Table 8.

Overview of expectations of evidence that are likely to be required to support a global/regional/national policy recommendation, or financing for LICs.

Parameter for policy/financing consideration	Assumptions	Guidance/reports available
Consensus building to define priority public health goals for the vaccine candidate	Need to establish norovirus as a competitive global public health priority in the landscape of all enteric infections and other priority global health pathogens. Formulate and promulgate a WHO Preferred Product Characteristics for Vaccines Against Norovirus.	WHO Technical document. From Vaccine Development to Policy: A Brief Review of WHO Vaccine-Related Activities and Advisory Processes (2017) [81]. WHO | WHO Preferred Product Characteristics (PPCs) [82].
Facilitation and acceleration of product development to achieve WHO public health goals in accordance with WHO recommend norms and standards	Improve global estimates of disease burden and better characterize the epidemiology of norovirus infection. Support further description of the spectrum of natural disease history including post-infectious consequences. Support vaccine antigen selection decisions to cover broad variation of global norovirus strains to assure adequate coverage. Develop consensus guidance about the use of LMIC human challenge models to support regulatory considerations and approvals. Support the characterization of immunological surrogates/correlates of protection. Define appropriate clinical development pathways for vaccine approval in LMIC populations (children and adults).	WHO Technical Document. From Vaccine Development to Policy: A Brief Review of WHO Vaccine-Related Activities and Advisory Processes (2017) [81].
Registration of product by a functional National Regulatory Authority	Given the dual use potential of a norovirus vaccine for reduction of disease morbidity and mortality in a HIC, a norovirus vaccine would likely receive either a national regulatory authority approval.
Review of key evidence inputs by SAGE working group (WG) to inform optimal use of vaccine from public health perspective, including safety, operational issues and implementation research, and programmatic suitability, as well as the quality of the evidence, values and preferences, equity, feasibility, etc.	Detailed information on epidemiological features of norovirus disease burden globally and regionally to include age-specific mortality, morbidity, and social impact. Genotype distribution over time and the likelihood of vaccine coverage would be critical to review. Clinical considerations of the norovirus may be important including challenges in clinical management, and long-term health complications (if any). Analysis of alternatives for disease prevention and control such as emerging therapeutics, or improved strategies of ORS delivery and management of childhood diarrheal/vomiting. Vaccine and immunization characteristics would be key considerations including efficacy, herd immunity, safety, cold chain, vaccine availability, schedule, and ability to reach target populations and monitor an impact of an immunization program. Formal cost-effectiveness analyses would be beneficial, ideally at region and country level. Affordability of vaccine/cost key. Evaluation of interactions with other interventions and control strategies as well as impact of vaccine introduction on the wider health system could be considered. Social, legal, ethical considerations are entertained.	WHO Guidance for the development of evidence- based vaccination-related recommendations [83].
SAGE recommendations (from SAGE WG) to WHO are adapted into global policy published as Vaccine Position Paper	Vaccine position paper development at the World Health Organization based on SAGE recommendation is a complex, rigorous, multifaceted process involving many stakeholders and occurring over roughly a two- year timeline. SAGE accepts or modifies the proposed WG recommendations or states the need for revisiting steps in the process. In the latter case, the issue is revisited at a later SAGE meeting. SAGE decisions are reached by consensus as opposed to using a voting mechanism, thus promoting in-depth discussion of the evidence and careful weighing of benefits and harms. SAGE is the arbiter with respect to the recommendations included in the position paper and is independent of WHO. Initial draft is subject to an iterative process with multiple stakeholder reviews (both internal and external) and revisions with final publication in the Weekly Epidemiological Record.	WHO Supplement to WHO Vaccine Position Papers. Guideline Development Group [83].
Concurrent with or following SAGE recommendation for widespread use, companies can submit their dossier for WHO prequalification	While HIC countries are likely to develop a norovirus vaccine, vaccine supply will likely require production from a non-HIC country vaccine manufacturer. To be eligible for prequalification, the NRA of record would need to meet certain requirements defined by WHO. Currently, common global suppliers of prequalified vaccines for low-income country markets include those based in India and China. Partnership with the International Federation of Pharmaceutical Manufacturers Association (IFPMA) and the Developing Country Vaccine Manufacturer Network (DCVMN) regarding norovirus vaccines may be helpful. Combination vaccine approaches with IFPMA and DCVMN rotavirus manufactures may be strategic.	FDA. WHO Vaccine Pre-qualification Program. 2018 [84,85]. WHO Guidance Documents. WHO - Prequalification of Medical Products (IVDs, Medicines, Vaccines and Immunization Devices, Vector Control) [86].
Develop a package of information to meet Gavi’s approach to prioritizing adoption of support of new vaccines	Gavi’s approach to prioritizing new vaccines for investment include the following categories would need to be addressed through consultations with in-country stakeholders, peer-reviewed literature, expert and partner input, health impact modelling and analytics developed for the VIS process. Rigorous assessment of health impact to include the impact of immunization program on child mortality, overall mortality and overall morbidity. Defining of additional impact considerations with norovirus to include epidemic potential, alignment with global/regional health priorities, herd immunity, analysis of alternatives, socio-economic inequity considerations, gender inequity, and/or disease of regional importance. Development of implementation feasibility to include capacity and supplier base, GAVI market shaping potential, ease of supply chain integration, ease of programmatic integration, vaccine efficacy and safety. Formal conduct of cost and value analysis which includes vaccine procurement cost, in-country operational cost, procurement cost per event averted.	Gavi Vaccine Investment Strategy [80].