Yusuf S, Wittes J, Probstfield J, Tyroler H A
Division of Epidemiology and Clinical Applications, National Heart, Lung, and Blood Institute, Bethesda, Md 20892.
JAMA. 1991 Jul 3;266(1):93-8.
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.
亚组结果解释的一个关键原则是，定量相互作用（程度差异）比定性相互作用（性质差异）更有可能出现。无论定量相互作用是否明显，它们都可能真实存在，而明显的定性相互作用通常不应被采信，因为它们通常未得到一致的重复验证。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效应的方向。未预先设定假设、未考虑多重比较或未校正P值会增加发现虚假亚组效应的可能性。相反，样本量不足、将患者错误分类到亚组以及相互作用检验效能低会使发现真正的亚组效应变得困难。我们建议检查试验中亚组的整体架构，分析独立试验中的相似亚组，并结合已知的生物学机制和患者预后对证据进行解释。
