An adaptive seamless phase II/III design for oncology trials with subpopulation selection using correlated survival endpoints
An adaptive seamless phase II/III design for oncology trials with subpopulation selection using correlated survival endpoints
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DOI：
10.1002/pst.472
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发表时间：
2011-07-01
影响因子：
1.5
通讯作者：
Jennison, Christopher
中科院分区：
文献类型：
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作者：
Jenkins, Martin;Stone, Andrew;Jennison, Christopher
尽管支持有效自适应无缝设计的统计方法越来越成熟，但在进行此类试验时，继续使用最适合相关治疗领域和开发阶段的终点和规范非常重要。存在允许适应性设计在患者亚群或整个人群中无缝继续的方法，这些方法基于从II/III期设计的第一阶段获得的数据：我们提出的设计增加了额外的灵活性，还允许在所有患者中继续试验，但亚群和整个人群作为共同主要人群。此外，当II期和III期终点不同但至事件时间终点相关时，提供了将I类错误率控制在2.5%以下的方法。操作特点的设计描述沿着与讨论的实际方面，在肿瘤学设置。版权所有（C）2010约翰威利父子有限公司
Although the statistical methods enabling efficient adaptive seamless designs are increasingly well established, it is important to continue to use the endpoints and specifications that best suit the therapy area and stage of development concerned when conducting such a trial. Approaches exist that allow adaptive designs to continue seamlessly either in a subpopulation of patients or in the whole population on the basis of data obtained from the first stage of a phase II/III design: our proposed design adds extra flexibility by also allowing the trial to continue in all patients but with both the subgroup and the full population as co-primary populations. Further, methodology is presented which controls the Type-I error rate at less than 2.5% when the phase II and III endpoints are different but correlated time-to-event endpoints. The operating characteristics of the design are described along with a discussion of the practical aspects in an oncology setting. Copyright (C) 2010 John Wiley & Sons, Ltd.