title: 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.
  
  
  CONCLUSIONS
  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.
authors: Department of Mathematics, Vassar College, 124 Raymond Avenue, Poughkeepsie, NY 12604, USA.
authors: Ming-Wen
authors: MW
authors: An
authors: Emory University, Atlanta, GA 30322, USA.
authors: Xin
authors: X
authors: Lu
authors: Mayo Clinic, Rochester, MN 55905, USA.
authors: Daniel J
authors: DJ
authors: Sargent
authors: Mayo Clinic, Rochester, MN 55905, USA.
authors: Sumithra J
authors: SJ
authors: Mandrekar
mesh_terms: D017322:Clinical Trials, Phase II as Topic; D003198:Computer Simulation; D006801:Humans; D015233:Models, Statistical; D011897:Random Allocation; D015203:Reproducibility of Results; D012107:Research Design; D018401:Sample Size; D012984:Software; D013223:Statistics as Topic
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