Table 8.

Regulatory basis for Modeling and Simulation in pediatrics.

International Guideline

• ICH E11 [17] → PK/PD modeling, population PK, and sparse sampling

FDA Guidelines

• General Considerations for Pediatric Pharmacokinetic Studies [38] → Population PK

• Exposure-Response Relationships [60] → Population PK and PK/PD modeling

EMA Guidelines

• Concept paper on the impact of liver immaturity [51] → Population PK and PK/PD modeling

• Discussion paper on the impact of renal immaturity [57] → Population PK

• Guideline on the role of pharmacokinetics in pediatrics [44] → Population PK and PK/PD modeling

• Guideline on clinical trials in small populations [61] → PK/PD modeling, Bayesian methods

• Guideline on the investigation of medicinal products in the term and preterm neonate [45] → PK/PD modeling, PBPK modeling, and Population PK

• Guideline on the format and content of applications for a pediatric investigation plan [25] → PD modeling

• Ethical considerations for clinical trials with the pediatric population [55] → Adaptive design