Estimating significance level and power comparisons for testing multiple endpoints in clinical trials
Estimating significance level and power comparisons for testing multiple endpoints in clinical trials
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DOI：
10.1016/s0197-2456(00)00049-0
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发表时间：
2000-08-01
期刊：
影响因子：
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通讯作者：
DeMets, DL
中科院分区：
文献类型：
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作者：
Gong, JJ;Pinheiro, JC;DeMets, DL
临床试验通常包括几个用于评估治疗疗效和危害的结果指标。传统上，选择单一指标（主要结局）作为设计的基础，包括样本量和功效。次要结果通常根据其临床相关性和重要性进行排序。虽然这已成为传统的范例，但最近的试验表明，需要采取其他方法。在这种情况下，两个结果被视为关键，其中任何一个都足以证明疗效，但有优先顺序。在这种情况下，基本问题是如何控制试验的总体显著性水平。我们描述和比较两种方法来检验主要和次要终点，占其层次性质的排序偏好。这两种方法都是序贯的，也就是说，仅在主要结局未能达到显著性时才检验次要终点。第一种方法使用主要和次要终点组合的全局检验，而第二种方法使用部分Bonferroni校正。仿真结果表明，Bonferroni平差方法在大多数情况下与全局检验方法性能相当，在某些情况下甚至更好。(C)Elsevier Science Inc. 2000.
Clinical trials generally include several outcome measures of interest for assessing treatment efficacy and harm. Traditionally a single measure, the primary outcome, is selected and used as the basis for the design, including sample size and power. Secondary outcomes are then generally ordered with respect to their clinical relevance and importance. While this has become the traditional paradigm, recent trials have suggested the need for additional approaches. In this setting, two outcomes are viewed as key, either one being sufficient for proof of efficacy, but with an ordering of preference. The basic question, in such cases, is how to control the overall significance level for the trial. We describe and compare two methods for testing primary and secondary endpoints, accounting for their hierarchical nature-the ordering preference. Both methods are sequential, in the sense that the secondary endpoint is only tested when the primary outcome fails to reach significance. The first method uses a global test for the combination of the primary and secondary endpoints, while the second uses a partial Bonferroni correction. Simulation results indicate that the Bonferroni adjustment method performs as well as the global test method in most cases, and even better in some cases. (C) Elsevier Science Inc. 2000.