Request for Information (RFI): Registration and Results Reporting Standards for Prospective Basic Science Studies Involving Human Participants

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Background

Over the past six years, the 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:

In October 2014, the NIH issued a definition of clinical trials. In November 2014, the 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 Food and Drug Administration Amendments Act (FDAAA). The NIH received approximately 240 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, the NIH issued its policy on registration and reporting. At the same time, it issued policies to assure—as recommended by the U.S. Government Accountability Office—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 and interviews (e.g., in Nature Human Behavior). The 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 1,700 also list a study start date of after January 18, 2017, the effective date of the Final Rule and NIH policy. The 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 (RFI)

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. The 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. The 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.” The 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 the 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, the NIH recommends reviewing the ClinicalTrials.gov registration and results information submission requirements as described in the Protocol Registration and Results System (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 review criteria. Sections 9 and 10 of the PRS User’s Guide describe 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 PRS; contact register@clinicaltrials.gov to request access to the PRS Test system.

Responses

Responses to this RFI must be submitted electronically at https://grants.nih.gov/grants/rfi/rfi.cfm?ID=80.

Responses must be received by November 12, 2018.

Read the full RFI at Grants.NIH.gov.