Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
National Institute for Health Research.
Am J Epidemiol. 2018 May 1;187(5):1113-1122. doi: 10.1093/aje/kwx344.
Flaws in the design of randomized trials may bias intervention effect estimates and increase between-trial heterogeneity. Empirical evidence suggests that these problems are greatest for subjectively assessed outcomes. For the Risk of Bias in Evidence Synthesis (ROBES) Study, we extracted risk-of-bias judgements (for sequence generation, allocation concealment, blinding, and incomplete data) from a large collection of meta-analyses published in the Cochrane Library (issue 4; April 2011). We categorized outcome measures as mortality, other objective outcome, or subjective outcome, and we estimated associations of bias judgements with intervention effect estimates using Bayesian hierarchical models. Among 2,443 randomized trials in 228 meta-analyses, intervention effect estimates were, on average, exaggerated in trials with high or unclear (versus low) risk-of-bias judgements for sequence generation (ratio of odds ratios (ROR) = 0.91, 95% credible interval (CrI): 0.86, 0.98), allocation concealment (ROR = 0.92, 95% CrI: 0.86, 0.98), and blinding (ROR = 0.87, 95% CrI: 0.80, 0.93). In contrast to previous work, we did not observe consistently different bias for subjective outcomes compared with mortality. However, we found an increase in between-trial heterogeneity associated with lack of blinding in meta-analyses with subjective outcomes. Inconsistency in criteria for risk-of-bias judgements applied by individual reviewers is a likely limitation of routinely collected bias assessments. Inadequate randomization and lack of blinding may lead to exaggeration of intervention effect estimates in randomized trials.
随机试验设计中的缺陷可能会使干预效果估计产生偏差,并增加试验间的异质性。实证证据表明,这些问题在主观评估结果中最为严重。在风险偏差评估证据综合(ROBES)研究中,我们从发表在 Cochrane Library(2011 年 4 月第 4 期)的大量荟萃分析中提取了风险偏差判断(用于序列生成、分配隐藏、盲法和不完整数据)。我们将结果指标分为死亡率、其他客观结果或主观结果,并使用贝叶斯层次模型估计偏差判断与干预效果估计之间的关联。在 228 项荟萃分析的 2443 项随机试验中,与低风险偏差判断相比,高风险或不确定(而非低)风险偏差判断的试验中,干预效果估计平均被夸大(比值比(OR)=0.91,95%可信区间(CrI):0.86,0.98),对于序列生成(OR=0.92,95%CrI:0.86,0.98)、分配隐藏(OR=0.92,95%CrI:0.86,0.98)和盲法(OR=0.87,95%CrI:0.80,0.93)。与之前的工作不同,我们没有观察到与死亡率相比,主观结果的偏差存在一致性差异。然而,我们发现,在没有盲法的荟萃分析中,主观结果的试验间异质性增加。个别审查员应用风险偏差判断标准的不一致性很可能是常规收集偏差评估的一个局限性。随机分配不足和缺乏盲法可能导致随机试验中干预效果估计的夸大。
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