On July 20, 2018, the NIH released Guide Notice NOT-OD-18-212, “Delayed Enforcement and Short-Term Flexibilities for Some Requirements Affecting Prospective Basic Science Studies Involving Human Participants.” For “prospective basic science studies involving human participants” that the NIH considered as meeting its revised definition of a clinical trial for the purposes of its clinical trials policies, this notice provides the following flexibilities until September 24, 2019, during which time the NIH will assess its approach to registration and reporting for these studies and seek feedback from the research community on its registration and reporting requirement for these studies:
- Registration and Reporting: NIH will delay enforcement of its policies that investigators register and report their studies in clinicaltrials.gov. Basic research studies involving human participants are still expected to register and report their studies, but with the additional flexibility of doing so in registration and reporting portals other than clinicaltrials.gov.
- Study-Type Specific FOAs: NIH has instituted a period of leniency for applications submitted to the incorrect FOA based on study-type designation (e.g., clinical trials required, clinical trials optional, clinical trials not allowed). NIH will not administratively reject any applications submitted to an incorrect study-type FOA, and applications will be reviewed based on the review criteria of the FOA to which they are submitted.
The NIH, however, continues to expect all personnel involved in the conduct, oversight, or management of prospective basic research studies involving human participants to obtain Good Clinical Practice (GCP) training. OBSSR provides access to behaviorally oriented GCP training developed by the University of Michigan CTSA. There is also no change to the previously published review criteria.
NIH also plans to issue FOAs specifically for prospective basic science studies involving human participants. These FOAs are anticipated to be published in November 2018 with due dates beginning January 25, 2019. Therefore, those submitting on or after the February 2019 due dates will have FOAs specifically designed for these prospective basic science studies with humans.
All studies meeting the NIH definition of a clinical trial that do not meet the definition of a prospective basic science study involving human participants are expected to continue to comply fully with the clinical trials policies. To illustrate this point with a behavioral science example, if you are proposing a study to evaluate the effects of a stress management program to prevent or treat hypertension, you must continue to comply with the clinical trials policies. If, however, you are experimenting or manipulating brain, behavioral, and/or social processes hypothesized to increase or decrease psychosocial stress in humans or are manipulating processes by which stress influences blood pressure in humans, then during this interim period until Sept 24, 2019, you can register and report your study on alternative platforms other than clinicaltrials.gov if you wish, and will not have your application administratively withdrawn if you fail to submit it under a “clinical trials required” FOA.
Since confusion regarding definitions of scientific terminology is partly responsible for the need for the accommodations provided in this notice, some grounding for the term “prospective basic science studies with humans” seems appropriate. The NIH is basing this term on the definition of basic research in federal code (32 CFR 272.3), “the systematic study directed toward greater knowledge or understanding of the fundamental aspects of phenomena or of observable facts without specific applications towards processes or products in mind.” Clearly, most basic research funded by the NIH is not basic behavioral or social sciences research, but because basic behavioral and social sciences research is conducted predominately with humans, these clinical trials policies affected most of this basic research community. The definition of basic research (32 CFR 272.3) was generated for the Department of Defense, but this definition also served as the basis for the basic behavioral and social sciences research definition in the 2004 Report of the Working Group of the NIH Advisory Committee to the Director on Research Opportunities in the Basic Behavioral and Social Sciences, so its relevance to all basic research, including behavioral and social sciences research, seems appropriate.
“Prospective” refers to the “prospectively assigned” criterion from the NIH clinical trials definition. In prior blogs and in a Nature Human Behaviour commentary, I have described these as “experimental basic studies with humans”. Essentially, observational studies in which the human participants are not prospectively assigned to a condition, or the independent variables are not manipulated by the researcher, have been excluded consistently from the clinical trials policies and are not considered “prospective basic science studies involving humans.” However, if the study is designed prospectively to manipulate an independent variable in humans for understanding fundamental aspects of some phenomenon, then the study is a “prospective basic science study involving humans.”
Over the next few months, the basic behavioral and social science research community, and the basic science community more broadly, will have the opportunity to provide input on the NIH policies for these prospective basic science studies involving humans. Next month, NIH anticipates releasing an RFI requesting input on the registration and reporting of prospective basic science studies with humans. The NIH also has committed to community engagement in refining the FOAs for these prospective basic science studies with humans. The coming months will be an important time for the research community to work with the NIH on these issues, and I encourage all of you affected by these policies to provide constructive feedback that will address the concerns of the basic science community while ensuring appropriate registration, reporting, and NIH monitoring of studies involving the experimental manipulation of variables in humans.