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An Alternative Approach for the Assessment of Bioequivalence Between Two Formulations of a Drug
Author(s) -
Chow SheinChung,
Shao Jun
Publication year - 1990
Publication title -
biometrical journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 63
eISSN - 1521-4036
pISSN - 0323-3847
DOI - 10.1002/bimj.4710320810
Subject(s) - bioequivalence , confidence interval , mathematics , food and drug administration , ellipse , bounded function , statistics , medicine , pharmacokinetics , pharmacology , mathematical analysis , geometry
The problem of the assessment of bioequivalence between a test formulation ( T ) and a reference formulation ( R ) of a drug using a two‐way crossover experiment is considered. To claim bioequivalence between two formulations, it is required by the United States Food and Drug Administration (FDA) to demonstrate that the true ratio of means μ T /μ R of pharmacokinetic parameters of concern falls within some reasonable limits (e.g., (80%, 120%)) with certain assurance. A commonly used approach is to construct an approximate 90% confidence interval for μ T /μ R and compare it with (80%, 120%). In this paper, an exact approach according to the FDA's criteria is proposed. The proposed procedure is derived by constructing an exact confidence region (an ellipse) for (μ R , μ T ) and comparing it with the region bounded by μ T = 0.8 μ R and μ T = 1.2 μ R . Bioequivalence is concluded if the ellipse is within the critical region.