Shan Guogen
Epidemiology and Biostatistics Program, Department of Environmental and Occupational Health, School of Community Health Sciences, University of Nevada Las Vegas, Las Vegas, NV 89154.
Statistics (Ber). 2018;52(5):1086-1095. doi: 10.1080/02331888.2018.1469023. Epub 2018 May 8.
In addition to point estimate for the probability of response in a two-stage design (e.g., Simon's two-stage design for a Phase II clinical trial with binary endpoints), confidence limits should be Cute the confidence interval does not guarantee coverage probability in a two-stage setting. The existing exact approach to calculate one-sided limits is based on the overall number of responses to order the sample space. This approach could be conservative because many sample points have the same limits. We propose a new exact one-sided interval based on p-value for the sample space ordering. Exact intervals are computed by using binomial distributions directly, instead of a normal approximation. Both exact intervals preserve the nominal confidence level. The proposed exact interval based on the p-value generally performs better than the other exact interval with regard to expected length and simple average length of confidence intervals. Therefore, the new interval calculation based on p-value is recommended for use in practice.
除了两阶段设计中反应概率的点估计（例如，针对具有二元终点的II期临床试验的西蒙两阶段设计）外，还应计算置信限，因为在两阶段设置中，置信区间并不能保证覆盖概率。现有的计算单侧限的精确方法是基于反应的总数来对样本空间进行排序。这种方法可能是保守的，因为许多样本点具有相同的限值。我们提出了一种基于p值对样本空间进行排序的新的精确单侧区间。精确区间通过直接使用二项分布来计算，而不是使用正态近似。两种精确区间都保持了名义置信水平。就置信区间的期望长度和简单平均长度而言，所提出的基于p值的精确区间通常比其他精确区间表现更好。因此，建议在实际应用中使用基于p值的新区间计算方法。
