Balancing multiple baseline characteristics in randomized clinical trials

It is of vital importance to the success of a randomized clinical trial to maintain the balance of baseline characteristics (covariates) that could potentially confound the outcomes of the trial. Various randomization methods have been proposed to increase the likelihood of having balanced covariates at the end of a trial, most of which only apply to categorical covariates. An optimization approach to maintaining the balance of multiple covariates in randomized clinical trials is proposed, which is applicable to both continuous and categorical covariates and allows the covariates to be ranked according to their clinical importance as perceived by the clinical trial practitioners. Simulation results show that the proposed algorithm significantly outperforms the standard randomization approach via flipping an unbiased coin. The proposed randomization method can be easily implemented and generalized for cases where there are multiple treatment arms with equal or unequal randomization probabilities. (C) 2011 Elsevier Inc. All rights reserved.