DDT-COA-000-163 Accelerating the FDA COA Qualification Package for thePSYCHS as a ClinRO measure

ABSTRACT The Clinical High-Risk Syndrome for Psychosis (CHR-P) is a DSM-5-recognized condition affecting youth and young adults who experience attenuated delusions, hallucinations, and thought disturbances that, while subthreshold for full psychosis, are distressing and impair daily functioning. Attenuated Psychosis Syndrome (APS), listed under "Conditions for Further Study" in DSM-5, affects approximately 1.7% of the general youth population and nearly 20% of youth presenting to psychiatric services, yet remains under-recognized and poorly served by qualified assessment tools. Current clinical outcome assessments (COAs) for APS include the Structured Interview for Psychosis-Risk Syndromes (SIPS) and the Comprehensive Assessment of At-Risk Mental States (CAARMS). Differences between these instruments have historically hindered harmonization across research and clinical trials. In response, the National Institute of Mental Health led a harmonization effort that resulted in the Positive SYmptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS (PSYCHS), a semi-structured ClinRO instrument designed to assess 15 distinct attenuated positive symptoms organized into three general concepts: attenuated delusions, hallucinations, and thought disorder. There are currently no FDA-qualified COAs for measuring APS severity in CHR-P clinical trials, presenting a major obstacle to drug development. The PSYCHS is now implemented in the FNIH-funded AMP SCZ observational study and will be further evaluated in the upcoming ProCAN randomized controlled trial, which includes PSYCHS assessments, blinded raters, and ecological momentary assessment. These data provide a unique opportunity to establish the PSYCHS as a reliable and valid ClinRO for use in regulatory trials. The objective of this project is to develop a comprehensive Full Qualification Package (FQP) for the PSYCHS. We aim to: (a) engage the FDA to refine our Qualification Plan through ongoing consultation; (b) systematically evaluate content validity using input from clinicians, researchers, patients, and trainers; and (c) conduct preliminary qualitative and quantitative studies to assess test–retest reliability, recall periods, clinically meaningful change, and within-patient thresholds. The FQP will integrate data from previous studies, ongoing observational research, and a forthcoming clinical trial to support regulatory qualification of the PSYCHS instrument.