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American Journal of Epidemiology Advance Access originally published online on October 3, 2008
American Journal of Epidemiology 2008 168(10):1204-1210; doi:10.1093/aje/kwn236
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American Journal of Epidemiology © The Author 2008. Published by the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

PRACTICE OF EPIDEMIOLOGY

Combining Matched and Unmatched Control Groups in Case-Control Studies

Saskia le Cessie, Nico Nagelkerke, Frits R. Rosendaal, Karlijn J. van Stralen, Elisabeth R. Pomp and Hans C. van Houwelingen

Correspondence to Dr. Saskia le Cessie, Department of Medical Statistics and Bioinformatics, S5-P, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, the Netherlands (e-mail: cessie{at}lumc.nl).

Received for publication February 8, 2008. Accepted for publication July 14, 2008.

Multiple control groups in case-control studies are used to control for different sources of confounding. For example, cases can be contrasted with matched controls to adjust for multiple genetic or unknown lifestyle factors and simultaneously contrasted with an unmatched population-based control group. Inclusion of different control groups for a single exposure analysis yields several estimates of the odds ratio, all using only part of the data. Here the authors introduce an easy way to combine odds ratios from several case-control analyses with the same cases. The approach is based upon methods used for meta-analysis but takes into account the fact that the same cases are used and that the estimated odds ratios are therefore correlated. Two ways of estimating this correlation are discussed: sandwich methodology and the bootstrap. Confidence intervals for the pooled estimates and a test for checking whether the odds ratios in the separate case-control studies differ significantly are derived. The performance of the method is studied by simulation and by applying the methods to a large study on risk factors for thrombosis, the MEGA Study (1999–2004), wherein cases with first venous thrombosis were included with a matched control group of partners and an unmatched population-based control group.

bootstrap; case-control studies; control groups; matching; sandwich estimator; venous thrombosis

Abbreviations: MEGA, Multiple Environmental and Genetic Assessment of Risk Factors for Venous Thrombosis


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