Implementing a medication-based index to account for comorbidity in pharmacoepidemiologic studies: The Rx-Risk Comorbidity Index

Background: Methods that account for a wide range of comorbidities are needed when attempting to identify causal associations in registry-based studies. We aimed to implement the prescription-based Rx-Risk Comorbidity Index (abbreviated Rx-Risk) in nationwide data from Norway, to study the association between Rx-Risk and mortality by history of hip fracture, and to quantify the contribution of Rx-Risk in explaining the excess mortality after hip fracture. Methods: Rx-Risk was based on filled prescriptions in the Norwegian Prescription Database. Medications were mapped to 46 comorbidity categories by Anatomical Therapeutic Chemical code. The study population comprised all individuals aged 65 years and older who were alive by the end of 2013 and had filled at least one prescription in an outpatient pharmacy in Norway in 2013 (n=735 968). Twenty-year history of hip fracture (1994–2013) was available in the Norwegian Epidemiologic Osteoporosis Studies (NOREPOS) hip fracture database, and year of death was obtained from Statistics Norway. We estimated one-year mortality according to Rx-Risk based on dispensed prescriptions in 2013, history of hip fracture, age and sex using Poisson regression. Results: Mortality increased exponentially with increasing Rx-Risk scores, and it was highest in persons with a history of hip fracture across the major range of Rx-Risk scores. Age- and sex-adjusted mortality risk difference according to history of hip fracture (yes vs no) was 4.4 percentage points (7.8% vs 3.4%). Adjustment for Rx-Risk score attenuated the risk difference to 3.3 percentage points. Conclusion: The Rx-Risk Comorbidity Index, based on dispensed drugs in outpatient pharmacies, can serve as a useful tool to account for comorbidity in pharmacoepidemiologic studies. History of hip fracture and comorbidity scores were both independent risk factors for mortality in the community-dwelling older population in Norway. Comorbidity explained a quarter of the excess mortality in persons with a history of hip fracture.