Adaptive Dunnett tests for treatment selection

Clinical trials incorporating treatment selection at pre-specified interim analyses allow to integrate two clinical studies into a single, confirmatory study. In an adaptive interim analysis, treatment arms are selected based on interim data as well as external information. The specific selection rule does not need to be pre-specified in advance in order to control the multiple type I error rate. We propose an adaptive Dunnett test procedure based on the conditional error rate of the single-stage Dunnett test. The adaptive procedure uniformly improves the classical Dunnett test, which is shown to be strictly conservative if treatments are dropped at interim. The adaptive Dunnett test is compared in a simulation with the classical Dunnett test as well as with adaptive combination tests based on the closure principle. The method is illustrated with a real-data example.