Empirical Evidence of Study Design Biases in Randomized Trials: Systematic Review of Meta-Epidemiological Studies.
Empirical Evidence of Study Design Biases in Randomized Trials: Systematic Review of Meta-Epidemiological Studies.
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DOI：
10.1371/journal.pone.0159267
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Savović J
中科院分区：
文献类型：
--
作者：
Page MJ;Higgins JP;Clayton G;Sterne JA;Hróbjartsson A;Savović J
综合与随机试验报告方法学特征相关的平均偏倚和异质性的证据。元流行病学研究的系统综述。我们检索了近期关于该主题的AHRQ-EPC综述中纳入的合格研究（最新检索2012年9月），并检索了奥维德MEDLINE和奥维德EMBASE中2012年1月至2015年5月期间索引的研究。数据由一位作者提取并由另一位作者验证。我们使用随机效应模型在荟萃分析中合并了平均偏倚的估计值（例如比值比（ROR）或标准化均值差（dSMD））。分析按结局类型分层（“死亡率”与“其他客观”与“主观”）。将效应方向标准化，使得ROR < 1和dSMD < 0表示在特征不充分或不明确（与充分相比）的试验中更大的干预效应估计值。共纳入24项研究。现有证据表明，在序列生成不充分/不明确（相对于充分）（ROR 0.93，95% CI 0.86 - 0.99; 7项研究）和分配隐藏（ROR 0.90，95% CI 0.84 - 0.97; 7项研究）的试验中，干预效应估计值可能被夸大。对于这些特征，与其他客观结局相比，主观结局试验的平均偏倚似乎较大。此外，在缺乏/不清楚受试者设盲的试验中，主观结局的干预效果似乎被夸大了（相对于设盲）（dSMD-0.37，95% CI -0.77至0.04; 2项研究），结局评估者设盲缺乏/不明确（ROR 0.64，95% CI 0.43 - 0.96; 1项研究）和缺乏/不清楚双盲（ROR 0.77，95% CI 0.61 - 0.93; 1项研究）。其他特征（例如，揭盲试验人员、减员）的影响尚不清楚。随机试验的某些特征可能会夸大干预效果的估计。在主观结果的试验中，平均偏倚似乎最大。需要对几个特征，特别是自然减员和选择性报告进行更多的研究。
To synthesise evidence on the average bias and heterogeneity associated with reported methodological features of randomized trials. Systematic review of meta-epidemiological studies. We retrieved eligible studies included in a recent AHRQ-EPC review on this topic (latest search September 2012), and searched Ovid MEDLINE and Ovid EMBASE for studies indexed from Jan 2012-May 2015. Data were extracted by one author and verified by another. We combined estimates of average bias (e.g. ratio of odds ratios (ROR) or difference in standardised mean differences (dSMD)) in meta-analyses using the random-effects model. Analyses were stratified by type of outcome (“mortality” versus “other objective” versus “subjective”). Direction of effect was standardised so that ROR < 1 and dSMD < 0 denotes a larger intervention effect estimate in trials with an inadequate or unclear (versus adequate) characteristic. We included 24 studies. The available evidence suggests that intervention effect estimates may be exaggerated in trials with inadequate/unclear (versus adequate) sequence generation (ROR 0.93, 95% CI 0.86 to 0.99; 7 studies) and allocation concealment (ROR 0.90, 95% CI 0.84 to 0.97; 7 studies). For these characteristics, the average bias appeared to be larger in trials of subjective outcomes compared with other objective outcomes. Also, intervention effects for subjective outcomes appear to be exaggerated in trials with lack of/unclear blinding of participants (versus blinding) (dSMD -0.37, 95% CI -0.77 to 0.04; 2 studies), lack of/unclear blinding of outcome assessors (ROR 0.64, 95% CI 0.43 to 0.96; 1 study) and lack of/unclear double blinding (ROR 0.77, 95% CI 0.61 to 0.93; 1 study). The influence of other characteristics (e.g. unblinded trial personnel, attrition) is unclear. Certain characteristics of randomized trials may exaggerate intervention effect estimates. The average bias appears to be greatest in trials of subjective outcomes. More research on several characteristics, particularly attrition and selective reporting, is needed.