Hospital Pharmacy Department, Virgen del Rocio University Hospital, Seville, Spain.
Br J Clin Pharmacol. 2021 Jul;87(7):2635-2644. doi: 10.1111/bcp.14689. Epub 2020 Dec 23.
To assess the appropriateness of the use and interpretation of subgroup analysis in haematology randomized clinical trials (RCTs).
A systematic review of Medline, including haematology phase III RCTs published between January 2013 and October 2019, was carried out to identify reported subgroup analysis. Information related to trial characteristics, subgroup analysis and claims of subgroup difference were collected.
The initial search identified 1622 studies. A total of 98 studies reporting subgroup analyses were identified. Of those, 24 RCT reported 46 claims of subgroup difference. Among them, 44 were claims for the primary outcome, of which 25 were considered strong claims and 17 were considered suggestions of a possible effect. Authors included subgroup variables for the primary outcome measured at baseline for 38 claims (n = 86.36%), used a subgroup variable as a stratification factor at randomization for 15 (34.09%), clearly prespecified their hypothesis for 11 (25%), the subgroup effect was one of a small number of hypothesised effects tested (≤ 5) for 17 (38.64%), carried out a test of interaction that provide statistically significant for 18 (40.91%), documented replication of a subgroup effect with previously related studies for 11 (25%), identified the consistency of a subgroup effect across related outcome for 10 (22.72%) and provided a biological rationale for the effect for 8 (18.18%). Of the 44 claims for the primary outcome, 34 (77.27%) met four or fewer of the 10 credibility criteria.
The subgroup claims reported in haematology RCTs lack credibility, even when the claims are strong. Information about subgroup difference should be interpreted cautiously.
评估血液学随机临床试验（RCT）中亚组分析的使用和解释是否恰当。
对 Medline 进行系统回顾，包括 2013 年 1 月至 2019 年 10 月期间发表的血液学 III 期 RCT，以确定报告的亚组分析。收集与试验特征、亚组分析和亚组差异主张相关的信息。
初步搜索确定了 1622 项研究。共确定了 98 项报告亚组分析的研究。其中，24 项 RCT 报告了 46 项亚组差异主张。其中，44 项是针对主要结局的主张，其中 25 项被认为是强有力的主张，17 项被认为是可能有效果的建议。作者在 38 项主张（n=86.36%）中纳入了基线时主要结局的亚组变量，在 15 项主张（34.09%）中使用亚组变量作为随机分层因素，11 项主张（25%）明确规定了其假设，亚组效应是少数假设效应之一（≤5）在 17 项主张中进行了测试（38.64%），进行了交互检验，18 项主张具有统计学意义（40.91%），11 项主张（25%）记录了与先前相关研究的亚组效应的复制，10 项主张（22.72%）确定了亚组效应在相关结局中的一致性，8 项主张（18.18%）为该效应提供了生物学依据。在 44 项针对主要结局的主张中，34 项（77.27%）符合 10 项可信度标准中的 4 项或更少。
血液学 RCT 中报告的亚组主张缺乏可信度，即使这些主张是强有力的。关于亚组差异的信息应谨慎解释。
