ClinicalTrials.gov

See here for an “At a Glance” summary spreadsheet of registration requirements.

See here for UH-specific instructions

What is ClinicalTrials.gov?

ClinicalTrials.gov is a web-based resource that provides patients, their family members, health care professionals, researchers, and the public with easy access to information on publicly and privately supported clinical studies on a wide range of diseases and conditions.

ClinicalTrials.gov (CT.gov) is a public registry aimed at increased transparency and improved public awareness of research. The website is maintained by the National Library of Medicine (NLM) at the National Institutes of Health (NIH), and registration is required by law for certain clinical trials of drugs, medical devices, biological products and NIH-funded clinical trials. Registration is also required in many cases for journal publication.

To ensure compliance as well as to avoid publication concerns, please make sure you read through the definitions and timelines carefully. The new NIH rules and International Committee of Medical Journal Editors (ICMJE) have very broad definitions of clinical trial. Contact the UH IRB if you have any questions at CPHS@central.uh.edu.

What is the purpose of registering a study?

Registration provides a mechanism to ensure continuity in the research enterprise, which supports research integrity through the dissemination of research results, whether positive or negative.

The new common rule found at 45 CFR Part 46 also requires that federally funded studies considered to be clinical trials post a copy of the informed consent form to a publicly available Federal Web site that will be established as a repository for such informed consent forms. At this time, two publicly available federal websites that will satisfy the consent form posting requirement, as required by the revised Common Rule, have been identified: ClinicalTrials.gov and a docket folder on Regulations.gov (Docket ID: HHS-OPHS-2018-0021). See here for instructions on posting to this docket.

What studies must be registered and/or post a copy of the consent form?

Certain FDA-regulated studies, NIH-funded studies and other unfunded studies with an intent to publish in an ICMJE journal require registration in ClinicalTrials.gov.

Other federally funded studies are required by the new common rule to post a copy of the consent form on a publicly available Federal Web site that will be established as a repository.

FDA

Released in 2007, the Food and Drug Administration Amendments Act of 2007 (FDAAA) required clinical trial registration and results information submission for certain studies. The “Final Rule,” which clarified these FDAAA requirements for registering studies in ClinicalTrials.gov, became effective in 2017.

Research that must be registered under FDA requirements generally includes interventional studies (one or more arms) of drugs, biological products, or devices that are subject to FDA regulation, meaning that the trial has one or more sites in the U.S., involves a drug, biologic, or device that is manufactured in the U.S. (or its territories), or is conducted under an investigational new drug application (IND) or investigational device exemption (IDE).

If the FDA regulated study is federally funded, a copy of the consent form must also be posted to a publicly available Federal Web site that will be established as a repository for such informed consent forms. At this time, two publicly available federal websites that will satisfy the consent form posting requirement, as required by the revised Common Rule, have been identified: ClinicalTrials.gov and a docket folder on Regulations.gov (Docket ID: HHS-OPHS-2018-0021). See here for instructions on posting to this docket.

Are there any tools to help determine which FDA studies are required to be registered on ClinicalTrials.gov?

A checklist for determining whether your FDA regulated study is required to be registered at ClinicalTrials.gov can be found here
You can read the Final Rule that clarified FDA requirements for registering studies in ClinicalTrials.gov here

NIH

NIH’s policy applies to clinical trials funded in whole or in part through the NIH extramural and intramural programs. The new common rule found at 45 CFR Part 46 requires that NIH funded clinical trials post a copy of the informed consent form to a publicly available Federal Web site that will be established as a repository for such informed consent forms. At this time, two publicly available federal websites that will satisfy the consent form posting requirement, as required by the revised Common Rule, have been identified: ClinicalTrials.gov and a docket folder on Regulations.gov (Docket ID: HHS-OPHS-2018-0021). See here for instructions on posting to this docket.

NIH defines a clinical trial as: a study where 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. This policy does not apply to NIH-funded clinical trials initiated before the effective date of January 18, 2017, clinical trials that use NIH-supported infrastructure but do not receive NIH funds to support their conduct, or clinical trials of ongoing, non-competing awards. If the answers to the following four questions are yes, your study meets the NIH definition of a clinical trial:

Does the study involve human participants research?
Are participants prospectively assigned to an intervention?
Is the study designed to evaluate the effect of the intervention on the participants?
Is the effect being evaluated a health-related biomedical or behavioral outcome?

Note that if the answers to all four questions above are yes, your study meets the NIH definition of a clinical trial, even if…

You are studying healthy participants
Your study is a single intervention with no comparison group (e.g., placebo or control)
Your study is only designed to assess the pharmacokinetics, safety, and/or maximum tolerated dose of an investigational drug
Your study is utilizing a behavioral intervention

Are there any tools to help determine which NIH-funded studies are required to be registered on ClinicalTrials.gov?

Checklists for determining whether your NIH-funded study is required to be registered at ClinicalTrials.gov can be found here and here.
You can read the NIH policy explaining requirements for registering studies in ClinicalTrials.gov here.

ICMJE

Even if your study is not federally funded and not required to be registered as an FDA requirement, you should become familiar with ICMJE requirements for registration of certain studies on clinicaltrials.gov. In 2005, the ICMJE required that all clinical trials be entered into a public registry. The ICMJE defines a clinical trial as 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:

Health-related interventions include any 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 measures obtained in patients or participants, including pharmacokinetic measures and adverse events.

Additionally, for trials that start enrolling participants on or after January 1, 2019, ICMJE will require data sharing statements in the ClinicalTrials.gov registration as a condition of publication. These statements will also be required in manuscripts submitted to ICMJE journals starting in July 2018. See here for more information and examples of these statements.

Are there any tools to help determine which studies the ICMJE require to be registered on ClinicalTrials.gov?

An FAQ to help with determining whether your study is required to be registered at ClinicalTrials.gov is available here.
For more information regarding the ICMJE data sharing statement requirement, please see here.

WHO

Signatories to the May 18, 2017 World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), including such funding agencies as the Bill and Melinda Gates foundation, require registration and results reporting by their grant recipients.

UH principal investigators should become familiar with the terms of their research foundation sponsors, which may include registering a study for public results dissemination.

Other federally funded studies (such as CDC, HRSA, etc.)

The new common rule found at 45 CFR Part 46 requires that for each clinical trial conducted or supported by a Federal department or agency, one IRB-approved informed consent form used to enroll subjects must be posted on a publicly available Federal Web site that will be established as a repository for such informed consent forms. At this time, two publicly available federal websites that will satisfy the consent form posting requirement, as required by the revised Common Rule, have been identified: ClinicalTrials.gov and a docket folder on Regulations.gov (Docket ID: HHS-OPHS-2018-0021). See here for instructions on posting to this docket.

The common rule defines a clinical trial as 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 the interventions on biomedical or behavioral health-related outcomes.

Who is responsible for registering a study and/or posting a copy of the informed consent form?

The responsible party is as follows, based on agency:

FDA-regulated studies

The sponsor of the clinical trial, or

The principal investigator (PI) of such clinical trial if so designated by the 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 FDA’s requirements for submission of clinical trial information.

NIH-funded studies

The awardee or the investigator is responsible for registering the study and posting a copy of the informed consent form.

ICMJE requirements

The ICMJE expects the authors to ensure that the study is registered appropriately.

If it is unclear who is responsible for 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.

Other federally funded studies

The awardee or the Federal department or agency component conducting the trial is responsible for posting the informed consent form on the public website.

What are the compliance timelines for registering a study and/or posting a copy of the informed consent form?

FDA Compliance Dates

The most recent requirements related to initial study registration (from the “Final Rule”) apply to studies initiated on or after January 18, 2017, and results submission requirements apply to trials that reach their primary completion date on or after January 18, 2017. Trials initiated after September 27, 2007 but before January 18, 2017 still require registration; however, those studies would be held to the criteria previously in place before the Final Rule became effective. If you have a study that was initiated during this specific time period that is not yet listed in ClinicalTrials.gov, see guidance here for assistance.

Registration compliance deadline: 21 days after enrollment of first subject.
If the study is also federally funded and must post a copy of the informed consent form: after the clinical trial is closed to recruitment, and no later than 60 days after the last study visit by any subject
Results submission compliance deadline: No later than 1 year after the completion date (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.

NIH Policy Compliance Dates

The policy applies to applications submitted on or after January 18, 2017 for clinical trials initiated on or after January 18, 2017, and competing renewal applications that include a new clinical trial (i.e., a clinical trial initiated on or after January 18, 2017).

Registration compliance deadline: 21 days after enrollment of first subject.
Posting a copy of the informed consent form: after the clinical trial is closed to recruitment, and no later than 60 days after the last study visit by any subject.
Results submission compliance deadline: No later than 1 year after the completion date (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 Compliance Dates

Investigators should register trials that began enrolling patients any time before July 1, 2005 as soon as possible if they wish to submit them to a journal that follows the ICMJE policy. Beginning September 13, 2005, ICMJE journals will consider trials for publishing only if they were adequately registered before journal submission.

Registration compliance deadline: At or before the time of first patient enrollment.
Results submission compliance deadline: ICMJE does not require results to be submitted; however, ICMJE encourages registry results reporting even when not required. Results should be submitted no later than 1 year after the completion date (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.

Other federally funded studies

The informed consent form must be posted on the Federal Web site after the clinical trial is closed to recruitment, and no later than 60 days after the last study visit by any subject.

How often must a study record be updated?

The following data elements must be updated not later than 30 calendar days after a change occurs:

Study start date
Intervention name(s)
Availability of Expanded Access
Expanded Access status
Overall recruitment status
Explanation for change in status
Actual enrollment data
Individual site status
IRB status
Completion Date
Responsible Party
Official Title
Contact Information

Each record must be reviewed for accuracy, and the Record Verification Date updated at least every 12 months, even if there have been no changes to the study. The need to update ends when the study is completed or terminated and the results are entered, approved and posted. Results must be submitted no later than 12 months after (Primary) Completion Date.