31 An update on the challenges of conducting pediatric clinical trials: 15 years of progress since EMA regulation implementation

Background/Aims Still 60% of drugs used in children are off label. Although the EMA regulation, increased largely the timely submission of Pediatric Investigational plans (PIP) and initiation of clinical trials (CT), the majority of these CT's remained unsuccessful due to insufficient recruitment, administrative burden, inadequate methodology, among others. Historically, the concept was largely developed for blockbuster drugs where the adult indication and design, was translated into the pediatric population. Method This report describes the core principles of conducting trials in a pediatric setting, gathered through literature and a collected global expertise of over 30 years of clinical trials in children. Results The main principles include adapting trial study teams for pediatric needs, limiting sampling and optimizing imaging, communication between trial site and sponsor (with or without network aid), as well as placing child and/or parent centrally within the trial design, targeting the pediatric indication of the drug. The increasing number of orphan drugs, with often major only indication in children, demands specific expertise. Alternative solution to sampling, such as sparse sampling and dry blood sampling are recommended. Novel anesthesiology and play therapy are highly encouraged and more widespread available. US-based and European networks have been developed (IMI2 conect4children (c4c), I-Act for Children) with increasing connectivity with rare diseases consortia (ERN, EJPRD, ERICA, EPTRI) and patient/parent organizations- Regarding patient engagement, a special focus on patient-reported outcomes is mandatory. Moreover, a national and continental budgeting plan for a pediatric setting has been developed, to speed up the initiation of the trials Conclusion In efforts to making the utopian completely on-label prescription of drugs in children a reality, learnings and expertise needs to be grouped and widely distributed. A dedicated expert or course in the conduct of pediatric clinical trials for young investigators could be beneficial.