模擬研究 - 非經腸胃道藥物之生物相等性

Simulation study - Bioequivalence for non-systematic drug

陳耀庭(Yao-Ting Chen)

指導教授 ： 歐士田

國立臺北大學/商學院/統計學系/碩士(2010年)

摘要

生物相等性 (Bioequivalence, BE) 在學名藥物上市的應用上扮演極重要角色。因經腸胃道 (systematic) 藥物與非經腸胃道 (non-systematic) 藥物對身體的作用方式不同，故生物相等性之判定過程也不一樣。針對非經腸胃道 (non-systematic) 藥物之生物相等性研究，莊易等人 (2004) 提出一套更有效率的試驗設計。一般而言，學名藥上市之前，臨床試驗的首要目的須先確認 (Validity)原廠藥是否優於安慰劑(Validity)；接著檢測有效性 (Efficacy)，即比較學名藥是否優於安慰劑；再者針對學名藥與原廠藥，利用Schuirmann (1987) 所提出的兩個單邊檢定，來檢定此兩種藥物的顯著效果為何，如果療效差距為合理範圍之內，那麼即判定兩種藥物具有生物相等性。
本篇文章延續莊易等人 (2004) 的研究內容，同時考慮 O’Brien Fleming (1979) 的顯著水準消費函數 (alpha- spending function) 與Pocock (1977) 的顯著水準消費函數來做為評判生物相等性的準則。藉由統計模擬來探討比較兩種顯著水準消費函數的效率，提供更多資訊給廠商做決策之用。不僅如此，還可比較兩種方法的優缺點以及所造成的成本效應為何等等。

關鍵字

生物相等性 ； 非經腸胃道藥物 ； 學名藥 ； 原廠藥 ； 顯著水準消費函數

並列摘要

Bioequivalence plays an important role in test drug application of marketing. Determination of bioequivalence for systematic drug and non-systematic drug are not the same process, because it’s effects on the body in different ways. For non-systematic drug bioequivalence studies, Tsong et al. (2004) proposed a more efficient test design. In general, before test drug on the market, the primary purpose of clinical trials must first confirm reference drug is better than placebo. Second, then test the effectiveness, means the test drug is better than placebo. In the end, compare the test drug and reference drug. Using Schuirmann (1987) proposed two sided test, test the significant effect of these two drugs,
if the effect of difference within reasonable limits, then the judge has the bioequivalent of the two drugs.
This article continuation of Tsong et al. (2004), taking into account the O'Brien Fleming (1979) alpha-spending function and Pocock (1977) alpha-spending function to do the evaluation criteria for bioequivalence. By comparing statistical simulation to research two efficiency of alpha-spending function, and provide more information to manufacturer to make decision. Not only that, comparing the two methods advantages and disadvantages, also be caused by the cost-effectiveness, and so on.

並列關鍵字

Bioequivalence ； Non-systematic drug ； Test drug ； Reference drug ； Alpha-spending function

參考文獻

Tsong, Y., Hung, H. M. J., Wang, S. J., & Cui, L. (2000). Dropping a treatment arm in clinical trial: Re-distributing remaining sample size scheme. In: Proceedings of the Biopharmaceutical Section. The American Statistical Association, 138-143.

Tsong, Y., Hung, H. M. J., Wang, S. J., Cui, L., & Nuri, W. A. (1997). Dropping a treatment arm in clinical trial with multiple arms. In: Proceedings of the Biopharmaceutical Section. The American Statistical Association, 58-63.

Chow, S. C. (1999). Individual bioequivalence - a review of the fda draft guidance. Drug Inform. J., 33, 435-444.

Chow, S. C. & Liu, J. P. (1999). Design and Analysis of Bioavailabibity and Bioequivalence Studies. Marcel Dekker, New York.

Chow, S. C., Shao, J., & Wang, H. (2002). Individual bioequivalence testing under 2x3 designs. Statistics In Medicine, 21, 629-648.