Innovative clinical trial design for pediatric therapeutics

Abstract

Until approximately 15 years ago, sponsors rarely included children in the development of therapeutics. US and European legislation has resulted in an increase in the number of pediatric trials and specific label changes and dosing recommendations, although infants remain an understudied group. The lack of clinical trials in children is partly due to specific challenges in conducting trials in this patient population. Therapeutics in special populations, including premature infants, obese children and children receiving extracorporeal life support, are even less studied. National research networks in Europe and the USA are beginning to address some of the gaps in pediatric therapeutics using novel clinical trial designs. Recent innovations in pediatric clinical trial design, including sparse and scavenged sampling, population pharmacokinetic analyses and ‘opportunistic’ studies, have addressed some of the historical challenges associated with clinical trials in children.

Keywords::

• clinical trial simulation
• opportunistic study
• pediatrics
• pharmacodynamics
• pharmacokinetics
• pharmacometrics
• therapeutics

Acknowledgements

The authors thank Michael O’Shea from Wake Forest University School of Medicine for his thoughtful review of this manuscript.

Financial & competing interests disclosure

Matthew M Laughon receives support from the US Government for his work in pediatric and neonatal clinical pharmacology (Government Contract HHSN267200700051C, principal investigator: Benjamin) and from the NICHD (1K23HL092225-01). Daniel K Benjamin Jr receives support from the US Government for his work in pediatric and neonatal clinical pharmacology (1R01HD057956-02, 1R01FD003519-01, 1U10-HD45962-06, 1K24HD058735-01, and Government Contract HHSN267200700051C), the nonprofit Thrasher Research Foundation for his work in neonatal candidiasis (www.thrasherresearch.org) and from industry for neonatal and pediatric drug development. Phillip Brian Smith receives support from the US Government for his work in pediatric and neonatal clinical pharmacology (Government Contract HHSN267200700051C, principal investigator: Benjamin), from the NICHD (1K23HD060040-01) and from AHRQ (1R18AE000028-01). Michael Cohen-Wolkowiez receives support from the NICHD (1K23HD064814-01) and the nonprofit Thrasher Research Foundation for his work in neonatal pharmacology. This study was supported by contract #HHSN275000002I-00001 under the Best Pharmaceuticals for Children Act. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.