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GUIDANCE DOCUMENT

Adjusting for Covariates in Randomized Clinical Trials for Drugs and Biological Products May 2023

Download the Final Guidance Document Read the Federal Register Notice
Final Level 1 Guidance
Docket Number:
FDA-2019-D-0934
Issued by:
Guidance Issuing Office
Center for Drug Evaluation and Research
Center for Biologics Evaluation and Research

This guidance describes FDA’s current recommendations regarding adjusting for covariates in the statistical analysis of randomized clinical trials in drug development programs. This guidance provides recommendations for the use of covariates in the analysis of randomized, parallel group clinical trials that are applicable to both superiority trials and noninferiority trials. The main focus of the guidance is on the use of prognostic baseline covariates to improve statistical efficiency for estimating and testing treatment effects. This guidance does not address use of covariates to control for confounding variables in non-randomized trials, the use of covariates in models to account for missing outcome data (National Research Council 2010), the use of covariate adjustment for analyzing longitudinal repeated measures data, the use of Bayesian methods for covariate adjustment, or the use of machine learning methods for covariate adjustment.

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All written comments should be identified with this document's docket number: FDA-2019-D-0934.

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