The bootstrap procedure in individual bioequivalence.

Abstract

A bootstrap-type hypothesis test procedure for assessing individual (or population) bioequivalence between two drug formulations is suggested in a draft guidance from the United States Food and Drug Administration (FDA). The purpose of this article is to study the unknown properties of this test procedure and propose some improved test procedures. We find that: the FDA's bootstrap computation is not correct; the power of the FDA's test can be very low; the use of the REML method suggested in the draft guidance does not have any advantage over the use of simpler methods such as the moment method; and the method of sample size determination in the draft guidance is inappropriate. We study the size and power of different bootstrap test procedures and suggest a method for sample size determination. It is our hope that this article will draw some attention to further research in this area, and eventually a satisfactory statistical method can be implemented for assessing individual (or population) bioequivalence.