Table 1

Population, concept and context elements - Review inclusion criteria

Types of participantsPublic health immunisation is a broad endeavour, and it is aimed at the entire population. All strata and categories of individuals will be suitable for inclusion: males and females of any age group, condition or profession, as long as the off-label schedule is applicable to the group in a public health recommendation.
  • Non-human subjects (eg, preclinical studies). Phase I, II or III clinical trials, unless it is used as an evidence in a recommendation

  • Self-reporting of off-label-use of vaccine at the individual patient/physician level, as this is not representative of a public health approach (no case report).

ConceptMethodically, any indication of use that would be different from the prescribing information provided in the label of a vaccine should be considered off-label immunisation. The most frequent off-label recommendations are for doses, population groups, indications, posology or injection site,7 8 but should not be limited to these aspects. An objective of our review is to identify all existing recommendations that address off-label vaccination in public health. The implementation of the recommendation for off-label vaccine use is considered an outcome when recommendations are part of published vaccination programmes. The review uses the vaccine licensure as a starting point to determine the eligibility of a paper, and the label is considered the baseline for each vaccine. Various terms and definitions may have been used through the years. However, as ‘off-label’ is a relatively new term that has been introduced in search engines in approximately 2010, the review intends to provide a clear definition for off-label vaccine use.
  • Unlabelled vaccine use

  • Superfast-track approval is not considered off-label use.

  • Non-adherent behaviours that result in different dosing are not considered as off-label use.

ContextOff-label recommendations will be broadly sought from within the global context of immunisation. There will be no limitation in the geographic location or in the settings. This review is intended to map the evidence that emerges from any context, including pandemics and shortages, and to provide findings that support the development of an analytical framework applicable to any context.No exclusion criteria.
Types of sourcesAny and all documents included in the decision process of the initial off-label use of vaccine recommendations will be included in this review. The reference lists of identified reports will be manually searched for additional studies.
All types of studies and documents: product monographs, official documents, recommendations (NITAG, SAGE, etc), health authority vaccine updates, and accessible documentary evidence submitted for licensing (from clinical trials: quality, safety, and efficacy data), or from studies made after licensing. Any valuable written sources will be included to supplement the information on the vaccines.
The period considered will be from the date of vaccine first licensing for the country, for each vaccine. Documents in all languages will be eligible at the initial phase. If texts are available in languages other than English or French, they will be translated and included in the review.
No exclusion criteria.
  • NITAG, National Immunisation Technical Advisory Group; SAGE, WHO Strategic Advisory Group of Experts.