Identification of possible adverse drug reactions in clinical notes: The case of glucose-lowering medicines
Pernille Warrer1, Peter Bjødstrup Jensen2, Lise Aagaard3, Lars Juhl Jensen2, Søren Brunak4, Malene Hammer Krag1, Peter Rossing5, Thomas Almdal5, Henrik Ullits Andersen5, Ebba Holme Hansen1
1 Department of Pharmacy, Section for Social and Clinical Pharmacy, University of Copenhagen, Copenhagen, Denmark
2 Novo Nordisk Foundation Centre for Protein Research, University of Copenhagen, Copenhagen, Denmark
3 Department of Public Health, University of Southern Denmark, Odense, Denmark
4 Department of Systems Biology, Centre for Biological Sequence Analysis, Technical University of Denmark, Kongens Lyngby, Denmark
5 Steno Diabetes Center, Gentofte, Denmark
Department of Public Health, University of Southern Denmark, Odense
Source of Support: None, Conflict of Interest: PR is employed at the Steno Diabetes Centre owned by Novo Nordisk, has received fees to institution for consultancy or lectures from Abbott, Astra Zeneca, BMS, Boehringer Ingelheim, Eli Lilly and Novo Nordisk and has
shares in Novo Nordisk. HUA is employed at the Steno Diabetes Centre and has received fees to institution for consultancy from Abbott and has shares in Novo Nordisk. TA has shares in Novo Nordisk A/S. PWA, PBJ, LJJ, LAA, SB, MHK, and EHH have no conflicting interests to declare regarding the content of this article.
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.
Findings: 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."
Conclusion: 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.