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Comparison Between Paediatric and Adult Suspected Adverse Drug Reactions Reported to the European Medicines Agency: Implications for Pharmacovigilance

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Abstract

Background

Databases systematically collecting reports of suspected adverse drug reactions (ADRs) are a cornerstone of pharmacovigilance in that they provide on-going large-scale surveillance in the ‘real-world’ setting. Several studies have provided data on ADRs in children reported to national databases. EudraVigilance (EV) is the European Medicines Agency’s (EMA) web-based system for reporting and evaluating suspected ADRs. Due to requirements on pharmaceutical companies to report ADRs that originate both inside and outside Europe, the data in EudraVigilance are global in nature. As such, it is potentially a rich source of information for paediatric pharmacovigilance.

Aim

The present study sought to provide a descriptive overview comparing ADRs involving children and adolescents aged less than 18 years with those involving adults reported to EudraVigilance across national boundaries. The results will serve as a baseline to explore whether lessons can be learned for paediatric pharmacovigilance.

Methods

All ADR reports received in EudraVigilance up to 13 June 2013 were analysed for overall numbers, age, gender, and geographic origin. Accurate age was determined when reported in valid format or calculated from the interval between date of birth and the reaction start date. The nature of the ADRs and the most frequently reported drug substances and drug event combinations were evaluated using Medical Dictionary for Regulatory Activities (MedDRA) ‘preferred terms’ (PTs) and ‘system organ classes’ (SOCs). The distribution over time of reported paediatric ADRs was also analysed.

Results

As of 13 June 2013, EudraVigilance contained 3,291,593 spontaneous reports, for 75.9 % of which accurate age was determined; 11.2 % of these were paediatric reports. Paediatric ADRs were more common than those in adults under the MedDRA SOCs ‘general and administration site’, ‘nervous system’, ‘skin and subcutaneous’ and ‘infections and infestations’. For children, the three most frequently reported MedDRA PTs, i.e. pyrexia, vomiting and convulsion (13, 6 and 4 % of reports, respectively), accounted for a greater proportion of reports than the corresponding top three in adults, i.e. nausea, dyspnoea and pyrexia (4, 4 and 3 % of reports, respectively). The 20 most reported active substances (12 of which are vaccines) together accounted for 52 % of paediatric reports as compared with 28 % of adult reports.

Conclusions

The present study applied a first-time approach to one of the largest databases worldwide of reported ADRs. It confirmed that reports of reactions in children were different to those in adults, not only in terms of reactions and drugs involved but also more concentrated around limited sets of reaction types and drugs. The possible causal association between a medicine or vaccine and the suspected ADR was not formally assessed in this study since the study analysed the characteristics of reported ADRs that were suspected and therefore not proven. However, the findings may help to identify pharmacovigilance activities that should be strengthened to reduce the burden of ADRs in children.

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Acknowledgments

The authors would like to thank Chris Turner, Paolo Tomasi, Gianmario Candore, Hans-Georg Eichler, Alessandro Spina and Xavier Kurz for their constructive comments.

Disclaimer

The views expressed in this article are the personal views of the authors and may not be understood or quoted as being made on behalf of or reflecting the position of the EMA or one of its committees or working parties.

Contributors

KB is the guarantor and takes responsibility for the integrity of the work as a whole, from inception to publication, contributed to the conception of the analysis, interpreted the data, did the first draft of the article and approved the final version of the manuscript. CZ and FD analysed and interpreted the data cited, contributed to the drafting of the article, and approved the final version of the manuscript. ELM, ASR and AHS contributed to the conception of the analysis, interpretation of the data, the drafting of the article and approved the final version of the manuscript. All authors had full access to all of the data in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis.

Funding

This initiative received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors; support came from EMA resources. The EMA does not profit financially from EudraVigilance.

Competing interests

All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Data sharing

EudraVigilance data is available subject to the ‘EudraVigilance access policy for medicines for human use’ available at http://eudravigilance.ema.europa.eu/human/EudraVigilanceAccessPolicy.asp.

The lead author affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

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Authors and Affiliations

  1. European Medicines Agency, 7 Westferry Circus, Canary Wharf, London, E14 4HB, UK

    Kevin V. Blake, Cosimo Zaccaria, Francois Domergue, Edith La Mache, Agnes Saint-Raymond & Ana Hidalgo-Simon

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  1. Kevin V. Blake
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Correspondence to Kevin V. Blake.

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Blake, K.V., Zaccaria, C., Domergue, F. et al. Comparison Between Paediatric and Adult Suspected Adverse Drug Reactions Reported to the European Medicines Agency: Implications for Pharmacovigilance. Pediatr Drugs 16, 309–319 (2014). https://doi.org/10.1007/s40272-014-0076-2

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