Impact of blinding on estimated treatment effects in randomised clinical trials: meta-epidemiological study
Impact of blinding on estimated treatment effects in randomised clinical trials: meta-epidemiological study
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DOI：
10.1136/bmj.l6802
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发表时间：
2020-01-21
影响因子：
105.7
通讯作者：
Hrobjartsson, Asbjorn
中科院分区：
文献类型：
--
作者：
Moustgaard, Helene;Clayton, Gemma L.;Hrobjartsson, Asbjorn
目的 研究盲法对估计治疗效果的影响及其试验之间的差异；区分患者、医疗保健提供者和观察者的盲法；检测偏差和性能偏差；设计元流行病学研究。数据来源 Cochrane 系统评价数据库 (2013-14)。选择研究的资格标准对任何主题进行盲法和非盲法荟萃分析。审查方法从试验出版物和作者中检索盲态状态，并从 Cochrane 系统评价数据库中自动检索结果。贝叶斯分层模型估计了非盲试验（或状态不明确）与盲试验的平均比值比 (ROR)，并估计了试验之间异质性的增加。二次分析根据分配隐藏的充分性、自然减员和试验规模进行调整，并探讨结果主观性（高、中、低）和平均偏倚之间的关联。 ROR 低于 1 表明在未采用盲法的试验中夸大了效应估计。结果该研究包括 142 项荟萃分析（1153 项试验）。在 18 项患者报告结果的荟萃分析中，未对患者实施盲法的 ROR 为 0.91（95% 可信区间为 0.61 至 1.34），在 14 项由盲法观察者报告结果的荟萃分析中，ROR 为 0.98（0.69 至 1.39）。在 29 项针对医疗保健提供者决策结果（例如，再入院）的荟萃分析中，未对医疗保健提供者实施盲法的 ROR 为 1.01（0.84 至 1.19），在 13 项由盲法患者或观察者报告的结果荟萃分析中，ROR 为 0.97（0.64 至 1.45）。在 46 项具有主观观察者报告结果的荟萃分析中，未对观察者施盲的 ROR 为 1.01（0.86 至 1.18），主观程度没有明显影响。信息不足以确定缺乏盲法是否与试验之间的异质性增加有关。在 74 项荟萃分析中，未报告为双盲的试验与双盲试验的 ROR 为 1.02（0.90 至 1.13）。 结论 没有发现证据表明有或没有盲法患者、医疗保健提供者或结果评估者的试验之间估计治疗效果的平均差异。这些结果可能反映出，盲法并不像通常认为的或元流行病学研究的局限性（例如残余混杂或不精确性）那么重要。在这个阶段，建议重复这项研究，并且盲法应该仍然是试验中的方法学保障。
OBJECTIVES To study the impact of blinding on estimated treatment effects, and their variation between trials; differentiating between blinding of patients, healthcare providers, and observers; detection bias and performance bias; and types of outcome (the MetaBLIND study).DESIGN Meta-epidemiological study.DATA SOURCE Cochrane Database of Systematic Reviews (2013-14).ELIGIBILITY CRITERIA FOR SELECTING STUDIESMeta-analyses with both blinded and non-blinded trials on any topic.REVIEW METHODSBlinding status was retrieved from trial publications and authors, and results retrieved automatically from the Cochrane Database of Systematic Reviews. Bayesian hierarchical models estimated the average ratio of odds ratios (ROR), and estimated the increases in heterogeneity between trials, for non-blinded trials (or of unclear status) versus blinded trials. Secondary analyses adjusted for adequacy of concealment of allocation, attrition, and trial size, and explored the association between outcome subjectivity (high, moderate, low) and average bias. An ROR lower than 1 indicated exaggerated effect estimates in trials without blinding.RESULTSThe study included 142 meta-analyses (1153 trials). The ROR for lack of blinding of patients was 0.91 (95% credible interval 0.61 to 1.34) in 18 meta-analyses with patient reported outcomes, and 0.98 (0.69 to 1.39) in 14 meta-analyses with outcomes reported by blinded observers. The ROR for lack of blinding of healthcare providers was 1.01 (0.84 to 1.19) in 29 meta-analyses with healthcare provider decision outcomes (eg, readmissions), and 0.97 (0.64 to 1.45) in 13 meta-analyses with outcomes reported by blinded patients or observers. The ROR for lack of blinding of observers was 1.01 (0.86 to 1.18) in 46 meta-analyses with subjective observer reported outcomes, with no clear impact of degree of subjectivity. Information was insufficient to determine whether lack of blinding was associated with increased heterogeneity between trials. The ROR for trials not reported as double blind versus those that were double blind was 1.02 (0.90 to 1.13) in 74 meta-analyses.CONCLUSIONNo evidence was found for an average difference in estimated treatment effect between trials with and without blinded patients, healthcare providers, or outcome assessors. These results could reflect that blinding is less important than often believed or meta-epidemiological study limitations, such as residual confounding or imprecision. At this stage, replication of this study is suggested and blinding should remain a methodological safeguard in trials.