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

Doi, Suhail A. R. and Barendregt, Jan J. and Khan, Shahjahan and Thalib, Lukman and Williams, Gail M. (2015) Advances in the meta-analysis of heterogeneous clinical trials I: the inverse variance heterogeneity model. Contemporary Clinical Trials, 45 (A). pp. 130-138. ISSN 1551-7144


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 REmodel estimator, regardless of heterogeneity.When the proposed IVhetmethod is applied to the controversialmeta-analysis of intravenousmagnesium 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 REmodels. To facilitate this, it has been implemented into freemeta-analysis software called MetaXL which can be downloaded from

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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Additional Information: Permanent restricted access to Published version in accordance with the copyright policy of the publisher.
Faculty/School / Institute/Centre: Current - Faculty of Health, Engineering and Sciences - School of Agricultural, Computational and Environmental Sciences
Date Deposited: 07 Dec 2015 04:36
Last Modified: 27 Sep 2016 04:56
Uncontrolled Keywords: fixed effect; heterogeneity; meta-analysis; quasi-likelihood; random effects
Fields of Research : 11 Medical and Health Sciences > 1199 Other Medical and Health Sciences > 119999 Medical and Health Sciences not elsewhere classified
01 Mathematical Sciences > 0104 Statistics > 010402 Biostatistics
Socio-Economic Objective: E Expanding Knowledge > 97 Expanding Knowledge > 970111 Expanding Knowledge in the Medical and Health Sciences
E Expanding Knowledge > 97 Expanding Knowledge > 970101 Expanding Knowledge in the Mathematical Sciences
Identification Number or DOI: 10.1016/j.cct.2015.05.009

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