Abstract
The clinical problem of testing for equivalence in comparative bioavailability trials is restated in terms of the proper statistical hypotheses. A simple t-test procedure for these hypotheses has been devloped that is more powerful than the methods based on usual (shortest) and symmetric confidence intervals. In this note, this new procedure is explained and an example is given, including the method for sample size determination.
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S. Anderson and W. W. Hauck. A new procedure for testing equivalence in comparative bioavailability and other clinical trials.Comm. Stat. A12:2663–2692 (1983).
C. W. Dunnett and M. Gent. Significance testing to establish equivalence between treatments, with special reference to data in the form of 2×2 tables.Biometrics 33: 593–602 (1977).
T. B. L. Kirkwood. Bioequivalence testing—a need to rethink.Biometrics 37: 589–591 (1981).
D. Mandallaz and J. Mau. Comparison of different methods for decision-making in bioequivalence assessment.Biometrics 37: 213–222 (1981).
C. M. Metzler. Bioavailability—a problem in equivalence.Biometrics 30: 309–317 (1974).
C. M. Metzler and D. C. Huang. Statistical methods for bioavailability and bioequivalence.Clin. Res. Pract. Drug Res. Affairs 1: 109–132 (1983).
D. J. Schuirmann. Fixed sample tests for interval hypotheses associated with bioequivalence trials. Presented at Joint Statistical Meetings, Cincinnati, August, 1982.
M. R. Selwyn, A. P. Dempster, and N. R. Hall. A Bayesian approach to bioequivalence for the 2×2 changeover design.Biometrics 37: 11–21 (1981).
W. J. Westlake. Use of confidence intervals in analysis of comparative bioavailability trials.J. Pharm. Sci 61: 1340–1341 (1972).
W. J. Westlake. The design and analysis of comparative blood-level trials. In J. Swarbrick (ed),Current Concepts in the Pharmaceutical Sciences, Dosage Form Design and Bioavailability, Lea & Febiger, Philadelphia, 1973, pp. 149–179.
W. J. Westlake. Symmetric confidence intervals for bioequivalence trials.Biometrics 32: 741–744 (1976).
W. J. Westlake. Design and statistical evaluation of bioequivalence studies in man. In J. Blanchard, R. W. Sawchuk, and B. B. Brodie (ed),Principles and Perspectives in Drug Bioavailability, Karger, Basel, 1979, pp. 192–210.
W. J. Westlake. Response to bioequivalence testing—a need to rethink.Biometrics 37: 591–593 (1981).
D. Clayton and A. Leslie. The bioavailability of erythromycin stearate versus enteric-coated erythromycin base when taken immediately before and after food.J. Int. Med. Res. 9: 470–477 (1981).
Food and Drug Administration. The bioavailability protocol guideline for ANDA and NDA submission. Division of Biopharmaceutics, Drug Monographs/Bureau of Drugs, Food and Drug Administration, 1977.
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Preparation of this manuscript was supported in part by Grant #CA15145 from the National Cancer Institute.
An erratum to this article is available at http://dx.doi.org/10.1007/BF01059559.
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Hauck, W.W., Anderson, S. A new statistical procedure for testing equivalence in two-group comparative bioavailability trials. Journal of Pharmacokinetics and Biopharmaceutics 12, 83–91 (1984). https://doi.org/10.1007/BF01063612
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DOI: https://doi.org/10.1007/BF01063612