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An approximate method for population toxicokinetic analysis with aggregated data

Abstract : Standard statistical models for analyzing inter-individual variability in clinical pharmacokinetics (nonlinear mixed effects; hierarchical Bayesian) require individual data. However, for environmental or occupational toxicants only aggregated data are usually available, so toxicokinetic analyses typically ignore population variability. We propose a hierarchical Bayesian approach to estimate inter-individual variability from the observed mean and variance at each time point, using a bivariate normal (or lognormal) approximation to their joint likelihood. Through analysis of both simulated data and real toxicokinetic data from 1,3-butadiene exposures, we conclude that given information on the form of the individual-level model, useful information on inter-individual variability may be obtainable from aggregated data, but that additional sensitivity and identifiability checks are recommended.
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Weihsueh A. Chiu, Frédéric Y. Bois. An approximate method for population toxicokinetic analysis with aggregated data. Journal of Agricultural Biological and Environmental Statistics, 2007, 12 (3), pp.346-363. ⟨10.1198/108571107X229340⟩. ⟨ineris-00961914⟩

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