In a blog last October, I described a series of policies recently released by the NIH to improve transparency and our stewardship of clinical trials. In that blog, I noted that the definition of a clinical trial was being interpreted broadly, and that most research with humans that involved a prospective experimental manipulation of an independent variable likely would fall under these policies. With further guidance from the NIH Office of Extramural Research and in recently released case studies, it is clear that the intent of the NIH is to interpret the clinical trials definition broadly to include any NIH-supported study of humans that involves experimental manipulation (described as “prospectively assigned to one or more interventions” in the clinical trials definition).
Although the clinical trials definition and policies have produced considerable debate about what does or does not constitute a clinical trial, there is general agreement regarding the goals these policies are intended to achieve. The problem of unreported study results is well-documented. Taxpayers provide the funds to conduct these studies. Study participants donate their valuable time and accept both known and unknown risks, as well as unknown outcomes to help advance our understanding of health and disease. These groups rightly expect that their sacrifices benefit scientific progress. Minimally, this requires that the findings from the studies they support and participate in are communicated transparently and in a timely manner to the scientific community. Requiring the registration and reporting of human experimental research in clinicaltrials.gov ensures the transparent communication of research findings that study participants, our research colleagues, and the taxpayers deserve.
The other significant requirement of the clinical trials policies is that these studies submit their grant applications under a specific funding announcement that includes completion of a form that details the key aspects of the trial (participants, design, outcomes). This requirement will allow the NIH to track and report standardized data on the nature and types of clinical trials. Improved tracking, as well as procedures for monitoring and managing this research, will help the NIH be better stewards of the human experimental research we fund and manage.
Beyond requiring that grant applications are submitted under a specific funding announcement and that studies are registered and reported in clinicaltrials.gov, NIH requires that investigators whose research falls under the clinical trials definition complete Good Clinical Practice (GCP) training. In addition to standard GCP training available at most institutions, the Office of Behavioral and Social Sciences Research has made available the materials for a behaviorally oriented GCP training that was developed by the University of Michigan CTSA. Several professional organizations and academic institutions have incorporated these materials into their learning management system, and behavioral and social scientists should encourage their institutions to make this training available.
We have appreciated the input from the research community about treating research not traditionally considered clinical trials as clinical trials, and understand the concerns about attempting to fit basic mechanistic studies into policies that appear to be developed for traditional clinical trials. Behavioral and social science staff throughout the NIH, including our Behavioral and Social Sciences Coordinating Committee Work Group on Clinical Trials Policies, have been involved in various aspects of policy implementation to ensure that these policies fit the broad range of research subject to them. If we step back for a moment from the debate of what is or is not a clinical trial, what the NIH is requiring is that investigators conducting NIH-supported experimental studies with humans: (1) submit grant applications under a specific funding announcement with form fields that allow the NIH to more easily track these studies, (2) register the study in clinicaltrials.gov within 21 days of the first participant entering the study, (3) report the findings in clinicaltrials.gov within one year of the last participant completing the last assessment, and (4) take an online training in Good Clinical Practice (see https://grants.nih.gov/policy/clinical-trials.htm for more details and information on these requirements). Adequately powered, well-conducted experimental studies with humans in which the hypotheses and design are registered a priori and the findings reported regardless of the outcome will contribute to a more transparent, open, and cumulative science.
