The bootstrap procedure in individual bioequivalence

A bootstrap-type hypothesis test procedure for assessing individual (or pop ulation) bioequivalence between two drug formulations is suggested in a dra ft guidance from the United States Food and Drug Administration (FDA). The purpose of this article is to study the unknown properties of this test pro cedure and propose some improved test procedures. We find that: the FDA's b ootstrap computation is not correct; the power of the FDA's test can be ver y low; the use of the REML method suggested in the draft guidance does not have any advantage over the use of simpler methods such as the moment metho d; and the method of sample size determination in the draft guidance is ina ppropriate. We study the size and power of different bootstrap test procedu res 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, an d eventually a satisfactory statistical method can be implemented for asses sing individual (or population) bioequivalence. Copyright (C) 2000 John Wil ey & Sons, Ltd.