Copyright ©2012 Baishideng. All rights reserved.
World J Clin Pediatr. Aug 8, 2012; 1(2): 3-7
Published online Aug 8, 2012. doi: 10.5409/wjcp.v1.i2.3
Clinical pharmacological studies in children: From exploratory towards confirmation driven methodology
Karel Allegaert
Karel Allegaert, Division of Woman and Child, Neonatal Intensive Care Unit, University Hospital, 3000 Leuven, Belgium
Author contributions: Allegaert K solely contributed to this manuscript.
Supported by The Fund for Scientific Research, Flanders (Belgium) (FWO Vlaanderen) by a Fundamental Clinical Investigatorship (1800209N); A Research Grant (1506409N)
Correspondence to: Karel Allegaert, MD, PhD, Division of Woman and Child, Neonatal Intensive Care Unit, University Hospital, Herestraat 49, 3000 Leuven, Belgium. karel.allegaert@uz.kuleuven.ac.be
Telephone: +32-16-343850 Fax: +32-16-343209
Received: February 4, 2012
Revised: July 31, 2012
Accepted: August 5, 2012
Published online: August 8, 2012

Just like children are not small adults, pediatric studies are not just subgroup-adult studies. Clinical pharmacology aims to predict these effects based on drug, population and/or patient-specific pharmacokinetics (concentration-time profiles) and -dynamics (concentration-effect profile). The most essential characteristics of childhood are growth and maturation. Both phenomena are most prominent during infancy making the claim that “an infant is not just a small child” as relevant compared to the paradigm that “a child is not just a small adult”. From a clinical pharmacology perspective, the consequence of such a dynamic setting is extensive variability throughout childhood in both the pharmacokinetics and pharmacodynamics. Trial design probably has impact on recruitment to an even greater extent compared to adult studies. In general, if a study is designed well, with a clear clinical question with which parents and children can identify, they are likely to consider participation. Open communication with all stakeholders involved will most likely result in ethically correct, practically feasible, scientifically sound, and economical reasonable studies to provide children with the appropriate treatment. From an academic perspective, feasibility, relevance, applicability and costs of clinical pharmacological studies in children can be significantly improved by new sampling concepts (e.g., saliva, urine, dried spot blood) and the systematic introduction of already known information into the trial design through model based pediatric drug development, that mainly affect feasibility of pharmacokinetic studies. In contrast, for the pharmacodynamic part of pediatric studies, development and validation of population specific biomarkers or robust outcome variables is urgently needed.

Keywords: Infant, Child, Developmental pharmacology, Trial design, Pharmacokinetics, Pharmacodynamics