ABSTRACT

We propose a new adaptive threshold detection and enrichment design in which the biomarker threshold is adaptively estimated and updated by optimizing a trade-off between the size of the biomarker positive population and the magnitude of the treatment effect in that population. Enrichment is based on an enrollment criterion that accounts for the uncertainty in estimation of the threshold. Early termination for futility is allowed based on predictive success probability. Valid testing and estimation techniques for the treatment effect overall and inpatient subgroups are studied. Simulations and an example demonstrate advantages of the proposed design over existing designs.

摘要

我们提出了一种新的自适应阈值检测和富集设计，其中通过优化生物标志物阳性群体的大小和该群体中治疗效果的大小之间的权衡来自适应地估计和更新生物标志物阈值。富集基于考虑阈值估计不确定性的注册标准。根据预测的成功概率，允许提前终止无效。研究了对整体治疗效果和住院患者亚组的有效测试和估计技术。仿真和示例展示了所提议的设计优于现有设计的优势。