PHARMACOEPIDEMIOLOGY AND PRESCRIPTION
Adverse drug reaction reporting: how can drug consumption
information add to analyses using spontaneous reports?
Kjell H. Halvorsen
Received: 4 May 2017 /Accepted: 4 December 2017 /Published online: 18 December 2017
Springer-Verlag GmbH Germany, part of Springer Nature 2017
Purpose 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.
Methods We combined all Norwegian ADR reports in 2004–2013 from the EudraVigilance database (n = 14.028) with dispens-
ing 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.
Results 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.
Conclusions 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.
Keywords Drug consumption
Only a limited amount of information about adverse drug
reactions (ADRs) is available when a drug receives marketing
authorisation and enters the market. To ensure patient safety, it
is essential for regulatory authorities to quickly obtain post-
marketing information about ADRs. Spontaneous reporting of
ADRs is therefore a cornerstone in pharmacovigilance [1, 2].
Out of the approximately 2300 ADR signals assessed by the
European Medicines Agency (EMA) in 2015, 88% were
based on ADR reports from the European pharmacovigilance
database EudraVigilance .
In pharmacovigilance, spontaneous ADR reports have
formed basis for many studies with different research ques-
tions, such as assessing ADRs in children , studying
avoidability of ADRs  and exploring differences between
patient and health care professional reporting . ADR reports
• Adjusting the ADR reporting rates with consumption data provides
important additional information.
• Consumption-adjusted adverse drug reaction reporting rates (CADRRs)
can be used when comparing different drugs, different sub-populations
and when studying reporting trends over time.
Early preliminary results have been presented as a poster at the 31st ICPE
Electronic supplementary material The online version of this article
(https://doi.org/10.1007/s00228-017-2396-y) contains supplementary
material, which is available to authorized users.
* Kristian Svendsen
Tromsø Hospital Pharmacy, University Hospital of North Norway,
N-9038 Tromsø, Norway
Department of Pharmacy, UiT – The Arctic University of Norway,
Regional Medicines Information and Pharmacovigilance Centre
(RELIS), University Hospital of North Norway, Tromsø, Norway
Norwegian Medicines Agency, Oslo, Norway
European Journal of Clinical Pharmacology (2018) 74:497–504