Comparing adaptive interventions under a general sequential multiple assignment randomized trial design via multiple comparisons with the best

Abstract

This paper considers screening of adaptive interventions or adaptive treatment strategies embedded in a sequential multiple assignment randomized trial (SMART). As a SMART typically consists of numerous adaptive interventions, inferential procedures based on pairwise comparisons of all interventions may suffer substantial loss in efficiency after accounting for multiplicity. We propose simultaneous confidence intervals that compare the values of interventions of interest to that of the unknown best intervention by generalizing the method in Edwards and Hsu (1983). The multiple comparison with the best (MCB) intervals are applied as screening tool: an intervention with MCB interval excluding zero will be declared as inferior to the true best at a pre-specified confidence level, and hence excluded from further exploration. Simulation studies show that the proposed method outperforms the multiple comparison procedures based on Bonferroni’s correction in terms of width of confidence intervals for estimation. The method is applied to analyze data from the CODIACS trial in patients with depression.