以貝氏一致性方法評估銜接性試驗

銜接性試驗(bridging study)是全球化藥物發展之一大重要臨床試驗設計，此概念源自於1998年國際醫藥法規機構(International Conference on Harmonization)所建立之ICH E5發展而來。E5的主題為「Ethnic Factors in the Acceptability of Foreign Clinical Data」，其目的主要是藉由評估種族因素於藥物效能上的衝擊，繼而協助藥物於ICH區域上市。根據ICH E5 的定義，當某種新藥已經在某一地區證實其有效性、安全性且上市之後，此種新藥如要在另一地區註冊上市，而在當地所執行新藥的臨床試驗，此種試驗便稱為銜接性試驗。由於政府對於國外新藥的引進，自2004年開始，必須先執行銜接性臨床試驗的評估，由此可見銜接性臨床試驗的研究之重要性。Tsou. et al.(2007)提出了一個貝氏方法合併銜接性試驗和國外臨床數據來估計兩區域的相似性。然而，即使兩個區域皆具有正向的藥效反應，它們兩者之間的藥效依舊有可能不相似。因此，在本文中，我們提出一個貝氏一致性方法來評估兩區域藥效的相似性。另外我們也建立統計理論來計算銜接性試驗所需要的樣本數。並用例子說明在不同的情況下，如何應用我們提出的方法。

關鍵字

銜接性試驗；貝氏方法；一致性；相似性

並列摘要

In 1998, the International Conference on Harmonization (ICH) published a guidance to facilitate the registration of medicines among ICH regions including European Union, the United States of America, and Japan by recommending a framework for evaluating the impact of ethnic factors on a medicine’s effect such as its efficacy and safety at a particular dosage and dose regimen (ICH E5, 1998). The purpose of ICH E5 is not only to evaluate the ethnic factor influence on safety, efficacy, dosage and dose regimen, but also more importantly to minimize duplication of clinical data allow extrapolation of foreign clinical data to a new region. Tsou et al. (2007) have proposed a Bayesian approach to synthesize the data generated by the bridging study and foreign clinical data generated in the original region for assessment of similarity based on superior efficacy of the test product over a placebo control. However, for Tsou et al. (2007), even if both regions have positive treatment effect, their effect sizes might in fact be different. That is, their approach could not truly assess the similarity between two regions. Therefore, in this article we develop a Bayesian consistency approach for assessment of similarity between a bridging study conducted in a new region and studies conducted in the original region. Methods for sample size determination for the bridging study are also proposed. Numerical examples illustrate applications of the proposed procedures in different scenarios.

並列關鍵字

Bridging Study ； Bayesian Approach ； Consistency ； Similarity

參考文獻

Chow S. C., Shao J., Hu O. Y. P. (2002). Assessing sensitivity and similarity in bridging studies. Journal of Biopharmaceutical Statistics 12:385-400.

Hsiao C. F., Hsu Y. Y., Tsou H. H. (2007). Use of prior information for Bayesian evaluation of bridging studies. Journal of Biopharmaceutical Statistics 17:109-121.

ICH, International Conference on Harmonisation. (1998). Tripartite guidance E5 ethic factors in the acceptability of foreign data. The U.S. Federal Register 83:31790-31796.

Lan K. K. G., Soo Y., (2005). The use of weighted z-tests in medical research. Journal of Biopharmaceutical Statistics 15:625-639.

Lawrence J., Belisle P. (1997). Bayesian sample size determination for normal means and differences between normal means. The statistician 46:209-226.

國際替代計量

以貝氏一致性方法評估銜接性試驗

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