Thall P F, Cheng S C
Department of Biostatistics, Box 447, The University of Texas, M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
Stat Med. 2001 Apr 15;20(7):1023-32. doi: 10.1002/sim.717.
In clinical trials designed to evaluate treatment efficacy, it is common practice to terminate a treatment arm in which the observed rate of an adverse event is unacceptably high. This practice may be formalized by a group-sequential test based on a multivariate outcome including both adverse and efficacy events. Recently, Thall and Cheng proposed a family of tests for randomized trials of an experimental treatment versus a standard where patient outcome is bivariate with entries characterizing efficacy and safety. The test is motivated by the idea that clinically meaningful improvements over the standard may be characterized by a two-dimensional parameter quantifying trade-offs between efficacy and safety. We provide optimal two-stage designs based on this test that minimize either the mean sample size under the null hypothesis of no treatment difference, or the maximum sample size if the trial continues to a second stage. A more general group-sequential version of the design also is described, an illustration is provided, and application to the special case of single-arm phase II trials is discussed.
在旨在评估治疗效果的临床试验中，常见的做法是终止不良事件发生率高到不可接受的治疗组。这种做法可以通过基于包括不良事件和疗效事件的多变量结果的序贯检验来形式化。最近，索尔和程提出了一族用于实验性治疗与标准治疗的随机试验的检验方法，其中患者结局是双变量的，其条目表征疗效和安全性。该检验的动机是这样一种观点，即相对于标准治疗的具有临床意义的改善可以由一个量化疗效和安全性之间权衡的二维参数来表征。我们基于此检验提供了最优两阶段设计，该设计在无治疗差异的原假设下最小化平均样本量，或者在试验进入第二阶段时最小化最大样本量。还描述了该设计更一般的序贯版本，给出了一个示例，并讨论了其在单臂II期试验特殊情况下的应用。
