On group sequential procedures under variance heterogeneity

Abstract

In this paper, we consider group sequential procedures for clinical trials under variance heterogeneity. Group sequential procedures typically involve small samples at each interim analysis. We advocate Welch’s correction for variance heterogeneity, and present a natural application of the significance level method for such situations. Currently available procedures are based on a large sample method, with no allowance for corrections of heterogeneity. Unless the sample size is large, the results are not valid. On the basis of simulation studies, comparing their abilities to control Type I error rates, we recommend using Welch’s correction for sequential trials involving small samples under variance heterogeneity.

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