Correction for bias introduced by truncation in pharmacokinetic studies of environmental contaminants
✍ Scribed by Joel E. Michalek; Ram C. Tripathi; Pandurang M. Kulkarni; Pushpa L. Gupta; Kandansamy Selvavel
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 150 KB
- Volume
- 9
- Category
- Article
- ISSN
- 1180-4009
No coin nor oath required. For personal study only.
✦ Synopsis
Pharmacokinetic studies of biomarkers for environmental contaminants in humans are generally restricted to a few measurements per subject taken after the initial exposure. Subjects are selected for inclusion in the study if their measured body burden is above a threshold determined by the distribution of the biomarker in a control population. Such selection procedures introduce bias in the ordinary weighted least squares estimate of the decay rate l caused by the truncation. We show that if the data are conditioned to lie above a line with slope Àl on the log scale then the weighted least squares estimate of l is unbiased. We give an iterative estimation algorithm that produces this unbiased estimate with commercially available software for ®tting a repeated measures linear model. The estimate and its eciency are discussed in the context of a pharmacokinetic study of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Unbiasedness and eciency are demonstrated with a simulation.