Abstract
Background
Herpes zoster (HZ) is one of the most common diseases among adults. Its reactivation is characterized by a severe and painful complication. In addition to the existing herpes zoster vaccine (ZVL), the FDA approved a new adjuvanted subunit zoster vaccine (RZV) in 2017 for use in adults aged 50 years and older. Several studies have assessed the cost-effectiveness of ZVL, many of which were conducted before the long-term vaccine efficacy data was available in 2014.
Objective
Our objectives were to (i) summarize and compare the cost-effectiveness analyses (CEAs) of ZVL conducted before and after 2014, (ii) summarize the CEAs of RZV, and (iii) critically assess the cost-effectiveness models and identify key parameters to consider for future CEAs of RZV.
Methods
We searched PubMed and two other databases from inception to March 2018 for original cost-effectiveness, cost-utility, or cost-benefit analyses of HZ vaccines. Three investigators independently reviewed and assessed full-text articles after screening the titles and abstracts to determine eligibility. For all included studies, we assessed study quality using the Drummond and Jefferson's checklist and extracted study characteristics, model structure, vaccine characteristics, incidence of HZ and complications, incremental cost-effectiveness ratio, and sensitivity analyses. We summarized data by type of vaccine, year of publication, and funding sources.
Results
Twenty-seven studies met eligibility criteria. All studies were from high-income countries and were of moderate-to-high or high quality. Twenty studies repeatedly used four cost-effectiveness models. The assumption on long-term efficacy of ZVL was not based on clinical trial data in > 50% of studies. Fifteen out of 25 studies concluded that ZVL was cost-effective compared with no vaccine at a vaccine price ranging between US$93 and US$236 per dose (2018 US$), 40% of which were published after 2014. All industry-funded studies favored the use of ZVL. The single study assessing RZV found it to be more effective and less costly than ZVL, and cost-effective compared with no vaccination. More studies conducted after 2014 included various efficacy endpoints for ZVL, adverse reactions, and productivity loss compared with those conducted before 2014.
Conclusions
A majority of studies of ZVL found it to be cost-effective compared with no vaccine using the authors’ chosen willingness-to-pay thresholds. RZV was dominant in the single study comparing the two vaccines, but the finding needs to be confirmed with further studies in different settings. Future studies should assume vaccine efficacy in line with clinical data, account for more efficacy endpoints for ZVL, and include other HZ long-term complications, vaccine adverse reactions, and productivity loss.
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References
Cohen JI. Herpes zoster. N Engl J Med. 2013;369(3):255–63.
Kawai K, Yawn BP, Wollan P, Harpaz R. Increasing incidence of herpes zoster over a 60-year period from a population-based study. Clin Infect Dis. 2016;63(2):221–6.
Varghese L, Standaert B, Olivieri A, Curran D. The temporal impact of aging on the burden of herpes zoster. BMC Geriatr. 2017;17(1):30.
Kawai K, Gebremeskel BG, Acosta CJ. Systematic review of incidence and complications of herpes zoster: towards a global perspective. BMJ Open. 2014;4(6):e004833.
Oster G, Harding G, Dukes E, Edelsberg J, Cleary PD. Pain, medication use, and health-related quality of life in older persons with postherpetic neuralgia: results from a population-based survey. J Pain. 2005;6(6):356–63.
Johnson BH, Palmer L, Gatwood J, Lenhart G, Kawai K, Acosta CJ. Annual incidence rates of herpes zoster among an immunocompetent population in the United States. BMC Infect Dis. 2015;15(1):502.
Yawn BP, Itzler RF, Wollan PC, Pellissier JM, Sy LS, Saddier P. Health care utilization and cost burden of herpes zoster in a community population. In: Mayo clinic proceedings. Elsevier; 2009. p. 787–94.
Chen N, Li Q, Yang J, Zhou M, Zhou D, He L. Antiviral treatment for preventing postherpetic neuralgia. Cochrane Database Syst Rev. 2014;2:CD006866.
Johnson RW. Herpes zoster and postherpetic neuralgia. Expert Rev Vaccines. 2010;9(3 Suppl):21–6.
Centers for Disease C, Prevention. Update on herpes zoster vaccine: licensure for persons aged 50 through 59 years. MMWR Morb Mortal Wkly Rep. 2011;60(44):1528.
Mitka M. FDA approves shingles vaccine: herpes zoster vaccine targets older adults. JAMA. 2006;296(2):157–8.
Morrison VA, Johnson GR, Schmader KE, Levin MJ, Zhang JH, Looney DJ, et al. Long-term persistence of zoster vaccine efficacy. Clin Infect Dis. 2014;60(6):900–9.
Schmader K, Oxman M, Levin M, Johnson G, Zhang J, Betts R, et al. Persistence of the efficacy of zoster vaccine in the shingles prevention study and the short-term persistence substudy. Clin Infect Dis. 2012;55(10):1320–8.
Harpaz R, Ortega-Sanchez IR, Seward JF. Prevention of herpes zoster: recommendations of the Advisory Committee on Immunization Practices (ACIP). Morb Mort Wkly Rep Recomm Rep. 2008;57(5):1–30.
Dooling KL, Guo A, Patel M, Lee GM, Moore K, Belongia EA, et al. Recommendations of the Advisory Committee on Immunization Practices for use of herpes zoster vaccines. Am J Transplant. 2018;18(3):756–62.
Cunningham AL, Lal H, Kovac M, Chlibek R, Hwang S-J, Díez-Domingo J, et al. Efficacy of the herpes zoster subunit vaccine in adults 70 years of age or older. N Engl J Med. 2016;375(11):1019–32.
Lal H, Cunningham AL, Godeaux O, Chlibek R, Diez-Domingo J, Hwang SJ, et al. Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults. N Engl J Med. 2015;372(22):2087–96.
Szucs TD, Pfeil AM. A systematic review of the cost effectiveness of herpes zoster vaccination. PharmacoEconomics. 2013;31(2):125–36.
Kawai K, Preaud E, Baron-Papillon F, Largeron N, Acosta CJ. Cost-effectiveness of vaccination against herpes zoster and postherpetic neuralgia: a critical review. Vaccine. 2014;32(15):1645–53.
Damm O, Ultsch B, Horn J, Mikolajczyk RT, Greiner W, Wichmann O. Systematic review of models assessing the economic value of routine varicella and herpes zoster vaccination in high-income countries. BMC Public Health. 2015;5(15):533.
Centers for Disease Control and Prevention. Adult vaccine price list. 2018. http://www.cdc.gov/vaccines/programs/vfc/awardees/vaccine-management/price-list/. Accessed 28 Sept 2018.
Bilcke J, Verelst F, Beutels P. Sponsorship bias in base-case values and uncertainty bounds of health economic evaluations? A systematic review of herpes zoster vaccination. Med Decis Mak. 2018;38(6):730–45.
Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151(4):264–9, W64.
Shea BJ, Grimshaw JM, Wells GA, Boers M, Andersson N, Hamel C, et al. Development of AMSTAR: a measurement tool to assess the methodological quality of systematic reviews. BMC Med Res Methodol. 2007;7:10.
Drummond MF, Jefferson TO. Guidelines for authors and peer reviewers of economic submissions to the BMJ. The BMJ Economic Evaluation Working Party. BMJ (Clinical research ed). 1996;313(7052):275–83.
Le P, Nghiem VT, Mullen PD, Deshpande A. Cost-effectiveness of competing treatment strategies for clostridium difficile infection: a systematic review. Infect Control Hosp Epidemiol. 2018;39(4):412–24.
Statistics; BoL. CPI Inflation Calculator. Available from: https://www.bls.gov/data/inflation_calculator.htm. Accessed 20 Apr 2018.
Organisation for Economic Co-operation Development. Consumer Price Indices. Available from: http://stats.oecd.org/index.aspx?datasetcode=mei_prices. Accessed 15 Apr 2018.
The World Bank. World Bank Country and Lending Groups. Available from: https://datahelpdesk.worldbank.org/knowledgebase/articles/906519. Accessed 2 Oct 2018.
Préaud E, Uhart M, Böhm K, Aidelsburger P, Anger D, Bianic F, et al. Cost-effectiveness analysis of a vaccination program for the prevention of herpes zoster and post-herpetic neuralgia in adults aged 50 and over in Germany. Hum Vaccines Immunother. 2015;11(4):884–96.
Le P, Rothberg MB. Determining the optimal vaccination schedule for herpes zoster: a cost-effectiveness analysis. J Gen Intern Med. 2017;32(2):159–67.
Le P, Rothberg MB. Cost effectiveness of a shingles vaccine booster for currently vaccinated adults in the US. Am J Prev Med. 2017;53(6):829–36.
Le P, Rothberg MB. Cost-effectiveness of the adjuvanted herpes zoster subunit vaccine in older adults. JAMA Intern Med. 2018;178(2):248–58.
Lopez-Belmonte JL, Cisterna R, Gil de Miguel A, Guilmet C, Bianic F, Uhart M. The use of Zostavax in Spain: the economic case for vaccination of individuals aged 50 years and older. J Med Econ. 2016;19(6):576–86.
Moore L, Remy V, Martin M, Beillat M, McGuire A. A health economic model for evaluating a vaccine for the prevention of herpes zoster and post-herpetic neuralgia in the UK. Cost Eff Resour Alloc. 2010;8(1):7.
Pan J, Hsu T-Y, Johnson KD, Xu R, Acosta CJ, Kawai K. Cost-effectiveness analysis of herpes zoster vaccine in adults above 50 in Singapore. Dermatol Sin. 2017;35(4):177–81.
Ultsch B, Weidemann F, Reinhold T, Siedler A, Krause G, Wichmann O. Health economic evaluation of vaccination strategies for the prevention of herpes zoster and postherpetic neuralgia in Germany. BMC Health Serv Res. 2013;26(13):359.
Annemans L, Bresse X, Gobbo C, Papageorgiou MA. Health economic evaluation of a vaccine for the prevention of herpes zoster (shingles) and post-herpetic neuralgia in adults in Belgium. J Med Econ. 2010;13(3):537–51.
Bilde L, Nielsen TT, Ronholt F, Kruse M. The cost-effectiveness of introducing a vaccine for the prevention of herpes zoster and post-herpetic neuralgia in elderly Danes. Nordic J Health Econ. 2016;5(2):1–21.
Blank PR, Ademi Z, Lu X, Szucs TD, Schwenkglenks M. Herpes zoster vaccine: a health economic evaluation for Switzerland. Hum Vaccines Immunother. 2017;13(7):1495–504.
Bresse X, Annemans L, Préaud E, Bloch K, Duru G, Gauthier A. Vaccination against herpes zoster and postherpetic neuralgia in France: a cost–effectiveness analysis. Expert Rev Pharmacoecon Outcomes Res. 2013;13(3):393–406.
Coretti S, Codella P, Romano F, Ruggeri M, Cicchetti A. Cost-effectiveness analysis of herpes zoster vaccination in Italian elderly persons. Int J Technol Assess Health Care. 2016;32(4):233–40.
Szucs TD, Kressig RW, Papageorgiou M, Kempf W, Michel JP, Fendl A, et al. Economic evaluation of a vaccine for the prevention of herpes zoster and post-herpetic neuralgia in older adults in Switzerland. Hum Vaccin. 2011;7(7):749–56.
Le P, Rothberg MB. Cost-effectiveness of herpes zoster vaccine for persons aged 50 years. Ann Intern Med. 2015;163(7):489–97.
Rothberg MB, Virapongse A, Smith KJ. Cost-effectiveness of a vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. Clin Infect Dis. 2007;44(10):1280–8.
Edmunds W, Brisson M, Rose J. The epidemiology of herpes zoster and potential cost-effectiveness of vaccination in England and Wales. Vaccine. 2001;19(23–24):3076–90.
Pellissier JM, Brisson M, Levin MJ. Evaluation of the cost-effectiveness in the United States of a vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. Vaccine. 2007;25(49):8326–37.
Belchior E, Lévy-Bruhl D, Le Strat Y, Herida M. Cost-effectiveness of a herpes zoster vaccination program among the French elderly people. Hum Vaccines Immunother. 2016;12(9):2378–82.
Van Hoek A, Gay N, Melegaro A, Opstelten W, Edmunds W. Estimating the cost-effectiveness of vaccination against herpes zoster in England and Wales. Vaccine. 2009;27(9):1454–67.
van Lier A, van Hoek AJ, Opstelten W, Boot HJ, de Melker HE. Assessing the potential effects and cost-effectiveness of programmatic herpes zoster vaccination of elderly in the Netherlands. BMC Health Serv Res. 2010;10(1):237.
Najafzadeh M, Marra CA, Galanis E, Patrick DM. Cost effectiveness of herpes zoster vaccine in Canada. Pharmacoeconomics. 2009;27(12):991–1004.
Bilcke J, Marais C, Ogunjimi B, Willem L, Hens N, Beutels P. Cost-effectiveness of vaccination against herpes zoster in adults aged over 60 years in Belgium. Vaccine. 2012;30(3):675–84.
de Boer PT, Pouwels KB, Cox JM, Hak E, Wilschut JC, Postma MJ. Cost-effectiveness of vaccination of the elderly against herpes zoster in The Netherlands. Vaccine. 2013;31(9):1276–83.
Hoshi S-L, Kondo M, Okubo I. Cost-effectiveness of varicella vaccine against herpes zoster and post-herpetic neuralgia for elderly in Japan. Vaccine. 2017;35(24):3264–71.
Brisson M, Pellissier JM, Camden S, Quach C, De Wals P. The potential cost-effectiveness of vaccination against herpes zoster and post-herpetic neuralgia. Hum Vaccines. 2008;4(3):238–45.
Oxman M, Levin M, Johnson G, Schmader K, Straus S, Gelb L, et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med. 2005;352(22):2271–84.
Schmader KE, Levin MJ, Gnann JW Jr, McNeil SA, Vesikari T, Betts RF, et al. Efficacy, safety, and tolerability of herpes zoster vaccine in persons aged 50–59 years. Clin Infect Dis. 2012;54(7):922–8.
Brisson M, Pellissier JM, Levin MJ. Cost-effectiveness of herpes zoster vaccine: flawed assumptions regarding efficacy against postherpetic neuralgia. Clin Infect Dis. 2007;45(11):1527–9.
Hornberger J, Robertus K. Cost-effectiveness of a vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. Ann Intern Med. 2006;145(5):317–25.
Li X, Zhang JH, Betts RF, Morrison VA, Xu R, Itzler RF, et al. Modeling the durability of ZOSTAVAX(R) vaccine efficacy in people ≥ 60 years of age. Vaccine. 2015;33(12):1499–505.
Chlibek R, Smetana J, Pauksens K, Rombo L, Van den Hoek JA, Richardus JH, et al. Safety and immunogenicity of three different formulations of an adjuvanted varicella-zoster virus subunit candidate vaccine in older adults: a phase II, randomized, controlled study. Vaccine. 2014;32(15):1745–53.
Bell CM, Urbach DR, Ray JG, Bayoumi A, Rosen AB, Greenberg D, et al. Bias in published cost effectiveness studies: systematic review. BMJ (Clinical research ed). 2006;332(7543):699–703.
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AD conducted the literature search. ETC, VTN, and LZ independently reviewed papers, extracted and analyzed data. Disagreement was resolved by discussing with PL. All authors contributed to the interpretation of results and report writing. PL acts as the guarantor. All authors approved the final version of the manuscript as submitted.
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No funding was received for this study or manuscript.
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Abhishek Deshpande is on the Speaker Bureau (non-product) for Merck. Other authors (Edward T. Chiyaka, Van T. Nghiem, Lu Zhang, Patricia D. Mullen, and Phuc Le) declare that they have no conflict of interest.
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Chiyaka, E.T., Nghiem, V.T., Zhang, L. et al. Cost-Effectiveness of Herpes Zoster Vaccination: A Systematic Review. PharmacoEconomics 37, 169–200 (2019). https://doi.org/10.1007/s40273-018-0735-1
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DOI: https://doi.org/10.1007/s40273-018-0735-1