Optimising the dosing of medicines for neonates and children remains a challenge. The importance of pharmacokinetic (PK) and pharmacodynamic (PD) research is recognised both in medicines regulation and paediatric clinical pharmacology, yet there remain barriers to undertaking high-quality PK and PD studies. While these studies are essential in understanding the dose–concentration–effect relationship and should underpin dosing recommendations, this review examines how challenges affecting the design and conduct of paediatric pharmacological studies can be overcome using targeted pharmacometric strategies. Model-based approaches confer benefits at all stages of the drug life-cycle, from identifying the first dose to be used in children, to clinical trial design, and optimising the dosing regimens of older, off-patent medications. To benefit patients, strategies to ensure that new PK, PD and trial data are incorporated into evidence-based dosing recommendations are needed. This review summarises practical strategies to address current challenges, particularly the use of model-based (pharmacometric) approaches in study design and analysis. Recommendations for practice and directions for future paediatric pharmacological research are given, based on current literature and our joint international experience. Success of PK research in children requires a robust infrastructure, with sustainable funding mechanisms at its core, supported by political and regulatory initiatives, and international collaborations. There is a unique opportunity to advance paediatric medicines research at an unprecedented pace, bringing the age of evidence-based paediatric pharmacotherapy into sight.
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Contributors CISB, JFS, LEK and ACN conceptualised the review, designed the study, conducted the literature review, drafted the initial manuscript and revised the final manuscript. LHF, SNdW, MJR and MO conceptualised this review, drafted the manuscript and revised the final manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.
Funding The research leading to these results has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no 261060 (Global Research in Paediatrics—GRiP Network of Excellence), which funded CISB as a Clinical Research Fellow. CISB also receives funding from the National Institute for Health Research (NIHR) as an Academic Clinical Fellow (ACF-2016-18-016). JFS has received funding from UK Medical Research Council Fellowships (grants G1002305 and M008665). CISB and JFS have been supported by the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London. LEK is supported by the Children’s Hospital Research Institute of Manitoba.
Competing interests None declared.
Patient consent Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
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