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Abstract

In comparative bioavailability trials, the focus in the determination of bioequivalence has been to show that the average bioavailability on a test formulation is similar to the average bioavailability on a reference formulation. It has been argued that this is not adequate to ensure interchangeability of formulations. In this paper, a linear model framework in which the concepts of interchangeability and individual bioequivalence can be expressed is established. A moment-based criterion which ensures interchangeability for at least a certain proportion of the population is introduced and a general statistical testing procedure to establish individual bioequivalence is developed. For the case of a balanced four-period two-sequence crossover experiment, an explicit test is given and the test's favorable statistical properties are shown.

Keywords

Bioequivalence Individual bioequivalence Interaction Interchange-ability Variance components

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A Moment-Based Criterion for Determining Individual Bioequivalence

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