title: Active safety monitoring of newly marketed medications in a distributed data network: application of a semi-automated monitoring system.
abstract: We developed a semi-automated active monitoring system that uses sequential matched-cohort analyses to assess drug safety across a distributed network of longitudinal electronic health-care data. In a retrospective analysis, we show that the system would have identified cerivastatin-induced rhabdomyolysis. In this study, we evaluated whether the system would generate alerts for three drug-outcome pairs: rosuvastatin and rhabdomyolysis (known null association), rosuvastatin and diabetes mellitus, and telithromycin and hepatotoxicity (two examples for which alerting would be questionable). Over >5 years of monitoring, rate differences (RDs) in comparisons of rosuvastatin with atorvastatin were -0.1 cases of rhabdomyolysis per 1,000 person-years (95% confidence interval (CI): -0.4, 0.1) and -2.2 diabetes cases per 1,000 person-years (95% CI: -6.0, 1.6). The RD for hepatotoxicity comparing telithromycin with azithromycin was 0.3 cases per 1,000 person-years (95% CI: -0.5, 1.0). In a setting in which false positivity is a major concern, the system did not generate alerts for the three drug-outcome pairs.
authors.affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. jgagne1@partners.org
authors.forename: J J
authors.initials: JJ
authors.lastname: Gagne
authors.forename: R J
authors.initials: RJ
authors.lastname: Glynn
authors.forename: J A
authors.initials: JA
authors.lastname: Rassen
authors.forename: A M
authors.initials: AM
authors.lastname: Walker
authors.forename: G W
authors.initials: GW
authors.lastname: Daniel
authors.forename: G
authors.initials: G
authors.lastname: Sridhar
authors.forename: S
authors.initials: S
authors.lastname: Schneeweiss
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000009:adverse effects; D017963:Azithromycin / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology*; D003920:Diabetes Mellitus / Q000139:chemically induced / Q000453:epidemiology; D016903:Drug Monitoring / Q000379:methods*; D001330:Electronic Data Processing; D057286:Electronic Health Records; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects*; D048628:Ketolides / Q000009:adverse effects*; D008297:Male; D017063:Outcome Assessment, Health Care; D011358:Product Surveillance, Postmarketing; D012189:Retrospective Studies; D012206:Rhabdomyolysis / Q000139:chemically induced / Q000453:epidemiology
chemical_list: D000900:Anti-Bacterial Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D048628:Ketolides; D017963:Azithromycin; C106791:telithromycin