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August 2008 Handling Covariates in the Design of Clinical Trials
William F. Rosenberger, Oleksandr Sverdlov
Statist. Sci. 23(3): 404-419 (August 2008). DOI: 10.1214/08-STS269


There has been a split in the statistics community about the need for taking covariates into account in the design phase of a clinical trial. There are many advocates of using stratification and covariate-adaptive randomization to promote balance on certain known covariates. However, balance does not always promote efficiency or ensure more patients are assigned to the better treatment. We describe these procedures, including model-based procedures, for incorporating covariates into the design of clinical trials, and give examples where balance, efficiency and ethical considerations may be in conflict. We advocate a new class of procedures, covariate-adjusted response-adaptive (CARA) randomization procedures that attempt to optimize both efficiency and ethical considerations, while maintaining randomization. We review all these procedures, present a few new simulation studies, and conclude with our philosophy.


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William F. Rosenberger. Oleksandr Sverdlov. "Handling Covariates in the Design of Clinical Trials." Statist. Sci. 23 (3) 404 - 419, August 2008.


Published: August 2008
First available in Project Euclid: 28 January 2009

zbMATH: 1329.62350
MathSciNet: MR2483911
Digital Object Identifier: 10.1214/08-STS269

Keywords: Balance , covariate-adaptive randomization , covariate-adjusted response-adaptive randomization , efficiency , ethics

Rights: Copyright © 2008 Institute of Mathematical Statistics


Vol.23 • No. 3 • August 2008
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