Objective Meta-analyses of observational studies are frequently published in the literature, but they are generally considered suboptimal to those involving randomised controlled trials (RCTs) only. This is due to the increased risk of biases that observational studies may entail as well as because of the high heterogeneity that might be present. In this article, we highlight aspects of meta-analyses with observational studies that need more careful consideration in comparison to meta-analyses of RCTs. Methods We present an overview of recommendations from the literature with respect to how the different steps of a meta-analysis involving observational studies should be comprehensively conducted. We focus more on issues arising at the step of the quantitative synthesis, in terms of handling heterogeneity and biases. We briefly describe some sophisticated synthesis methods, which may allow for more flexible modelling approaches than common meta-analysis models. We illustrate the issues encountered in the presence of observational studies using an example from mental health, which assesses the risk of myocardial infarction in antipsychotic drug users. Results The increased heterogeneity observed among studies challenges the interpretation of the diamond, while the inclusion of short exposure studies may lead to an exaggerated risk for myocardial infarction in this population. Conclusions In the presence of observational study designs, prior to synthesis, investigators should carefully consider whether all studies at hand are able to answer the same clinical question. The potential for a quantitative synthesis should be guided through examination of the amount of clinical and methodological heterogeneity and assessment of possible biases.

中文翻译：

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观察性研究荟萃分析的挑战。

客观观察性研究的荟萃分析经常在文献中发表，但它们通常被认为不适合那些仅涉及随机对照试验 (RCT) 的研究。这是由于观察性研究可能带来的偏差风险增加以及可能存在的高度异质性。在本文中，我们重点介绍了观察性研究的荟萃分析的各个方面，与随机对照试验的荟萃分析相比，这些方面需要更仔细的考虑。方法我们概述了文献中关于如何全面进行涉及观察性研究的荟萃分析的不同步骤的建议。我们更关注定量综合步骤中出现的问题，即处理异质性和偏差。我们简要描述了一些复杂的综合方法，这些方法可能比常见的荟萃分析模型更灵活的建模方法。我们使用心理健康的一个例子来说明观察性研究中遇到的问题，该研究评估抗精神病药物使用者发生心肌梗死的风险。结果 研究中观察到的异质性增加对钻石的解释提出了挑战，而纳入短时间暴露研究可能会导致该人群发生心肌梗塞的风险被夸大。结论 在存在观察性研究设计的情况下，在综合之前，研究人员应仔细考虑手头的所有研究是否能够回答相同的临床问题。应通过检查临床和方法学异质性的数量以及评估可能的偏差来指导定量综合的潜力。