Public Law 110-85 (PDF - 549 KB) [also known as the FDA Amendments Act (FDAAA)], which was enacted on September 27, 2007 amends the Public Health Service Act to mandate registration and results reporting of “applicable clinical trials” (see Definitions) in ClinicalTrials.gov.

FDAAA also includes a requirement that if an “applicable clinical trial” is funded in whole or in part by a grant from any agency of the Department of Health and Human Services, any grant or progress report forms required under such grant shall include a certification that the Responsible Party (see Definitions) has made all required submissions for the applicable clinical trial to ClinicalTrials.gov.

The entity responsible for registering the trial is the “responsible party.” FDAAA requires “responsible parties” to register their “applicable clinical trials” and submit trial summary results to ClinicalTrials.gov.  Failure to comply with Title VIII of FDAAA can result in civil penalties and the withdrawal of NIH funding.  

Any applicable clinical trial with funding from the National Institutes of Health must be in full compliance with FDAAA.

This Web site seeks to help NIH awardees understand their roles and responsibilities in relation to FDAAA, and how to certify compliance.

1) Register NIH-supported Applicable Clinical Trials

“Applicable Clinical Trials” must be registered with ClinicalTrials.gov via a web based data entry system called the Protocol Registration System (PRS). The entity responsible for registering is the “responsible party.” 

If you are the responsible party, go to the ClinicalTrials.gov Protocol Registration System Information Web site and follow directions for registration of any and all “applicable clinical trials” included in the competing application or active grant.

The first step in the registration process is to obtain a ClinicalTrials.gov Protocol Registration System (PRS) organization or individual account. Many organizations already have accounts that house their investigators’ trials (check with your Institutional Official). A list of organizations with PRS accounts is available at http://prsinfo.clinicaltrials.gov/gettingOrgAccount.html.

Responsible parties are urged to fill in all applicable data elements and to make sure that the information is accurate.  It is particularly important that information about the responsible party and the expected completion date are correct. This information will enable ClinicalTrials.gov to send automated reminders about the need to report results data.

If you are not the responsible party, you should not register the trial. Instead, contact the responsible party to ensure that the responsible party registers the trial.  

The responsible party for the trial must register the trial before you certify compliance.

Not sure who is the responsible party? Investigators are encouraged to consult with their sponsored research office, institutional counsel, or other institutional officials to determine whether they are the responsible party for an applicable clinical trial.

In general, the law defines responsible party as the sponsor (as the term is defined in FDA regulations at 21 CFR 50.3) of the applicable clinical trial OR the Principal Investigator if so designated by the sponsor, grantee, contractor or awardee so long as the Principal Investigator is conducting the trial and has sufficient data rights in accord with the law.  Additional information on determining who is the responsible party for an applicable clinical trial is available at http://prsinfo.clinicaltrials.gov/ElaborationsOnDefinitions.pdf.

2) Include Required Information in your NIH Applications and Progress Reports Certifying Completion of the Required Submissions to ClinicalTrials.gov

For competing applications (new and renewal) that include applicable clinical trial/s: the NCT number/s, Brief Title/s (protocol title intended for the lay public) and the identity (name, organization) of the responsible party (or parties) and their contact information (e-mail address-required for internal administrative use only) must be provided in the Human Subjects section of the Research Plan under a section heading entitled ClinicalTrials.gov.  If a new applicable clinical trial is proposed, the Human Subjects section of the Research Plan should include a statement, under the heading ClinicalTrials.gov, that the application includes a trial which requires registration in ClinicalTrials.gov. The signature on the application of the Authorized Organizational Representative will assure compliance for the registration of any such trial.

When submitting a non-competing progress report for a project that includes applicable clinical trial/s that must be registered in ClinicalTrials.gov: clearly identify the NCT number/s, Brief Title/s (protocol title intended for the lay public), and the identity (name, organization) of the responsible party (or parties) and their contact information (e-mail address-required for internal administrative use only) in the Human Subjects section of the progress report under a section heading entitled ClinicalTrials.gov. If a new applicable clinical trial is proposed, provide a clear statement in the Human Subjects section of the progress report that the application includes a trial which requires registration in ClinicalTrials.gov. The signature on the non-competing continuation progress report of the Authorized Organizational Representative will assure compliance for the registration of any such trial.

• Name/Official Title - for either the principal investigator or sponsor contact
• Organization - the sponsor or the principal investigator's organizational affiliation
• Contact Information - [required for internal administrative use only; not revealed to public] provide telephone number and e-mail address

As required by FDAAA, responsible parties must submit basic results information for registered applicable clinical trials of FDA-approved drugs, biological products, and medical devices, not later than 1 year after the completion date of the trial, where “completion date” is defined as the date that the final subject was examined or received an intervention for the purpose of final collection of data for the primary outcome. Responsible parties may request extensions to the results reporting deadline via the ClinicalTrials.gov Protocol Registration System (PRS). They may also certify via the PRS that a later deadline for results reporting applies because they are seeking initial approval or approval of a new use for the drug, biological product, or device under study (see http://prsinfo.clinicaltrials.gov/DelayedSubmission.html). 

Five general categories of basic results information are required to be submitted to ClinicalTrials.gov:

1) Demographic and baseline characteristics of the patient sample (overall and by arm), including number dropped out of trial and number excluded from analysis (i.e., participant flow);

2) Primary and secondary outcomes (for each arm);

3) Serious and other (non-serious) frequent adverse events (number and frequency in each arm, grouped by organ system);

4) Point of contact for scientific information about the clinical trial results; and

5) Certain agreements that restrict the ability of the Principal Investigator to discuss or publish the results of the trial after trial completion.

A detailed list of the data elements to be submitted for basic results reporting can be found on the PRS Information Website at http://prsinfo.clinicaltrials.gov/results_definitions.html. Distinctions are made between those data elements that are required in order for the results record to be processed, those that must be submitted only in certain circumstances, and those that are optional. Additional Basic Results Database resources are available at http://prsinfo.clinicaltrials.gov/fdaaa.html. Basic results summary data will be publicly posted on ClinicalTrials.gov. See Results Reporting.

• Protocol Registration System (PRS) and Public Law 110-85
• About ClinicalTrials.gov
• Public Meeting on U.S. Public Law 110-85 held on April 20, 2009 by the NIH to receive public input on the expanded registry and results data bank.

• NOT-OD-10-007 (10/23/2009) - Clarification of Registration in ClinicalTrials.gov According to Date of Initiation and Status as an “Ongoing” Trial
• NOT-OD-09-147 (09/04/2009) - Clarification of NOT-OD-08-014 Regarding Obtaining Assistance from NIH for Registration and Reporting of Results in ClinicalTrials.gov
• NOT-OD-09-030 (12/11/2008) - Clarification of NOT-OD-08-014 and NOT-OD-08-023 Regarding Registration in ClinicalTrials.gov
• NOT-OD-08-023 (12/21/2007) - Clinical Trials Registration in ClinicalTrials.gov (Public Law 110-85): Competing Applications and Non-Competing Progress Reports
• NOT-OD-08-014 (11/16/2007) - Guidance on New Law (Public Law 110-85) Enacted to Expand the Scope of ClinicalTrials.gov: Registration

• The NIH Office of Extramural Research (OER) Frequently Asked Questions about Clinical Trial Registration in ClinicalTrials.gov
• ClinicalTrials.gov PRS (Protocol Registration System) Information site on registration of clinical trials, including PRS account application process.
• NLM Fact Sheet (PDF - 47 KB) on registration in ClinicalTrials.gov, including general requirements, timing of registration, and penalties for failure to register.

See Definitions. 

• NLM information on Basic Results Reporting, including the “Basic Results” Provisions (PDF - 14 KB) from FDAAA.
• NLM information on Adverse Event Reporting, including the Adverse Event Reporting Provision (PDF - 16 KB) from FDAAA

For general inquiries or comments related to the ClinicalTrials.gov Protocol Registration System (PRS), contact register@clinicaltrials.gov.

Additional questions about the ClinicalTrials.gov requirements may be directed to the NIH Office of Extramural Research at OEPmailbox@mail.nih.gov.