clinical trials.gov Is a serachable database of clinicial trials, increases public trust through increased transparency and makes it easier for potential participants to find studies
  • A resource that provides access to information on clinical trials studying a wide range of diseases, conditions and interventions.

  • Studies listed in the database are conducted in all 50 States and in 220 countries.

  • Each ClinicalTrials.gov record includes summary information about studies such as:

    • Study design and Intervention
    • Disease or condition
    • Requirements for participation (eligibility criteria)
    • Locations and Contact information
    • Some records may include outcomes of the study
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Why Do I Need to Register My Trial and Submit Results to ClinicalTrials.gov?

Why Do I Need to Register My Trial and Submit Results to ClinicalTrials.gov? Here are just some of the reasons…

What is the penalty for non-compliance?

(Decortative) Envelope with a letter that says "FDA Warning"

Under NIH Policy: Noncompliance with the terms and conditions of the NIH award may provide a basis for enforcement actions, such as withholding current and future funding [45 CFR 75.37142 CFR 11.66]

Under Final Rule, responsible parties could be held accountable for noncompliance, with the potential for substantial civil monetary penalties, the withholding of grant funding from HHS agencies, and criminal proceedings.[2016 NEJM article]

  • Case in point:
    On 28 April 2021, the FDA issued its first Notice of Noncompliance to Georgia-based Accuitis who failed to submit required summary results information. The company could be “subject to a civil monetary penalty of $10,000 for each day of the violation” until the noncompliance is corrected.

ICMJE: authors failing to prospectively register a trial risk its inadmissibility to journals following the ICMJE’s trial registration policy.

Summary of requirements:

EntityRegistrationResults ReportingPenalties
Health and Human Services
(HHS)
Within 21 days of enrollmentWithin 365 days of primary completion date for ACTs

  • $12,316/study/day

  • Criminal proceedings

  • Loss of grant funding

National Istitutes of Health
(NIH)
Within 21 days of enrollmentWithin 365 days of primary completion date
for clinical trials receiving NIH funding

  • Loss of grant funding (to include the institution)

National Cancer Institute
(NCI)
Within 21 days of enrollmentWithin 365 days of primary completion date of NCI-supported clinical trials (in a peer-reviewed journal and/or ClinicalTrials.gov)

  • Loss of grant funding

Veterans Health Administration
(VHA)
Prior to release of funding. Prior to enrollmentWithin 365 days of primary completion date

  • Loss of grant funding

Centers for Medicare & Medicaid Services
(CMS)
All qualifying clinical trialsStudy-specific

  • Coverage denial

  • Costs and fraud investigations

Patient-Centered Outcomes Research Institute
(PCORI)
All Clinical studies (including observational)Expected of all PCORI
Clinical studies – 500 word abstract published on PCORI website

  • Loss of grant funding

International Committee of Medical Journal Editors
(ICMJE)
Prior to enrollment

  • Ineligibility to publish

Department of Defense
(DoD)
Prior to enrollment.
Prior to release of funding.
Study-specific

  • $12,103/study/day

  • Withholding or recovery of award funds

Registration may be required if one (or more) of the following is true:

NIH funded clinical trials are required to be registered:

  • If your study is NIH funded and meets the NIH definition of a clinical trial, then clinicaltrials.gov registration is required.
  • For NIH funded research, use the following four questions to determine the difference between a clinical study and a clinical trial:
    • Does the study involve human participants?
    • Are the participants prospectively assigned to one or more interventions?
    • 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?
  • If the answers to ALL 4 questions are “yes”, your study meets the NIH definition of a clinical trial.

NIH Definition of an “INTERVENTION”:

An "intervention" is defined as 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.

This Includes

- studies with healthy participants

Phase 1 trials of FDA-regulated drugs and biological products

Small feasibility studies of FDA regulated device products

– studies with no comparison group (placebo or control)

– studies designed to assess the pharmacokinetics / safety of an investigational drug

– Studies where only one aim or sub-aim meets the clinical trial definition.

Wide Range of NIH Interventions include: mechanic, exploratory/development, piot/feasibility, other interventional, behavioral, basic experimental
Basic experimental studies involving humans (BESH)

Some NIH funded Basic experimental studies involving humans are also required to be registered:

Basic experimental studies involving humans (BESH) are studies that meet both the definition of basic research and the NIH definition of a clinical trial.

  • Basic research uses a range of probes or experimental manipulations to perturb a physiological process (including cognitive and perceptual processes).
  • NIH published clinical trial case studies with examples of BESH (cases 9, 14, 40 & 41).
  • Example: healthy volunteers randomized to different durations of sleep deprivation where the dependent variable is stress hormone levels.

The Food and Drug Administration Amendments Act of 2007 (FDAAA) established legal requirements for sponsors and designated principal investigators (i.e., responsible parties) to report specified clinical trial information for certain ACT’s to ClinicalTrials.gov.

The requirements are designed to

  • provide potential participants with information about trials of interest,
  • reduce publication bias,
  • help institutional review boards (IRBs) determine the appropriateness of a research study,
  • and promote more efficient allocation of research funds.
(Decorative) FDA Stamp of approval

Registration is also required if your study meets the DHHS definition of an Applicable Clinical Trial (ACT) These include:

  • Controlled clinical investigations (other than phase 1 investigations) of any U.S. Food and Drug Administration (FDA) -regulated drug or biological product for any disease or condition
  • It also includes certain studies of FDA-regulated medical devices, and FDA-required pediatric post market surveillances of a device product

Researchers can use the following tools to determine if their trial meets the DHHS definition of an ACT:

ACT – important definitions:

Is the study interventional (a clinical trial)?

  • Interventional is defined in the final rule to mean, with respect to a clinical study or a clinical investigation, that participants are assigned prospectively to an intervention or interventions according to a protocol to evaluate the effect of the intervention(s) on biomedical or other health-related outcomes. [Source: 42 CFR 11.10(a); 81 FR 65140-41]

Does the study evaluate at least one U.S. FDA-regulated drug, biological, or device product?

  • A device product is considered to be subject to section 510(k), 515, or 520(m) of the FD&C Act if any of the following is required before it may be legally marketed in the United States: (1) a finding of substantial equivalence under section 510(k) of the FD&C Act, (2) an order under section 515 of the FD&C Act approving a premarket approval application (PMA) for the device product, or (3) an HDE under section 520(m) of the FD&C Act.
  • Device products that are considered to be subject to section 510(k), 515, or 520(m) of the FD&C Act include significant risk devices for which approval of an IDE is required, non-significant risk devices that are considered to have an approved IDE in accordance with 21 CFR 812.2(b), or device products that are exempt from the submission requirements of 21 CFR part 812. [Source: 81 FR 65012]

Registration Requirements per International Committee of Medical Journal Editors (ICMJE):

Image of multiple medical journals
  • In 2005, the ICMJE defined trials that must be registered in order to be considered for publication in journals that adhere to ICMJE standards.
    • "we will consider a trial for publication only if it has been registered before the enrollment of the first patient. This policy applies to trials that start recruiting on or after July 1, 2005. Because many ongoing trials were not registered at inception, we will consider for publication ongoing trials that are registered before September 13, 2005.
  • In 2007, the ICMJE expanded the definition of trials that must be registered.
  • Many journals (not limited to medical journals) have adopted the registration policy.
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In June 2007 the ICMJE adopted the WHO's definition of 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.”

  • With or without concurrent comparison or control groups,
  • Health-related interventions are those used to modify a biomedical or health-related outcome; examples include drugs, surgical procedures, devices, behavioral treatments, educational programs, dietary interventions, quality improvement interventions, and process-of-care changes.
  • Health outcomes are any biomedical or health-related measures obtained in patients or participants, including pharmacokinetic measures and adverse events.
  • Purely observational studies (those in which the assignment of the medical intervention is not at the discretion of the investigator) will not require registration.
  • …encourages registration of research with non-trial designs (e.g., observational studies)
  • …journals will consider trials beginning on or after July 1, 2005 only if registration occurred before the first patient was enrolled ("prospective registration").
  • …does not define the timing of first participant enrollment, but best practice dictates registration by the time of first participant consent.
  • An acceptable registry must include the minimum 24-item trial registration data set at the time of registration.

**Those who are uncertain whether their trial meets the expanded ICMJE definition should err on the side of registration if they wish to seek publication in an ICMJE journal**

If your clinical trial will bill routine costs to Medicare, the study must be registered on ClinicalTrials.gov

If you have a clinical trial that includes a drug that's available via expanded access:

  • Under FDA regulations (21 CFR 312.300), expanded access allows for the use of unapproved drugs and biologics outside of a clinical trial for patients with serious diseases or conditions when there is no satisfactory alternative therapy to treat the patient’s disease or condition. This is sometimes referred to as compassionate use or treatment use.

Expanded access records which describe the procedure for obtaining an experimental drug or device outside of a clinical trial are required to be submitted to the ClinicalTrials.gov database.