Estimating Conditional Power for Sequential Monitoring of Covariate Adaptive Randomized Designs: The Fractional Brownian Motion Approach

Conditional power based on classical Brownian motion (BM) has been widely used in sequential monitoring of clinical trials, including those with the covariate adaptive randomization design (CAR). Due to some uncontrollable factors, the sequential test statistics under CAR procedures may not satisfy the independent increment property of BM. We confirm the invalidation of BM when the error terms in the linear model with CAR design are not independent and identically distributed. To incorporate the possible correlation structure of the increment of the test statistic, we utilize the fractional Brownian motion (FBM). We conducted a comparative study of the conditional power under BM and FBM. It was found that the conditional power under FBM assumption was mostly higher than that under BM assumption when the Hurst exponent was greater than 0.5.