Global Regulatory Sciences, Pharmacovigilance and Epidemiology, Bristol-Myers Squibb, NJ 08534, USA.
Pharmacoepidemiol Drug Saf. 2011 Oct;20(10):1014-20. doi: 10.1002/pds.2208. Epub 2011 Aug 19.
In recent years, comparative effectiveness research has been more aggressively pursued as a means to improve health care, including systematic reviews and meta-analyses to inform health policy decision making. Because most clinical trials have pre-specified approaches to collecting data on efficacy, the value of systematic reviews and meta-analyses in assessing efficacy outcomes is generally accepted. In contrast, collection of data on adverse events is seldom well structured. Hence, the methodological considerations for comparing adverse events from such non-aligned sources differ substantially from those for comparing efficacy endpoints. We address several important pitfalls in performing systematic reviews and meta-analyses on adverse events in clinical trials, and we offer recommendations for remedies. Some pitfalls arise from the fact that adverse events often are not the primary endpoints in clinical trials, hence incomplete reporting, inconsistent event definitions, various level of effort in reporting unexpected adverse events, and inappropriate use of statistical testing. Others are posed by certain important characteristics of adverse events data. The very concept of "adverse events" may skew the ascertainment, attribution, and reporting of the events. In addition, problems for meta-analysis methods arise in situations involving zero or rare events and withdrawal or loss to follow-up because of adverse events. We highlight recent initiatives that may improve the assessment and cross-study summary of adverse events. We anticipate that future guidance for conducting systematic reviews and meta-analyses will evolve to address the important methodological pitfalls we highlight here, and the practice of assessing the totality of evidence on drug safety will be improved.
近年来，人们更加积极地开展了比较疗效研究，以改善医疗保健，包括系统评价和荟萃分析，为卫生政策决策提供信息。由于大多数临床试验都预先规定了收集疗效数据的方法，因此系统评价和荟萃分析在评估疗效结果方面的价值是普遍被接受的。相比之下，不良事件数据的收集很少有良好的结构化。因此，从非对齐来源比较不良事件的方法学考虑与比较疗效终点的方法学考虑有很大不同。我们讨论了在临床试验中进行不良事件的系统评价和荟萃分析时存在的几个重要陷阱，并提出了补救建议。一些陷阱源于这样一个事实，即不良事件通常不是临床试验的主要终点，因此报告不完整、事件定义不一致、报告意外不良事件的努力程度不同以及统计检验的不当使用。其他陷阱则是由不良事件数据的某些重要特征造成的。“不良事件”的概念本身就可能扭曲事件的确定、归因和报告。此外，在涉及零事件或罕见事件以及因不良事件而退出或失访的情况下，荟萃分析方法也会出现问题。我们强调了一些可能改善不良事件评估和跨研究总结的最新举措。我们预计，未来将制定关于进行系统评价和荟萃分析的指南，以解决我们在这里强调的重要方法学陷阱，并且对药物安全性的整体证据的评估实践将会得到改善。
