检测急性损伤风险的潜在药物相互作用:使用可解释的机器学习模型进行基于人口的病例控制研究
Hayato Akimoto1,2, Takashi Hayakawa1,2, Takuya Nagashima1,2
1Division of Pharmacology, Department of Biomedical Sciences, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan.
Frontiers in pharmacology
|June 8, 2023
概括
结合循环利尿剂和组胺H2抑制剂会增加急性损伤 (AKI) 的风险. 机器学习模型识别了这种药物相互作用,提供了超越传统统计方法预测药物不良事件的洞察力.
科学领域:
- 药物监督 药物监督 药物监督
- 计算医学是一种计算医学.
- 腎臟病學 (nephrology) 是一種醫學.
背景情况:
- 急性损伤 (AKI) 是一种常见的不良药物事件,通常与毒药物有关.
- 药物相互作用分析的传统统计模型可能会过度匹配数据,限制可靠性.
- 可解释机器学习提供了一种新的方法来识别AKI风险因素.
研究的目的:
- 使用可解释的机器学习模型检测与AKI风险增加相关的药物相互作用.
- 克服传统统计模型在评估AKI药物相互作用方面的局限性.
- 为了确定构成AKI显著风险的特定药物组合.
主要方法:
- 在电子医疗记录上开发和训练了六个机器学习模型 (MLR,LLR,随机森林,XGBoost,SVM).
- 解释高性能XGBoost和LLR模型使用SHAP和RERI进行药物相互作用分析.
- 分析了大约250万患者的数据,其中有5319例AKI病例和60348例对照病例.
主要成果:
- 循环利尿剂和胰岛素H2抑制剂的组合被确定为AKI的重要危险因素.
- 在XGBoost模型中,这种药物组合的平均SHAP值为0.011.
- 该LLR模型显示了一个协同作用的相互作用与相对过度风险由于相互作用 (RERI) 的1.289 (95% CI:0.226-5.591).
结论:
- 同时使用循环利尿剂和组胺H2抑制剂与AKI的风险增加有关.
- 可解释的机器学习模型为AKI预测提供了对药物相互作用的宝贵见解.
- 虽然这种药物组合的影响比年龄或性别要小,但对于AKI预防,这种药物组合需要临床关注.
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