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Review
. 2019 Apr;85(4):675-679.
doi: 10.1111/bcp.13809. Epub 2018 Dec 18.

Paediatric extrapolation: A necessary paradigm shift

Cécile Ollivier  1 , Yeruk Lily Mulugeta  2 , Lucia Ruggieri  1 , Agnes Saint-Raymond  1 , Lynne Yao  2
Affiliations
Review

Paediatric extrapolation: A necessary paradigm shift

Cécile Ollivier et al. Br J Clin Pharmacol. 2019 Apr.

Abstract

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.

Keywords: clinical pharmacology; drug regulation; evidence-based medicine; optimal design pharmacodynamics; paediatrics.

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Conflict of interest statement

There are no competing interests to declare.

The views expressed in this article are the personal views of the author(s) and may not be understood or quoted as being made on behalf of or reflecting the position of the EMA or one of its committees or working parties, or that of the US FDA.

Figures

Figure 1
Figure 1
Paediatric population in clinical trials for authorization of HIV medicines in 1997–2006 and 2007–2016
See this image and copyright information in PMC

Comment in

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