Single IRB Reliance

IRB Reliance SOP [C1.0350]

NIH Single IRB Policy

I understand the University of Kentucky’s policies concerning research involving human subjects, and by digitally signing my E-IRB Abbreviated Application (AA) for Reliance, I agree: 

1. To comply with all of the Reviewing/Relying IRB’s and the UK IRB/Human Research Protection Program’s (HRPP) policies, decisions, conditions, and requirements.
2. To accept responsibility for the scientific and ethical conduct of the research study.
3. To obtain prior approval from the Reviewing IRB before amending or altering the research protocol or implementing changes in the approved consent/assent form.
4. To report to the Reviewing/Relying IRB and the UK IRB, in accord with IRB and Institutional policies, any adverse event(s) and/or unanticipated problem(s) involving risks to subjects. Each institution may have unique policies and procedures for reporting.
5. To complete, on request from the Reviewing IRB, the Continuation/Final Review Forms.
6. To notify the UK Office of Sponsored Projects Administration (OSPA) and the UK IRB of the development of any financial conflict of interest not already disclosed.
7. To verify that each individual listed as study personnel at UK for this application has completed the mandatory human research protections education (e.g., CITI).
8. To verify that each individual listed as study personnel at UK for this application possesses the necessary experience and qualifications for conducting the research activities in the role described for this research study.
9. To verify that I have appropriate facilities and resources for conducting the study.

The University of Kentucky and another institution (Relying Site) entered into a Reliance Agreement ceding IRB review to the University of Kentucky IRB. When this arrangement is made, it is important for investigators at both sites to understand their responsibilities. This checklist reviews the responsibilities for the PIs at each site to ensure compliance with all applicable regulations and protocol responsibilities.

Note: There may be additional responsibilities for researchers utilizing SMART IRB, IREx, or conducting cooperative research with Norton Healthcare.

The University of Kentucky (UK) Principal Investigator will: 

1. Collect information from the Relying Site PI for the protocol application, including but not limited to the information listed below, and information regarding any special local considerations to be made by the UK IRB. Provide the information to the UK IRB.
2. Include in the UK IRB protocol application the following:
   • The list of the Relying Site PI and other research personnel involved in the study at the Relying Site;
   • Documentation of human subjects protection training for the Relying Site PI and research personnel at the Relying Site; and
   • Any financial conflict of interest disclosure for the Relying Site PI and each research personnel involved in the Study at the Relying Site, and any associated management plans, if applicable.
3. Promptly provide the Relying Site PI with:
   • Current approved protocol and consent documents;
   • Approved modifications, amendments, or changes to the protocol;
   • Approval of continuing reviews, reviews of unanticipated problems involving risk to subjects or others, and serious or continuing noncompliance; and
   • Any other information required by the UK IRB to be provided to the Relying Site.
4. Notify the Relying Site PI of the standards and guidelines of the UK IRB regarding reporting of any post IRB-approval events, such as those listed below. The UK PI should collect these reports from the Relying Site PI and submit them to the UK IRB for review:
   • Proposed amendments or changes in study activities;
   • Injuries, adverse events, or unanticipated problems involving risks to subjects or others;
   • Serious or continuing noncompliance;
   • Protocol violations; or
   • Findings from Federal inspections or Quality Improvement inspections.
5. Collect required information from the Relying Site PI in order to complete the continuing review submission form. The UK continuing review must cover information from all Relying Sites.
6. Notify the Relying Site PI of any lapses of approval. Forward to the UK IRB any request from the Relying Site PI for continuation of a specific patient on a research protocol during a lapsed period of approval.

The Relying Site PI

The Relying Site PI understands that the Relying Site has ceded IRB review to UK and, therefore, IRB responsibilities for the study will be assumed by the UK IRB. The Relying Site PI has direct responsibilities to the UK IRB, as described below.

The Relying Site PI will: 

1. Notify the UK PI about any special local considerations that must be considered by the UK IRB for the Relying Site (e.g. applicable state laws).
2. Provide to the UK PI:
   • The list of all research personnel involved in the study at the Relying Site;
   • Documentation of human subjects protection training for the Relying Site PI and all research personnel involved in the study at the Relying Site;
   • Assurance(s) of the qualifications of relying site personnel to conduct the research as approved by the UK IRB;
   • Any conflicts of interest/financial interest disclosures for the relying site personnel and any associated management plans, if applicable; and
   • Any other information required by the UK IRB regarding the Relying Site PI and/or research personnel involved in the study.
3. Assure that any additional local requirements for ancillary human research protection reviews (pharmacy, nursing, radiation safety, etc.) are obtained and followed at the Relying Site.
4. Assure that research activities at the Relying Site are not initiated until all UK and Relying Site requirements for the study regarding funding and clinical trial agreements are finalized and the protocol has been reviewed and approved by the UK IRB.
5. Conduct the protocol and obtain informed consent as approved by the UK IRB.
6. As requested on a continuing basis provide the UK PI with any information necessary for the continuing review process. This may include, but is not limited to, information regarding:
   • Subject recruitment;
   • Summary of all enrolled subjects;
   • Minor violations;
   • Screen failures;
   • Summary of adverse events; and
   • Subject complaints or withdrawals.
7. If at any time study approval lapses, cease all human subject research work related to the protocol at the Relying Site. If the Relying Site determines that subjects who are already enrolled in the trial may be harmed if research ceases, notify the UK PI about the individual subject(s) and the justification for remaining on the trial.
8. Consistent with UK policies, report to the UK PI all post-IRB approval events such as:
   • Proposed amendments;
   • Deviations;
   • Subject injuries;
   • Serious or continuing noncompliance;
   • Unanticipated problems involving risks to subjects;
   • Protocol violations; or
   • Findings from Federal inspections or Quality Improvement inspections.
9. Promptly cooperate with any UK or Relying Site investigation regarding serious or continuing noncompliance or an unanticipated problem upon request.
10. Promptly cooperate with any UK or Relying Site quality assurance/quality improvement review or monitoring of the Study protocol upon request.
11. In the event of the need for an audit, allow the UK PI and reviewing UK institutional officials access to research-related records.
12. Maintain records of all research and related activities conducted under the Agreement for at least six years, and longer if required by law, after completion of any study.
13. Promptly respond to all requests for information from the UK PI or UK IRB, including but not limited to the information set forth in the Agreement.

(For assistance with reporting requirements, please refer to the “University of Kentucky Investigator Quick Guide to IRB Reporting Requirements.”) 

Please contact the IRB Reliance Team with any questions. 

For questions about the rights and welfare of subjects in research, contact the staff in the Office of Research Integrity between the business hours of 8 am and 5 pm EST, Mon-Fri at the University of Kentucky at 859-257-9428 or toll-free at 1-866-400-9428. 

This guidance was adapted from the Boston Children’s Hospital/Susan Kornetsky.

Below are step-by-step instructions that the University of Kentucky (UK) has established to help principal investigators (PIs) in completing IRB Authorization Agreements (IAAs) when requesting to rely on an external IRB.

Note: Although we have tried to simplify the process as much as possible, UK’s E-IRB platform is limited in streamlining the process for ceding review, as the system was not originally designed with Single IRB and Reliance in mind.

1. In order for UK to agree to cede review and oversight to (or rely on) an external/reviewing IRB:
   1. The UK PI completes a written request to defer IRB review to the external IRB using the Reliance Request/Registration Form.
   2. The PI submits this form to the IRB Reliance Team for a determination as to whether the PI can cede review to an external IRB.
   3. Once a determination is made for the UK PI to cede IRB review, the PI/study team creates an Abbreviated Application (AA) in UK’s E-IRB system (contact the IRB Reliance Team for instructions on submitting AA). Note: Before you can submit the abbreviated application in E-IRB, the PI and Department Chairperson's signatures are required.*
2. Reliance managers, UK IRB, and the VPR (and in some instances, ORI director and UK legal counsel) will review the protocol after the AA is submitted in E-IRB. Local ancillary reviews that may occur include:
   1. HIPAA
   2. Conflict of Interest
   3. Institutional Biosafety Committee
   4. Investigational Drug Service, and
   5. Other state and local requirements (only if applicable).
3. If the PI/study team did not submit a consent form during initial E-IRB submission, the research may still be ceded to an external IRB; however, upon completion of the Consent/HIPAA combined form, the PI will need to:
   1. Submit a modification request to the E-IRB AA so that UK Reliance Team can review to ensure the documents meet all local/institution-specific requirements; and
   2. Ensure that the risk level documented in the AA matches the risk level determination of the reviewing IRB.
4. The IAA between UK and the external IRB will be submitted to the external IRB administrator for signature and returned to the UK Reliance Team, who will ensure the IAA is appropriately processed. Once the IAA and all supporting documentation are complete, these documents will be uploaded to E-IRB (and e-mailed to the PI/Regulatory Director, if that need is indicated).
5. Via e-mail, an E-IRB notification of the “Reliance Determination Letter” is issued, and includes confirmation that UK has agreed to cede review and oversight of the protocol. Additional instructions and document links will be included in this letter. This determination letter and the IAA can be downloaded from E-IRB and forwarded to any parties who need this documentation.
6. Once you receive the reviewing IRB’s approval letter for activation of UK’s site to participate in the proposed research, please modify the AA by attaching the letter to your currently approved AA in E-IRB and sending it on for “review and approval” by UK’s Reliance Team.

Purpose: When the Overall Principal Investigator and/or Lead Study Team is located at UK, this checklist can be used to provide them with guidance regarding the additional responsibilities accrued in assuming that role. 

As the Overall Principal Investigator for a study for which research activities involving human subjects will be overseen by the UK IRB for all or most sites, you should be aware of your additional responsibilities in assuming that role. Once you have agreed to collaborate with investigators at another institution(s) and intend to use a single IRB (sIRB) for oversight of this study, you should contact the IRB Reliance Staff at UK to: 

• Discuss whether UK's IRB can act as the sIRB for all or some institutions participating in this study, or whether another external IRB would be appropriate.
• Identify who will act in the role of the Lead Study Team (e.g., your own study team, a coordinating center, or both). The Lead Study Team assumes additional responsibilities when sIRB review will be used.
• Provide relying sites with details about the study, including the study-wide protocol and template consent document(s), which will help facilitate the discussion with the UK IRB/HRPP.
• Identify all sites that will be engaged in human subjects research and thus need IRB coverage. 

If UK agrees to serve as sIRB for the study, you will need to ensure the Lead Study Team does the following: 

• Completes a reliance request with the UK IRB using the process required by the UK HRPP.
• Works in collaboration with the UK IRB to determine and document specific roles and responsibilities for communicating and coordinating key information to Relying Institutions; this includes developing a plan for communicating with collaborators across the lifetime of the study (i.e., regular conference calls, site initiation procedures, and training materials).
• Promptly responds to questions or requests for information from study teams and IRB/HRPP personnel at institutions who are relying on the UK IRB.
• Participates in conference calls regarding a study as requested.
• Provides the Site Investigators with the IRB policies of the UK IRB. This includes, but is not limited to, policies for reporting unanticipated problems, noncompliance, and subject complaints.
• Provides participating Relying Site Study Teams with the IRB-approved versions of all study documents (e.g., consent and authorization forms, protocol, recruitment materials).
• Prepares and submits IRB applications on behalf of all sites (UK and relying), including initial reviews, local amendments, personnel updates, local reportable events, and study-wide information for continuing review. 

As part of preparing the IRB application, the Lead Study Team (or designee) must: 

• Have a mechanism in place to obtain and collate information from Relying Site Study Teams and/or Relying Site Points of Contacts (POCs), depending on who is designated to provide that information at the Relying Institution, regarding local variations in study conduct, such as recruitment materials and process, consent process and language, and subject identification processes.
• Assist Relying Site Study Teams and/or POCs at the Relying Institution(s), depending on who is designated to provide that information, in ensuring consent documents follow the UK IRB’s template form and include applicable local institutional required language from each Relying Institution.
• Notifies Site Investigators of all UK IRB determinations and communications, including those for initial review, continuing review, amendments, reportable events, suspensions, and terminations.
• When agreed upon, in coordination with the UK IRB, promptly reports to the Site Investigator (or designee on the Relying Site Study Team) any unanticipated problems involving risks to subjects or others, research-related subject injuries, or subject complaints that are related to or may affect subjects participating in the research (i.e., the specific study or studies ceded to the UK IRB) at the Relying Institution.
• If a Relying Site Study Team does not provide the Lead Study Team (or designee) with the site-specific required progress report information before the continuing review application is submitted to the UK IRB, then report the absence of this information as part of the continuing review and notify affected Relying Site Study Team of the approval expiration for their site and any applicable corrective action plans.
• Providing access, upon request, to study records for audit by the Relying Institution, the UK IRB, and other regulatory or monitoring entities.
• Follow all requirements of the Relying Institution with regard to ceded review, such as ensuring administrative requirements for documenting ceded review have been met before study activation occurs at a Relying Institution. 

Purpose: When a study is under the oversight of an IRB external to UK, this checklist can be used to provide UK's local study team with guidance regarding the investigator's responsibilities. 

As Principal Investigator (PI) at UK (Relying Institution) for a study that may be overseen by an external IRB, you should be aware of your responsibilities. Once you have agreed to collaborate with an investigator at another institution and plan to use an external IRB for oversight of this study, you should contact the UK IRB Reliance Staff to: 

• Discuss whether ceding IRB oversight to an external IRB is appropriate.
• Provide UK IRB Reliance Staff with details about the study (including your study team’s role), the proposed reviewing IRB, and the lead PI's name and institution by completing a Reliance Request Form.
• Obtain a copy of the study-wide protocol and template consent documents(s), which will help facilitate the discussion with the UK Reliance Staff and the IRB.

If the UK IRB agrees to cede review to an external IRB, you will be asked to: 

• Provide the UK IRB with:
  • Protocol-specific information by submitting an Abbreviated Application (AA) for Reliance in E-IRB.
  • Any management plans for potential conflicts of interest (COI) relevant to the study that will be ceded to the external IRB, including any new or altered management plans put in place throughout the lifespan of the study.
• Register the study at UK according to local processes (such as creating an abbreviated application in the E-IRB, or submitting pertinent study documents via e-mail). See "Steps to Creating an Abbreviated sIRB..."
• Promptly respond to questions or requests for information from the Lead Study Team/PI/Reviewing IRB.
• Participate, as required, in conference calls regarding the study as requested by the Lead Study Team/PI, Reviewing IRB, or UK IRB/HRPP.
• Become familiar with the reportable event policy of the Reviewing IRB to ensure that you appropriately report protocol deviations/violations, noncompliance, significant subject complaints, subject injuries, unanticipated problems, or other events required by the Reviewing IRB to be reported and within the timeframes required.
• Ensure completion of all local reviews and sign-offs that, in addition to IRB approval, are in place before a study is activated, such as coverage analysis, department approvals, data use agreements, material transfer agreements, and ancillary committee reviews (e.g., radiology, nursing, and pharmacy).
• Work with the Lead Study Team and the Reliance staff from UK's IRB/HRPP to incorporate locally required language into the consent template to be used by the local study team, such as institutionally required compensation for injury language, local study team contact information, and additional costs that subjects may incur that differ from those identified in the template consent form.
• For externally funded studies, provide OSPA with documentation that IRB oversight for a study has been ceded to and approved by an external IRB.
• Notify UK ORI Reliance Staff of any staff changes so they can confirm training is current and help ensure any relevant COI management plans are communicated to the Reviewing IRB.
• Notify the lead PI of:
  • Any reportable events that occur locally, according to regulations and the Reviewing IRB’s policy.
  • Any changes (including those related to funding and personnel) in accordance with the Reviewing IRB’s policies and procedures for timing and content of such submissions.
  • Any management plans, including any updates to these plans, as relevant to the study.
  • Any applicable information for continuing review progress reports in accordance with the Reviewing IRB’s policies and procedures for timing and content of such submissions.
• Follow all determinations of the Reviewing IRB.
• Only implement changes of protocol, including local variations, after the Reviewing IRB has approved them, except in cases where a change is required to avoid an apparent immediate hazard to participants.
• Provide, upon request, access to study records for audit by the UK HRPP/IRB, the Reviewing IRB’s institution, and other regulatory or monitoring entities.

Communication Plan Form Template (SMART IRB)

(Word/Accessible forms can be found on the SMART IRB Resources website)

Contact the IRB Reliance Team to request the form needed for your research:

Individual Investigator Agreement [D83.0000]

Individual Investigator Agreement for minors [D183.0100]

Institutional Review Board (IRB)/Independent Ethics Committee (IEC) Authorization Agreement [D12.0000]

Off-Site Research: Letter of Support, Local Context, & Additional Requirements

OHRP's "Guidance on Engagement of Institutions in Human Subjects Research"

Sample Protocol for Reliance

Adding Non-UK Study Personnel [D163.0000]

A single IRB is when one institution engaged in human subject research agrees to be the reviewing IRB for another institution for a cooperative study.  Single IRB is mandated when institutions located within the US are engaged in cooperative research conducted or supported by a Common Rule department or agency.  Generally, UK should be the IRB for any studies in which a UK investigator is the Principal Investigator.

List of the common rule departments or agencies

Yes, for non-exempt non-federally funded studies, please submit an IRB Reliance Request/Registration Form to the IRB Reliance Team. Some of the items that are considered for non-federally funded studies include:

• Sponsor’s requirement for single IRB,
• Accreditation status,
• The number of sites and the research activities conducted for the project. 

Not all multi-site studies require a single IRB. If interested in using a Single IRB, please submit an IRB Reliance Request/Registration Form to the IRB Reliance Team.

The following are less likely to qualify for require a single IRB:

• Exempt research,
• Research that is being conducted under research training awards,
• If a single IRB is unable to meet the needs of a specific population, especially if there are federal, tribal, or state laws surrounding research involving the population,
• If the research sites are only international.

• You want an external IRB to be the reviewing IRB,
• You want UK to serve as the reviewing IRB for a multi-site study,
• You are transferring your project to UK or want to work with your previous institution on a project,
• You or your colleagues are transferring to another institution and want to continue to work on the project,
• You have reliance questions about a project.

There are three criteria that must be met for single IRB to be mandated by the federal regulations (45 CFR 46.114) for a protocol: federal funding from one of twenty different federal departments/agencies, a non-Exempt protocol (i.e., an Expedited or Full-Board Review protocol), and engagement of human subject research by more than one institution.

A good rule of thumb is when the individual is consenting participants, intervening/interacting with participants, and/or viewing identifiable participant information (See UK’s guidance on Study Personnel for further information). If the engaged individual is an ‘agent’ of an institution, the institution is considered engaged. Agent is defined as the faculty, staff, or volunteers of a specific institution and UK Legal is often consulted to determine the status of a specific individual.

A PI requests the use of a single IRB by completing a Reliance Request Form or contacting the IRB Reliance Team.

Yes, but different institutions have further criteria to determine if an IAA/Reliance Agreement is suitable for protocols that do not have a single IRB mandate. At UK, the type of review (i.e., Exempt, Expedited, Full-Board Review), the risk level of the protocol (minimal risk vs. greater than minimal risk), and the level of engagement by UK individuals is considered when determining if a protocol that does not meet the requirements for single IRB should have an exception be made.

Yes, UK can still collaborate on projects with other institutions even when a Reliance Agreement will not be signed. When other institutions are engaged in human subject research, but a Reliance Agreement is not signed, the non-UK individuals should seek IRB approval from their own IRB (known as local IRB approval).

UK’s ORI requires three documents when single IRB has been deemed mandatory or suitable: A completed IAA (signed by both institutions), a Communications Plan, and (if applicable) a Local Context Form.

Local Context is the Local Laws, Regulations, or Policies that may affect a multi-site study. At UK, it is provided by the Reliance Team when UK is ceding IRB Review and the Laws or Policies may impact the conduct of the study. The Reliance Team obtains the Local Context from other sites when UK is the Reviewing IRB. Examples include mandatory disease reporting, use of Short Forms, Age of Majority, and many others.

A Communications Plan is developed by the Reviewing IRB & Relying Site jointly to ensure everyone understands their communications responsibilities. UK’s Reliance Team completes the form and provides it to the HRPP staff at the other site for consideration and approval.

When research activities will occur at a site that is not owned or operated by UK and the other site is not engaged in human subject research.

Off-Site Research: Letter of Support, Local Context, & Additional Requirements  

An IIA is required when an individual is engaged in human subject research but does not have access to an IRB.

• IRB Authorization Agreement (IAA) – A legal document between two institutions that are engaged in human subject research wherein one institution (the Relying IRB) chooses to rely on the ethical and regulatory determinations made by the other institution’s IRB (Reviewing IRB). UK agrees to cover the activities of another institution.
• Individual Investigator Agreement (IIA) – A legal document between an individual who, generally, does not have access to an IRB, but who is engaged in human subject research alongside an institution with an IRB.
• Reviewing IRB – an IRB that reviews the ethical and regulatory aspects of a multi-site study for all participating sites.
• Relying IRB – an IRB that relies on another IRB for review of the ethical and regulatory aspects of a multi-site study.
• Reliance Agreement – synonymous with IAA.
• Single IRB – When an IRB reviews a protocol as a multi-site study on behalf of the other sites. An IAA/Reliance Agreement is used to document this arrangement. See the Code of Federal Regulations on Cooperative Research (45 CFR 46.114).