Two-Stage Designs with Additional Futility Tests For Phase Ⅱ Clinical Trials with Heterogeneous Patient Populations
The patient population for a phase Ⅱ clinical trial sometimes consists of multiple subgroups categorized by different prognostic factors such as age,disease stage,etc.Response rates across such subgroups often are heterogeneous;i.e.,the therapy under study may be inefficacious in some groups but efficacious in others.In this article,we propose a two-stage testing procedure consisting of futility tests and efficacy tests.The futility test is performed first within each subgroup.If there is strong evidence that the therapy is inefficacious in some subgroups,these subgroups are excluded from further consideration.The test then is performed across only the remaining subgroups.We carefully define and compute the Type Ⅰ error rate and powers under various alternative hypotheses.Our numerical studies show that with proper designs,the addition of futility tests causes little loss of power under the alternative hypothesis that the study therapy is efficacious in all subgroups.Simultaneously,the proposed testing procedure detects inefficacious subgroups with a moderate or high probability when true response rates in these subgroups are low.Finally,we present an application to a Children”s Oncology Group phase Ⅱ clinical trial in relapsed neuroblastoma patients.
Futility test efficacy test sample-size determination power analysis.
Myron Chang Sin-Ho Jung Samuel S Wu
Department of Biostatistics,University of Florida,Gainesville,FL,U.S.A. Cancer and Leukemia Group B Statistical Center and Department of Biostatistics and Bioinformatics,Du
国内会议
北京
英文
1-21
2011-07-02（万方平台首次上网日期，不代表论文的发表时间）