Abstract
Clinical trials are at the core of evidence-based medicine, but many are underpowered and fail to inform clinical practice. In mental health, the number of regulatory drug approvals has consistently lagged behind other areas of medicine, the effects of established therapies may vary, and comparative effectiveness data for available treatments are scarce. Thus, there is an urgent need for more efficient, faster and more collaborative ways of generating evidence. Traditional approaches of ‘one treatment, one trial’ are slow, inefficient, and limit comparability across trials. In contrast, platform trials use a shared infrastructure for many treatments, shared control group(s) and a master protocol that allows treatments to be added over time and ineffective ones to be dropped early. Here we present examples of platform trials in mental health (M-PACT, EU-PEARLDIVER, PUMA and RESiLIENT) and discuss their potential to increase speed, reduce operational costs and participant burden, and improve statistical power and comparability.
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Fig. 1: Examples of platform trial and master protocol designs in mental health.
Fig. 2: Efficiencies of a mental health platform trial with regard to sample size and statistical power.
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Authors and Affiliations
Department of Psychiatry, Charité – Universitätsmedizin Berlin, Berlin, Germany
Stefan M. Gold, Jelena Brasanac, Michaela Maria Freitag & Christian Otte
Medical Department, Section Psychosomatic Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
Stefan M. Gold
German Center for Mental Health (DZPG), Berlin, Germany
Stefan M. Gold & Christian Otte
Institut für Neuroimmunologie und Multiple Sklerose (INIMS), Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
Stefan M. Gold
Lived Experience Expert, Helsinki, Finland
Fanni-Laura Mäntylä
Mental Health Team – Translation, Wellcome Trust, London, UK
Kim Donoghue
Center for Medical Data Science, Institute of Medical Statistics, Medical University of Vienna, Wien, Austria
Franz König & Martin Posch
Department of Mental Health, Hospital Universitari Vall d’Hebron, Barcelona, Spain
J. Antoni Ramos-Quiroga
Vita-Salute San Raffaele University, Milan, Italy
Francesco Benedetti
Psychiatry & Clinical Psychobiology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy
Francesco Benedetti
Psychosis Research Unit, Aarhus University Hospital Psychiatry, Aarhus, Denmark
Ole Köhler-Forsberg
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
Ole Köhler-Forsberg
Department of Psychiatry, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands
Nina Grootendorst & Witte Hoogendijk
Institute of Psychiatry, Psychology and Neuroscience, Department of Psychological Medicine, Maurice Wohl Clinical Neuroscience Institute, King’s College London, London, UK
Carmine M. Pariante
National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London, London, UK
Carmine M. Pariante
Defense Health Agency Operational Medical Systems, Fort Detrick, MD, USA
Elyse R. Katz
Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Australia
Steve Webb
Kyoto University Office of Institutional Advancement and Communications, Kyoto, Japan
Belinda Lennox
Department of Psychiatry, University of Oxford, Oxford, UK
Toshi A. Furukawa
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Stefan M. Gold
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2. Fanni-Laura Mäntylä
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3. Kim Donoghue
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4. Jelena Brasanac
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Contributions
S.M.G. and C.O. developed the overall concept. S.M.G. wrote the first draft of the manuscript and Table 1. S.M.G., J.B., M.M.F., F.K., M.P., E.R.K. and T.A.F. prepared the figures. E.R.K., S.M.G., B.L. and T.A.F. wrote Box 1. F.-L.M. and K.D. wrote Box 2. F.-L.M., K.D., J.B., M.M.F., F.K., M.P., J.A.R.-Q., F.B., O.K.-F., N.G., W.H., C.M.P., E.R.K., S.W., B.L., T.A.F. and C.O. edited, reviewed and refined all versions of the manuscript.
Corresponding author
Correspondence to Stefan M. Gold.
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Competing interests
S.M.G. reports honoraria from Hexal, Angelini and Tegus. O.K.-F. reports honoraria for lectures for Lundbeck Pharma A/S and consultant work for WCG Clinical. J.A.R.-Q. was on the speakers’ bureau and/or acted as consultant for Biogen, Idorsia, Casen-Recordati, Janssen-Cilag, Novartis, Takeda, Bial, Sincrolab, Neuraxpharm, Novartis, BMS, Medice, Rubió, Uriach, Technofarma and Raffo in the last three years. He also received travel awards (air tickets and hotel) for taking part in psychiatric meetings from Idorsia, Janssen-Cilag, Rubió, Takeda, Bial and Medice. The Department of Psychiatry chaired by him has received unrestricted educational and research support from the following companies in the last three years: Exeltis, Idorsia, Janssen-Cilag, Neuraxpharm, Oryzon, Roche, Probitas and Rubió. C.P. reports consultation and speaker’s fees from Boehringer-Ingelheim, Eli Lilly, Compass, Eleusis, GH Research, Lundbeck and Värde Partners. T.A.F. reports personal fees from Boehringer-Ingelheim, Daiichi Sankyo, DT Axis, Kyoto University Original, Shionogi, SONY and UpToDate, a grant from DT Axis and Shionogi, patent 7448125 concerning use of machine learning in internet cognitive–behavioural therapy (iCBT), and a pending patent 2022-082495 about prediction models for depression relapse, and intellectual properties for Kokoro-app (a smartphone CBT app) licensed to Mitsubishi-Tanabe. C.O. reports honoraria for lectures and/or scientific advice from Boehringer-Ingelheim, Janssen, Neuraxpharm, Oberberg Kliniken, Peak Profiling and Limes Klinikgruppe. The remaining authors declare no competing interests.
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Gold, S.M., Mäntylä, FL., Donoghue, K. et al. Transforming the evidence landscape in mental health with platform trials. Nat. Mental Health (2025). https://doi.org/10.1038/s44220-025-00391-w
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Received:07 August 2024
Accepted:27 January 2025
Published:10 March 2025
DOI:https://doi.org/10.1038/s44220-025-00391-w
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