Benefit-risk assessment of vaccines.

Benefit-risk assessment (BRA) is critical for decision-making throughout the vaccine life cycle. It requires scientific assessment of evidence to make an informed judgment on whether the vaccine has a favourable benefit-risk profile i.e. the benefits of the vaccine outweigh its risks for use in its intended indication. The assessment must also consider data gaps and uncertainties, using sensitivity analyses to show the impact of these uncertainties in the assessment. The BRA field has advanced considerably over the past years, including the use of structured BRA frameworks, quantitative BRA models and use of the patient experience data. Analytical tools and procedures to standardize BRA implementation have become increasingly important. A Benefit-Risk Assessment Module has been prepared to enable the planning, assessment, and communication of relevant BRA information via a structured B-R framework. The module can help facilitate the conduct and communication of defensible BRAs by vaccine developers, funders, regulators and policy makers in high, middle or low-income countries, both for regulatory submissions and in public health responses to infectious diseases, including for epidemics.

Considerations for unblinding individual study participants during vaccine trials.

Premature unblinding of individual participants is rarely reported in publications, but such unblinding can disrupt vaccine trials by causing worry and drop-out of other participants or "pseudo unblinding," in which participants or investigators over-interpret certain symptoms as being related to receiving an investigational product. This review summarizes appropriate reasons for unblinding in vaccine trials. Regulatory guidance could be improved by distinguishing guidance for vaccine trials from drug trials, with the recognition that unblinding individual participants in vaccine studies is rarely needed for management of adverse events following immunization.

Vaccine Licensure in the Absence of Human Efficacy Data.

Clinical vaccine development and regulatory approval generally occurs in a linear, sequential manner: Phase 1: safety, immunogenicity; Phase 2: immunogenicity, safety, dose ranging, and preliminary efficacy; Phase 3: definitive efficacy, safety, lot consistency; and following regulatory approval, Phase 4: post-marketing safety and effectiveness. For candidate filovirus vaccines, where correlates of protection have not been identified, and phase 2 and 3 efficacy of disease prevention trials untenable, large and/or protracted, each trial may span decades, with full licensure expected only after several decades of development. Given the urgent unmet need for new Marburg virus and Ebola Sudan virus vaccines, the Sabin Vaccine Institute hosted a key stakeholder virtual meeting in May 2021 to explore the possibility of licensure by use of an "animal rule-like" licensure process, based on a risk/benefit assessment specific to regional needs and informed by epidemiology. This may be appropriate for diseases where there are no or limited treatment options, and those prone to sporadic outbreaks with high rates of transmission, morbidity, and mortality. The discussion focused on two contexts: licensure within the Ugandan regulatory environment, a high burden country where Ebola vaccine trials are ongoing, and licensure by the United States FDA-a well-resourced regulatory agency.

Medical countermeasures against henipaviruses: a review and public health perspective.

Henipaviruses, including Nipah virus, are regarded as pathogens of notable epidemic potential because of their high pathogenicity and the paucity of specific medical countermeasures to control infections in humans. We review the evidence of medical countermeasures against henipaviruses and project their cost in a post-COVID-19 era. Given the sporadic and unpredictable nature of henipavirus outbreaks, innovative strategies will be needed to circumvent the infeasibility of traditional phase 3 clinical trial regulatory pathways. Stronger partnerships with scientific institutions and regulatory authorities in low-income and middle-income countries can inform coordination of appropriate investments and development of strategies and normative guidelines for the deployment and equitable use of multiple medical countermeasures. Accessible measures should include global, regional, and endemic in-country stockpiles of reasonably priced small molecules, monoclonal antibodies, and vaccines as part of a combined collection of products that could help to control henipavirus outbreaks and prevent future pandemics.

IABS/CEPI platform technology webinar: Is it possible to reduce the vaccine development time?

The International Alliance for Biological Standardization and the Coalition for Epidemic Preparedness Innovations organized a joint webinar on the use of platform technologies for vaccine development. To tackle new emerging infectious diseases, including SARS-CoV-2, rapid response platforms, using the same basic components as a backbone, yet adaptable for use against different pathogens by inserting new genetic or protein sequences, are essential. Furthermore, it is evident that development of platform technologies needs to continue, due to the emerging variants of SARS-CoV-2. The objective of the meeting was to discuss techniques for platform manufacturing that have been used for COVID-19 vaccine development, with input from regulatory authorities on their experiences with, and expectations of, the platforms. Industry and regulators have been very successful in cooperating, having completed the whole process from development to licensing at an unprecedented speed. However, we should learn from the experiences, to be able to be even faster when a next pandemic of disease X occurs.