C4C - Paediatric pharmacovigilance: Methodological Considerations in
Research and Development of Medicines for Children – A c4c Expert Group
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.