title: Pharmacosurveillance without borders: electronic health records in different countries can be used to address important methodological issues in estimating the risk of adverse events.
abstract: Evaluate methodological advantages and limitations of an international pharmacosurveillance system based on electronic health records (EHRs).
  
  
  
  Type 2 diabetes was used as an exemplar. Cohorts of newly treated diabetics were followed in each country (Quebec, Canada; Massachusetts, United States; Manchester, UK) from 2009 to 2012 using local EHR systems. Cox proportional hazards models were used to assess the risk of cardiovascular events.
  
  
  
  A total of 44,913 newly treated diabetics were identified; 82.6% (United States) to 93.1% (Canada) were started on biguanides; 13% of patients failed to fill initial prescriptions. An increased risk of cardiovascular events with sulfonylureas was observed when dispensing [hazard ratio (HR): 2.83] vs. EHR prescribing (HR: 2.47) data were used. The addition of clinical data produced a threefold to 10-fold increase in comorbidity for obesity and renal disease, but had no impact on the risk of different hypoglycemic therapies. The risk of cardiovascular events with sulfonylureas was higher in the United States [HR: 3.4; 95% confidence interval (CI): 2.1, 5.5] compared to England (HR: 1.3; 95% CI: 1.1, 1.6).
  
  
  
  An international surveillance system based on EHRs may provide more timely information about drug safety and new opportunities to estimate potential sources of bias and health system effects on drug-related outcomes.
authors.affiliation: Department of Epidemiology, Biostatistics and Occupational Health, Purvis Hall, McGill University, 1020 Pine Avenue West, Montreal, Quebec H3A 1A2, Canada; Department of Medicine, McGill University Health Center, 1001 Decarie Boulevard, Montreal, Quebec H4A 3J1, Canada; Clinical and Health Informatics Research Group, McGill University, 1140 Pine Avenue, Montreal, Quebec H3A 1A3, Canada. Electronic address: robyn.tamblyn@mcgill.ca.
authors.forename: Robyn
authors.initials: R
authors.lastname: Tamblyn
authors.affiliation: Clinical and Health Informatics Research Group, McGill University, 1140 Pine Avenue, Montreal, Quebec H3A 1A3, Canada.
authors.forename: Nadyne
authors.initials: N
authors.lastname: Girard
authors.affiliation: Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, Manchester Academic Health Science Centre, The University of Manchester, 2nd Floor, Stopford Building, Oxford Road, Manchester M13 9PT, UK.
authors.forename: William G
authors.initials: WG
authors.lastname: Dixon
authors.affiliation: Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Haas
authors.affiliation: Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Bates
authors.affiliation: Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, Manchester Academic Health Science Centre, The University of Manchester, 2nd Floor, Stopford Building, Oxford Road, Manchester M13 9PT, UK.
authors.forename: Thérèse
authors.initials: T
authors.lastname: Sheppard
authors.affiliation: Department of Epidemiology, Biostatistics and Occupational Health, Purvis Hall, McGill University, 1020 Pine Avenue West, Montreal, Quebec H3A 1A2, Canada.
authors.forename: Tewodros
authors.initials: T
authors.lastname: Eguale
authors.affiliation: Department of Epidemiology, Biostatistics and Occupational Health, Purvis Hall, McGill University, 1020 Pine Avenue West, Montreal, Quebec H3A 1A2, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Buckeridge
authors.affiliation: Department of Epidemiology, Biostatistics and Occupational Health, Purvis Hall, McGill University, 1020 Pine Avenue West, Montreal, Quebec H3A 1A2, Canada.
authors.forename: Michal
authors.initials: M
authors.lastname: Abrahamowicz
authors.affiliation: The Ottawa Hospital, 501 Smyth Road, Ottawa, Ontario K1H 8L6, Canada.
authors.forename: Alan
authors.initials: A
authors.lastname: Forster
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001900:Boston / Q000453:epidemiology; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D015984:Causality; D015331:Cohort Studies; D015897:Comorbidity; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000453:epidemiology*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology*; D057286:Electronic Health Records / Q000706:statistics & numerical data*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011792:Quebec / Q000453:epidemiology; D012306:Risk; D006113:United Kingdom / Q000453:epidemiology; D055815:Young Adult
chemical_list: D007004:Hypoglycemic Agents
keywords: Adverse outcome; Electronic health record; Health informatics; Medication adherence; Pharmacoepidemiology; Pharmacosurveillance; ​Risk assessment