BACKGROUND Subgroup analyses are frequently used to assess heterogeneity of treatment effects in randomised clinical trials. Inconsistent, improper and incomplete implementation, reporting and interpretation have been identified as ongoing challenges. Further, subgroup analyses were frequently criticised because of unreliable or potentially misleading results. More recently, recommendations and guidelines have been provided to improve the reporting of data in this regard. METHODS This systematic review was based on a literature search within the digital archives of three selected medical journals, The New England Journal of Medicine, The Lancet and Circulation. We reviewed articles of randomised clinical trials in the domain of cardiovascular disease which were published in 2015 and 2016. We screened and evaluated the selected articles for the mode of implementation and reporting of subgroup analyses. RESULTS We were able to identify a total of 130 eligible publications of randomised clinical trials. In 89/130 (68%) articles, results of at least one subgroup analysis were presented. This was dependent on the considered journal (p < 0.001), the number of included patients (p < 0.001) and the lack of statistical significance of a trial's primary analysis (p < 0.001). The number of reported subgroup analyses ranged from 1 to 101 (median = 13). We were able to comprehend the specification time of reported subgroup analyses for 71/89 (80%) articles, with 55/89 (62%) articles presenting exclusively pre-specified analyses. This information was not always traceable on the basis of provided trial protocols and often did not include the pre-definition of cut-off values for the categorization of subgroups. The use of interaction tests was reported in 84/89 (94%) articles, with 36/89 (40%) articles reporting heterogeneity of the treatment effect for at least one primary or secondary trial outcome. Subgroup analyses were reported more frequently for larger randomised clinical trials, and if primary analyses did not reach statistical significance. Information about the implementation of subgroup analyses was reported most consistently for articles from The New England Journal of Medicine, since it was also traceable on the basis of provided trial protocols. We were able to comprehend whether subgroup analyses were pre-specified in a majority of the reviewed publications. Even though results of multiple subgroup analyses were reported for most published trials, a corresponding adjustment for multiple testing was rarely considered. CONCLUSION Compared to previous reviews in this context, we observed improvements in the reporting of subgroup analyses of cardiovascular randomised clinical trials. Nonetheless, critical shortcomings, such as inconsistent reporting of the implementation and insufficient pre-specification, persist.

中文翻译：

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心血管疾病随机临床试验中亚组分析的系统评价

背景 亚组分析经常用于评估随机临床试验中治疗效果的异质性。不一致、不当和不完整的实施、报告和解释已被确定为持续的挑战。此外，由于结果不可靠或可能具有误导性，亚组分析经常受到批评。最近，已提供建议和指导方针以改进这方面的数据报告。方法 本系统评价基于对三个选定医学期刊的数字档案中的文献搜索，即新英格兰医学杂志、柳叶刀和循环。我们回顾了 2015 年和 2016 年发表的心血管疾病领域的随机临床试验文章。我们针对亚组分析的实施和报告模式筛选并评估了所选文章。结果 我们能够确定总共 130 篇符合条件的随机临床试验出版物。在 89/130 (68%) 篇文章中，提供了至少一项亚组分析的结果。这取决于所考虑的期刊 (p < 0.001)、纳入的患者数量 (p < 0.001) 以及试验主要分析缺乏统计学意义 (p < 0.001)。报告的亚组分析数量从 1 到 101（中位数 = 13）。我们能够理解 71/89 (80%) 文章报告的亚组分析的规范时间，其中 55/89 (62%) 文章仅呈现预先指定的分析。根据提供的试验方案，这些信息并不总是可追溯的，并且通常不包括用于亚组分类的临界值的预定义。84/89 (94%) 篇文章报告了相互作用测试的使用，其中 36/89 (40%) 篇文章报告了至少一项主要或次要试验结果的治疗效果的异质性。对于大型随机临床试验，如果主要分析未达到统计显着性，则更频繁地报告亚组分析。《新英格兰医学杂志》的文章报告了有关亚组分析实施情况的最一致的信息，因为它也可以根据提供的试验方案进行追踪。我们能够理解大多数审查的出版物中是否预先指定了亚组分析。尽管大多数已发表试验报告了多个亚组分析的结果，但很少考虑对多重测试进行相应调整。结论 与之前在此背景下的综述相比，我们观察到心血管随机临床试验亚组分析报告的改进。尽管如此，诸如实施报告不一致和预先规范不足等关键缺陷仍然存在。