Journal of Pharmacokinetics and Biopharmaceutics

, Volume 15, Issue 6, pp 657–680 | Cite as

A comparison of the Two One-Sided Tests Procedure and the Power Approach for assessing the equivalence of average bioavailability

  • Donald J. Schuirmann
Pharmacometrics

Abstract

The statistical test of the hypothesis of no difference between the average bioavailabilities of two drug formulations, usually supplemented by an assessment of what the power of the statistical test would have been if the true averages had been inequivalent, continues to be used in the statistical analysis of bioavailability/bioequivalence studies. In the present article, this Power Approach (which in practice usually consists of testing the hypothesis of no difference at level 0.05 and requiring an estimated power of 0.80) is compared to another statistical approach, the Two One-Sided Tests Procedure, which leads to the same conclusion as the approach proposed by Westlake (2) based on the usual (shortest) 1–2α confidence interval for the true average difference. It is found that for the specific choice of α=0.05 as the nominal level of the one-sided tests, the two one-sided tests procedure has uniformly superior properties to the power approach in most cases. The only cases where the power approach has superior properties when the true averages are equivalent correspond to cases where the chance of concluding equivalence with the power approach when the true averages are notequivalent exceeds 0.05. With appropriate choice of the nominal level of significance of the one-sided tests, the two one-sided tests procedure always has uniformly superior properties to the power approach. The two one-sided tests procedure is compared to the procedure proposed by Hauck and Anderson (1).

Key words

bioavailability bioequivalence hypothesis testing interval hypotheses 

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References

  1. 1.
    W. W. Hauck and S. Anderson. A new statistical procedure for testing equivalence in two-group comparative bioavailability trials.J. Pharmacokin. Biopharm. 12:83–91 (1984).CrossRefGoogle Scholar
  2. 2.
    W. J. Westlake. Response to T. B. L. Kirkwood: Bioequivalence testing-a need to rethink.Biometrics 37:589–594 (1981).CrossRefGoogle Scholar
  3. 3.
    S. Anderson and W. W. Hauck. A new procedure for testing equivalence in comparative bioavailability and other clinical trials.Comm. Stat. A 12:2663–2692 (1983).CrossRefGoogle Scholar
  4. 4.
    D. M. Rocke. On testing for bioequivalence.Biometrics 40:225–230 (1984). (See also Correspondence inBiometrics 4:561–563 (1985).)PubMedCrossRefGoogle Scholar
  5. 5.
    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 and Febiger, Philadelphia, 1973, pp. 149–179.Google Scholar
  6. 6.
    D. Mandallaz and J. Mau. Comparison of different methods for decision-making in bio-equivalence assessment.Biometrics 37:213–222 (1981).PubMedCrossRefGoogle Scholar
  7. 7.
    C. S. Locke. An exact confidence interval from untransformed data for the ratio of two formulation means.J. Pharmacokin. Biopharm. 12:649–655 (1984).CrossRefGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1987

Authors and Affiliations

  • Donald J. Schuirmann
    • 1
  1. 1.Division of Biometrics, Center for Drug Evaluation and ResearchU.S. Food and Drug AdministrationRockville

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