Toward actionable biomarkers in psychiatry: a collaborative roadmap for precision clinical trials. An ACNP position paper

Abstract

Abstract Psychiatric drug development remains constrained by diagnostic heterogeneity, insufficient and inconsistent drug response, high placebo response rates, and the absence of validated biomarkers that can reliably guide patient stratification, trial design, and regulatory decision-making. Despite substantial advances in neuroscience, few biomarkers in psychiatry have progressed beyond exploratory use, limiting the translation of mechanistic insights into effective therapeutics. The process of implementing biomarkers in psychiatry requires new levels of organization and coordination across many stakeholders, each with their own priorities. To date, however, no comprehensive roadmap exists to align scientific, regulatory, clinical, and commercial stakeholders around the development and implementation of predictive biomarkers in psychiatry. This position paper, developed by the American College of Neuropsychopharmacology (ACNP) Precompetitive Stakeholder Task Force and informed by work from the European College of Neuropsychopharmacology (ECNP) on the Precision Psychiatry Roadmap, brings together key stakeholders to begin the process of engaging in coordinated efforts. By integrating scientific, regulatory, and commercial perspectives, we clarify biomarker definitions and contexts of use, review current FDA regulatory pathways and gaps, and synthesize lessons from real-world examples. We highlight emerging biomarker modalities including fluid-based, digital, electrophysiological, neuroimaging, and multimodal approaches, and propose strategies to de-risk their adoption through standardized platforms, early regulatory engagement, and scalable trial designs. Emphasis is placed on precompetitive collaboration, large-scale data harmonization, and stakeholder alignment to accelerate reproducibility, regulatory interpretability, clinical utility, and improved use of experimental systems. This roadmap identifies actionable strategies to advance biomarker-enabled precision psychiatry and nurture cooperation, which will accelerate therapeutic innovation and improve clinical outcomes.