Influence of Reported Study Design Characteristics on Intervention Effect Estimates From Randomized, Controlled Trials
Influence of Reported Study Design Characteristics on Intervention Effect Estimates From Randomized, Controlled Trials
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DOI：
10.7326/0003-4819-157-6-201209180-00537
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发表时间：
2012-09-18
影响因子：
39.2
通讯作者：
Sterne, Jonathan A. C.
中科院分区：
文献类型：
--
作者：
Savovic, Jelena;Jones, Hayley E.;Sterne, Jonathan A. C.
已发表的证据表明，试验设计的各个方面导致干预效果估计有偏倚，但不同研究的结果不一致。本研究结合了7项荟萃流行病学研究的数据，剔除了重叠部分，得出了包含1973项试验的234项独特荟萃分析的最终数据集。结果测量分为“死亡率”、“其他客观”、“或主观”，贝叶斯层次模型用于估计试验特征与平均偏倚和试验间异质性的关联。在随机序列生成不充分或不明确（95%可信区间{CrI}， 0.82至0.96）和分配隐藏不充分或不明确（95%可信区间{CrI}， 0.87至0.99）的试验中，干预效果估计似乎被夸大了（优势比比，0.93 [CrI， 0.87至0.99]）。缺乏或不明确双盲（与双盲相比）与干预效果平均夸大13%相关（优势比为0.87 [CrI， 0.79至0.96]），并且这类研究的试验间异质性增加（标准差增加，0.14 [CrI， 0.02至0.30]）。对于每个特征，平均偏倚和试验间异质性的增加主要是由主观结果的试验驱动的，在客观和死亡率结果的试验中几乎没有偏倚的证据。本研究受到试验报告不完整的限制，研究结果可能被其他研究设计特征所混淆。与研究设计特征相关的偏倚可能导致干预效果估计的夸大，以及报告主观评估结果的试验中试验间异质性的增加。
Published evidence suggests that aspects of trial design lead to biased intervention effect estimates, but findings from different studies are inconsistent. This study combined data from 7 meta-epidemiologic studies and removed overlaps to derive a final data set of 234 unique meta-analyses containing 1973 trials. Outcome measures were classified as "mortality," "other objective," "or subjective," and Bayesian hierarchical models were used to estimate associations of trial characteristics with average bias and between-trial heterogeneity. Intervention effect estimates seemed to be exaggerated in trials with inadequate or unclear (vs. adequate) random-sequence generation (ratio of odds ratios, 0.89 [95% credible interval {CrI}, 0.82 to 0.96]) and with inadequate or unclear (vs. adequate) allocation concealment (ratio of odds ratios, 0.93 [CrI, 0.87 to 0.99]). Lack of or unclear double-blinding (vs. double-blinding) was associated with an average of 13% exaggeration of intervention effects (ratio of odds ratios, 0.87 [CrI, 0.79 to 0.96]), and between-trial heterogeneity was increased for such studies (SD increase in heterogeneity, 0.14 [CrI, 0.02 to 0.30]). For each characteristic, average bias and increases in between-trial heterogeneity were driven primarily by trials with subjective outcomes, with little evidence of bias in trials with objective and mortality outcomes. This study is limited by incomplete trial reporting, and findings may be confounded by other study design characteristics. Bias associated with study design characteristics may lead to exaggeration of intervention effect estimates and increases in between-trial heterogeneity in trials reporting subjectively assessed outcomes.