In a Nutshell

Studies must be registered with ClinicalTrials.gov if:

  1. they involve drugs, devices, or biologics that are regulated by the Food and Drug Administration (FDA), OR
  2. they are funded by the National Institutes of Health (NIH) AND meet the NIH definition of a clinical trial, OR
  3. there is a plan to publish the results in a medical journal AND the study meets the International Committee of Medical Journal Editors (ICMJE) definition of a clinical trial

Background

ClinicalTrials.gov is a databank or registry of federally funded, privately supported, and unfunded clinical trials involving human subjects. It is managed by the National Library of Medicine within the National Institutes of Health (NIH). ClinicalTrials.gov is the result of a federal law requiring that clinical trials be registered to improve public access to information about clinical research, promote public trust in research, and inform future research. In some cases, registration is also required for journal publication. This guidance document provides information about clinical trial registration requirements set forth by the Food and Drug Administration, the National Institutes of Health, and the International Committee of Medical Journal Editors.

Applicability

Food and Drug Administration Registration Requirements

The Food and Drug Administration (FDA) requires registration with ClinicalTrials.gov for all applicable clinical trials (ACTs) that were initiated after 9/27/2007, or were initiated before 9/27/2007, but were ongoing as of 12/26/2007.

Definitions

Applicable Clinical Trials:

  • Drugs and Biologics: A controlled clinical investigation, other than a Phase 1 clinical investigation, of a drug or biologic product subject to FDA regulation.
  • Medical Devices: A prospective clinical study of health outcomes comparing an intervention with a medical device against a control, or pediatric postmarket surveillance required by the 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 (IND) or investigational device exemption (IDE)
  • The trial involves a drug, biologic, or device that is manufactured in the United States or its territories and is exported for research

Registration is not required for small trials to determine the feasibility of a device or to test prototype devices where the primary outcome measure relates to feasibility, and not to health outcomes.

Resources

ClinicalTrials.gov FDAAA

Guidance for drugs and biologics

Guidance for devices

National Institutes of Health Registration Requirements

Effective January 18, 2017, National Institutes of Health (NIH) requires registration at ClinicalTrials.gov for all clinical trials funded wholly or partially by NIH.

Effective March 23, 2018, US Congress directs NIH to delay enforcement of new clinical trials policy. The policy includes a new definition of clinical trial that would have required that many basic and behavioral studies be registered with clinicaltrials.gov.  

Definitions

Clinical Trial: 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. This includes Phase 1 clinical trials, and trials that do not involve any FDA-regulated products (such as trials involving only behavioral interventions). [See note above regarding delayed enforcement]

Prospectively Assigned: A pre-defined process (e.g., randomization) specified in an approved protocol that stipulates the assignment of research subjects (individually or in clusters) to one or more arms (e.g., intervention, placebo, or other control) of a clinical trial.

Intervention: A manipulation of the subject or subject’s environment for the purpose of modifying one or more health-related biomedical or behavioral processes and/or endpoints. Examples include: drugs/small molecules/compounds; biologics; devices; procedures (e.g., surgical techniques); delivery systems (e.g., telemedicine, face-to-face interviews); strategies to change health-related behavior (e.g., diet, cognitive therapy, exercise, development of new habits); treatment strategies; prevention strategies; and, diagnostic strategies.

Health-related biomedical or behavioral outcomes: The pre-specified goal(s) or condition(s) that reflect the effect of one or more interventions on human subjects’ biomedical or behavioral status or quality of life. Examples include: positive or negative changes to physiological or biological parameters (e.g., improvement of lung capacity, gene expression); positive or negative changes to psychological or neurodevelopmental parameters (e.g., mood management intervention for smokers; reading comprehension and /or information retention); positive or negative changes to disease processes; positive or negative changes to health-related behaviors; and, positive or negative changes to quality of life.

Resources

NIH Clinical Trial Requirements for Grants and Contracts

Hudson 2016 - Toward a New Era of Trust and Transparency in Clinical Trials

New NIH Human Subjects and Clinical Trial Information Form

Lauer 2017 - Continuing to Clarify the NIH Definition of a Clinical Trial

Lauer 2017 - Further Refining Case Studies and FAQs about the NIH Definition of a Clinical Trial in Response to Your Questions

New NIH Clinical Trials Policies: Implications for Behavioral and Social Science Researchers

ICMJE Registration Requirements

As of 2005, most medical journals, including member publications of the International Committee of Medical Journal Editors (ICMJE), require registration with ClinicalTrials.gov as a condition of publication. Thus, researchers who plan to publish in an ICMJE member journal must meet ICMJE guidelines for clinical trial registration.

Definitions

Clinical Trial: 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.

Resource

ICMJE on clinical trials registration

Frequently Asked Questions

Who is responsible for registration and reporting results?

Responsibility for registration falls to the individual designated to be the responsible party. In some cases, the sponsor of the trial is the responsible party. However, the principal investigator is the responsible party in cases where there is no sponsor (Investigator-initiated trials) or for NIH-funded clinical trials that do not involve FDA-regulated components. Additionally, the sponsor can delegate all registration and reporting responsibilities to the principal investigator under the following conditions:

  • The trial is initiated by the investigator
  • The investigator has access to and control over the data from the clinical trial, and
  • The investigator has the right to publish the results of the clinical trial.

For research involving an IND or IDE with the FDA, the holder of the IND or IDE is the responsible party unless responsibility has been delegated to the principal investigator.

It is very important for researchers to know who the responsible party is, related to these requirements. Substantial penalties (i.e., monetary fines, withholding federal funds, denial of publication in an ICMJE journal, etc.) can be levied against responsible parties for failure to meet these requirements. Beginning January 18, 2017, applications for NIH funding must include a plan describing how the registration and reporting requirements will be met.

Principal investigators who are the responsible party may designate an individual to register the trial and complete registration information. However, it is ultimately the responsibility of the PI to ensure that registration occurs and the information provided is accurate and current. Research teams should identify the responsible party and ensure their responsibilities are clearly articulated prior to starting a clinical trial.

How are clinical trials registered?

Clinical trials are registered via a web-based protocol registration system (PRS). Instructions for completing registration can be found here.

OSU researchers may request an account by emailing a request to the PRS Account Administrator in the Human Research Protection Program at irb@oregonstate.edu.

The PRS Account Administrator’s role is to help establish an account for the responsible party. The PI is responsible for accurate and timely registration and reporting to ClinicalTrials.gov.

How is registration handled for research projects conducted at multiple institutions?

The sponsor is responsible for registering the trial. In cases where there is no sponsor, investigators involved in the research must work with each other to identify a responsible party and ensure the trial is registered only once for the entire project.

When must clinical trials be registered?

Federal regulations require that applicable clinical trials and NIH-funded clinical trials be registered no later than 21 days after enrollment of the first participant. However, researchers should be aware that ICMJE requires registration prior to enrollment of any subjects, and member journals may decline publication articles from studies that were not registered in accordance with this requirement.

When must results from clinical trials be reported to ClinicalTrials.gov?

Results from clinical trials must be reported to ClinicalTrials.gov no later than 12 months after the primary completion date. The primary completion date is defined as the date that the final subject 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.

What specific information must be provided to ClinicalTrials.gov?

Detailed information on the data elements required by FDA and the NIH for registration and results reporting can be found on the ClinicalTrials.gov PRS (Protocol Registration System) Information web site:

How often must data on ClinicalTrials.gov be updated?

For clinical trials initiated on or after January 18, 2017, information submitted to ClinicalTrials.gov must be updated at least once every 12 months.

How does registration of clinical trials relate to IRB review and approval?

IRB review is a completely separate process from clinical trial registration. IRB approval is not required prior to initial registration at ClinicalTrials.gov, nor does the IRB review any information submitted for registration. However, IRB approval is needed before research activity with human subjects is initiated.

The Protocol Registration System requires some information about IRB approval of Clinical Trials.

If your clinical trial was approved by the OSU IRB, please use the following information in the registration:

Unique Protocol ID:   Use the number assigned by the OSU HRPP/IRB
Board Name: Oregon State University IRB
Board Affiliation: Oregon State University
Board Contact: Phone: 541-737-8008
  Email: irb@oregonstate.edu
  Address: Human Research Protection Program
B308 Kerr Admin Bldg.
Corvallis, OR 97331

Do I need to inform research participants about ClinicalTrials.gov Registration?

Yes! Research participants must be informed of the availability of clinical trial information on ClinicalTrials.gov. Federal regulations require the following language to be included verbatim in informed consent documents for applicable clinical trials initiated on or after March 7, 2012 and for all NIH-funded clinical trials subject to registration:

A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. Law. This website will not include information that can identify you. At most, the website will include a summary of the results. You can search this website at any time.

What are the consequences for failure to properly register a clinical trial?

Under federal law, penalties for failure to register, or for providing incomplete, false, or misleading registration information (including updates subsequent to initial registration) may include civil monetary penalties of up to $10,000 per incident and/or per day, non-compliance notices from the FDA, and, for federally-funded trials, the withholding or recovery of grant funds.

Compliance with ClinicalTrials.gov registration requirements will be a term and condition of NIH awards. NIH grantees are required to certify their compliance with registration and reporting requirements in grant applications and progress reports. Failure to comply may lead to suspension or termination of funding and publicly identifying the clinical trial record as noncompliant in clinicaltrials.gov. NIH may consider compliance with these requirements in decisions about future funding.

Additionally, unregistered or improperly registered trials risk not being accepted for consideration by ICMJE member or other journals.

 

Adapted with permission from Iowa State University’s guidance (08/07/2017)