Table 1.

Some of the hurdles and challenges to conduct clinical research in neonatal pharmacotherapy

Circumstantial issues related to studies

• Ethics, parental consent (e.g., during pregnancy, information strategy)

• Study facilities (investigators, research facilities)

• Recruitment strategies, the need for multicenter collaboration

• Perceived risks and fear of negative outcomes, perceptions of society

• Drug development programs initially develop for other populations, and subsequently fitted to the neonatal population, not primary driven by neonatal diseases and needs

• Neonatal drug therapy development is a perceived "must," instead of an opportunity

Pharmacokinetics/pharmacodynamics

• Sample collection (limit number and volume), specific analytical techniques

• Population pharmacokinetic modeling (mechanism, physiology based) not always sufficiently validated to support study design and sampling strategy, and uncertainty about extrapolation

• Extensive variability in pharmacokinetics/pharmacodynamics within the neonatal population

• How to assess efficacy? Robust and relevant pharmacodynamics endpoints are needed. Neurodevelopmental outcome is most relevant, but cannot reliably be done in early infancy

• Data on formulation, including stability and compatibility (e.g., human milk, other drugs, parenteral nutrition)

• Safety: how to assess (serious) adverse reactions when overall morbidity is already high?