Centre for Evidence-Based Medicine Odense (CEBMO), Odense University Hospital, Odense C, Denmark.
Department of Clinical Research, University of Southern Denmark, Odense M, Denmark.
Res Synth Methods. 2020 Mar;11(2):260-274. doi: 10.1002/jrsm.1392. Epub 2020 Jan 20.
Randomized clinical trials underpin evidence-based clinical practice, but flaws in their conduct may lead to biased estimates of intervention effects and hence invalid treatment recommendations. The main approach to the empirical study of bias is to collate a number of meta-analyses and, within each, compare the results of trials with and without a methodological characteristic such as blinding of participants and health professionals. Estimated within-meta-analysis differences are combined across meta-analyses, leading to an estimate of mean bias. Such "meta-epidemiological" studies are published in increasing numbers and have the potential to inform trial design, assessment of risk of bias, and reporting guidelines. However, their interpretation is complicated by issues of confounding, imprecision, and applicability. We developed a guide for interpreting meta-epidemiological studies, illustrated using MetaBLIND, a large study on the impact of blinding. Applying generally accepted principles of research methodology to meta-epidemiology, we framed 10 questions covering the main issues to consider when interpreting results of such studies, including risk of systematic error, risk of random error, issues related to heterogeneity, and theoretical plausibility. We suggest that readers of a meta-epidemiological study reflect comprehensively on the research question posed in the study, whether an experimental intervention was unequivocally identified for all included trials, the risk of misclassification of the trial characteristic, and the risk of confounding, i.e the adequacy of any adjustment for the likely confounders. We hope that our guide to interpretation of results of meta-epidemiological studies is helpful for readers of such studies.
随机临床试验是循证临床实践的基础,但在实施过程中的缺陷可能导致干预效果的估计存在偏差,从而导致无效的治疗建议。对偏倚进行实证研究的主要方法是整理一系列荟萃分析,并在每个荟萃分析中比较有和没有某种方法学特征(如参与者和卫生专业人员的盲法)的试验的结果。估计的荟萃分析内差异在荟萃分析之间进行合并,从而得出平均偏倚的估计值。这种“meta-epidemiological”研究越来越多,有可能为试验设计、偏倚风险评估和报告指南提供信息。然而,由于混杂、不精确性和适用性等问题,其解释变得复杂。我们制定了一个解释 meta-epidemiological 研究的指南,使用 MetaBLIND(一项关于盲法影响的大型研究)来说明。我们应用研究方法学的普遍接受原则来进行 meta-epidemiology 研究,提出了涵盖解释此类研究结果时需要考虑的主要问题的 10 个问题,包括系统误差风险、随机误差风险、与异质性相关的问题以及理论上的合理性。我们建议,meta-epidemiological 研究的读者应全面思考研究中提出的研究问题,是否明确确定了所有纳入试验的实验干预措施,试验特征的错误分类风险以及混杂风险,即对可能的混杂因素进行适当调整的风险。我们希望我们对 meta-epidemiological 研究结果解释的指南对这些研究的读者有所帮助。
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