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

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.

Innovative Methodologies in paediatric drug development: a conect4children (c4c) special issue

“…headache in a non-verbal child, may present as irritability and it will hard to identify the exact cause of this irritability. Aurich et al, present these child-specific issues and discuss methodological challenges during paediatric drug development, including considerations to be taken into account to overcome them 5 .…”

Quo vadis (where are you going) pharmacovigilance?

“…Fortunately, the landscape of pharmacovigilance regulation is changing, and more countries are now harmonizing their efforts towards having a centralized system of surveillance of therapy‐related harms. One such example is the white paper published in a recent themed issue, providing practical considerations for paediatric pharmacovigilance, throughout the life cycle of medicinal products 5 …”

Medicine use in children aged under 12 years—Population survey in Finland

“…Children are a vulnerable patient group due to their phase of development and growth. Furthermore, paediatric medicines are often used off label and children have different responses to pharmacotherapy than adults 5–8 …”

“…Furthermore, paediatric medicines are often used off label and children have different responses to pharmacotherapy than adults. [5][6][7][8] In order to keep track of children's medicine use and the various potential challenges associated with it, comprehensive population studies on medicine use and related factors are needed. Research on medicine use aims to promote safe and effective use of medicines by identifying the factors that lead to appropriate and inappropriate use.…”