Opportunities For Enhancing Signal Detection In Schizophrenia Trials

By David Daniel, MD., Joan Busner, PhD., and Alan Kott, MUDr

Schizophrenia clinical trials encounter significant challenges in signal detection due to a limited understanding of the disorder's biological mechanisms, inadequate trial designs, and difficulties in patient selection and efficacy endpoints. A major issue is the recent phase 3 trial failures despite successful phase 2 results. Rater performance is essential once a study is underway but poorly understood, with phase 3 trials often plagued by expectation bias and calibration issues across diverse sites and cultures. Data quality issues, even among trained investigators, result in inconsistencies during clinical trial visits. Effective rater training and calibration, including live actor interviews, can enhance precision and reduce placebo responses. The role of informants in rating scales is critical but often overlooked; inconsistent use can obscure results. Training should include both patients and informants to mitigate expectation bias.

Here we gain further insight into placebo response, complex rating scales, inconsistent rater performance, and data quality issues and their effects on schizophrenia trials.