UK Policy Registration, Dissemination and Results Reporting of Clinical Trial Data in ClinicalTrials.gov Responsible Office: Vice President for Research

It is the policy of the University that any clinical trials subject to the policies below will be registered in accordance with the most stringent policy that applies. Not all clinical trials are required to be registered.

A. Food and Drug Administration (FDA): The Final Rule for Clinical Trial Registration and Results Information Submission (42 CFR Part 11) clarifies and expands the requirements of the Food and Drug Administration Amendments Act of 2007, Section 801 (FDAAA 801) registration and reporting requirements. FDAAA 801 defines Applicable Clinical Trials (ACT)¹ that must be registered in ClinicalTrials.gov as those meeting the following criteria.

1. Interventional clinical trial;
2. Meets at least one of the following criteria;
   1. Trials with one or more sites in the US;
   2. Trials conducted under an FDA Investigational New Drug Application (IND) or Investigational Device Exemption (IDE) application; and/or
   3. Trials involving a drug, device or biologic that is manufactured in the US or its territories and exported for research;
3. Evaluates at least one drug, device or biologic regulated by the FDA; and
4. Is other than a Phase I trial or device feasibility study.

B. National Institutes of Health (NIH): The NIH defines a clinical trial as a research study in which one or more human participants are prospectively assigned to one or more interventions (which may include a placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes. The NIH Policy on the Dissemination of NIH-Funded Clinical Trial Information (NOT-OD-16-149) went into effect on January 18, 2017. The NIH requires clinical trial registration and results submission to ClinicalTrials.gov for all studies funded wholly or in part by the NIH regardless of study phase, type of intervention, or whether it is subject to FDAAA Section 801. NIH grantees must certify compliance with FDAAA 801 in competing applications and noncompeting progress reports for any NIH grant that supports a clinical trial.

C. International Committee of Medical Journal Editors (ICMJE) and Department of Veterans Affairs Office of Research and Development (VA ORD): Clinical trials are defined by the ICMJE and VA ORD as any research project that prospectively assigns people or a group of people to an intervention, with or without concurrent comparison or control groups, to study the relationship between a health-related intervention and a health outcome. The ICMJE requires prospective registration in ClinicalTrials.gov as a precondition of consideration for publication of research results generated by a clinical trial in any of their participating journals. The VA-ORD requires registration as a pre condition of funding.

D. Centers for Medicare and Medicaid Services (CMS): The National Coverage Determination (NCD) for Routine Costs in Clinical Trials, Section 310.1 requires that claims for routine costs of qualifying clinical trials, as well as reasonable and necessary items and services used to diagnose and treat complications arising from participation in all clinical trials covered by Medicare, will require health care providers and suppliers to report a ClinicalTrials.gov Identifier (NCT Number). Thus, any trial requiring CMS coverage must be registered in ClinicalTrials.gov.

E. Patient-Centered Outcomes Research Institute (PCORI): PCORI policy requires that all clinical trials or observational comparative effectiveness studies of human participants be registered prior to enrollment of the first participant. Results must be submitted to ClinicalTrials.gov before the draft final research report is submitted to PCORI.

F. Other sponsors whose policies require registration or results reporting.

*Overview Requirements

^{1. All pediatric postmarket surveillance studies of device products (on or after January 18, 2017) meet the definition of an ACT.}

Public registration and dissemination of clinical trial data are required by the US Department of Health and Human Services (DHHS), for-profit industry sponsors, and many private foundations. Additionally, the World Health Organization (WHO) and World Medical Association (WMA, Declaration of Helsinki) have issued recommendations for public clinical trial registration and results dissemination. ClinicalTrials.gov, the clinical trial registry and results data bank operated by the National Library of Medicine (NLM) of the National Institutes of Health (NIH), is the primary designated platform to meet these requirements in the United States.

The University has an ethical obligation to ensure that ongoing clinical trials are accessible to the public and that data resulting from those trials contribute to generalizable knowledge and the advancement of public health. This commitment to transparency increases patient enrollment in clinical trials, enhances adherence to research protocols, mitigates information bias, reduces duplication of effort, and supports public access to and trust in the clinical trial process.

This policy outlines the University’s expectations regarding clinical trial registration and results dissemination in ClinicalTrials.gov.

This policy applies to all University faculty, staff, employees, students, or other individuals conducting clinical trials as defined by the Food and Drug Administration and National Institutes of Health. Clinical trials that receive support from the Veterans Health Administration, Patient Centered Outcomes Research Institute or other sponsors that require registration or results reporting are subject to these guidelines. Adherence to ClinicalTrials.gov requirements is also required for publication of clinical trial data in any journal that adheres to International Committee of Medical Journal Editor (ICMJE) standards.

A. ClinicalTrials.gov: the public registry developed by the National Library of Medicine (NLM) as a mandate from the Food and Drug Administration Modernization Act (FDAMA). ClinicalTrials.gov supports registration and results reporting for clinical trials.

B. Clinical Trials Compliance Administrator: the individual designated by the Director of the Clinical Research Support Office to oversee organizational compliance with public registration and dissemination of clinical trial data regulations and requirements at the University.

C. Enrollment: placing a consenting human research subject into a clinical trial.

D. Primary Completion Date: the date the final subject was examined or received an intervention for the purposes of final collection of data for the primary outcome measure. This is used by ClinicalTrials.gov to determine the timing of results reporting deadlines.

E. ClinicalTrials.gov Protocol Registration System (PRS): the web-based data entry system used by PIs in ClinicalTrials.gov to register a clinical study or submit results information for a registered study. The University has an assigned PRS organizational account and individual PIs must have a PRS user account to register study information on ClinicalTrials.gov.

F. Protocol Registration and Results System (PRS) Administrator: the individual responsible for the process by which clinical trial information is released to ClinicalTrials.gov on behalf of the University.

G. Responsible Party: The sponsor of the clinical trial, as defined in 21 CFR 50.3; or the PI of such clinical trial if so designated by a sponsor, grantee, contractor, or awardee, so long as the PI is responsible for conducting the trial, has access to and control over the data from the clinical trial, has the right to publish the results of the trial, and has the ability to meet all of the requirements for the submission of clinical trial information. The University delegates the responsibilities of the Responsible Party to the PI.

A. The Vice President for Research: The Vice President for Research (VPR) is the institutional official with responsibility for compliance with funding agency regulations related to ClinicalTrials.gov.

B. Office of Sponsored Projects Administration: The Office of Sponsored Projects Administration (OSPA), a unit in the Office of the VPR, has the responsibility for ensuring compliance with the terms and conditions of sponsored grants and contracts, including sponsor regulations governing public dissemination and reporting of clinical trial results data through ClinicalTrials.gov.

C. Clinical Research Support Office: The Clinical Research Support Office (CRSO) designates the Clinical Trials Compliance Administrator to act as the University’s primary Protocol Registration and Results System (PRS) Administrator with oversight of the responsibilities outlined in section V.F.

D. Clinical Trials Compliance Administrator: The Clinical Trials Compliance Administrator is the primary PRS Administrator responsible for organizational oversight and the following functions associated with ClinicalTrials.gov:

Responsible Party (PI) Assistance

1. Provide individual or group training, educational resources, and assistance with user accounts.
2. Assist the PI and study teams with registration, updates and results reporting in ClinicalTrials.gov.
3. Proactively work with the PI and study teams to meet reporting deadlines, identify updates, and solve problems.
4. Act as a liaison between PRS Reviewers (ClinicalTrials.gov staff) and the PI, study teams, and sponsors to facilitate communication and maintain compliance.
5. Notify the Responsible Party of non-compliances.
6. Facilitate record transfer, completion, or termination for Investigators who are leaving or have left the University.
7. Transfer non-compliant records to a new Responsible Party to maintain compliance with federal regulations.

University Compliance Assistance

1. Provide oversight of the organizational ClinicalTrials.gov account and provide compliance reports to the OVPR.
2. Notify the applicable Department Chair or Division Chief of records that are persistently delinquent. Continued non-compliance will be escalated to the Associate Dean for Research of the applicable college.
3. Notify the Office of Research Integrity, applicable Department Chair or Division Chief, and Associate Dean for Research of any FDAAA 801 or NIH NOT-OD-16 149 violation

E. Principal Investigator/Responsible Party: The Principal Investigator (PI) is responsible for conducting the clinical trial, has access to and control over the data from the clinical trial, has the right to publish the results of the clinical trial, and has the responsibility to meet all of the FDA requirements for submission of clinical trial information.

Under FDAAA guidelines, the Responsible Party assumes responsibility for all aspects of the ClinicalTrials.gov record, including registration, updates, and results reporting. The University delegates the responsibilities of the Responsible Party to the PI for government-funded clinical trials, clinical trials that receive support from the Veterans Health Administration, Patient Centered Outcomes Research Institute or other sponsors that require registration or results reporting, investigator-initiated clinical trials (IIT), clinical trials conducted under an Investigational New Drug (IND) or Investigational Device Exemption (IDE), and clinical trials with no external funding.

The PI is responsible for the following functions in ClinicalTrials.gov:

1. Registration: Trials must be registered in ClinicalTrials.gov prior to enrolling the first participant.
2. Updates: Records in ClinicalTrials.gov must be updated per ClinicalTrials.gov timelines including, but not limited to, annual record verification, study start and completion dates, and changes in protocol methodology or study status.
3. Summary Results Reporting: For Applicable Clinical Trials and studies funded in whole or part by the NIH, National Cancer Institute (NCI), VA ORD, PCORI or other sponsor with such requirements, summary results information must be reported in ClinicalTrials.gov no later than one year after the primary completion date.
4. Posting the Informed Consent Document: For any clinical trial supported by a Federal department or agency as of January 21, 2019, one copy of the Institutional Review Board (IRB)-approved informed consent document (ICF) must be posted on ClinicalTrials.gov after recruitment closes and no later than 60 days after the last study visit.
5. Data Sharing: A Data Sharing Plan must be included during registration on ClinicalTrials.gov to comply with NIH and ICMJE requirements.

F. Department Chair or College Associate Dean for Research: If the PI leaves the University with open records in ClinicalTrials.gov, the Department Chair or Associate Dean for Research or their designee will assign a new PI or assume that role until the record is compliant and/or closed. The disposition of ClinicalTrials.gov records is a data field on the “MOU for Departing Investigators” so faculty, chairs and ADRs should all have addressed this prior to the investigator departure.

A. Failure to comply with federal regulations and sponsor or journal requirements for registration or results reporting will follow those regulations and requirements which may result in civil monetary penalties, revocation of grant or contract funding, refusal to publish resulting manuscripts by journals, and identification on public watchdog lists.

B. The applicable college or department will be notified when the record becomes noncompliant and will be held accountable for all financial penalties (after a 30 day grace period) that the University may receive as the result of noncompliance by a PI in their college or department.

C. The following acts and failures violate the provisions of this regulation:

1. Failure to update the ClinicalTrials.gov record within the timeframes required by sponsor requirements, or federal regulations.
2. Providing incomplete, erroneous or misleading information on a ClinicalTrials.gov record.
3. Failure to respond timely to notices from the Clinical Trials Compliance Administrator, sponsors, or federal agencies or in ClinicalTrials.gov PRS.
4. Failure to correct ClinicalTrials.gov records or take other appropriate action when requested to do so by the Clinical Trials Compliance Administrator, sponsors, or federal agencies or when notified in ClinicalTrials.gov.

D. Sanctions that may be imposed by the University or outside entities* (see overview of requirements, section II) for violation(s) of this regulation include but are not limited to any one or more of the following. The Institution’s PRS Administrator will work closely with the PI and study teams to proactively address problems before non-compliances are escalated. If the PI is non-responsive after three attempts, the PI will be given an additional 5 business days to respond to the PRS administrator before escalating to the applicable party.

1. The PRS Administrator may notify the applicable department chair, division chief, research dean, VPR, or other institutional official of PIs with records with delinquent requirements that fall outside of the timeframes required by sponsors or federal regulations*;
2. Notification to the IRB of record noting regulatory noncompliance in registration and/or results reporting outside of the timeframes required by sponsors or federal regulations*;
3. Funds may be withheld for any sponsored activity until a PI’s ClinicalTrials.gov record has been submitted and approved by Clinical Trials.gov PRS*;
4. Suspension of active research or other sponsored projects and prohibition from applying for extramural support, including renewal of any active sponsored agreement*;
5. Notification to regulatory bodies*;
6. Notification to actual or potential research funding sponsors and agencies;
7. Special monitoring and/or conditions of future work;
8. Mandated actions to address the consequences of the misconduct; and/or
9. Restitution of funds that were used to perform the research in which the conduct occurred.

E. To the extent required to impose any sanction, any proceedings required by Governing Regulations, other Administrative Regulations, the Human Resources Policy and Procedures, or the Student Code of Conduct, will be conducted as appropriate.

Food and Drug Administration Amendments Act of 2007, Section 801 (FDAAA 801)

45 CFR Subpart A –US Department of Health and Human Services Policy for the Protection of Human Subjects

42 CFR Part 11 –Clinical Trials Registration and Results Information Submission

National Institutes of Health Policy on the Dissemination of NIH-Funded Clinical Trial Information, NOT-OD-16-149

Centers for Medicare and Medicaid Services Clinical Trial Policies and Medicare Learning Network #SE1344