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Review
. 2022 Dec;88(12):4997-5016.
doi: 10.1111/bcp.15119. Epub 2021 Dec 18.

c4c: Paediatric pharmacovigilance: Methodological considerations in research and development of medicines for children - A c4c expert group white paper

Beate Aurich  1 , Dina Apele-Freimane  2 , Tobias Banaschewski  3 , Laurent Chouchana  4 , Simon Day  5 , Florentia Kaguelidou  6 , Lauren E Kelly  7 , Jenny M Kindblom  8 , Antje Neubert  9 , Ian C K Wong  10   11
Affiliations
Review

c4c: Paediatric pharmacovigilance: Methodological considerations in research and development of medicines for children - A c4c expert group white paper

Beate Aurich et al. Br J Clin Pharmacol. 2022 Dec.

Abstract

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 regard 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 are 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, 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.

Keywords: adverse drug reaction; benefit-risk assessment; clinical trial protocol; paediatric; paediatric investigation plan; pharmacovigilance; risk management; safety specification; signal detection.

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Conflict of interest statement

B.A. has worked for GlaxoSmithKline and holds company shares. She has also worked for Novartis. The work for the present article is not related to these previous employments. T.B. served in an advisory or consultancy role for ADHS digital, Infectopharm, Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmbH, Roche and Takeda. He received conference support or speaker's fee by Medice and Takeda. He received royalties from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press; the present work is unrelated to these relationships. S.D. works as a paid consultant to the pharmaceutical industry. I.W. reports grants from Research Grant Council Hong Kong; personal fees from Medice; and grants and personal fees from Janssen, outside the submitted work. All other authors declared not having any conflict of interest.

Figures

FIGURE 1
FIGURE 1
Relationship between paediatric safety specification, pharmacovigilance and risk minimisation in paediatric studies and clinical. PK, Pharmacokinetics; PD, PHarmacodynamics; ADR, Adverse drug reaction
FIGURE 2
FIGURE 2
Key elements of the paediatric pharmacovigilance cycle
See this image and copyright information in PMC

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