COST-EFFECTIVENESS OF Mallards Reach, Bridge Avenue STRATEGIES TO PREVENT INFECTIOUS DISEASES: Maidenhead United Kingdom A SYSTEMATIC LITERATURE REVIEW SL6 1QP ISPOR Europe 2018 PMU57 10th -14th November 2018 Barcelona Clark-Wright, JF1, Hudson, P2, McCloskey, C2, Carroll S1 1Sanofi Pasteur UK & Ireland, Maidenhead, UK 2 DRG Abacus, Bicester, Oxfordshire, UK

INTRODUCTION RESULTS ECONOMIC EVALUATIONS PERTUSSIS; N=12 • Cost-effectiveness of VPW Cost-effective • The electronic searches identified 7,659 publications. Van Hoek et al., • Cost-effectiveness (payer): highly dependent on the • Vaccination is a crucial public health strategy, particularly when considering 34 in high incidence UK 2016 future incidence of pertussis. At incidence of 2012-level: 1, 2 scenarios paediatric immunisation programmes. ICER of £16,865 • After removal of duplicates, application of exclusion criteria, and addition of sources identified via hand-searching, 31 publications were available for Fernandez- • 2012 birth cohort • As with other healthcare interventions, cost-effectiveness, in conjunction Cano et al., • VPW or cocooning vs SOC Unfavourable BCR analysis. 201524 • BCR (payer): 0.15 for VPW and 0.04 for cocooning with clinical effectiveness, is a key criterion for determining population- SPAIN • 2009 birth cohort level access to vaccination programmes. 5-12 13-22 23-34 • Eight publications were on Hib, 10 on Hep B, 12 on pertussis, • VPW (DTaP), postpartum DTaP, or limited cocooning Terranella et 35 (DTaP) vs SOC Not cost-effective • Childhood vaccination programmes against , pertussis, and one on poliomyelitis , respectively. US al., 201333 • ICER (societal): US $414,523 for VPW, US $1.2 million Haemophilus influenzae type b (Hib), tetanus, polio, and hepatitis B (Hep for postpartum DTaP, US $2.0 million for cocooning B), have been shown to be highly effective. However, forecasts indicate that a number of countries may fail to reach the World Health Organization H. INFLUENZAE VACCINATION ECONOMIC EVALUATIONS; N=8 (WHO)-recommended childhood vaccination coverage rate of 90%.3 • VPW • Cost-effectiveness of Hib vaccination Russell et • Bangladesh, Nigeria, Brazil Cost-effective Not cost-effective Clark et al., • 20 birth cohorts (2012–2031) al., 201631 • Cost-effective (payer) in scenarios with higher 5 (cost/DALY < per • In view of the continuously changing and adapting childhood vaccination 2013 • Cost per DALY averted: US $192–1,033 (government MATERNAL/COCOONING capita GDP) than actual infant mortality rates landscape, there is an ongoing need for cost-effectiveness analyses of new perspective), US $155–939 (societal perspective) LOW- AND MIDDLE vaccines, changes in vaccination schedules, or vaccination of previously • Cost-effectiveness of adding pentavalent INCOME COUNTRIES (including Hib) to standard of care (no Hib) unvaccinated populations. Cost-effective Gupta et al., • 2010 birth cohort until 2024 (Haryana, India) • Universal maternal DTaP INDIA (cost/DALY < per Cost-effective 9 Sartori et • ICERs (payer and societal): US $42,500 per case 2013 • The incremental cost per DALY averted: US $819 (ICER < 3x per capita • The aim of this study was to provide an overview of recent economic capita GNI) al., 201632 avoided, US $1.1 million per death avoided and (government perspective) and US $277 (societal GDP) analyses around vaccines against diphtheria, tetanus, pertussis, Hep B, perspective) BRAZIL US $15,600 per life year saved poliomyelitis, and Hib.

• Introduction of Hib vaccination, several low- and VACCINATION • 10-year model of replacing aP with wP vaccine middle-income countries in Africa and Asia Cost-effective DeAngelis (first dose of schedule only) Griffithset al., • Incremental cost per DALY averted: US $25–453 23 Dominant (cost/DALY < per US et al., 2016 • Societal perspective; QALY gains and cost savings 20138 (government perspective) and cost-saving to US $369 capita GNI) (US $142 million per year) (societal perspective) CHILDHOOD • GAVI support assumed for lower income countries METHODS PERTUSSIS VACCINATION VACCINATION

• 65-year old patients • Introduction of Hib vaccination in Somalia Cost-effective Cost-effective Gargano et McGarry et • DTaP vs SOC Td decennial booster • Incremental cost per DALY averted: US $202.93 (compared with 29 in high incidence • Embase, MEDLINE, Cochrane Library, four key conferences (2015-2017), 6 al., 2013 • ICERs (societal and payer) range: US $17,150 (high al., 2015 scenario and additional sources/websites were searched. References of included (healthcare system perspective) GDP) incidence) to US $336,108 (low incidence) • Hib vaccination in Sudanese refugee camp Cost-effective • Universal DTaP (vs no DTaP) for people aged publications were also hand searched. Gargano et • Costs per DALY averted: from US $211–310 (payer (cost/DALY < per McGarry et >65 years NFLUENZAE 7 al., 2017 US Dominant 28 th CHILDHOOD VACCINATION perspective) capita GDP) al., 2014 • One year (payer and societal): US $47.7 million saved

• Systematic searches were conducted on September 6 , 2017. H. I and 3,387 QALYs gained • Adding Hib vaccination (as ) to AFRICA AND ASIA standard of care (no Hib) in Vietnam Cost-effective Kamiya et • Second DTaP in adolescents • Search terms included diphtheria, tetanus, pertussis, Hep B, poliomyelitis, Le et al., Not cost-effective • 2011 birth cohort (cost/DALY < per al., 201627 • ICER (societal): US $19.7 million and H. influenzae, and, for example, cost-effective, cost consequence and 201510 • Cost per DALY averted: US $1,373 (government capita GDP) cost-utility. Free text, MeSH terms and Boolean operators were used. perspective) and US $1,231 (societal perspective) • Adolescent and/or adult booster doses (vs no Rozenbaum booster) Cost-effective • Adding Hib to the existing Moradi- 30 THE • Economic evaluations could be analyses of cost-effectiveness, cost-utility, Cost-effective (BCR ADULT/ADOLESCENT et al., 2012 • ICERs (societal): €5,600 to €16,872, depending on (ICER < €20,000) Lakeh et al., • 2008 birth cohort of 2.14) booster schedule 201211 • Costs per DALY averted: US $4,535 (societal perspective) cost-minimisation or cost-benefit. Epidemiological impact models/outbreak NETHERLANDS

forecasting analyses and budget impact models were also eligible for • 5-year budget impact of pentavalent vaccine (with Hib) vs • Different adolescent booster schedules (DTaP vs Td Cost-effective Teimouri et separate vaccines (without Hib) Itatani et inclusion. alone) in high incidence

IRAN BI analysis al., 201712 • Annual net BI of US $8 –9 million and a cumulative net al., 201326 • ICERs (societal) were strongly dependent on pertussis scenarios • There were no restrictions on intervention, comparator, study design, or BIof US $43.4 million JAPAN incidence and ranged from dominant to dominated publication date. Abbreviations: BCR, benefit to cost ratio; BI, budget impact; DALY, disability-adjusted life year; GAVI, • Maximum cost-effective price increase for pertussis The Vaccine Alliance; GDP, gross domestic product; GNI, gross national income; Hib, H. influenzae Fitzpatrick type b. 25 vaccines in US NA

US et al., 2016

• Only English-language publications were included, and a post-hoc exclusion ANY • US $39 per dose of publications from before 2012 was applied. HEPATITIS B VACCINATION ECONOMIC EVALUATIONS; N=10 Abbreviations: aP, acellular pertussis; BCR, benefit to cost ratio; DTaP, diphtheria, tetanus, acellular • Inclusion criteria were aligned with the PICOS (population, interventions, pertussis vaccination; ICER, incremental cost-effectiveness ratio; NA, not apllicable; SOC, standard of • 2002 birth cohort, Vietnam Cost-effective Tu et al., comparators, outcomes, and study design) criteria. • Cost-effectiveness of Hep B childhood vaccination (ICER/QALY < per care; Td, tetanus, diphtheria; VPW, vaccination of pregnant women; wP, whole-cell pertussis. 201220 • ICER/QALY gained: US $3.77 capita GDP) • Quality assessment was conducted using the adapted method of Drummond ECONOMIC EVALUATION POLIO; N=1 • 2013 birth cohort, North Korea 4 and Jefferson. ASIA • Universal birth dose vs selective birth dose or birth dose Lee et al., offered monthly Dominant 201617 • Introduce IPV and reduce OPV • Universal birth dose less costly and more efficacious than CHILDHOOD Khan et al., FIGURE 1: PRISMA FLOW DIAGRAM • Annual cost-savings (payer) from US $4.0 million to BIM – cost saving the comparator strategies 201735 US $10.1 million in 2014–2017 INDIA • 2002 birth cohort, universal childhood Hep B vaccination POLIO VACCINATIO CHILDHOOD Lu et al., vs no vaccination 18 Dominant No. of records identified through database; n=7,659 2013 • Cost saving: US $1.0 billion (payer perspective) or US Abbreviations: BIM, budget impact model; IPV, inactivated ; OPV, oral polio vaccine. Embase=4,721; Medline=2.089 ; Cochrane=736; EconLit=113 $1.4 billion (societal perspective)

• 2013 birth cohort Yin et al., • Increasing the dose of the childhood vaccination from Dominant Duplicates; n=1,665 201521 CHILDHOOD 5 μg to 10 μg) • Improvements in health outcomes and cost savings CONCLUSIONS • Hypothetical cohort of adult patients, Hep B vaccination

CHINA with or without screening Zheng et al., Positive BCR (>1) for • The cost-effectiveness of childhood has been tested in • Favourable BCRs for patients aged 21-39 years Exclusion 1st pass; n= 5,621 201522 younger population No. of records screened (by title and abstract) : (regardless of screening) and for the overall population different settings and regions and they are consistently considered Study design, n=1,937 n=5,994 (aged 21-59) with screening Review/ editorial, n=1,657 to be highly cost-effective. • Cost-effectiveness of catch-up Hep B vaccination Patient population, n=1,221 Jia et al., for older children (not covered by the childhood 14 Dominant • The cost-effectiveness of additional doses (birth doses, catch- Copy/duplicate, n=546 2014 vaccination schedule)

Intervention, (screening) n=175 B VACCINATION HEPATITIS • Cost-savings and QALY gain (societal perspective) up doses, or adult doses) is primarily dependent on the disease ADULT/ADOLESCENT Animal/in vitro study, n=56 incidence, but also the population considered. Outcomes, n=29 • 2008 birth cohort Cost-effective (Cost/ Klingler et al., • Introduction of Hep B birth vaccine birth dose • Vaccination against polio, close to eradication, was only evaluated 15 DALY < per capita 2012 • Incremental costs per DALY averted (payer): were GDP) US $251 in a single study, in India, where the vaccination programme is still CHILDHOOD MOZAMBIQUE being optimised. No. of articles assessed for eligibility; Cost-effective Hoerger et • Adult patients with diabetes (by full paper); n= 373 (ICER/QALY < US al., 201313 • ICER/QALY (payer): US $75,094 for the overall population • No economic evaluations of diphtheria or tetanus vaccinations Exclusion 2nd pass; n=100 $100,000

were identified, most likely indicating that these are Outcomes, n=30 • Hypothetical cohort of adult patients, Hep B US Study design, n=27 Additional records vaccination with or without screening Dominant or well-controlled with current established vaccination programmes. ADULT Kuan et al., • Favourable BCRs for patients aged 21-39 years cost-effective (ICER Patient population, n=12 201316 identified through hand (regardless of screening) and for the overall population QALY < US $100,000) • These findings highlight the value of vaccination as part of wider Review/editorial, n=13 searching, n= 13 (aged 21-59) with screening Copy/duplicate, n=7 public health strategies to control and eradicate infectious diseases

• Cost-effectiveness of financial incentives to PWIDs for Cost-effective in Intervention, n=9 Rafiaet al., Hep B vaccination 19 high incidence and the importance of future vaccine innovations to deliver additional UK 2016 Language, n=1 Included studies, n=286 • Cost-effective if Hep B incidence in PWIDs is >1.2% scenarios ADULT public health gains. Unavailable, n=1 Full publications, n=211 Abbreviations: BCR, benefit to cost ratio; DALY, disability-adjusted life year; GDP, gross domestic Abstracts, n=75 product; Hep B, hepatitis B; ICER, incremental cost-effectiveness ratio; PWID, people who inject drugs; QALY, quality-adjusted life year.

Excluded publications; n=217 REFERENCES Pre-2012 publications, n=173 1. World Health Organization. 2018. 13. Hoerger TJ, et al. Diabetes Care. 2013;36(1):63-9. 24. Fernandez-Cano MI, et al. Vaccine. 2015;33(19):2213-20. Post-2012 abstracts, n=44 2. Ehreth J. Vaccine. 2003;21(7-8):596-600. 14. Jia Y, et al. Human Vaccines and Immunotherapeutics. 25. Fitzpatrick MC, et al. Vaccine. 2016;34(29):3405-11. 3. de Figueiredo A, et al. Lancet Glob Health. 2016;4(10):e726-35. 2014;10(10):2983-91. 26. Itatani T, et al. Vaccine. 2013;31(27):2891-7. 4. Drummond MF, et al. Bmj. 1996;313(7052):275-83. 15. Klingler C, et al. Vaccine. 2012;31(1):252-9. 27. Kamiya H, et al. Vaccine. 2016;34(15):1832-8. Included studies, n=69 5. Clark AD, et al. Journal of Pediatrics. 2013;163(1 SUPPL):S60-S72. 16. Kuan RK, et al. Vaccine. 2013;31(37):4024-32. 28. McGarry LJ, et al. PLoS ONE. 2014;9(1):e72723. 6. Gargano LM, et al. Prehospital & Disaster Medicine. 2015;30(4):402-11. 17. Lee D, et al. PLoS ONE. 2016;11 (11). 29. McGarry LJ, et al. PLoS ONE. 2013;8 (9):e67260. Excluded publications n=38 7. Gargano LM, et al. Vaccine. 2017;35(3):435-42. 18. Lu SQ, et al. Vaccine. 2013;31(14):1864-9. 30. Rozenbaum MH, et al. Vaccine. 2012;30(50):7327-31. Post-2012 treatment, n=31 8. Griffiths UK,et al. Journal of Pediatrics. 2013;163(1 SUPPL):S50-S9.e9. 19. Rafia R,et al. Addiction. 2016;111(9):1616-27. 31. Russell LB, et al. Clinical Infectious Diseases. 2016;63 Post-2012 non-vaccine 9. Gupta M, et al. Health policy and planning. 2013;28(1):51-61. 20. Tu HAT, et al. Value in Health Regional Issues. (suppl 4):S227-S35. prevention, n=7 10. Le P, et al. Vaccine. 2015;33(36):4639-46. 2012;1(1):7-14. 32. Sartori AM, et al. Vaccine. 2016;34(13):1531-9. 11. Moradi-Lakeh M, et al. International Journal of Preventive Medicine. 21. Yin J, et al. Vaccine. 2015;33(31):3731-8. 33. Terranella A, et al. Pediatrics. 2013;131(6):e1748-56. 2012;3(5):332-40. 22. Zheng H, et al. Vaccine. 2015;33(48):6831-9. 34. van Hoek AJ, et al. Journal of . 2016;73(1):28-37. Extracted studies, n=31 12. Teimouri F, et al. DARU, Journal of Pharmaceutical Sciences. 23. DeAngelis H, et al. JAMA Pediatrics. 2016;170(5): 35. Khan MM, et al. Public Health. 2017;142:31-8. 2017;25(1):1-8. 459-65.

This study was funded by Sanofi Pasteur. The analyses were conducted by DRG Abacus. All rights reserved.