Toward actionable biomarkers in psychiatry: a collaborative roadmap for precision clinical trials. An ACNP position paper
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.
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BibTeX
@article{khalsa2026toward,
title = {{Toward actionable biomarkers in psychiatry: a collaborative roadmap for precision clinical trials. An ACNP position paper}},
author = {Sahib S Khalsa and Deanna Barch and Linda S Brady and Teresa Buracchio and William A Carlezon and Christopher Chatham and Wayne C Drevets and C. Neill Epperson and Amit Etkin and Bernard Fischer and Danielle L Graham and Steven C Hoffmann and Bashkim Kadriu and Martien J H Kas and Hartmuth Kolb and Marion Leboyer and Sarah H Lisanby and Lauren Liss and Husseini K Manji and Valentina Mantua and Hugh M Marston and William Potter and Frank Yocca and Kerry J Ressler},
journal = {NPP—Digital Psychiatry and Neuroscience},
year = {2026},
month = sep,
doi = {10.1038/s44277-026-00069-w},
url = {https://inserm.hal.science/inserm-05803569v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Toward actionable biomarkers in psychiatry: a collaborative roadmap for precision clinical trials. An ACNP position paper
AU - Sahib S Khalsa
AU - Deanna Barch
AU - Linda S Brady
AU - Teresa Buracchio
AU - William A Carlezon
AU - Christopher Chatham
AU - Wayne C Drevets
AU - C. Neill Epperson
AU - Amit Etkin
AU - Bernard Fischer
AU - Danielle L Graham
AU - Steven C Hoffmann
AU - Bashkim Kadriu
AU - Martien J H Kas
AU - Hartmuth Kolb
AU - Marion Leboyer
AU - Sarah H Lisanby
AU - Lauren Liss
AU - Husseini K Manji
AU - Valentina Mantua
AU - Hugh M Marston
AU - William Potter
AU - Frank Yocca
AU - Kerry J Ressler
PY - 2026
DA - 2026/09/18
JO - NPP—Digital Psychiatry and Neuroscience
DO - 10.1038/s44277-026-00069-w
UR - https://inserm.hal.science/inserm-05803569v1
AB - 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.
SN - 2948-1570
SN - 2948-1570
ER -