Statin‐use phenotyping in the advanced elderly ‐ validation in a large, population‐based DNA Biobank

Abstract

Hydroxy-methyl-glutaryl (HMG) coenzyme A reductase inhibitors (statins) are considered both safe and efficacious. To quantify statin use in the advanced elderly, a cohort of subjects over 80 years of age was identified within the Marshfield Clinic Personalized Medicine Research Project (PMRP). The PMRP represents one of the largest population-based DNA Biobanks in the world (Science 298 1158–1161, 2002). Ninety-five subjects were identified (mean age 88.3 + 3.2 years), and retrospective drug-use histories were constructed through manual data abstraction. Twenty-one percent of subjects were using a statin at most recent examination (95% C.I. 13.4 – 30.6). To assess the utility of electronic phenotyping, we constructed independent statin use histories in the same subjects through the application of natural language processing software (Language and Computing, Inc.). The electronic phenotype for current medication use was 100% sensitive and 96% specific. The initial positive predictive value (PPV) was 87%. After programmatic selection of only those electronic free text data containing a dose, PPV improved to 95%. Electronic statin use histories were then constructed for a 10-year period, and collated with electronically abstracted lipid panels, for each respective subject. This phenotyping strategy should facilitate characterization of electronic dose response curves in large population-based cohorts, and position investigators to conduct pharmacogenetic association studies on an unprecedented scale. (This work was funded by a grant from the Marshfield Clinic Research Foundation.)