Thall P F, Russell K E
Department of Biomathematics, M. D. Anderson Cancer Center, University of Texas, Houston 77030, USA.
Biometrics. 1998 Mar;54(1):251-64.
We propose a design strategy for single-arm clinical trials in which the goals are to find a dose of an experimental treatment satisfying both safety and efficacy requirements, treat a sufficiently large number of patients to estimate the rates of these events at the selected dose with a given reliability, and stop the trial early if it is likely that no dose is both safe and efficacious. Patient outcome is characterized by a trinary ordinal variable accounting for both efficacy and toxicity. Like Thall, Simon, and Estey (1995, Statistics in Medicine 14, 357-379), we use Bayesian criteria to generate decision rules while relying on frequentist criteria obtained via simulation to determine a design parameterization with good operating characteristics. The strategy is illustrated by application to a bone marrow transplantation trial for hematologic malignancies and a trial of a biologic agent for malignant melanoma.
我们提出了一种单臂临床试验的设计策略，其目标是找到一种满足安全性和有效性要求的实验性治疗剂量，治疗足够多的患者，以便在选定剂量下以给定的可靠性估计这些事件的发生率，并在很可能不存在既安全又有效的剂量时提前终止试验。患者结局由一个同时考虑疗效和毒性的三元有序变量来表征。与Thall、Simon和Estey（1995年，《医学统计学》14卷，357 - 379页）一样，我们使用贝叶斯标准来生成决策规则，同时依靠通过模拟获得的频率主义标准来确定具有良好操作特性的设计参数化。通过应用于血液系统恶性肿瘤的骨髓移植试验和恶性黑色素瘤的生物制剂试验来说明该策略。
