Pediatric Clinical Endpoint and Pharmacodynamic Biomarkers: Limitations and Opportunities

Medical research in children typically lags behind that of adult research in both quantity and quality. The conduct of rigorous clinical trials in children can raise ethical concerns because of children's status as a 'vulnerable' population. Moreover, carrying out studies in pediatrics also requires logistical considerations that rarely occur with adult clinical trials. Due to the relatively smaller number of pediatric studies to support evidence-based medicine, the practice of medicine in children is far more reliant upon expert opinion than in adult medicine. Children are at risk of not receiving the same level of benefits from precision medicine research, which has flourished with new technologies capable of generating large amounts of data quickly at an individual level. Although progress has been made in pediatric pharmacokinetics, which has led to safer and more effective dosing, gaps in knowledge still exists when it comes to characterization of pediatric disease and differences in pharmacodynamic response between children and adults. This review highlights three specific therapeutic areas where biomarker development can enhance precision medicine in children: asthma, type 2 diabetes mellitus, and pain. These 'case studies' are meant to update the reader on biomarkers used currently in the diagnosis and treatment of these conditions, and their shortcomings within a pediatric context. Current research on surrogate endpoints and pharmacodynamic biomarkers in the above therapeutic areas will also be described. These cases highlight the current lack in pediatric specific surrogate endpoints and pharmacodynamic biomarkers, as well as the research presently being conducted to address these deficiencies. We finally briefly highlight other therapeutic areas where further research in pediatric surrogate endpoints and pharmacodynamic biomarkers can be impactful to the care of children.