The role of biomarkers in clinical development of drugs for neuropsychiatric disorders - A pragmatic guide

Abstract

The failure rate of drugs being developed for neuropsychiatric indications remains high. Optimizing drug discovery and development requires not only a better neurobiological understanding of disease aetiology and development, but also the means by which we can measure relevant biological and clinical processes related to disease progression, drug target engagement, and sensitivity to treatment. Here we address the role and key considerations for the selection of biomarkers in clinical drug development for neuropsychiatric disorders. We do not provide an exhaustive list of biomarkers; rather we lay out a pragmatic, well-defined biomarker selection strategy that addresses the main goals for each of the phases in the drug development cycle. We discuss the key questions and issues that concern biomarker selection and implementation in each phase of development. For the better development of biomarkers, we emphasize the need to focus on discrete biological dysfunction and/or symptom domains rather than diagnoses. We also advocate the use of biomarker-based patient stratification in phase 2 and 3 to increase sensitivity and power and reduce costs. Our aim is to enhance precision and chances of success for these complex and heterogeneous brain disorders with a high unmet medical need.