Adjusting for Covariates in Randomized Clinical Trials for Drugs and Biological Products Draft Guidance for Industry May 2021
Not for implementation. Contains non-binding recommendations.
- Docket Number:
- Issued by:
Guidance Issuing OfficeCenter for Drug Evaluation and ResearchCenter for Biologics Evaluation and Research
This guidance represents FDA’s current thinking on 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 factors to improve precision for estimating treatment effects rather than the use of predictive biomarkers to identify groups more likely to benefit from treatment. This guidance does not address use of covariates to control for confounding variables in non-randomized trials or the use of covariate adjustment for analyzing longitudinal repeated measures data.
This guidance revises the draft guidance for industry Adjusting for Covariates in Randomized Clinical Trials for Drugs and Biologics with Continuous Outcomes issued in April 2019. This revision provides more detailed recommendations for the use of linear models for covariate adjustment and also includes recommendations for covariate adjustment using nonlinear models.
You can submit online or written comments on any guidance at any time (see 21 CFR 10.115(g)(5))
If unable to submit comments online, please mail written comments to:
Food and Drug Administration
5630 Fishers Lane, Rm 1061
Rockville, MD 20852
All written comments should be identified with this document's docket number: FDA-2019-D-0934.