Thall P F, Simon R
Department of Biomathematics, Anderson Cancer Center, University of Texas, Houston 77030.
Biometrics. 1994 Jun;50(2):337-49.
A Phase IIB clinical trial typically is a single-arm study aimed at deciding whether a new treatment E is sufficiently promising, relative to a standard therapy, S, to include in a large-scale randomized trial. Thus, Phase IIB trials are inherently comparative even though a standard therapy arm usually is not included. Uncertainty regarding the response rate theta s of S is rarely made explicit, either in planning the trial or interpreting its results. We propose practical Bayesian guidelines for deciding whether E is promising relative to S in settings where patient response is binary and the data are monitored continuously. The design requires specification of an informative prior for theta s, a targeted improvement for E, and bounds on the allowed sample size. No explicit specification of a loss function is required. Sampling continues until E is shown to be either promising or not promising relative to S with high posterior probability, or the maximum sample size is reached. The design provides decision boundaries, a probability distribution for the sample size at termination, and operating characteristics under fixed response probabilities with E.
一项IIB期临床试验通常是一项单臂研究，旨在确定相对于标准疗法S而言，新疗法E是否具有足够的前景，从而纳入大规模随机试验。因此，IIB期试验本质上是比较性的，尽管通常不设置标准疗法组。无论是在试验规划还是结果解读中，关于S的缓解率θs的不确定性很少被明确提及。我们提出了实用的贝叶斯指南，用于在患者反应为二元且数据持续监测的情况下，判断E相对于S是否有前景。该设计需要指定θs的信息性先验、E的目标改善程度以及允许样本量的界限。无需明确指定损失函数。抽样持续进行，直到E相对于S被证明有前景或没有前景的后验概率很高，或者达到最大样本量。该设计提供了决策边界、终止时样本量的概率分布以及在E的固定反应概率下的操作特征。
