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.

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.

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.

From global to regional: the importance of pneumococcal disease in Latin America.

Latin America is estimated to have 3637 cases of meningitis, 14,548 cases of bacteremia, 192,761-318,238 cases of pneumonia, and about 5.6 million cases of otitis media annually. Pneumococcal conjugate vaccines (PCVs) have proven to be effective in preventing paediatric pneumococcal disease. Monitoring serotypes and anti-microbial resistance in Latin American children by collecting clinical and epidemiological data at regular intervals is essential. It is important to identify and support systems for surveillance of invasive pneumococcal disease based on population to demonstrate the impact of PCVs. Surveillance should include pneumococcal disease in adults to estimate the indirect effects of the vaccine.

The burden of pneumococcal disease among Latin American and Caribbean children: review of the evidence.

OBJECTIVE: To conduct a comprehensive review of data on pneumococcal disease incidence in Latin America and the Caribbean and project the annual number of pneumococcal disease episodes and deaths among children < 5 years of age in the region. METHODS: We carried out a systematic review (1990 to 2006) on the burden of pneumococcal disease in children < 5 years of age in the region. We summarized annual incidence rates and case fatality ratios using medians and interquartile ranges for invasive pneumococcal disease (IPD) (including all-IPD and separately abstracting pneumococcal meningitis, pneumonia, bacteremia, and sepsis data), pneumonia (all cause and radiologically confirmed), and acute otitis media by age group: < 1 year, < 2 years, and < 5 years. We modeled age-specific cumulative incidence of disease obtained from standard Kaplan-Meier analysis and projected data to obtain regional estimates of disease burden. We adjusted burden estimates by serotype coverage, vaccination coverage, and vaccine efficacy to estimate the number of cases and deaths averted. RESULTS: Of 5 998 citations identified, 26 papers from 10 countries were included. The estimated annual burden of pneumonia, meningitis, and acute otitis media caused by pneumococcus in children < 5 years of age ranged from 980 000 to 1 500 000, 2 600 to 6 800, and 980 000 to 1 500 000, respectively. An estimated 12 000 to 28 000 deaths due to pneumococcal disease occur in the region annually. Pneumococcal conjugate vaccine could save 1 life per 1 100 and prevent 1 case per 13 children vaccinated. CONCLUSION: A substantial burden of pneumococcal disease in the region is potentially preventable with pneumococcal conjugate vaccines and should be considered in regional vaccine decision making. Results are limited by the very few studies, conducted in selected settings, included in this review.

Human papillomavirus vaccine policy and delivery in Latin America and the Caribbean.

Cervical cancer caused by human papillomavirus (HPV) is a major preventable public health problem. Two vaccines are now available for primary prevention of HPV infection and their introduction offers new opportunities to enhance comprehensive cervical cancer prevention and control. Currently, HPV vaccine price is a significant barrier to rapid vaccine introduction and access. Therefore, making evidence-based decisions about whether and how to introduce HPV vaccine into the immunization schedule in the countries of Latin America and the Caribbean (LAC) requires a rigorous analysis of several factors. These include: estimates of disease burden, cost-effectiveness, operational feasibility of reaching a population of adolescent females and other key analyses that have been used in recent years to support the introduction of other vaccines, such as rotavirus and pneumococcal conjugate vaccines. Given the large number of public health priorities that are competing for limited public resources, developing and using a sound evidence base is of particular importance for vaccines, like HPV, which are currently available only at prices higher than other vaccines now in use. HPV vaccination provides the opportunity to dramatically improve women's health and partnerships must also be broad-based and effectively coordinated. This can be achieved by developing programs based on the lessons learned from vaccination strategies used to eliminate rubella and neonatal tetanus and for scaling up influenza vaccination in countries of LAC.

Recommendations for cervical cancer prevention in Latin America and the Caribbean.

Cervical cancer control in the Latin America and Caribbean (LAC) region has been, and remains, a priority and a major public health challenge. It also provides the opportunity for the advancement of research into novel cervical cancer preventative tools including the use of prophylactic human papillomavirus (HPV) vaccines, HPV-based screening options and low technology visual inspection methods. The challenges for prevention are compounded because cervical cancer cases continue to cluster in the low socio-economic and rural populations, thus requiring strong political and social commitments to ensure effective implementation in the region. Although cytology-based screening activities exist in the majority of LAC countries, these have been largely based on opportunistic screening services. Evaluation of the impact of screening is often focused on assessing coverage of the population with Pap smears. However, regardless of the chosen technology a screening program requires a complex set of activities that must also be of high quality such us ensuring access of the underserved populations to the program, maintaining routine quality controls of the screening procedures and organizing the proper follow-up of women with abnormal screening results. The cost of the HPV vaccine and of the delivery infrastructure required is currently a significant obstacle for widespread introduction that will require collaborative resolve between public health organizations, governments and vaccine manufacturers. It is important to ensure that HPV vaccines are made available to the wider public, not only to those who can afford it. This monograph and the associated regional reports have carefully identified and discussed the many challenges and opportunities to be considered for policy decisions, in particular the complex interplay between vaccination strategies and subsequent screening requirements. An advanced cost-benefit analysis, using models calibrated to specific countries in the region, presents the range of options and relative costs thus providing evidence-based scientific guidance to governments and providers in the context of a significant and systematic international review effort.

Cost-effectiveness of pneumococcal conjugate vaccination in Latin America and the Caribbean: a regional analysis.

OBJECTIVE: In Latin America and the Caribbean, routine vaccination of infants against Streptococcus pneumoniae would need substantial investment by governments and donor organizations. Policymakers need information about the projected health benefits, costs, and cost-effectiveness of vaccination when considering these investments. Our aim was to incorporate vaccine, demographic, epidemiologic, and cost data into an economic analysis of pneumococcal vaccination of infants in Latin America and the Caribbean. METHODS: We previously used a structured literature review to develop regional estimates of the incidence of disease. Cost data were collected from physician interviews and public fee schedules. We then constructed a decision analytic model to compare pneumococcal conjugate vaccination of infants with no vaccination across this region, examining only vaccine's direct effects on children. RESULTS: Pneumococcal vaccination at the rate of diphtheria-tetanus-pertussis vaccine coverage was projected to prevent 9 500 deaths per year in children aged 0 to 5 years in the region, or approximately one life saved per 1 100 infants vaccinated. These saved lives as well as averted cases of deafness, motor deficit, and seizure result in 321 000 disability-adjusted life years (DALYs) being averted annually. At vaccine prices between US$5 and US$53 per dose, the cost per DALY averted from a societal perspective would range from US$154 to US$5 252. CONCLUSION: Pneumococcal conjugate vaccine was highly cost-effective up to $40 per dose. Introduction of pneumococcal vaccine in the Latin American and Caribbean region is projected to reduce childhood mortality and to be highly cost-effective across a range of possible costs.

Cost-effectiveness of measles elimination in Latin America and the Caribbean: a prospective analysis.

BACKGROUND: In 1994, the Americas set a goal of interrupting indigenous measles transmission from the Western Hemisphere by 2000. To accomplish this goal, the Pan American Health Organization (PAHO) developed an enhanced measles vaccination strategy. METHODS: Cost data was collected at PAHO for Latin American and Caribbean (LAC) countries covering 96% of the region's population on components of the routine programs, and the 'follow-up' activities from member countries. In order to interpret our findings we have compared the present scenario regarding measles with one that would have ensued if past trends continued. RESULTS: For the entire LAC population, estimated cost of elimination program will be US$ 571 million in present value terms. INTERPRETATION: The vaccination strategy toward achieving elimination of measles costs USD 244 million, incremental from the cost of vaccination before the elimination program. Within 2000-2020, the current program will have prevented the occurrence of 3.2 million cases of measles and 16,000 deaths. Thus, vaccination strategy prevents a single case of measles at the cost of USD 71.75 and prevents a death due to measles at the cost of USD 15,000. The case fatality rate depends on a well functioning treatment program for measles cases. The vaccination strategy saves a total of USD 208 million in treatments costs due to reduced incidence of measles.