Pediatric Extrapolation for Pediatric Indication

In a previous post "Pediatric Study Plan (PSP) and Paediatric Investigation Plan (PIP)", we discussed the requirements for PSP and PIP and the importance of incorporating the pediatric investigation plan into the overall clinical development program.
Doing clinical trials in the pediatric population is always challenging. It is not feasible to have a pediatric investigation plan that is too big to implement. Ethically, it is also not a wise decision to expose too many children in clinical trials (especially the placebo-controlled trials).
Regulatory agencies (such as FDA and EMA) realized the challenges in the clinical development program in children and have issued guidelines that encourage the sponsors to use an approach called 'pediatric extrapolation'.

• FDA guidance for industry (2014) “General Clinical Pharmacology Considerations for Pediatric Studies for Drugs and Biological Products”
• EMA (2017) “Reflection paper on the use of extrapolation in the development of medicines for paediatrics”
• FDA guidance (2016) “Leveraging Existing Clinical Data for Extrapolation to Pediatric Uses of Medical Devices”
• Extrapolation in Pediatric Drug Development: An Evolving Science by Dr Lynne P. Yao from FDA’s Division of Pediatric and Maternal Health, CDER
• Pediatric Extrapolation: Using exposure as a surrogate for efficacy by Dr Robert ‘Skip’ Nelson from FDA’s Office of Pediatric Therapeutics, Office of the Commissioner
• From a presentation on “Paediatric Investigation Plans and the EMA Extrapolation Framework” by Dr. Christoph Male, Austrian Delegate to the EMA Paediatric Committee (PDCO), delivered to the June 2013 GRiP Workshop held in Glascow, Scotland, UK

We have already seen that some sponsors use the pediatric extrapolation to obtain the pediatric indication successfully.

• Vimpat (lacosamide) for treatment of partial-onset seizures as monotherapy or adjunctive therapy for patients 4 years of age and older
• Fycompa for treatment of partial onset seizures with or without secondarily generalized seizures in patients with epilepsy 2 years of age and older
• Bosentan for treatment of pulmonary arterial hypertension in pediatrics