Adjusting for time-varying confounding in the subdistribution analysis of a competing risk |
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Authors: | Maarten Bekaert Stijn Vansteelandt Karl Mertens |
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Institution: | 1.Department of Applied Mathematics and Computer Science,Ghent University,Ghent,Belgium;2.Epidemiology Unit,Scientific Institute of Public Health,Brussels,Belgium |
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Abstract: | Despite decades of research in the medical literature, assessment of the attributable mortality due to nosocomial infections
in the intensive care unit (ICU) remains controversial, with different studies describing effect estimates ranging from being
neutral to extremely risk increasing. Interpretation of study results is further hindered by inappropriate adjustment (a)
for censoring of the survival time by discharge from the ICU, and (b) for time-dependent confounders on the causal path from
infection to mortality. In previous work (Vansteelandt et al. Biostatistics 10:46–59), we have accommodated this through inverse
probability of treatment and censoring weighting. Because censoring due to discharge from the ICU is so intimately connected
with a patient’s health condition, the ensuing inverse weighting analyses suffer from influential weights and rely heavily
on the assumption that one has measured all common risk factors of ICU discharge and mortality. In this paper, we consider
ICU discharge as a competing risk in the sense that we aim to infer the risk of ‘ICU mortality’ over time that would be observed
if nosocomial infections could be prevented for the entire study population. For this purpose we develop marginal structural
subdistribution hazard models with accompanying estimation methods. In contrast to subdistribution hazard models with time-varying
covariates, the proposed approach (a) can accommodate high-dimensional confounders, (b) avoids regression adjustment for post-infection
measurements and thereby so-called collider-stratification bias, and (c) results in a well-defined model for the cumulative
incidence function. The methods are used to quantify the causal effect of nosocomial pneumonia on ICU mortality using data
from the National Surveillance Study of Nosocomial Infections in ICU’s (Belgium). |
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