Tsai Wei-Yann, Chi Yunchan, Chen Chia-Min
Department of Biostatistics, Columbia University, New York City, NY, U.S.A.
Stat Med. 2008 Jan 15;27(1):15-35. doi: 10.1002/sim.2930.
Generally, a two-stage design is employed in Phase II clinical trials to avoid giving patients an ineffective drug. If the number of patients with significant improvement, which is a binomial response, is greater than a pre-specified value at the first stage, then another binomial response at the second stage is also observed. This paper considers interval estimation of the response probability when the second stage is allowed to continue. Two asymptotic interval estimators, Wald and score, as well as two exact interval estimators, Clopper-Pearson and Sterne, are constructed according to the two binomial responses from this two-stage design, where the binomial response at the first stage follows a truncated binomial distribution. The mean actual coverage probability and expected interval width are employed to evaluate the performance of these interval estimators. According to the comparison results, the score interval is recommended for both Simon's optimal and minimax designs.
一般来说，在II期临床试验中采用两阶段设计以避免让患者使用无效药物。如果具有显著改善的患者数量（这是一个二项式反应）在第一阶段大于预先指定的值，那么在第二阶段也会观察到另一个二项式反应。本文考虑在允许第二阶段继续进行时反应概率的区间估计。根据该两阶段设计的两个二项式反应构建了两个渐近区间估计量，即Wald估计量和得分估计量，以及两个精确区间估计量，即Clopper-Pearson估计量和Sterne估计量，其中第一阶段的二项式反应遵循截断二项分布。使用平均实际覆盖概率和预期区间宽度来评估这些区间估计量的性能。根据比较结果，对于Simon最优设计和极小极大设计，均推荐使用得分区间。
