How to optimise drug study design: pharmacokinetics and pharmacodynamics studies introduced to paediatricians.
OBJECTIVE
In children, there is often lack of sufficient information concerning the pharmacokinetics (PK) and pharmacodynamics (PD) of a study drug to support dose selection and effective evaluation of efficacy in a randomised clinical trial (RCT). Therefore, one should consider the relevance of relatively small PKPD studies, which can provide the appropriate data to optimise the design of an RCT.


METHODS
Based on the experience of experts collaborating in the EU-funded Global Research in Paediatrics consortium, we aimed to inform clinician-scientists working with children on the design of investigator-initiated PKPD studies.


RESULTS
The importance of the identification of an optimal dose for the paediatric population is explained, followed by the differences and similarities of dose-ranging and efficacy studies. The input of clinical pharmacologists with modelling expertise is essential for an efficient dose-finding study.


CONCLUSIONS
The emergence of new laboratory techniques and statistical tools allows for the collection and analysis of sparse and unbalanced data, enabling the implementation of (observational) PKPD studies in the paediatric clinic. Understanding of the principles and methods discussed in this study is essential to improve the quality of paediatric PKPD investigations, and to prevent the conduct of paediatric RCTs that fail because of inadequate dosing.
Pediatric Clinical Research Office, Emma Children's Hospital, Academic Medical Center, Amsterdam, The Netherlands.
Eric
E
Vermeulen
Division of Pediatric Clinical Pharmacology, Children's National Health System, Washington, DC, USA.|Division of Paediatric Pharmacology and Pharmacometrics, University of Basel Children's Hospital, Basel, Switzerland.|Intensive Care and Department of Pediatric Surgery, Erasmus Medical Center, Sophia Children's Hospital, Rotterdam, The Netherlands.
John N
JN
van den Anker
Clinical Pharmacology Modelling & Simulation, GlaxoSmithKline, Stockley Park, UK.|Clinical Pharmacology & Therapeutics, University College London, London, UK.
Oscar
O
Della Pasqua
Poison Information Centre, Helsinki University Central Hospital, Helsinki, Finland.
Kalle
K
Hoppu
Pediatric Clinical Research Office, Emma Children's Hospital, Academic Medical Center, Amsterdam, The Netherlands.
Johanna H
JH
van der Lee
D002648:Child; D006801:Humans; D000072143:Pediatricians; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000378:metabolism*; D010819:Physician's Role; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012107:Research Design
D004364:Pharmaceutical Preparations
paediatrics; pharmacodynamics; pharmacokinetics
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