Introduction of New Vaccines in Latin America and the Caribbean: Decision-Making LUCIA HELENA DE OLIVEIRA AND BARBARA JAUREGUI

Introduction of New Vaccines in Latin America and the Caribbean: Decision-Making LUCIA HELENA DE OLIVEIRA AND BARBARA JAUREGUI

2 Introduction of New Vaccines in Latin America and the Caribbean: Decision-Making Introduction of New Vaccines in Latin America and the Caribbean: Decision-Making Lucia Helena De Oliveira New Vaccines Advisor, Immunization Unit/FGL, Pan American Health Organization/World Health Organization Barbara Jauregui International Consultant, Comprehensive Family Immunization Unit, Pan American Health Organization/World Health Organization Introduction Biotechnological advances in recent decades have resulted in the proliferation of new vaccines at an unprecedented pace. The Region of the Americas has been at the forefront of the introduction of new vaccines in the national immunization schedules, particularly in connection with the introduction of the rotavirus, pneumococcus, and human papillomavirus (HPV) vaccines. 1,2 In general, new vaccines have demanded more years of research for their development and have frequently required the use of new and more complex technologies, which make them more expensive. 3 To minimize the inequalities resulting from the lack of access to vaccines in developing countries, it is necessary to support the decision-making process with a broader and more solid evidence base to make a case for such investment. 4 Consequently, the Ministries of Health in Latin America and the Caribbean (LAC) adopted a Pan-American Health Organization (PAHO) resolution to call for broader evidence to be used for informed decision-making on the introduction of vaccines with the technical support of PAHO. They urged Member States to mobilize additional resources to support analyses for the introduction of new vaccines. 5 VACCINOLOGY IN LATIN AMERICA

De Oliveira and Jauregui 3 Figure 1. Universal Introduction of the RV and PCV Vaccines in the EPI, Region of the Americas, 2016 BOTH PCV & RV 1. Argentina 2. Bolivia 3. Brazil 4. Cayman Islands 5. Colombia 6. Dominican Republic 7. Ecuador 8. El Salvador 9. Guatemala 10. Guyana 11. Honduras 12. Mexico 13. Nicaragua 14. Panama 15. Paraguay 16. Peru 17. United States of America 18. Venezuela ONLY PCV 1. Aruba 2. Bahamas 3. Barbados 4. Bermuda 5. Bonaire 6. Canada 7. Chile 8. Costa Rica 9. Curacao 10. French Guiana 11. Guadeloupe 12. Martinique 13. Saba 14. St. Eustatius 15. Trinidad & Tobago 16. Uruguay ONLY RV 1. Haiti PCV: 34 countries & territories /// RV: 19 countries & territories Source: PAHO/WHO country reports

4 Introduction of New Vaccines in Latin America and the Caribbean: Decision-Making Criteria for Decision-Making The decision-making process for the introduction of a new vaccine is complex and should be undertaken with absolute caution and responsibility to guarantee a successful and sustainable introduction in the long term. Ultimately, upon introduction of a vaccine in the national immunization schedule, withdrawal is not a good practice given its ethical, political and social implications. To ensure that vaccine introductions achieve the greatest sustainable impact, experts have identified three essential factors. 6 1. Decisions should be nationally based, since countries have different burdens of disease, infrastructure, and budget. 2. Scientific evidence used to support decisions must be broad based, including cost-effectiveness and financial sustainability measures. 3. Infrastructure must be in place to support nationally based decision-making, including a National Immunization Technical Advisory Group (NITAG) or another independent advisory body. Additionally, based on vaccine introduction guidelines issued by the Word Health Organization (WHO), PAHO developed the Field Guide for the Introduction and Implementation of New Vaccines, describing the various criteria to be taken into account when considering adding a new vaccine to the national schedule. 3,7 These can be broken down into political and technical considerations, and program and feasibility considerations. Political and Technical Considerations Political and technical considerations lay the foundational support and scientific evidence upon which a recommendation to introduce or to not introduced a health strategy will be based. Beyond the political considerations which fall under the responsibility of high level authorities, all technical aspects are usually reviewed and discussed by the National Immunization Technical Advisory Group (NITAG) or similar national committee. This important independent advisory body makes technical recommendations to the Ministry of Health on the best control measures against the disease to be prevented. Public Health Priority. The Ministries of Health first assess if the vaccine-preventable disease is a public health priority in their country. Therefore, the opinion of various key stakeholders needs to be established and documented through qualitative evaluations. The more awareness there is about the problem, the broader the acceptance of the vaccine introduction will be, and strategies for awareness raising are often times the first step in the policymaking process. Importantly, awareness raising requires supporting data and evidence about the magnitude of the problem, and this is where burden of disease comes into play. VACCINOLOGY IN LATIN AMERICA Burden of Disease. To make an informed decision, it is essential to be aware of the magnitude of the disease burden intended to reduce. This requires national studies on incidence, prevalence, disability, hospital admissions, and mortality. Ideally, this information can be obtained through surveillance data and/or special studies. When country-level research and surveillance data are available, disease burden is easily recognized, facilitating policy development. On the other hand, when there is a lack of sufficient national-level data, disease burden is difficult to estimate, and policymakers are left with neighboring country or even broad regional or international estimations to inform their decisions.

De Oliveira and Jauregui 5 Vaccine Efficacy and Safety. Vaccine efficacy and safety are established in clinical trials under ideal conditions prior to the licensing of the vaccine and during the post-marketing phase. This critical piece of information is considered by Ministries of Health to determine the potential added value of the intervention as an effective and safe public health strategy. Comparison with Other Interventions (Including Other Vaccines). For some diseases, there are a number of vaccines to select from and other non-vaccination interventions available. Comparison of the various control interventions requires the proper analysis level for each of them. The key aspects to consider in a comparative analysis are burden of disease, effectiveness, costs of each intervention, and cost-effectiveness results. 8,9 Comparisons between interventions require the use of national-level data to the extent possible, since there is great variability in disease burden, immunization program and healthcare costs, and even vaccine effectiveness data, where it exists. Economic and Financial Criteria. Assessment of the economic and financial implications of the new vaccines provides valuable information for the decision-making process of governments and their partners. Different types of economic analyses assess health interventions, including: cost analysis, cost-minimization analysis, cost-benefit analysis, cost-effectiveness analysis and return on investment analysis. These types of analyses are described further in the chapter, Stronger Immunization Policy in Latin America and the Caribbean: Vaccine impact, costs and cost-effectiveness evidence. Program and Feasibility Considerations Program and feasibility considerations are related to the characteristics of the product to be introduced. They need to be assessed by technical experts since they imply an analysis of the functioning, logistics, supply, performance, and delivery of the vaccine by the immunization program. These considerations often have the final say in the decision-making process, since sometimes technically sound recommendations cannot be put in practice in imperfect real-world conditions. Vaccine Characteristics and Supply. Countries should determine if the vaccine characteristics, administration route, and formulation available in the market is adequate for the national program or if problems with the program logistics or functioning can be anticipated, including additional cold chain capacity requirements, or the need to change the delivery strategy, among others. Likewise, vaccine supply needs to be considered to ensure an uninterrupted offer of the product to the country s population. Performance of the Immunization Program. The introduction of a new vaccine may increase community demand and/or weaken the immunization program. Therefore, prior to the introduction of a new vaccine, it is important to assess the current performance of the program and work on the aspects that need to be strengthened or prepared in advance for a successful introduction.

6 Introduction of New Vaccines in Latin America and the Caribbean: Decision-Making Decision-Making Process The criteria above constitute the necessary elements to be considered by the national immunization program manager to justify a preliminary technical decision. This decision should also consider discussions among the interdisciplinary groups of the Ministries of Health that are relevant to the health problem being addressed. This includes the teams performing cost-effectiveness studies with PAHO s ProVac tools, as presented in greater detail in the chapter, Stronger Immunization Policy in Latin America and the Caribbean: Vaccine impact, costs and costeffectiveness evidence. This analysis usually concludes with a two-way decision: recommend the introduction of the new vaccine or defer its introduction. Often times, however, decisions to scale up or change a vaccination strategy are also made, with the aim to improve vaccination coverage and the performance of the program. Regional Evaluation of New Vaccine Introduction in Latin America A regional study performed in 2009 analyzed the existence and functioning of the national immunization technical advisory groups in the Americas as components of the decision-making process on the introduction of new vaccines. 10 Of the 29 countries that returned the questionnaire, 17 reported that they had a NITAG. The participating countries underscored the need to strengthen the immunization policy decision-making process by: Creating or strengthening the existing NITAG; Improving coordination among stakeholders of the decision-making process; Increasing political commitment for immunization; Strengthening national data collection systems; Securing vaccine financing; and Generating economic evaluations. Since then, countries in the Americas have been making steady though variable progress on these dimensions. These conditions allow national governments to make better technical decisions about immunization programs, take responsibility for helping to pay for and distribute vaccines, and reduce the gap between developed countries and developing countries in the prevention of cases and deaths due to vaccine-preventable diseases. 11 VACCINOLOGY IN LATIN AMERICA To improve knowledge and promote understanding of the new vaccine introduction process in the Region of Latin America, in 2012 a systematic qualitative assessment was performed with specific emphasis on the rotavirus vaccine (RV) and the pneumococcal conjugate vaccine (PCV.) 1 The decision-making process, the existing program structure, and the key factors that influenced the introduction of new vaccines were assessed, including national data on morbidity and mortality available and considered before the introduction of vaccines, sources of financing and mechanisms for vaccine introduction, implementation challenges and evaluation of vaccine impact. The countries included were Bolivia, Brazil, Nicaragua, Peru, and Venezuela. Their decision-making process was assessed through interviews with key participants in each country and a systematic review of published data, gray literature, official technical documents and country-specific health indicators.

De Oliveira and Jauregui 7 The study results showed the potential of new vaccines to reduce mortality, as established in the Millennium Development Goal Number 4, was an important consideration that led to the introduction of vaccines in all of the countries assessed. Additionally, other key components of the decision-making process in these countries included availability of funds, existence of adequate evidence for vaccine introduction, and the feasibility of sustained financing. Finally, the study concluded that the decision-making process in the countries assessed does not follow a systematic approach. However, available evidence on efficacy, potential impact, and cost-effectiveness, even without local data, are significant elements in the decision-making process for the introduction of vaccines in Latin America. Conclusions For the introduction of new vaccines to be successful several criteria should be considered and agreed amongst various stakeholders. Latin America and the Caribbean countries have introduced new vaccines at a very high pace, and in doing so, some countries have followed the criteria described in this chapter more rigorously and comprehensively than other countries. As new and more expensive vaccines continue to emerge and as the national immunization programs require an increasingly higher budget, it will become important to count on the scientific evidence base to achieve successful and sustained introductions of new vaccines. The creation and strengthening of NITAGs allow for a broad and independent evaluation of all the vaccinerelated technical evidence under consideration. Lastly, quality national-level data on vaccine-preventable diseases is a critical component to be able to support the decision-making process within the national context.

8 Introduction of New Vaccines in Latin America and the Caribbean: Decision-Making References 1. Oliveira L, Toscano C, Sanwogou N, et al. Documentación sistemática de la introducción de nuevas vacunas en países seleccionados de la Región de América Latina. Vaccine 2013; 31S: C118-127. 2. Oliveira L, Danovaro-Holliday C, Ruiz Matus C and Andrus JK. Rotavirus vaccine introduction in the Americas: progress and lessons learned. Expert Rev. Vaccines 2008; 7(3), 345 353. 3. World Health Organization. Vaccine Introduction Guidelines. Adding a vaccine to a national immunization program: decision and implementation. Geneva, Switzerland: WHO, 2005. 4. Andrus J, Dietz V, Fitzsimmons J, et al. Accelerating Policy, Deployment and Access to New and Underutilized Vaccines in Developing Countries. Harvard Health Policy Review 2006; 7(2): 91 101. 5. PAHO Resolution. Regional Strategy for Sustaining National Immunization Programs in the Americas, 58th Session of the Regional Committee in Washington DC, September 2006. 6. Andrus J, Toscano C, Lewis M, et al. A Model for Enhancing Evidence-based Capacity to Make Informed Policy Decisions on the Introduction of New Vaccines in the Americas: PAHO s Provac Initiative. International Observer 2007; 122; 811 15. 7. PAHO. Epidemiological Surveillance of Diarrheal Diseases due to Rotavirus: Field Guide. Washington DC: PAHO; 2007. 8. Jauregui B, Sinha A, Clark A, et al. Strengthening the technical capacity at country-level to make informed policy decisions on new vaccine introduction. Vaccine 2011; 29(5):1099 1106. 9. Janusz C, Jauregui B, Sinha A, et al. Performing Country-led Economic Evaluations to Inform Immunization Policy. Value in Health Regional Issues 2012; 1(248):53. 10. Burns JE, Mitrovich RC, Jauregui B, et al. Descriptive analysis of immunization policy decision making in the Americas. Pan Am J Public Health 2009; 26(5):398 404. 11. Andrus J, Jauregui B, Oliviera L, Matus C. Challenges to Building Capacity for Evidence-Based New Vaccine Policy in Developing Countries. Health Affairs 2011; 26(30):1 8. VACCINOLOGY IN LATIN AMERICA