A system of machine learning (“ML”) models for making actionable predictions regarding low-incidence events, including a generative ML model that produces synthetic minority-class records to form an augmented training data set, a predictive ML model that has been trained on the augmented training data set, a certainty ML model that produces a certainty estimate, and an explanatory model that produces an explanation. A method for producing actionable predictions of a low-incidence event by applying ML models to imbalanced class data by producing a prediction by a predictive ML model that has been trained on a data set comprising synthetic minority-class data records produced by a generative ML model, and producing a certainty estimate and an explanation. At least one of the certainty estimate or explanation determines an effective or appropriate response to the prediction. The low-incidence event may comprise risk of opioid use disorder.