Improving the Balance of Unobserved Covariates From Information Theory in Multi-Arm Randomization with Unequal Allocation Ratio

Multi-arm randomization has increasingly widespread applications recently and it is also crucial to ensure that the distributions of important observed covariates as well as the potential unobserved covariates are similar and comparable among all the treatment. However, the theoretical properties of unobserved covariates imbalance in multi-arm randomization with unequal allocation ratio remains unknown. In this paper, we give a general framework analysing the moments and distributions of unobserved covariates imbalance and apply them into different procedures including complete randomization (CR), stratified permuted block (STR-PB) and covariate-adaptive randomization (CAR). The general procedures of multi-arm STR-PB and CAR with unequal allocation ratio are also proposed. In addition, we introduce the concept of entropy to measure the correlation between discrete covariates and verify that we could utilize the correlation to select observed covariates to help better balance the unobserved covariates.