Model-based bioequivalence test in 2x2 crossover design

• Main Authors: Chi-Hsuan Huang, 黃啟軒
• Other Authors: Yuh-Ing Chen
• Format: Others
• Language: zh-TW
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/32236639245742134858

博士 === 國立中央大學 === 統計研究所 === 98 === To evaluate globally the average bioequivalence of a test drug to a reference drug in a pharmacokinetic study under a 2x2 crossover design, we consider directly comparing the associated drug concentration-time curves. Statistical models for the drug concentrations are suggested when the concentrations measured at different time points are distributed according to a generalized gamma distribution and the mean concentrations over time are described by a one-compartment pharmacokinetic model. A multiple test based on the supreme distance between the two curves over the time interval under study is then proposed for testing the equivalence of the two drug concentration-time curves. We also propose a semi-parametric model for drug concentrations in blood or plasma over time. The semi-parametric model primarily includes smooth mean drug concentration-time curves that can be estimated by using natural cubic splines. Based on the difference of the two estimated natural cubic splines, we then suggest a test for the bioequivalence of the two drugs. The robustness of the level and power performances of the suggested tests are further investigated in a simulation study. Finally, we illustrate two datasets for the bioequivalence study by using the proposed models and tests.