Abstract:We intend to create a new risk assessment methodology that combines the best characteristics of both risk score and machine learning models. More specifically, we aim to develop a method that, besides having a good performance, offers a personalized model and outcome for each patient, presents high interpretability, and incorporates an estimation of the prediction reliability which is not usually available. By combining these features in the same approach we expect that it can boost the confidence of physicians to use such a tool in their daily activity. In order to achieve the mentioned goals, a three-step methodology was developed: several rules were created by dichotomizing risk factors; such rules were trained with a machine learning classifier to predict the acceptance degree of each rule (the probability that the rule is correct) for each patient; that information was combined and used to compute the risk of mortality and the reliability of such prediction. The methodology was applied to a dataset of patients admitted with any type of acute coronary syndromes (ACS), to assess the 30-days all-cause mortality risk. The performance was compared with state-of-the-art approaches: logistic regression (LR), artificial neural network (ANN), and clinical risk score model (Global Registry of Acute Coronary Events - GRACE). The proposed approach achieved testing results identical to the standard LR, but offers superior interpretability and personalization; it also significantly outperforms the GRACE risk model and the standard ANN model. The calibration curve also suggests a very good generalization ability of the obtained model as it approaches the ideal curve. Finally, the reliability estimation of individual predictions presented a great correlation with the misclassifications rate. Those properties may have a beneficial application in other clinical scenarios as well. [abridged]