Model-based bioequivalence test in 2x2 crossover design
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...
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ndltd-TW-098NCU053370162016-04-20T04:17:47Z http://ndltd.ncl.edu.tw/handle/32236639245742134858 Model-based bioequivalence test in 2x2 crossover design 2x2交叉設計下根據模型之生物相等性檢定 Chi-Hsuan Huang 黃啟軒 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. Yuh-Ing Chen 陳玉英 2010 學位論文 ; thesis 83 zh-TW |
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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.
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author2 |
Yuh-Ing Chen |
author_facet |
Yuh-Ing Chen Chi-Hsuan Huang 黃啟軒 |
author |
Chi-Hsuan Huang 黃啟軒 |
spellingShingle |
Chi-Hsuan Huang 黃啟軒 Model-based bioequivalence test in 2x2 crossover design |
author_sort |
Chi-Hsuan Huang |
title |
Model-based bioequivalence test in 2x2 crossover design |
title_short |
Model-based bioequivalence test in 2x2 crossover design |
title_full |
Model-based bioequivalence test in 2x2 crossover design |
title_fullStr |
Model-based bioequivalence test in 2x2 crossover design |
title_full_unstemmed |
Model-based bioequivalence test in 2x2 crossover design |
title_sort |
model-based bioequivalence test in 2x2 crossover design |
publishDate |
2010 |
url |
http://ndltd.ncl.edu.tw/handle/32236639245742134858 |
work_keys_str_mv |
AT chihsuanhuang modelbasedbioequivalencetestin2x2crossoverdesign AT huángqǐxuān modelbasedbioequivalencetestin2x2crossoverdesign AT chihsuanhuang 2x2jiāochāshèjìxiàgēnjùmóxíngzhīshēngwùxiāngděngxìngjiǎndìng AT huángqǐxuān 2x2jiāochāshèjìxiàgēnjùmóxíngzhīshēngwùxiāngděngxìngjiǎndìng |
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