Off-label drug use in children: prevalence, risks, and regulation

In pediatrics, drugs require specific study in children rather than being prescribed based on data extrapolated from adults. Historically, this requirement was hindered by various challenges, resulting in widespread off-label drug use. The extent of such use has been extensively investigated, and new regulations in the US and Europe came into force.

We conducted a narrative review addressing the epidemiology, associated risks, and regulatory implications of off-label drug use. This involved performing a targeted PubMed search and synthesizing relevant review articles and policy guidelines. The included studies, despite being informative, showed substantial heterogeneity, limiting the comparability and interpretability of their findings. Particularly, quantitative evidence regarding associated risks remains scarce. In addition to risks to patients, liability represents an important concern. Although regulatory policies vary between countries, the level of supporting evidence and accepted standards of practice are consistently central considerations.

Future efforts should therefore focus on using available data to inform individual treatment decisions, ensuring this knowledge is accessible to prescribers, and addressing areas where evidence is particularly limited and patient safety is most compromised. Artificial intelligence and modeling may facilitate evidence generation and improve clinical-trial efficiency. Nevertheless, these approaches should complement, not replace, research conducted directly in pediatric patients.