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Evaluation of supervised machine learning algorithms in predicting the poor anticoagulation control and stable weekly doses of warfarin

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Abstract

Background

Machine learning algorithms (MLAs) carry a huge potential in identifying predicting factors and are being explored for their utility in the field of personalized medicine.

Aim

We aimed to investigate MLAs for identifying predictors (clinical and genetic) of poor anticoagulation status (ACS) and stable weekly warfarin dose (SWWD).

Method

Clinical factors, in addition to the CYP2C9, VKORC1, and CYP4F2 genotypes, were obtained for patients receiving warfarin for at least the previous six months. The C5.0 decision tree classification algorithm was used to predict poor ACS while classification and regression tree analysis (CART), in addition to the Chi-square automatic interaction detector (CHAID), was used to predict SWWD. The percentage of patients within 20% of the actual dose, root mean squared error (RMSE), and area under the receiver-operating characteristics curve (AUROC) were identified as performance indicators of the models.

Results

In the C5.0 classification decision tree, the CYP4F2 genotype was the strongest predictor of ACS (AUROC = 0.53). In the CART analysis of SWWD, VKORC1 polymorphisms were the most significant predictor, followed by the CYP2C9 genotype (percentage of patients within 20% of the actual dose = 38.2%, RMSE = 13.6). For the CHAID algorithm, the percentage of patients within 20% of the actual dose was 49%, while the RMSE was found to be 13.4.

Conclusion

Genetic and non-genetic predictive factors were identified by the MLAs for ACS and SWWD. Further, the need to externally validate the MLAs in a prospective study was highlighted.

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Acknowledgements

We thank the staff nurses in the anticoagulation clinic for their immense co-operation during the data collection.

Funding

The study was carried out as a part of warfarin pharmacogenetic study, with the Funding Number: AGU RCSI-2019-02.

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Authors and Affiliations

  1. Department of Pharmacology and Therapeutics, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Kingdom of Bahrain

    Kannan Sridharan

  2. Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, USA

    Murali Ramanathan

  3. Department of Cardiology, Salmaniya Medical Complex, Manama, Kingdom of Bahrain

    Rashed Al Banna

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  1. Kannan Sridharan
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  2. Murali Ramanathan
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  3. Rashed Al Banna
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Correspondence to Kannan Sridharan.

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Sridharan, K., Ramanathan, M. & Al Banna, R. Evaluation of supervised machine learning algorithms in predicting the poor anticoagulation control and stable weekly doses of warfarin. Int J Clin Pharm 45, 79–87 (2023). https://doi.org/10.1007/s11096-022-01471-y

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