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Review
. 2019 May;59(5):625-637.
doi: 10.1002/jcph.1359. Epub 2018 Dec 18.

Accelerating Drug Development in Pediatric Oncology With the Clinical Pharmacology Storehouse

Mohamad Shebley  1 , Rajeev M Menon  1 , John P Gibbs  1 , Nimita Dave  1 , Su Y Kim  2 , Patrick J Marroum  1
Affiliations
Review

Accelerating Drug Development in Pediatric Oncology With the Clinical Pharmacology Storehouse

Mohamad Shebley et al. J Clin Pharmacol. 2019 May.

Abstract

Pediatric drug development is a challenging process due to the rarity of the population, the need to meet regulatory requirements across the globe, the associated uncertainty in extrapolating data from adults, the paucity of validated biomarkers, and the lack of systematic testing of drugs in pediatric patients. In oncology, pediatric drug development has additional challenges that have historically delayed availability of safe and effective medicines for children. In particular, the traditional approach to pediatric oncology drug development involves conducting phase 1 studies in children once the drug has been characterized and in some cases approved for use in adults. The objective of this article is to describe clinical pharmacology factors that influence pediatric oncology trial design and execution and to highlight efficient approaches for designing and expediting oncology drug development in children. The topics highlighted in this article include (1) study design considerations, (2) updated dosing approaches, (3) ways to overcome the significant biopharmaceutical challenges unique to the oncology pediatric population, and (4) use of data analysis strategies for extrapolating data from adults, with case studies. Finally, suggestions for ways to use clinical pharmacology approaches to accelerate pediatric oncology drug development are provided.

Keywords: PK/PD; clinical pharmacology; drug development; modeling and simulation; oncology; pediatric.

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Figures

Figure 1
Figure 1
Role of clinical pharmacology in pediatric oncology drug development. Strategically designed PK/PD and biomarker sampling in pediatric oncology trials enables collection of the right data, which feed into advanced and prespecified modeling and simulation approaches, thus enabling rational dose selection for modern molecularly targeted cancer therapies in children. Extrapolation of relative bioavailability information to inform dosing using physiologically based PK modeling enables acceleration of pediatric oncology drug development when studies in adults are limited or absent. Clinical pharmacology tools represent an essential piece of the challenging pediatric oncology drug development puzzle. PD, pharmacodynamics; PK, pharmacokinetics.
Figure 2
Figure 2
Comparison of adult and pediatric doses for 15 oncology drugs that obtained approval of a pediatric indication since 2002.
See this image and copyright information in PMC

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