A survey of the likelihood approach to bioequivalence trials.

Bioequivalence (BE) trials are abbreviated clinical trials whereby a generic drug or new formulation is evaluated to determine if it is 'equivalent' to a corresponding previously approved brand-name drug or formulation. In this paper, we survey the process of testing BE and advocate the likelihood paradigm for representing the resulting data as evidence. We emphasize the unique conflicts between hypothesis testing and confidence intervals in this area--which we believe are indicative of the existence of the systemic defects in the frequentist approach--that the likelihood paradigm avoids. We suggest the direct use of profile likelihoods for evaluating BE. We discuss how the likelihood approach is useful to present the evidence for both average and population BE within a unified framework. We also examine the main properties of profile likelihoods and estimated likelihoods under simulation. This simulation study shows that profile likelihoods offer a viable alternative to the (unknown) true likelihood for a range of parameters commensurate with BE research. Copyright 2008 John Wiley & Sons, Ltd.