Aronson D
Doron Aronson, MD, Department of Cardiology, Rambam Medical Center, Bat Galim, POB 9602, Haifa 31096, Israel, Tel.: +972 48 542790, Fax: +972 48 542176, E-mail:
Thromb Haemost. 2014 Jul 3;112(1):16-25. doi: 10.1160/TH13-09-0801. Epub 2014 Mar 6.
Controlled trials estimate treatment effects averaged over the reference population of subjects. However, physicians are interested in whether the treatment effect varies across subgroups (effect heterogeneity) in order to target specific subgroups to maximise the benefit of treatment and minimise harm. Therefore, large clinical trials of antiplatelet agents include subgroup analyses that examine whether treatment effects differ between subgroups of subjects identified by baseline characteristics. Reporting subgroup is pervasive and often accompanied by claims of difference of treatment effects between subgroups with potential important implications for clinical practice. However, subgroup-specific analyses of clinical trial data have inherent limitations that reduce their reliability. These include reduced statistical power, failure to specify the subgroups of interest a priori, failure to account for examining large numbers of subgroups, lack of strong rationale for biological response modification, and performing analyses based on variables measured post randomisation or in trials showing no overall difference between treatments. Rules for interpretation of subgroup findings in subgroups have been suggested but are frequently not applied. In this article we draw attention to the pitfalls of subgroup analyses in the context of recent trials of antiplatelet agents.
对照试验估计的是受试者参考人群的平均治疗效果。然而，医生感兴趣的是治疗效果在各亚组间是否存在差异（效应异质性），以便针对特定亚组，使治疗效益最大化并将危害降至最低。因此，抗血小板药物的大型临床试验包括亚组分析，以检验根据基线特征确定的受试者亚组之间治疗效果是否存在差异。亚组报告很普遍，而且常常伴随着关于亚组间治疗效果存在差异的说法，这可能对临床实践产生重要影响。然而，临床试验数据的亚组特异性分析存在固有局限性，会降低其可靠性。这些局限性包括统计功效降低、未事先明确感兴趣的亚组、未考虑对大量亚组进行检验、缺乏生物反应修饰的充分理由，以及基于随机化后测量的变量或在各治疗组间无总体差异的试验中进行分析。虽然已经提出了亚组结果解释的规则，但这些规则常常未得到应用。在本文中，我们提请注意在近期抗血小板药物试验背景下亚组分析所存在的缺陷。
