International Vaccine Access Center at Johns Hopkins Generating potential demand and impact estimates to inform dengue vaccine introduction in Brazil and Mexico Asia Dengue Summit 13-14 January, 2016 Bangkok, Thailand International Vaccine Access Center Johns Hopkins Bloomberg School of Public Health (JHBSPH)
Solution space for key stakeholders Industry can see volumes, revenues, NPVs, and timing. Can judge credibility of financing Industry willing to supply Access achieved when all key stakeholders converge in middle See value for money with clear health impact and alignment with stated priorities Buyers willing to pay Countries willing and able to introduce Demand tied to willingness to pay, sustainable pricing and financing. Need to determine budgetary and systems impacts
Dengue strategic demand forecast DSDF aids in overall strategic planning for dengue vaccine introduction that align stakeholder interests 1. Who will pay for a dengue vaccine? 2. What vaccine price will be offered? 3. What year will a dengue vaccine be adopted? 4. What age groups will be targeted? 5. What coverage in each age group will be considered? 6. What will each payer be willing to pay for a dengue vaccine?
VACCINE INTRODUCTION PROJECTIONS IN BRAZIL USING THE BUTANTAN DENGUE VACCINE CANDIDATE
Burden of dengue across Brazil Dengue disease burden: Population 201 Million (2013) More than 2 million dengue cases reported in 2013 (SINAN) - Highest annual incidence registered in the country since the dengue surveillance was implemented in the 1980s 3 700,000 new cases annually - Highest incidence of disease of any country in the Americas 1 Economic burden of dengue: US$135 million to US$3 billion dollars annually 2,4 US$126 million total cost in the public payer sector (2013) 5 Total average cost per ambulatory case: US$383 to US$889 per hospitalized case 4 Source: (1)Teixeira MG,et al. 2009; (2) Martins VC, et al. 2011; (3) Teixeira M, et al. 2013; (4) Stalh HC, et al. 2013; (5) Turchi CM, et al 2015
Population x10000 25,000.00 Estimated population distribution 20,000.00 15,000.00 10,000.00 5,000.00 0.00 0-4 5-9 10-14 15-29 30-64 65+ Age in Years PN MG RJ SP DF GO Source: IBGE/Diretoria de Pesquisas. Coordenação de População e Indicadores Sociais. Gerência de Estudos e Análises da Dinâmica Demográfica. Projeção da população do Brasil e Unidades da Federação por sexo e idade para o período 2000-2030
Data collection methods 50+ stakeholder interviews conducted across 5 target states and the capitals o Goiás, Minas Gerais, Pernambuco, Rio de Janeiro, São Paulo, Brasilia Included federal and state level Ministry of Health, Butantan Research Institute, and key experts Interview topics addressed: o Manufacturer timeline and capacity o Cost of production o PNI priorities and policies
Baseline assumptions Model Parameter Baseline category description value Variance Source Time frame Time frame 40+ years None Stakeholder Number of doses 1 dose None Manufacturer Doses per vial 10 doses None Manufacturer Vaccine Vaccine efficacy 80% 70-90% Manufacturer product Duration of protection 10 years <10 years; lifetime Manufacturer Vaccine production capacity Vaccination strategies Vaccine price Booster dose Every 10 years up to 3 Manufacturer No boosters frequency boosters and stakeholder 1 st year vaccine available 2019 2020; 2021 Manufacturer Capacity in year 1 50 million doses None Manufacturer Maximum annual 150 mil doses by year 100 mi doses by year 3 Manufacturer capacity 3 Production costs Variable cost: $0.37/dose Introduction strategies Routine introduction; Price per dose $5 per dose (WTP set at $5 per dose) None Varies by target age (see age group scenarios) $1-5 per dose Mahoney et al. Manufacturer MoH Manufacturer and stakeholder
Initial vaccine introduction scenarios
Dengue strategic demand forecast Initial strategies targeting all ages or 18 year olds exceeded capacity and considered not feasible Demand for strategies targeting children 18 years within capacity For adults 18-59 years, demand exceeded capacity by year 2024 except when stratifying by ages 19-31 years and 31-46 years Combination introduction targeting children and adults: Stakeholders prioritized vaccinating ages 7-60 years in the first 3 years followed by routine immunization in ages 2-6 years, but expected capacity can only meet 76% of the demand over the first 3 years Focusing on ages 2-46 years and staggering introduction over the first 5 years was feasible and had the greatest impact on reducing cases (90%) and deaths (79%) and on treatment cost savings (84%)
Potential estimated demand in doses Scenario Ages 2-60 (staggered II) Staggering introduction over the first 5 years was feasible with an annual average of 37m doses during 2019-23 and 24m doses after to vaccinate introduction
Introduction cost results per scenario Vaccine price per dose is assumed to be $5/dose until 2019 and decreases decreases 20% over the first 5 years for all age groups The total vaccine demand for 40 projected years is between 241 million to 706 million doses at a cost of $692 million to $2,401 million
2019 2020 2021 2022 2023 2024 2025 2026 2027 2028 2029 2030 2031 2032 2033 2034 2035 2036 2037 2038 2039 2040 2041 2042 2043 2044 2045 2046 2047 2048 2049 2050 2051 2052 2053 2054 2055 2056 2057 2058 Cost (M$) Distribution of vaccine costs Average annual cost (vaccine investment + program implementation) for 2-60 year old staggered vaccine introduction scenario 400 350 300 250 200 150 100 50 Total vaccine cost in the public sector 0 Vaccine Cost (M$) Fixed Implementation Cost (M$) Year Vaccination Equipment Cost (M$) Variable Implementation Cost (M$) *Vaccine price per dose decreases 20% over the first 5 years for all age groups in the public sector
Disease burden impact by vaccine scenario Targeting adults then children has the greatest impact Average annual cost (vaccine investment + program implementation) for 2-60 year old staggered (67% and vaccine 76% reduction introduction by year scenario 5 and 38)
Overview of key findings Estimated demand patterns: The demand decreases over time for all scenarios, even for the adult scenarios, which follows the overall population distribution The demand as the cohorts age into adulthood will significantly increase if boosters are needed every 10 years Vaccine introduction scenarios: The demand for targeting adults initially and then children is within capacity and is the most feasible strategy generating the greatest public health impact Production capacity is not a major driver of the demand, except when boosting the adult population Vaccine introduction costs: At $5 per dose, the average annual cost of introduction ranged from $21.1-405.8M in the first 10 years to $52.6-810.4M in the last 10 years The most affordable scenario was children in the younger age group
VACCINE INTRODUCTION PROJECTIONS IN MEXICO USING DENGVAXIA
Burden of dengue in Mexico Dengue disease burden: Population 117 Million (2013) DHF cases in Mexico have increased from 1,400 in 1996, to 5,500 in 2006, and to 10,000 in 2010 1 Mortality is reported at 1-2.6% Urban areas primarily affected by dengue transmission; rural areas with an increase in transmission Economic burden of dengue: The annual cost, including surveillance and vector control, is about US$170 million, or US$1.56 per capita, comparable to other countries 2 Source: (1) SINAVE/DGE/Sistema de Vigilancia Epidemiologica de Dengue. Acceso a la Plataforma de Informacion. 2014. (2) Undurraga et al. Economic and disease burden of dengue in Mexico. 2015. PLoS Negl Trop Dis 9(3):e0003547. doi:10.1371/jouirnalpntd.0003547
Estimated population distribution Source: Undurraga et al. Economic and disease burden of dengue in Mexico. 2015. PLoS Negl Trop Dis 9(3):e0003547. doi:10.1371/jouirnalpntd.0003547
Data collection methods Stakeholder interviews conducted across 4 target states and capital o Tabasco, Veracruz, Tamaulipas, Chiapas, Mexico City Included federal and state level Ministry of Health and key experts Interview topics addressed: o Manufacturer timeline and capacity o Cost of production o PNI priorities and policies Tamaulipas Veracruz Tabasco Chiapas
Baseline assumptions
Initial vaccine introduction scenarios
Preliminary vaccine demand and costs per scenario The total vaccine demand for 35 projected years is between 357 million to 440 million doses at a cost of $3.6 million to $4.5 million
2019 2020 2021 2022 2023 2024 2025 2026 2027 2028 2029 2030 2031 2032 2033 2034 2035 2036 2037 2038 2039 2040 2041 2042 2043 2044 2045 2046 2047 2048 2049 2050 2051 2052 2053 2054 2055 2056 2057 2058 % of Total Cases Averted Disease burden impact by vaccine scenario 30.00% Proportion of Cases Averted by Vaccine Scenario Age Groups 25.00% 20.00% 15.00% 10.00% 5.00% 0.00% Year 2-9 Routine 2-9 Routine 10-19 Camping 5-9 Routine 10-19 Campaign 1-2 Routine 10-19 Routine Targeting children 2-9 years in routine program is the most affordable but has delayed impact with 7% and 24% reduction in cases by year 5 and 35 years Targeting the population of 2-9 year olds in routine and campaign programs is the most expensive but has the greatest impact (10% and 27% reduction) by year 5 and 35 years
Overview of key findings Introduction of a dengue vaccine in Mexico should take a phased approach, first delivering the vaccine to targeted highrisk areas and population groups in urban and heavily populated areas, expanding as cost goes down and supply goes up The total vaccine demand for 35 projected years is between 357 million to 440 million doses at a cost of $3.6 million to $4.5 million The dengue vaccine has the potential to substantially reduce cases, deaths, and costs due to dengue fever using various introduction strategies
In summary Introduction cost for all scenarios is feasible within Brazil s and Mexico s vaccine program budget Vaccinating adults followed by children yields the greatest impact in Brazil, whereas in Mexico targeting high-risk areas in urban and heavily populated area yields the greatest impact Vaccine price, introduction strategy, age, and booster doses are major drivers of demand Dengue vaccination has potential to substantially reduce cases, deaths, and associated costs using various introduction strategies SDF models has potential to improve and accelerate vaccine introduction
International Vaccine Access Center Studies made possible with sponsored grants from the Federal Republic of Germany (BMBF) and Sanofi Pasteur Project team at JHSPH Dagna Constenla, PhD, PI Cristina Garcia, MHS Marta Wilson-Barthes, MSPH Jorge Martin del Campo, MSPH Gatien de Broucker, MHS Alexandra Greenberg, BA Ministry of Health - Brazil Geovanini, Coelho, PhD Carla Domingues, MD Joao Bosco Siqueira, MD, PhD Ministry of Health - Mexico Pablo Kuri, MD Jesús Felipe González Roldán, MD Romeo Rodríguez Suárez, MD