Balanced covariates with response adaptive randomization

Response adaptive randomization (RAR) methods for clinical trials are susceptible to imbalance in the distribution of influential covariates across treatment arms. This can make the interpretation of trial results difficult, because observed differences between treatment groups may be a function of the covariates and not necessarily because of the treatments themselves. We propose a method for balancing the distribution of covariate strata across treatment arms within RAR. The method uses odds ratios to modify global RAR probabilities to obtain stratum-specific modified RAR probabilities. We provide illustrative examples and a simple simulation study to demonstrate the effectiveness of the strategy for maintaining covariate balance. The proposed method is straightforward to implement and applicable to any type of RAR method or outcome.