Observed rates

WHO has, since 2000, published information on the observed rates of adverse reactions following vaccination. Since 2012, this information has been included in a number of information sheets available from the WHO global vaccine safety website.⁵ Each information sheet is specific for an individual vaccine antigen and supports the position paper⁶ that provides the WHO recommendations for the use of this vaccine. An information sheet provides a brief overview of the vaccine and the observed rates of adverse reactions (mild/moderate and severe) as identified by experts from a review of published and non-published evidence. The intended audience for this information is immunization programme managers and health-care providers involved in vaccine administration. These information sheets describe known and expected reactions to vaccines to assist with safety communication and investigation of adverse events following immunization (AEFI). They also provide an indication of the expected rates of adverse reactions to facilitate comparison of observed AEFI rates measured through vaccine safety surveillance and determine whether any reactions have been reported with a higher frequency than expected. In addition, this information is referenced and used during WHO vaccine safety training. It also provides an estimation of known vaccine risks as part of WHO position papers.

The aim of this GACVS session was to discuss a revised approach for updating the existing information sheets and for developing new ones for newly available vaccines. This methodological revision also provides an opportunity to enhance the systematic approach to reviewing the relevant literature, and to evaluate the quality of the evidence available. WHO has previously adopted the GRADE methodology for assessing quality of evidence and has published guidelines on evaluating evidence for the purpose of preparing public health guidelines.⁷ The revised methodology will incorporate these recommendations wherever possible. However, as most serious vaccine safety issues are rare events, established methods of assessing the quality of evidence (including GRADE) are not readily applicable: whereas common adverse reactions to a vaccine can usually be identified during randomized controlled clinical trials, severe or unusual reactions are generally ascertained only later from observational studies after the product has been available for large-scale use. Most studies which provide relevant vaccine safety information on rare events are post-licensure case-based studies or retrospective cohort studies. Whilst GACVS acknowledges the importance of using the GRADE methodology whenever it is applicable, alternative tools specifically designed for assessment of unusual and rare events recorded in observational studies also need to be included in a vaccine safety review process.

The proposed revised approach for WHO vaccine safety information sheets will focus on specific safety questions that will be formulated by a GACVS subcommittee dedicated to AEFI monitoring. The subcommittee will identify events that have been suspected to be causally associated with the vaccine and will formulate the safety issues requiring review of the evidence. An example of such a question would be: “what is the attributable risk of intussusception following rotavirus vaccination?”. The committee will focus on severe reactions and reactions of special interest. Where appropriate, safety reviews will also be prioritized based on the development of WHO position papers on vaccines, following discussions with the WHO Strategic Advisory Group of Experts on immunization (SAGE); vaccine risk information is an essential component of the WHO position papers on vaccines as the recommendations are based on a benefit-risk assessment. Review of the specific safety question will include both published and unpublished (for example, product information) evidence. Individual articles or review articles will be categorized according to a methodology including the assessment of the quality of the evidence. This information will be included in tables summarizing the findings and be further simplified for inclusion in the revised information sheets. The source and summary information will be available, for reference, on the internet.

⁵ http://www.who.int/vaccine_safety/initiative/tools/vaccinfosheets/en/

⁶ http://www.who.int/immunization/policy/position_papers/en/

⁷ WHO handbook for guideline development available at http://www.who.int/entity/kms/handbook_2nd_ed.pdf

Full report of GACVS meeting of 10-11 June 2015, published in the WHO Weekly Epidemiological Record of 17 July 2015