Blinded sample size re-estimation with unequal variances and center effects in clinical trials

The two-stage sample size re-estimation procedure developed previously in the literature (e.g.,Shih, 1992; Gould and Shih, 1992) treats the blinded data from a randomized clinical trial as a sample from a mixture of two normal distributions of equal variances.This paper investigates the procedure when being applied to the situations where the variances are unequal and blocking effects by clinical centers are present.We show by simulations that in both situations the re-estimation procedure is still capable to update the sample size properly for attaining the required power and preserving the type-1 error at the nominal level.