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.

Neonatal medicines research: challenges and opportunities

“…However, it provides a valuable aid to decision-making with regard to first-time dosing in children and study design. The clinical study then becomes 'confirmatory' rather than 'exploratory' [57][58][59][60][61][62]. Regulatory bodies increasingly encourage the use of modeling and simulation methods for all pediatric drug development programs [63] which also is reflected in a number of regulatory guidance documents [64].…”

“…Therefore, every effort should be made to simultaneously collect data on covariates to unveil indicators related to maturational changes in PK or PD. Consequently, it is advisable to include data on covariates like gestational age, postnatal age, postmenstrual age, birth weight, body weight, renal function, albumin, concomitant medication or co-morbidity in PK/PD studies [57][58][59][60][61][62]. Guidance is generated through, for example, the EMA modeling and simulation work group and workshops are organized on this topic [65,66].…”

Pharmacotherapy during pediatric extracorporeal membrane oxygenation: a review

“…Management Protection system (VAMP™, Edward Life Sciences), and sampling techniques such as sparse sampling, microsampling, scavenge sampling, and dried blood spot (DBS) sampling will become more important for blood PK samples [106][107][108][109].…”

Clinical trials of medicines in neonates: the influence of ethical and practical issues on design and conduct

“…http://clinicaltrial.gov/ct2/ show/NCT01651637). Innovative designs for phase 2 PK studies will improve the yield of drug development in this group [41].…”