Adaptive seamless designs with interim treatment selection: a case study in oncology
Adaptive seamless designs with interim treatment selection: a case study in oncology
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DOI：
10.1002/sim.6407
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发表时间：
2015-04-15
影响因子：
2
通讯作者：
Brannath, Werner
中科院分区：
文献类型：
--
作者：
Carreras, Maximo;Gutjahr, Georg;Brannath, Werner
讨论了具有无缝II/III期适应性设计的肿瘤学临床试验的规划。在中期分析中，将试验性治疗的两种方案与对照进行比较，并选择最有希望的方案与对照一起继续进行，直到研究结束。由于在临时方案选择分析中，主要终点预期为不成熟，因此考虑在方案选择过程中结合主要终点和替代终点的设计。在研究结束时，根据主要终点比较所选方案与对照组的最终疗效测试使用在方案选择分析之前和之后收集的所有相关数据。关于功率和I类错误率，评估了检验基本假设的几种方法。由于这些设计的运行特性取决于所考虑的具体方案选择规则，因此提出了在方案选择分析中使用完美代理和不使用代理的基准场景。这些基准方案的操作特征提供了实际研究设计的预期范围。还讨论了检测主要和关键次要终点的家庭误差率控制，以及对所选方案的最终治疗效果估计的偏差评估。版权所有(C)2015 John Wiley&Sons，Ltd.
The planning of an oncology clinical trial with a seamless phase II/III adaptive design is discussed. Two regimens of an experimental treatment are compared to a control at an interim analysis, and the most-promising regimen is selected to continue, together with control, until the end of the study. Because the primary endpoint is expected to be immature at the interim regimen selection analysis, designs that incorporate primary as well as surrogate endpoints in the regimen selection process are considered. The final testing of efficacy at the end of the study comparing the selected regimen to the control with respect to the primary endpoint uses all relevant data collected both before and after the regimen selection analysis. Several approaches for testing the primary hypothesis are assessed with regard to power and type I error rate. Because the operating characteristics of these designs depend on the specific regimen selection rules considered, benchmark scenarios are proposed in which a perfect surrogate and no surrogate is used at the regimen selection analysis. The operating characteristics of these benchmark scenarios provide a range where those of the actual study design are expected to lie. A discussion on family-wise error rate control for testing primary and key secondary endpoints as well as an assessment of bias in the final treatment effect estimate for the selected regimen are also presented. Copyright (c) 2015 John Wiley & Sons, Ltd.