An Overview of Design and Evaluation of Multiregional Clinical Trials

多區域臨床試驗之設計與評估之概觀

吳裕振(Yuh-Jenn Wu) ； 陳啟天(Chi-Tian Chen) ； 蕭金福(Chin-Fu Hsiaoy)

《中國統計學報》 53卷1期 (2015/03) Pp. 64-78

摘要

近年來，多區域臨床試驗的設計已成為全球性生技藥品研發一項嶄新的策略。所謂多區域臨床試驗意旨同時在全球多個國家且在同一臨床試驗計畫書所執行之臨床試驗。其主要目的為當全球資料顯示藥物具有效能性時，亦能夠同時在臨床試驗所涵蓋的國家中，同步申請許可、以及同步通過上市。為達到多區域臨床試驗的目標，許多法規與統計方法已陸續建立。本文首先會簡要地探討一些多區域臨床試驗的法規。此外，我們亦將介紹兩種多區域臨床試驗的評估與設計。其一假設藥物效能性無區域間之差異；其二則假設區域間具藥物效能性之差異。最後，我們亦針對多區域臨床試驗的執行，提出合理分配各區域樣本數之方法，期能使各區域新藥效能性達成一致性之機率為最高。

關鍵字

多區域臨床試驗 ； 銜接性試驗 ； 一致性

並列摘要

In recent years, the design of multiregional clinical trials (MRCTs) has become a new strategy for global drug development. A MRCT is a clinical trial which incorporates subjects from many countries around the world under the same protocol. After showing the overall efficacy of a drug in all global regions, one can concurrently assess the chance of applying the overall trial results to each region and consequently support new drug approval in each region. To achieve the goal of conducting MRCT, several regulatory guidelines and statistical methods have been established. In this paper, we will briey describe the regulatory requirements for MRCTs. Also in this article, two statistical approaches for design and evaluation of MRCTs were reviewed. One assumes that the treatment effect is uniform across regions, while the other uses the random effect model to address the heterogeneous treatment effect across regions. Special consideration was also placed on the determination of the number of subjects in a specific region to establish the consistency of treatment effects between the specific region and the entire group.

並列關鍵字

multiregional clinical trial ； bridging study ； consistent trend

參考文獻

Caraco, Y.(2004).Genes and the response to drugs.The New England Journal of Medicine.351(27),2867-2869.

Chen, C. T.,Hung, H. M. J.,Hsiao, C. F.(2012).Design and evaluation of Multiregional trials with heterogeneous treatment effect across region.Journal of Biopharmaceutical Statistics.22,1037-1050.

DerSimonia, R.,Laird, N.(1986).Meta-analysis in clinical trials.Controlled Clinical Trials.7,177-188.

Eichebaum, M.,Spannbrucker, N.,Steincke, B.(1979).Defective N-oxidation of sparteine in man: a new pharmacogenetic defect.European Journal of Clinical Pharmacology.16,183-7.

Hung, H. M. J.,Wang, S. J.,O'Neill, R.(2010).Consideration of regional difference in design and analysis of multi-regional trials.Pharmaceutical Statistics.9(3),173-178.