Abstract
A three-stage parametric statistical analysis for destructive toxicokinetic studies is described. It provides an alternative to Bailer's method. In the first stage of the analysis either the log-normal or gamma distribution is fitted to observed concentrations. The analysis of variance (deviance) of concentrations is used to test treatment by time interactions and for preliminary assessment of dose-proportionality. In Stage 2, trapezoidal AUC estimates and their variances are calculated from the corresponding maximum-likelihood estimates of each treatment by time concentration. Stage 3 comprises a weighted regression analysis of the AUCs that give tests of dose-proportionality and experimental factors of interest. The tests of dose-proportionality are not new, but they are presented in a form that facilitates graphical presentation.
The choice of gamma or lognormal distribution is justified by a distributional study of four cases. The defects of the Bailer plus Satterthwaite correction method is discussed with the aid of two Monte-Carlo studies. The proposed parametric methods preserve many of the features of the Bailer method but provide superior statistical inference using standard software tools.
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