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基于机器学习的中国异基因造血干细胞移植患者环孢素 A 谷浓度预测模型。

A model based on machine learning for the prediction of cyclosporin A trough concentration in Chinese allo-HSCT patients.

机构信息

Department of Pharmacy, the First Affiliated Hospital of Soochow University, Suzhou, China.

College of Pharmaceutical Sciences, Soochow University, Suzhou, China.

出版信息

Expert Rev Clin Pharmacol. 2023 Jan;16(1):83-91. doi: 10.1080/17512433.2023.2142561. Epub 2022 Nov 16.

Abstract

BACKGROUND

Cyclosporin A is a calcineurin inhibitor which has a narrow therapeutic window and high interindividual variability. Various population pharmacokinetic models have been reported; however, professional software and technical personnel were needed and the variables of the models were limited. Therefore, the aim of this study was to establish a model based on machine learning to predict CsA trough concentrations in Chinese allo-HSCT patients.

METHODS

A total of 7874 cases of CsA therapeutic drug monitoring data from 2069 allo-HSCT patients were retrospectively included. Sequential forward selection was used to select variable subsets, and eight different algorithms were applied to establish the prediction model.

RESULTS

XGBoost exhibited the highest prediction ability. Except for the variables that were identified by previous studies, some rarely reported variables were found, such as norethindrone, WBC, PAB, and hCRP. The prediction accuracy within ±30% of the actual trough concentration was above 0.80, and the predictive ability of the models was demonstrated to be effective in external validation.

CONCLUSION

In this study, models based on machine learning technology were established to predict CsA levels 3-4 days in advance during the early inpatient phase after HSCT. A new perspective for CsA clinical application is provided.

摘要

背景

环孢素 A 是一种钙调磷酸酶抑制剂,具有较窄的治疗窗和较高的个体间变异性。已有多种群体药代动力学模型被报道;然而,这些模型需要专业软件和技术人员,且模型的变量有限。因此,本研究旨在建立一种基于机器学习的模型,以预测中国异基因造血干细胞移植(allo-HSCT)患者的环孢素 A 谷浓度。

方法

回顾性纳入 2069 例 allo-HSCT 患者的 7874 例环孢素 A 治疗药物监测数据。采用逐步向前选择法选择变量子集,并应用八种不同的算法建立预测模型。

结果

XGBoost 表现出最高的预测能力。除了先前研究确定的变量外,还发现了一些很少被报道的变量,如炔诺酮、白细胞计数、前白蛋白和 hCRP。实际谷浓度的预测精度在±30%以内的准确率均高于 0.80,并且模型的预测能力在外验证中得到了证明。

结论

本研究建立了基于机器学习技术的模型,以预测 HSCT 后住院早期 3-4 天的环孢素 A 水平,为环孢素 A 的临床应用提供了新的视角。

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