評估藥物最適劑量之跨區域臨床試驗設計策略

Design Strategy in Multiregional Clinical Trial to Assess Regional Optimal Dose

王玫(Mey Wang) ； 程毅豪(Yi-Hau Chen)

《中國統計學報》 53卷1期 (2015/03) Pp. 55-63

摘要

本研究將藥物「最適劑量」的觀念納入跨區域臨床試驗的設計策略中，我們認為跨區域臨床試驗不僅可評估試驗藥物在不同區域病人族群的療效，且可評估不同劑量的試驗用藥，對不同區域病人族群的療效，亦即在同一跨區域臨床試驗中，可同時探討試驗藥物對特定區域病人族群的療效及其最適劑量。執行跨區域臨床試驗最大的好處，在於評估某特定區域次群體的療效時，即便整體療效未具顯著，同一試驗中其他區域的療效資料仍可銜接使用，以增強其統計檢定力。本研究應用程等（2009）之貝氏方法估算各區域樣本數分配的比率，所估算的樣本數於分析跨區域臨床試驗資料時，具有相當高的統計檢定力偵測試驗藥物在特定區域的療效。

關鍵字

跨區域臨床試驗 ； 最適劑量 ； 樣本數分配比率 ； 貝氏方法 ； 銜接

並列摘要

The current work will introduce an important concept of ＂optimal dosing＂ into the design of a phase III multi-regional trial. The main idea is that a multiregional trial can be utilized to assess treatment effects not only across different regions but also across different dose treatments. That is, the dose-region profile of drug efficacy can be assessed in a unifying multiregional trial. To this end, we propose the use of a three-arm multiregional trial including the placebo (control), high- and low-dose treatment groups, so that the drug effects under different doses in different regions are evaluated simultaneously. A major advantage of the use of a multiregional trial is that, when assessing regional treatment effect, cross-regional information can be utilized to enhance statistical power for detecting the treatment effect for certain regions, even if the global (overall) treatment effect is insignificant. We also examine the regional sample size allocation in the proposed multiregional trial for ensuring a desired power in a local region, using the Bayesian approach we proposed previously for analyzing the multiregional trial data.

並列關鍵字

multiregional clinical trial ； optimal dose ； sample size allocation ； Bayesian method ； bridging

參考文獻

Chen, Y. H.,Wu, Y. H.,Wang, M.(2009).A Bayesian approach to evaluating regional treatment effect in a multiregional trial.Journal of Biopharmaceutical Statistics.19,900-915.

Malinowski, H. J.,Westelinck, A.,Sato, J.(2008).Same drug, different dosing: Differences in dosing for drugs approved in the United States, Europe, and Japan.J Clin Pharmacol.48,900-902.