Comparison of multivariate linear regression and a machine learning algorithm developed for prediction of precision warfarin dosing in a Korean population

J Thromb Haemost. 2021 Jul;19(7):1676-1686. doi: 10.1111/jth.15318. Epub 2021 Apr 21.

Abstract

Background: Personalized warfarin dosing is influenced by various factors including genetic and non-genetic factors. Multiple linear regression (LR) is known as a conventional method to develop predictive models. Recently, machine learning approaches have been extensively implemented for warfarin dosing due to the hypothesis of non-linear association between covariates and stable warfarin dose.

Objective: To extend the multiple linear regression algorithm for personalized warfarin dosing in a Korean population and compare with a machine learning--based algorithm.

Method: From this cohort study, we collected information on 650 patients taking warfarin who achieved steady state including demographic information, indications, comorbidities, comedications, habits, and genetic factors. The dataset was randomly split into training set (90%) and test set (10%). The LR and machine learning (gradient boosting machine [GBM]) models were developed on the training set and were evaluated on the test set.

Result: LR and GBM models were comparable in terms of accuracy of ideal dose (75.38% and 73.85%), correlation (0.77 and 0.73), mean absolute error (0.58 mg/day and 0.64 mg/day), and root mean square error (0.82 mg/day and 0.9 mg/day), respectively. VKORC1 genotype, CYP2C9 genotype, age, and weight were the highest contributors and could obtain 80% of maximum performance in both models.

Conclusion: This study shows that our LR and GMB models are satisfactory to predict warfarin dose in our dataset. Both models showed similar performance and feature contribution characteristics. LR may be the appropriate model due to its simplicity and interpretability.

Keywords: anticoagulants; linear models; supervised machine learning; thrombosis; warfarin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Anticoagulants*
  • Cohort Studies
  • Cytochrome P-450 CYP2C9 / genetics
  • Genotype
  • Humans
  • Linear Models
  • Machine Learning
  • Republic of Korea
  • Vitamin K Epoxide Reductases / genetics
  • Warfarin*

Substances

  • Anticoagulants
  • Warfarin
  • Cytochrome P-450 CYP2C9
  • VKORC1 protein, human
  • Vitamin K Epoxide Reductases