title: Discrepancies in listed adverse drug reactions in pharmaceutical product information supplied by the regulatory authorities in Denmark and the USA.
abstract: Pharmaceutical product information (PI) supplied by the regulatory authorities serves as a source of information on safe and effective use of drugs. The objectives of this study were to qualitatively and quantitatively compare PIs for selected drugs marketed in both Denmark and the USA with respect to consistency and discrepancy of listed adverse drug reaction (ADR) information. We compared individual ADRs listed in PIs from Denmark and the USA with respect to type and frequency. Consistency was defined as match of ADRs and of ADR frequency or match could not be ruled out. Discrepancies were defined as ADRs listed only in one country or listed with different frequencies. We analyzed PIs for 40 separate drugs from ten therapeutic groups and assigned the 4003 identified ADRs to System Organ Classes (Medical Dictionary for Regulatory Activities [MedDRA] terminology). Less than half of listed ADRs (n = 1874; 47%) showed consistency. Discrepancies (n = 2129; 53%) were split into ADRs listed only in the USA (n = 1558; 39%), ADRs listed only in Denmark (n = 325; 8%) and ADRs listed with different frequencies (n = 246; 6%). The majority of listed ADRs were of the type "gastrointestinal disorders" and "nervous system disorders". Our results show great differences in PIs for drugs approved in both Denmark and the USA illuminating concerns about the credibility of the publicly available PIs. The results also represent an argument for further harmonization across borders to improve consistency between authority-supplied information.
authors.affiliation: Department of Disease Systems Biology, NNF Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen Blegdamsvej 3B, DK-2200, Copenhagen, Denmark ; Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark Kemitorvet, DK-2800, Lyngby, Denmark.
authors.forename: Robert
authors.initials: R
authors.lastname: Eriksson
authors.affiliation: Institute of Public Health, Clinical Pharmacology, Faculty of Health Sciences, University of Southern Denmark J.B. Winsløws Vej 19, DK-5000, Odense, Denmark ; Danish Pharmacovigilance Research Project (DANPREP) Copenhagen, Denmark.
authors.forename: Lise
authors.initials: L
authors.lastname: Aagaard
authors.affiliation: Department of Disease Systems Biology, NNF Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen Blegdamsvej 3B, DK-2200, Copenhagen, Denmark.
authors.forename: Lars Juhl
authors.initials: LJ
authors.lastname: Jensen
authors.affiliation: Danish Pharmacovigilance Research Project (DANPREP) Copenhagen, Denmark ; Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen Universitetsparken 2, DK-2100, Copenhagen, Denmark.
authors.forename: Liza
authors.initials: L
authors.lastname: Borisova
authors.affiliation: Danish Pharmacovigilance Research Project (DANPREP) Copenhagen, Denmark ; Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen Universitetsparken 2, DK-2100, Copenhagen, Denmark.
authors.forename: Dorte
authors.initials: D
authors.lastname: Hørlück
authors.affiliation: Department of Disease Systems Biology, NNF Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen Blegdamsvej 3B, DK-2200, Copenhagen, Denmark ; Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark Kemitorvet, DK-2800, Lyngby, Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Brunak
authors.affiliation: Danish Pharmacovigilance Research Project (DANPREP) Copenhagen, Denmark ; Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen Universitetsparken 2, DK-2100, Copenhagen, Denmark.
authors.forename: Ebba Holme
authors.initials: EH
authors.lastname: Hansen
keywords: Adverse drug reaction; Denmark; European Medicines Agency; Food and Drug Administration; Product information; Regulatory affairs; Summary of Product Characteristics; United States; drug approval; drug labeling; drug legislation