Monitoring Pairwise Comparisons in Multi-Armed Clinical Trials

Abstract

This paper proposes a method for monitoring multi-armed clinical trials on the basis of pairwise comparisons between arms. The set of pairwise test statistics is examined during the course of the trial in order to make decisions about hypotheses, continuation of treatment arms, and continuation of the trial. Strong control of the Type I error rate is achieved by modifying two-armed group sequential procedures of Pocock (1977, Biometrika 64, 191-199), O'Brien and Fleming (1979, Biometrics 35, 549-556), and Lan and DeMets (1983, Biometrika 70, 659-663) to multi-armed trials. In the fixed-sample situation, these methods reduce to either Dunnett's or Tukey's procedure for multiple comparisons. A simpler, more flexible approximation based on the Bonferroni inequality is suggested, as well as an analogue to a sequentially rejective procedure.