A small n sequential multiple assignment randomized trial design for use in rare disease research

BackgroundClinical trials in rare diseases are difficult to conduct due to the limited number of patients available with each disorder. We developed a Phase 2 trial which is a small n sequential multiple assignment randomized trial (snSMART) design to test several treatments for a rare disease for which no standard therapy exists.PurposeThis paper illustrates the design, sample size estimation and operating characteristics of an snSMART.MethodsWe investigate the performance of a class of weighted Z statistics via computer simulations.ResultsWe demonstrate the increase in power over traditional single stage designs, and indicate how the power changes as a function of the weight given to each stage.ConclusionThe snSMART design is promising in a rare disease setting where several alternative treatments are under consideration and small sample sizes are necessary.