A regulatory perspective on choice of margin and statistical inference issue in non-inferiority trials
A regulatory perspective on choice of margin and statistical inference issue in non-inferiority trials
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DOI：
10.1002/bimj.200410084
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发表时间：
2005-02-01
影响因子：
1.7
通讯作者：
O'Neill, R
中科院分区：
文献类型：
--
作者：
Hung, HMJ;Wang, SJ;O'Neill, R
如果没有安慰剂组，在活性对照试验环境下评估安慰剂效应的任何非劣效性推断都是困难的。除非恒定性假设大致认为，在可以评估对照效应的历史试验环境下，活性对照的效应可用于非劣效性试验环境，否则无法评估得出非劣效性错误结论的统计风险。由于在非劣效性试验中缺失安慰剂组，因此无法检查恒定性假设。根据违反假设的严重程度，可能需要寻求替代设计策略，包括非常保守的非劣效性分析的缓冲或显示实验治疗优于对照。非劣效性界值的确定取决于非劣效性分析预期达到的目标。余量可以是固定余量或功能上定义的余量。试验间差异总是存在的，需要适当考虑。
Without a placebo arm, any non-inferiority inference involving assessment of the placebo effect under the active control trial setting is, difficult. The statistical risk for falsely concluding non-inferiority cannot be evaluated unless the constancy assumption approximately holds that the effect of the active control under the historical trial setting where the control effect can be assessed carries to the noninferiority trial setting. The constancy assumption cannot be checked because of missing the placebo arm in the non-inferiority trial. Depending on how serious the violation of the assumption is thought to be, one may need to seek an alternative design strategy that includes a cushion for a very conservative non-inferiority analysis or shows superiority of the experimental treatment over the control. Determination of the non-inferiority margin depends on what objective the non-inferiority analysis is intended to achieve. The margin can be a fixed margin or a margin functionally defined. Between-trial differences always exist and need to be properly considered.