Assessing Average Bioequivalence for 2×2 Crossover Design with Covariates Jeong, Gyu-Jin; Park, Sang-Gue; Kim, Kwan-Yup;
The primary variables are often systematically related to other influences apart from drug effect. For instance, there may be relationships to covariates such as health conditions or prognostic factors. When a crossover experiment for bioequivalence is designed, the statistical adjustment for the influence of covariates should be considered if some covariates influence the drug effect. Statistical inference for assessing average bioequivalence for a crossover design with covariates is given and an illustrated example is presented with discussion.
On Evaluation of Bioequivalence for Highly Variable Drugs, Korean Journal of Applied Statistics, 2011, 24, 6, 1055
식품의약품안전청 (2010). 생물학적동등성시험기준(고시 제2010-43호).
Chow, S. C. and Liu, J. P. (2008). Design and Analysis of Bioavailability and Bioequivalence Studies, 3rd edition, Chapman & Hall/CRC.
Ko, S. and Oh, H. (1999). Assessment and Interpretation for Two Drug Formulations using Crossover Design, The Korean Communications in Statistics, 6, 601–609.
Patel, H. I. (1983). Use of baseline measurements in the two-period crossover design, Communications in Statistics, Theory & Methods, 12, 2693–2712.
Schuirmann, D. J. (1987). A comparison of the two one-sided tests procedure and the power approach for assessing the equivalence of average bioavailability, Journal of Pharmacokinetics and Pharmacodynamics, 15, 657–680.