A Goneral Procedure for Testing Equivalence

  • Published : 1998.08.01

Abstract

Motivated by bioequivalence studies which involve comparisons of pharmaceutically equivalent dosage forms, we propose a more general decision rule for showing equivalence simultaneously between multiple means and a control mean. Namely, this testing procedure is concerned with the situation in that one must make decisions as to the bioequivalence of an original drug product and several generic formulations of that drug. This general test is developed by considering a spherical confidence region, which is a direct extension of the usual t-based confidence interval rule formally approved by the U.S. Food and Drug Administration. We characterize the test by the probability of rejection curves and assess its performance via Monte-Carlo simulation. Since the manufacturer's main concern is the proper choice of sample sizes, we provide optimal sample sizes from the Monte-Carlo simulation results. We also consider an application of the generalized equivalence test to a repeated measures design.

Keywords

References

  1. Clinical Pharmacology and Therapeutics v.28 Determining the probability of an important difference in bioavailability Rodda, B. E.;Davis, R. L.
  2. Biometrics v.37 Comparison of different methods for decision making in bioequivalence assessment Mandallaz, D.;Mau, J.
  3. Mathematical Computation v.18 Numerical integration over the n-dimensional spherical shell Mustard, D.
  4. Biometrics v.32 Symmetric confidence intervals for bioequivalence trials Westlake, W. J.
  5. Statistics in Medicine v.10 Sample sizes for bioequivalence studies Metzler, C. M.
  6. Encyclopedia of Pharmaceutical Technology v.1 Bioavailability of drugs and bioequivalence Meyer, M. C.
  7. Communications in Statistics - Theory and Methods v.12 A new procedure for testing equivalence in comparative bioavailability and other clinical trials Anderson, S.;Hauck, W. W.
  8. Journal of Korean Society for Quality Management v.22 Probability of rejection curve for equivalence testing procedure Sung, N. K.
  9. Statistical methods for deciding bioequivalence of formulations, in Drug absorption from sustained release formulations Metzler, C. M.;Yacobi, A.(ed.);Halperin-Walega, E.(ed.)
  10. Biometrics v.30 Bioavailability - a problem in equivalence Metzler, C. M.
  11. American Statistician v.48 Fisher on statistical tests: A 1935 exchange from Nature Inman, H. F.
  12. Journal of the Korean Statistical Society v.23 Equivalence testing as an alternative to significance testing Huh, M. H.
  13. Journal of Pharmaceutical Sciences v.61 Use of confidence intervals in analysis of comparative bioavailability trials Wwstlake, W. J.