The assessment of individual and population bioequivalence.
We develop a statistical methodology for the assessment of individual bioequivalence when a crossover design is invoked. The location parameters for our model consist of population-averaged parameters for formulation, population-averaged parameters for nuisance effects (sequence, period, carryover, etc.), and subject-specific parameters for formulation. We do not impose any distributional assumptions other than the existence of first- and second-order moments. We derive unbiased estimators for all of the parameters in the model and construct subject-specific bioequivalence scores which exclude the effects of the nuisance parameters. We assess individual bioequivalence by constructing distribution-free tolerance intervals based on the sample of bioequivalence scores.
Chinchilli
V M
VM
Center for Biostatistics and Epidemiology, Pennsylvania State University, Hershey 17033, USA.
D002121:Calcium Channel Blockers / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D006801:Humans; D015233:Models, Statistical; D010599:Pharmacokinetics; D011153:Population; D012107:Research Design; D013223:Statistics as Topic; D013810:Therapeutic Equivalency; D014700:Verapamil / Q000493:pharmacokinetics
D002121:Calcium Channel Blockers; D014700:Verapamil