Advancing Therapeutics for Children with Medical Complexity: The Role of Model‐Informed Precision Dosing and Genotype‐Stratified Trials

Model-informed drug development (MIDD) and model-informed precision dosing (MIPD) increasingly guide drug development, regulatory decision-making, and individualized therapy but rely on robust data. Current models inadequately represent children with medical complexity (CMC), whose unique physiology, comorbidities, and polypharmacy contribute to substantial variability in drug exposure and response. We propose a framework using genotype-stratified trials to characterize pharmacogenetic sources of variability, informing MIDD and MPID models while helping identify additional determinants of therapeutic response in CMC.