Handling Sparsity with Random Forests When Predicting Adverse Drug Events from Electronic Health Records

When using electronic health record (EHR) data to build models for predicting adverse drug effects (ADEs), one is typically facing the problem of data sparsity, i.e., Drugs and diagnosis codes that could be used for predicting a certain ADE are absent for most observations. For such tasks, the ability to effectively handle sparsity by the employed machine learning technique is crucial. The state-of-the-art random forest algorithm is frequently employed to handle this type of data. It has however recently been demonstrated that the algorithm is biased towards the majority class, which may result in a low predictive performance on EHR data with large numbers of sparse features. In this study, approaches to handle this problem are empirically evaluated using 14 ADE datasets and three performance metrics, F1-score, AUC and Brier score. Two resampling based techniques are investigated and compared to two baseline approaches. The experimental results indicate that, for larger forests, the resampling methods outperform the baseline approaches when considering F1-score, which is consistent with the metric being affected by class bias. The approaches perform on a similar level with respect to AUC, which can be explained by the metric not being sensitive to class bias. Finally, when considering the squared error (Brier score) of individual predictions, one of the baseline approaches turns out to be ahead of the others. A bias-variance analysis shows that this is an effect of the individual trees being more correct on average for the baseline approach and that this outweighs the expected loss from a lower variance. The main conclusion is that the suggested choice of approach to handle sparsity is highly dependent on the performance metric, or the task, of interest. If the task is to accurately assign an ADE to a patient record, a sampling based approach is recommended. If the task is to rank patients according to risk of a certain ADE, the choice of approach is of minor impor- ance. Finally, if the task is to accurately assign probabilities for a certain ADE, then one of the baseline approaches is recommended.