400-22: Clinical Trials Registration & Reporting

This policy establishes UCSF standards for registering and reporting results information for Clinical Trials on ClinicalTrials.gov, ensuring compliance with federal regulations and policy (e.g., the Food and Drug Administration Modernization Act of 1997 (FDAMA), Section 801 of the Food and Drug Administration Amendments Act (FDAAA 801) and Final Rule for Clinical Trials Registration and Results Information Submission (42 CFR Part 11), the National Institutes of Health (NIH), the Center for Medicare and Medicaid Services (CMS), and the International Committee of Medical Journal Editors (ICMJE) criteria). Timely and accurate submissions to ClinicalTrials.gov ensure ethical conduct, enhance transparency in research, and facilitate the publication of trial results, thereby reducing publication bias and optimizing the use of research funds.

This policy applies to UCSF Principal Investigators (PIs) conducting Investigator-Initiated Clinical Trials that are initiated and overseen by UCSF faculty, regardless of funding source. For industry or externally sponsored trials, the industry or external sponsor will generally be responsible for trial registration and results reporting, absent an agreement between the sponsor and the UCSF PI delegating these responsibilities to the UCSF PI.

1. Clinical Trial Registration

   Please note that registration of clinical trials is a separate process from results reporting. ClinicalTrials.gov registration means posting key information about a trial’s design and objectives, while results reporting (covered in Section C) means posting a summary of the trial’s findings.

   1. Applicability:
      1. UCSF Principal Investigators (PIs) who are conducting an Investigator-Initiated “Clinical Trial” as defined by this Policy are required to register the trial in the ClinicalTrials.gov PRS. UCSF’s adopted definition of a “Clinical Trial,” which is a modified version of ICMJE’s definition, is broad enough to encompass the FDA, NIH, CMS, ICMJE, and FDAMA definitions of a Clinical Trial and, therefore, compliant with their registration requirements.
         1. Exemption: Unfunded research with no intent to publish in an ICMJE journal, that is not otherwise subject to any clinical trial registration requirements (e.g., FDA, NIH, CMS), is exempt from the above provision. Please contact the UCSF ClinicalTrials.gov Regulatory Support Team at [email protected] for guidance.
         2. Please note that in the context of this policy, unfunded means research not directly charged or recovered from externally funded research grants or contracts.
      2. Funding entities may also independently require ClinicalTrials.gov registration of certain research, even if the research does not meet this Policy’s “Clinical Trial” definition. PIs must review the terms and conditions of funding agreements/awards to determine if registration is required by their funding entity (e.g., PCORI, DoD).
      3. Expanded Access: Expanded access protocols for drugs, biologics, or devices should only be registered on ClinicalTrials.gov by UCSF PIs when they are both the sponsor and the manufacturer (the investigational product is manufactured on campus) (42 CFR 11.28(c)).
   2. Record Owner: The PI listed in the Institutional Review Board (IRB) application should hold the Record Owner role for the Clinical Trial, not a sub-investigator or clinical research coordinator. If the PI listed in the IRB application differs from the PI listed in the grant or funding agreement, contact the UCSF ClinicalTrials.gov Regulatory Support Team at [email protected].
   3. Access: The ClinicalTrials.gov PRS can be accessed at register.clinicaltrials.gov. UCSF maintains an institutional PRS account as “UCaliforniaSF,” which must be used for all Clinical Trials initiated by UCSF PIs. New user accounts can be requested from the UCSF ClinicalTrials.gov Regulatory Support Team at [email protected].
   4. Timing: All Investigator-Initiated Trials must be registered in the ClinicalTrials.gov PRS before enrolling the first participant to comply with ICMJE publication requirements.
   5. Funding: Any federal grant/funding number(s) must be listed as a “Secondary ID” in the study record.
   6. Unique Protocol ID: At UCSF, enter the Organization's Unique Protocol ID as follows:
      • For grant-funded projects, use the Sponsor-issued grant or award number
      • For industry-funded projects, use the Sponsor’s protocol ID number
      • For cancer center projects, the Helen Diller Family Comprehensive Cancer Center (HDFCCC) ID is assigned by the Protocol Review and Monitoring Committee (PRMC) as the unique protocol ID number
      • For all others, if no other unique identifier assigned by funder is available, use Institutional Review Board (IRB) study number (YY-XXXXX)
   7. Data Sharing Statements: As a condition of publication of Clinical Trial results, ICMJE journals require the inclusion of an Individual Patient Data (IPD) Sharing Statement in the trial’s registration (required prior to enrollment). ClinicalTrials.gov records satisfy this requirement through a registration module called Individual Participant Data (IPD) Sharing Statement. Please note that the module lets investigators identify ‘Yes’, ‘No’, or ‘Undecided’, but only a ‘Yes’ or ‘No’ will satisfy ICMJE’s requirement.
2. Maintaining Records
   1. All studies registered on ClinicialTrials.gov must be maintained according to ClinicalTrials.gov requirements, which are as follows:
      1. Records must be reviewed and verified at least once every 12 months, even if there are no changes to the study. It is recommended that the Record Verification Date be updated at least every 6 months.

      2. The following data elements must be updated within 30 days of becoming aware of the following changes:

         • Study start date
         • Intervention name(s)
         • Availability of Expanded Access
         • Expanded Access status
         • Expanded Access type
         • Overall recruitment status
         • Individual site status
         • IRB review status
         • Primary Completion Date
         • Study Completion Date
         • Responsible Party
           • Official Title
           • Contact Information

         Note: The regulatory requirement is that investigators submit the necessary updates within 30 days of becoming aware of the changes; it does not require that ClinicalTrials.gov approve the changes within that timeframe.

      3. The following data elements must be updated within 15 days of becoming aware of the change:
         • Device product not approved or cleared by the FDA (change in approval or clearance status)
3. Clinical Trial Results Reporting
   1. Applicability: The following Investigator-Initiated Trials require reporting of Summary Results through ClinicalTrials.gov PRS, as specified by law or funding source:
      1. FDA: “Applicable Clinical Trials” (ACTs) (initiated after 09/27/2007).
      2. NIH: Clinical Trials directly funded in whole, or in part by the NIH (proposed after 01/18/2017)
      3. Funding entity: Clinical Trials funded by an entity that requires results reporting (e.g, Patient-Centered Outcomes Research Institute (PCORI)).
         
         Note: ICMJE and CMS do not currently have results reporting requirements, therefore results reporting is voluntary for Clinical Trials that only fall under their purview.
   2. Timing: Results must be submitted within the following timeframes, according to ClinicalTrials.gov requirements:
      1. Primary outcome measure(s) must be submitted no later than 12 months after the Primary Completion Date (the date when the final participant was examined or received an intervention for the purposes of final collection of data for the primary outcome, whether the Clinical Trial concluded according to the pre-specified protocol or was terminated).
      2. Secondary outcome measure(s) must be submitted no later than 12 months after the Study Completion Date (the date when the final participant was examined or received an intervention for purposes of final collection of data for the primary and secondary outcome measures and adverse events (for example, last participant’s last visit)).
      3. Good Cause Extensions may be requested from the ClinicalTrials.gov PRS team prior to the due date for reporting results in certain circumstances. Contact the UCSF ClinicalTrials.gov Regulatory Support Team at [email protected] for assistance with the extension.
         1. Please see the following document for official guidance on Good Cause Extensions.
4. Other Document Submissions
   1. Protocol and Statistical Analysis Plan (SAP): For Clinical Trials required to report results that have a Primary Completion Date on or after 01/18/2017, the protocol and SAP must be uploaded at the time of results submission. Only the most recent IRB-approved study documents should be uploaded.
   2. Informed Consent Form: the Revised Common Rule section §46.116 requires posting of Clinical Trial consent forms. For federally funded studies that were initially approved by the Institutional Review Board (IRB) on or after January 21, 2019, the PI must ensure that an IRB-approved informed consent form is uploaded to ClinicalTrials.gov (or an alternative database at Regulations.gov) after the Clinical Trial is closed to recruitment, and no later than 60 days after the last study visit by any subject, as required by the protocol.
       
5. Transfer of Principal Investigator (PI) Responsibilities
   1. During the course of a Clinical Trial, the PI may relocate to another institution or otherwise be unavailable to fulfill his/her role and responsibilities as PI.
   2. Prior to departure, the PI must notify the UCSF ClinicalTrials.gov Regulatory Support Team at [email protected] to transfer or complete the study record. If applicable, a plan for providing results will be required.
   3. If a Clinical Trial remains at UCSF and there are continuing registry reporting obligations, the PI named on the IRB application would assume any remaining reporting obligations.
   4. If a PI who is designated as a Responsible Party for a study transfers from another institution to UCSF, the PI must notify the UCSF ClinicalTrials.gov Regulatory Support Team at [email protected] to determine whether any action needs to be taken.

1. Noncompliance with NIH Policy (for NIH-funded Clinical Trials)
   1. Expectations for registration and results submission are included in the award terms and conditions.
   2. Noncompliance with the terms and conditions of the NIH award can be grounds for enforcement actions, including:
      1. Inability to submit Research Performance Progress Reports (RPPRs);
      2. Suspension or termination of grant or contract funding;
      3. Consideration of previous noncompliance when deciding future funding;
   3. NIH initiated a process in 2022 for notifying grant recipients of possible noncompliance.
2. Noncompliance with FDA Regulations (for Applicable Clinical Trials)
   1. Compliance with FDA regulations is a legal requirement. Failure to comply with the results reporting requirements relating to Applicable Clinical Trials (ACTs) may result in FDA regulatory action for the “Responsible Party”, including:
      1. the issuance of a Notice of Noncompliance;
      2. civil money penalties;
      3. injunction;
      4. criminal prosecution;
      5. public identification of the Clinical Trial record as non-compliant.
   2. FDA Notification Process: If the FDA identifies that a Responsible Party has failed to submit any required Clinical Trial information to ClinicalTrials.gov and/or submitted information that is false or misleading, the FDA sends a “Preliminary Notice of Noncompliance (Pre-Notice) Letter” outlining the potential violation. The Responsible Party must address potential violations within 30 days. If noncompliance persists after 30 days, the FDA conducts further review and assessment. If noncompliance is established, the FDA issues a Notice of Noncompliance, allowing 30 days for remedy.
   3. The PI’s Department/Division will be responsible for any civil monetary penalties incurred due to noncompliance.
3. Noncompliance with CMS Policy (for CMS Qualifying Clinical Trials)
   • Denial of Medicare claims.
4. Noncompliance with ICMJE Criteria (for all Clinical Trials)
   • Failure to register prior to enrollment of the first participant can result in the inability to publish in an ICMJE journal.
5. Escalation of Noncompliance
   1. Official Notice Letters: Any employee who receives a letter about a potentially non-compliant Clinical Trial from the FDA and/or NIH must immediately notify the UCSF ClinicalTrials.gov Regulatory Support Team at [email protected] and their UCSF Office of Sponsored Research (OSR) contacts. Oncology researchers must also notify the Helen Diller Family Comprehensive Cancer Center (HDFCCC) Data Integrity and Research Compliance Team.
      • UCSF staff will work with the PI to address any deficiencies with the study record and submit a timely response to the oversight agency.
      • If the PI fails to respond to requests to correct their non-compliant study record, UCSF staff will escalate to the PI’s department leadership.
   2. Inspection Observations: Any employee who receives notice of noncompliance with ClinicalTrials.gov requirements during an FDA inspection must immediately contact the UCSF Office of Ethics and Compliance staff at [email protected] and [email protected].
   3. Regulatory Support Compliance Notices: The ClinicalTrials.gov Regulatory Support Team will regularly send PIs and study teams notices regarding record registration and results due dates.
      • If the PI fails to respond to Regulatory Support Team notices, the Regulatory Support Team will escalate to the PI’s department leadership or the Chief Administrative Officer of the PI’s school.
   4. Repeated Violations: Repeated violations of ClinicalTrials.gov regulatory requirements may result in possible sanctions and/or disciplinary actions in accordance with University policy and relevant bargaining agreements.

1. Principal Investigator (PI)
   1. Determine whether the research is an Investigator-Initiated Trial subject to registration and reporting requirements;
   2. Register the Clinical Trial in the ClinicalTrials.gov PRS before the first participant is enrolled.
   3. Serve as the Record Owner in the PRS for the Clinical Trial study record;
   4. Correctly designate the Responsible Party and the Sponsor in the PRS (refer to Definitions);
   5. Certify compliance with ClinicalTrials.gov requirements when applicable:
      1. If subject to the NIH policy, certify compliance in NIH grant applications, contract proposals, and progress reports.
      2. For FDA Applicable Clinical Trials (ACTs), submit a Form FDA 3674 with certain applications to the FDA.
   6. Update the record within 30 days of a change to the data elements listed in this policy;
   7. Update or verify the ClinicalTrials.gov record at least once every 12 months;
   8. Submit results to ClinicalTrials.gov no later than 1 year after the Primary Completion Date if results submission is required;
   9. Resolve all Clinical Trial study records in the PRS before separating from UCSF by ensuring that studies are closed or transferred to another investigator or institution in the PRS;
   10. Escalate notices of noncompliance to the institutional contacts in this policy.
        

2. The Office of Ethics and Compliance

   The Office of Ethics and Compliance is responsible for the general oversight of ClinicalTrials.gov compliance and enforcement of this policy.

3. The Institutional Review Board
   • The Institutional Review Board (IRB) has the final authority to decide whether an Investigator-Initiated Clinical Trial meets this Policy’s definition of a Clinical Trial. The IRB is not responsible for advising on any other Clinical Trial definitions, any other requirements to register, or any requirement to submit results.
     • This authority also applies to research where UCSF relies on an external IRB.
     • When the research is multi-site, meaning that the same protocol is conducted at multiple sites, only the primary awardee will have responsibility for registration and results reporting.
   • The IRB’s decision on ClinicalTrials.gov registration applicability is final. PIs will not have an opportunity to appeal the decision.

• UCSF Campus Code of Conduct
• U.S. Public Law 110-85, H.R. 3850, Food and Drug Administration Amendments Act of 2007 http://www.gpo.gov/fdsys/pkg/PLAW-110publ85/pdf/PLAW-110publ85.pdf
• UCSF Clinical Research Resource HUB
• FDAMA Section 113 – Guidance for Industry “Information Program on Clinical Trials for Serious or Life-Threatening Diseases and Conditions”.
• International Committee of Medical Journal Editors (ICMJE) “Frequently Asked Questions about Clinical Trials Registration”
• U.S. National Library of Medicine/National Institutes of Health “FAQ: ClinicalTrials.gov Questions”
• National Institutes of Health Office of Extramural Research “FDAAA – Further Resources for NIH Grantees”
• “Elaboration of Definitions of Responsible Part and Applicable Clinical Trials” http://prsinfo.clinicaltrials.gov/ElaborationsOnDefinitions.pdf