Exact confidence limits for the response rate in two-stage designs with over- or under-enrollment in the second stage.
Exact confidence limits for the response rate in two-stage designs with over- or under-enrollment in the second stage.
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DOI：
10.1177/0962280216650918
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发表时间：
2018-04
影响因子：
2.3
通讯作者：
Shan G
中科院分区：
文献类型：
--
作者：
Shan G
Simon的两阶段设计已广泛用于早期临床试验，以评估新研究治疗的活性。在实践中，实际样本量并不总是精确地遵循研究设计，特别是在第二阶段。当研究中出现过度入组或入组不足时，研究设计的原始临界值不再有效，无法在临床试验中进行适当的统计推断。这类研究的假设总是片面的，当只观察到少数反应时，零假设被拒绝。因此，单侧下限区间适用于检验假设。常用的置信区间构造方法是基于渐近方法。这些方法通常不保证覆盖概率。因此，Clopper-Pearson方法可用于计算精确的置信区间。这种方法必须与对样本空间进行排序的方法结合使用。常用的方法是基于响应率的点估计，但这种排序有太多的关系，导致确切的区间的保守性。我们建议根据p值开发精确的单侧区间来排序样本空间。所提出的方法优于现有的渐近和精确的方法。因此，建议在实践中使用。
Simon’s two-stage design has been widely used in early phase clinical trials to assess the activity of a new investigated treatment. In practice, the actual sample sizes do not always follow the study design precisely, especially in the second stage. When over- or under-enrollment occurs in a study, the original critical values for the study design are no longer valid for making proper statistical inference in a clinical trial. The hypothesis for such studies is always one-sided, and the null hypothesis is rejected when only a few responses are observed. Therefore, a one-sided lower interval is suitable to test the hypothesis. The commonly used approaches for confidence interval construction are based on asymptotic approaches. These approaches generally do not guarantee the coverage probability. For this reason, Clopper-Pearson approach can be used to compute exact confidence intervals. This approach has to be used in conjunction with a method to order the sample space. The frequently used method is based on point estimates for the response rate, but this ordering has too many ties which lead to conservativeness of the exact intervals. We propose developing exact one-sided intervals based on the p-value to order the sample space. The proposed approach outperforms the existing asymptotic and exact approaches. Therefore, it is recommended for use in practice.
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影响因子：
4
作者：
Zhao J;Yu M;Feng XP
通讯作者：
Feng XP
影响因子：
45.3
作者：
Friedberg, Jonathan W.;Mahadevan, Daruka;Bernstein, Steven H.
通讯作者：
Bernstein, Steven H.
相对风险和优势比的确切置信区间。
影响因子：
1.9
作者：
Wang W;Shan G
通讯作者：
Shan G
影响因子：
4
作者：
Porcher R;Desseaux K
通讯作者：
Desseaux K
影响因子：
2
作者：
Koyama T;Chen H
通讯作者：
Chen H