In October 2014, the National Institutes of Health (NIH) announced a change in its definition of a clinical trial, to take effect in January 2015. The new definition, which applies only to NIH-funded clinical trials, reads: “A research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include a placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.” At the time, few in the research community paid attention, but as the implementation begins, researchers are learning more about who will be affected.
NIH defines intervention as “a manipulation of the subject or subject’s environment for the purpose of modifying one or more health-related biomedical or behavioral processes and/or endpoints,” and health-related biomedical or behavioral outcome as “the pre-specified goal(s) or conditions(s) that reflect the effect of one or more interventions on human subjects’ biomedical or behavioral status or quality of life.”
These definitions both explicitly and implicitly encompass nearly all clinical, behavioral, cognitive, and educational research being conducted with human subjects, thus increasing the scope of research encompassed by the clinical trial moniker.
Subsequently, in September 2016 NIH introduced policies affecting the award, conduct, and reporting of NIH-funded clinical trials. These policies were released through both internal and external channels, with the stated – and laudable – goals of improving transparency and public trust in the clinical trials process. But many people were unaware of the new policies’ implications on studies previously not considered to be clinical trials.
First, the updated policy on registering and reporting results from NIH-supported clinical trials on the website Clinicaltrials.gov requires investigators to register their trials within three weeks of enrolling volunteers, and to submit trial results within one year of completion; this policy took effect in January 2017.
Second, also effective January 2017, all investigators and staff involved in any capacity with clinical trials must complete Good Clinical Practice training. Finally, beginning in January 2018, all grant applications proposing clinical trials must be submitted through clinical trial-specific Funding Opportunity Announcements (FOAs), as opposed to existing parent announcements.
Concerns from the Community
Because of the more inclusive language, NIH employed in its definition, most human subjects research now qualifies as a clinical trial. However, if a researcher’s work had not previously been categorized as a clinical trial, she likely would not have been attentive to a definition change or all the ensuing clinical trials policies. With two major policy changes in effect and implementation of another rapidly approaching, a lack of awareness still exists in the research community regarding these changes and their implications.
Some question if the new requirements make sense for non-traditional (e.g., exploratory, mechanistic, or observational) trials. Another cause of concern is whether the Clinicaltrials.gov website is capable of handling the increased data uploads and traffic that will result from the new registering and reporting requirements. And some wonder how the FOA policy will apply to investigators in the Small Business Innovation Research (SBIR) program or those funded through grant mechanisms intended to replace a researcher’s R01 portfolio (i.e., the R35). FASEB raised these various concerns with the NIH Office of Extramural Research.
NIH officials maintain that the community was given ample time to prepare for the changes, noting that the new clinical trial definition took effect in 2015, and the Notice of Proposed Rulemaking (NPRM) regarding the new registration and reporting requirements was released in 2014. FASEB responded to the NPRM, but did not foresee the inclusion of “basic” research in the clinical trial reporting regulations as an outcome of the proposal. Based on its response to an open sign-on letter and meetings with community stakeholders, NIH seems unlikely to change or delay implementation of clinical trial-related policies.
What This Means for You
If you conduct research with human subjects, visit the NIH decision tool to determine whether NIH considers your work to be a clinical trial – even if you do not. The answer has implications for your funding as well as for laboratory and administrative practices, as outlined above.
In addition to the decision tool, NIH has produced a video tutorial, Case Studies, and Frequently Asked Questions to help investigators better understand how the clinical trials definition and policies apply to their research. Other useful resources and explanations can be found on the NIH clinical trials webpage.
Be in close contact with your Program Officer (PO), who understands the nuances of the NIH clinical trial definition and implications for your research, and should be able to answer questions that the case studies and FAQs cannot.
Finally, familiarize yourself with the FOAs that pertain to your work. NIH recently released the parent announcements (PAs) for clinical trial eligible R01s and R21s, and while many Institutes are accepting applications through the PAs, some are not. Moreover, Institutes have been clarifying through Notices what kinds of research applications they will accept through the PAs, and will continue to release clinical trial-eligible, topical Requests for Applications.