Advertisement

A new statistical procedure for testing equivalence in two-group comparative bioavailability trials

  • Walter W. Hauck
  • Sharon Anderson
Pharmacometrics

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.

Key words

bioavailability bioequivalence hypothesis tests sample size determination 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    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).CrossRefGoogle Scholar
  2. 2.
    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).PubMedCrossRefGoogle Scholar
  3. 3.
    T. B. L. Kirkwood. Bioequivalence testing—a need to rethink.Biometrics 37: 589–591 (1981).CrossRefGoogle Scholar
  4. 4.
    D. Mandallaz and J. Mau. Comparison of different methods for decision-making in bioequivalence assessment.Biometrics 37: 213–222 (1981).PubMedCrossRefGoogle Scholar
  5. 5.
    C. M. Metzler. Bioavailability—a problem in equivalence.Biometrics 30: 309–317 (1974).PubMedCrossRefGoogle Scholar
  6. 6.
    C. M. Metzler and D. C. Huang. Statistical methods for bioavailability and bioequivalence.Clin. Res. Pract. Drug Res. Affairs 1: 109–132 (1983).CrossRefGoogle Scholar
  7. 7.
    D. J. Schuirmann. Fixed sample tests for interval hypotheses associated with bioequivalence trials. Presented at Joint Statistical Meetings, Cincinnati, August, 1982.Google Scholar
  8. 8.
    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).PubMedCrossRefGoogle Scholar
  9. 9.
    W. J. Westlake. Use of confidence intervals in analysis of comparative bioavailability trials.J. Pharm. Sci 61: 1340–1341 (1972).PubMedCrossRefGoogle Scholar
  10. 10.
    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.Google Scholar
  11. 11.
    W. J. Westlake. Symmetric confidence intervals for bioequivalence trials.Biometrics 32: 741–744 (1976).PubMedCrossRefGoogle Scholar
  12. 12.
    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.Google Scholar
  13. 13.
    W. J. Westlake. Response to bioequivalence testing—a need to rethink.Biometrics 37: 591–593 (1981).Google Scholar
  14. 14.
    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).PubMedGoogle Scholar
  15. 15.
    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.Google Scholar

Copyright information

© Plenum Publishing Corporation 1984

Authors and Affiliations

  • Walter W. Hauck
    • 1
  • Sharon Anderson
    • 2
    • 3
  1. 1.Northwestern University Cancer Center and Department of Community Health and Preventive MedicineNorthwestern University Medical SchoolChicago
  2. 2.American Critical CareMcGaw Park
  3. 3.Department of Epidemiology and BiometryUniversity of Illinois, School of Public HealthChicago

Personalised recommendations