1.29 ClinicalTrials.gov Reporting

1.0 Purpose

The purpose of this policy and procedure is to describe the requirements and procedures for submission of clinical trials to ClinicalTrials.gov.


2.0 Policy

  • 2.1. It is the Policy of the Organization that all applicable drug, biologic, and device clinical trials will be registered and updated as required on ClinicalTrials.gov in compliance with HHS regulations at 42 CFR 11 (Final Rule for Clinical Trials Registration and Results Information Submission).
  • 2.2. It is the Policy of the Organization that all NIH funded clinical trials will be registered and updated as required on ClinicalTrials.gov in compliance with the NIH Policy on the Dissemination of NIH-Funded Clinical Trial Information.
  • 2.3. The Organization requires that investigators adhere to the statutory provisions of 42 CFR 11 (rather than the abbreviated provisions described in this policy when there are discrepancies), as well as clarifications and definitions found at www.clinicaltrials.gov.

3.0 Definitions

  • 3.1. Clinical Trial:
    • 3.1.1. Per 42 CFR 11.10(a) a clinical trial is a “clinical investigation (or clinical study) in which human subject(s) are prospectively assigned, according to a protocol, to one or more interventions (or no intervention) to evaluate the effect(s) of the intervention(s) on biomedical or health-related outcomes”
    • 3.1.2. Per NIH Policy NOT-OD-16-149 a clinical trial is a "research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.”
      • 3.1.2.1. For the purposes of this Policy, the regulatory definition at 42 CFR 11.10(a) and the definition in NIH policy are treated as synonymous.
      • 3.1.2.2. The NIH definition of "clinical trial" is, however, broader than the term "applicable clinical trial" as defined in 42 CFR 11 (below).
  • 3.2. Applicable Clinical Trials (ACTs)
    • 3.2.1. ACT generally include interventional studies (with one or more arms) of FDA-regulated drugs, biological products, or devices that meet one of the following conditions:
      • 3.2.1.1. The trial has one or more sites in the United States.
      • 3.2.1.2. The trial is conducted under an FDA investigational new drug application or investigational device exemption.
      • 3.2.1.3. The trial involves a drug, biologic, or device that is manufactured in the United States or its territories and is exported for research.
    • 3.2.2. Applicable Clinical Trials include the following:
      • 3.2.2.1. Trials of drugs and biologics: Controlled clinical investigations, other than phase 1 clinical investigations, of drugs or biological products subject to Food and Drug Administration (FDA) regulation
      • 3.2.2.2. Trials of devices: 1) Controlled trials with health outcomes of devices subject to FDA regulation, other than small feasibility studies, and 2) pediatric postmarket surveillance required by FDA
  • 3.3. *Responsible Party:
    • 3.3.1. The sponsor of the trial will be considered the responsible party unless and until a principal investigator has been designated the responsible party in accordance with 42 CFR 11.4(c)(2).
    • 3.3.2. If an ACT or clinical trial is being conducted under an IND or IDE, then the holder of the IND or IDE is the responsible party regardless of how the clinical trial is being funded.
    • 3.3.3. For clinical trials not conducted under an IND or IDE:
      • 3.3.3.1. If the clinical trial is being conducted under a grant or sponsored research agreement, the funding recipient is generally considered to be responsible party.
      • 3.3.3.2. If the clinical trial is being conducted under a contract, the funder is generally considered to be the responsible party
      • 3.3.3.3. If there is no funding agreement supporting the clinical trial, the person or entity who initiated the clinical trial by preparing and/or planning the clinical trial is considered to be the responsible party.
    • 3.3.4. The sponsor of the clinical trial may designate the principal investigator to be the responsible party, if the PI satisfies the requirements of 42 CFR 11.4(c)(2).
    • 3.3.5. For NIH funded clinical trials, the awardee is usually the responsible party. If he/she is not the responsible party, then he/she is still obligated to coordinate with the responsible party to ensure that all regulatory requirements are met.

4.0 Investigator Responsibilities

Per 42 CFR 11 and the NIH Policy the Responsible Party is responsible to register the ACT and/or the NIH-funded clinical trial, and fulfil reporting responsibilities as described in those regulations and NIH Policy. The following describes the responsibilities of the PI if he/she is the Responsible Party. If he/she is not the Responsible Party, then the UNMC HRPP Policies do not apply

  • 4.1. The PI must register the ACT and/or NIH-funded clinical trial and submit results as required by 42 CFR 11 and the NIH Policy.
  • 4.2. Registration and Reporting Requirements for Applicable Clinical Trials
    • 4.2.1. Registration is required for trials that meet the definition of an "applicable clinical trial" (ACT)

    • 4.2.2. The following types of studies are generally excluded from the registration and results submission requirements of 42 CFR 11. This is not a complete list.

      • 4.2.2.1. Phase 1 drug trials, including studies in which investigational drugs are used as research tools to explore biological phenomena or disease processes
      • 4.2.2.2. Small clinical trials to determine the feasibility of a device or a clinical trial to test prototype devices, where the primary outcome measure relates to feasibility and not to health outcomes
      • 4.2.2.3. Trials that do not include drugs, biologics, or devices (such as behavioral interventions)
      • 4.2.2.4. Non-interventional (observational) clinical research (such as cohort or case-control studies)
    • 4.2.3. The IRB will not issue full approval of any protocol where the Responsible Person is part of the Organization until the ACT is registered.

      Note: Per the requirements of 42 CFR 11 the Responsible Party for an ACT must submit the required clinical trial information no later than 21 days after enrollment of the first participant; however, the Organization requires registration prior to full IRB approval.

    • 4.2.4. If the ACT is amended in such a manner that changes are communicated to human subjects in the clinical trial, the PI must update any relevant clinical trial registration information data elements not later than 30 days after the protocol amendment is approved by the IRB (42 CFR 11.64(a)(1)(ii)(O)).

      • 4.2.4.1. The IRB will not issue full approval of protocol amendment until the ClinicalTrials.gov PRS database has been updated, unless such change is necessary to reduce immediate risk to subjects.
      • 4.2.4.2. The PI must review and update ClinicalTrials.gov PRS database at the time of each annual Continuing Review.
        • 4.2.4.2.1. The IRB will not issue full re-approval of the protocol until the ClinicalTrials.gov PRS database has been updated
      • 4.2.4.3. For ACTs with a Primary Completion Date on or after January 18, 2017, the PI is required to submit the results information specified in 42 CFR 11.48
        • 4.2.4.3.1. The results must be submitted no later than 1 year after the study's Primary Completion Date, unless the ACT satisfies the conditions for delayed submission of results information under 42 CFR 11.44(b).
        • 4.2.4.3.2. If the ACT includes a device not previously approved or cleared by FDA for any use, full posting of the trial information on ClinicalTrials.gov will be delayed until after the device has been approved or cleared.
  • 4.3. Registration and Reporting Requirements for NIH funded clinical trials
    • 4.3.1. All NIH-funded awardees and investigators conducting clinical trials will register and report the results of their trial in Clinicaltrials.gov regardless of study phase, type of intervention, or whether they are subject to 42 CFR 11.

      Note: For example, NIH-funded phase 1 clinical trials of an FDA-regulated product are covered by this policy as are clinical trials studying interventions not regulated by the FDA, such as behavioral interventions.

    • 4.3.2. The IRB will not issue full approval of any protocol where the Responsible Person is part of the Organization until the NIH-funded clinical trial is registered.

    • 4.3.3. If the NIH-funded clinical trial is amended, the PI must update any relevant clinical trial registration information data elements as required by the NIH Policy.

      • 4.3.3.1. The IRB will not issue full approval of protocol amendment until the ClinicalTrials.gov PRS database has been updated, unless such change is necessary to reduce immediate risk to subjects.
    • 4.3.4. The PI must review and update ClinicalTrials.gov PRS database at the time of each annual Continuing Review.

      • 4.3.4.1. The IRB will not issue full re-approval of the protocol until the ClinicalTrials.gov PRS database has been updated
    • 4.3.5. The PI is required to submit the results information specified in the NIH Policy

  • 4.4. The PI is responsible for assuring that the IRB Application correctly reflects that a clinical trial is registered with clinicaltrials.gov and that the NCT number is accurate, and for uploading a copy of the ClinicalTrials.gov front sheet into RSS
  • 4.5. If the clinical trial is not registered with ClinicalTrials.gov the PI must provide justification why the trial is not registered.

5.0 ORA Procedures

  • 5.1. At the time of the initial IRB review and approval of all clinical trials, the IRB administrator responsible for the trial will confirm that the application states the trial is registered (and that the front sheet from ClinicalTrials.gov is uploaded into RSS), or presents adequate justification for absence of registration.
  • 5.2. Full approval of an ACT or of an NIH-funded clinical trial will not be granted until the trial is registered.
  • 5.3. If the responsible party is not part of the Organization (that is, if it is an external investigator or sponsor) no further action regarding Clinicaltrial.gov reporting will be taken. If the responsible party is part of the Organization, the following additional procedures will be followed:
    • 5.3.1. At time of each annual Continuing Review, the administrator will be responsible for assuring that the PI has updated the ClinicalTrials.gov PRS database. This assurance can take the form of an assertion from the PI that such an update has been made.
    • 5.3.2. At the time of any protocol change for which changes are communicated to human subjects in the clinical trial, the administrator is responsible for assuring that the PI has updated the ClinicalTrials.gov PRS database. This assurance can take the form of an assertion from the PI that such an update has been made.
    • 5.3.3. When an ACT or an NIH-funded clinical trial is completed (that is, when the investigator files a completion report, or when the trial is closed by the ORA for non-response to continuing review, the ORA will notify the responsible party that submission deadline for results information is no later than 1 year after the study's Primary Completion Date, unless the ACT satisfies the conditions for delayed submission of results information under 42 CFR 11.44(b). The ORA will repeat the notification as per standard operating procedures.
    • 5.3.4. The ORA will periodically (but not less often than monthly) review the Clinicaltrials.gov PRS database to determine any trials that non-compliant.
    • 5.3.5. ORA will contact Responsible Party of non-compliant trials as per standard operating procedures. Investigators who remain non-compliant 30 days after the first notice will be subject to disciplinary actions as per HRPP policy 8.4 (Review of Noncompliance Involving the PI and Study Personnel), and per the Office of the Vice-Chancellor for Research.

ADMINISTRATIVE APPROVAL: BRUCE G. GORDON, MD IRB EXECUTIVE CHAIR & ASSISTANT VICE CHANCELLOR FOR REGULATORY AFFAIRS CHRISTOPHER KRATOCHVIL, MD INSTITUTIONAL OFFICIAL

POLICY AMENDED:

 INITIAL MAY 31, 2018