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异质性临床试验的Meta分析进展I:逆方差异质性模型

Advances in the meta-analysis of heterogeneous clinical trials I: The inverse variance heterogeneity model.

作者信息

Doi Suhail A R, Barendregt Jan J, Khan Shahjahan, Thalib Lukman, Williams Gail M

机构信息

Research School of Population Health, Australian National University, Canberra, Australia.

Epigear International, Sunrise Beach, Australia; School of Population Health, University of Queensland, Brisbane, Australia.

出版信息

Contemp Clin Trials. 2015 Nov;45(Pt A):130-8. doi: 10.1016/j.cct.2015.05.009. Epub 2015 May 21.

Abstract

This article examines an improved alternative to the random effects (RE) model for meta-analysis of heterogeneous studies. It is shown that the known issues of underestimation of the statistical error and spuriously overconfident estimates with the RE model can be resolved by the use of an estimator under the fixed effect model assumption with a quasi-likelihood based variance structure - the IVhet model. Extensive simulations confirm that this estimator retains a correct coverage probability and a lower observed variance than the RE model estimator, regardless of heterogeneity. When the proposed IVhet method is applied to the controversial meta-analysis of intravenous magnesium for the prevention of mortality after myocardial infarction, the pooled OR is 1.01 (95% CI 0.71-1.46) which not only favors the larger studies but also indicates more uncertainty around the point estimate. In comparison, under the RE model the pooled OR is 0.71 (95% CI 0.57-0.89) which, given the simulation results, reflects underestimation of the statistical error. Given the compelling evidence generated, we recommend that the IVhet model replace both the FE and RE models. To facilitate this, it has been implemented into free meta-analysis software called MetaXL which can be downloaded from www.epigear.com.

摘要

本文探讨了一种用于异质性研究荟萃分析的随机效应(RE)模型的改进替代方法。研究表明,RE模型中已知的统计误差低估和虚假过度自信估计问题,可以通过使用基于拟似然方差结构的固定效应模型假设下的估计器——IVhet模型来解决。大量模拟证实,无论异质性如何,该估计器都能保持正确的覆盖概率,且观察到的方差比RE模型估计器更低。当将所提出的IVhet方法应用于关于静脉注射镁预防心肌梗死后死亡率的有争议的荟萃分析时,合并的比值比为1.01(95%置信区间0.71 - 1.46),这不仅有利于规模较大的研究,而且表明点估计周围存在更多不确定性。相比之下,在RE模型下,合并的比值比为0.71(95%置信区间0.57 - 0.89),鉴于模拟结果,这反映了统计误差的低估。鉴于所产生的有力证据,我们建议用IVhet模型取代固定效应(FE)模型和RE模型。为便于使用,它已被应用到一款名为MetaXL的免费荟萃分析软件中,该软件可从www.epigear.com下载。

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