Notice Number: NOT-OD-08-023
Update: The following update relating to this announcement has been issued:
Release Date: December 21, 2007
National Institutes of Health (NIH), (http://www.nih.gov)
Recent legislation has expanded the scope of ClinicalTrials.gov (see NOT-OD-08-014). This notice provides information to NIH applicants and grantees on new responsibilities related to registration of their “applicable clinical trials” in ClinicalTrials.gov.
New Law Enacted to Expand ClinicalTrials.gov:
Public Law 110-85 (also known as the FDA Amendments Act), which was enacted on September 27, 2007 [http://frwebgate.access.gpo.gov/cgi-bin/getdoc.cgi?dbname=110_cong_public_laws&docid=f:publ085.110.pdf] amends the Public Health Service Act to mandate registration and results reporting of “applicable clinical trials” (see below) in ClinicalTrials.gov. This legislation 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 shall include a certification that the responsible party has made all required submissions for the applicable trial to ClinicalTrials.gov.
Which Trials Must be Registered and Certified in Grant Applications and Progress Reports?
Under the statute, the “applicable clinical trials” trials generally include:
(1) Trials of Drugs and Biologics: Controlled, clinical investigations, other than Phase 1 investigations, of a product subject to FDA regulation;
(2) Trials of Devices: Controlled trials with health outcomes, other than small feasibility studies, and pediatric postmarket surveillance.
How To Determine If This Applies To Your Research?
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) [ http://a257.g.akamaitech.net/7/257/2422/14mar20010800/edocket.access.gpo.gov/cfr_2003/aprqtr/pdf/21cfr50.3.pdf], or
(2) the principal investigator of such clinical trial if so designated by a sponsor, grantee, contractor, or awardee (provided that “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” for submitting information under the law.) [http://frwebgate.access.gpo.gov/cgi-bin/getdoc.cgi?dbname=110_cong_public_laws&docid=f:publ085.110.pdf] See PL 110-85, Section 801(a), (adding new 42 U.S.C. 282(j)(1)(A)(ix)).
Investigators are encouraged to consult with their sponsored research office, institutional counsel, or other institution officials to determine if they are the responsible party for registering a trial. It is the applicant or grantee’s responsibility to determine if they are obligated to register their clinical trials under this legislation. For NIH-funded clinical trials where there is an IND holder, consistent with FDA regulations, the IND holder is the sponsor, and will be considered the responsible party unless this obligation is delegated to the principal investigator. For NIH-funded clinical trials where there is no IND holder, the funding recipient will be considered the responsible party.
When Must I Register My Trial?
1) Trials initiated after 9/27/2007, or trials initiated before that date and ongoing on 12/26/2007 that involve a “serious or life threatening disease or condition,” must be registered in full by: the later of 12/26/2007 or 21 days after the first patient is enrolled.
2) Trials that were initiated before 9/27/07 that are “ongoing” as of 12/26/2007, and which do not involve a “serious or life threatening disease or condition,” must be registered by 9/27/2008.
3) Trials that were initiated before 9/27/07 and are “ongoing” as of 12/26/2007, which do involve a “serious or life threatening disease or condition,” and are completed (meaning, not “ongoing”) by 12/26/2007 are not subject to these requirements, though they may be subject to pre-existing registering requirements.
(“Ongoing” in this context means a trial had one or more patients enrolled, but had not reached its “completion date,” meaning, examined the final subject or provided the final subject an intervention for the purposes of final collection of data for the primary outcome as of 9/27/2007.)
How are Trials Registered?
To register go to the ClinicalTrials.gov Protocol Registration System Information Website (http://prsinfo.clinicaltrials.gov/) and follow directions for registration of any and all “applicable clinical trials” included in the competing application or active grant. A unique identifier, called an “NCT” number, will be generated during the registration process,
What Needs To Be Included In Grant Applications And Progress Reports To Provide Certification?
For competing applications (new and renewal) that include applicable clinical trial/s: the NCT number/s, Brief Title/s (as defined by ClinicalTrials.gov, see http://prsinfo.clinicaltrials.gov/definitions.html), and the identity of the responsible party (or parties) must be provided in the Human Subjects Section of the Research Plan. If a new applicable clinical trial is proposed, the human subjects section of the research plan should include a statement that the application includes a trial which requires registration in ClinicalTrials.gov. The signature on the application of the Authorized Organizational Representative will now also assure compliance for the registration of any such trial.
When submitting a non-competing progress report that includes applicable trial/s: NCT number/s, Brief Title/s (as defined by ClinicalTrials.gov, see http://prsinfo.clinicaltrials.gov/definitions.html), and the identity of the responsible party (or parties) are to be included in the Human Subjects section of the progress report.
When Does The Requirement to Report Trial Registration Go Into Effect?
Competing applications: All applications submitted to the NIH on or after January 25, 2008, which incorporate an applicable clinical trial in their proposed project, are required to provide the information as detailed above.
Non-competing progress reports: All progress reports for grants which include an applicable clinical trial with budget start dates of April 1, 2008 or later are required to provide the information as detailed above.
What Are The Penalties For Failing To Register An “Applicable Clinical Trial?”
Penalties for responsible parties who fail to register, or provide the assurance described above to the NIH, or who submit false or misleading information in connection with “applicable clinical trials” are significant, and may include civil monetary penalties and, for federally-funded trials, the withholding or recovery of grant funds. See PL 110-85, Sections 801(a), (b), (adding new 42 U.S.C. 282(j), and new 21 U.S.C. 331(jj)). NIH will verify that each “applicable clinical trial” for which the grantee is the responsible party has been registered in ClinicalTrials.gov.
Obtaining Assistance from NIH:
You may register your trial directly by following the procedures outlined at http://prsinfo.clinicaltrials.gov/.
Alternatively, you may request registration assistance from an NIH Institute or Center (IC), in which case you are responsible for ensuring that all necessary information is provided to the IC in sufficient time to review and coordinate before the statutory deadlines described above for submission to ClinicalTrials.gov are triggered. You will need to stay in contact with the IC liaison to ensure that your information has been registered properly. Submission of registration information to an IC is not sufficient to satisfy the statutory obligations for submission to ClinicalTrials.gov. You remain legally responsible for submission of information to ClinicalTrials.gov in accord with all applicable legal mandates.
For additional information please see FAQ: https://grants.nih.gov/ClinicalTrials_fdaaa/faq.htm
Inquiries regarding this Notice should be directed to:
Office of Extramural Programs
Office of Extramural Research
National Institutes of Health