Analyzing the Placebo Response and Identifying Influential Factors in Oral Medication Trials for Acute-Phase Schizophrenia

Abstract Background and Hypothesis This study aims to develop a placebo response and dropout rate model for acute-phase schizophrenia medication trials and assess factors affecting this response to inform future trial design. Study Design We conducted a literature update using a comprehensive meta-analysis of schizophrenia medication trials, focusing on oral placebo-controlled studies. We modeled the placebo response on the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impressions-Severity of Illness (CGI-S) scale over time and analyzed dropout rates. Influential factors were explored using covariate models and subgroup analyses. Study Results Aggregate-level data from 48 publications were analyzed. The placebo response reached a plateau at different weeks for PANSS and CGI-S scale scores. The lower the baseline of PANSS total score, older age, heavier body weight, a higher proportion of male or Black patients, smaller sample sizes, single-country trials, older studies, and the use of the Last Observation Carried Forward imputation were associated with a lower placebo response. Maximum response of PANSS Total score and gender significantly influenced dropout rates. Conclusions We present a model predicting placebo response in schizophrenia trials, offering insights into the impact of various trial characteristics, aiding in the design and interpretation of future clinical studies.