Equivalence of Bioavailability and Efficacy in Drug Testing
In the last 15 years much attention has been given to evaluating the relative bioavailability of two formulations, and particularly to the problem of deciding if a “test” formulation is equivalent to a “standard” or “reference” formulation. For much of this period statistics has not provided good tools for helping pharmaceutical scientists in these problems, but in recent years a number of methods have been proposed for decision rules based on solid statistical foundations. I have reviewed some of these rules and reported simulations that have evaluated their performance (Metzler and Huang, 1983; Metzler, 1986; Metzler, 1987). In this paper I will briefly review that previous work, report on some extensions, and consider some further questions that still await answers. I assume that the reader is familiar with the concepts of bioavailability and with those parameters, such as AUC (area under the curve), CMAX, TMAX or total amount of drug eliminated, that are most often used to characterize the bioavailaabilty of pharmaceutical formulations. These parameters are computed from observed concentrations of drug in blood and urine.
KeywordsDecision Rule Test Formulation Relative Bioavailability Pharmaceutical Scientist Error Standard Deviation
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- Fluehler, H., Hirtz, J. and Moser, H. A. 1981, An aid to decision-making in bioequivalence assessment. J. Pharmacokin. Biopharm. 9: 235–243.Google Scholar
- Hollander, M., and Wolfe, D. A. 1973, “Nonparametric Statistical Methods”, John Wiley and Sons, New York.Google Scholar
- Metzler, C. M., 1987, Statistical methods for deciding bioequivalaence of formulations, in: “Drug Absorption from Sustained Release Formulations,” A. Yacobi and E. Halperin-Walega, eds., Pergamon Press, New York.Google Scholar