Precision clinical trials: a framework for getting to precision medicine for neurobehavioural disorders.

The goal of precision medicine (individually tailored treatments) is not being achieved for neurobehavioural conditions such as psychiatric disorders. Traditional randomized clinical trial methods are insufficient for advancing precision medicine because of the dynamic complexity of these conditions. We present a pragmatic solution: the precision clinical trial framework, encompassing methods for individually tailored treatments. This framework includes the following: (1) treatment-targeted enrichment, which involves measuring patients' response after a brief bout of an intervention, and then randomizing patients to a full course of treatment, using the acute response to predict long-term outcomes; (2) adaptive treatments, which involve adjusting treatment parameters during the trial to individually optimize the treatment; and (3) precise measurement, which involves measuring predictor and outcome variables with high accuracy and reliability using techniques such as ecological momentary assessment. This review summarizes precision clinical trials and provides a research agenda, including new biomarkers such as precision neuroimaging, transcranial magnetic stimulation-electroencephalogram digital phenotyping and advances in statistical and machine-learning models. Validation of these approaches - and then widespread incorporation of the precision clinical trial framework - could help achieve the vision of precision medicine for neurobehavioural conditions.

Informations de copyright

© 2021 Joule Inc. or its licensors

Déclaration de conflit d'intérêts

E. Lenze has received research support from NIH, the Patient Centered Outcomes Research Institute, the McKnight Brain Research Foundation, the Taylor Family Institute for Innovative Psychiatric Research and the Center for Brain Research in Mood Disorders (Department of Psychiatry, Washington University), the Barnes Jewish Foundation, MagStim, Aptinyx, Takeda, Acadia, and Lundbeck; he has served as a consultant for Janssen and Jazz Pharmaceuticals. G. Nicol has received research funding from NIMH, Otsuka America, Inc., Alkermes, the Center for Brain Research in Mood Disorders, the Center for Diabetes Translational Research, the Institute for Public Health and the McDonnell Center for Neuroscience at Washington University, and the Barnes Jewish Hospital Foundation. She also serves as a consultant for Sunovion, Alkermes and Supernus Pharmaceuticals, Inc. D. Barbour has received research support from the National Institute of Deafness and other Communication Disorders, the National Center for Advancing Translational Sciences, the National Science Foundation, the McDonnell Center for Systems Neuroscience, the Children’s Discovery Institute, the Center for Integration of Medicine and Innovative Technology, the Hope Center for Neurological Disorders, the Wallace H. Coulter Foundation, the American Hearing Research Foundation and the Skandalaris Center for Interdisciplinary Innovation and Entrepreneurship. Dr. Barbour has equity ownership in Bonauria, LLC. T. Kannampallil has research support from the Agency for Healthcare Research and Quality, the National Institute for Nursing Research and Pfizer. A. Wong has received research support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (National Center for Medical Rehabilitation Research), the National Institute on Disability, Independent Living, and Rehabilitation, and the Craig H. Neilsen Foundation. J. Piccirillo has received research funding from the National Institute on Deafness and Other Communication Disorders, Barnes Jewish Hospital Foundation and Bind On-Demand Health Care. C. Sylvester has received research support from NIMH, the McDonnell Foundation, the Brain and Behavior Research Foundation, the Taylor Family Foundation, and the Parker Fund. J.P. Miller has received research support from the Patient Outcomes Research Institute and NIH. S. Lenze has received research support from NIMH, the Center for Brain Research in Mood Disorders, the Barnes Jewish Hospital Foundation, the Center for Dissemination and Implementation (Washington University Institute for Public Health), and the McDonnell Center for Neuroscience. K. Freedland has research support from NIH and receives an editorial honorarium from the Society for Health Psychology (Division 38 of the American Psychological Association). T. Rodebaugh has received research support from NIMH, the National Institute on Deafness and other Communication Disorders, the Brain Behavior Research Foundation, and the McDonnell Center for Systems Neuroscience.