Model Design & Inputs • An age-structured and serotype- specific deterministic compartmental model which incorporates seasonality, host- vector interactions and 4 dengue virus serotypes immunological interactions was adopted 5 . • The model was calibrated and validated with Malaysia specific epidemiological data and vaccine efficacy data from phase-III efficacy studies 6 . • Two vaccination strategies (Table1), were simulated to evaluate the vaccine cost- effectiveness. • Malaysia is currently experiencing the most serious dengue epidemic in its history, with the number of dengue cases 5-7 times higher than the median between 2011-2015 1 . • On April 15 th 2016, WHO-SAGE on immunization recommended the use of dengue vaccine in countries with high endemicity 2 . • The first dengue vaccine, Dengvaxia® by Sanofi Pasteur, has been registered in 4 countries. • With the rapid advancement of dengue vaccine development and projected availability by this year, a Malaysia-specific economic evaluation of dengue vaccine is needed urgently to inform decision makers on the available options for controlling and preventing dengue disease with vaccines. Both strategies showed a consistent reduction on dengue cases (40%) and dengue-related mortality (43%) compared to no vaccination. Acknowledgement: This study was funded by Sanofi-Aventis Singapore Pte. Ltd. SCHOOL OF PHARMACEUTICAL SCIENCES EXPLORING THE COST-EFFECTIVE THRESHOLD PRICE OF DENGUE VACCINATION PROGRAMS IN MALAYSIA: A VALUE-BASED PRICING ASSESSMENT Hui Yee YEO 1 , Asrul Akmal SHAFIE 1 , Laurent COUDEVILLE 2 , Lucas STEINBERG 3 , Balvinder-Singh GILL 4 , Rohani JAHIS 4 1 Universiti Sains Malaysia, Penang, Malaysia, 2 Sanofi Pasteur, Lyon, France, 3 Sanofi Pasteur, Petaling Jaya, Malaysia, 4 Disease Control Division, Ministry of Health, Malaysia BACKGROUND OBJECTIVES 1. To assess the potential health and economic impact of a 3-dose tetravalent dengue vaccine in Malaysia under different vaccination strategies. 2. To determine the cost-effective threshold price of the dengue vaccine for different vaccination strategies. METHODS Model parameters Vaccination strategy 1: NW R9C17 Vaccination strategy 2: THS R9C17 References Geographical location Nationwide 6 hotspot districts* Expert opinion Routine + catch-up age cohort 9 years old + 10 – 17 years old Expert opinion Catch-up duration 1 year Expert opinion Vaccine coverage + compliance 95% + 90% Malaysia statistics, Expert opinion Underreporting factor – hospitalized 1.7 [3] Underreporting factor – ambulatory 3.79 [3] Vaccine wastage 20% Expert opinion Discount rate 3% MPG** Vaccine protection duration 10 years Assumption DALY loss per dengue case – hospitalized 0.031 [4] DALY loss per dengue case – ambulatory 0.01 [4] Treatment cost / hospitalized dengue case US$ 672.51 [3] Treatment cost / ambulatory dengue case US$ 326.51 [3] Malaysia GDP/capita, 2013 US$ 10,456.89 IMF report 2014 * Kuala Lumpur, Petaling, Klang, Hulu Langat, Gombak and Putrajaya. ** MPG = Malaysia Pharmacoeconomics Guideline Table 1: Model inputs and simulation parameters Analysis Perspective • Malaysia public provider. Time Horizon • 10 years (2016 – 2025) Outcomes / Impacts • Dengue cases, dengue-related mortality, years-of-life lost (YLL), disability-adjusted- life-year (DALY), dengue treatment cost, and highly cost-effective threshold price (<1x Malaysia GDP per capita). All costs were expressed in 2013 US$. Sensitivity Analyses • Probabilistic sensitivity analysis (PSA) was performed by 1,000 Monte Carlo sampling from the joint distribution of plausible ranges of values on dengue treatment cost per case (±20%), vaccine administration cost (±20%), vaccine coverage (90-100%), vaccine wastage (±10%), vaccine protection duration (5-30 years), annual endemicity (1-1000), vaccine efficacy (1-100), and relative efficacy against infection (0-1). • One-way deterministic sensitivity analysis (DSA) was performed on the highly cost-effective threshold price for the following parameter uncertainties: discount rate (0-5%), vaccine protection duration (5-30 years), model time horizon (5-30 years), catch-up vaccine coverage (±30%), hospitalized underreporting factor (1.0-2.45), ambulatory underreporting factor (1.0-10.38), dengue treatment cost per case (±20%), vaccine administration cost (±20%), and vaccine wastage (±10%). RESULTS OBJECTIVE 1 RESULTS OBJECTIVE 2 CONCLUSIONS The results of this study were robust to a wide range of sensitivity. Our analysis demonstrated that introducing a dengue vaccination program in Malaysia has the potential to substantially reduce the disease and economic burden (40% and 43% respectively), especially if it is introduced during current dengue epidemic. Nationwide vaccination showed a bigger overall impact compared to targeted hotspot vaccination. Our study suggested that dengue vaccination is a potentially good investment if the purchaser could negotiate a price at or below the highly cost-effective threshold price, i.e. US$ 12.60 for nationwide vaccination and US$ 34.29 for targeted hotspot vaccination. We hope this study would inform the decision makers on the fair vaccine price and that it could be a medium for negotiations between stakeholders when considering the incorporation of the dengue vaccine into the National Immunization Program. Table 2: Cumulative vaccination impact on dengue cases & dengue related mortality of both NW and THS vaccination over 10 years (2016-2025) Dengue Cases Dengue Related Mortality NW no vaccination 2,123,995 (95% CI: 1,828,532 – 2,544,115) 2,289 (95% CI: 1,972 – 2,742) NW R9C17 vaccination 1,261,000 (95% CI: 888,176 – 1,697,554) 1,308 (95% CI: 914 – 1,785) Reduction - 858,559 - 976 Dengue Cases Dengue Related Mortality THS no vaccination 904,259 (95% CI: 778,470 – 1,083,117) 973 (95% CI: 838 – 1,165) THS R9C17 vaccination 536,860 (95% CI: 378,135 – 722,720) 556 (95% CI: 388 – 759) Reduction - 365,510 - 415 Figure 1: Vaccination impact on health consequences over year 2016-2025 46,964 (95%CI: 40,812-55,568) 29,517 (95%CI: 20,633-40,161) 19,967 (95%CI: 17,350-23,627) 12,549 (95%CI: 8,771-17,074) 68,010 (95%CI: 59,010-80,415) 43,439 (95%CI: 30,401-59,185) 28,926 (95%CI: 25,098-34,201) 18,475 (95%CI: 12,931-25,172) - 20,000 40,000 60,000 80,000 100,000 120,000 NW No Vaccination NW R9C17 Vaccination THS No Vaccination THS R9C17 Vaccination YEARS YLL DALY Both NW and THS vaccination strategies exhibited a reduction of year-of- life lost (YLL) and disability-adjusted-life-year (DALY) compared to no vaccination. Figure 2: Vaccination impact on on dengue treatment cost (ambulatory and hospitalized) and total dengue management cost The model predicted that both NW and THS vaccination strategies would reduce the total dengue treatment cost and total dengue management cost over 10 years (2016-2025). 487.61 275.94 763.55 287.33 155.87 581.30 207.67 117.31 324.98 122.37 66.27 213.53 0 100 200 300 400 500 600 700 800 Dengue Treatment Cost (Ambulatory) Dengue Treatment Cost (Hospitalized) Total Dengue Management Cost US$ MILLIONS NW No Vaccination NW R9C17 Vaccination THS No Vaccination THS R9C17 Vaccination 44% (95% CI: 35 – 53) 41% (95% CI: 33 – 50) 34% (95% CI: 27 – 42) 44% (95% CI: 35 – 53) 41% (95% CI: 33 – 50) 24% (95% CI: 18 – 30) References : 1. World Health Organization. Dengue Situation Updates. [5/4/16];http://www.wpro.who.int/emerging_diseases/dengue_biweekly_20160405.pdf?ua=1 2. http://www.who.int/immunization/research/development/dengue_vaccines/en/ 3. Shepard, D.S., et al., Use of multiple data sources to estimate the economic cost of dengue illness in Malaysia. Am J Trop Med Hyg, 2012. 87(5): p. 796-805. 4. Salomon, J.A., et al., Healthy life expectancy for 187 countries, 1990–2010: a systematic analysis for the Global Burden Disease Study 2010. The Lancet. 380(9859): p. 2144-2162. 5. Coudeville, L. and G.P. Garnett, Transmission Dynamics of the Four Dengue Serotypes in Southern Vietnam and the Potential Impact of Vaccination. PLoS ONE, 2012. 7(12): p. e51244. 6. Shafie AA, et al., A Dynamic Transmission Model For Dengue Virus Infection In Malaysia. [Unpublished] 2015. Figure 3: Acceptability curve on highly cost-effective threshold price (<1x GDP/capita) of the PSA from public provider perspective 0 10 20 30 40 50 60 70 80 90 100 0 10 20 30 40 50 60 70 Probability Vaccine Being Highly Cost- Effective, % Vaccine Threshold Price per Dose, US$ NW R9C17 THS R9C17 • The price threshold for NW vaccination strategy (US$ 12.60, 95%CI: US$ 8.11 – 18.70) is found to be lower than the THS vaccination strategy (US$ 34.29, 95%CI: US$ 23.60 – 48.83). • At a price of US$ 10.00, the THS vaccination is 80% highly cost- effective. • At a price of US$ 25.00, the NW vaccination is 95% highly cost- effective. Figure 4a & 4b: One-way DSA on highly cost-effective threshold price (<1x GDP/capita) for both NW and THS vaccination strategies from public provider perspective over 10 years The threshold price from both vaccination strategies were most sensitive to the ambulatory underreporting factor, vaccine protection duration and hospitalized underreporting factor. It is least sensitive to the vaccine administration cost and vaccine coverage for catch-up cohort. 14.3 14.95 12.43 16.45 19.27 20.92 10 10.67 8.79 14.2 13.51 16.03 12 12.73 14.76 18.8 19.87 27.15 5 10 15 20 25 30 Vaccine coverage rate for catch up (90%/100%) Vaccine administration cost (80%/120%) Dengue treatment cost (80%/120%) Vaccine wastage (10%/30%) Discount rate (0%/5%) Model time horizon (5/30 years) Underreporting factors - hospitalized (1/2.45) Vaccine protection duration (5/30 years) Underreporting factors - ambulatory (1/10.38) Cost-Effectiveness Threshold Price/dose, US$ Upper Lower 38.3 38.85 33.91 43.34 49.95 53.79 28.08 29.81 25.32 38.06 37.41 42.35 32.91 37.44 39.37 48.87 51.36 68.76 20 25 30 35 40 45 50 55 60 65 70 Vaccine coverage rate for catch up (90%/100%) Vaccine administration cost (80%/120%) Total dengue treatment cost (80%/120%) Vaccine wastage (10%/30%) Discount rate (0%/5%) Model time horizon (5/30 years) Underreporting factors - hospitalized (1/2.45) Vaccine protection duration (5/30 years) Underreporting factors - ambulatory (1/10.38) Cost-Effectiveness Threshold Price/dose, US$ Upper Lower 4a 4b Contact: [email protected]