Keywords: pediatric, extrapolation, Modeling and simulation
Although many recent advances have been achieved in pediatric development, there is still a significant time lapse between adult drug approval and label update with pediatric data in average. Before pediatric information becomes available in the label, patients face either drug being unavailable or off-label use. Slow study progression and high failure rate are common in pediatric studies. Difficulties in recruitment, especially for the placebo arm, and study decision issue such as selecting the wrong dose are among contributing factors. Modeling, simulation and extrapolation approaches are recommended to leverage existing data/knowledge, provide quantitative decision input and promote a more thorough study planning. ICH 11 recent addendum emphasized the usage of modeling, simulation and extrapolation in pediatric drug development. Considering the usual sequential drug development strategy from adult to pediatric, advanced methodologies relying on modeling, prediction and information borrowing can be naturally adapted. These methods served important roles in advancing the pediatric drug development. We will discuss modeling, simulation and extrapolation approaches under different pediatric development paths, especially partial extrapolation path with exposure response relationship consistency assessment and partial or no extrapolation with Bayesian borrowing and clinical trial simulation.