Impact and cost-effectiveness of rotavirus vaccination in 73 Gavi countries

August 29, 2018 Impact and cost-effectiveness of rotavirus vaccination in 73 Gavi countries Thirteenth International Rotavirus Symposium 29 31 August 2018 Minsk, Belarus Frédéric Debellut Health Economist, PATH s Center for Vaccine Innovation and Access

Study collaborators Clint Pecenka (PATH) Andrew Clark (LSHTM) Jackie Tate (US CDC) Ranju Baral (PATH) Laura Kallen (PATH) Deborah Atherly (PATH) 2 CENTER FOR VACCINE INNOVATION AND ACCESS

Prior estimates of global impact and costeffectiveness Rotavirus vaccine is highly cost-effective for Gavi countries overall and in each Gavi-eligible country. 2009 Over 20 years, rotavirus vaccines have the potential to prevent 2.4 million child deaths and more than 80 million disability-adjusted lifeyears (DALYs). 2012 Overall cost-effectiveness ratio of US$42-43 per DALY averted. 3 CENTER FOR VACCINE INNOVATION AND ACCESS

Changing landscape Global rotavirus mortality decreased from 528,000 deaths in 2000 to 215,000 deaths in 2013, according to WHO/CDC. Increasing number of countries using rotavirus vaccines: As of August 2018, 96 countries have introduced, including 46 Gavi countries. 16 additional Gavi countries planning to introduce. Many countries experiencing economic growth and transitioning from international support. Decrease in vaccine price. New products entering the market. As a result, current analysis shows that rotavirus vaccination has a higher ICER, but still excellent value for money. 4 CENTER FOR VACCINE INNOVATION AND ACCESS

Overview of analysis Conducted a cost-effectiveness analysis of rotavirus vaccination in 73 Gavi countries. Projected the costs and benefits of vaccination across 10 birth cohorts, from 2018 to 2027, compared to no vaccine. Analyzed from government and societal perspectives. Did not explore potential herd effect. Used discount rate of 3%. Used monetary units of 2015 US$. 5 CENTER FOR VACCINE INNOVATION AND ACCESS

UNIVAC model UNIVAC is a single, universal vaccine impact and costeffectiveness decision support model developed in a standardized, accessible Excelbased interface. Developed as a follow-on to PAHO s TRIVAC model, which has been used in many studies worldwide. 6 CENTER FOR VACCINE INNOVATION AND ACCESS

Selected model inputs Input Value Source Incidence 10,000 cases per 100,000 children <5 Bilcke et al. 2009 Mortality Vaccine efficacy Health system cost per dose Treatment costs (government perspective) Country-specific; global averages: Global average: 44 deaths per 100,000 AFRO: 64 per 100,000 EURO: 6.5 per 100,000 Varies per mortality settings: Low mortality 98% after 2 weeks, 94% after 12 months Med. mortality 82% after 2 weeks, 70% after 12 months High mortality 81% after 2 weeks, 36% after 12 months $1.25 in LIC $1.86 in MIC Country-specific; global averages: Outpatient visits: $6.18 ($4; $16.86) Hospitalizations: $72.43 ($17.27; $350.04) 2015 median value from IHME, MCEE, WHO/CDC Efficacy of live oral rotavirus vaccines based on published randomized controlled trials. Clark A. et al (forthcoming) ICAN Modelled data using WHO CHOICE 7 CENTER FOR VACCINE INNOVATION AND ACCESS

Rotavirus vaccine assumptions With the exception of India, the analysis only explores the use of RV1 (ROTARIX ) or RV5 (RotaTeq ) (Gavi choices at end of 2017). Vaccine preference based on current country selection, expressed preference through Gavi application, or probabilistic determination. Base case scenario modelling all 73 Gavi countries using the vaccine nationwide from 2018. 8 CENTER FOR VACCINE INNOVATION AND ACCESS

Vaccine price assumptions Assume constant price over 10 years. Gavi price per dose: $2.02 for ROTARIX $3.20 for RotaTeq $1 for ROTAVAC Related income group price (as reported to WHO V3P) for countries not accessing the Gavi price: $6.20 for ROTARIX $3.62 for RotaTeq Variable duration Threshold $1,045 GNI pc Variable duration Eligibility threshold: $1,580 GNI pc 5 years Looked at countries paying full price of the vaccine as well as only the co-financing share for those receiving Gavi support. 9 CENTER FOR VACCINE INNOVATION AND ACCESS

Results: Health benefits (2018-2027) Over 10 years, routine nationwide rotavirus vaccination in all Gavi countries would avert approximately: 165.5 million cases 82.7 million outpatient visits 8.2 million hospitalizations ~ 582,000 deaths 14.7 million DALYs* * Discounted value Averted rotavirus deaths per WHO region WPR, 7,740, 1.3% AMR, 4,059, 0.7% EMR, 73,109, 12.6% EUR, 3,004, 0.5% SEAR, 132,409, 22.8% AFR, 361,305, 62.1% 10 CENTER FOR VACCINE INNOVATION AND ACCESS

Results: Economic benefits (2018-2027) Over 10 years, rotavirus vaccination in all Gavi countries would generate approximately: US$771.7 million in health care cost savings to country governments; and US$1.1 billion in health care cost savings to society. Averted health care costs (millions US$, discounted) Government perspective Societal perspective Cost of outpatient visits $421.3 $649.7 Cost of hospitalizations $350.5 $469.7 Total $771.8 $1,119.4 11 CENTER FOR VACCINE INNOVATION AND ACCESS

Results: Incremental cost-effectiveness ratios (ICERs) From the government perspective and accounting for Gavi support, the average cost per DALY averted (ICER) in 73 Gavi countries is US$247, or 0.15 times the GDP per capita. Cost per DALY averted by WHO region* WHO region ICER ICER as share of GDP per capita AFR $94 0.08 AMR $431 0.13 EMR $157 0.11 EUR $1,044 0.48 SEAR $642 0.34 WPR $717 0.34 Number of countries in each ICER category Share of GDP p.c. Number of countries < 0.1 21 0.1-0.25 23 0.25-0.5 17 0.5 1.0 6 1.0 3.0 5 * DPR Korea not included as no GDP data available. 12 CENTER FOR VACCINE INNOVATION AND ACCESS

Country ICER as a share of GDP per capita 13 CENTER FOR VACCINE INNOVATION AND ACCESS

Rough comparison with prior studies 350 300 250 200 $330 Cost per DALY averted in Gavi countries Government perspective without Gavi subsidy 150 100 50 $117 $95 $77 $69 $42 0 Current analysis (no Gavi subsidy) Using 2008 mortality data No assumed decline in <5 mortality w/o vaccine Lower health system cost per dose Without countries not accessing Gavi price Atherly et al. 2012 14 CENTER FOR VACCINE INNOVATION AND ACCESS

Conclusions Rotavirus vaccination remains cost-effective in Gavi countries, despite global trends contributing to higher ICERs. Rotavirus vaccine is likely cost-effective in countries that have not yet adopted, showing opportunities for averting additional rotavirus deaths and disease New vaccines with lower prices will make rotavirus vaccination even more cost-effective in transitioning countries as well as in other non-gavi-eligible middle-income countries. PATH can support countries interested in economic evaluations of rotavirus vaccination. 15 CENTER FOR VACCINE INNOVATION AND ACCESS

For more information, please attend Session XI: Vaccine economics and financing on Friday! Country-specific costeffectiveness studies Financial sustainability post Gavi support 16 CENTER FOR VACCINE INNOVATION AND ACCESS

Thank you! Frédéric Debellut Health Economist, PATH s Center for Vaccine Innovation and Access fdebellut@path.org 17 CENTER FOR VACCINE INNOVATION AND ACCESS

19 CENTER FOR VACCINE INNOVATION AND ACCESS Back up slides

Countries considered in the analysis Gavi status (at study onset) Initial selffinancing Preparatory transition Accelerated transition Fully selffinancing Benin Burkina Faso Burundi CAR Chad Comoros Congo DR Eritrea Ethiopia Cameroon Cote d'ivoire Ghana WHO Region AFR AMR EMR EUR SEAR WPR Gambia Guinea Guinea- Bissau Liberia Madagascar Malawi Mali Mozambique Kenya Lesotho Nigeria Sao Tome & Principe Angola Congo Niger Rwanda Senegal Sierra Leone Tanzania Togo Uganda Zimbabwe Mauritania Zambia Haiti Afghanistan Somalia South Sudan Djibouti Pakistan Sudan Yemen Kyrgyzstan Tajikistan DPR Korea Nepal Bangladesh Myanmar Nicaragua Uzbekistan India Bolivia Cuba Guyana Honduras Armenia Azerbaijan Georgia Moldova Ukraine Bhutan Indonesia Sri Lanka Timor-Leste Cambodia Lao PDR PNG Solomon I. Vietnam Kiribati Mongolia 20 CENTER FOR VACCINE INNOVATION AND ACCESS

Building on recent data updates Systematic reviews informing: Rotavirus vaccine efficacy and duration of protection Rotavirus disease age distribution Rotavirus mortality estimates Timeliness of vaccination coverage (DHS/MICS survey analysis) Incidence and age distribution of intussusception Risk of intussusception linked to RV vaccination 21 CENTER FOR VACCINE INNOVATION AND ACCESS

Key model inputs Input Value Source Incidence 10K/100K Under five Bilcke et al. 2009 Severe cases Mortality Varies by WHO region: 20.5% on average (24.6% AFR; 13.3% EUR) Country specific: 44/100K on average (64 in AFR; 6.5 in EUR) Fischer-Walker et al. 2013 Vaccine coverage Country specific coverage for DTP WUENIC 2017 2015 median value from IHME, MCEE, WHO CDC Vaccine efficacy Varies per mortality settings Low mortality 98% after 2 weeks, 94% after 12 months Med. mortality 82% after 2 weeks, 70% after 12 months High mortality 81% after 2 weeks, 36% after 12 months Efficacy of live oral RV vaccines based on published Randomized Controlled Trials Clark A. et al. Forthcoming Health system cost per dose $1.25 in LIC, $1.86 in MIC ICAN Treatment seeking Outpatient visit 50%, Hospitalization 0.5% Assumptions Treatment costs Government perspective Country specific Outpatient visits: $6.18 ($4; $16.86) Hospitalizations: $72.43 ($17.27; $350.04) Modelled data using WHO CHOICE 22 CENTER FOR VACCINE INNOVATION AND ACCESS

Additional assumptions Infected U5 children can get non-severe or severe RVGE: Non-severe disease results in recovery with or without informal or outpatient treatment Severe disease results in recovery or death with or without informal or inpatient treatment DALY weight from 2013 Global Burden of Disease study (Solomon 2015): Non-severe RVGE: 0.188 Severe RVGE: 0.257 Duration of illness: 3 days for non-severe RVGE, 7 days for severe RVGE Health care seeking behavior: 1 visit per 2 cases for severe and non-severe RVGE Hospitalizations rate for severe RVGE: 500 per 100,000 23 CENTER FOR VACCINE INNOVATION AND ACCESS

Vaccine program costs Using health system cost per dose data from the Immunization Costing Action Network (ICAN)* LIC $1.25 per dose LMIC & UMIC $1.86 per dose Other costs: Handling: 3.5% of vaccine price International delivery: 6% of vaccine price Safety disposal bag: $0.80 for a capacity of 100 tubes Wastage: 5% *Immunization Costing Action Network (ICAN). 2018. Unit Cost Repository for Immunization Delivery. ThinkWell, Washington, DC. 24 CENTER FOR VACCINE INNOVATION AND ACCESS

Countries not accessing Gavi price ROTARIX @ $6.20 Azerbaijan Bhutan Cuba Kiribati Mongolia Timor Leste Ukraine RotaTeq @ $3.62 Indonesia Sri Lanka 25 CENTER FOR VACCINE INNOVATION AND ACCESS

Country vaccine preference, price per dose, and average co-financing Country Vaccine preference Vaccine price per dose US$ Average Cofinancing per dose over the period US$ Country Vaccine preference Vaccine price per dose US$ Average Cofinancing per dose over the period US$ Country Vaccine preference Vaccine price per dose US$ Average Cofinancing per dose over the period US$ Afghanistan Rotarix 2.02 0.20 Georgia Rotarix 2.02 2.02 Niger Rotarix 2.02 0.20 Angola Rotarix 2.02 2.02 Ghana Rotarix 2.02 0.59 Nigeria Rotarix 2.02 1.69 Armenia Rotarix 2.02 2.02 Guinea RotaTeq 3.20 0.13 Pakistan Rotarix 2.02 1.10 Azerbaijan Rotarix 6.20 6.20 Guinea- Papua New Rotarix 2.02 0.20 Bissau Guinea Rotarix 2.02 1.85 Bangladesh Rotarix 2.02 0.78 Guyana RotaTeq 3.20 3.20 Moldova Rotarix 2.02 2.02 Benin Rotarix 2.02 0.26 Haiti Rotarix 2.02 0.20 Rwanda RotaTeq 3.20 0.14 Bhutan Rotarix 6.20 6.20 Honduras Rotarix 2.02 2.02 Sao Tome & P. RotaTeq 3.20 2.36 Bolivia Rotarix 2.02 2.02 India ROTAVAC 1.00 1.00 Senegal Rotarix 2.02 0.20 Burkina Faso RotaTeq 3.20 0.13 Indonesia RotaTeq 3.62 3.62 Sierra Leone Rotarix 2.02 0.20 Burundi Rotarix 2.02 0.20 Kenya Rotarix 2.02 0.77 Solomon Islands Rotarix 2.02 1.70 Cambodia Rotarix 2.02 0.42 Kiribati Rotarix 6.20 6.20 Somalia RotaTeq 3.20 0.13 Cameroon Rotarix 2.02 0.79 Kyrgyzstan Rotarix 2.02 0.57 South Sudan Rotarix 2.02 0.20 CAR Rotarix 2.02 0.20 Lao PDR Rotarix 2.02 1.66 Sri Lanka RotaTeq 3.62 3.62 Chad Rotarix 2.02 0.20 Lesotho Rotarix 2.02 0.40 Sudan Rotarix 2.02 1.18 Comoros Rotarix 2.02 0.20 Liberia Rotarix 2.02 0.20 Tajikistan Rotarix 2.02 0.53 Congo Rotarix 2.02 2.02 Madagascar Rotarix 2.02 0.20 Timor-Leste Rotarix 6.20 6.20 Côte d'ivoire RotaTeq 3.20 1.56 Malawi Rotarix 2.02 0.20 Togo Rotarix 2.02 0.20 Cuba Rotarix 6.20 6.20 Mali RotaTeq 3.20 0.13 Uganda Rotarix 2.02 0.20 DPR Korea Rotarix 2.02 0.20 Mauritania Rotarix 2.02 0.48 Ukraine Rotarix 6.20 6.20 DR Congo Rotarix 2.02 0.20 Mongolia Rotarix 6.20 6.20 Tanzania Rotarix 2.02 0.36 Djibouti Rotarix 2.02 0.47 Mozambique Rotarix 2.02 0.20 Uzbekistan Rotarix 2.02 2.02 Eritrea Rotarix 2.02 0.23 Myanmar Rotarix 2.02 0.62 Viet Nam Rotarix 2.02 2.02 Ethiopia Rotarix 2.02 0.21 Nepal Rotarix 2.02 0.20 Yemen Rotarix 2.02 0.60 Gambia RotaTeq 3.20 0.13 Nicaragua RotaTeq 3.20 2.95 Zambia Rotarix 2.02 0.66 Zimbabwe Rotarix 2.02 0.20 26 CENTER FOR VACCINE INNOVATION AND ACCESS

Rotavirus treatment costs Conducted initial literature review Modelled estimates of direct medical costs using WHO CHOICE data and commodities costs. Validated modelled estimates against data in the literature For the government perspective, accounting for direct medical costs. For the societal perspective, accounting for direct medical costs, non-medical costs, and indirect costs. Indirect costs calculated based on lost caretakers days as witnessed in the GEMS study and valued based on GDP per Capita. 27 CENTER FOR VACCINE INNOVATION AND ACCESS

Modelled rotavirus treatment costs for 73 Gavi countries (2015 US$) Inpatient Outpatient Total Direct Medical Direct Non- Medical Indirect Total Direct Medical Direct Non- Medical Indirect All 73 countries Mean 72.43 54.33 13.79 4.37 9.49 6.18 2.24 1.09 Maximum 350.04 262.48 66.60 20.96 28.19 16.86 6.10 5.24 Minimum 17.27 13.17 3.34 0.76 5.63 4.00 1.45 0.19 Low income countries (n=31) Mean 31.44 23.77 6.03 1.69 6.83 4.71 1.71 0.42 Maximum 48.43 36.09 9.16 3.17 7.98 5.41 1.96 0.79 Minimum 17.27 13.17 3.34 0.00 5.63 4.00 1.45 0.00 Lower-middle income countries (n=38) Mean 88.54 66.29 16.82 5.43 10.60 6.79 2.46 1.36 Maximum 192.58 145.98 37.04 11.31 17.40 10.70 3.87 2.83 Minimum 39.58 29.03 7.37 2.46 7.75 5.11 1.85 0.62 Upper-middle income countries (n=4) Mean 237.06 177.49 45.04 14.53 19.66 11.77 4.26 3.63 Maximum 350.04 262.48 66.60 20.96 28.19 16.86 6.10 5.24 Minimum 106.52 76.29 19.36 10.87 12.28 7.02 2.54 2.72 28 CENTER FOR VACCINE INNOVATION AND ACCESS

Intussusception costs Modelled using similar method to rotavirus treatment costs. Longer length of stay. WHO CHOICE data for bed day cost in secondary-level hospital. Cost of surgery and non-operative management from a single source.* Indirect cost based on 1/365 GDP per capita, assuming the care taker loses as many days as the patient. *Ogundoyin OO et al. Childhood intussusception: A prospective study of management trend in a developing country. Afr J Paediatr Surg. 2015. 29 CENTER FOR VACCINE INNOVATION AND ACCESS

Modelled intussusception costs for 73 Gavi countries (2015 US$) Total Direct Medical Direct Non-Medical Indirect All 73 countries Mean 678.92 519.42 131.80 27.70 Maximum 1,204.56 853.46 216.56 134.54 Minimum 573.29 453.37 115.04 0.00 Low income countries (n=31) Mean 600.23 470.38 119.36 10.49 Maximum 634.91 490.16 124.38 20.38 Minimum 573.29 453.37 115.04 0.00 Lower-middle income countries (n=38) Mean 710.12 538.61 136.67 34.83 Maximum 896.99 666.50 169.13 72.59 Minimum 620.75 478.82 121.50 15.82 Upper-middle income countries (n=4) Mean 992.32 717.07 181.96 93.29 Maximum 1,204.56 853.46 216.56 134.54 Minimum 765.19 554.66 140.74 69.78 30 CENTER FOR VACCINE INNOVATION AND ACCESS

Analysis outcomes Health impact Cases averted Outpatient visits and hospitalizations averted Deaths averted Economic impact Cost of vaccination program Cost of care averted by vaccination Main outcome: Incremental cost-effectiveness ratio (ICER) expressed in US$ per Disability Averted Life Year 31 CENTER FOR VACCINE INNOVATION AND ACCESS

Study limitations Analysis assumes a constant vaccine price over 10 years and does not account for other products that may become available during the study period. Health system cost-per-dose data relies on a limited number of available data points and is applied to different products without distinction. Not accounting for herd effect Not exploring relative coverage Static model although data from transmission models applied to LMICs (Niger, India) suggests marginal benefit of developing a transmission model to estimate impact on mortality. 1,2 Probabilistic sensitivity analysis is yet to be implemented. Cost effectiveness acceptability curve. 1. Rose et al. Health impact and cost-effectiveness of a domestically-produced rotavirus vaccine in India: A model based analysis. Plos One 2017 2. Park et al. An ensemble approach to predicting the impact of vaccination on rotavirus disease in Niger. Vaccine 2017 32 CENTER FOR VACCINE INNOVATION AND ACCESS

Use of Thresholds to interpret ICER Former WHO guidance 1, updated in 2016 to highlight the need to consider factors other than CE (affordability, feasibility, etc ) as well as developing country specific thresholds 2. Cost Saving US$ / DALY averted is negative Highly Cost- Effective 0 - <1 x GDP per capita Cost-Effective 1 - <3 x GDP per capita Woods et al. 3 attempt at defining country CE thresholds in a context of financial constraints (limited budget) accounting for opportunity cost in terms of the health foregone because other interventions cannot be provided Not Cost- Effective >3 x GDP per capita 1 The world health report 2002: reducing risks, promoting healthy life. Geneva: World Health Organization; 2002. 2 Bertram MY, Lauer JA, De Joncheere K, Edejer T, Hutubessy R, Kieny M-P, et al. Cost-effectiveness thresholds: pros and cons. Bull World Health Organ 2016;94:925 30. 3 Woods B. et al., Country-Level Cost-Effectiveness Thresholds: Initial Estimates and the Need for Further Research, Value in health 19 (2016) 929-935. 33 CENTER FOR VACCINE INNOVATION AND ACCESS