Abstract

Simultaneous global drug development with multiregional studies is becoming a common strategy for increasing efficiency of the development process. In particular, multiregional dose-finding studies can be informative to identify inter-ethnic difference in dose-response relationships early in development. An application of MCP-Mod to multiregional studies is discussed in this article. We consider sample size allocation to one specific region and provide three methods for demonstrating consistency in the dose-response relationship between the entire population and one specific region: two methods use contrast statistics to show consistency in dose-response signals, and the third method uses the maximum absolute difference between two dose-response curves to show consistency in the dose-response profiles. The proposed methods do not require studies to have sufficient power to detect a truly consistent dose-response relationship in a confirmatory manner, but rather to allow for quantitative design considerations that can ensure such a relationship is observed at the end of the study with acceptable probability. The three methods are illustrated through an anti-anxiety drug example, resulting in a recommended proportion of 20% for subjects in one specific region. The illustration indicates the recommended proportion could vary depending on the total study sample size.

摘要

与多区域研究同时进行的全球药物开发正在成为提高开发过程效率的常见策略。特别是，多区域剂量发现研究可以提供信息，以在开发早期识别剂量反应关系的种族间差异。本文讨论了 MCP-Mod 在多区域研究中的应用。我们考虑将样本量分配到一个特定区域，并提供三种方法来证明整个人群和一个特定区域之间剂量反应关系的一致性：两种方法使用对比统计来显示剂量反应信号的一致性，第三种方法使用两条剂量反应曲线之间的最大绝对差异，以显示剂量反应曲线的一致性。提议的方法不需要研究具有足够的功效以验证方式检测真正一致的剂量反应关系，而是允许进行定量设计考虑，以确保在研究结束时以可接受的概率观察到这种关系. 这三种方法通过一个抗焦虑药的例子来说明，得出一个特定区域的受试者的推荐比例为20%。插图表明推荐的比例可能因研究总样本量而异。这三种方法通过一个抗焦虑药的例子来说明，得出一个特定区域的受试者的推荐比例为20%。插图表明推荐的比例可能会因总研究样本量而异。这三种方法通过一个抗焦虑药的例子来说明，得出一个特定区域的受试者的推荐比例为20%。插图表明推荐的比例可能因研究总样本量而异。