Table 1.

Recommendations to overcome challenges in B/R assessment of vaccines

Challenge	Recommendation	Approach to overcome the challenge (examples)
Assess B/R over time	B/R assessment should be considered as a continuum. It should start at the early stages of vaccine development; continue through the marketed life of the product and be updated as new data become available and/or by considering additional relevant endpoints.	Periodic Benefit-Risk Evaluation Report (PBRER) of European Medicines Agency
Optimize B/R assessment	Tools for assessing B/R of vaccines exist but need to be optimized by having more accurate data on vaccine exposure as well as outcomes (e.g. laboratory confirmation of cases). While these methodologies will support decision-making, they are not intended to replace medical judgment for individual patients.	Initiatives for better data and data sharing (ADVANCE, principles of data sharing, databases)
Establish harmonized frameworks for the evaluation of B/R in vaccinology	Networking, more interaction between regulatory authorities, vaccine manufacturers and academics	Set-up of more collaborative studies such as ADVANCE (EU), Mini-Sentinel (US)
Assess from a population perspective	Including not only qualitative and quantitative data, but also subjective values from a population perspective for B/R assessment. This can lead to more clinically relevant decisions.	Involvement of stakeholders such as patients and the public
Specific populations	It is crucial to be able to assess the B/R balance in specific medical conditions or risk groups not studied in clinical trials.	Consider adapting Pediatric Investigation Plan (EU) for monitoring, registers for pregnant women
Communication	Reporting of B/R assessments should be transparent as to how they were conducted	integrate Social Sciences activities in B/R evaluation and communication for more user-friendly reporting