The purpose of clinical trial registration is to promote the public good by ensuring that the existence, design and results of both ongoing and closed clinical trials are publicly available. Since November 1997, the FDA has mandated registration of clinical trials for serious or life-threatening diseases and conditions on the ClinicalTrials.gov Web registry. In 2007 new legislation was enacted expanding the scope of clinical trials that must be registered.
What are the consequences for failing to register applicable trials?
- Penalties for failing to register trials are significant and may include civil monetary penalties and, for federally-funded trials, the withholding or recovery of grant funds.
- The International Committee of Medical Journal Editors (ICMJE) journals, such as JAMA, NEJM and Pediatrics, will not publish any articles on research initiated after July 1, 2005, that were not listed with ClinicalTrials.gov prior to patient enrollment. If a trial was ongoing as of July 1, 2005, ICMJE will accept articles for review, as long as the trial is registered prior to submission.
Which trials must be registered?
International Committee of Medical Journal Editors (ICMJE)
According to the International Committee of Medical Journal Editors (ICMJE): "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."
This definition includes Phase 1 trials.
Deadlines for registration: studies must be registered before the first patient is enrolled.
Food and Drug Administration Amendments Act (FDAAA)
According to the FDA and the NIH: 2007 definition: The Food and Drug Administration Amendments Act (Title VIII. Sec. 801) requires registration for all "applicable clinical trials," including federal, industry-sponsored, and investigator-initiated which are:
- Trials of drugs and biologics: Controlled, clinical investigations, other than Phase I investigations, of a product subject to FDA regulation
- Trials of devices: Prospective clinical studies of health outcomes comparing an intervention with a device against a control in human subjects (other than small clinical trials to determine the feasibility of a device, or clinical trials to test prototype devices where the primary outcome measure relates to feasibility and not to health outcomes); and pediatric postmarket surveillance studies, as required under the Federal Food, Drug and Cosmetic Act
Deadlines for registration: studies must be registered within 21 days after the first patient is enrolled.
Who is responsible for registering clinical trials?
- The sponsor of the clinical trial
- Usually the clinical trial will be registered by the sponsor. NIH-sponsored trials should be registered by the institute that is funding the research. Industry-sponsored trials (industry-written protocols) should be registered by the industry sponsor. Multi-site trials should be coordinated among the sites and registered by the "lead sponsor" so that ClinicalTrials.gov does not receive multiple registrations for the same trial.
- The principal investigator (PI) of the clinical trial
- Investigator-initiated trials (for which industry has supplied drug or grant funds) should be registered by the PI. Trials for which PIs hold their own INDs or IDEs should be registered by the PI. Additionally, trials that the sponsor has declined to register should be registered by the PI. PIs should always verify the completion and accuracy of a sponsor's registration by looking at the ClinicalTrials.gov listing.
What is the process for registering a trial?
Guidance for registering a trial is provided to ClinicalTrials.gov user account holders on the ClinicalTrials.gov Protocol Registration System (PRS). If you do not have a Seattle Children's ClinicalTrials.gov user account, or if you have any questions, please email Lindsey Johnson.
The National Institutes of Health ClinicalTrials.gov website has some good resources and information for researchers: FDAAA 801 Requirements.
The Protocol Registration Service also has a PowerPoint web presentation on entering study results: ClinicalTrials.gov Results Database (PDF).