基于机器学习的模型选择和平均值优于单模型方法对先验的万科米辛精确剂量.
Wisse van Os1,2, Amaury O'Jeanson3, Carla Troisi4
1Division of Systems Pharmacology & Pharmacy, Leiden Academic Centre for Drug Research, Leiden University, Leiden, the Netherlands.
机器学习 (ML) 模型可以指导选择适当的人口药代动力学 (PK) 模型用于万科米辛剂量. 这可以在没有治疗药物监测 (TDM) 样本的情况下提高精确剂量,从而使患者具体预测更加准确.
科学领域:
- 药物指标 (Pharmacometrics) 是一个指标.
- 医疗保健中的机器学习
- 药物剂量优化 药物剂量优化
背景情况:
- 在基于模型的精确剂量 (MIPD) 中,为个体患者选择最佳的人口药理动力学 (PK) 模型是具有挑战性的,特别是没有治疗药物监测 (TDM) 数据.
- 由于其狭窄的治疗指数和潜在的毒性,科米辛的剂量需要仔细考虑.
研究的目的:
- 开发和评估一个机器学习 (ML) 模型,以指导选择适当的PK模型,以先验MIPD的vancomycin.
- 在没有TDM样本的情况下,提高香草素剂量预测的准确性和可靠性.
主要方法:
- 在156个医疗保健中心对343,636名Vancomycin TDM成年患者的记录进行了回顾性分析.
- 开发一个ML多标签分类模型 (XGBoost) 来预测六种现有的PK模型的性能.
- 根据它们与观察到的TDM值的接近程度 (80%-125%) 来标记PK模型预测.
主要成果:
- 基于ML的最高排名的PK模型的ML引导选择和基于ML的模型平均值显著超过了单个PK模型,基于BMI的选择和天真平均值.
- 机器学习方法显示出改善了人口水平的准确性,在目标范围内的预测比例更高,并且没有系统偏差.
- 预测性能随着ML分配的模型排名较低而下降,这表明了ML驱动的排名系统的实用性.
结论:
- 基于ML的PK模型选择和平均值为vancomycin的先验MIPD提供了一个强大的策略.
- 这些ML方法可以通过指导选择合适的模型并避免低于最佳的模型来增强早期的万科米辛剂量决定.
- 这些发现表明,ML可以在有限或没有TDM数据的场景中优化精确剂量.
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