Clinical trials VS Research

NIMH has been in the spotlight lately for proposing the Research Domain Criteria or RDoC, a new framework for classifying mental disorders. One of the aims of RDoC is to help refocus clinical research, aligning it with what we are learning from biological, cognitive, and social science. This week, we are taking the first step in an initiative that, like RDoC, aims to realign research—but this time, the target is treatment development, an area in which progress has been frustratingly slow. In a series of funding announcements released this week, NIMH is making three important changes to how we will fund clinical trials.

First, future trials will follow an experimental medicine approach in which interventions serve not only as potential treatments, but as probes to generate information about the mechanisms underlying a disorder. Trial proposals will need to identify a target or mediator; a positive result will require not only that an intervention ameliorated a symptom, but that it had a demonstrable effect on a target, such as a neural pathway implicated in the disorder or a key cognitive operation. While experimental medicine has become an accepted approach for drug development, we believe it is equally important for the development of psychosocial treatments. It offers us a way to understand the mechanisms by which these treatments are leading to clinical change. Moreover, a subset of the funding announcements will support clinical trials that evaluate the effectiveness or increase the clinical impact of pharmacological, somatic, psychosocial, rehabilitative, and combination interventions.

Second, future trials will need to meet new standards for efficiency, transparency, and reporting. In an accompanying article, Changing NIMH Clinical Trials: Efficiency, Transparency, and Reporting Nitin Gogtay, NIMH Associate Director for Clinical Research, and I review the clinical trials portfolio at NIMH for each of these measures. Recent performance in our clinical trials program is not acceptable: recruitment is too slow, registration in public databases is not consistent, and reporting takes too long to meet the needs of the public for better treatments. To respond to the public concern that “time matters, ” we will be establishing new requirements for timelines, trial registration, publication, and data sharing.