Model-based bioequivalence test in 2x2 crossover design
| Autor: | Chi-Hsuan Huang, 黃啟軒 |
|---|---|
| Rok vydání: | 2010 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 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. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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