Registration for Clinical Research Trials
This guidance offers support to researchers who must register and report clinical research trials to ClinicalTrials.gov, a database of clinical research trials conducted in the United States and around the world.
What is ClinicalTrials.gov?
ClinicalTrials.gov is a registry of federally and privately supported research studies conducted in the United States and around the world. Each entry is provided by the sponsor and includes a summary of the trial protocol, including the purpose, recruitment status, and criteria for patient participation. Trial locations and specific contact information are provided to assist enrollment. Some entries provide summary study results, including number of participants starting and completing the trial, baseline characteristics, outcome measures, and adverse events information. ClinicalTrials.gov is a free service of the U.S. National Institutes of Health (NIH), developed by the National Library of Medicine.
Required by law. Section 801 of the Food and Drug Administration (FDA) Amendments Act mandates the registration with ClinicalTrials.gov of certain clinical trials of drugs (including biological products) and medical devices subject to FDA regulations for any disease or condition. For details, see http://prsinfo.ClinicalTrials.gov.
Required for journal publication. The International Committee of Medical Journal Editors (ICMJE) requires trial registration as a condition for publication of research results generated by a clinical trial. http://www.icmje.org
Which clinical investigations or trials must be registered?
Trials that must be registered under the FDA Amendments Act of 2007 (FDAAA) are called “Applicable Clinical Trials.” Under the statute, these trials generally include:
- Trials of Drugs and Biologics: Controlled, *clinical investigations, other than Phase 1 investigations, of a product subject to FDA regulation; and
- Trials of Devices: Controlled trials with health outcomes, other than small feasibility studies, and pediatric post-market surveillance.
- ClinicalTrials.gov accepts registration of all clinical trials (1) approved by a human subject review board and (2) conforming to the regulations of the appropriate national health authorities. Both interventional and observational studies are accepted.
- Trials can be registered at any time, but many policies require registration prior to the enrollment of the first participant. Information about these policies and background materials are available at http://prsinfo.ClinicalTrials.gov.
* The FDA defines a clinical investigation as any experiment in which a drug is administered or dispensed to, or used, involving one or more human subjects. An experiment is any use of a drug except for the use of a marketed drug in the course of medical practice. Purely observational studies are exempt from registration requirements
Investigators should review the statutory definition of applicable clinical trial to identify if any of their trials must be registered to comply with the law. NIH encourages registration of ALL trials whether required under the law or not, and ICMJE advises that those who are uncertain whether their trial meets the ICMJE definition of eligible trials should consider registering if they wish to seek publication in an ICMJE journal. If you need additional clarification regarding registration of your clinical trial, please send an inquiry message directly to clinicaltrials.gov. via their website at: prsinfo.clinicaltrials.gov
Since responsibility for registering trials lies with the lead sponsor of the clinical study, most “industry sponsored” trials will be registered by the sponsor, which can be a pharmaceutical company or CRO. UMKC sponsor-investigator studies (also known as “investigator-initiated studies”), or those who hold an IND or IDE that meet the eligibility criteria, will all need to be registered by the investigator prior to study enrollment, where applicable. If the sponsor of a clinical trial is someone other than the PI, investigators should communicate with the study sponsor to determine the Responsible Party for protocol registration, and personally check the registry to ensure that all of the required registration elements are included.
Who is responsible for registering trials on ClinicalTrials.gov?
The entity responsible for registering is the “responsible party.” The statute defines the responsible party as:
(1) the sponsor of the clinical trial (as defined in 21 C.F.R. 50.3)
(2) the principal investigator of such clinical trial if so designated by a sponsor, grantee, contractor, or awardee, so long as the principal investigator 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 requirements under this subsection for the submission of clinical trial information.”
When to Register
By law, registration of Applicable Clinical Trials is required to occur within 21 days of first subject enrollment. However, UMKC recommends registration of all trials into the ClinicalTrials.gov database prior to first subject enrollment, to satisfy both the law and ICMJE requirements.
ICMJE guidelines currently define 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.” Purely observational studies (those in which the assignment of the medical intervention is not at the discretion of the investigator) will not require registration.
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.
When to Report Results
FDAAA requires reporting of study results for Applicable Clinical Trials no later than 12 months after the date of final data collection for the primary outcome measure, referred to as the “Primary Completion Date.”
Reporting of results can be delayed beyond the 12-month required timeline if:
- The trial is of a drug or device that has not been approved for marketing by the FDA for any indication; result reporting will be required within 30 days of initial approval;
- The trial is of a drug or device for which the manufacturer has filed or is preparing to file an application seeking approval of the new use studied in the trial; or
- A request for delay that “demonstrates good cause” has been granted by the Director of the NIH.
NOTE: Per FDAAA, sponsors must also include study results in the registry. The results submissions should include lay language summaries of subject demographics and characteristics, primary and secondary outcomes, and disclosures of any privacy agreements. Timelines for this information are set forth (see related links below). At this time, the ICMJE does not require the recording of study results in the ClinicalTrials.gov database. UMKC recommends that PIs stay informed about these requirements, as they evolve.
Guidance for Results and Adverse Events Reporting
Adverse Event Reporting - information on the requirements for reporting adverse events
Guide to Results Data Entry - (CHEST, 2009 Jul;136(1):295-303) - article includes summary results reporting requirements, brief descriptions of the results database modules, and suggestions for preparing results submissions
Pre-Submission Checklist (pdf) (DRAFT) - a short reminder checklist to assist in results data entry
Common errors (pdf) (DRAFT) - overview of common types of errors identified in submitted records with "basic results"
Helpful hints (pdf) - tips on entering results data, including three examples of common study models (parallel design, crossover design, and diagnostic accuracy studies), reporting measure types, including information on reporting outcomes measured with a scale.
"Basic Results" Data Element Definitions (DRAFT) - details on the information that is entered about results, including adverse events, via the PRS.
Results Detailed Review Items (pdf) (DRAFT) - describes items evaluated by ClinicalTrials.gov after results have been submitted.
Basic Results Provisions (pdf) - extracted from FDAAA 801.
Delayed Submission of Results - information on submitting certifications or requests for extension
Recorded Presentation (Adobe Flash: 37 minutes) and accompanying >slides (pdf)
- Module 1: ClinicalTrials.gov Overview and PL 110-85 Requirements
- Module 2: "Basic Results" Data Entry
- Module 3: Posted Results at ClinicalTrials.gov