Adjusting for covariates in randomized clinical trials for drugs and biological products

Abstract

In May 2023, the US Food and Drug Administration released a guidance document on adjusting for covariates in randomized clinical trials for drugs and biological products. This article provides a summary of motivations for the US Food and Drug Administration guidance document, recommendations in the guidance document, considerations for covariate adjustment in large trials and small trials, and additional topics beyond the scope of the guidance document that may benefit from greater consensus on best practices. A covariate-adjusted prespecified primary analysis can have advantages over an unadjusted analysis and is generally acceptable to the US Food and Drug Administration.