A Modeling and Simulations Framework to Support Global Regulatory Strategies for Pediatric Drug Development Programs

Trial simulations have emerged as a promising tool to optimize pediatric drug development programs. As the current FDA legislation on pediatric drugs and devices was updated to mirror the EMA legislation, pediatric programs must be developed with global strategies that support a Pediatric Investigation Plan (PIP) for the EMA and a Pediatric Study Plan (PSP) for the FDA. A pharmacometrics framework is proposed to support global regulatory strategies for pediatric drug development programs. The framework describes specific trigger points and opportunities for applying modeling and simulation techniques to design the PIP and PSP and ultimately optimize pediatric drug development programs. The development of pediatric protocols by simulations and execution plans is deemed critical in defining expectations and ensuring the future success of these global programs. This can lead to clinical trial designs that are more efficient, less prone to failure, and ultimately, less costly.

[1]  V. Hasselblad,et al.  Pediatric Antihypertensive Trial Failures: Analysis of End Points and Dose Range , 2008, Hypertension.

[2]  B. Meibohm,et al.  Physiologically Based Pharmacokinetic (PBPK) Modeling in Children , 2012, Clinical pharmacology and therapeutics.

[3]  F. Bellanti,et al.  Modelling and simulation as research tools in paediatric drug development , 2011, European Journal of Clinical Pharmacology.

[4]  J. Schellens,et al.  Optimizing drug development of anti‐cancer drugs in children using modelling and simulation , 2013, British journal of clinical pharmacology.

[5]  L B Sheiner,et al.  Learning versus confirming in clinical drug development , 1997, Clinical pharmacology and therapeutics.

[6]  B. Meibohm,et al.  The In Silico Child: Using Simulation to Guide Pediatric Drug Development and Manage Pediatric Pharmacotherapy , 2009, Journal of clinical pharmacology.

[7]  C. Knibbe,et al.  Knowledge of developmental pharmacology and modeling approaches should be used to avoid useless trials in children , 2009, European Journal of Clinical Pharmacology.

[8]  M. Mouksassi,et al.  Clinical Trial Simulations in Pediatric Patients Using Realistic Covariates: Application to Teduglutide, a Glucagon‐Like Peptide‐2 Analog in Neonates and Infants With Short‐Bowel Syndrome , 2009, Clinical pharmacology and therapeutics.

[9]  Steven Edward Kern,et al.  The Need for Modeling and Simulation to Design Clinical Investigations in Children , 2010, Journal of clinical pharmacology.

[10]  J. Zisowsky,et al.  Drug Development for Pediatric Populations: Regulatory Aspects , 2010, Pharmaceutics.

[11]  Eric L Eisenstein,et al.  Economic return of clinical trials performed under the pediatric exclusivity program. , 2007, JAMA.

[12]  Stephanie Läer,et al.  Population pharmacokinetic studies in pediatrics: Issues in design and analysis , 2005, The AAPS Journal.

[13]  Yaning Wang,et al.  Impact of pharmacometrics on drug approval and labeling decisions: A survey of 42 new drug applications , 2005, The AAPS Journal.