Drug Evaluation Committee Covariate Adjustment of Randomized Controlled Trials Based on FDA Guidance
June 2025
In 2023, the FDA issued the guidance document “Adjusting for Covariates in Randomized Clinical Trials for Drugs and Biological Products.” This guidance focuses on the treatment of baseline prognostic covariates, with the primary objective of improving statistical efficiency in estimating and testing treatment effects.Improving statistical efficiency is a critical topic that can contribute to increasing the probability of trial success through enhanced statistical power and reducing the required sample size. Therefore, understanding this guidance is considered beneficial not only for statisticians but also for all development personnel involved in any aspect of clinical trial planning, conduct, analysis, or reporting.
In this report, we provide an explanation of the FDA guidance while taking into account the content of the ICH E9 and EMA guidelines, which have been referenced regarding covariate adjustment. The main text of the report includes an explanation of the guidance, including a Japanese translation, and we have also prepared an appendix containing an excerpt of the Japanese translation only. We hope this report will contribute to improving the efficiency of future clinical trials.
Japan Pharmaceutical Manufacturers Association (JPMA) Drug Evaluation Committee
Data Science Subcommittee FY2024 Task Force 3-1