Khan Muhammad Shahzeb, Khan Muhammad Arbaz Arshad, Irfan Simra, Siddiqi Tariq Jamal, Greene Stephen J, Anker Stefan D, Sreenivasan Jayakumar, Friede Tim, Tahhan Ayman Samman, Vaduganathan Muthiah, Fonarow Gregg C, Butler Javed
Department of Medicine, Cook County Health Sciences, Chicago, IL, USA.
Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan.
ESC Heart Fail. 2021 Feb;8(1):26-36. doi: 10.1002/ehf2.13122. Epub 2020 Nov 30.
This study aimed to investigate the reporting of subgroup analyses in heart failure (HF) randomized controlled trials (RCTs) and to determine the strength and credibility of subgroup claims.
All primary HF RCTs published in nine high-impact journals from 1 January 2008 to 31 December 2017 were included. Multivariable regression analysis was used to identify factors that may favour the reporting of results in specific subgroups. Strength of the subgroup effect claimed was classified into (i) strong, (ii) likely, or (iii) suggestive. Credibility of subgroup claim was scored using a pre-specified 10 pointer criteria. Of the 261 HF RCTs studied, 107 (41%) reported subgroup analyses. Twenty-five (23%) RCTs claimed a subgroup effect for the primary outcome of which six (24%) made a strong claim, eight (32%) claimed a likely effect, and 11 (44%) suggested a possible subgroup effect. Seven of the 25 RCTs did not employ interaction testing for subgroup claims of the primary outcome. Three out of 10 pre-specified credibility criteria were satisfied by half of the trials. Fourteen trials justified the choice of subgroups, and 10 explicitly stated they were underpowered to detect differences within subgroups. Source of funding did not influence the frequency of reporting subgroup analyses (OR 0.53, 95% CI 0.78-3.62, P = 0.52).
Appropriate credibility criteria were rarely met even by HF RCTs that held strong subgroup claims. Subgroup analyses should be pre-specified, be adequately powered, present interaction terms, and be replicated in independent data before being integrated into clinical decision making.
本研究旨在调查心力衰竭（HF）随机对照试验（RCT）中分组分析的报告情况，并确定分组声明的强度和可信度。
纳入2008年1月1日至2017年12月31日在9种高影响力期刊上发表的所有原发性HF RCT。采用多变量回归分析来确定可能有利于特定亚组结果报告的因素。所声称的亚组效应强度分为：（i）强，（ii）可能，或（iii）提示性。使用预先指定的10分标准对亚组声明的可信度进行评分。在研究的261项HF RCT中，107项（41%）报告了分组分析。25项（23%）RCT声称主要结局存在亚组效应，其中6项（24%）做出了强有力的声明，8项（32%）声称可能存在效应，11项（44%）提示可能存在亚组效应。25项RCT中有7项未对主要结局的亚组声明进行交互作用检验。10项预先指定的可信度标准中有3项被一半的试验满足。14项试验对亚组的选择进行了说明，10项明确表示其检测亚组内差异的效能不足。资金来源并未影响分组分析报告的频率（比值比0.53，95%置信区间0.78 - 3.62，P = 0.52）。
即使对于有强有力分组声明的HF RCT，也很少能满足适当的可信度标准。在将分组分析纳入临床决策之前，应预先指定分组分析，有足够的效能，呈现交互项，并在独立数据中进行重复验证。
