Clinical Trials Registration

On September 27, 2007 Congress enacted U.S. Public Law 110-85 (also known as H.R. 3580, or Food and Drug Administration Amendments Act of 2007). This act mandates the expansion of ClinicalTrials.gov, expands the required submission elements and establishes penalties for not listing a trial.

The FDA requirements are in addition to the 2005 policy established by the International Committee of Medical Journal Editors (ICMJE) requiring the entry of clinical trials in a public registry prior to subject enrollment as a condition of consideration for publication of the trial results.

All applicable clinical trials must be registered as required by FDA regulation.
 

Who is responsible for registering a study?

What are my responsibilities once I register a trial?

How do I register a trial on ClinicalTrials.gov?

What is the URL for the ClinicalTrials.gov registration site?

Which studies are required by the FDA regulation to be registered?

What are the International Committee of Medical requirements for registering clinical trials?

What are the NIH Requirements for ClinicalTrials.gov Registration Information in Applications and Progress Reports?

How do I report results and AEs for terminated studies?

How do the FDA registration requirements affect NIH funded studies?

Do the FDA regulations have any special requirements for IND, IDE or BLA studies?

Where can I find more information from the NIH about the requirement to register clinical trials?

What is the “Informed Consent Regulation”?

Who can I contact at Duke for more information about the requirements to register clinical trials?

Are there other sources of information about clinical trial registration?


Who is responsible for registering a study?

 The Responsible Party for a clinical trial must register the trial and submit results information. The Responsible Party is defined as:

  • The sponsor of the clinical trial; or
  • The principal investigator (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 FDAAA's requirements for the submission of clinical trial information.

For complete statutory definitions and more information on the meaning of "responsible party" and "sponsor," see Elaboration of Definitions of Responsible Party and Applicable Clinical Trial (PDF). See also the Responsible Party data element on ClinicalTrials.gov.

  • For sponsor-initiated trials the sponsor is responsible for registration
  • For trials sponsored or funded wholly or in part by the NIH the grantee is responsible for registration
  • For trials associated with Investigational New Drug (IND) or Investigational Device Exemption (IDE) applications with the FDA the IND/IDE holder is responsible for registration
  • The sponsor, grantee, contractor, or awardee may designate the principal investigator of a clinical trial as the responsible party, provided that the principal investigator 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 submitting information under the law.

If unclear who is responsible registering an applicable clinical trial, investigators should consult with the sponsor, funding agency, and/or other study investigators to define who the responsible party will be.

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What are my responsibilities once I register a trial?

You are responsible for ensuring that the information is complete, accurate and updated. This includes reviewing the listing and making necessary changes every 6 months or more frequently if significant changes occur. You are also responsible for noting when enrollment ceases.

How do I register a trial on ClinicalTrials.gov?

Please see the Duke Office of Clinical Research (DOCR) website for instructions regarding how to establish a user account and register a trial using the ClinicalTrials.gov Protocol Registration System (PRS).

What is the URL for the ClinicalTrials.gov registration site?

The URL for the registration site is: https://register.clinicaltrials.gov/

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Which studies are required by the FDA regulation to be registered?

Registration is required for trials according to Section 113 of FDAMA which requires information be submitted to clinical-trials.gov for a clinical trial conducted under an investigational new drug (IND) application if it is for a drug to treat a serious or life-threatening disease or condition and it is a trial to test effectiveness (regardless of Phase).

Registration is required for trials that meet the FDAAA 801 definition of an "applicable clinical trial" and were either initiated after September 27, 2007, or initiated on or before that date and were still ongoing as of December 26, 2007. Trials that were ongoing as of September 27, 2007 and reached the Completion Date (see Primary Completion Date data element on ClinicalTrials.gov) before December 26, 2007, are excluded. "Applicable Clinical Trials" include the following:

  • Trials of drugs and biologics. Controlled (Note: controls used in clinical investigations may be: (1) placebo concurrent control; (2) dose-comparison control; (3) no intervention concurrent control; (4) active intervention concurrent control; and (5) historical control ) clinical investigations other than phase 1 clinical investigations, of drugs or biological products subject to Food and Drug Administration (FDA) regulation
  • 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

"Applicable clinical trials" generally include interventional studies (with one or more arms) of FDA-regulated drugs, biological products, or devices that meet one of the following conditions:

  • The trial has one or more sites in the United States
  • The trial is conducted under an FDA investigational new drug application or investigational device exemption
  • The trial involves a drug, biologic, or device that is manufactured in the United States or its territories and is exported for research

For complete statutory definitions and more information on the meaning of "applicable clinical trial," see Elaboration of Definitions of Responsible Party and Applicable Clinical Trial (PDF).

The following types of studies are generally excluded from the registration (and results submission) requirements of FDAAA 801. This is not a complete list.

  • Phase 1 drug trials including studies in which investigational drugs are used as research tools to explore biological phenomena or disease processes
  • 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
  • Trials that do not include drugs, biologics, or devices (such as behavioral interventions)
  • Non-interventional (observational) clinical research, such as cohort or case-control studies
  • Trials that were ongoing as of September 27, 2007, and reached the Completion Date (Primary Completion Date data element on ClinicalTrials.gov) before December 26, 2007

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What are the International Committee of Medical requirements for registering clinical trials?

To promote transparency of the clinical trial process, the International Committee of Medical Journal Editors (ICMJE) established a policy in 2005 requiring the entry of clinical trials in a public registry prior to subject enrollment as a condition of consideration for publication of the trial results. The ICMJE requires “any research project that prospectively assigns human participants or groups of humans to one or more health-related interventions to evaluate the effects on health outcomes”.  Health-related interventions include an intervention used to modify a biomedical or health-related outcome (for example, drugs, surgical procedures, devices, behavioral treatments, dietary interventions, and process of care changes).    Health outcomes include any biomedical or health-related measure obtained in patients or participants, including pharmacokinetic measures and adverse events.


What are the NIH Requirements for ClinicalTrials.gov Registration Information in Applications and Progress Reports?

Trials subject to FDAAA are called “applicable clinical trials”. Any ACT supported in whole or in part by an NIH grant (including cooperative agreements) must be in full compliance with FDAAA.
The trial’s “responsible party” is responsible for two basic elements of compliance:

  • the registration of the ACTs in ClinicalTrials.gov, and
  • the reporting of summary results information (including adverse events)


A third basic element of compliance specific to the NIH implementation of FDAAA is a requirement for all NIH grantees, regardless of whether or not they are the “responsible party” under FDAAA:

  • certify in the grant application and progress report forms that the responsible party has made all required submissions to ClinicalTrials.gov for ACTs funded in whole or in part by the NIH.

To help understand if a grant supports an ACT and which entity or individual is the responsible party for the trial, please review “Steps to Compliance for NIH Grantees.”

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How do I report results and AEs for terminated studies?

For studies where recruitment or enrollment of participants has halted prematurely (and will not resume) and participants are no longer being examined or treated, ClinicalTrials.gov has specific requirements for results and adverse event reporting. If no participants were ever enrolled in the trial, set the Overall Recruitment Status to "Withdrawn", and no further results information needs to be submitted.

For a trial that was terminated after participants were enrolled, provide any available data.  The overall status field for the study should be "terminated", and Basic results including participant flow, baseline characteristics, primary and secondary outcomes, and adverse event information should be entered. If data for any of the outcome measures are not available, "0" can be included for number of participants analyzed, and the value fields for each of the outcome measures can be left blank. In this case, provide an explanation in the Analysis Population Description for why zero participants were analyzed and, if appropriate, provide information in the Limitations and Caveats module. Even if data are not entered for Outcome Measures, submit the available data for the enrolled participants in the Participant Flow, Baseline Characteristics, and Adverse Events modules.


How do the FDA registration requirements affect NIH funded studies?

Competing renewal applications that include studies that are required to be registered must include as part of the Human Subjects Section of the Research Plan the following items:

  • A statement that “This application includes a trial which requires registration in ClinicalTrials.gov,”
  • The National Clinical Trial (NCT) number (i.e. the ClinicalTrials.gov number)
  • Brief Title as listed in ClinicalTrials.gov, and
  • The name of the individual or entity responsible for registering the study (responsible party) for each study being conducted under the application. (As grantee, Duke University designates the lead investigator of the trial as the responsible party.)

If the application does not include studies that are required to be registered the Human Subjects Section of the Research Plan should include a statement that “This application does not include a trial which requires registration in ClinicalTrials.gov.” These requirements apply to all competing applications submitted to the NIH on or after January 25, 2008.

New applications that include studies that are required to be registered must include as part of the Human Subjects Section of the Research Plan a statement that “This application includes a trial which requires registration in ClinicalTrials.gov.” The study would then need to be registered and the National Clinical Trial (NCT) number, Brief Title as listed in ClinicalTrials.gov and the individual or entity responsible for registering the study (responsible party) for each study being conducted under the application as part of the Just-In-Time (JIT) information. If a New application does not include studies that are required to be registered the Human Subjects Section of the Research Plan should include a statement that “This application does not include a trial which requires registration in ClinicalTrials.gov.”

Non-competing progress reports that include studies that are required to be registered must include as part of the Human Subjects Section of the Progress Report the following items:

  • A statement that “This application includes a trial which requires registration in ClinicalTrials.gov,”
  • The National Clinical Trial (NCT) number (i.e. the ClinicalTrials.gov number),
  • Brief Title as listed in ClinicalTrials.gov and,
  • the name of the individual or entity responsible for registering the study (responsible party) for each study being conducted under the application. (As grantee, Duke University designates the lead investigator of the trial as the responsible party.)

If the application does not include studies that are required to be registered the Human Subjects Section of the Research Plan should include a statement that “This application does not include a trial which requires registration in ClinicalTrials.gov.” These requirements apply to all non-competing progress reports with budget start dates of April 1, 2008 or later (applications due on or after 2/1/08).

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Do the FDA regulations have any special requirements for IND, IDE or BLA studies?

Studies conducted under an IND or IDE must include in the informed consent documents and the informed consent process a statement that clinical trial information for the study has been or will be submitted for inclusion in ClinicalTrials.gov as required by FDA regulations.

  • A certification must accompany human drug, biological, and device product submissions made to FDA. At the time of submission of an IND, IDE or BLA application or submission of a report, amendment, supplement or resubmission, such application or submission must be accompanied by a certification that all applicable requirements related to clinical trial registration have been met. Where available, such certification must include the appropriate National Clinical Trial (NCT) numbers.
  • The official certification form, Form FDA 3674 entitled "Certification of Compliance with Requirements of ClinicalTrials.gov Data Bank, is available on FDA's Web site.
  • For sponsor held INDs, IDEs and BLAs the sponsor must provide the certification. For investigator held INDs, IDEs and BLAs the individual holding the IND, IDE or BLA must provide the certification.


Where can I find more information from the NIH about the requirement to register clinical trials?

The NIH has a posted information on clinical trials registration at:  http://grants.nih.gov/clinicaltrials_fdaaa/
 

What is the “Informed Consent Regulation”?

On January 4, 2011 the US Food and Drug Administration (FDA) published a regulation that changed the required elements of informed consent to include a statement regarding ClinicalTrials.gov registration. Studies approved after March 7, 2012 that are required by FDA regulation to be listed on ClinicalTrials.gov will be required to have the following statement in the consent: ‘‘A description of this clinical trial will be available on ClinicalTrials.gov,as required by U.S. Law. This Web site will not include information that can identify you. At most, the Web site will include a summary of the results. You can search this Web site at any time.’’

Amendment of consents approved before March 7, 2012 to include this language is not required and reconsent of subject is not required. However, some sponsors may elect to add the new language to existing consent forms. If a consent form is being amended to add the new language it must be the exact language specified in the regulation and you need to confirm that the study has been listed on ClinicalTrials.gov.

Informed Consent Regulation at 21 CFR 50.25(c)

Federal Register Notice of the Informed Consent Elements Final Rule (76 FR 270)

See the statutory provision requiring FDA to amend the informed consent regulations (PDF).

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Who can I contact at Duke for more information about the requirements to register clinical trials?

Contact the Duke Office of Clinical Research by email at DOCR.help@dm.duke.edu or by calling 681-6665 with further questions.

Are there other sources of information about clinical trial registration?