Abstract

An evolutionary ensemble modeling (EEM) method is developed to improve the accuracy of warfarin dose prediction. In EEM, genetic programming (GP) evolves diverse base models, and the genetic algorithm optimizes the parameters of the GP. The EEM model is assembled by using the prepared base models through a technique called "bagging." In the experiment, a dataset of 289 Chinese patients, which was provided by the First Affiliated Hospital of Soochow University, is used for training, validation, and testing. The EEM model with selected feature groups is benchmarked with four machine-learning methods and three conventional regression models. Results show that the EEM model with the M2+G group, namely age, height, weight, gender, CYP2C9, VKORC1, and amiodarone, presents the largest coefficients of determination (R2), the highest percentage of the predicted dose within 20% of the actual dose (20%-p), the smallest mean absolute error, mean squared error, and root-mean-squared error on the test set, and the least decrease in R2 from the training set to the test set. In conclusion, the EEM method with M2+G delivers superior performance and can, therefore, be a suitable prediction model of warfarin dose for clinical applications.

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