FDA Releases Final Guidance on Adjusting for Covariates in Randomized Clinical Trials

FDA released its final guidance concerning covariate adjustments in randomized clinical trials on May 30, 2023. The guidance, which applies to randomized, parallel group clinical trials for both drugs and biological products, focuses on the use of prognostic baseline covariates “to improve statistical efficacy for estimating and testing treatment effects,” according to an agency press release.

The guidance does not address use of covariates to control for confounding variables in non-randomized trials, in models to account for missing outcome data, or for analyzing longitudinal repeated measures data. Additionally, the use of Bayesian methods or machine learning methods for covariate adjustment is not addressed.