A threshold sample-enrichment approach in a clinical trial with heterogeneous subpopulations.

Background Large comparative clinical trials usually target a wide-range of patients population in which subgroups exist according to certain patients’ characteristics. Often, scientific knowledge or existing empirical data support the assumption that patients’ improvement is larger among certain subgroups than others. Such information can be used to design a more cost-effective clinical trial.Purpose The goal of the article is to use such information to design a more cost-effective clinical trial.Methods A two-stage sample-enrichment design strategy is proposed that begins with enrollment from certain subgroup of patients and allows the trial to be terminated for futility in that subgroup.Results Simulation studies show that the two-stage sample-enrichment strategy is cost-effective if indeed the null hypothesis of no treatment improvement is true, as also so illustrated with data from a completed trial of calcium to prevent preeclampsia.Limitations Feasibility of the proposed enrichment design relies on...