论文标题
与生物标志物亚群的小组顺序试验的多重性
Multiplicity for a Group Sequential Trial with Biomarker Subpopulations
论文作者
论文摘要
生物标志物亚群对于靶向疗法的药物开发变得越来越重要。生物标志物的使用有可能通过适当指导患者选择来促进更有效的结果，从而提高利益风险的概况并提高试验能力。同时研究广泛的人群与更有针对性的人群可以确定治疗有效的人群，并允许将批准的监管标签具有适当的包容性。我们研究了与嵌套亚组中假设的组顺序设计中完整相关结构的新方法。这些设计提供了对家庭型错误率的全面控制。对以前的方法的扩展，该方法对组顺序设计或子组之间的相关性提高了效率（功率或样本量），而不是用于测试嵌套种群的典型Bonferroni方法。
Biomarker subpopulations have become increasingly important for drug development in targeted therapies. The use of biomarkers has the potential to facilitate more effective outcomes by guiding patient selection appropriately, thus enhancing the benefit-risk profile and improving trial power. Studying a broad population simultaneously with a more targeted one allows the trial to determine the population for which a treatment is effective and allows a goal of making approved regulatory labeling as inclusive as is appropriate. We examine new methods accounting for the complete correlation structure in group sequential designs with hypotheses in nested subgroups. The designs provide full control of family-wise Type I error rate. This extension of previous methods accounting for either group sequential design or correlation between subgroups improves efficiency (power or sample size) over a typical Bonferroni approach for testing nested populations.
