Evidence-based decision-making for vaccine introductions: Overview of the ProVac International Working Group's experience.

INTRODUCTION: Pan American Health Organization's (PAHO) ProVac Initiative aims to strengthen countries' technical capacity to make evidence-based immunization policy. With financial support from the Bill and Melinda Gates Foundation, PAHO established the ProVac International Working Group (IWG), a platform created for two years to transfer the ProVac Initiative's tools and methods to support decisions in non-PAHO regions. METHODS: In 2011, WHO Regional Offices and partner agencies established the IWG to transfer the ProVac framework for new vaccine decision support, including tools and trainings to other regions of the world. During the two year period, PAHO served as the coordinating secretariat and partner agencies played implementing or advisory roles. RESULTS: Fifty nine national professionals from 17 countries received training on the use of economic evaluations to aid vaccine policy making through regional workshops. The IWG provided direct technical support to nine countries to develop cost-effectiveness analyses to inform decisions. All nine countries introduced the new vaccine evaluated or their NITAGs have made a recommendation to the Ministry of Health to introduce the new vaccine. DISCUSSION: Developing countries around the world are increasingly interested in weighing the potential health impact due to new vaccine introduction against the investments required. During the two years, the ProVac approach proved valuable and timely to aid the national decision making processes, even despite the different challenges and idiosyncrasies encountered in each region. The results of this work suggest that: (1) there is great need and demand for technical support and for capacity building around economic evaluations; and (2) the ProVac method of supporting country-owned analyses is as effective in other regions as it has been in the PAHO region. CONCLUSION: Decision support for new vaccine introduction in low- and middle-income countries is critical to guiding the efficient use of resources and prioritizing high impact vaccination programs.

An analysis of government immunization program expenditures in lower and lower middle income countries 2006-12.

Financing is becoming increasingly important as the cost of immunizing the world's children continues to rise. By 2015, that cost will likely exceed US$60 per infant as new vaccines are introduced into national immunization programs. In 2006, 51 lower and lower middle income countries reported spending a mean US$12 per surviving infant on routine immunization. By 2012, the figure had risen to $20, a 67% increase. This study tests the hypothesis that lower and lower middle income countries will spend more on their routine immunization programs as their economies grow. A panel data regression approach is used. Expenditures reported by governments annually (2006-12) through the World Health Organization/UNICEF Joint Reporting Form are regressed on lagged annual per capita gross national income (GNI), controlling for prevailing mortality levels, immunization program performance, corruption control efforts, geographical region and correct reporting. Results show the expenditures increased with GNI. Expressed as an elasticity, the countries spent approximately $6.32 on immunization for every $100 in GNI increase from 2006 to 2012. Projecting forward and assuming continued annual GNI growth rates of 10.65%, countries could be spending $60 per infant by 2020 if national investment functions increase 4-fold. Given the political will, this result implies countries could fully finance their routine immunization programs without cutting funding for other programs.

Development of a cholera vaccination policy on the Island of Hispaniola, 2010-2013.

Deployment of oral cholera vaccine (OCV) on the Island of Hispaniola has been considered since the emergence of the disease in October of 2010. At that time, emergency response focused on the time-tested measures of treatment to prevent deaths and sanitation to diminish transmission. Use of the limited amount of vaccine available in the global market was recommended for demonstration activities, which were carried out in 2012. As transmission continues, vaccination was recommended in Haiti as one component of a comprehensive initiative supported by an international coalition to eliminate cholera on the Island of Hispaniola. Leveraging its delivery to strengthen other cholera prevention measures and immunization services, a phased OCV introduction is pursued in accordance with global vaccine supply. Not mutually exclusive or sequential deployment options include routine immunization for children over the age of 1 year and campaigns in vulnerable metropolitan areas or rural areas with limited access to health services.

Perspectives on the role of surveillance in eliminating rubella and congenital rubella syndrome in the Americas.

Effective management and coordination in regions currently lacking surveillance capacity will require significant increases in existing human resources to manage vitally needed expanded national surveillance systems. An adequate investment in human resources and infrastructure capacity is essential for ensuring surveillance functions well. This was the experience in the Americas, particularly with the recent elimination of rubella and congenital rubella syndrome. By taking this path, other benefits to the overall public health of the nations will occur. The purpose of this paper is to present perspectives on the role of surveillance in the elimination of rubella in the Americas and to share related perspectives on capacity development in developing countries. Hopefully, these perspectives will aid efforts to strengthen surveillance and advance rubella elimination in other regions of the world.

Overcoming perceptions of financial barriers to rotavirus vaccine introduction in Asia.

Despite a WHO recommendation in 2009, reaffirmed in 2013, that all countries should consider introducing rotavirus vaccines into their National Immunization Programs, as of June 2013 only 45 have done so. One major consideration appears to have been the costs of the vaccine to countries. Of concern, is that Asian countries have been slow to introduce rotavirus vaccines despite having robust data that could inform the decision-making process. Although decisions on new vaccine introduction are very complex and vary by country and region, economic evaluations are often pivotal once vaccine efficacy and safety has been established, and disease burden documented and communicated. Unfortunately, with private sector list prices of vaccines often used in economic evaluations, rather than a potential public health sector pricing structure, policy-makers may defer decisions on rotavirus vaccine introduction based on the belief that "the vaccine price is too high," even though this might be based on erroneous data. The Pan American Health Organization's Revolving Fund provides one example of how vaccine price can be made more competitive and transparent through a regional tendering process. Other mechanisms, such as tiered pricing and UNICEF procurement, also exist that could help Asian and other countries move forward more quickly with rotavirus vaccine introduction.

Strengthening surveillance: confronting infectious diseases in developing countries.

Effective management and coordination in regions currently lacking surveillance capacity will require significant increases in existing human resources to manage vitally needed expanded national systems. An adequate investment in human resources is essential for ensuring surveillance functions well. This was the experience in the Americas. By taking this path, other benefits to the overall public health of nations will occur. Monitoring deaths will help as an indicator for impending epidemics or other threats. Better equipped labs will detect antigen shifts in virus and circulating bacterial serotypes more rapidly and other earlier changes in patterns of transmission more efficiently. Any strategy must promote and galvanize the commitment of countries to excellence, equity, and access, above all.

Measles and rubella eradication in the Americas.

The challenge for regions embarking on measles elimination will be to maintain high population immunity with excellent vaccination coverage and high-quality surveillance. Meeting this challenge will be especially critical for dealing with importations of measles virus that will occur as long as the virus is circulating anywhere in the world. Implementation of measles elimination strategies will uncover the "hidden" disease burden of rubella and congenital rubella syndrome. As was the experience in countries of Latin America and the Caribbean (LAC), integrating the elimination of measles with the elimination of rubella will greatly enhance the capacity of countries to sustain progress in the reduction of measles mortality. Countries of LAC prioritized the routine national immunization program over short-term successes. While doing so, they have also encountered new opportunities to expand the benefits of disease control and elimination activities to other aspects of public health, most importantly towards improving health care for women and newborns and reducing inequities in health in the region's poorest communities. Implementation of similar strategies could lead to the global eradication of measles, rubella, and congenital rubella syndrome early this century, while strengthening routine immunization programs, and developing the capacity to introduce new and underutilized vaccines.

Researching routine immunization-do we know what we don't know?

BACKGROUND: The Expanded Programme on Immunization (EPI), launched in 1974, has developed and implemented a range of strategies and practices over the last three decades to ensure that children and adults receive the vaccines they need to help protect them against vaccine-preventable diseases. Many of these strategies have been implemented, resulting in immunization coverage exceeding 80% among children one year of age in many countries. Yet millions of infants remain under-immunized or unimmunized, particularly in poorer countries. In November 2009, a panel of external experts met at the United States Centers for Disease Control and Prevention (CDC) to review and identify areas of research required to strengthen routine service delivery in developing countries. METHODS: Research opportunities were identified utilizing presentations emphasizing existing research, gaps in knowledge and key questions. Panel members prioritized the topics, as did other meeting participants. FINDINGS: Several hundred research topics covering a wide range were identified by the panel members and participants. However there were relatively few topics for which there was a consensus that immediate investment in research is warranted. The panel identified 28 topics as priorities. 18 topics were identified as priorities by at least 50% of non-panel participants; of these, five were also identified as priorities by the panel. Research needs included identifying the best ways to increase coverage with existing vaccines and introduce new vaccines, integrate other services with immunizations, and finance immunization programmes. INTERPRETATION: There is an enormous range of research that could be undertaken to support routine immunization. However, implementation of strategic plans, rather than additional research will have the greatest impact on raising immunization coverage and preventing disease, disability, and death from vaccine-preventable diseases. The panel emphasized the importance of tying operational research to programmatic needs, with a focus on efforts to scale up proven best practices in each country, facilitating the full implementation of immunization strategies.

Creating sustainable financing and support for immunization programs in fifteen developing countries.

Immunization programs are important tools for reducing child mortality, and they need to be in place for each new generation. However, most national immunization programs in developing countries are financially and organizationally weak, in part because they depend heavily on funding from foreign sources. Through its Sustainable Immunization Financing Program, launched in 2007, the Sabin Vaccine Institute is working with fifteen African and Asian countries to establish stable internal funding for their immunization programs. The Sabin program advocates strengthening immunization programs through budget reforms, decentralization, and legislation. Six of the fifteen countries have increased their national immunization budgets, and nine are preparing legislation to finance immunization sustainably. Lessons from this work with immunization programs may be applicable in other countries as well as to other health programs.

The future of immunisation policy, implementation, and financing.

Vaccines have already saved many lives and they have the potential to save many more as increasingly elaborate technologies deliver new and effective vaccines against both infectious diseases--for which there are currently no effective licensed vaccines--such as malaria, tuberculosis, and HIV and non-infectious diseases such as hypertension and diabetes. However, these new vaccines are likely to be more complex and expensive than those that have been used so effectively in the past, and they could have a multifaceted effect on the disease that they are designed to prevent, as has already been seen with pneumococcal conjugate vaccines. Deciding which new vaccines a country should invest in requires not only sound advice from international organisations such as WHO but also a well informed national immunisation advisory committee with access to appropriate data for local disease burden. Introduction of vaccines might need modification of immunisation schedules and delivery procedures. Novel methods are needed to finance the increasing number of new vaccines that have the potential to save lives in countries that are too poor to afford them. Here, we discuss some options.

The role of research in viral disease eradication and elimination programs: lessons for malaria eradication.

By examining the role research has played in eradication or regional elimination initiatives for three viral diseases--smallpox, poliomyelitis, and measles--we derive nine cross-cutting lessons applicable to malaria eradication. In these initiatives, some types of research commenced as the programs began and proceeded in parallel. Basic laboratory, clinical, and field research all contributed notably to progress made in the viral programs. For each program, vaccine was the lynchpin intervention, but as the programs progressed, research was required to improve vaccine formulations, delivery methods, and immunization schedules. Surveillance was fundamental to all three programs, whilst polio eradication also required improved diagnostic methods to identify asymptomatic infections. Molecular characterization of pathogen isolates strengthened surveillance and allowed insights into the geographic source of infections and their spread. Anthropologic, sociologic, and behavioural research were needed to address cultural and religious beliefs to expand community acceptance. The last phases of elimination and eradication became increasingly difficult, as a nil incidence was approached. Any eradication initiative for malaria must incorporate flexible research agendas that can adapt to changing epidemiologic contingencies and allow planning for posteradication scenarios.

Experiences with smallpox eradication in Ethiopia.

The smallpox eradication campaign operated in Ethiopia from 1970 until 1977. During this time Ethiopia had only 84 hospitals, 64 health centres and fewer than 400 physicians in a country of 25 million people. In 1970 smallpox vaccination was relatively unknown in the country, and the government actually contested the fact that smallpox was present in the country. Most of the resources of the Ministry of Health were used for malaria eradication. Initial pessimism from the Ministry of Health and others was eventually overcome as the smallpox eradication campaign continued to pick up steam but many remained unenthusiastic. Ethiopia was the first country in the world to start its smallpox eradication campaign from day one with the strategy of "Surveillance and Containment". Establishing a surveillance system in a country with a limited health infrastructure was a daunting challenge. At the end of the first year of the programme in 1971, 26,000 cases of smallpox had been registered through the growing surveillance system. Throughout revolution of 1974 the smallpox campaign was the only UN program to operate in the country; in fact it expanded with the hire of many locals leading to a "nationalized" program. This development ushered in the most successful final phase of the program. As the program progressed cases were diminishing in most regions, however transmission continued in the Ogaden desert. Over the course of the campaign approximately 14.3 million US dollars was spent. Working conditions were extremely challenging and a variety of chiefs, guerrillas, landowners and governments had to be appeased. The programme was successful due to the dedicated national and international staff on the ground and by having the full support of the WHO HQ in Geneva.