On Group-Sequential Multiple Testing Controlling Familywise Error Rate

Abstract

The importance of multiplicity adjustment has gained wide recognition in modern scientific research. Without it, there will be too many spurious results and reproducibility becomes an issue; with it, if overtly conservative, discoveries will be made more difficult. In the current literature on repeated testing of multiple hypotheses, Bonferroni-based methods are still the main vehicle carrying the bulk of multiplicity adjustment. There is room for power improvement by suitably utilizing both hypothesis-wise and analysis- wise dependencies. This research will contribute to the development of a natural group-sequential extension of the classical stepwise multiple testing procedures, such as Dunnett’s stepdown and Hochberg’s step-up procedures. It is shown that the proposed group-sequential procedures strongly control the familywise error rate while being more powerful than the recently developed class of group-sequential Bonferroni-Holm’s procedures. Particularly in this research, a convexity property is discovered for the distribution of the maxima of pairwise null P-values with the underlying test statistics having distributions such as bivariate normal, t, Gamma, F, or Archimedean copulas. Such property renders itself for an immediate use in improving Holm’s procedure by incorporating pairwise dependencies of P-values. The improved Holm’s procedure, as all stepdown multiple testing procedures, can also be naturally extended to group-sequential setting.