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ClinicalTrials.gov – What, Why, Which Studies, When

What is ClinicalTrials.gov?

ClinicalTrials.gov is a US government web-based resource maintained by the National Library of Medicine (NLM) at the National Institutes of Health (NIH) where clinical studies can be registered, information updated, and if required, results and documents posted. Federal law, some journal publication standards, and some funders (carefully review your award letter) require that clinical trials and even some clinical studies be registered on this publicly accessible database that supports compliance with these rules and regulations.  However, investigators can register any interventional clinical trial or observational clinical study, and once registered it must conform to verification and updating requirements of ClinicalTrials.gov. Four out of five studies registered are interventional clinical trials and 20% are observational studies. As of April 2020, there are about 338,000 studies listed from all 50 states and 211 countries. ClinicalTrials.gov receives about 3.5 million visitors monthly.

For key historical highlights of ClinicalTrials.gov click here.


Why register, update, and report results on ClinicalTrials.gov?

Registration, updating records, results reporting, and posting documents for clinical trials have two main purposes:  to inform potential subjects, and to increase the likelihood that negative results of trials will be publically available, thereby promoting transparency and scientific integrity. The database also provides tools for researchers, as it is a searchable database like PubMed (also maintained by NLM).

Click this link for more information on why to register on ClinicalTrials.gov.

Once a registration record on ClinicalTrials.gov is completed, approved by the institution’s PRS (Protocol Registration System) Administrator, released for ClinicalTrials.gov PRS review, and determined to be appropriately completed, it will be issued a ClinicalTrials.gov NCT (National Clinical Trials) number and it is registered. A trial should only be registered and listed once.


Which studies must be registered and regularly updated on ClnicalTrials.gov?

BMC/BU Medical Campus policy requires that all studies meeting the definition of a clinical trial according to the International Committee of Medical Journal Editors (ICJME)* must be registered with ClinicalTrials.gov before final IRB approval is issued (note that IRB submission and review can proceed while the NCT# is being obtained).

 *ICMJE definition of a clinical trial: Any research project that prospectively assigns people or a group of people to an intervention, with or without concurrent comparison or control groups, to study the cause-and-effect relationship between a health-related intervention and a health outcome. 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.

NIH definition of a 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.

The HHS Final Rule and the NIH Policy describe which studies must be registered and post results on ClinicalTrials.gov. Summary of HHS Final Rule and NIH Policy on Registration/Reporting in ClinicalTrials.gov in NEJM (Nov. 2016)

HHS Final Rule on Clinical Trial Reporting in ClinicalTrials.gov

Applies to: Clinical trials of drug and biological products that are controlled, clinical investigations, other than phase 1 investigations, of a product subject to FDA regulation (i.e. “Applicable clinical trials”); and (2) prospective clinical studies of health outcomes comparing an intervention with a device product against a control in humans (other than small feasibility studies) or any pediatric post-market surveillance studies required by FDA under the FD&C Act.  (Does not apply to phase 1 trials or small feasibility device studies.)

Registration: Not later than 21 days after enrollment of the first participant. (However per BMC/BU Medical Campus Policy registration must take place before IRB approval of the research.)

Results Reporting: Not later than 12 months after primary completion date; possible delay of up to an additional 2 years for trials of unapproved products or of products for which initial FDA marketing approval or clearance is being sought, or approval or clearance of a new use is being sought.

NIH Policy

Applies to: All clinical trials funded wholly or partially by NIH.  Includes phase 1 clinical trials and trials that do not involve any FDA regulated product such as trials involving only behavioral interventions.  Applies to NIH-funded clinical trials where applications or proposals are received by NIH on or after the policy’s effective date (Jan. 18, 2017).  Applies to NIH-conducted clinical trials initiated on or after the policy’s effective date.

Registration: Not later than 21 days after enrollment of the first participant.  (However per BMC/BU Medical Campus Policy registration must take place before IRB approval of the research.)

Results Reporting: Not later than 12 months after primary completion date; possible delay of up to an additional 2 years for trials of unapproved products or of products for which initial FDA marketing approval or clearance is being sought, or approval or clearance of a new use is being sought.

Other Relevant Definitions (from BMC Registering, Updating and Posting on ClinicalTrials.gov (09_24_000 Rev Sep 2019):

Applicable Clinical Trial (ACT): Interventional studies of drugs, biologics and devices if the trial is subject to the registration and results reporting requirements in the FDA Administration Act (FDAAA). An applicable drug clinical trial is a controlled clinical investigation, other than a Phase I clinical investigation, of a drug subject to section 505 of the Federal Food, Drug, and Cosmetic Act or section 351 of the Public Health Service Act. An applicable device clinical trial is either: (1) a prospective clinical study of health outcomes comparing an intervention with a device subject to section 510(k), 515, or 520(m) of the Federal Food, Drug, and Cosmetic Act against a control in human subjects (other than a small clinical trial 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) or (2) a pediatric post-market surveillance of a device as required under section 522 of the Federal Food, Drug, and Cosmetic Act. To determine if your trial meets the criteria for an ACT fill out the ACT checklist.

Responsible Party (RP): The Responsible Party (RP) is the Sponsor of the clinical study or the Principal Investigator if so designated by the Sponsor, grantee, contractor, or awardee. If the study has no external funding, the Responsible Party is either the institution (eg BMC or BU Medical Campus, specifically the BMC/BU Medical Campus Administrator of ClinicalTrials.gov) or the Principal Investigator. At any time during the conduct of the study if the Responsible Party is the Principal Investigator but they do not comply with all requirements of this policy for that research, then the institution (BMC/BU Medical Campus Administrator of ClinicalTrials.gov) can assume the role of the Responsible Party.

Sponsor: The Sponsor is a person or entity who takes responsibility for and initiates a research study. The sponsor may be an individual or pharmaceutical company, governmental agency, academic institution, private organization, academic medical center, or other organization.

Primary Completion Date: 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. In the case of clinical trials with more than one primary outcome measure with different completion dates, the term refers to the date on which data collection is completed for all of the primary outcomes.

 

Which studies must post results on ClnicalTrials.gov?

All NIH funded clinical trials (even pilot and phase 1 trials) submitted on or after January 18, 2017, all Applicable Clinical Trials (ACTs), certain clinical trials subject to the requirements of Section 801 of the Food and Drug Administration Amendments Act (FDAAA 801), and all studies where the award letter stipulates that results must be posted on ClinicalTrials.gov are required to post results no later than 10 months after the primary completion date.  There can be a possible delay of up to an additional 2 years for trials of unapproved products or of products for which initial FDA marketing approval or clearance is being sought, or approval or clearance of a new use is being sought. These delays should be discussed with the PRS Administrator.