Classification of drug use patterns

Abstract

Characterizing long-term prescription data is challenging due to the time-varying nature of drug use. Conventional approaches summarize time-varying data into categorical variables based on simple measures, such as cumulative dose, while ignoring patterns of use. The loss of information can lead to misclassification and biased estimates of the exposure-outcome association. We introduce a classification method to characterize longitudinal prescription data with an unsupervised machine learning algorithm. We used administrative databases covering virtually all 1.3 million residents of Manitoba and explicitly designed features to describe the average dose, proportion of days covered (PDC), dose change, and dose variability, and clustered the resulting feature space using K-means clustering. We applied this method to metformin use in diabetes patients. We identified 27,786 metformin users and showed that the feature distributions of their metformin use are stable for varying the lengths of follow-up and that these distributions have clear interpretations. We found six distinct metformin user groups: patients with intermittent use, decreasing dose, increasing dose, high dose, and two medium dose groups (one with stable dose and one with highly variable use). Patients in the varying and decreasing dose groups had a higher chance of progression of diabetes than other patients. The method presented in this paper allows for characterization of drug use into distinct and clinically relevant groups in a way that cannot be obtained from merely classifying use by quantiles of overall use.

Keywords: Clustering; K-means; drug exposure; machine learning; pharmacoepidemiology.