Role of Clinical Pharmacology in the Development of Paediatric Clinical Development Plans

The new regulations in the field of paediatrics, especially in the European Union, have led to a significant increase in interest and resources dedicated to paediatric drug development. Designing a paediatric plan is a challenging and interdisciplinary task which requires input and close collaboration of clinicians with expertise in the disease and in paediatrics, clinical pharmacologists, pharmacometricians, statisticians with expertise
in innovative study designs, regulatory affairs specialists, and toxicologists with specific knowledge in the conduct of studies in juvenile animals. 

A paediatric clinical development plan should not be a new plan modelled after the investigational plan in adults with sequential phase 1, phase 2 and phase 3 studies, but rather should effectively take advantage of all the prior knowledge acquired from adult studies and translate this knowledge into a plan of necessary and informative paediatric studies. 

One particular challenge is the dose selection in the different age groups. The understanding of the pharmacokinetic/ pharmacodynamic (PK/PD) relationship in adults can be of great help here to define the dose or dose range to be studied in paediatric patients. The concept for bridging from adults to paediatrics, or paediatric bridging, is to leverage prior drug knowledge in adults (PK, efficacy, safety, exposure response relationships) and experience in developing compounds in the same indication to inform the design of the necessary paediatric studies and get approval for a paediatric use in the drug label. When used appropriately, paediatric bridging can streamline paediatric investigations, with fewer children in trials exposed to sub-therapeutic or toxic doses and yield earlier availability of medicines with high medical need in children.

An article by Bruno Reigner, Bénédicte M. Ricci and Xavier Liogier d’Ardhuy explores various options on the best way to conduct research in the field, like a two-step model for the Paediatric Clinical
Development Plan.  It also goes into paediatric bridging and regulatory guidance as well as exploring the challenges and future directions in Paediatric Drug Development. Download the complimentary 9-page article here: Paediatric Drug Development.