Questions and Answers on the NIH FDAAA Policy

Please note that the following information is a DRAFT and has not yet been fully approved by the Office of Intramural Research (OIR).

The new NIH Policy on Food and Drug Administration Amendments Act (FDAAA) requirements applied to extramurally funded Clinical Trials also applies to the IRP. Although there are similarities in the proposed changes to FDAAA listed in the Notice of Public Rule Making (NPRM), there are distinct differences.

1. Why was the draft policy developed?
   The policy was developed to increase the transparency of NIH-funded clinical trials. Public access to clinical trial information drives scientific progress and optimizes the return on the nation’s investment in clinical trials. It helps inform future research, improve study design, and prevent duplication of unsafe and unsuccessful trials. Dissemination of positive and negative clinical trial results can also inform patient care. In addition, there is an important ethical dimension to dissemination of clinical trial results because individuals who volunteer to participate in such studies, and who may assume risks, trust that what we learn will contribute to generalizable knowledge about human health. Finally, enhancing transparency also increases public trust in clinical research.
   The policy will ensure for that all NIH-funded clinical trials, whether funded through grants, contracts, or the intramural research program, are held to the same high standard for registration and results reporting as those subject to Food and Drug Administration Amendments Act (FDAAA). Recent studies have added to a growing body of evidence that an unacceptable number of NIH-funded clinical trial results are not being published. The policy provides another avenue for investigators to disseminate their results.
2. How is the draft policy different from the FDAAA NPRM?
   The draft policy applies to all NIH-funded awardees and investigators conducting clinical trials, funded in whole or in part by NIH, regardless of the study phase, or type of intervention. The FDAAA Notice of Public Rule Making (NPRM) applies only to applicable clinical trials, whether NIH-funded or not. However, the draft policy is also complementary in that it will expect investigators to submit the same type of registration and results information and in the same timeframes as investigators subject to the law.
3. Why are you issuing this as a policy not a regulation?
   A policy approach is standard for NIH, and we have used it before to promote broad access to research results. Examples include the NIH Data Sharing Policy, Model Organism Sharing Policy, and Genomic Data Sharing Policy.
4. The draft policy says that NIH “expects” investigators to register and submit results to ClinicalTrials.gov. Why not make it a requirement? How will the expectation be enforced?
   While the policy is an expectation, once an applicant accepts NIH funding, policy expectations become a term and condition of award. We anticipate that the scientific community will recognize the value of registration and results submission and willingly fulfill the terms of the policy. However, should an investigator fail to meet reporting deadlines or to respond to efforts to remedy non-compliance, NIH may take enforcement actions, including termination of funding, consistent with 45 CFR 74.62 and/or other authorities.
5. Why does the draft policy require registration and results submission for phase 1 clinical trials? Why doesn’t the NPRM include phase 1 trials?
   There are a number of reasons why sharing clinical trial results is important, and they all apply to phase 1 trials as well as later stage trials (which generally involve more participants). Sharing information about phase1 trials has a particular ethical imperative given that they focus on assessing the safety of the intervention. The NPRM does not include phase 1 trials because FDAAA excludes them from the requirement. We recognize that private sector commercial interests must also be considered in the development of laws that apply across all types of funders and performers of research. Since the NIH policy applies only to NIH-funded investigators, those considerations do not apply in most situations.
6. Since the draft policy applies to phase 1 trials, but the NPRM does not, will the private sector have concerns about collaborating with NIH funded investigators in the development of new interventions?
   We don’t anticipate that the NIH Policy will discourage public-private partnerships. Considerable information about NIH-funded phase 1 trials is already in the public domain via our grants information system, and this transparency has not been an impediment to public-private partnerships. Also, most phase 1 trials are likely to involve unapproved products or new uses of approved products, and, if the sponsor intends to continue development, with an eye toward submitting a marketing application, they will have an opportunity to delay results submission as long as 3 years after the completion date of the trial. These time frames provide sufficient time to pursue any intellectual property filings deemed necessary. For clinical trials funded through SBIRs that are not subject to FDAAA, the timeframe for reporting results will follow the SBIR Policy Directive, which generally prohibits the agency from releasing SBIR data for at least four years from completion of the study unless the awardee consents to an earlier release. However, NIH will encourage SBIR awardees to adhere to the Policy’s reporting timeframes.
7. The draft policy applies to NIH-funded investigators “who have committed to NIH that they will comply with this policy.” How is this commitment obtained and documented?
   The commitment is reflected in the institutional official’s signature on applications to NIH, and is a term and condition of award that takes effect as soon as the awardee accepts NIH funds.
8. What will happen if an investigator fails to comply?
   We anticipate that the scientific community will recognize the value of registration and results submission and willingly fulfill the terms of the policy. While we do not anticipate the need for extensive enforcement actions, if an investigator fails to meet reporting deadlines or to respond to efforts to remedy non-compliance, NIH may take enforcement actions, including termination of funding, consistent with 45 CFR 74.62 and/or other authorities. Intramural investigators will be required to follow the policy, and there will be similar consequences for failing to do so, e.g., suspension of support. NIH-funded investigators who are out of compliance with the NIH policy will not, however, be subject to the civil monetary penalties in FDAAA unless they are also subject to FDAAA.
9. Why is the clinical trial definition in the NIH draft policy different from the definition in the FDAAA NPRM?
   The wording of the two definitions is slightly different because the NIH definition of clinical trial, which is what is used in the policy, more clearly reflects the scope of NIH-funded clinical trials. For example, NIH supports trials involving behavioral interventions. Behavioral interventions are not regulated by FDA and, therefore, are not subject to the registration and reporting requirements under FDAAA.
10. Who is responsible for registration and results submission under the NIH policy, the institution or the investigator?
    Both have responsibilities under the draft NIH policy. The investigator, who is responsible for the conduct of the trial and the data gathered from it, is responsible for carrying out the registration and results submission. The extramural institution that receives an award is accountable for ensuring that NIH policy expectations are fulfilled. An NIH funded trial that meets the definition of an applicable clinical trial described in the NPRM and is required to be registered or have results submitted under the NPRM must be registered and have results submitted by the responsible party, as that term is defined in the NPRM.
11. What effect does submission of results to ClinicalTrials.gov have on the ability to publish of the trial results?
    The submission of clinical trial results to ClinicalTrials.gov should have no effect on the ability to publish an analysis of the trial results in a scientific journal. The International Committee of Medical Journal Editors issued a policy in 2004 that requires registration of a clinical trial in a public registry, such as ClinicalTrials.gov, in order to be considered for publication. The ICMJE policy also encourages the posting of clinical trial results in public registries and states that a public posting of results will not be considered a prior publication of those results if they are presented in a structured format. See http://www.icmje.org/recommendations/browse/publishing-and-editorial-issues/clinical-trial-registration.html.
12. The draft policy does not spell out the details of what information should be submitted. How will investigators know what to submit?
    Clinical trials covered by the policy will be expected to submit the same type of registration and results data and in the same timeframes as the trials subject to FDAAA. The specific registration and results information to be submitted will be indicated at the ClinicalTrials.gov site.
13. When will the draft policy be finalized? What will the effective date be?
    The draft policy, like the NPRM, is being issued for a 90-day public comment period. NIH will consider the public comments before finalizing the policy. The effective date of the final Policy will be determined after the public comment process is completed.
14. We have heard investigators complain about how long it takes to submit their results to ClinicalTrials.gov. They say the database is hard to use. Shouldn’t the database be redesigned before moving forward with this policy?
    The data submission system is undergoing important upgrades, and additional resources are being devoted to improving the data submission process to streamline the data submission task. These improvements will be helpful to current users as well as investigators who will be expected by the policy to submit results. While we know that summarizing clinical trial results is not always a simple task, it is important that those results be made available for all of NIH-funded clinical trials.