A Computer-Aided System for Determining the Application Range of a Warfarin Clinical Dosing Algorithm Using Support Vector Machines with a Polynomial Kernel Function

Determining the optimal initial dose for warfarin is a critically important task. Several factors have an impact on the therapeutic dose for individual patients, such as patients' physical attributes (Age, Height, etc.), medication profile, co-morbidities, and metabolic genotypes (CYP2C9 and VKORC1). These wide range factors influencing therapeutic dose, create a complex environment for clinicians to determine the optimal initial dose. Using a sample of 4,237 patients, we have proposed a companion classification model to one of the most popular dosing algorithms (International Warfarin Pharmacogenetics Consortium (IWPC) clinical model), which identifies the appropriate cohort of patients for applying this model. The proposed model functions as a clinical decision support system which assists clinicians in dosing. We have developed a classification model using Support Vector Machines, with a polynomial kernel function to determine if applying the dose prediction model is appropriate for a given patient. The IWPC clinical model will only be used if the patient is classified as "Safe for model". By using the proposed methodology, the dosing mode's prediction accuracy increases by 15 percent in terms of Root Mean Squared Error and 17 percent in terms of Mean Absolute Error in dose estimates of patients classified as "Safe for model".Comment: 6 pages, 8 tables, 1 figur

Warfarin dose estimation on multiple datasets with automated hyperparameter optimisation and a novel software framework

Warfarin is an effective preventative treatment for arterial and venous thromboembolism, but requires individualised dosing due to its narrow therapeutic range and high individual variation. Many machine learning techniques have been demonstrated in this domain. This study evaluated the accuracy of the most promising algorithms on the International Warfarin Pharmacogenetics Consortium dataset and a novel clinical dataset of South African patients. Support vectors and linear regression were amongst the top performers in both datasets and performed comparably to recent stacked ensemble approaches, whilst neural networks were one of the worst performers in both datasets. We also introduced genetic programming to automatically optimise model architectures and hyperparameters without human guidance. Remarkably, the generated models were found to match the performance of the best models hand-crafted by human experts. Finally, we present a novel software framework (Warfit-learn) for warfarin dosing research. It leverages the most successful techniques in preprocessing, imputation, and parallel evaluation, with the goal of accelerating research and making results in this domain more reproducible.Comment: 19 pages, 4 tables, 3 figure