ANALYSIS AND INTERPRETATION OF TREATMENT EFFECTS IN SUBGROUPS OF PATIENTS IN RANDOMIZED CLINICAL-TRIALS
ANALYSIS AND INTERPRETATION OF TREATMENT EFFECTS IN SUBGROUPS OF PATIENTS IN RANDOMIZED CLINICAL-TRIALS
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DOI：
10.1001/jama.266.1.93
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发表时间：
1991-07-03
影响因子：
120.7
通讯作者：
TYROLER, HA
中科院分区：
文献类型：
--
作者：
YUSUF, S;WITTES, J;TYROLER, HA
解释亚组结果的一个关键原则是定量相互作用（程度差异）比定性相互作用（种类差异）更有可能。定量的相互作用可能是真实存在的，无论它们是否明显，而明显的定性相互作用通常不应该被相信，因为它们通常不会被一致地复制。因此，总体试验结果通常比亚组内观察到的明显效应更能指导亚组的效应方向。未能指定先验假设、解释多重比较或校正P值会增加发现虚假亚组效应的机会。相反，样本量不足，将患者分类为错误的亚组，以及相互作用检验的低功效使得难以找到真正的亚组效应。我们建议检查试验中整个亚组的结构，分析独立试验中的类似亚组，并在已知生物学机制和患者预后的背景下解释证据。
A key principle for interpretation of subgroup results is that quantitative interactions (differences in degree) are much more likely than qualitative interactions (differences in kind). Quantitative interactions are likely to be truly present whether or not they are apparent, whereas apparent qualitative interactions should generally be disbelieved as they have usually not been replicated consistently. Therefore, the overall trial result is usually a better guide to the direction of effect in subgroups than the apparent effect observed within a subgroup. Failure to specify prior hypotheses, to account for multiple comparisons, or to correct P values increases the chance of finding spurious subgroup effects. Conversely, inadequate sample size, classification of patients into the wrong subgroup, and low power of tests of interaction make finding true subgroup effects difficult. We recommend examining the architecture of the entire set of subgroups within a trial, analyzing similar subgroups across independent trials, and interpreting the evidence in the context of known biologic mechanisms and patient prognosis.