Table 3

Steps to planning paediatric and neonatal pharmacokinetic studies

Protocol development	The study team receives input from suitably trained expert(s), including paediatric/neonatal clinical pharmacologists, analytical chemists and pharmacometricians (with expertise in popPK modelling and statistics).
Study design	The suitability and feasibility of optimal design is assessed. Consider the potential influence of formulation on PK studies designed to optimise dose.
Sample size	The sample size calculation is informed by ‘optimal design’. The target age range(s) of study participants and the number of participants in each age group are determined. In preterm neonatal PK studies, investigators define how many subgroups of prematurity are included (usually banded by gestational age at birth and postnatal age).
Sampling plans	The number of samples needed per participant and their timing (optimum timing vs opportunistic, or a combination) is justified. Acceptable method(s) of sampling is defined.
Patient involvement	Determine if there is a role for parent/child involvement in study design.
Analytical chemistry	Preferred matrix is confirmed (eg, blood vs serum or other biospecimen) and whether total or unbound concentrations will be measured. Stability of analytes in this matrix is verified (short-term and long-term, in relevant storage conditions).
Pharmacometrics	Input from popPK statisticians is used for design questions above, and to plan which type of PK modelling is used and how to plan covariate analyses.
Implementation (1)	Discuss with formulary committee where feasible to verify quantity and quality of new PK/PD data required to update paediatric or neonatal dosing recommendations.
Implementation (2)	For larger, multicentre/international studies, liaison with the regulators can also be helpful to explore, for off-patent drugs, how much (new) paediatric/neonatal PK data would be required to change the labelling.

PD, pharmacodynamic; PK, pharmacokinetic; popK, population PK.