Institution: Department of Medical Statistics, University of Vienna
Street: Schwarzspanierstrasse 17
Authors: Brannath,W., P.Bauer, M.Posch, W. Maurer
Title: Sequential Tests for Noninferiority and Superiority
Abstract: The problem of simultaneous sequential tests for noninferiority and superiority of a treatment as compared to an active control is considered in terms of continuous hierarchical families of one sided null hypotheses in the framework of adaptive two stage designs. The crucial point is that the decision boundaries for the individual null hypotheses may vary over the parameter space. This allows to construct designs where a rigid stopping criterion is fixed rejecting or accepting all individual null hypotheses simultaneously. Another possibility is to get monitoring type stopping boundaries, which leave some flexibility to the experimenter: he can decide at the interim analysis if he is satisfied with the noninferiority margin achieved at this stage or if he wants to go for more at the second stage. In case of proceeding to the second stage he may perform midtrial design modifications (e.g. reassess the sample size). The proposed approach allows to ``spend`` e.g. less of alpha for an early proof of noninferiority than for an early proof of superiority. The approach is illustrated by typical examples.