A Method for Mining Infrequent Causal Associations and Its Application in Finding Adverse Drug Reaction Signal Pairs

In many real-world applications, it is important to mine causal relationships where an event or event pattern causes certain outcomes with low probability. Discovering this kind of causal relationships can help us prevent or correct negative outcomes caused by their antecedents. In this paper, we propose an innovative data mining framework and apply it to mine potential causal associations in electronic patient data sets where the drug-related events of interest occur infrequently. Specifically, we created a novel interestingness measure, exclusive causal-leverage, based on a computational, fuzzy recognition-primed decision (RPD) model that we previously developed. On the basis of this new measure, a data mining algorithm was developed to mine the causal relationship between drugs and their associated adverse drug reactions (ADRs). The algorithm was tested on real patient data retrieved from the Veterans Affairs Medical Center in Detroit, Michigan. The retrieved data included 16,206 patients (15,605 male, 601 female). The exclusive causal-leverage was employed to rank the potential causal associations between each of the three selected drugs (i.e., enalapril, pravastatin, and rosuvastatin) and 3,954 recorded symptoms, each of which corresponded to a potential ADR. The top 10 drug-symptom pairs for each drug were evaluated by the physicians on our project team. The numbers of symptoms considered as likely real ADRs for enalapril, pravastatin, and rosuvastatin were 8, 7, and 6, respectively. These preliminary results indicate the usefulness of our method in finding potential ADR signal pairs for further analysis (e.g., epidemiology study) and investigation (e.g., case review) by drug safety professionals.