What is FDA’s Role Related to ClinicalTrials.gov?
The Food and Drug Administration Amendments Act of 2007 (FDAAA) requires that the “Responsible Party” for certain clinical trials register with, and submit the results information of some trials to, the ClinicalTrials.gov databank (www.ClinicalTrials.gov).
FDA has been given the following implementation and compliance/enforcement responsibilities related to Title VIII of FDAAA:
- Requiring a certification regarding compliance with ClinicalTrials.gov requirements to accompany certain human drug, biological product, and device applications and submissions to FDA.
- Requiring the inclusion of a particular statement in the informed consent documents for “applicable clinical trials” (trials that will be entered into the ClinicalTrials.gov databank as required by FDAAA).
- Compliance and enforcement activities related to the failure to submit required clinical trial information to ClinicalTrials.gov under HHS regulations at 42 CFR Part 11.
The operation and development of the ClinicalTrials.gov databank and the drafting of regulations related to the databank are the responsibility of the National Institutes of Health (NIH)/National Library of Medicine (NLM).
What Does FDA Require Regarding Certification?
To certify compliance with ClinicalTrials.gov requirements, FDA requires that applicants complete and submit Form FDA 3674 with certain human drug, biological product, and device applications and submissions. In general, FDA recommends that a Form FDA 3674 accompany the following applications and submissions to FDA:
- Investigational New Drug Application (IND)
- New Clinical Protocol Submitted to an IND
- New Drug Application (NDA)
- Efficacy Supplement to an Approved NDA
- Biologics License Application (BLA)
- Efficacy Supplement to an Approved BLA
- Abbreviated New Drug Application (ANDA)
- Premarket Approval Application (PMA)
- PMA Panel Track Supplement
- Humanitarian Device Exemption (HDE)
- 510(k) submissions that refer to, relate to, or include information on a clinical trial
Note – FDA does not require the submission of a Form FDA 3674 with an Investigational Device Exemption (IDE) application, as this was not required by FDAAA.
Instructions for completing Form FDA 3674 are located at http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM354618.pdf.
In addition, FDA has issued guidance related to Form FDA 3674 which may be found at http://www.fda.gov/RegulatoryInformation/Guidances/ucm125335.htm.
What Are the Informed Consent Requirements Related to ClinicalTrials.gov?
The following exact statement must be included in the informed consent documents of “applicable clinical trials”:
“A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. Law. This Web site will not include information that can identify you. At most, the Web site will include a summary of the results. You can search this Web site at any time.”
FDA has issued guidance related to this new informed consent element which can be found at http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM291085.pdf
Historical Background Information
The Food and Drug Administration Amendments Act of 2007 (FDAAA), Public Law 110-85 (September 27, 2007), amended the Public Health Service (PHS) Act and is designed, in part, to promote transparency of clinical research to trial participants and the public.
Title VIII of FDAAA amended the PHS Act by adding new section 402(j), 42 U.S.C. § 282(j). The new provisions require that additional information be submitted to the clinical trials data bank (www.ClinicalTrials.gov) previously established by the NIH/ NLM, including expanded information on clinical trials and information regarding the results of clinical trials.
HHS issued a final rule, which is codified at 42 CFR Part 11, as required by Title VIII of FDAAA, to clarify and expand the requirements for registering clinical trials and submitting results information. [September 21, 2016, 81 FR 64981]
A certification of compliance with ClinicalTrials.gov requirements is required by 42 U.S.C. § 282(j)(5)(B), section 402(j)(5)(B) of the PHS Act. The certification requirement went into effect on December 26, 2007. To assist sponsors, industry, researchers, and investigators in complying with the requirement, FDA created a certification form to be used to satisfy the certification requirement. This form is Form FDA 3674, OMB Control No. 0910-0616
As required by FDAAA, FDA published a final regulation (21 CFR § 50.25(c)) [January 4, 2011, 76 FR 256] amending the current informed consent regulations to require that informed consent documents and processes for applicable drug (including biological products) and device clinical trials include a specific statement that clinical trial information may be entered into the ClinicalTrials.gov databank. Compliance with this new requirement was effective on March 7, 2012.
ClinicalTrials.gov regulations (42 CFR Part 11) can be found at https://www.federalregister.gov/documents/2016/09/21/2016-22129/clinical-trials-registration-and-results-information-submission
Details of the statutory language of Title VIII of FDAAA can be found at http://www.gpo.gov/fdsys/pkg/PLAW-110publ85/pdf/PLAW-110publ85.pdf#page=82
NIH elaboration of definitions of “responsible party” and “applicable clinical trial” can be found at http://prsinfo.clinicaltrials.gov/ElaborationsOnDefinitions.pdf (NIH site)
FDA Guidance on Form FDA 3674 http://www.fda.gov/RegulatoryInformation/Guidances/ucm125335.htm
FDA Guidance on Informed Consent Element at 21 CFR 50.25(c) http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM291085.pdf
Questions Related to ClinicalTrials.gov
Any questions related to the following should be addressed to the ClincialTrials.gov staff at the NIH at NLM Helpdesk :
1. Regulations at 42 CFR Part 11
2. How to register studies and enter clinical trial results information
3. Technical issues related to submission of information to the ClinicalTrials.gov databank,
Questions and information (other than technical issues or complaints) related to compliance and enforcement of NIH ClinicalTrials.gov databank requirements can be addressed to FDA at email@example.com.
Complaints should be reported to the office handling the type of study involved. FDA contact information for complaints can be found at http://www.fda.gov/ScienceResearch/SpecialTopics/RunningClinicalTrials/ComplaintsrelatingtoClinicaltrials/default.htm.
Office of Good Clinical Practice
Office of Special Medical Programs
Food and Drug Administration
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