Applied Health Economics and Health Policy

, Volume 11, Issue 1, pp 65–78 | Cite as

Cost-Effectiveness Analysis of Boceprevir for the Treatment of Chronic Hepatitis C Virus Genotype 1 Infection in Portugal

  • Elamin H. Elbasha
  • Jagpreet Chhatwal
  • Shannon A. Ferrante
  • Antoine C. El Khoury
  • Pedro A. Laires
Original Research Article



The recent approval of two protease inhibitors, boceprevir and telaprevir, is likely to change the management of chronic hepatitis C virus (HCV) genotype 1 infection.


We evaluated the long-term clinical outcomes and the cost effectiveness of therapeutic strategies using boceprevir with peginterferon plus ribavirin (PR) in comparison with PR alone for treating HCV genotype 1 infection in Portugal.


A Markov model was developed to project the expected lifetime costs and quality-adjusted life-years (QALYs) associated with PR alone and the treatment strategies outlined by the European Medicines Agency in the boceprevir summary of product characteristics. The boceprevir-based therapeutic strategies differ according to whether or not the patient was previously treated and whether or not the patient had compensated cirrhosis. The model simulated the experience of a series of cohorts of chronically HCV-infected patients (each defined by age, sex, race and fibrosis score). All treatment-related inputs were obtained from boceprevir clinical trials – SPRINT-2, RESPOND-2 and PROVIDE. Estimates of the natural history parameters and health state utilities were based on published studies. Portugal-specific annual direct costs of HCV health states were estimated by convening a panel of experts to derive health state resource use and multiplying the results by national unit costs. The model was developed from a healthcare system perspective with a timeframe corresponding to the remaining duration of the patients’ lifetimes. Both future costs and QALYs were discounted at 5 %. To test the robustness of the conclusions, we conducted deterministic and probabilistic sensitivity analyses.


In comparison with the treatment with PR alone, boceprevir-based regimens were projected to reduce the lifetime incidence of advanced liver disease, liver transplantation, and liver-related death by 45–51 % and increase life expectancy by 2.3–4.3 years. Although the addition of BOC increased treatment costs by €13,300–€19,700, the reduction of disease burden resulted in a decrease of €5,400–€9,000 in discounted health state costs and an increase of 0.68–1.23 in discounted QALYs per patient. The incremental cost-effectiveness ratios of the boceprevir-based regimens compared with PR among previously untreated and previously treated patients were €11,600/QALY and €8,700/QALY, respectively. The results were most sensitive to variations in sustained virologic response rates, discount rates and age at treatment.


Adding boceprevir to PR was projected to reduce the number of liver complications and liver-related deaths, and to be cost effective in treating both previously untreated and treated patients.



The authors would like to thank Drs John R. Cook and Erik J. Dasbach (Merck) for providing helpful suggestions during model development and Jane Liao (Merck) for providing programming support in the analysis of data from SPRINT-2 and RESPOND-2 studies. The authors would also like to acknowledge the contribution of a panel of eight anonymous Portuguese clinical experts in estimating resource use. All panel members received compensation for their participation, and some members had received speaker’s and investigator’s fees from MSD Portugal in the past.


This study was sponsored by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ, USA. Dr. Chhatwal was a former employee of and has received consulting fees from Merck. Dr. El Khoury was a former employee and Drs Elbasha, Ferrante and Laires are current employees of Merck and all hold stocks and/or stock options.

Author contributions

E.H. Elbasha, J. Chhatwal, S.A. Ferrante and A.C. El Khoury developed the model. P.A. Laires contributed to data collection and analysis. All authors provided critical input to the draft. All authors reviewed the final draft and agree with its content. E.H. Elbasha is a guarantor for the overall content.

Supplementary material

40258_2012_7_MOESM1_ESM.pdf (266 kb)
Supplementary material 1 (PDF 114 kb)


  1. 1.
    World Health Organization. Hepatitis C. Fact sheet N°164, June 2011. [Accessed 27 Mar 2012].
  2. 2.
    Marinho R, Giria J, Ferrinho P, Moura MC. Epidemiological aspects of hepatitis C in Portugal. J Gastroenterol Hepatol. 2001;16:1076–7.PubMedCrossRefGoogle Scholar
  3. 3.
    Simmonds P, Bukh J, Combet C, Deleage G, Enomoto N, Feinstone S, et al. Consensus proposals for a unified system of nomenclature of hepatitis C virus genotypes. Hepatology. 2005;42:962–73.PubMedCrossRefGoogle Scholar
  4. 4.
    Cornberg M, Razavi HA, Alberti A, et al. A systematic review of hepatitis C virus epidemiology in Europe, Canada and Israel. Liver Int. 2011;31(Suppl. 2):30–60.PubMedCrossRefGoogle Scholar
  5. 5.
    Direcção Geral de Saúde. Incidência da Hepatite C. In: Plano Nacional de Saúde 2004/2010. Vol I – Prioridades. Ministério da Saúde 2011. [Accessed 2012 Dec 12].
  6. 6.
    Seeff LB. Natural history of hepatitis C. Hepatology Rev. 2005;2:88–96.Google Scholar
  7. 7.
    Strader DB, Wright T, Thomas DL, Seeff LB. Diagnosis, management, and treatment of hepatitis C. Hepatology. 2004;39:1147–71.PubMedCrossRefGoogle Scholar
  8. 8.
    Vieira AM, Freire R, Mangualde J, et al. Hepatite C: casuística da consulta de hepatologia de um hospital distrital. GE - J Port Gastrenterol. 2007;14:134–40.Google Scholar
  9. 9.
    Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N England J Med. 2002;347(13):975–82.CrossRefGoogle Scholar
  10. 10.
    Hadziyannis SJ, Sette H Jr, Morgan TR, et al. Peginterferon-α2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med. 2004;140(5):346–55.PubMedCrossRefGoogle Scholar
  11. 11.
    Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358(9286):958–65.PubMedCrossRefGoogle Scholar
  12. 12.
    Asselah T, Marcellin P. New direct-acting antivirals’ combination for the treatment of chronic hepatitis C. Liver Int. 2011;31(1):68–77.PubMedCrossRefGoogle Scholar
  13. 13.
    Poordad F, McCone J Jr, Bacon BR, SPRINT-2 Investigators, et al. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med. 2011;364(13):1195–206.PubMedCrossRefGoogle Scholar
  14. 14.
    Bacon BR, Gordon SC, Lawitz E, HCV RESPOND-2 Investigators, et al. Boceprevir for previously treated chronic HCV genotype 1 infection. N Engl J Med. 2011;364(13):1207–17.PubMedCrossRefGoogle Scholar
  15. 15.
    Jensen DM. A new era of HCV therapy begins. N Engl J Med. 2011;364:1272–4.PubMedCrossRefGoogle Scholar
  16. 16.
    Ferrante SA, Chhatwal J, Elbasha E, Dasbach E, Bronowicki J-P, Poordad F, et al. Cost-effectiveness of boceprevir based regimens in previously untreated adult subjects with chronic hepatitis C genotype 1. Hepatology. 2011;54(S1):795A–6A.Google Scholar
  17. 17.
    Chhatwal J, Ferrante SA, Dasbach E, El Khoury A, Brass C, Burroughs M, et al. Cost-effectiveness of boceprevir use in patients with chronic hepatitis C genotype-1 who failed prior treatment with peginterferon/ribavirin. Hepatology. 2012;54(S1):801A–2A.Google Scholar
  18. 18.
    Buti M, Medina M, Casado MA, Wong JB, Fosbrook L, Esteban R. A cost-effectiveness analysis of peginterferon alfa-2b plus ribavirin for the treatment of naive patients with chronic hepatitis C. Aliment Pharmacol Ther. 2003;17(5):687–94.PubMedCrossRefGoogle Scholar
  19. 19.
    Salomon JA, Weinstein MC, Hammitt JK, Goldie SJ. Cost-effectiveness of treatment for chronic hepatitis C infection in an evolving patient population. JAMA. 2003;290(2):228–37.PubMedCrossRefGoogle Scholar
  20. 20.
    Siebert U, Sroczynski G, Rossol S, Wasem J, Ravens-Sieberer U, Kurth BM, German Hepatitis C Model (GEHMO) Group; International Hepatitis Interventional Therapy (IHIT) Group, et al. Cost effectiveness of peginterferon-2b plus ribavirin versus interferon-2b plus ribavirin for initial treatment of chronic hepatitis C. Gut. 2003;52(3):425–32.PubMedCrossRefGoogle Scholar
  21. 21.
    Sullivan SD, Craxi A, Alberti A, Giuliani G, De Carli C, Wintfeld N, et al. Cost effectiveness of peginterferon alpha-2a plus ribavirin versus interferon alpha-2b plus ribavirin as initial therapy for treatment-naive chronic hepatitis C. Pharmacoeconomics. 2004;22(4):257–65.PubMedCrossRefGoogle Scholar
  22. 22.
    Younossi ZM, Singer ME, McHutchison JG, Shermock KM. Cost effectiveness of interferon 2b combined with ribavirin for the treatment of chronic hepatitis C. Hepatology. 1999;30(5):1318–24.PubMedCrossRefGoogle Scholar
  23. 23.
    Cardoso AC, Moucari R, Figueiredo-Mendes C, Ripault MP, Giuily N, Castelnau C, et al. Impact of peginterferon and ribavirin therapy on hepatocellular carcinoma: incidence and survival in hepatitis C patients with advanced fibrosis. J Hepatol. 2010;52:652–7.PubMedCrossRefGoogle Scholar
  24. 24.
    European Medicines Agency. Annex I. summary of product characteristics. [Accessed 27 Mar 2012].
  25. 25.
    Dieterich DT, Rizzetto M, Manns MP. Management of chronic HCV: definition of relapse and nonresponse. J Viral Hepat. 2009;16(12):833–43.PubMedCrossRefGoogle Scholar
  26. 26.
    Velosa J, Serejo F, Bana T, Redondo I, Simão A, et al. Chronic hepatitis C treated with peginterferon alfa plus ribavirin in clinical practice. Hepatogastroenterology. 2011;58(109):1260–6.PubMedCrossRefGoogle Scholar
  27. 27.
    Areias J, Gomes H, Mocho ML, et al. Epidemiological characterization of chronic hepatitis C in Portugal. XXI Annual Congress of the “Fundacion y Associacion Espanola para el estudio del higado”, 15–17 Feb 2006; Madrid, Spain.Google Scholar
  28. 28.
    Vierling JM, Flamm SL, Gordon SC, Lawitz E, Bronowicki J, Davis M, et al. Efficacy of boceprevir in prior null responders to peginterferon/ribavirin: the PROVIDE study. Hepatology. 2011;54(Suppl):796A.Google Scholar
  29. 29.
    Poynard T, Colombo M, Bruix J, Schiff E, Terg R, Flamm S, et al. Peginterferon alfa-2b and ribavirin: effective in patients with hepatitis C who failed interferon alfa/ribavirin therapy. Gastroenterology. 2009;136:1618–28.PubMedCrossRefGoogle Scholar
  30. 30.
    Instituto Nacional de Estatistica, Statistics Portugal. Portuguese Life Table 2007–2009. [Accessed 1 Jun 2010].
  31. 31.
    Infarmed, Prontuário Terapêutico On-Line. 2011. [Accessed 27 Mar 2012].
  32. 32.
    Ministério da Saúde, Diário da República—I Série, n°16 (Portaria n° 110-A/2011) de 23 de Janeiro de 2011.Google Scholar
  33. 33.
    ACSS –online catalogue. [Accessed 27 Mar 2012].
  34. 34.
    Data on file, MSD Portugal, 2010.Google Scholar
  35. 35.
    INFARMED. Guidelines for Economic Drug Evaluation Studies. Nov 1998. Published in Despacho n° 19064/99; 9 Sep 1999. Google Scholar
  36. 36.
    Weinstein MC, Toy EL, Sandberg EA, et al. Modeling for health care and other policy decisions: uses, roles, and validity. Value Health. 2001;4(5):348–61.PubMedCrossRefGoogle Scholar
  37. 37.
    Wright M, Grieve R, Roberts J, Main J, Thomas HC; UK Mild Hepatitis C Trial Investigators. Health benefits of antiviral therapy for mild chronic hepatitis C: randomised controlled trial and economic evaluation. Health Technol Assess 2006;10:1–113, iii.Google Scholar
  38. 38.
    Wilson J, Yao GL, Raftery J, Bohlius J, Brunskill S, Sandercock J et al. A systematic review and economic evaluation of epoetin alfa, epoetin beta and darbepoetin alfa in anaemia associated with cancer, especially that attributable to cancer treatment. Health Technol Assess 2007;11:iii–120.Google Scholar
  39. 39.
    Chong CA, Gulamhussein A, Heathcote EJ, Lilly L, Sherman M, Naglie G, Krahn M. Health-state utilities and quality of life in hepatitis C patients. Am J Gastroenterol. 2003;98:630–8.PubMedCrossRefGoogle Scholar
  40. 40.
    Fenwick E, Claxton K, Sculpher M. Representing uncertainty: the role of cost-effectiveness acceptability curves. Health Econ. 2001;10:779–87.PubMedCrossRefGoogle Scholar
  41. 41.
    El-Kamary SS, Jhaveri R, Shardell MD. All-cause, liver-related, and nonliver-related mortality among HCV-infected individuals in the general US population. Clin Infect Dis. 2011;53:150–7.PubMedCrossRefGoogle Scholar
  42. 42.
    Butt AA, Kanwal F. Boceprevir and telaprevir in the management of hepatitis C virus-infected patients. Clin Infect Dis. 2012;54(1):96–104.PubMedCrossRefGoogle Scholar
  43. 43.
    World Health Organization. Macroeconomics and health: investing in health for economic development: Report for the Commission on Macroeconomics and Health, Geneva, Switzerland, 2001.Google Scholar
  44. 44.
    Sroczynski G, Esteban E, Conrads-Frank A, Schwarzer R, Mühlberger N, Wright D, et al. Long-term effectiveness and cost-effectiveness of antiviral treatment in hepatitis C. J Viral Hepat. 2010;17(1):34–50.PubMedCrossRefGoogle Scholar
  45. 45.
    Liu S, Cipriano LE, Holodniy M, Owens DK, Goldhaber-Fiebert JD. New protease inhibitors for the treatment of chronic hepatitis C: a cost-effectiveness analysis. Ann Intern Med. 2012;156(4):279–90.PubMedCrossRefGoogle Scholar
  46. 46.
    Cammà C, Petta S, Enea M, Bruno R, Bronte F, Capursi V, et al.; on behalf of the WEF Study Group. Cost-effectiveness of boceprevir or telaprevir for untreated patients with genotype 1 chronic hepatitis C. Hepatology 2012 Mar 27. doi: 10.1002/hep.25734 [Epub ahead of print].
  47. 47.
    Arase Y, Suzuki F, Suzuki Y, et al. Sustained virological response reduces incidence of onset of type 2 diabetes in chronic hepatitis C. Hepatology. 2009;49:739–44.PubMedCrossRefGoogle Scholar
  48. 48.
    Pearlman B, Traub N. Sustained virologic response to antiviral therapy for chronic hepatitis C virus infection: a cure and so much more. Clin Infect Dis. 2011;52:889–900.PubMedCrossRefGoogle Scholar
  49. 49.
    Butt AA, Wang X, Moore CM. Effect of HCV and its treatment upon survival. Hepatology. 2009;50:387–92.PubMedCrossRefGoogle Scholar
  50. 50.
    Papatheodoridis GV, Papadimitropoulos VC, Hadziyannis SJ. Effect of interferon therapy on the development of hepatocellular carcinoma in patients with hepatitis C virus-related cirrhosis: a meta-analysis. Aliment Pharmacol Ther. 2001;15:689–98.PubMedCrossRefGoogle Scholar
  51. 51.
    Rothwell PM. Subgroup analysis in randomised controlled trials: importance, indications, and interpretation. Lancet. 2005;365:176–86.PubMedCrossRefGoogle Scholar
  52. 52.
    Thein HH, Yi Q, Dore GJ, Krahn MD. Estimation of stage-specific fibrosis progression rates in chronic hepatitis C virus infection: a meta-analysis and meta-regression. Hepatology. 2008;48(2):418–31.PubMedCrossRefGoogle Scholar
  53. 53.
    Benvegnù L, Noventa F, Bernardinello E, Pontisso P, Gatta A, Alberti A. Evidence for an association between the aetiology of cirrhosis and pattern of hepatocellular carcinoma development. Gut. 2001;48(1):110–5.PubMedCrossRefGoogle Scholar
  54. 54.
    Fattovich G, Giustina G, Degos F, Tremolada F, Diodati G, Almasio P, Nevens F, et al. Morbidity and mortality in compensated cirrhosis type C: a retrospective follow-up study of 384 patients. Gastroenterology. 1997;112:463–72.PubMedCrossRefGoogle Scholar
  55. 55.
    Gentilini P, Laffi G, La Villa G, Romanelli RG, Buzzelli G, Casini-Raggi V, et al. Long course and prognostic factors of virus-induced cirrhosis of the liver. Am J Gastroenterol. 1997;92(1):66–72.PubMedGoogle Scholar
  56. 56.
    Sangiovanni A, Prati GM, Fasani P, Ronchi G, Romeo R, Manini M, et al. The natural history of compensated cirrhosis due to hepatitis C virus: a 17 year cohort study of 214 patients. Hepatology. 2006;43:1303–10.PubMedCrossRefGoogle Scholar
  57. 57.
    Serfaty L, Aumaître H, Chazouillères O, Bonnand AM, Rosmorduc O, Poupon RE, Poupon R. Determinants of outcome of compensated hepatitis C virus-related cirrhosis. Hepatology. 1998;27:1435–40.PubMedCrossRefGoogle Scholar
  58. 58.
    Bruno S, Silini E, Crosignani A, Borzio F, Leandro G, Bono F, et al. Hepatitis C virus genotypes and risk of hepatocellular carcinoma in cirrhosis: a prospective study. Hepatology. 1997;25:754–8.PubMedCrossRefGoogle Scholar
  59. 59.
    Tsukuma H, Hiyama T, Tanaka S, Nakao M, Yabuuchi T, Kitamura T, et al. Risk factors for hepatocellular carcinoma among patients with chronic liver disease. N Engl J Med. 1993;328(25):1797–801.PubMedCrossRefGoogle Scholar
  60. 60.
    Tateyama M, Yatsuhashi H, Taura N, Motoyoshi Y, Nagaoka S, Yanagi K, et al. Alpha-fetoprotein above normal levels as a risk factor for the development of hepatocellular carcinoma in patients infected with hepatitis C virus. J Gastroenterol. 2011;46(1):92–100.PubMedCrossRefGoogle Scholar
  61. 61.
    Yoshida H, Shiratori Y, Moriyama M, Arakawa Y, Ide T, Sata M, Inoue O, et al. Interferon therapy reduces the risk for hepatocellular carcinoma: national surveillance program of cirrhotic and noncirrhotic patients with chronic hepatitis C in Japan. IHIT Study Group. Inhibition of Hepatocarcinogenesis by Interferon Therapy. Ann Intern Med. 1999;131(3):174–81.PubMedCrossRefGoogle Scholar
  62. 62.
    Planas R, Ballesté B, Alvarez MA, et al. Natural history of decompensated hepatitis C virus-related cirrhosis: a study of 200 patients. J Hepatol. 2004;40(5):823–30.PubMedCrossRefGoogle Scholar
  63. 63.
    Thuluvath PJ, Guidinger MK, Fung JJ, Johnson LB, Rayhill SC, Pelletier SJ. Liver transplantation in the United States, 1999–2008. Am J Transplant. 2010;10(4 Pt 2):1003–19.PubMedCrossRefGoogle Scholar
  64. 64.
    Davis GL, Alter MJ, El-Serag H, Poynard T, Jennings LW. Aging of hepatitis C virus (HCV)-infected persons in the United States: a multiple cohort model of HCV prevalence and disease progression. Gastroenterology. 2010;138(2):513–21.PubMedCrossRefGoogle Scholar
  65. 65.
    Lang K, Danchenko N, Gondek K, Shah S, Thompson D. The burden of illness associated with hepatocellular carcinoma in the United States. J Hepatol. 2009;50(1):89–99.PubMedCrossRefGoogle Scholar
  66. 66.
    Saab S, Hunt DR, Stone MA, McClune A, Tong MJ. Timing of hepatitis C antiviral therapy in patients with advanced liver disease: a decision analysis model. Liver Transpl. 2010;16(6):748–59.PubMedGoogle Scholar
  67. 67.
    Wolfe RA, Roys EC, Merion RM. Trends in organ donation and transplantation in the United States, 1999–2008. Am J Transplant. 2010;10(4 Pt 2):961–72.PubMedCrossRefGoogle Scholar
  68. 68.
    ACSS – Catálogo. Disponível em: [Accessed 27 Mar 2012].
  69. 69.
    Data on file, Merck Sharp & Dohme (MSD).Google Scholar
  70. 70.
    Base de Dados do INFARMED – Infomed. [Accessed 27 Mar 2012].
  71. 71.
    Portaria n.º 132/2009, de 30 de Janeiro - Alterada pela Portaria n.º 839 -A/2009, de 31 de Julho, e pela Portaria n.º 19/2012, de 20 de Janeiro. [Accessed 27 Mar 2012].

Copyright information

© Springer International Publishing Switzerland 2013

Authors and Affiliations

  • Elamin H. Elbasha
    • 1
    • 4
  • Jagpreet Chhatwal
    • 2
  • Shannon A. Ferrante
    • 1
  • Antoine C. El Khoury
    • 1
  • Pedro A. Laires
    • 3
  1. 1.Merck Sharp & Dohme Corp.Whitehouse StationUSA
  2. 2.University of PittsburghPAUSA
  3. 3.MSD PortugalOeirasPortugal
  4. 4.Merck & Co., Inc., UG1C-60North WalesUSA

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