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Open Access Technical advance

On the proportional hazards model for occupational and environmental case-control analyses

Héloïse Gauvin12, Aude Lacourt123 and Karen Leffondré123*

Author affiliations

1 Department of Social and Preventive Medicine, University of Montreal, PO Box 6128, Downtown Station, Montreal, Quebec H3C 3J7, Canada

2 CHUM Research Centre, 3875 rue Saint-Urbain, Montreal, Quebec H2W 1V1, Canada

3 University of Bordeaux, ISPED, Centre INSERM U897-Epidemiology-Biostatistics, 146 rue Leo Saignat, Bordeaux, F-33000, France

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Citation and License

BMC Medical Research Methodology 2013, 13:18  doi:10.1186/1471-2288-13-18

Published: 15 February 2013

Abstract

Background

Case-control studies are generally designed to investigate the effect of exposures on the risk of a disease. Detailed information on past exposures is collected at the time of study. However, only the cumulated value of the exposure at the index date is usually used in logistic regression. A weighted Cox (WC) model has been proposed to estimate the effects of time-dependent exposures. The weights depend on the age conditional probabilities to develop the disease in the source population. While the WC model provided more accurate estimates of the effect of time-dependent covariates than standard logistic regression, the robust sandwich variance estimates were lower than the empirical variance, resulting in a low coverage probability of confidence intervals. The objectives of the present study were to investigate through simulations a new variance estimator and to compare the estimates from the WC model and standard logistic regression for estimating the effects of correlated temporal aspects of exposure with detailed information on exposure history.

Method

We proposed a new variance estimator using a superpopulation approach, and compared its accuracy to the robust sandwich variance estimator. The full exposure histories of source populations were generated and case-control studies were simulated within each source population. Different models with selected time-dependent aspects of exposure such as intensity, duration, and time since cessation were considered. The performances of the WC model using the two variance estimators were compared to standard logistic regression. The results of the different models were finally compared for estimating the effects of correlated aspects of occupational exposure to asbestos on the risk of mesothelioma, using population-based case-control data.

Results

The superpopulation variance estimator provided better estimates than the robust sandwich variance estimator and the WC model provided accurate estimates of the effects of correlated aspects of temporal patterns of exposure.

Conclusion

The WC model with the superpopulation variance estimator provides an alternative analytical approach for estimating the effects of time-varying exposures with detailed history exposure information in case-control studies, especially if many subjects have time-varying exposure intensity over lifetime, and if only one control is available for each case.

Keywords:
Case-control study; Cox model; Logistic regression; Time-dependent variables; Variance estimator; Occupational exposures; Environmental exposures; Superpopulation