Centre for Evidence-Based Medicine Odense (CEBMO), Odense University Hospital, Kløvervænget 10, DK-5000 Odense C, Denmark
Nordic Cochrane Centre, Copenhagen, Denmark.
BMJ. 2020 Jan 21;368:l6802. doi: 10.1136/bmj.l6802.
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.
目的:研究盲法对估计治疗效果的影响及其在试验间的差异;区分患者、医疗保健提供者和观察者的盲法;检测偏倚和操作偏倚;以及结局类型(MetaBLIND 研究)。 设计:Meta-流行病学研究。 资料来源:Cochrane 系统评价数据库(2013-14 年)。 选择研究的资格标准:任何主题的盲法和非盲法试验的荟萃分析。 研究方法:从试验出版物和作者处检索盲法状态,并自动从 Cochrane 系统评价数据库中检索结果。贝叶斯分层模型估计了非盲法试验(或状态不明)与盲法试验之间比值比(ROR)的平均比值,并估计了试验间异质性的增加。次要分析调整了分配隐匿性、失访和试验规模的充分性,并探讨了结局主观性(高、中、低)与平均偏倚之间的关系。ROR 低于 1 表明无盲法试验的效应估计值过高。 结果:该研究纳入了 142 项荟萃分析(1153 项试验)。18 项患者报告结局的荟萃分析中,患者未盲的 ROR 为 0.91(95%可信区间 0.61 至 1.34),14 项由盲法观察者报告结局的荟萃分析中,ROR 为 0.98(0.69 至 1.39)。29 项医疗保健提供者决策结局(如再入院)的荟萃分析中,医疗保健提供者未盲的 ROR 为 1.01(0.84 至 1.19),13 项由盲法患者或观察者报告结局的荟萃分析中,ROR 为 0.97(0.64 至 1.45)。46 项主观观察者报告结局的荟萃分析中,观察者未盲的 ROR 为 1.01(0.86 至 1.18),且无明显的主观性程度影响。信息不足,无法确定缺乏盲法是否与试验间异质性增加有关。未报告为双盲的试验与报告为双盲的试验的 ROR 为 1.02(90 至 1.13),74 项荟萃分析中。 结论:没有证据表明有盲法和无盲法患者、医疗保健提供者或结局评估者的治疗效果估计值存在平均差异。这些结果可能反映出盲法的重要性不如人们通常认为的那样,或者是荟萃分析研究的局限性,如残余混杂或不精确。在现阶段,建议对这项研究进行复制,并且在试验中盲法应仍然是一种方法学保障。
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