Over the past six years, the National Institutes of Health (NIH) has considered, developed, issued, and begun to implement policies designed to enhance transparency and oversight of the clinical trials it conducts or funds. These policies addressed two overarching problems:
- Many investigators who conduct NIH-funded clinical trials fail to publicize their trials’ main results, in a timely manner (e.g. within two years of completion). This serious under-reporting problem was first noted in 2012, was confirmed in 2013, and was confirmed again in 2016. Furthermore, it appears that the problem is particularly serious for those trials which don’t focus on classic “clinical” endpoints (like death or heart attack).
- As an agency, NIH fails to collect and consider the minimum data about trials needed for it to act as an effective steward of precious taxpayer funds.
In October 2014 NIH issued a definition of clinical trials. In November 2014, NIH issued a proposed policy to require registration and reporting in ClinicalTrials.gov of all trials it funds, not just those trials covered under the FDAAA. NIH received ~240 comments, comments from individuals, organizations, and societies (including the Federation of American Societies of Experimental Biology which represents over 100,000 basic scientists). In September 2016 NIH issued its policy on registration and reporting. At the same time, it issued policies to assure, as recommended by the GAO, proper oversight of trials; these policies covered processes affecting applications and training.
Since September 2016 the NIH has taken steps to communicate its clinical trials policies. These steps include the original Federal Register notice, multiple blogs, posts in the NIH Guide, published articles in high-circulation medical journals, dedicated web pages, presentations at major meetings, and published articles / interviews (e.g. in Nature Human Behavior).
NIH recognizes that not all studies that meet the definition of “clinical trial” are “clinical,” that is a study that occurs within a clinical environment or that tests a clinical intervention (like a drug or implanted device). For example, some trials test public health interventions (like programs to enhance physical activity in schools) which occur entirely outside the clinical sphere. Other trials are aimed at answering basic science questions; in other words, they are conducting prospective experiments on human participants without any specific applications towards processes or products in mind. As of August 1, 2018, ClinicalTrials.gov contains 10,199 interventional study records listing "basic science" as the primary purpose. Of those, over 1700 also list a study start date of after January 18, 2017, the effective date of the Final Rule and NIH policy.
NIH recognizes that there is concern about applying its registration and reporting policy (as described in the Federal Register on September 21, 2016) to research studies that meet the NIH definition of clinical trials as described here and meet the definition for basic research, but do not meet the FDAAA definition of “applicable clinical trials.” Basic research is “systematic study directed toward greater knowledge or understanding of the fundamental aspects of phenomena and of observable fact without specific applications towards processes or products in mind.” We have designated basic research studies that meet the NIH definition of a clinical trial as “prospective basic science studies involving human participants.”
Request for Information
This RFI seeks additional input from stakeholders throughout the scientific research community and the general public regarding how best to implement the NIH Policy on the Dissemination of NIH-Funded Clinical Trial Information (NOT-OD-16-149) for prospective basic science studies involving human participants. NIH is specifically interested in learning more about studies that meet the NIH definition of a clinical trial (NOT-OD-15-015) but are not defined as applicable clinical trials (42 CFR Part 11), and also meet the definition of fundamental research.
NIH is equating “fundamental research” as stated in the 2018 appropriations act with “basic research” as defined in 32 CFR 272.3 as a “systematic study directed toward greater knowledge or understanding of the fundamental aspects of phenomena and of observable facts without specific applications towards processes or products in mind.” NIH is considering prospective basic science studies involving human participants to be those that overlap with both the definition of fundamental research and the definition of a clinical trial.
The NIH seeks comments on any of the following topics:
- Specific examples of prospective basic science studies involving human participants that pose the greatest challenges in meeting the registration and results information submission requirements at ClinicalTrials.gov, including specific reasons for these challenges (e.g., specific data elements);
- Strengths and weaknesses of potential alternative platforms that might function as conduits for timely registration and reporting of prospective basic science studies involving human participants;
- Additional data elements or modification to existing data elements that could be applied to ClinicalTrials.gov to better meet the needs of the public and of researchers in assuring timely registration and results information submission of prospective basic science studies involving human participants;
- Other existing reporting standards for prospective basic science studies involving human participants and how such standards would fulfill the aims described in the NIH Policy on the Dissemination of NIH-Funded Clinical Trial Information; and
- Any other point the respondent feels is relevant for NIH to consider in implementing this policy for timely registration and reporting of prospective basic science studies involving human participants.
To inform comments on this RFI, NIH recommends reviewing the ClinicalTrials.gov registration and results information submission requirements as described in the PRS User’s Guide. The guide provides an overview of the submission process and requirements for registration and results data elements, validation rules, as well as the quality control (QC) review criteria. Sections 9 and 10 of the PRS User’s Guide also describes how content can be transferred to ClinicalTrials.gov by the study sponsor or investigator using the XML upload mechanism. ClinicalTrials.gov requirements can be further explored using the test version of the Protocol Registration and Results System (PRS); contact email@example.com to request access to the PRS Test system.
Responses to this RFI must be submitted electronically at:
Responses must be received by November 12, 2018.