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American Journal of Epidemiology Advance Access originally published online on August 12, 2009
American Journal of Epidemiology 2009 170(6):687-694; doi:10.1093/aje/kwp175
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American Journal of Epidemiology Published by the Johns Hopkins Bloomberg School of Public Health 2009.

PRACTICE OF EPIDEMIOLOGY

Time-modified Confounding

Robert W. Platt, Enrique F. Schisterman and Stephen R. Cole

Correspondence to Dr. Robert W. Platt, Montreal Children's Hospital Research Institute, 4060 Ste. Catherine Street West, No. 205, Westmount, QC, Canada H3Z 2Z3 (e-mail: robert.platt{at}mcgill.ca).

Received for publication November 30, 2008. Accepted for publication June 2, 2009.

According to the authors, time-modified confounding occurs when the causal relation between a time-fixed or time-varying confounder and the treatment or outcome changes over time. A key difference between previously described time-varying confounding and the proposed time-modified confounding is that, in the former, the values of the confounding variable change over time while, in the latter, the effects of the confounder change over time. Using marginal structural models, the authors propose an approach to account for time-modified confounding when the relation between the confounder and treatment is modified over time. An illustrative example and simulation show that, when time-modified confounding is present, a marginal structural model with inverse probability-of-treatment weights specified to account for time-modified confounding remains approximately unbiased with appropriate confidence limit coverage, while models that do not account for time-modified confounding are biased. Correct specification of the treatment model, including accounting for potential variation over time in confounding, is an important assumption of marginal structural models. When the effect of confounders on either the treatment or outcome changes over time, time-modified confounding should be considered.

bias (epidemiology); confounding factors (epidemiology); structural model


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