What is a clinical trial? | Policy Statement | Dissemination Plan for NIH Clinical Trials | Consent form posting | Responsibilities for Registration & Reporting | Overview of Requirements

Clinical Trials

What is a clinical trial?

That National Institutes of Health (NIH), U.S. Food and Drug Administration (FDA), and the International Committee of Medical Journal Editors (ICMJE) definitions of a “clinical trial” vary. It’s important to know which definition(s) you’re operating under as you determine compliance requirements, particularly as they relate to reporting in ClinicalTrials.gov.  

A “clinical trial” is defined as follows:

  • FDA: a prospective clinical study of health outcomes that compares an intervention of an FDA regulated drug or device against a control in human subjects.

  • NIH: 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. (Click here for more information about NIH clinical trials.)

  • ICMJE: any research study that prospectively assigns human participants or groups of humans to one or more health-related interventions to evaluate the effects on health outcomes. (More information about the ICMJE requirements can be found here.)

The bottom line?

The FDA, NIH and the ICMJE each has its own requirements for Clinicaltrials.gov registration, and while some of the requirements overlap, there are important differences. If you want to preserve your ability to publish in an ICMJE journal, take note that it applies the broadest definition of a clinical trial and requires prospective registration as a precondition of consideration for publication of research results generated by a clinical trial.

Brown University’s Policy Statement

Brown is committed to complying with all applicable laws, regulations and policies governing registration and submission of results information in ClinicalTrials.gov. This includes, but is not limited to:

Brown University investigators are required to follow the Responsibilities for Registration and Reporting outlined below and act in accordance with the Overview of Requirements.

Dissemination Plan for NIH Clinical Trials

NIH proposals for clinical trials now require additional information, including a dissemination plan  that describes how the investigator will fulfill ClinicalTrials.gov registration and reporting requirements for NIH-funded clinical trials. The plan must contain sufficient information to assure the following:

  • the applicant will ensure that clinical trial(s) under the award are registered and results information is submitted to ClinicalTrials.gov as outlined in the policy and according to the specific timelines stated in the policy;
  • informed consent documents for the clinical trial(s) will include a specific statement relating to posting of clinical trial information at ClinicalTrials.gov; and
  • the recipient institution has an internal policy in place to ensure that clinical trials registration and results reporting occur in compliance with policy requirements.

The Brown HRPP offers the below text as suggested language for inclusion in a dissemination plan:

The Principal Investigator (PI) will serve as the responsible party for the ClinicalTrials.gov record(s) associated with the study or studies funded by this award. [He/she] will ensure the trial is registered no later than 21 days after IRB approval, in accordance with Brown University Policy. Once a record is established, the PI will confirm the accuracy of record content, resolve problems, and verify and update the record. The PI will also report results and adverse events in ClinicalTrials.gov within 12 months of the primary and study completion dates, respectively. The Brown University Human Research Protection Program (HRPP) monitors and enforces investigator compliance with required registration and reporting in ClinicalTrials.gov. The Brown HRPP assists investigators serving as the responsible party in the registration, record maintenance, and reporting processes, including providing deadline reminders and guidance for resolving errors. As part of the review process, the Brown University Institutional Review Board will confirm that the consent form(s) follow NIH policy by requiring a specific statement relating to the posting of the study or studies on ClinicalTrials.gov.

Consent form posting

The Final Rule (45 CFR 46.116(h)) includes consent form posting requirements for clinical trials conducted or supported by any Federal department or agency (not just NIH). For such studies, one IRB-approved version of a consent form that has been used to enroll participants must be posted on a public federal website designated for posting such consent forms. The informed consent form must be posted after recruitment closes and no later than 60 days after the last study visit. 

Which websites can be used? 

There are two approved sites for posting consent forms:

  1. ClinicalTrials.gov
    This is likely the easiest choice if the researcher has already registered the clinical trial at ClinicalTrials.gov. Specific instructions on how to register with ClinicalTrials.gov and upload documents (including consent forms) can be found on the ClinicalTrials.gov website. If the study is already registered, see Appendix A.1 of the ClinicalTrials.gov Results Data Elements Definitions document for information on posting consent forms.
     
  2. Regulations.gov
    Upload the consent form to docket folder HHS-OPHS-2018-0021 by following the instructions located on the Clinical Trial Informed Consent Form Posting webpage of the federal Office of Human Research Protections.

Additional guidance:

  • If  the study has more than one consent form (for example, there may be different consent forms for each study group), only one consent form is required to be posted  The PI may decide which one to post.
  • If the study has assent and/or parental permission forms, the study is only required to post one of these two forms. If the study has a consent form, assent form, and parental permission form, the PI may choose which one to post.
  • If the consent form is revised during the study, only one version of the consent form should be posted. It is not required to replace an already-posted consent form with the revised version, although this can be done voluntarily.
  • If the study has a separate HIPAA authorization form, do not post the HIPAA authorization form.
  • See this federal website at the Office of Human Research Protections for additional information and any updates.

Responsibilities for Registration & Reporting

Principal Investigator

For investigator-initiated clinical trials, it is the responsibility of the Principal Investigator to:

  1. Register the clinical trial before the first subject is enrolled;
  2. Designate the Responsible Party in the Protocol Registration and Results System (PRS) as either Brown University as the sponsor, or the PI him/herself if there is an FDA IND/IDE;
  3. Update ClinicalTrials.gov records at least once every 12 months (Recruitment Status and Primary Completion Date). It is recommended that the Record Verification Date be updated at least every 6 months for studies that have not yet been completed, even if there were no changes to the record;
  4. Close-out any studies before leaving Brown University, including ensuring that studies are properly closed or transferred to another investigator; and
  5. Submit summary results to ClinicalTrials.gov no later than one year after the Primary Completion Date (applicable clinical trials only).

Brown's Human Research Protection Program

  1. The Brown University Human Research Protection Program is responsible for general oversight and support of ClinicalTrials.gov registration and enforcement of Brown’s statement of compliance. Please note that Brown's HRPP reserves the right to take appropriate action against a party that has not obtained IRB approval from the Brown University IRB for a clinical trial, but registers a clinical trial identifying Brown University as the sponsor.

Overview of Requirements

 

FDA Final Rule

NIH Policy

ICMJE

2018 Common Rule (currently active)

SCOPE

Applies to all ​FDA regulated clinical trials (drug, biological, device products, and pediatric post-market device surveillance studies under FD&C Act).

Does not include Phase 1 studies or small device feasibility studies.

Applies to all studies that meet the NIH’s expanded definition of a clinical trial. Applies to all “clinical trials” funded wholly or in part by NIH.

Includes Phase 1 studies.

Applies to all studies that meet the ICMJE definition of a clinical trial.

Applies to all clinical trials conducted or supported by a federal department or agency that has adopted the 2018 Common Rule. The 2018 Common Rule uses the same definition of "clinical trial" as the NIH's expanded definition.

REGISTRATION

Must occur within 21 days of enrollment of 1st participant

Must occur within 21 days of enrollment of 1st participant.

Must be registered prior to informed consent of the first subject.

N/A

RESULTS REPORTING

Submission of results information must occur no later than 1 year after the completion date. This is referred to as the “primary completion date” of the clinical trial, which is defined as the date of final data collection for the primary outcome measure.

Submission of results information must occur no later than 1 year after the completion date. This is referred to as the “primary completion date” of the clinical trial, which is defined as the date of final data collection for the primary outcome measure.

ICMJE does not require results reporting for registered trials.

One IRB-approved consent form used to enroll participants must be posted on a publicly available federal website after the study is closed to recruitment, but no later than 60 days after the last study visit by any participant. The two federal websites that currently satisfy this requirement are ClinicalTrials.gov and a docket folder on Regulations.gov (Docket ID: HHS-OPHS-2018-0021)

POTENTIAL CONSEQUENCES OF NON-COMPLIANCE

If federally funded, grant funding can be withheld.

Civil monetary penalties of up to $12,000 per day.

Record in ClinicalTrials.gov will be marked as non-compliant.

May lead to suspension or termination of grant or contract.

Can affect future funding decisions.

Record in ClinicalTrials.gov will be marked as non-compliant.

ICMJE journals will not accept for publication any study that meets its definition of a clinical trial that is not registered.

May lead to suspension or termination of grant or contract.

EFFECTIVE DATE

January 18, 2017

Compliance date was 90 days from the effective date.

Effective for all competing application and contract proposals submitted on or after January 18, 2017.

ICMJE journals will accept retrospective registration of trials that began before July 1, 2005.

Clinical trials beginning on or after July 1, 2005 will only be considered for publication if registration occurred before the first patient was enrolled.

Effective for all Brown University clinical trials. Brown University transitioned all ongoing non-exempt research to the current, 2018 Common Rule as of January 21, 2019.

QUESTIONS?

Please contact Sheila Vandal