this form and approval from the OSPA Director, OSPA may proceed to establish an E-account with the written understanding that no activity involving human subjects will take place until the PI obtains IRB approval. For clinical trials, an e-account is not established without special circumstances.
   
   If OSPA establishes an account prior to IRB approval, the OSPA staff add the following statement to the first Project Account Data Record (PADR) in the OSPA electronic database: “This account has been established in advance of approval or exemption by the IRB. You may not enroll subjects, initiate any contact with prospective human subjects, collect data on human subjects or use existing data/specimens collected from living human subjects until IRB approval or exemption is obtained.
3. Once the OSPA RA receives the IRB approval letter from the ORI, the PI or study personnel, he/she enters the IRB protocol number in the OSPA electronic database.
4. UK will not disburse sponsored research funds until the PI has completed a financial conflict of interest disclosure and, if appropriate, a management plan is in place for the PI or other investigator on a project.

Negotiation of Subaward Agreements for Off-Site Sponsored Research

1. The OSPA SA contacts ORI reliance management staff for advice whenever questions arise in subaward agreements for off-site human research.
2. The OSPA SA uses Attachment 2 of the FDP template to facilitate communication and exchange of the required information between subrecipients for the involvement of human subjects.
3. The PI completes the eIAF before submitting a proposal to an extramural sponsor, checking yes if the project uses subcontracted or outside consultants.
4. The OSPA RA checks the proposal budget and the award documents to identify proposals which include subaward agreements as part of the proposed research and directs the PI to the online Sub-agreement Request Form. The AA sends instructions with PADR1 cover page and the CGOs are provided with a monthly report of the new accounts with subaward G/Ls in the budget. The CGO will then contact the PI and direct them to the subaward database.
5. The PI completes the online Sub-agreement Request Form, checking “yes” if the subcontracted portion of the project includes human subjects. The PI attaches a detailed scope of the work to be completed by the subrecipient, a budget, and a description of the plan for both supervising/monitoring the subrecipient’s performance and reporting. The subrecipient shares responsibility for detailing the scope of work and budget.
6. OSPA uses the Federal Demonstration Partnership (FDP) subaward template whenever appropriate and maintains templates for subawards when the FDP template cannot be used. The PI may obtain the template from the SA.
7. The OSPA SA ensures the subaward agreement includes clauses which require the subrecipient to abide by all applicable human research regulations and which specify that the subrecipient bears full responsibility for the proper and safe performance of its work and services involving human subjects.
8. In the subaward agreement, the OSPA SA identifies the subrecipient’s work under the subaward as involving human subjects by checking “yes” for that statement. In the FDP subaward template, the standard IRB clause is added to Attachment 4: Reporting and Monitoring Requirements.
9. If the OSPA SA checks “yes” indicating that the subrecipient’s scope of work involves human subjects, the subrecipient provides documentation to the OSPA SA that an IRB has reviewed and approved the work.
10. The Federalwide Assurance (FWA) number is captured on the Subcommitment Form or is listed in the entity profile if the subrecipient is part of the FDP expanded clearinghouse.
11. The OSPA SA checks the OHRP database for the subrecipient’s active approved FWA number before submitting the subaward for full execution.

Negotiation of Subaward Agreements for Off-Site Research Sponsored by the U.S. Department of Health and Human Services

1. If research is federally funded by the U.S. Department of Health and Human Services (HHS), each performance site must independently assure HHS of its intent to comply with federal regulations for the protection of human subjects. To do so, each site negotiates approval of its own written assurance with the Office for Human Research Protections (OHRP).
2. OSPA maintains a template for subaward agreements for prime awards funded by an agency of the HHS and uses the FDP template whenever appropriate. The PI may obtain the template from the SA. The subaward agreement for HHS-sponsored research involving human subjects includes clauses that require the subrecipient to abide by all applicable human research regulations and specify that the subrecipient bears full responsibility for the proper and safe performance of its work and services involving human subjects.
3. If the subrecipient’s work involves human subjects, the PI checks “yes” for that statement on the online Sub-agreement Request Form. The subaward agreement contains provisions requiring the subrecipient to provide the institution’s federally assigned assurance number to the OSPA SA along with documentation that an IRB has reviewed and approved the research described in the sub-agreement scope of work.
4. For HHS-sponsored projects, the subrecipient also provides a letter from an IRB representative indicating the date of review/approval and committing to submit the IRB’s federally assigned assurance number to the PI.
5. The SA checks the OHRP database for the subrecipient’s active approved Federalwide Assurance number before submitting the subaward for full execution.
6. The PI is responsible for submitting the federalwide assurance numbers for each site to the IRB annually and for maintaining current documentation for the entire project throughout the course of the research in accordance with federal and UK IRB requirements.
7. In the subaward agreement for HHS-sponsored projects, the subrecipient certifies that his/her institution has a human subjects education program that complies with federal requirements if required by the terms and conditions of the prime award.
8. The subaward agreement and any subsequent amendments for continued funding also contain a certification statement that the project is under a currently active IRB approval.

NIH-funded Research that generates large-scale Genomic Data subject to the Genomic Data Sharing (GDS) Policy

1. A PI who seeks or receives NIH-funding for research that will generate large-scale human genomic data submits to the IRB an initial application or modification request including a protocol for the collection of genomic and/or phenotypic data and genomic data sharing plan. 
   
   The IRB reviews and verifies that the protocol and plans for subsequent data sharing for future research:
   • meet human subject regulations and GDS policy standards;
   • are consistent with the informed consent of study participants from which the data were obtained;
   • delineate data that is excluded from sharing based on options or conditions in the informed consent (i.e., data use limitation statement);
   • include, if applicable, safeguards (e.g., Certificate of Confidentiality) to minimize potential for individual, family, or group harm (e.g., stigmatizing genetic trait, discrimination based on genetic variant); and,
   • include adequate de-identification of data, consistent with HHS and HIPAA standards.
2. ORI indicates any identified data use limitations in the IRB approval letter.
3. Once approved, the PI submits the IRB approval letter to OSPA.
4. The OSPA Director signs an Institutional Certification verifying that:
   • the protocol and data sharing plan has IRB approval based on conditions above;
   • sharing is consistent with applicable national, tribal, and state laws, regulations, as well as relevant institutional policies; and
   • any limitations on the future research use of the data, as expressed in the informed consent documents or IRB review, are delineated.

Access to NIH-Designated Data Repositories subject to the NIH Genomic Data Sharing (GDS) Policy

1. A PI who plans to seek data from a controlled-access NIH data repository contacts OSPA to develop a data access request. OSPA consults with the PI and the information technology representative from the PI’s department to ensure compliance with data security standards.
2. OSPA gathers signed documentation from all individuals who will have access to the data confirming their acknowledgment of data policies.
3. The PI and OSPA co-sign a Data Use Certification (DUC) Agreement to complete the submission of the request for review by an NIH Data Access Committee (DAC).
4. Generally, access to GDS datasets do not stipulate IRB review and approval; however, in the rare occurrence that the NIH DAC requires local IRB review for a specific dataset, the PI submits the appropriate IRB application.

Terminations or Lapses in IRB Approval for Sponsored Research

1. PADRs for non-competing years require active IRB approvals to be in place to ensure IRB approval for ongoing sponsored research has not lapsed or been terminated by the IRB. The OSPA RA will not add funds to an existing account for a sponsored project including human subjects research in non-competing years unless an active IRB approval is in place.
2. If the IRB terminates approval of a sponsored project due to noncompliance, the RCO provides the OSPA Director with a copy of the resulting termination letter.
3. OSPA takes the appropriate action in accordance with the sponsor requirements.
4. If IRB approval lapses due to failure of the PI to submit a continuation review application, ORI staff send the PI a lapse of approval letter. The PI is responsible for informing the project sponsor and OSPA that IRB approval has expired.

REFERENCES

Not applicable

ATTACHMENT

University of Kentucky IRB Fee Schedule

Table 1 below shows the IRB fees for protocols submitted to the UK IRB for review after February 1, 2017.  With the exceptions described below, these fees apply to human subjects clinical trial protocols supported by industry funding.  Sponsors will be invoiced for industry-sponsored studies reviewed by the UK IRB.

Table 1

Exceptions:

• Human subjects research that qualifies for Exempt IRB review.
• Protocols involving the non-research use of a Humanitarian Use Device.
• Protocols for an emergency or one-time use of an investigational drug, biologic, or device.
• Industry support is limited to the provision of a drug or device.

Table 2 below shows the IRB fees for industry-sponsored protocols submitted to a non-UK IRB for review after February 1, 2017. Protocols submitted to a non-UK IRB must be registered with the UK ORI.

Table 2

Approved By: ORI Director, Nonmedical IRB Chair, Medical IRB Chair

Date First Effective: July 5, 2005

Last Revision Date: August 30, 2017

Revision #6

OBJECTIVE 

To describe the policies and procedures for identifying and managing any significant financial interest held by University of Kentucky (UK) Investigators (as defined below) that could affect research involving human subjects

GENERAL DESCRIPTION

The University of Kentucky (UK) is committed to conducting all research activities in accordance with the highest standards of integrity and ethics. Institutional regulations (AR 7:2 Financial Conflicts of Interest in Research) set forth principles, policies, and procedures to ensure that Investigator financial interests do not compromise the objectivity with which the Investigator designs, conducts, and reports the research. These regulations apply equally to all research whether the study is funded or non-funded.  The Office of Sponsored Projects Administration (OSPA) is the central administrative unit that administers the UK individual conflict of interest policy.

The UK Institutional Review Board (IRB) has established procedures to coordinate with OSPA and to ensure that Investigator financial interests do not affect the rights and welfare of human subjects in research. IRB policy requires that Investigators report all significant financial interests on each study to the IRB for review to assure protection of the rights and welfare of human subjects participating in research. 

Definitions 

Investigator, as defined by AR 7:2 Financial Conflicts of Interest in Research, means the project director or principal investigator/program director, co-investigator, collaborator, senior/key personnel, faculty associate, and any other person, regardless of title or position, who is responsible for the design, conduct, reporting, or proposing of research.

A potential or actual Conflict of Interest (COI) exists when a significant financial interest (as defined below) of an Investigator or an immediate family member of the Investigator could directly and significantly affect the design, conduct, or reporting of research. Immediate family is defined as a spouse or dependent child.

Significant Financial Interest means a financial interest consisting of one or more of the following interests of an Investigator or family member that reasonably appears related to the individual’s institutional responsibilities: 

• With regard to any publicly traded entity, a significant financial interest exists if the value of any remuneration received from the entity in the 12 months preceding the disclosure and the value of any equity interest in the entity as of the date of disclosure, when aggregated, exceeds $5,000;
• With regard to any non-publicly traded entity, a significant financial interest exists if the value of any remuneration received from the entity during the 12 months preceding the disclosure, when aggregated, exceeds $5,000, or when the Investigator or family member holds any equity interest in the entity;
• A significant financial interest includes any intellectual property rights and interests (e.g., patents, copyrights), upon receipt of income related to such rights and interests;
• For an Investigator who applies for or receives funding through a Public Health Service (PHS) grant, cooperative agreement, or contract, a significant financial interest includes any reimbursed or sponsored travel (i.e., paid on behalf of the Investigator rather than being reimbursed) that reasonably appears related to their institutional responsibilities. Excluded is travel that is reimbursed or sponsored by a federal, state, or local government agency, an institution of higher education as defined at 20 U.S.C. 1001(a), an academic teaching hospital, or a medical center or a research institute that is affiliated with an institution of higher education.

The term, for human subjects research, does not include: 

• Salary or other remuneration from UK;
• Income from seminars, lectures, or teaching engagements sponsored by a federal, state, or local government agency;
• Income from service on advisory committees or review panels for a federal, state, or local government agency.

RESPONSIBILITY

Execution of SOP: Investigators (as defined above), IRB, Office of Research Integrity (ORI) staff, ORI Director, Office of Sponsored Projects Administration (OSPA) Conflict of Interest Administrator (COIA), OSPA Director, Research Conflict of Interest Committee (RCOIC) , Institutional Official (IO; i.e. Vice President for Research) 

PROCEDURES

Disclosure Requirements for Externally-funded Research

1. All UK Investigators conducting externally-funded research must complete the online Financial Disclosure Statement (FDS), disclosing any significant financial interest, prior to submission of a proposal for external funding, as defined in AR 7:2 Financial Conflicts of Interest in Research. The Investigator must complete an FDS at least annually or within 30 days of acquiring a new financial interest that reasonably appears related to his or her institutional responsibilities.
2. The FDS contains questions designed to determine whether the Investigator or anyone in his/her immediate family has significant financial interests which could impact the objective pursuit of the research.
3. The PI completes education about disclosures and responsibilities related to financial conflicts of interest each year when completing the annual disclosure, or if an Investigator is found to be noncompliant with the regulation, or if the regulations change researcher requirements.
4. The PI completes the questions regarding disclosure of financial interest in the IRB application. The PI also polls all other Investigators involved with the project and asks them if there is a financial conflict of interest. The PI completes the questions based on financial interest of all investigators involved with the project.  
5. If the PI indicates in the IRB application that there is a significant financial interest and it relates to the project, the ORI notifies the OSPA COIA and requests a Conflict of Interest Management Plan.
6. The Institutional Official (IO) or designee reviews the completed FDS and refers any potential financial conflict of interest to the appropriate University official, i.e., the college dean, center director, or senior administrator.

Disclosure Requirements for Non-funded and Internally-Funded Research

1. If the study is not funded or internally-funded, the Principal Investigator (PI) may not have completed the FDS prior to IRB submission.
2. The PI conducting non-funded or internally-funded research completes the questions regarding disclosure of financial interest in the IRB application. The PI also polls all other Investigators involved with the project and asks them if there is a financial conflict of interest. The PI completes the questions based on financial interest of all investigators involved with the project.
3. If the PI answers the question indicating that he/she or another investigator involved with the project has a significant financial interest requiring disclosure, the PI or the investigator with the conflict completes the online FDS.
4. The ORI notifies the OSPA COIA that the Investigator has disclosed a significant financial interest in the IRB application. The OSPA COIA contacts the Investigator to initiate the process described in AR 7:2.
5. The Investigator must complete an FDS at least annually or within 30 days of acquiring a new financial interest that reasonably appears related to his or her institutional responsibilities.
6. The PI completes education about disclosures and responsibilities related to financial conflicts of interest each year when completing the annual disclosure, or if an Investigator is found to be noncompliant with the regulation, or if the regulation changes researcher requirements.

Review of Disclosures and Management of Conflicts

1. The IO or designee reviews the FDS to assess whether or not the significant financial interest constitutes a financial conflict of interest. The IO or designee may involve the Investigator in the determination of whether a disclosed significant financial interest is related to the Investigator’s research.
2. If the review reveals that the disclosed significant financial interests do not represent a financial conflict of interest, the determination is recorded and no further action is required.
3. If a potential financial conflict of interest exists, the IO or designee notifies the Investigator and the appropriate dean or director.
4. The dean or director reviews the FDS along with the Investigator to determine if the Investigator can eliminate the conflict. If the Investigator can eliminate the conflict, the dean or director provides a written copy of the agreement to the IO or designee and, if the IO or designee approves the plan, no further action is needed.
5. If the Investigator cannot eliminate the conflict, the Investigator proposes a plan to manage or reduce the conflict. If the research involves human subjects, the Investigator must design the plan so that the financial interest does not affect the risk to or welfare of research subjects.   The IO or designee reviews the plan and refers the case to the Research Conflict of Interest Committee (RCOIC) for review.
6. The RCOIC may accept the recommended plan, add to it, or create a new plan. As outlined in AR 7:2, the RCOIC has broad discretion to recommend a variety of conditions to manage, reduce, or eliminate the conflict. The RCOIC sends its recommendations to the IO.
7. The IO may accept the recommendation or modify the proposed plan. The IO makes the final decision to approve a management plan.
8. If the research involves human subjects, the OSPA Director or designee is responsible for forwarding a copy of the final approved management plan to the ORI.

IRB Review of the Approved Management Plan

1. The IRB does not complete its review and approval of the IRB application until it receives the final approved management plan. Upon receipt of the plan from OSPA, ORI staff send the plan to the appropriate IRB.  The IRB reviews the plan using either the convened IRB or expedited procedures based upon whether the study is eligible for expedited review.
2. The IRB determines whether the conditions in the approved plan for managing the financial interest adequately protect the rights and welfare of human subjects or whether additional actions are necessary to minimize the risks to subjects. The IRB determines the kind, amount, and level of detail of information the PI must provide to subjects in the informed consent process regarding source of funding, funding arrangements, financial interests of parties involved in research, and any techniques applied to manage financial COI.
3. The IRB has the final authority to decide whether the interest and management, if any, allows the research to be approved.  The IRB may impose further restrictions on the protocol or disapprove the protocol. The IRB does not have the authority to disapprove the final IO approved management plan but may require additional protections for human subjects before the research can be initiated.

Sponsor-Investigator Clinical Trials 

If the PI is also considered the sponsor who holds an investigational new drug (IND) or an investigational device exemption (IDE), he/she follows Food and Drug Administration (FDA) requirements for reporting financial disclosures as outlined in 21 CFR 54. 

REFERENCES:

Department of Health and Human Services Final Guidance Document, Financial Relationships and Interest in Research Involving Human Subject: Guidance for Human Subjects Protection

Public Health Service 42 CFR 50 Subpart F

National Science Foundation Grants Policy Manual Section 510

Food and Drug Administration 21 CFR 54

AR 7:2 Financial Conflicts of Interest in Research

Approved By: ORI Director, Nonmedical IRB Chair, Medical IRB Chair

Date First Effective: August 15, 2005

Last Revision Date: July 24, 2006

Revision #2

OBJECTIVE 

To describe the procedures for the coordination between the Institutional Review Board (IRB)/Office of Research Integrity (ORI) and the University of Kentucky (UK) Radioactive Drug Research Committee (RDRC) on protocols involving the use of radioactive drugs for research projects designed to obtain basic information regarding metabolism (e.g., kinetics, distribution, and localization) or human physiology, pathophysiology, or biochemistry

GENERAL DESCRIPTION

Both the Radioactive Drug Research Committee and the IRB are committed to ensuring the protection of human subjects involved in research. They have enacted a number of coordination activities in significant areas including: joint committee membership; protocol review; complaints and alleged noncompliance; quality assurance/improvement findings; and joint policy/procedures. Coordination is also facilitated through ORI, administrator of both the RDRC and IRB.

UK’s RDRC is responsible for reviewing and approving all radioactive drug research projects that fall under the purview of the Food and Drug Administration (FDA) regulations as specified in 21 CFR 361. Investigators must submit research projects which meet the criteria for review as outlined in the regulations to the RDRC for approval prior to initiation of the study. IRB approval is also required before initiation of the study.

RDRC review is not required if the use of radioactive drugs is for immediate, diagnostic, or similar purposes, or use of safety and effectiveness of drugs in humans (i.e., to carry out a clinical trial).

Review by the RDRC occurs prior to review by the Medical IRB so that the IRB may rely upon the expertise of the RDRC in reviewing protocols that involve radioactive drugs for research purposes.

RESPONSIBILITY 

Execution of SOP: Radioactive Drug Research Committee (RDRC), IRB Members, ORI Staff, ORI Quality Improvement Program (QIP) Coordinator, ORI Research Compliance Officer (RCO), Principal Investigator (PI)/Study Personnel 

PROCEDURES

Protocol Review Procedures

1. When a PI proposes research which falls under the purview of the RDRC, the PI must submit his/her protocol to the RDRC via the ORI. The IRB application forms also serve as the RDRC application. The PI may submit copies of the RDRC and IRB applications simultaneously. However, the RDRC review must occur prior to IRB review.
    
2. If ORI staff receive a proposal that may require RDRC review in addition to IRB review, ORI staff contact the RDRC Chair for assistance in determining whether RDRC review is required. If the proposal does fall under the purview of the RDRC, the RDRC schedules a meeting and places the protocol on the agenda for RDRC review. IRB review takes place after RDRC review. ORI staff inform the PI of both RDRC and IRB review dates.
3. Upon receipt of an appropriately completed protocol submission that falls under purview of the RDRC, ORI staff assign an IRB number to the IRB protocol and an RDRC number to the RDRC protocol. ORI staff maintain two separate files.
4. ORI staff are responsible for providing the RDRC initial review letter to IRB members with IRB protocol review packets, following standard ORI operating procedures for disseminating information prior to the IRB meeting.
5. The RDRC provides the IRB with data safety expertise, especially with respect to risk assessment through the initial review letter sent to the PI. The RDRC sends a copy to the IRB at initial review. ORI staff maintain a copy in the RDRC file in the ORI.
6. The RDRC membership includes someone who is also a member (voting or ex officio) of the IRB. That member serves as a liaison between the two committees, answering questions as needed, especially if IRB members have questions regarding revisions requested by the RDRC as conveyed in the initial review letter to the PI.
7. ORI staff assigned to the RDRC also manage an IRB and serve as a liaison between both the RDRC and IRB.

Complaints and Alleged Noncompliance

1. If the RDRC receives a complaint from a subject, subject family member, staff, or researcher concerning alleged noncompliance or subject rights and welfare, the RDRC immediately (i.e., within 2 days) notifies the ORI Research Compliance Officer. The RDRC may confer with the ORI RCO to assess whether the complaint/alleged noncompliance falls under the purview of the IRB, RDRC, or both committees.
2. If the RCO receives a complaint or alleged noncompliance involving an RDRC protocol, he/she immediately (i.e., within 2 days) notifies the RDRC. The ORI RCO may confer with the RDRC Chair to assess whether the complaint/alleged noncompliance falls under the purview of the IRB, RDRC, or both committees.
3. If the complaint/alleged noncompliance falls under IRB or RDRC purview, the ORI initiates an inquiry following standard ORI/IRB operating procedures. The IRB is also responsible for determining whether the incident meets requirements for reporting to the federal regulatory agencies. In making the determination, standard operating procedures for reporting are followed. The RDRC is responsible for adhering to Food and Drug Administration requirements. (See the Mandated Reporting to External Agencies SOP)
4. After review of the complaint/alleged noncompliance is complete, the ORI RCO is responsible for providing the RDRC with a copy of the final deliberations. If the IRB determines that the incident is reportable to a federal regulatory agency, the RCO is responsible for sending a copy of the federal report to the RDRC.

Quality Assurance/Improvement Findings

1. If the ORI Quality Improvement Program Coordinator conducts a directed or routine Quality Improvement Review of an RDRC protocol, the QIP Coordinator is responsible for providing the RDRC with a copy of the findings.
2. If the RDRC audits or inspects a protocol, the RDRC is responsible for providing the ORI QIP Coordinator with a copy of the report. The ORI QIP Coordinator is responsible for sending the report to the IRB to determine whether additional IRB action is necessary.

Joint Policy/Procedures

1. The ORI Director, when appropriate, is responsible for initiating efforts to establish joint IRB/RDRC policy, procedures, and submission forms.
2. RDRC staff, ORI staff, the IRB, or UK researchers or administrators may submit suggestions or recommendations for the joint policy/procedure/form initiatives to the ORI Director. 

REFERENCES

21 CFR 361

Approved By: ORI Director, Nonmedical IRB Chair, Medical IRB Chair

Date First Effective: November 10, 2009

Last Revision Date: August 4, 2020

Revision #4

OBJECTIVE

To describe policies and procedures at the University of Kentucky (UK) for institutional review and oversight of research supported by the Department of Defense (DoD) that involves human subjects

GENERAL DESCRIPTION 

Human research supported by the DoD is subject to the Federal Policy for the protection of human subjects in research (i.e., the Common Rule). However, because of the DoD culture, organizational structure, and population, DoD Instruction 3216.02 lays out additional requirements that apply. These requirements are designed to cover risks unique to DoD personnel that differ from civilians in both the conduct of and participation in research (e.g., deployability, personal conduct standards, and duty to report certain personnel actions). The procedures outlined in this SOP ensure UK research supported by the DoD complies with DoD regulations governing human research.

UK’s existing Federalwide Assurance (FWA) of compliance approved by the Office of Human Research Protections (OHRP) meets the DoD requirement that the institution holds a federal assurance. However, the existing FWA may be augmented with a DoD Addendum to inform institutions of additional DoD requirements.

The principal investigator (PI), with assistance from the ORI, submits documentation of Institutional Review Board (IRB) approval, the risk level, and the expiration date of the research to the DoD Component sponsoring or supporting the study. The DoD may also request additional documentation to verify compliance with federal and DoD policies, including minutes related to the research, determinations that an activity is not human research, any exemption determinations, and/or documentation of continuation review approval.

The DoD applies the provisions in 45 CFR 46, Subparts B, C, and D with modifications for the protection of vulnerable classes of subjects. Additionally, DoD has limitations on the involvement of detainees in DoD supported research. Additional safeguards apply when the study involves DoD personnel (both military and civilian) or international citizen populations as subjects. UK does not apply DoD policies when a study is not sponsored or supported by the DoD and when U.S. military DoD personnel incidentally participate as subjects (i.e., they were not the intended target population).

Both classified research and the subset of research involving human beings as Experimental Subjects include limitations on the waiver of informed consent.

Definitions

Research Involving a Human Being as an Experimental Subject is defined as an activity, for research purposes, where there is an intervention or interaction with a living individual for the primary purpose of obtaining data regarding the effect of the intervention or interaction [32 CFR 219.102(e)(1)(i)]. Research involving a human being as an experimental subject is a subset of research involving human subjects. Examples include but are not limited to a physical procedure, a drug, a manipulation of the subject or subject’s environment, the withholding of an intervention that would have been undertaken if not for the research purpose. This definition does not include activities that are not considered research involving human subjects, activities that meet exemption criteria, and research involving the collection or study of existing data, documents, records, or specimens from living individuals.

The term DoD Components refers collectively to the organizational entities within the DoD that are subject to the human subjects protections laid out in Department of Defense Instruction 3216.02. These entities include the Office of the Secretary of Defense, the Military Departments, the Chairman of the Joint Chiefs of Staff, the Combatant Commands, the Office of the Inspector General of the Department of Defense, the Defense Agencies, the DoD Field Activities, and all other organizational entities within the DoD.

Support of a study generally means the provision of at least a portion of the funding, personnel, facilities, and all other resources. Under this definition, studies that may be wholly funded internally or by a non-DoD Component, such as an agency within the Department of Health and Human Services, but focus, for example, on a health concern prevalent in military populations may still fall under DoD purview. Such studies may, for example, require the commitment of DoD personnel as subjects, access to or information about DoD personnel for recruitment, identifiable data or specimens from living individuals, or the use of other DoD data resources.

A DoD Addendum to the institution’s existing FWA is one of several methods that can be used to inform institutions (Institutional Officials and IRB chairs) of DoD research requirements that differ from the OHRP-approved FWA. The DoD Addendum may include designation of the relied-upon IRB(s) and/or an outline of requirements specific to a given DoD Component. The DoD Addendum is effective if the FWA is in force.

Detainee is defined as any person captured, detained, held or otherwise under the control of DoD personnel (military, civilian, or contractor employee). It does not include persons being held primarily for law enforcement purposes, except where the United States is the occupying power.

DoD Personnel includes DoD civilian employees and members of the military services, unit officers, and noncommissioned officers (NCOs). 

RESPONSIBILITY

Execution of SOP: PI/Study Personnel, Vice President for Research (VPR), IRB, IRB Chair, Office of Research Integrity (ORI) Director, ORI Staff, Office of Sponsored Projects Administration (OSPA) Staff

PROCEDURES

Department of Defense Addendum to the Existing FWA

1. After a PI submits an application to a DoD Component, OSPA may receive notice from the DoD that a DoD Addendum to the existing FWA may facilitate the sponsored research agreement for a pending award. OSPA staff notify the PI and the ORI of the DoD request.
2. The ORI Director or designee reviews the requirements of the DoD Addendum and designates select UK IRB(s) to review and oversee DoD-sponsored research.
3. The VPR, who serves as the Institutional Official (IO), the appropriate IRB Chair, and the ORI Director review and sign the DoD Addendum.
4. Once a DoD Addendum is in place, it covers all UK DoD-sponsored research for that Component; however, various DoD Components may use other processes or have additional requirements. The PI, with assistance from ORI, is responsible for identifying additional requirements and conveying those requirements to the IRB, as appropriate. 

Exempt Human Subject Research

1. When human subject research meets the criteria for exemption at 45 CFR 46.104, the PI follows standard procedures in accord with the Exempt Review SOP. The PI sends a copy of the IRB Exemption approval letter with the justification to the DoD for review and concurrence.
2. The UK IRB does not use exempt procedures to review DoD research involving children. 

Expedited Human Subject Research

1. The IRB uses expedited review procedures to review minimal risk, non-exempt research involving human subjects using materials (e.g., data, documents, records, or specimens) that have previously been collected for purposes other than the currently proposed research.
2. The UK IRB does not use expedited procedures to review DoD classified research or DoD research involving prisoners. 

Submission of DoD Supported Research to the IRB

1. DoD requires a scientific review of the protocol. The PI is responsible for obtaining a comprehensive scientific review from his/her Department Chair or designee prior to submission of the application to the IRB. The Department Chair or designee is responsible for conducting the scientific review and signing the IRB application. The IRB considers the scientific merit of the study relative to human subject protection.
2. The PI or designee completes an application for IRB review of the protocol and makes the initial determination identifying the research as supported by a DoD Component (as defined in Department of Defense Instruction 3216.02) and submits it to the ORI.
3. The PI is responsible for checking the appropriate DoD-relevant items on the IRB application. The PI indicates in the application whether DoD personnel or international citizen populations are subjects.
4. Upon receipt of the application, ORI staff screen it for completeness and accuracy consistent with the Initial Review SOP and make a preliminary determination that the research is DoD-supported. ORI staff also make preliminary determinations of the level of risk, the type of review, the type of subjects involved (i.e., DoD personnel or international citizen populations), and the potential need for an ad hoc or cultural consultant.
5. ORI staff advise the PI and the IRB of DoD-specific requirements as outlined in guidance documents and checklists. The PI is responsible for communicating with the DoD to identify DoD Component requirements specified in the grant application guidelines and advising the ORI staff and IRB of the requirements.
6. The PI and study personnel are responsible for completing processes specified in the DoD Addendum or DoD guidelines and submitting documentation, as appropriate, to the ORI as an attachment to the IRB application.

Department of Defense Ethics Education Requirements

1. The PI and research team complete all initial and continuing mandatory education requirements for human subjects protections in accordance with UK policy. (See FAQ’s on Mandatory Training.)
2. The PI, with assistance from ORI staff, is responsible for identifying specific educational or certification requirements of the sponsoring DoD Component and conveying those requirements to the IRB. The PI consults the DoD Component, as appropriate, to identify education requirements.

Research Involving Vulnerable Populations

1. For research involving subjects defined in 45 CFR 46 Subpart B (pregnant women, fetuses and neonates), C (prisoners), or D (children), the IRB reviews according to procedures outlined in the Protection of Vulnerable Subjects SOP and the IRB Summary of Requirements for DoD Supported Human Research.
2. The PI identifies and informs the ORI/IRB of any regulatory subpart modifications or limitations imposed by the DoD (as defined in Department of Defense Instruction 3216.02) or DoD Component relative to the proposed research.
3. Active duty military and reserve members under the age of 18 (e.g., academy students/trainees) are considered adults with legal capacity to participate in DoD supported research. The participation of such members is not subject to Subpart D of 45 CFR 46. However, the IRB may consider and determine such members are not necessary or appropriate to include in the proposed research.
4. The ORI/IRB submits research requiring any action by an official of HHS about any requirements of subparts B, C, or D to the Assistant Secretary of Defense for Research and Engineering (ASD R&E).

Research Involving International Citizen Populations

1. In the IRB application, the PI provides the necessary information, as appropriate, on the subject populations, the cultural context, customs, practices, and the languages understood by the human subjects.
2. The PI is responsible for identifying and following national and/or local laws and regulations when designing and implementing research. The PI includes documentation in the IRB application that indicates the research plan complies with applicable local laws and regulations as confirmed by an official of the local government, local IRB, legal counsel, and/or other expert(s).
3. To ensure the IRB has appropriate knowledge of the local context, the IRB uses an ad hoc or cultural consultant in accord with its standard operating procedures outlined in the Initial Review SOP.

Research Involving U.S. DoD Personnel as Research Participants

1. For research involving clinical investigations, the PI includes women and minority military personnel, unless the DoD Component has waived this requirement.
2. Civilian researchers attempting to access military volunteers should seek collaboration with a military researcher familiar with service-specific requirements (e.g., military site personnel from target military facility/division).
3. In conducting the review, the IRB takes into consideration the unique risks involved in enrolling DoD personnel as research subjects. If the IRB does not have the relevant expertise, ORI obtains consultation from an ad hoc expert with working knowledge of the risks or from the DoD Component.
4. In cases where the research involves U.S. DoD personnel as subjects, the PI submits an IRB application and includes a subject recruitment plan that incorporates additional safeguards to minimize undue influence from individuals within a potential subject’s chain of command. The PI consults the sponsoring DoD Component, as necessary, for assistance.
5. For research involving greater than minimal risk to subjects and involving DoD personnel, the PI includes procedures in the subject recruitment plan to ensure that officers cannot influence the decision of their subordinates to participate in the research.
6. The PI includes, in the IRB application, procedures in the subject recruitment plan to ensure that superiors in the chain of command, officers, and senior or other non-commissioned officers cannot be present at the time of recruitment or consent of their subordinates.
7. The PI provides a separate opportunity or recruitment sessions for supervisors, officers, and senior non-commissioned officers to participate as research subjects.
8. For greater than minimal risk studies involving military service members in which subject recruitment occurs in a group setting, the PI ensures an ombudsperson shall be present during the recruitment and informed consent process to monitor the voluntary nature of participation and ensure that information provided is adequate and accurate. The ombudsperson must not have a conflict of interest with the research or be part of the research team and should be available to address concerns about participation. 

Compensation for Participation in Research 

1. The IRB reviews the proposed subject compensation plan to ensure the PI is aware of DoD policies and limitations depending on whether participation occurs during on-duty or off-duty status and whether funds used to compensate subjects come from a Federal source as follows:
   • DoD personnel (active duty and civilian):
     • On Duty: compensation limited to blood draws
       • May participate in research during work or duty hours with supervisor approval and no compensation other than $50 per blood draw
         • Compensation can be from Federal or non-Federal source
         • Off Duty:
           • No restrictions if the source of compensation is not Federal dollars, but compensation for up to $50 per blood draw can be from a Federal source
   • Non-DoD personnel:
     • No restrictions and compensation can be from a Federal or non-Federal source

Waiver of Informed Consent

1. If the research is minimal risk, the IRB may use criteria in (45 CFR 46.116 or 32 CFR 219.116) to approve a waiver of some elements of informed consent.
2. If the research meets the definition of “research involving human beings as experimental subjects” (as defined in DoD Instruction 3216.02), the PI obtains consent from the subject or the subject’s legally authorized representative (LAR).
3. The IRB makes the determination as to whether the research meets the definition of “research involving human beings as experimental subjects.” The IRB shall not approve a waiver of consent if the research includes subjects who meet the definition of “research involving a human being as an experimental subject,” even if minimal risk, unless the DoD has issued a waiver.
4. If consent will potentially be obtained from the subject’s LAR, the IRB ensures the research is intended to be beneficial to the experimental subjects.

Waiver of Informed Consent for Planned Emergency Research

1. As planned emergency research would meet the definition of “research involving human beings as experimental subjects,” DoD regulations prohibit a waiver of informed consent in planned emergency research unless the PI obtains approval of the study by DoD and in accordance with DoD Instruction 3216.02.
2. The IRB shall not approve an exception from informed consent in emergency medicine research unless the DoD has issued a waiver.

Classified Research

1. Research involving classified information requires prior approval from the Secretary of Defense. The PI works with the DoD Component to determine if information is considered classified; what information will be needed for IRB approval and oversight; and what information subjects will require during the consent process and during research.
2. The PI informs the ORI/IRB of the specified requirements.
3. Waiver of informed consent is prohibited. As part of the consent process, the PI identifies the DoD as supporting the research, states the research is classified, and explains the extent and impact of such classification.
4. The convened IRB reviews the protocol and determines whether potential human subjects need access to classified information to make a valid, informed consent decision.
5. After IRB approval, the DoD Component coordinates the submission for approval from the Secretary of Defense.

Multi-Site or Collaborative Research Requirements

1. A PI developing a proposal for DoD funding or other support that involves collaborating institutions consults the sponsoring DoD Component and ORI staff early in the proposal development process to identify additional requirements for multi-site research.
2. OSPA staff are responsible for negotiating formal agreements with collaborating institutions (see Office of Sponsored Projects Administration/IRB/ORI SOP). OSPA staff, in conjunction with the PI, ensure that the formal research agreement between participating institutions includes a statement of work and specifies the roles and responsibilities of each party.
3. For collaborative research involving UK and DoD researchers, UK may choose to rely upon the DoD IRB for review and oversight following the standard operating procedures outlined in the IRB Reliance SOP. For collaborative research involving UK and non-DoD institutions, UK follows standard operating procedures outlined in the IRB Reliance SOP. UK and the collaborating institution sign an IRB authorization agreement which includes a statement of work specifying the roles and responsibilities of the relied upon IRB.
4. To ensure consistent protection of subjects under DoD requirements, a PI conducting DoD-sponsored multi-site research submits information to the IRB on the federal assurance(s) held by collaborating institutions, including the existence of any DoD Addendum or other direct DoD assurance.
5. The PI provides the UK IRB additional information to ensure ongoing communication among participating IRBs and sites, as indicated in the IRB Reliance SOP.

Prohibition on Involvement of Detainees in Research

1. Under no circumstances shall the IRB approve research involving detainees as defined in DoD Directive 2310.01. (See Definitions above.)

This prohibition may not apply to certain investigational treatment studies conducted for the purpose of diagnosis or treatment of a medical condition in a patient. The PI works with the DoD Component to ensure compliance with limitations of this provision.

Additional DoD Review Required Prior to Initiation of Study

1. After the IRB completes its review and issues approval, the PI submits documentation of IRB approval, the risk level, and the expiration date of the research to the DoD Component sponsoring or supporting the study.
2. The DoD may also request additional documentation of initial and ongoing review to verify compliance with federal and DoD policies, including minutes related to the research. As appropriate, ORI staff provide the PI with any additional information pertinent to IRB review, which may not be under a PI’s purview. The PI sends requested information to the DoD.
3. The PI may not initiate the study until the human research protection officer (HRPO) within the sponsoring DoD Component reviews and approves the IRB approval and other submitted documentation.
4. If the study is for DoD-sponsored survey research or survey research within the DoD that involves DoD personnel, the PI, with assistance from ORI staff, identifies any requirements for an additional level of DoD review of the study. Surveys typically require DoD Survey Review and approval. The PI submits the surveys and all required documentation relevant to the survey research review to the requesting DoD Component.
5. The PI notifies OSPA and ORI staff upon receipt of relevant HRPO authorization and/or DoD Survey Review approval, as appropriate. OSPA staff establish the account only after receiving certification of final human subjects and survey review and approval from the HRPO or relevant DoD designee.

Reporting and Recordkeeping

1. The PI promptly (within 30 days) notifies the HRPO of:
   • IRB approval of significant changes to the research protocol;
   • Results of IRB continuing review;
   • Subject complaints;
   • Unanticipated problems involving risks to subjects or others;
   • Instances of serious or continuing noncompliance;
   • Suspension or termination of IRB approval;
   • Study closure;
   • When a previously enrolled human subject becomes pregnant or the researcher learns a previously enrolled human subject in pregnant, and the protocol was not approved to enroll pregnant women;
   • When a previously enrolled human subject becomes a prisoner and the protocol was not approved to enroll prisoners;
   • Change in reviewing IRB; and
   • Any Federal department or agency or national organization for cause investigation involving a DoD-supported human research protocol.  
2. ORI staff make records accessible for inspection by authorized representatives of the DoD and/or supporting DoD Component as specified in the Inspection by Regulatory Agencies SOP.
3. ORI staff secure and maintain IRB records for DoD-sponsored research in accord with the provisions of the IRB-ORI Recordkeeping SOP. In addition, the PI determines, in conjunction with the ORI, whether the DoD Component requires submission of IRB records to the DoD for archiving. The PI submits the relevant IRB records to the DoD, as appropriate with assistance from ORI staff. 

REFERENCES 

32 CFR 219.102

32 CFR 219.116

45 CFR 46.104

45 CFR 46.116

45 CFR 46 Subparts B, C, D

DoD Directive 2310.01

DoD Instruction 3216.02

Approved By: ORI Director, Nonmedical IRB Chair, Medical IRB Chair

Date First Effective: December 14, 2012

Last Revision Date: N/A

Revision #: N/A

OBJECTIVE

To describe policies and procedures at the University of Kentucky (UK) for institutional review and oversight of human subject research supported by the following agencies: Department of Justice (DOJ) [Bureau of Prisons and National Institute of Justice]; Department of Energy (DOE); Environmental Protection Agency (EPA); United States Department of Education (US DoED)

GENERAL DESCRIPTION 

Several of the federal agencies that adopted the Common Rule (i.e., Federal Policy for the Protection of Human Subjects) have issued policies and regulations that differ from the Food and Drug Administration (FDA) and the Office for Human Research Protections (OHRP) Department of Health and Human Services (DHHS) requirements. IRB policy dictates that agency-specific requirements must be met when reviewing and approving a study that is supported or funded by federal agencies, which have additional policies or regulations governing human research. The Principal Investigator (PI) is responsible for assisting the IRB in identifying applicable agency requirements, for implementing the research consistent with agency requirements, and for complying with the specific agency human subject protection regulations.

This SOP outlines general procedures for IRB review of human subject research supported or regulated by the following agencies: Department of Justice (DOJ) [Bureau of Prisons and National Institute of Justice]; Department of Energy (DOE); Environmental Protection Agency (EPA); United States Department of Education (US DoED).

Specific guidance on each of these agencies’ requirements serves to guide both Principal Investigators (PIs) and the IRB in ensuring compliance. ORI maintains agency-specific guidelines on the ORI website.

RESPONSIBILITY

Execution of SOP: PI/Study Personnel, IRB, IRB Chair, Office of Research Integrity (ORI) Director, ORI Staff

PROCEDURES

Submission and Screening

1. The PI is responsible for reviewing the ORI agency-specific guidance and for communicating with the regulatory/funding agency to identify its specific human research protection requirements.
2. The PI identifies the applicable agency in the IRB application and addresses in an attachment to the application any agency-specific requirements.
3. ORI staff screen the submission consistent with procedures in the IRB Review SOPs and Protection of Vulnerable Subjects SOP, taking into account any applicable agency-specific requirements as outlined in guidance documents and checklists. ORI staff provides IRB reviewers with web links or copies of the applicable guidance or checklists.

IRB Review

1. When reviewing research regulated or supported by the following agencies, the IRB utilizes ORI agency-specific guidance and IRB checklists:
   • Environmental Protection Agency (EPA) – (40 CFR 26, Subpart B, C, and D);
   • US Department of Education (US DoED) - (34 CFR 97 Subpart A and D, 34 CFR 98, 99, and 34 CFR 350, 356);
   • Department of Justice (DOJ) Bureau of Prisons – (28 CFR 46, 28 CFR 512), National Institute of Justice (28 CFR 22);
   • Department of Energy (DOE) – (10 CFR 745.103 and Directive DOE O 443.1B).
2. The IRB considers specific findings as required by the applicable agency. Specific findings are documented following standard operating procedures outlined in the applicable IRB Review SOP.
3. The PI is responsible for submitting to the applicable agency all reports and documentation required by the agency. Prior to initiation of the research, the PI is responsible for obtaining final agency approval if required by the agency.

Reporting and Recordkeeping

1. The PI is responsible for complying with both the IRB and agency-specific recordkeeping and reporting requirements.
2. ORI staff maintain IRB records in accordance with provisions of the applicable federal agency.
3. ORI staff make records accessible for inspection by authorized representatives of applicable federal agency.

REFERENCES

40 CFR 26, Subpart B, C, and D

34 CFR 97 Subpart A and D

34 CFR 98, 99

34 CFR 350, 356 

10 CFR 745.103

DOE O 443.1B

28 CFR 46

28 CFR 22

28 CFR 512

Approved By: ORI Director, Nonmedical IRB Chair, Medical IRB Chair

Date First Effective: April 8, 2013

Last Revision Date: N/A

Revision #: N/A

OBJECTIVE 

To describe the procedures for coordination of human subject protection activity between the Institutional Review Board (IRB)/Office of Research Integrity (ORI) and the Center for Clinical and Translational Science (CCTS) on research studies and their protocols to be conducted at the University of Kentucky (UK) CCTS.

GENERAL DESCRIPTION

Both the CCTS and the IRB are committed to ensuring the protection of human subjects involved in clinical research. This SOP describes the coordination activities that have been enacted between the CCTS and IRB to ensure effective communication of issues during the course of a clinical research trial and include: protocol review; data safety monitoring, quality assurance/improvement findings.

RESPONSIBILITY 

Execution of SOP: CCTS staff, CCTS Director Regulatory Support and Research Ethics, IRB Members, ORI Staff, ORI Quality Improvement Program (QIP) Coordinator, ORI Research Compliance Officer (RCO), Principal Investigator (PI)/Study Personnel, Clinical Services Core Review Committee (CSCRC), Data and Safety Monitoring Board (DSMB).

PROCEDURES

Protocol Review Procedures

1. Investigators submit proposed protocol to the IRB in accordance with IRB SOP for initial review. Investigators are responsible for indicating in the IRB application that the study is supported by CCTS.
2. ORI staff schedule the IRB application for review and the IRB proceeds with review in accordance with IRB SOP for initial review.

Complaints and Alleged Noncompliance

1. Research subjects, family members, or others may report any serious complaint concerning subject rights and welfare or make allegations of investigator noncompliance in a CCTS trial to the ORI Research Compliance Officer as outlined in IRB standard operating procedures.
2. If the CCTS receives a complaint, concern or allegation from a subject, subject family member, staff, or researcher concerning alleged noncompliance or issues with subject rights and welfare, involving a CCTS trial, the CCTS Director, Regulatory Support and Research Ethics or designee, informs the ORI RCO immediately (i.e., within 2 days). The CCTS Director, Regulatory Support and Research Ethics may confer with the ORI RCO to assess whether the complaint/alleged noncompliance falls under the purview of the IRB, CCTS, or both.
3. The ORI RCO handles the complaint, concern, or allegation in accord with standard IRB/ORI operating procedures.
4. At the completion of the IRB review of the complaint, concern, or alleged noncompliance regarding a CCTS trial, the ORI RCO provides the CCTS Director Regulatory Support and Research Ethics with a copy of the final IRB deliberation and any federal reports submitted as a result of the allegation. The CCTS Director, Regulatory Support and Research Ethics disseminates the copy of the final deliberation and/or federal report to the Director of the CCTS.

Quality Assurance/Improvement Findings

1. If the ORI Quality Improvement Program (QIP) Coordinator conducts a directed or routine Quality Improvement Review of a CCTS trial, the QIP Coordinator provides the CCTS Director, Regulatory Support and Research Ethics a copy of the final report within 15 working days of final review. The CCTS Director, Regulatory Support and Research Ethics disseminates a copy to the CCTS and appropriate personnel in accord with standard CCTS operating procedures.
2. If the CCTS QA auditor, during a routine or “for cause” audit, identifies: 1) evidence that research subjects have been placed at significant risk of harm or the welfare of subjects have been jeopardized, and 2) that the finding has not previously been reported to the RCO/IRB, the CCTS Director, Regulatory Support and Research Ethics notifies the RCO within 24 hours of identification of the issue.
3. If the CCTS DSMB suspends or terminates a study, the Chair of the CCTS DSMB notifies the RCO within 2 working days of suspension or termination of a study.
4. The CCTS Director, Regulatory Support and Research Ethics (or designee) forwards an electronic copy of the routine or “for cause” audit report to the RCO within 15 working days of final review by the DSMB. The CCTS DSMB Chair (or designee) forwards an electronic copy of the suspension or termination report to the RCO within 15 working days of final review by the CCTS DSMB. The RCO forwards the report to the IRB and/or the ORI Director in accord with standard ORI operating procedures.

REFERENCES

Unanticipated Problem/Adverse Event SOP

Termination and Suspension of Research by the IRB SOP

Mandated Reporting to External Agencies SOP