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C4C - Paediatric pharmacovigilance: Methodological Considerations in Research and Development of Medicines for Children – A c4c Expert Group White Paper
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  • Beate Aurich,
  • Dina Apele-Freimane,
  • Tobias Banaschewski,
  • Laurent Chouchana,
  • Simon Day,
  • Florentia Kaguelidou,
  • Lauren E Kelly,
  • Jenny Kindblom,
  • Antje Neubert,
Beate Aurich
Saint-Louis Hospital, Paris

Corresponding Author:[email protected]

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Dina Apele-Freimane
Neonatal Intensive Care, Women and Child Health Clinic, Pauls Stradins Clinical University Hospital, Riga, Latvia
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Tobias Banaschewski
Department of Child and Adolescent Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
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Laurent Chouchana
Hospital Cochin
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Simon Day
Clinical Trials Consulting & Training Limited.
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Florentia Kaguelidou
Department of Pediatric Pharmacology and Pharmacogenetics, APHP, Robert Debré Hospital; Center of Clinical Investigations, INSERM CIC1426; Université de Paris, EA7323, Paris, France.
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Lauren E Kelly
Department of Paediatrics and Child Health, Max Rady College of Medicine, University of Manitoba, Winnipeg, Canada.
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Jenny Kindblom
Pediatric Clinical Research Center at the Queen Silvia Children's Hospital
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Antje Neubert
Universitätsklinikum Erlangen
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Department of Pharmacology and Pharmacy
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Children frequently respond differently to therapies compared to adults. Differences also exist between paediatric age groups for pharmacokinetics and pharmacodynamics in both efficacy and safety. Paediatric pharmacovigilance requires an understanding of the unique aspects of children with regards to, for example, drug response, growth and development, clinical presentation of adverse drug reactions (ADRs), how they can be detected and population specific factors (e.g. more frequent use of off-label/unlicensed drugs). In recognition of these challenges a group of experts has been formed in the context of the conect4children (c4c) project to support paediatric drug development. This expert group collaborated to develop methodological considerations for paediatric drug safety and pharmacovigilance throughout the life-cycle of medicinal products which is described in this article. These considerations include practical points to consider for the development of the paediatric section of the risk management plan (RMP), safety in paediatric protocol development and safety data collection and analysis. Furthermore, they describe the specific details of post-marketing pharmacovigilance in children using, for example, spontaneous reports, electronic health care records, registries and record-linkage, as well as the use of paediatric pharmacoepidemiology studies for risk characterisation. Next the details of the assessment of benefit-risk and challenges related to medicinal product formulation in the context of a Paediatric Investigation Plan (PIP) are presented. Finally, practical issues in paediatric signal detection and evaluation are included. This paper provides practical points to consider for paediatric pharmacovigilance throughout the life-cycle of medicinal products for RMPs, protocol development, safety data collection and analysis and PIPs.
28 May 2021Submitted to British Journal of Clinical Pharmacology
31 May 2021Submission Checks Completed
31 May 2021Assigned to Editor
19 Jun 2021Reviewer(s) Assigned
10 Aug 2021Review(s) Completed, Editorial Evaluation Pending
16 Aug 2021Editorial Decision: Revise Minor
12 Oct 20211st Revision Received
15 Oct 2021Submission Checks Completed
15 Oct 2021Assigned to Editor
15 Oct 2021Review(s) Completed, Editorial Evaluation Pending
15 Oct 2021Editorial Decision: Accept
Dec 2022Published in British Journal of Clinical Pharmacology volume 88 issue 12 on pages 4997-5016. 10.1111/bcp.15119