Doubly robust methods for handling confounding by cluster

Biostatistics - Tập 17 Số 2 - Trang 264-276 - 2016
Johan Zetterqvist1, Stijn Vansteelandt2, Yudi Pawitan1, Arvid Sjölander1
1Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Nobels väg 12A, Solna, Sweden
2Department of Applied Mathematics, Computer Science and Statistics, Ghent University, Krijgslaan 281, S9, 9000, Ghent, Belgium

Tóm tắt

Abstract In clustered designs such as family studies, the exposure-outcome association is usually confounded by both cluster-constant and cluster-varying confounders. The influence of cluster-constant confounders can be eliminated by studying the exposure-outcome association within (conditional on) clusters, but additional regression modeling is usually required to control for observed cluster-varying confounders. A problem is that the working regression model may be misspecified, in which case the estimated within-cluster association may be biased. To reduce sensitivity to model misspecification we propose to augment the standard working model for the outcome with an auxiliary working model for the exposure. We derive a doubly robust conditional generalized estimating equation (DRCGEE) estimator for the within-cluster association. This estimator combines the two models in such a way that it is consistent if either model is correct, not necessarily both. Thus, the DRCGEE estimator gives the researcher two chances instead of only one to make valid inference on the within-cluster association. We have implemented the estimator in an R package and we use it to examine the association between smoking during pregnancy and cognitive abilities in offspring, in a sample of siblings.

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Tài liệu tham khảo

Cao, 2009, Improving efficiency and robustness of the doubly robust estimator for a population mean with incomplete data, Biometrika, 96, 723, 10.1093/biomet/asp033

Goetgeluk, 2008, Conditional generalized estimating equations for the analysis of clustered and longitudinal data, Biometrics, 64, 772, 10.1111/j.1541-0420.2007.00944.x

Kuja-Halkola, 2014, Maternal smoking during pregnancy and adverse outcomes in offspring: genetic and environmental sources of covariance, Behavior Genetics, 44, 456, 10.1007/s10519-014-9668-4

Neuhaus, 1998, Between-and within-cluster covariate effects in the analysis of clustered data, Biometrics, 54, 638, 10.2307/3109770

Neuhaus, 2006, Separating between-and within-cluster covariate effects by using conditional and partitioning methods, Journal of the Royal Statistical Society: Series B (Statistical Methodology), 68, 859, 10.1111/j.1467-9868.2006.00570.x

Robins, 1992, Estimating exposure effects by modelling the expectation of exposure conditional on confounders, Biometrics, 48, 479, 10.2307/2532304

Sjölander, 2012, Causal interpretation of between-within models for twin research, Epidemiologic Methods, 1, 217, 10.1515/2161-962X.1015

Tchetgen Tchetgen, 2010, On doubly robust estimation in a semiparametric odds ratio model, Biometrika, 97, 171, 10.1093/biomet/asp062

Vermeulen, 2014, Bias-reduced doubly robust estimation, Journal of the American Statistical Association, 10.1080/01621459.2014.958155