august 29, 2018 - sabinas of august 2018, 96 countries have introduced, including 46 gavi countries....

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

2 CENTER FOR VACCINE INNOVATION AND ACCESS

Clint Pecenka (PATH)Andrew Clark (LSHTM)Jackie Tate (US CDC)Ranju Baral (PATH)Laura Kallen (PATH)Deborah Atherly (PATH)

Study collaborators


• 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


• 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


• 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


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


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


• 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


• 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


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


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)


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)


Country ICER as a share of GDP per capita


$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


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.


For more information, please attend Session XI: Vaccine economics and financing on Friday!

Country-specific cost-

effectiveness studies

Financial sustainability post

Gavi support


Thank you! Frédéric Debellut

Health Economist, PATH’s Center for Vaccine Innovation and Access

[email protected]


Back up slides


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


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


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


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


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.


Countries not accessing Gavi price

ROTARIX @ $6.20AzerbaijanBhutanCubaKiribatiMongoliaTimor LesteUkraine

RotaTeq @ $3.62IndonesiaSri Lanka


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$


Vaccine price per

doseUS$



Vaccine price per

doseUS$


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


• 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


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


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.


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$)


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


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


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.

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