An Ensemble Model With Clustering Assumption for Warfarin Dose Prediction in Chinese Patients

The prediction of daily stable warfarin dosage for a specific patient is difficult. To improve the predictive accuracy and to build a highly accurate predictive model, we developed an ensemble learning method, called evolutionary fuzzy c-mean (EFCM) clustering algorithm with support vector regression (SVR). A dataset of 517 Han Chinese patients was collected from the data of The First Affiliated Hospital of Soochow University and dataset of International Warfarin Pharmacogenetics Consortium for training and testing. In EFCM+SVR, we adopted SVR to build a generalized base model (SVR model). To achieve an accurate prediction on patients with large dosage, we proposed an EFCM clustering algorithm that can be used to cluster the training set and designed a clustering model on clusters and centroids. The SVR and clustering models were integrated into an ensemble model by stepwise functions. In the experiment, three artificial neural networks, SVR, two ensemble models, and three regression models were used as comparators to the EFCM+SVR model, which obtained the smallest mean absolute error (0.67 mg/d) in warfarin dose prediction and the largest R-squared (43.9%). The model achieved satisfactory prediction in terms of the percentage of patients whose predicted dose of warfarin was within 15% and 20% of the actual stable therapeutic dose (15%-p of 36% and 20%-p of 46.6%).