A Practical Guide to Full Value of Vaccine Assessments.

Articulating the wide range of health, social and economic benefits that vaccines offer may help to overcome obstacles in the vaccine development pipeline. A framework to guide the assessment and communication of the value of a vaccine-the Full Value of Vaccine Assessment (FVVA)-has been developed by the WHO. The FVVA framework offers a holistic assessment of the value of vaccines, providing a synthesis of evidence to inform the public health need of a vaccine, describing the supply and demand aspects, its market and its impact from a health, financial and economic perspective. This paper provides a practical guide to how FVVAs are developed and used to support investment in vaccines, ultimately leading to sustained implementation in countries. The FVVA includes a range of elements that can be broadly categorised as synthesis, vaccine development narrative and defining vaccine impact and value. Depending on the features of the disease/vaccine in question, different elements may be emphasised; however, a standardised set of elements is recommended for each FVVA. The FVVA should be developed by an expert group who represent a range of stakeholders, perspectives and geographies and ensure a fair, coherent and evidence-based assessment of vaccine value.

Opportunities to accelerate immunization progress in middle-income countries.

There has been increasing recognition of vaccine access challenges in middle-income countries and the need for increased action, particularly in countries that are not eligible for or have transitioned out of Gavi, the Vaccine Alliance support. These countries' immunization systems are more vulnerable than ever as the COVID-19 pandemic exacerbates existing programme challenges, increasing the risk of delayed vaccine introductions, backsliding immunization coverage rates, and increased coverage inequity. The potential health and equity impact of improving immunization outcomes in middle-income countries is substantial. Modelling suggests that the introduction of pneumococcal conjugate vaccine and vaccines for rotavirus and human papillomavirus in this set of Gavi-transitioned and non-Gavieligible middle-income countries in 2020 could have saved an estimated 70,000 lives if 90 % coverage had been reached. Further, increasing coverage for already-introduced vaccines to 90 % could have saved an additional estimated 16,000 lives. Over the past decade, stakeholders have made considerable efforts to identify immunization challenges in middle-income countries as documented in the 2015 SAGE-endorsed Shared Partner Middle-Income Country Strategy. In the coming decade, new global platforms like Gavi 5.0 and the Immunization Agenda 2030 provide opportunities to align on MIC strategies and provide coordinated global support to middle-income countries. The international COVID-19 pandemic response has the potential to lay the foundation for long term support beyond the scope of COVID-19 to non-Gavi eligible middle-income countries. Meanwhile regional mechanisms to address immunization barriers in middle-income countries have grown in number and strength, offering sustainable platforms for cross-country collaboration and the provision of tailored technical support. To ensure that these opportunities are successfully acted upon and that middle-income countries achieve the Immunization Agenda 2030 goals, comprehensive, multi-stakeholder consultations were conducted to identify areas of action with the greatest potential to accelerate immunization progress. Stakeholders should work together to put these findings, highlighted in this paper, into action, adapting their approaches to specific country contexts and learning from and building on existing efforts.

Public health opportunities resulting from sufficient HPV vaccine supply and a single-dose vaccination schedule.

Many countries with the highest burdens of cervical cancer have not yet offered human papillomavirus (HPV) vaccines to most of their age-eligible girls, who as adults also have limited or no access to effective cervical cancer screening or treatment. There are now 2 complementary developments that could make HPV vaccines more accessible and affordable: 1) the current and projected increases in HPV vaccine supply; and 2) the permissive recommendation for single-dose HPV vaccination schedules. This change in policy paired with the healthier HPV vaccine supply is an incredible opportunity to facilitate rapid access and expansion of HPV vaccination. Female adolescent vaccination including multiage cohorts must be prioritized. In the coming decades, this is the most cost-effective approach to avert millions of projected cervical cancer cases, which account for most HPV-related cancers globally.

The Global Demand and Supply Balance of the Human Papillomavirus Vaccine: Implications for the Global Strategy for the Elimination of Cervical Cancer.

As of November 2023, 140 World Health Organization (WHO) member states had introduced human papillomavirus (HPV) vaccination in their routine immunization schedules. Despite a continuously increasing demand from countries across all income groups, supply constraints, COVID-19 pandemic disruptions, and other factors have slowed the pace of introduction, particularly in low-resource settings. Using a population-based forecasting methodology and leveraging the WHO's yearly vaccine supply data collection, we updated global demand and supply projections for the HPV vaccine for the period of 2022-2031. The analysis aimed at clarifying the magnitude of the challenges to bringing in equitable access to HPV vaccines, which can hinder the achievement of the Global Strategy for the Elimination of Cervical Cancer. The results of this analysis show that the risk of HPV shortages has significantly decreased, and global supply is now, under normal circumstances, sufficient to meet global demand. In the long term, HPV supply will be more than sufficient to meet the Global Strategy's goal of 90% of girls fully vaccinated with the HPV vaccine by the age of 15 years. Nonetheless, paying attention to the formulation of policies and carefully managing demand and supply will be required to ensure the long-term sustainability of the HPV vaccine program.

Improving access to human papillomavirus vaccines: A case study in the IA2030 core principle of partnership.

Partnerships are fundamental to progress in immunization, and this is especially true for human papillomavirus (HPV) vaccination, which must be delivered in the context of a broader immunization, sexual and reproductive health, and cervical cancer prevention programs. Starting from the discovery and development of HPV vaccines, through to implementation and improvement of the program's resilience, partnerships have played a critical role. In May 2018, the Global Strategy to Accelerate the Elimination of Cervical Cancer set a target for 90 % of girls to be fully vaccinated with HPV vaccine by age 15 years. This will require effective partnership and multisectoral collaboration among current and future partners to ensure alignment of interests, efficient execution, and the establishment of mechanisms to resolve emerging challenges and pre-empt foreseeable risks. In ramping up this partnering approach, HPV can provide a template for other health and immunization programs.

The quest for more effective vaccine markets - Opportunities, challenges, and what has changed with the SARS-CoV-2 pandemic.

The past two decades have seen important progress in access to timely, reliable, affordable, and quality-assured supplies of vaccines of global public health importance. The new vaccines developed are powerful tools to fight killers such as pneumonia, diarrhea, and cervical cancer. Global and regional financing and pooled procurement haveshortened the lag between access in high- andlower-income countries. The COVID-19 pandemic has shown that by addressing shortcomings and seizing opportunities, we can do even more. In response to COVID-19, vaccine development and access shifted from a sequential, risk-averse paradigm to a rapid approach with maximum compression of time to market while ensuring quality. Vast public investments and innovative technologies were key facilitators. The pandemic has shown that governments play a crucial role in investing in new vaccines and manufacturing capacity and sharing risks with industry. Despite impressive progress, equity in access remains elusive with important moral, economic, and health-related consequences. Global leaders are working on a new International Treaty for Pandemic Prevention, Preparedness, and Response. To apply the lessons of COVID-19, that treaty should include a new paradigm for access to vaccines in which governments agree to:This would ensure that COVID-19 catalyzes a shift toward greater access for all under Immunization Agenda 2030.

COVID-19 impact on infant and adolescent vaccine supplies.

Vaccine production is quadrupling rapidly, creating supply chain challenges.

Improving access to affordable vaccines for middle-income countries in the african region.

Despite the remarkable power of immunization reducing morbidity and mortality due to vaccine preventable diseases, one in five African children still does not receive all the basic, necessary vaccines. This is particularly true of the 10 middle-income countries (MICs) in the WHO African Region, where data demonstrates that immunization coverage is decreasing. These countries are not eligible for Gavi support in accessing new vaccines because of their relatively high per capita income level and will gradually increase with the transitioning of countries out of Gavi support. Thus, WHO was requested to facilitate access to affordable vaccines in relation to middle-income countries and those transitioning out of Gavi support in the near future. With commitment to address the issue, WHO Regional Office for Africa convened a consultative meeting from 09 to 11 April 2018 in Brazzaville, Congo to explore ways of improving access to affordable vaccines for MICs in the Region. The meeting brought together 17 low, middle and upper middle income countries in the African Region. Immunization partners and other WHO Regions also participated in the consultation to share experiences and explore ways of increasing access to affordable vaccines in MICs in the African Region. At the end of the meeting a number of solutions and action points were proposed for implementation in the Region.

Challenges to sustainable immunization systems in Gavi transitioning countries.

The Global Vaccine Action Plan 2011-2020 (GVAP) aims to extend the full benefit of vaccination against vaccine-preventable diseases to all individuals. More than halfway through the Decade of Vaccines, countries classified as Middle-Income by the World Bank struggle to achieve several GVAP targets. Countries transitioning from Gavi, the Vaccine Alliance, represent a key sub-group of Middle Income Countries. Through a review of available literature on the subject, this study documents the lack of comparative analyses on immunization system performance in countries transitioning from Gavi support. Despite increased emphasis on the importance of programmatic sustainability beyond financing through the Gavi 2016-2020 Strategy and availability of data, existing literature has predominantly documented challenges related to domestic financing of immunization. This study complements a review of current literature with an analysis of country assessments conducted by immunization partners since 2011, in an effort to document programmatic challenges related to decision-making for immunization policy, delivery of services, and access to affordable and timely supply in Gavi transitioning countries. In light of the findings, we suggest continued systematic compilation of country performance data beyond financing to inform policy-making, in particular for: (i) development of a more nuanced theory of change towards sustainable immunization programmes and (ii) measurement of progress and key areas for attention and investment.

Bacillus Calmette-Guérin (BCG) vaccine: A global assessment of demand and supply balance.

Over the past decade, several countries across all regions, income groups and procurement methods have been unable to secure sufficient BCG vaccine supply. While the frequency of stock-outs has remained rather stable, duration increased in 2014-2015 due to manufacturing issues and attracted the attention of national, regional and global immunization stakeholders. This prompted an in-depth analysis of supply and demand dynamics aiming to characterize supply risks. This analysis is unique as it provides a global picture, where previous analyses have focused on a portion of the market procuring through UN entities. Through literature review, supplier interviews, appraisal of shortages, stock-outs and historical procurement data, and through demand forecasting, this analysis shows an important increase in global capacity in 2017: supply is sufficient to meet forecasted BCG vaccine demand and possibly buffer market shocks. Nevertheless, risks remain mainly due to supply concentration and limited investment in production process improvements, as well as inflexibility in demand. Identification of these market risks will allow implementation of risk-mitigating interventions in three areas: (1) enhancing information sharing between major global health actors, countries and suppliers, (2) identifying interests and incentives to expand product registration and investment in the BCG manufacturing process, and (3) working with countries for tighter vaccine management.

Exceptional Financial Support for Introduction of Inactivated Polio Vaccine in Middle-Income Countries.

In May 2012, the World Health Assembly declared the completion of poliovirus eradication a programmatic emergency for global public health and called for a comprehensive polio endgame strategy. The Polio Eradication and Endgame Strategic Plan 2013-2018 was developed in response to this call and demands that all countries using Oral Polio Vaccine (OPV) only introduce at least 1 dose of Inactivated Polio Vaccine (IPV) into routine immunization schedules by the end of 2015. In November 2013, the Board of Gavi (the Vaccine Alliance) approved the provision of support for IPV introduction in the 72 Gavi-eligible countries. Following analytical work and stakeholder consultations, the IPV Immunization Systems Management Group (IMG) presented a proposal to provide exceptional financial support for IPV introduction to additional OPV-only using countries not eligible for Gavi support and that would otherwise not be able to mobilize the necessary financial resources within the Polio Eradication and Endgame Strategic Plan timelines. In June 2014, the Polio Oversight Board (POB) agreed to make available a maximum envelope of US $45 million toward supporting countries not eligible for Gavi funding. This article describes the design of the funding mechanism that was developed, its implementation and the lessons learned through this process.

Gavi HPV Programs: Application to Implementation.

Developing countries disproportionately suffer from the burden of cervical cancer yet lack the resources to establish systematic screening programs that have resulted in significant reductions in morbidity and mortality in developed countries. Human Papillomavirus (HPV) vaccination provides an opportunity for primary prevention of cervical cancer in low-resource settings through vaccine provision by Gavi The Vaccine Alliance. In addition to the traditional national introduction, countries can apply for a demonstration program to help them make informed decisions for subsequent national introduction. This article summarizes information from approved Gavi HPV demonstration program proposals and preliminary implementation findings. After two rounds of applications, 23 countries have been approved targeting approximately 400,000 girls for vaccination. All countries are proposing primarily school-based strategies with mixed strategies to locate and vaccinate girls not enrolled in school. Experiences to date include: Reaching marginalized girls has been challenging; Strong coordination with the education sector is key and overall acceptance has been high. Initial coverage reports are encouraging but will have to be confirmed in population based coverage surveys that will take place later this year. Experiences from these countries are consistent with existing literature describing other HPV vaccine pilots in low-income settings.

Lessons learned from HPV vaccine delivery in low-resource settings and opportunities for HIV prevention, treatment, and care among adolescents.

BACKGROUND: Human papillomavirus (HPV) vaccines to prevent cervical cancer have become available in recent years and presented a new challenge to health systems, since they prevent a sexually transmitted virus and are most effective if they are delivered to young adolescent girls, a group not widely served by other health programs. Demonstration and pilot HPV vaccination programs undertaken in the past 7-8 years in low-resource settings have produced lessons that may be more broadly applied to other adolescent health interventions, particularly to those that attempt to reduce human immunodeficiency virus (HIV) infection. METHODS: A systematic literature review was undertaken to identify formal and informal evaluations of HPV vaccine use in low- and middle-income countries. Special attention was devoted to the detailed evaluations carried out on large demonstration projects in India, Peru, Uganda, and Vietnam. RESULTS: These lessons fall into 2 main categories: service delivery operations and community outreach and mobilization. Operational issues included venue and timing of vaccinations, definition of target population, micro-planning and coordination, integration with other services, and training. Community issues included consent, messages and channels, endorsement and support, and timing of mobilization efforts. DISCUSSION: Careful planning, good coordination across sectors and levels, and sensitive attention to the expressed needs for information and preferences for communication channels among youth, parents, and communities more broadly were among the key lessons that are relevant for HIV interventions, but many of the smaller details were also important. CONCLUSIONS: Applying or adapting these lessons to adolescent HIV services could accelerate effective program design and enhance success.

Advance market commitment for pneumococcal vaccines: putting theory into practice.

Markets for life-saving vaccines do not often generate the most desired outcomes from a public health perspective in terms of product quantity, quality, affordability, programmatic suitability and/or sustainability for use in the lowest income countries. The perceived risks and uncertainties about sustainably funded demand from developing countries often leads to underinvestment in development and manufacturing of appropriate products. The pilot initiative Advance Market Commitment (AMC) for pneumococcal vaccines, launched in 2009, aims to remove some of these market risks by providing a legally binding forward commitment to purchase vaccines according to predetermined terms. To date, 14 countries have already introduced pneumococcal vaccines through the AMC with a further 39 countries expected to introduce before the end of 2013.This paper describes early lessons learnt on the selection of a target disease and the core design choices for the pilot AMC. It highlights the challenges faced with tailoring the AMC design to the specific supply situation of pneumococcal vaccines. It points to the difficulty - and the AMC's apparent early success - in establishing a long-term, credible commitment in a constantly changing unpredictable environment. It highlights one of the inherent challenges of the AMC: its dependence on continuous donor funding to ensure long-term purchases of products. The paper examines alternative design choices and aims to provide a starting point to inform discussions and encourage debate about the potential application of the AMC concept to other fields.