The direct assignment option as a modular design component: an example for the setting of two predefined subgroups.

ABSTRACT

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.