The subject-by-formulation interaction in multivariate bioequivalence.
This paper addresses hypothesis testing problems concerning the subject-by-formulation interaction matrix for the assessment of multivariate bioequivalence. Two problems are addressed: (a) the problem of testing if the subject-by-formulation interaction matrix itself is zero, and (b) the problem of testing if suitable scalar valued functions of the subject-by-formulation interaction matrix is below a threshold. Approximate tests are developed in both cases and the accuracy of the approximation is numerically investigated. The results are illustrated with an example. Even though the literature on univariate bioequivalence testing addresses average bioequivalence, variance bioequivalence and subject-by-formulation interaction, the literature on multivariate bioequivalence deals only with the problem of average bioequivalence. This work appears to be the first attempt to address tests for the subject-by-formulation interaction matrix for testing multivariate bioequivalence.
Cao
Li
L
Department of Mathematics and Statistics, University of Maryland Baltimore County, Baltimore, MD 21250, USA.
Mathew
Thomas
T
D002986:Clinical Trials as Topic / Q000379:methods / Q000706:statistics & numerical data*; D018592:Cross-Over Studies; D003627:Data Interpretation, Statistical; D004304:Dosage Forms; D016568:Drugs, Generic / Q000493:pharmacokinetics*; D006801:Humans; D008954:Models, Biological; D015233:Models, Statistical; D012107:Research Design; D013810:Therapeutic Equivalency
D004304:Dosage Forms; D016568:Drugs, Generic