The administration of vaccines outside the specifications of the official product label is termed “off-label use”. This practice is not uncommon and often arises to address populations excluded from clinical trials or to optimize vaccination schedules based on new evidence. A prominent example during the COVID-19 pandemic was the extension of dosing intervals for mRNA vaccines by many countries, a strategy later supported by evidence showing improved immune responses and reduced risks.
National Immunization Technical Advisory Groups (NITAGs) play a central role in national immunization policies. They provide scientific recommendations by reviewing evidence on vaccine safety, immunogenicity, efficacy, and disease epidemiology. In response to outbreaks, supply fluctuations, or risks to specific populations, NITAGs may adjust strategies, which can involve changes to the recommended age, number of doses, intervals, or vaccine interchangeability.
While the WHO provides general guidance, countries vary significantly in whether their NITAGs are authorized to make off-label recommendations and in their related evidence standards and legal frameworks. A recent study published in Vaccine surveyed national NITAGs on their policies, workflows, and practices regarding off-label use, revealing the challenges in evidence-to-policy translation and highlighting the pandemic’s role in driving more flexible immunization policies.
Post-Pandemic: The Shift from Emergency to Routine Policy
The survey of 76 countries found that 68% (52 countries) reported their NITAG had proposed off-label use. A clear policy shift was observed from the pre-pandemic period to the post-pandemic era. Before 2020, 48% of these 52 countries employed off-label use, while 21% used it only in emergencies. By 2022, 58% reported routine off-label use, with only 8% restricting it to emergencies. This indicates that the pandemic catalyzed a transition of off-label strategies from emergency measures to established policy in many settings.
Institutional Arrangements and Legal Considerations
Significant variations exist in institutional and legal support. Only 26% of the 76 respondent countries have a Vaccine Injury Compensation Program (VICP), and just over half of those cover off-label administration. Legal concerns were noted by 35% of countries. At the policy level, only 15% have formal procedures to implement off-label recommendations, and merely 21% conduct post-implementation evaluations, most commonly through program assessments or serosurveys.
Implications and Future Directions
The pandemic has generally made NITAGs more receptive to off-label recommendations. However, a gap remains between making such recommendations and having robust systems for their implementation, evaluation, and legal protection. The study suggests a need for more standardized global guidance, structured post-introduction studies, and enhanced knowledge-sharing. Future efforts should focus on understanding the drivers behind off-label decisions, improving communication with healthcare workers, and establishing clearer frameworks to support safe and effective adaptive immunization policies.
Content Editor: Xinyue Zhou
Page Editor: Ruitong Li
Reference
Roberts, C., Top, K. A., Henaff, L., Tunis, M., Singh, A., van Holten, J., Ruta, S., & Desai, S. (2025). Exploring off-label vaccine use: A survey of the global national immunization technical advisory group network. Vaccine, 62, 127581. https://doi.org/10.1016/j.vaccine.2025.127581
