Discussion of individual bioequivalence by M.-L. Chen.

We review and discuss some technical statistical issues and practical implementation issues associated with the use of individual as opposed to population average bioequivalence to express the relative bioavailabilities of alternative formulations of a drug. A number of promising methods for addressing individual bioequivalence have been described. Individual bioequivalence calculations can be done using standard crossover designs, although more sophisticated assessments that compare test-reference variability to reference-reference variability require more complex designs. However, more experience about the clinical implications of various degrees of individual bioinequivalence as expressed by various metrics should be accumulated before definitive regulations are set forth mandating the use of individual bioequivalence for expressing relative bioavailabilities.