Variance components in comparative bioavailability studies.
Variance components in comparative bioavailability studies are examined. Assay measurement error is shown to be negligible relative to other variance components, and hence, repeat assay does not appreciably increase study precision and is unnecessary. More important is the finding that repeat administration of each formulation to each subject may substantially decrease the variance of the formulation difference and may allow the use of fewer subjects in a study. The benefit of repeat administration depends on the relative sizes of the within-subject variance component and the subject-formulation interaction component. In addition, repeat administration allows separate estimation of the within-subject component and the subject-formulation component. The former component is important for assessing bioequivalence, and the latter component, for assessing interchangeability of formulations.
Gaffney
M
M
Pfizer, Inc., New York, NY 10017.
D000704:Analysis of Variance; D001682:Biological Availability; D004334:Drug Administration Schedule; D008432:Mathematical Computing; D008722:Methods; D015233:Models, Statistical; D010599:Pharmacokinetics