Taking Clinical Research to the Next Level

For more than five decades, NIMH has supported high-quality clinical research on the efficacy of psychosocial, somatic, and pharmacological treatments. Randomized clinical trials have helped us identify effective interventions for nearly all mental disorders.

Despite these successes, however, questions remain as to how best to optimize these treatments and why these treatments work for some and not others. We still do not know who will respond to a specific treatment. Clinicians often must resort to trial and error before finding a treatment regimen that works, often subjecting patients to weeks of ineffective treatment or aversive side effects in the process. For individuals and families contending with a life-threatening illness, the delay can be torturous.

Last year, I asked our National Mental Health Advisory Council to help us consider how we could best develop new interventions. A workgroup of the Council met through the winter to discuss opportunities and challenges in treatment development. To inform the process, they developed an outstanding report, From Discovery to Cure: Accelerating the Development of New and Personalized Interventions for Mental Illness. Among their many suggestions was: (a) a call to develop the next generation of interventions, based on a better understanding of the disorders and (b) a call to optimize the use of current treatments based on a better understanding of individual differences in response. Studies of individual differences, based on biomarkers, personal history or clinical features, forge the path to personalized medicine.

In response to our Council’s recommendations, NIMH will increasingly focus its resources on personalized and preemptive medicine. Yes, we will continue to develop new treatments based on an emerging understanding of the pathophysiology of each disorder. Indeed, we are currently developing novel compounds in several therapeutic areas. But for existing treatments, we want to shift from trials studying group differences or adapting these treatments to yet another sub-population to support trials that identify reliable predictors (e.g. biomarkers) of individual response, including who may benefit from and who may experience adverse effects of a particular treatment. We are also searching for preemptive treatments—interventions that can be used early in the course of a disorder to prevent disability. For instance, we are testing cognitive remediation during the prodromal phase of schizophrenia to preempt or forestall psychosis.

Today’s treatments are not good enough. Based on the results in other areas of medicine, we should be able to do better. Our Council workgroup told us that the path to finding new treatments is long, expensive, and essential. But even with current treatments, we can do much better if we learn how to tailor these treatments to the needs of each individual. Going forward, NIMH will be looking for clinical trials that are personalized (using predictive biomarkers) or preemptive (focused on early intervention) to maximize public health impact.