Revised FDA Guidance on Covariate Adjustment in Trials

FDA has published a draft guidance, Adjusting for Covariates in Randomized Clinical Trials for Drugs and Biologics, to provide recommendations for using covariates in the analysis of randomized, parallel-group clinical trials that apply to both superiority trials and non-inferiority trials. The document says its main focus is on using prognostic baseline factors to improve precision for estimating treatment effects rather than using predictive biomarkers to identify groups more likely to benefit from treatment. It does not address using covariates to control for confounding variables in non-randomized trials or using covariate adjustment for analyzing longitudinal repeated measures data.

The draft revises a 4/2019 draft guidance by providing more detailed recommendations for using linear models for covariate adjustment and including recommendations for covariate adjustment using non-linear models.