丹麦欧登塞大学医院Helene Moustgaard课题组研究了随机临床试验中盲法对估计治疗效果的影响。这一研究成果于2020年1月21日发表在国际顶尖学术期刊《英国医学杂志》上。

为了研究盲法对估计疗效的影响，以及试验之间的差异，区分患者、医疗保健提供者和观察者间的盲法检验和表现偏倚，以及结局类型等，研究组设计了一项流行病学的荟萃研究。

采用2013-2014年的Cochrane系统评估数据库，检索任意主题的双盲或单盲试验，采用贝叶斯层次模型对非盲试验和盲法试验的平均优势比（ROR）进行估计，并评估试验间异质性的增加程度。

研究组最终纳入142项荟萃分析，共1153项试验。18项由患者报告结果的荟萃分析中患者非盲的ROR为0.91，14项由盲观察者汇报结果的荟萃分析的ROR为0.98。29项由医疗保健提供者决定结局的荟萃分析中医疗保健提供者非盲的ROR为1.01，13项由盲患者或盲观察者报告结果的荟萃分析的ROR为0.97。

46项由主观观察者报告结果的荟萃分析中观察者非盲的ROR为1.01，主观程度无明确影响。上述信息不足以确定非盲与试验间异质性增加有关。74项荟萃分析中，非双盲试验与双盲试验的ROR为1.02。

总之，没有任何证据表明，在患者、健康保健提供者或结果评估者盲或非盲的试验中，估计的治疗效果存在平均差异。该结果反映出盲法与通常认为或流行病学荟萃研究的限制（如残余混杂或不精确性）相比，较不重要。

附：原文原文

Title: Impact of blinding on estimated treatment effects in randomised clinical trials: meta-epidemiological study

Author: Helene Moustgaard, Gemma L Clayton, Hayley E Jones, Isabelle Boutron, Lars Jrgensen, David L T Laursen, Mette F Olsen, Asger Paludan-Müller, Philippe Ravaud, Jelena Savovi, Jonathan A C Sterne, Julian P T Higgins, Asbjrn Hróbjartsson

Issue&Volume: 2020/01/21

Abstract: 

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 studies Meta-analyses with both blinded and non-blinded trials on any topic.

Review methods Blinding 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.

Results The 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.

Conclusion No 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.

DOI: 10.1136/bmj.l6802

Source: https://www.bmj.com/content/368/bmj.l6802