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

Background: Clinical 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. Purpose: This paper illustrates the design, sample size estimation and operating characteristics of an snSMART. Methods: We investigate the performance of a class of weighted Z statistics via computer simulations. Results: We 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. Conclusion: The snSMART design is promising in a rare disease setting where several alternative treatments are under consideration and small sample sizes are necessary. (C) 2015 Elsevier Inc. All rights reserved.