august 29, 2018 - sabinas of august 2018, 96 countries have introduced, including 46 gavi countries....
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Impact and cost-effectiveness of rotavirus vaccination in 73 Gavi countriesThirteenth International Rotavirus Symposium29 – 31 August 2018Minsk, Belarus
Frédéric Debellut
Health Economist, PATH’s Center for Vaccine Innovation and Access
August 29, 2018
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Clint Pecenka (PATH)Andrew Clark (LSHTM)Jackie Tate (US CDC)Ranju Baral (PATH)Laura Kallen (PATH)Deborah Atherly (PATH)
Study collaborators
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• Rotavirus vaccine is highly cost-effective for Gavicountries overall and in each Gavi-eligible country.
• Over 20 years, rotavirus vaccines have the potential to prevent 2.4 million child deaths and more than 80 million disability-adjusted life-years (DALYs).
• Overall cost-effectiveness ratio of US$42-43 per DALY averted.
2009
2012
Prior estimates of global impact and cost-effectiveness
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• Global rotavirus mortality decreased from 528,000 deaths in 2000 to 215,000 deaths in 2013, according to WHO/CDC.
• Increasing number of countries using rotavirus vaccines: As of August 2018, 96 countries have introduced, including 46 Gavi
countries. 16 additional Gavi countries planning to introduce.
• Many countries experiencing economic growth and transitioning from international support.
• Decrease in vaccine price.• New products entering the market.
As a result, current analysis shows that rotavirus vaccination has a higher ICER, but still excellent value for money.
Changing landscape
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• Conducted a cost-effectiveness analysis of rotavirus vaccination in 73 Gavi countries.
• Projected the costs and benefits of vaccination across 10 birth cohorts, from 2018 to 2027, compared to no vaccine.
• Analyzed from government and societal perspectives.• Did not explore potential herd effect.• Used discount rate of 3%.• Used monetary units of 2015 US$.
Overview of analysis
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UNIVAC is a single, universal vaccine impact and cost-effectiveness decision support model developed in a standardized, accessible Excel-based interface.
Developed as a follow-on to PAHO’s TRIVAC model, which has been used in many studies worldwide.
UNIVAC model
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Input Value Source
Incidence 10,000 cases per 100,000 children <5 Bilcke et al. 2009
Mortality
Country-specific; global averages:• Global average: 44 deaths per 100,000• AFRO: 64 per 100,000• EURO: 6.5 per 100,000
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 rotavirusvaccines 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 costs (government perspective)
Country-specific; global averages:• Outpatient visits: $6.18 ($4; $16.86)• Hospitalizations: $72.43 ($17.27; $350.04)
Modelled data using WHO CHOICE
Selected model inputs
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• With the exception of India, the analysis only explores the use of RV1 (ROTARIX®) or RV5 (RotaTeq®) (Gavichoices at end of 2017).
• Vaccine preference based on current country selection, expressed preference through Gaviapplication, or probabilistic determination.
• Base case scenario modelling all 73 Gavi countries using the vaccine nationwide from 2018.
Rotavirus vaccine assumptions
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• 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®
• Looked at countries paying full price of the vaccine as well as only the co-financing share for those receiving Gavi support.
Threshold $1,045 GNI
pcEligibility
threshold: $1,580 GNI pc
Variable duration
Variable duration
5 years
Vaccine price assumptions
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Over 10 years, routine nationwide rotavirus vaccination in all Gavicountries 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
Results: Health benefits (2018-2027)
AFR, 361,305, 62.1%
SEAR, 132,409, 22.8%
EMR, 73,109, 12.6%
WPR, 7,740, 1.3%
AMR, 4,059, 0.7%
EUR, 3,004, 0.5%
Averted rotavirus deaths per WHO region
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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
Results: Economic benefits (2018-2027)
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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
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.
Share of GDPp.c.
Number of countries
< 0.1 210.1 - 0.25 230.25 - 0.5 170.5 – 1.0 61.0 – 3.0 5
Cost per DALY averted by WHO region*
* DPR Korea not included as no GDP data available.
Number of countries in each ICER category
Results: Incremental cost-effectiveness ratios (ICERs)
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Country ICER as a share of GDP per capita
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$330
$117$95 $77 $69
$42
0
50
100
150
200
250
300
350
Currentanalysis (no
Gavi subsidy)
Using 2008mortality data
No assumeddecline in <5mortality w/o
vaccine
Lower healthsystem cost
per dose
Withoutcountries not
accessingGavi price
Atherly et al.2012
Cost per DALY averted in Gavi countriesGovernment perspective without Gavi subsidy
Rough comparison with prior studies
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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.
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For more information, please attend Session XI: Vaccine economics and financing on Friday!
Country-specific cost-
effectiveness studies
Financial sustainability post
Gavi support
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Thank you! Frédéric Debellut
Health Economist, PATH’s Center for Vaccine Innovation and Access
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Back up slides
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Gavi status(at study onset)
WHO Region
AFR AMR EMR EUR SEAR WPR
Initial self-financing
BeninBurkina Faso
BurundiCARChad
ComorosCongo DR
EritreaEthiopia
GambiaGuineaGuinea-BissauLiberia
MadagascarMalawi
MaliMozambique
NigerRwandaSenegal
Sierra LeoneTanzania
TogoUganda
Zimbabwe
HaitiAfghanistan
SomaliaSouth Sudan
DPR KoreaNepal
Preparatory transition
CameroonCote d'Ivoire
Ghana
KenyaLesotho
Mauritania Zambia
DjiboutiPakistanSudanYemen
KyrgyzstanTajikistan
BangladeshMyanmar Cambodia
Accelerated transition
NigeriaSao Tome & Principe Nicaragua Uzbekistan India
Lao PDRPNG
Solomon I. Vietnam
Fully self-financing
AngolaCongo
BoliviaCuba
GuyanaHonduras
ArmeniaAzerbaijan
GeorgiaMoldovaUkraine
BhutanIndonesiaSri Lanka
Timor-Leste
KiribatiMongolia
Countries considered in the analysis
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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 intussusceptionRisk of intussusception linked to RV vaccination
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Key model inputs
Input Value Source
Incidence 10K/100K Under five Bilcke et al. 2009
Severe cases Varies by WHO region: 20.5% on average(24.6% AFR; 13.3% EUR)
Fischer-Walker et al. 2013
Mortality Country specific: 44/100K on average(64 in AFR; 6.5 in EUR)
2015 median value from IHME, MCEE, WHO CDC
Vaccine coverage Country specific coverage for DTP WUENIC 2017
Vaccine efficacy Varies per mortality settingsLow mortality 98% after 2 weeks, 94% after 12 monthsMed. mortality 82% after 2 weeks, 70% after 12 monthsHigh mortality 81% after 2 weeks, 36% after 12 months
Efficacy of live oral RV vaccines based on published Randomized Controlled TrialsClark 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 perspectiveCountry specificOutpatient visits: $6.18 ($4; $16.86)Hospitalizations: $72.43 ($17.27; $350.04)
Modelled data using WHO CHOICE
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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: 0.257Duration of illness:• 3 days for non-severe RVGE, 7 days for severe RVGEHealth care seeking behavior:• 1 visit per 2 cases for severe and non-severe RVGE• Hospitalizations rate for severe RVGE: 500 per 100,000
Additional assumptions
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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%
Vaccine program costs
*Immunization Costing Action Network (ICAN). 2018. Unit Cost Repository for Immunization Delivery. ThinkWell, Washington, DC.
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Countries not accessing Gavi price
ROTARIX @ $6.20AzerbaijanBhutanCubaKiribatiMongoliaTimor LesteUkraine
RotaTeq @ $3.62IndonesiaSri Lanka
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Country vaccine preference, price per dose, and average co-financing
Country Vaccine preference
Vaccine price per
doseUS$
Average Co-financing per dose over the periodUS$
Country Vaccine preference
Vaccine price per
doseUS$
Average Co-financing per dose over the periodUS$
Country Vaccine preference
Vaccine price per
doseUS$
Average Co-financing per dose over the periodUS$
Afghanistan Rotarix® 2.02 0.20 Georgia Rotarix® 2.02 2.02 Niger Rotarix® 2.02 0.20Angola 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-Bissau Rotarix® 2.02 0.20 Papua New
Guinea Rotarix® 2.02 1.85
Bangladesh Rotarix® 2.02 0.78 Guyana RotaTeq® 3.20 3.20 Moldova Rotarix® 2.02 2.02Benin 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 0.20Burkina 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 0.13Cameroon 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 3.62Chad 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 0.53Congo 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 0.20Cuba 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 6.20DR 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 2.02Eritrea 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 0.60Gambia RotaTeq® 3.20 0.13 Nicaragua RotaTeq® 3.20 2.95 Zambia Rotarix® 2.02 0.66
Zimbabwe Rotarix® 2.02 0.20
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• 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 studyand valued based on GDP per Capita.
Rotavirus treatment costs
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Modelled rotavirus treatment costs for 73 Gavicountries (2015 US$)
Inpatient Outpatient
Total Direct Medical
Direct Non-Medical Indirect Total Direct
MedicalDirect Non-
Medical Indirect
All 73 countriesMean 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 5.24Minimum 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 0.79Minimum 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 2.83Minimum 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 5.24Minimum 106.52 76.29 19.36 10.87 12.28 7.02 2.54 2.72
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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. AfrJ Paediatr Surg. 2015.
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Total Direct Medical Direct Non-Medical Indirect
All 73 countriesMean 678.92 519.42 131.80 27.70
Maximum 1,204.56 853.46 216.56 134.54Minimum 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 20.38Minimum 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 72.59Minimum 620.75 478.82 121.50 15.82
Upper-middle income countries (n=4)Mean 992.32 717.07 181.96 93.29
Maximum 1,204.56 853.46 216.56 134.54Minimum 765.19 554.66 140.74 69.78
Modelled intussusception costs for 73 Gavicountries (2015 US$)
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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
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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 20172. Park et al. An ensemble approach to predicting the impact of vaccination on rotavirus disease in Niger. Vaccine 2017
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Use of Thresholds to interpret ICER
Former WHO guidance1, updated in 2016 to highlight the need to consider factors other than CE (affordability, feasibility, etc…) as well as developing country specific thresholds2.
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
1 - <3 x GDP per capita
0 - <1 x GDP per capita
>3 x GDP per capita
US$ / DALY averted
is negative
Cost-EffectiveHighly Cost-Effective
Not Cost-EffectiveCost Saving
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.