EVIDENT
Evidence-Based Validation & Innovation for Rapid Therapeutics in Behavioral Health

The Evidence-Based Validation & Innovation for Rapid Therapeutics in Behavioral Health (EVIDENT) program, aims to catalyze a new era in behavioral health by generating and validating objective FDA-ready clinical endpoints for emerging therapies, enabling rapid, personalized, and durable improvements in mental and behavioral health. By the end of the current effort, ARPA-H will produce gold-standard objective measures and a Rapid Response Data Repository to support future research and regulatory acceptance of emerging rapid-acting therapies. The current effort will enable better health outcomes through robust objective and predictive measures of intervention effects, improving the ability to identify when a specific therapy will be most effective and for whom, as well as monitoring rapid treatment effects when they are occurring. This will reduce the burden of mental illness, lower healthcare costs, and improve quality of life for millions of Americans. Commercially, the approach will drive new standards for drug development and clinical care, with broad public health impact. In addition, the current effort paves the way for gold-standard measurement and identification of mechanisms for other types of behavioral health interventions.

Current behavioral health endpoints are predominantly subjective and lack the temporal granularity needed to capture the onset and evolution of rapid-acting effects. Performers addressing TA1 will identify biological, digital, and physiological biomarkers of rapid clinical effects by leveraging multimodal data—including neuroimaging, digital phenotyping, and other biopsychosocial data collection—to monitor neuroplastic and clinical changes on a timescale of hours to days. Desired solutions will combine neuroimaging, wearable, and digital phenotyping data to establish measurable indicators of treatment response and recovery. The long-term goal is the ability to measure continuously, with minimally invasive and scalable technology, an indicator of behavioral health, be it a single biomarker or composite index of multiple biomarkers. Therefore, the goal for TA1 is to identify likely indicators for continuous behavioral health monitoring. Performers will discover new candidates for future clinical endpoints that reflect both immediate and sustained therapeutic impact.

The context and dynamics of therapeutic sessions are likely critical determinants of outcome but have not been systematically examined in existing research. Innovative, unobtrusive approaches to monitoring dyadic interactions between patient and facilitator are needed to discover interpersonal and therapy dynamics that increase effectiveness. TA2 performers will capture in-session data from patients, facilitators (e.g., therapists, guides, monitors), and/or the environment (e.g., setting, lighting, temperature) to enable identification of real-time predictors of clinical change. Desired solutions will use unobtrusive sensors, EEG, and/or behavioral analytics to map predictors of clinical effectiveness during treatment sessions. EEG in-session is encouraged, but proposals must describe an unobtrusive set-up and ability to collect data from locations of primary interest for examining neural indicators of rapid effects.

Personalized behavioral health care requires prediction of both risk and long-term benefit from rapid-acting interventions. TA3 performers will integrate clinical, genetic, and biomarker to develop predictive models that determine: (1) who is at-risk for an adverse event, and (2) who is most likely to respond to treatment immediately and with a durable effect at 3-, 6-, and/or 12-months following treatment. TA3 performers will acquire and analyze existing data or augment existing protocols to collect and analyze data that incorporate multimodal data streams. TA3 performers may use extant or new data collection to generate actionable insights for treatment-matching, risk mitigation, and monitoring. The goal is to enable early identification of who will respond to a rapid-acting therapy, who has other underlying health factors that preclude specific interventions, and which intervention is indicated to achieve durable effects for a given individual.

The development of objective measures of mental health and wellbeing will require novel data collection: multimodal, longitudinal data (e.g., psychological, social, digital, biological) collected in the context of registered, interventional clinical trials testing the effects of rapid-acting treatments for behavioral health (i.e., neuroplastogens, neuromodulation). Awarded performers will deliver deidentified data and biological samples to an ARPA-H designated Data Repository. Data will be curated and stored within the ARPA-H designated Data Repository to enable and accelerate future discoveries. In-scope clinical trials are those actively assigning participants to any rapid-acting treatment with prior evidence of safety in humans and rapid clinical effects (i.e. within 1-2 weeks) for mental and behavioral health symptoms or disorders. Observational studies and Phase I safety trials are out of scope. Eligible clinical trials must incorporate one or more current FDA-approved clinical endpoints.

SOLICITATIONS

ID: ARPA-H-CXHUB-26-109 and ARPA-H-CXHUB-26-110

The ARPA-H CX Hub invites interested parties to review the solicitations below. The solicitations outline the opportunity and its requirements, key dates and deadlines, submission documents and templates, evaluation criteria for submissions, and information on how to apply.

Questions Due: December 12, 2025 5PM ET

Solution Summary Due: TA1-3 proposals are due on December 22, 1PM ET. TA4 proposals will be accepted on a rolling basis starting
November 25th.

Submission Portal Open: TA4 estimated November 25, 2025, TA1-3 estimated December 11, 2025

Proposers’ Day on December 10, 2025

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Frequently Asked Questions

Interested proposers should submit any questions to the appropriate inbox.

Deadline for questions is 5PM ET, Friday, December 12, 2025.

Contractual Questions: arpa-h-cx-hub-contracts@ati.org

Technical and membership questions: arpa-h-cx-hub@ati.org