Measuring switchability and prescribability: When is average bioequivalence sufficient?

Abstract

Recent work, beginning with that of Anderson and Hauck in 1990, has led to a general acceptance of the need to ensure switchability in bioequivalence testing for approval of generic drugs. In other applications of bioequivalence testing, prescribability may be sufficient. However, there is less acceptance of the need to change statistical procedures and study designs from those currently used to assess the current criterion of average bioequivalence. We propose easily interpreted measures of switchability and prescribability. These measures provide bases for assessing conditions under which average bioequivalence is not sufficient to ensure switchability and prescribability, and hence for which a procedure for individual or population bioequivalence is required. The required conditions are sufficiently tight that they cannot be presumed to hold. Thus, there are reasonable conditions for which current practice is not sufficient. An outcome of this development is a connection between two current approaches for assessing individual bioequivalence.