Higgins Julian, Thompson Simon, Deeks Jonathan, Altman Douglas
MRC Biostatistics Unit, Institute of Public Health, Robinson Way, Cambridge CB2 2SR, UK.
J Health Serv Res Policy. 2002 Jan;7(1):51-61. doi: 10.1258/1355819021927674.
Heterogeneity between study results can be a problem in any systematic review or meta-analysis of clinical trials. Identifying its presence, investigating its cause and correctly accounting for it in analyses all involve difficult decisions for the researcher. Our objectives were: to collate recommendations on the subject of dealing with heterogeneity in systematic reviews of clinical trials; to investigate current practice in addressing heterogeneity in Cochrane reviews; and to compare current practice with recommendations.
We review guidelines for those undertaking systematic reviews and examine how heterogeneity is addressed in practice in a sample of systematic reviews, and their protocols, from the Cochrane Database of Systematic Reviews.
Advice to reviewers is on the whole consistent and sensible. However, examination of a sample of Cochrane protocols and reviews demonstrates that the advice is difficult to follow given the small numbers of studies identified in many systematic reviews, the difficulty of pre-specifying important effect modifiers for subgroup analysis or meta-regression and the unresolved debate concerning fixed versus random effects meta-analyses. There was disagreement between protocols and reviews, often either regarding choice of important potential effect modifiers or due to the review identifying too few studies to perform planned analyses.
Guidelines that address practical issues are required to reduce the risk of spurious findings from investigations of heterogeneity. This may involve discouraging statistical investigations such as subgroup analyses and meta-regression, rather than simply adopting a cautious approach to their interpretation, unless a large number of studies is available. The notion of a priori specification of potential effect modifiers for a retrospective review of studies is ill-defined, and the appropriateness of using a statistical test for heterogeneity to decide between analysis strategies is suspect.
在任何临床试验的系统评价或荟萃分析中，研究结果之间的异质性都可能是个问题。识别其存在、探究其原因并在分析中正确考虑它，这一切都给研究者带来了艰难的决策。我们的目标是：整理关于在临床试验系统评价中处理异质性问题的建议；调查Cochrane系统评价中处理异质性的当前实践；并将当前实践与建议进行比较。
我们查阅了针对进行系统评价的人员的指南，并检查了来自Cochrane系统评价数据库的系统评价样本及其方案在实践中是如何处理异质性的。
总体而言，给评价者的建议是一致且合理的。然而，对Cochrane方案和系统评价样本的检查表明，鉴于许多系统评价中纳入的研究数量较少，预先指定用于亚组分析或元回归的重要效应修饰因素存在困难，以及关于固定效应与随机效应荟萃分析的争论尚未解决，该建议难以遵循。方案和系统评价之间存在分歧，通常要么是关于重要潜在效应修饰因素的选择，要么是由于系统评价纳入的研究太少而无法进行计划的分析。
需要有解决实际问题的指南，以降低因异质性研究而得出虚假结果的风险。这可能涉及不鼓励进行亚组分析和元回归等统计调查，而不是简单地对其解释采取谨慎的方法，除非有大量研究可用。对于回顾性研究预先指定潜在效应修饰因素的先验概念定义不明确，使用异质性统计检验来决定分析策略的适用性也值得怀疑。
