Adverse drug reaction reporting: how can drug consumption information add to analyses using spontaneous reports?
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Spontaneous reporting of adverse drug reactions (ADRs) is a cornerstone in pharmacovigilance. However, information about the underlying consumption of drugs is rarely used when analysing spontaneous reports. The purpose of this study was to combine ADR reports with drug consumption data to demonstrate the additional information this gives in various scenarios, comparing different drugs, gender-stratified sub-populations and changes in reporting over time.
We combined all Norwegian ADR reports in 2004–2013 from the EudraVigilance database (n = 14.028) with dispensing data from the Norwegian Prescription Database (more than 800 million dispensed prescriptions during 2004–2013). This was done in order to calculate drug-specific consumption-adjusted adverse drug reaction reporting rates (CADRRs) by dividing the number of reports for each drug with the number of users of the drug during the same time period.
Among the ten drugs with the highest number of ADR reports and the ten drugs with the highest CADRR, only four drugs were in both categories. This indicates that drugs with a high number of reports often also have a high number of users and that CADRR captures drugs with potentially relevant safety issues but a smaller number of users. Comparing reported ADRs in females and males using methylphenidate, we found that the two groups report different ADRs. Finally, we showed that changes in ADR reporting for simvastatin and atorvastatin during 2004–2013 were due to changes in consumption and that atorvastatin had a higher CADRR but fewer reports than simvastatin.
CADRR provides additional information compared with number of reports alone in studies using spontaneous reports. It is important for researchers to adjust for consumption whenever possible in pharmacovigilance studies.
KeywordsDrug consumption Pharmacovigilance Adverse drug reactions Norway EudraVigilance
Contributions of authors
KS conceived the project and performed the analysis and first draft of paper. KH, SV and HS all contributed in the planning of the project as well as the writing of the manuscript. BH contributed in planning and writing and is the overall project manager.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- 1.European Medicines Agency (2015) 2014 Annual Report on EudraVigilance for the European Parliament, the Council and the Commission. http://www.ema.europa.eu/docs/en_GB/document_library/Report/2015/05/WC500186342.pdf. Accessed 14 Dec 2017
- 3.European Medicines Agency (2016) 2015 Annual Report on EudraVigilance for the European Parliament, the Council and the Commission. http://www.ema.europa.eu/docs/en_GB/document_library/Report/2016/03/WC500203705.pdf. Accessed 14 Dec 2017
- 7.McDonald CJ, Kalisch Ellett LM, Barratt JD, Caughey GE (2014) A cross-country comparison of rivaroxaban spontaneous adverse event reports and concomitant medicine use with the potential to increase the risk of harm. Drug Saf 37(12):1029–1035. https://doi.org/10.1007/s40264-014-0235-y CrossRefPubMedGoogle Scholar
- 8.Giezen TJ, Mantel-Teeuwisse AK, Meyboom RHB, Straus SMJM, Leufkens HGM, Egberts TCG (2010) Mapping the safety profile of biologicals: a disproportionality analysis using the WHO adverse drug reaction database, VigiBase. Drug Saf 33(10):865–878. https://doi.org/10.2165/11538330-000000000-00000 CrossRefPubMedGoogle Scholar
- 10.Tavassoli N, Lapeyre-Mestre M, Sommet A, Montastruc JL (2009) Reporting rate of adverse drug reactions to the French pharmacovigilance system with three step 2 analgesic drugs: dextropropoxyphene, tramadol and codeine (in combination with paracetamol). Br J Clin Pharmacol 68(3):422–426. https://doi.org/10.1111/j.1365-2125.2009.03472.x CrossRefPubMedPubMedCentralGoogle Scholar
- 13.Coloma PM, Schuemie MJ, Trifirò G, Gini R, Herings R, Hippisley-Cox J, Mazzaglia G, Giaquinto C, Corrao G, Pedersen L, van der Lei J, Sturkenboom M, on behalf of the EU-ADR consortium (2011) Combining electronic healthcare databases in Europe to allow for large-scale drug safety monitoring: the EU-ADR Project. Pharmacoepidemiol Drug Saf 20(1):1–11. https://doi.org/10.1002/pds.2053 CrossRefPubMedGoogle Scholar
- 14.Edlinger D, Sauter SK, Rinner C, Neuhofer LM, Wolzt M, Grossmann W, Endel G, Gall W (2014) JADE: a tool for medical researchers to explore adverse drug events using health claims data. Appl Clin Inform 5(3):621–629. https://doi.org/10.4338/ACI-2014-04-RA-0036 CrossRefPubMedPubMedCentralGoogle Scholar
- 16.Furu K (2008) Establishment of the nationwide Norwegian Prescription Database (NorPD)—new opportunities for research in pharmacoepidemiology in Norway. Nor J Epidemiol 18:129–136Google Scholar
- 17.The European Parliament and the Council of the European Union (2004) Regulation (EC) No 726/2004. http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2004:136:0001:0033:en:PDF. Accessed 14 Dec 2017
- 18.European Medicines Agency (2014) Guideline on good pharmacovigilance practices (GVP) Annex I. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2013/05/WC500143294.pdf. Accessed 14 Dec 2017
- 19.MSSO MedDRA hierarchy. http://www.meddra.org/how-to-use/basics/hierarchy. Accessed 14 Dec 2017
- 20.Storebø OJ, Ramstad E, Krogh HB et al (2015) Methylphenidate for children and adolescents with attention deficit hyperactivity disorder (ADHD). Cochrane Database Syst Rev. https://doi.org/10.1002/14651858.CD009885.pub2
- 22.Dagens Medisin (2009) Atorvastatin på blå resept igjen [Atorvastatin reimbursed again]. http://www.dagensmedisin.no/artikler/2009/05/20/atorvastatin-pa-bla-resept-igjen/. Accessed 14 Dec 2017
- 28.Hoffman KB, Demakas AR, Dimbil M, Tatonetti NP, Erdman CB (2014) Stimulated reporting: the impact of US Food and Drug Administration-issued alerts on the adverse event reporting system (FAERS). Drug Saf 37(11):971–980. https://doi.org/10.1007/s40264-014-0225-0 CrossRefPubMedPubMedCentralGoogle Scholar