Drug Evaluation Committee Covariate Adjustment of Randomized Controlled Trials Based on FDA Guidance
Data Science Subcommittee
June 2025
In 2023, the FDA issued the guidance "Adjusting for Covariates in Randomized Clinical Trials for Drugs and Biological Products. The guidance focuses on the treatment of baseline prognostic covariates, primarily to improve statistical efficiency in estimating and testing treatment effects. Improving statistical efficiency is an important topic, as it can contribute to increasing the probability of trial success through increased power and reducing the number of subjects required. Therefore, an understanding of this guidance will be beneficial not only to statisticians, but also to all development personnel involved in either planning, conducting, analyzing, or reporting clinical trials.
In this report, we have provided Explanation of the FDA Guidance, drawing on the ICH E9 and EMA guidelines that have been referenced in the past regarding covariate adjustment. Explanation of the guidance, including a Japanese translation, is provided in the main body of the report, and a Japanese translation excerpt has also been prepared as an Appendix. We hope that this report will help to improve the efficiency of clinical trials in the future.
Japan Pharmaceutical Manufacturers Association Drug Evaluation Committee
Data Science Subcommittee 2024 Task Force 3-1