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Computational and Mathematical Methods in Medicine
Volume 2015, Article ID 210817, 6 pages
Research Article

The Direct Assignment Option as a Modular Design Component: An Example for the Setting of Two Predefined Subgroups

1Department of Mathematics, Vassar College, 124 Raymond Avenue, Poughkeepsie, NY 12604, USA
2Emory University, Atlanta, GA 30322, USA
3Mayo Clinic, Rochester, MN 55905, USA

Received 25 November 2014; Revised 29 December 2014; Accepted 29 December 2014

Academic Editor: Maria N. D. S. Cordeiro

Copyright © 2015 Ming-Wen An et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Background. A phase II design with an option for direct assignment (stop randomization and assign all patients to experimental treatment based on interim analysis, IA) for a predefined subgroup was previously proposed. Here, we illustrate the modularity of the direct assignment option by applying it to the setting of two predefined subgroups and testing for separate subgroup main effects. Methods. We power the 2-subgroup direct assignment option design with 1 IA (DAD-1) to test for separate subgroup main effects, with assessment of power to detect an interaction in a post-hoc test. Simulations assessed the statistical properties of this design compared to the 2-subgroup balanced randomized design with 1 IA, BRD-1. Different response rates for treatment/control in subgroup 1 (0.4/0.2) and in subgroup 2 (0.1/0.2, 0.4/0.2) were considered. Results. The 2-subgroup DAD-1 preserves power and type I error rate compared to the 2-subgroup BRD-1, while exhibiting reasonable power in a post-hoc test for interaction. Conclusion. The direct assignment option is a flexible design component that can be incorporated into broader design frameworks, while maintaining desirable statistical properties, clinical appeal, and logistical simplicity.