本文研究在兩期雙序列交叉設計之下，受試藥及專利藥的生物對等性檢定。如果之前具有類似學名藥的試驗，則研究者具備此一受試藥生體可用性的先驗知識。所以，本文考慮使用貝氏方法分析生體可用性衡量值的穩健隨機效應模式，進行兩種藥物的貝氏生物對等性檢定。本文除了利用實例說明所提穩健模式及貝氏生物對等性檢定的應用，並且使用模擬方法研究在各種可能的隨機效應模式之下，此一貝氏生物對等性檢定的表現。

The article considers the bioequivalence test between the test drug and patent drug under a 2×2 crossover design. If there have been some generic drugs under study, then prior information about the bioavailability of the test drugs
would be available. Therefore, this article considers a Bayesian test for the bioequivalence of the two drugs based on a robust random effects model for the estimated bioavailability parameters. A real data is illustrated based on the proposed Bayesian bioequivalent test. Finally, a simulation study is implemented to investigate the performance of the proposed test.

1. Berger, R.L. and Hsu, J., Bioequivalence Trials, Intersection-union Tests and Equivalence Confidence Sets, Statistical Science, 11, p.283-319, 1996.

2. Chow, S. C. and Liu, J. P., Design and Analysis of Bioavailability and Bioequivalence Studies, Chapman and Hall/CRC, 2008.

3. Draper, N.R. and Smith, H., Applied Regression Analysis, 2nded., John Wiley & Sons, New York,1981.

4. Delyon, B., Lavielle, M., and Moulines, E., Convergence of a stochastic approximation version of the EM algorithm. Annals of Statistics,27(1), 94-128, 1999.

5. FDA. The FDA Guidance on Statistical Procedures for Bioequivalence Studies using a Standard Two-Treatment Crossover Design. Rockville, MD: Division of Bioequivalence, Office of Generic Drugs, Center for DrugEvaluation and Research, U.S. Food and Drug Administration, 1992.

6. FDA. Guidance for Industry: Statistical Approaches to Establishing Bioequivalence, Center for Drug Evaluation and Research, Food and DrugAdministration, U.S. Department of Health and Human Services, 2001.

7. Jeffreys, H. Theory of Probability, Clarendon Press, 1961.

8. Niazi, S., Handbook of Bioequivalence Testing, Informa Healthcare, 2007.

9. Patterson, S. D., and Jones, B., Bioequivalence and Statistics in Clinical Pharmacology, CRC Press, 39-76, 2006.

10. Rowland, M. and Tozer, T.N. Clinical Pharmacokinetics Concepts and Applications,
Lea&Febiger, Philadelphia,PA, 1980.

11. Souza, R. M.D., Achcar J. A. and Martinez E. Z., Use of Bayesian Methods for MultivariateBioequivalence Measures, Journal of Biopharmaceutical Statistics, 19, 42-66, 2009.

12. Spiegelhalter, D. J., Best, N. G., Carlin, B. P. and Van Der Linde, A., Bayesian measures
of model complexity and fit. Journal of the Royal Statistical Society: Series B (Statistical
Methodology), 64, 583-639, 2002.

13. Spiegelhalter, D., Thomas, A., Best, N. and Lunn, D., WinBUGS user manual.
Cambridge: MRC Biostatistics Unit, 2003.

14. Wei, G. C. G., and Tanner, M. A., “A Monte Carlo Implementation of the EM Algorithm
and the Poor Man’s Data Augmentation Algorithms,” Journal of the American Statistical
Association, 85, 699–704, 1990.

15.Yeh, K. C. and Kwan, K. C., A Comparison of Numerical Algorithms by Trapezoidal,
LaGrange, and spline approximations. Journal of Pharmacokinetics, 6, 79-98, 1978.

16.詹國松，「針對非對數常態資料的生體相等性檢定」，國立中央大學，碩士論文，民國101年

17.黃慧雯，「雙向交叉設計下生物相等性的多元檢定」，國立中央大學，碩士論
文，民國98年。