Paediatric extrapolation: A necessary paradigm shift.

Legislative initiatives have been successful in increasing the availability of approved therapies for paediatric patients. However, additional measures to ensure the timely completion of paediatric studies are necessary to further increase the number of medicines available to children. Over the last 3 years, international experts convened to revise the ICH E11 guideline on clinical investigations of medicinal products in paediatric populations to harmonize approaches to paediatric extrapolation, striving to reduce substantial differences between regions in the acceptance of data for global paediatric medicine development programmes. Several areas of therapeutics development in children, such as human immunodeficiency virus and partial-onset seizures, have been streamlined and require fewer children enrolled in clinical trials because of the appropriate application of paediatric extrapolation. Based on this experience, it is clear that for paediatric extrapolation strategies to reach their full potential there is the need to understand the quality and quantity of data, often collected in adult patients, that will inform the appropriateness of the use of paediatric extrapolation, as well as to identify gaps in knowledge with respect to disease pathophysiology, organ maturation or drug target ontogeny. The generation of information that enhances our current understanding of these gaps in knowledge can further decrease the need for larger, paediatric clinical trials and can increase the efficiency of paediatric therapeutics development as well as protect children from participation in unnecessary studies. We hope that this publication will increase awareness, input and support from all the stakeholders involved in paediatric therapeutics development.

Development of Drug Therapies for Newborns and Children: The Scientific and Regulatory Imperatives.

Pediatric legislation has generated information about the efficacy, safety, and dosing of more than 600 products in children. Extrapolation of adult efficacy data has been an integral part of pediatric drug development. Advances in our understanding of physiology and pharmacology have improved the approach to pediatric dose selection. However, a high percentage of pediatric trials do not meet their primary efficacy endpoint. Delays in initiating completing pediatric studies persist. This article describes these advances and provides innovative approaches to optimize pediatric drug development.