Peninsula College of Medicine and Dentistry, St Luke's Campus, University of Exeter, Exeter, UK.
BMC Med Res Methodol. 2012 May 3;12:64. doi: 10.1186/1471-2288-12-64.
Adverse consequences of medical interventions are a source of concern, but clinical trials may lack power to detect elevated rates of such events, while observational studies have inherent limitations. Meta-analysis allows the combination of individual studies, which can increase power and provide stronger evidence relating to adverse events. However, meta-analysis of adverse events has associated methodological challenges. The aim of this study was to systematically identify and review the methodology used in meta-analyses where a primary outcome is an adverse or unintended event, following a therapeutic intervention.
Using a collection of reviews identified previously, 166 references including a meta-analysis were selected for review. At least one of the primary outcomes in each review was an adverse or unintended event. The nature of the intervention, source of funding, number of individual meta-analyses performed, number of primary studies included in the review, and use of meta-analytic methods were all recorded. Specific areas of interest relating to the methods used included the choice of outcome metric, methods of dealing with sparse events, heterogeneity, publication bias and use of individual patient data.
The 166 included reviews were published between 1994 and 2006. Interventions included drugs and surgery among other interventions. Many of the references being reviewed included multiple meta-analyses with 44.6% (74/166) including more than ten. Randomised trials only were included in 42.2% of meta-analyses (70/166), observational studies only in 33.7% (56/166) and a mix of observational studies and trials in 15.7% (26/166). Sparse data, in the form of zero events in one or both arms where the outcome was a count of events, was found in 64 reviews of two-arm studies, of which 41 (64.1%) had zero events in both arms.
Meta-analyses of adverse events data are common and useful in terms of increasing the power to detect an association with an intervention, especially when the events are infrequent. However, with regard to existing meta-analyses, a wide variety of different methods have been employed, often with no evident rationale for using a particular approach. More specifically, the approach to dealing with zero events varies, and guidelines on this issue would be desirable.
医疗干预的不良后果是人们关注的一个问题，但临床试验可能缺乏发现此类事件发生率升高的能力，而观察性研究则存在固有局限性。荟萃分析可以合并个体研究，从而提高发现不良事件的能力并提供更强有力的证据。但是，不良事件的荟萃分析存在相关的方法学挑战。本研究的目的是系统地识别和审查主要结局为治疗干预后不良或非预期事件的荟萃分析中使用的方法。
使用先前确定的综述集，选择了 166 篇参考文献进行综述，其中至少有一篇综述的主要结局为不良或非预期事件。记录了每项综述中的干预措施性质、资金来源、进行的个体荟萃分析数量、综述中纳入的原始研究数量以及荟萃分析方法的使用情况。与所使用方法相关的特定关注领域包括结局指标的选择、处理稀疏事件的方法、异质性、发表偏倚和使用个体患者数据。
纳入的 166 篇综述发表于 1994 年至 2006 年之间。干预措施包括药物和手术等。许多被审查的参考文献包含多个荟萃分析，其中 44.6%（74/166）包含 10 个以上的荟萃分析。只有随机试验的荟萃分析占 42.2%（70/166），只有观察性研究的荟萃分析占 33.7%（56/166），观察性研究和试验混合的荟萃分析占 15.7%（26/166）。在两臂研究的 64 篇综述中发现了稀疏数据，表现为一种计数结局的事件中，一个或两个臂的零事件，其中 41 篇（64.1%）两个臂均为零事件。
不良事件数据的荟萃分析很常见，并且在提高发现与干预措施关联的能力方面非常有用，特别是在事件不常见的情况下。但是，对于现有的荟萃分析，使用了各种不同的方法，而且使用特定方法的理由通常不明显。更具体地说，处理零事件的方法各不相同，因此需要制定相关指南。
