虚拟人口发展的代理指导工作流
Lu Huang1,2,3, Yinbo Chen4, Satyendra Suryawanshi5
1Clinical Pharmacology, Pharmacometrics and Bioanalysis, Bristol Myers Squibb, Princeton, NJ, USA. dr.luhuang@gmail.com.
The AAPS journal
|October 13, 2025
概括
定量系统药理 (QSP) 模型加速药物开发. 一个新的代理引导工作流显著加快了虚拟群体 (VPops) 校准临床数据的速度,提高了效率.
科学领域:
- 制药指标 (Pharmacometrics) 是一个指标.
- 计算生物学 计算生物学
- 药物开发 药物开发
背景情况:
- 定量系统药理 (QSP) 模型对于药物开发至关重要,有助于探索患者变异性和预测治疗结果.
- QSP工具箱促进了对各种临床数据进行校准的虚拟人群 (VPops) 的开发.
- 当前的VPop校准工作流程通过反复优化流行度权重来减缓,以最大限度地提高适度良性 (GOF) 函数,标记为p.
研究的目的:
- 为 QSP 模型开发更快的 VPop 校准工作流.
- 引入代理的合适性 (GOF) 功能,以简化优化过程.
- 提高生成准确匹配临床数据的VPops的效率.
主要方法:
- 使用代理GOF功能实现代理指导的工作流.
- 减少代理GOF函数的最大化,以最小化凸的二次目标函数.
- 代理引导工作流与原始p引导工作流的速度和效率的比较.
主要成果:
- 代理引导的工作流成功地生成了具有高适合性 (p-fit) 的VPops,而无需持续最大化p.
- 新的工作流大大减少了VPop校准所需的计算时间.
- 代理引导校准比原来的p引导方法快得多.
结论:
- 代理指导的工作流为QSP模型开发中的VPops校准提供了显著的速度改进.
- 这种方法提高了在药物开发管道中使用QSP模型的效率.
- 该方法有助于创建可靠的VPops来探索患者的变化和预测治疗反应.
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