Bayesian Bioequivalence Test in 2х2 Crossover Design

兩期雙序列交叉設計下的貝氏生體相等性檢定

陳玉英(Yuh-Ing Chen)；黃啟軒(Chi-Hsuan Huang)

兩期雙序列交叉設計 ； 貝氏混合效應模式 ； 生體相等性檢定 ； 藥物動力學 ； 2х2 crossover design ； Bayesian mixed-effect model ； bioequivalence test ； pharmacokinetic study

統計與資訊評論

15卷（2013 / 12 / 01）

33 - 45

英文

評估測試藥與專利藥的生體相等性是製藥產業取得學名藥上市許可前的必要工作。為達此目的，經常在兩期雙序列交叉設計下執行藥物動力研究，其中藥物濃度時間剖面下的面積及此一剖面的最大濃度是生體相等性檢定的二個主要的生體可用性參數。本文首先以穩健的混合效應模式描述估計的受試者生體可用性參數，其中受試者之間的變異及測量誤差變數皆服從學生化t分布。然後根據上述模式建立生體相等性的貝氏檢定。進一步以模擬研究在不同模式及先驗分布下，生體相等性的後驗機率。最後，藉分析一筆資料說明所提模式及檢定的應用。

Assessment of the bioequivalence (BE) between the test drug and patent drug is a major issue to the biopharmaceutical industry for marketing the test drug as a generic drug. To do so, a 2х2 crossover design is usually conducted for a pharmacokinetic (PK) study where the bioavailability (BA) parameters such as area under the concentration-time curve (AUC) or maximum concentration (Cmax), are employed in a BE test. In this paper, we consider mixed-effect models for the estimated BA parameters where Student's t-distribution is used to describe the between-subject variation and measurement error variables. Based on the proposed robust model, we suggest a Bayesian test for the BE of the two drugs. A Monte Carlo study is further conducted to investigate the posterior probability of bioequivalence associated with different models under different prior distributions of the BA parameters. A real data set is finally illustrated by using the proposed model and test.