5/F, Xiangya School of Public Health, No. 238, Shang-ma-yuan-ling Alley, Kaifu district, Changsha, China.
Alice Lee Centre for Nursing Studies, National University of Singapore, Singapore, Singapore.
BMC Med Res Methodol. 2022 Jun 15;22(1):171. doi: 10.1186/s12874-022-01650-5.
To summarize the up-to-date empirical evidence on trial-level characteristics of randomized controlled trials associated with treatment effect estimates.
A systematic review searched three databases up to August 2020. Meta-epidemiological (ME) studies of randomized controlled trials on intervention effect were eligible. We assessed the methodological quality of ME studies using a self-developed criterion. Associations between treatment effect estimates and trial-level characteristics were presented using forest plots.
Eighty ME studies were included, with 25/80 (31%) being published after 2015. Less than one-third ME studies critically appraised the included studies (26/80, 33%), published a protocol (23/80, 29%), and provided a list of excluded studies with justifications (12/80, 15%). Trials with high or unclear (versus low) risk of bias on sequence generation (3/14 for binary outcome and 1/6 for continuous outcome), allocation concealment (11/18 and 1/6), double blinding (5/15 and 2/4) and smaller sample size (4/5 and 2/2) significantly associated with larger treatment effect estimates. Associations between high or unclear risk of bias on allocation concealment (5/6 for binary outcome and 1/3 for continuous outcome), double blinding (4/5 and 1/3) and larger treatment effect estimates were more frequently observed for subjective outcomes. The associations between treatment effect estimates and non-blinding of outcome assessors were removed in trials using multiple observers to reach consensus for both binary and continuous outcomes. Some trial characteristics in the Cochrane risk-of-bias (RoB2) tool have not been covered by the included ME studies, including using validated method for outcome measures and selection of the reported results from multiple outcome measures or multiple analysis based on results (e.g., significance of the results).
Consistently significant associations between larger treatment effect estimates and high or unclear risk of bias on sequence generation, allocation concealment, double blinding and smaller sample size were found. The impact of allocation concealment and double blinding were more consistent for subjective outcomes. The methodological and reporting quality of included ME studies were dissatisfactory. Future ME studies should follow the corresponding reporting guideline. Specific guidelines for conducting and critically appraising ME studies are needed.
总结与治疗效果估计相关的随机对照试验的最新试验水平特征的实证证据。
系统综述搜索了三个数据库，截止到 2020 年 8 月。干预效果的随机对照试验的元流行病学（ME）研究符合条件。我们使用自行制定的标准评估 ME 研究的方法学质量。使用森林图展示治疗效果估计与试验水平特征之间的关系。
共纳入 80 项 ME 研究，其中 25/80（31%）发表于 2015 年后。不到三分之一的 ME 研究（26/80，33%）批判性地评价了纳入的研究，发表了方案（23/80，29%），并提供了附有理由的排除研究清单（12/80，15%）。在随机序列生成（二分类结局为 3/14，连续结局为 1/6）、分配隐藏（11/18 和 1/6）、双盲（5/15 和 2/4）和样本量较小（4/5 和 2/2）方面高或不清楚（而非低）风险的试验与较大的治疗效果估计显著相关。在主观结局中，分配隐藏（二分类结局为 5/6，连续结局为 1/3）和高或不清楚（而非低）风险的双盲（4/5 和 1/3）与较大的治疗效果估计之间的关联更为常见。在使用多个观察者对二分类和连续结局达成共识的试验中，结局评估者未设盲与较大的治疗效果估计之间的关联被消除。Cochrane 偏倚风险（RoB2）工具中的一些试验特征未被纳入的 ME 研究所涵盖，包括对结局测量使用经过验证的方法，以及从多个结局测量或基于结果的多重分析中选择报告结果（例如，结果的显著性）。
发现较大的治疗效果估计与随机序列生成、分配隐藏、双盲和样本量较小的高或不清楚的偏倚风险之间存在一致的显著关联。对于主观结局，分配隐藏和双盲的影响更为一致。纳入的 ME 研究的方法学和报告质量并不令人满意。未来的 ME 研究应遵循相应的报告指南。需要制定具体的指南来进行和批判性地评价 ME 研究。
