title: Identification of possible adverse drug reactions in clinical notes: The case of glucose-lowering medicines.
abstract: OBJECTIVE
  Through manual review of clinical notes for patients with type 2 diabetes mellitus attending a Danish diabetes center, the aim of the study was to identify adverse drug reactions (ADRs) associated with three classes of glucose-lowering medicines: "Combinations of oral blood-glucose lowering medicines" (A10BD), "dipeptidyl peptidase-4 (DDP-4) inhibitors" (A10BH), and "other blood glucose lowering medicines" (A10BX). Specifically, we aimed to describe the potential of clinical notes to identify new ADRs and to evaluate if sufficient information can be obtained for causality assessment.
  
  
  METHODS
  For observed adverse events (AEs) we extracted time to onset, outcome, and suspected medicine(s). AEs were assessed according to World Health Organization-Uppsala Monitoring Centre causality criteria and analyzed with respect to suspected medicines, type of ADR (system organ class), seriousness and labeling status.
  
  
  RESULTS
  A total of 207 patients were included in the study leading to the identification of 163 AEs. 14% were categorized as certain, 60% as probable/likely, and 26% as possible. 15 (9%) ADRs were unlabeled of which two were serious: peripheral edema associated with sitagliptin and stomach ulcer associated with liraglutide. Of the unlabeled ADRs, 13 (87%) were associated with "other blood glucose lowering medications," the remaining 2 (13%) with "DDP-4 inhibitors."
  
  
  CONCLUSIONS
  Clinical notes could potentially reveal unlabeled ADRs associated with prescribed medicines and sufficient information is generally available for causality assessment. However, manual review of clinical notes is too time-consuming for routine use and hence there is a need for developing information technology (IT) tools for automatic screening of patient records with the purpose to detect information about potentially serious and unlabeled ADRs.
authors.affiliation: Department of Pharmacy, Section for Social and Clinical Pharmacy, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Pernille
authors.initials: P
authors.lastname: Warrer
authors.affiliation: Novo Nordisk Foundation Centre for Protein Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Peter Bjødstrup
authors.initials: PB
authors.lastname: Jensen
authors.affiliation: Department of Public Health, University of Southern Denmark, Odense, Denmark.
authors.forename: Lise
authors.initials: L
authors.lastname: Aagaard
authors.affiliation: Novo Nordisk Foundation Centre for Protein Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Lars Juhl
authors.initials: LJ
authors.lastname: Jensen
authors.affiliation: Department of Systems Biology, Centre for Biological Sequence Analysis, Technical University of Denmark, Kongens Lyngby, Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Brunak
authors.affiliation: Department of Pharmacy, Section for Social and Clinical Pharmacy, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Malene Hammer
authors.initials: MH
authors.lastname: Krag
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Rossing
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Almdal
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark.
authors.forename: Henrik Ullits
authors.initials: HU
authors.lastname: Andersen
authors.affiliation: Department of Pharmacy, Section for Social and Clinical Pharmacy, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ebba Holme
authors.initials: EH
authors.lastname: Hansen
keywords: Adverse drug reactions; adverse events; clinical notes; glucose-lowering medicines; manual review