Hernández Adrián V, Boersma Eric, Murray Gordon D, Habbema J Dik F, Steyerberg Ewout W
Center for Clinical Decision Sciences, Department of Public Health, Thoraxcenter, Erasmus University Medical Center, Rotterdam, The Netherlands.
Am Heart J. 2006 Feb;151(2):257-64. doi: 10.1016/j.ahj.2005.04.020.
Treatment decisions in clinical cardiology are directed by results from randomized clinical trials (RCTs). We studied the appropriateness of the use and interpretation of subgroup analysis in current therapeutic cardiovascular RCTs.
We reviewed main reports of phase 3 cardiovascular RCTs with at least 100 patients, published in 2002 and 2004, and from major journals (Circulation, J Am Coll Cardiol, Am Heart J, Am J Cardiol, N Engl J Med, Lancet, JAMA, BMJ, Ann Intern Med). Information on subgroups included prespecification, number, interaction test use, significant subgroups found, and emphasis on findings. We examined appropriateness of reporting and differences according to sample size, overall trial result, and CONSORT adoption.
We selected 63 RCTs, with a median of 496 (range 100-15,245) patients. Thirty-nine RCTs were reported with subgroup analyses and 26 with > 5 subgroups. No trial was specifically powered to detect subgroup effects, and only 14 RCTs were reported with fully prespecified subgroups. Only 11 RCTs were reported with interaction tests. Furthermore, 21 RCTs were reported with claims of significant subgroups and 15 with equal or more emphasis to subgroups than to the overall results. Subgroup analyses in large RCTs (> 500 patients) were reported more often than in small ones (24/30 vs 15/33, P = .005). No differences were found according to overall result (positive/negative) or CONSORT adoption.
Subgroup analyses in recent cardiovascular RCTs were reported with several shortcomings, including a lack of prespecification and testing of a large number of subgroups without the use of the statistically appropriate test for interaction. Reporting of subgroup analysis needs to be substantially improved because emphasis on these secondary results may mislead treatment decisions.
临床心脏病学中的治疗决策以随机临床试验（RCT）的结果为导向。我们研究了当前治疗性心血管RCT中亚组分析的使用和解释的适当性。
我们回顾了2002年和2004年发表在主要期刊（《循环》《美国心脏病学会杂志》《美国心脏杂志》《美国心脏病学杂志》《新英格兰医学杂志》《柳叶刀》《美国医学会杂志》《英国医学杂志》《内科学年鉴》）上的至少有100名患者的3期心血管RCT的主要报告。关于亚组的信息包括预先设定、数量、交互作用检验的使用、发现的显著亚组以及对结果的强调。我们根据样本量、总体试验结果和CONSORT采用情况检查了报告的适当性和差异。
我们选择了63项RCT，患者中位数为496名（范围100 - 15245名）。39项RCT报告了亚组分析，26项有超过5个亚组。没有试验专门为检测亚组效应而设计足够的效能，只有14项RCT报告了完全预先设定的亚组。只有11项RCT报告了交互作用检验。此外，21项RCT报告了存在显著亚组的说法，15项对亚组的强调等同于或超过对总体结果的强调。大型RCT（>500名患者）中的亚组分析报告比小型RCT更频繁（24/30对15/33，P = 0.005）。根据总体结果（阳性/阴性）或CONSORT采用情况未发现差异。
近期心血管RCT中的亚组分析报告存在若干缺陷，包括缺乏预先设定以及对大量亚组进行检验但未使用统计学上合适的交互作用检验。亚组分析的报告需要大幅改进，因为对这些次要结果的强调可能会误导治疗决策。
