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将健康志愿者的受体占用数据纳入第二阶段的概念验证试验,使用贝叶斯动态借款设计

Fulvio Di Stefano¹, Christelle Rodrigues², Stephanie Galtier³

¹Dipartimento di Scienze Matematiche (DISMA) "Giuseppe Luigi Lagrange,", Politecnico di Torino, Torino, Italy.

Biometrical journal. Biometrische Zeitschrift

|October 27, 2023

概括

这项研究将I期试验的受体占用数据与II期试验相结合,使用基于生理学的药物动力学建模. 这种方法提高了临床试验的功率,并保持了药物开发的统计准确性.

科学领域:

药理动力学和药理动力学
临床试验设计临床试验设计
翻译医学是一种翻译医学.

背景情况:

受体占用率 (RO) 是一个关键的药理动力学 (PD) 衡量标准,经常被用作药物疗效的替代品,以指导临床试验中的剂量选择.
将早期阶段 (第一阶段) 的RO数据整合到后期阶段 (第二阶段) 的试验中,可以通过利用所有可用的证据来改善决策.

研究的目的:

开发和评估一种新的临床试验设计,将I期研究中的受体占用数据纳入II期概念验证研究.
利用生理学基础的药理动力学 (PBPK) 建模来预测患者群体中的RO,并为II期试验设计提供信息.

主要方法:

开发了一个最小的PBPK模型来模拟健康志愿者的RO,并预测患者的RO,考虑到人口变化和疾病特异性差异.
根据估计的RO-临床终点关系得出了II期临床终点的信息性先前分布.
实施了贝叶斯动态借款设计,以整合衍生先前分布与并发的II期试验数据.

主要成果:

拟议的设计有效地将I期受体占用数据纳入II期试验.
在免疫炎症疾病模型中的模拟表明,设计增加了统计能力.
在现实的临床终点场景下,I型错误率保持在可接受的水平.

结论:

通过PBPK建模和贝叶斯动态借款集成受体占用数据,为提高II期临床试验效率提供了一个强大的策略.
这种方法可以通过最大限度地利用早期药理动力学数据来进行更明智的剂量选择和决策.
拟议的方法表明,通过提高早期临床研究的预测价值,可以优化药物开发.

关键词:

贝叶斯语贝叶斯语贝叶斯语贝叶斯语借贷借款借款借款借款早期阶段的早期阶段.历史数据历史数据第二阶段第二阶段.基于生理学的药理动力学.接收器占用率接收器占用率

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