Skip to main content
Log in

Systematic Review of Modelling Approaches for the Cost Effectiveness of Hepatitis C Treatment with Direct-Acting Antivirals

  • Systematic Review
  • Published:
PharmacoEconomics Aims and scope Submit manuscript

Abstract

Background

New direct-acting antivirals (DAAs) are highly effective for hepatitis C virus (HCV) treatment. However, their prices have been widely debated. Decision-analytic models can project the long-term value of HCV treatment. Therefore, understanding of the methods used in these models and how they could influence results is important.

Objective

Our objective was to describe and systematically review the methodological approaches in published cost-effectiveness models of chronic HCV treatment with DAAs.

Data Sources

We searched several electronic databases, including Medline, Embase and EconLit, from 2011 to 2015.

Study Eligibility

Study selection was performed by two reviewers independently. We included any cost-effectiveness analysis comparing DAAs with the old standard of care for HCV treatment. We excluded non-English-language studies and studies not reporting quality-adjusted life-years.

Study Appraisal and Synthesis Method

One reviewer collected data and assessed the quality of reporting, using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement. Another reviewer crosschecked the abstracted information. The development methods of the included studies were synthetized on the basis of good modelling practice recommendations.

Results

Review of 304 citations revealed 36 cost-effectiveness analyses. The reporting quality scores of most articles were rated as acceptable, between 67 and 100 %. The majority of the studies were conducted in Europe (50 %), followed by the USA (44 %). Fifty-six percent of the 36 studies evaluated the cost effectiveness of HCV treatment in both treatment-naive and treatment-experienced patients, 97 % included genotype 1 patients and 53 % evaluated the cost effectiveness of second-generation or oral DAAs in comparison with the previous standard of care or other DAAs. Twenty-one models defined health states in terms of METAVIR fibrosis scores. Only one study used a discrete-event simulation approach, and the remainder used state-transition models. The time horizons varied; however, 89 % of studies used a lifetime horizon. One study was conducted from a societal perspective. Thirty-three percent of studies did not conduct any model validation. We also noted that none of the studies modelled HCV treatment as a prevention strategy, 86 % of models did not consider the possibility of re-infection with HCV after successful treatment, 97 % of studies did not consider indirect economic benefits resulting from HCV treatment and none of the studies evaluating oral DAAs used real-world data.

Limitations

The search was limited by date (from 1 January 2011 to 8 September 2015) and was also limited to English-language and published reports.

Conclusions

Most modelling studies used a similar modelling structure and could have underestimated the value of HCV treatment. Future modelling efforts should consider the benefits of HCV treatment in preventing transmission, extra-hepatic and indirect economic benefits of HCV treatment, real-world cost-effectiveness analysis and cost effectiveness of HCV treatment in low- and middle-income countries.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. World Health Organization. Hepatitis C fact sheet. World Health Organization. 2015. http://www.who.int/mediacentre/factsheets/fs164/en. Accessed 8 Jun 2015.

  2. Rosen HR. Chronic hepatitis C infection. N Engl J Med. 2011;364(25):2429–38.

    Article  CAS  PubMed  Google Scholar 

  3. Denniston MM, et al. Chronic hepatitis C virus infection in the United States, National Health and Nutrition Examination Survey 2003 to 2010. Ann Intern Med. 2014;160(5):293–300.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Pearlman BL, 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(7):889–900.

    Article  PubMed  Google Scholar 

  5. Poordad F, et al. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med. 2011;364(13):1195–206.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Drenth JP. HCV treatment—no more room for interferonologists? N Engl J Med. 2013;368(20):1931–2.

    Article  CAS  PubMed  Google Scholar 

  7. Afdhal N, et al. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med. 2014;370(16):1483–93.

    Article  CAS  PubMed  Google Scholar 

  8. Kabiri M, et al. The changing burden of hepatitis C in the United States: model-based predictions. Ann Intern Med. 2014;161(3):170–80.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Razavi H, et al. Chronic hepatitis C virus (HCV) disease burden and cost in the United States. Hepatology. 2013;57(6):2164–70.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Hoofnagle JH, Sherker AH. Therapy for hepatitis C—the costs of success. N Engl J Med. 2014;370:1552–3.

    Article  CAS  PubMed  Google Scholar 

  11. Silverman E. ‘Unsustainable for our country’: Express Scripts calls out pricey meds. Wall Street Journal. 2014. http://blogs.wsj.com/corporate-intelligence/2014/04/08/unsustainable-for-our-country-express-scripts-calls-out-pricey-meds. Accessed 11 Apr 2014.

  12. First DataBank, Inc. Drug pricing policy. First DataBank, Inc. 2014. http://www.firstdatabank.com/Support/drug-pricing-policy.aspx. Accessed 6 Mar 2014.

  13. Chhatwal J, Mathisen M, Kantarjian HM. Are high drug prices of hematologic malignancies justified? A critical analysis. Cancer. 2015;121(19):3372–9.

    Article  PubMed  Google Scholar 

  14. Moher D, et al. Preferred Reporting Items for Systematic Reviews and Meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151(4):264–9.

    Article  PubMed  Google Scholar 

  15. Siebert U, et al. Systematic assessment of decision models in Parkinson’s disease. Value Health. 2004;7(5):610–26.

    Article  PubMed  Google Scholar 

  16. Rochau U, et al. Systematic assessment of decision-analytic models for chronic myeloid leukemia. Appl Health Econ Health Policy. 2014;12(2):103–15.

    Article  PubMed  Google Scholar 

  17. Caro JJ, et al. Modeling good research practices—overview. Med Decis Making. 2012;32(5):667–77.

    Article  PubMed  Google Scholar 

  18. Husereau D, et al. Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement. Pharmacoeconomics. 2013;31(5):361–7.

    Article  PubMed  Google Scholar 

  19. Linas BP, et al. The cost-effectiveness of sofosbuvir-based regimens for treatment of hepatitis c virus genotype 2 or 3 infection. Ann Intern Med. 2015;162(9):619–29.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Cure S, et al. Cost-effectiveness of telaprevir in combination with pegylated interferon alpha and ribavirin in treatment-experienced chronic hepatitis C genotype 1 patients. J Med Econ. 2014;17(1):77–87.

    Article  PubMed  Google Scholar 

  21. Cure S, et al. Cost-effectiveness of telaprevir in combination with pegylated interferon alpha and ribavirin in previously untreated chronic hepatitis C genotype 1 patients. J Med Econ. 2014;17(1):65–76.

    Article  PubMed  Google Scholar 

  22. Cure S, et al. Cost-effectiveness of sofosbuvir plus ribavirin with or without pegylated interferon for the treatment of chronic hepatitis C in Italy. J Med Econ. 2015;18(9):678–90.

    Article  PubMed  Google Scholar 

  23. Zhang S, Bastian ND, Griffin PM. Cost-effectiveness of sofosbuvir-based treatments for chronic hepatitis C in the US. BMC Gastroenterol. 2015;15:98.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Petta S, et al. Personalized cost-effectiveness of boceprevir-based triple therapy for untreated patients with genotype 1 chronic hepatitis C. Dig Liver Dis. 2014;46(10):936–42.

    Article  PubMed  Google Scholar 

  25. Petta S, et al. Cost-effectiveness of sofosbuvir-based triple therapy for untreated patients with genotype 1 chronic hepatitis C. Hepatology. 2014;59(5):1692–705.

    Article  PubMed  Google Scholar 

  26. Thein H, et al. 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.

    Article  PubMed  Google Scholar 

  27. Najafzadeh M, et al. Cost-effectiveness of novel regimens for the treatment of hepatitis C virus. Ann Intern Med. 2015;162(6):407–19.

    Article  PubMed  Google Scholar 

  28. Camma C, et al. Cost-effectiveness of boceprevir or telaprevir for untreated patients with genotype 1 chronic hepatitis C. Hepatology. 2012;56(3):850–60.

    Article  PubMed  Google Scholar 

  29. Chhatwal J, et al. Cost-effectiveness and budget impact of hepatitis C virus treatment with sofosbuvir and ledipasvir in the United States. Ann Intern Med. 2015;162(6):397–406.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Linas BP, et al. The cost-effectiveness of improved hepatitis C virus therapies in HIV/hepatitis C virus coinfected patients. Aids. 2014;28(3):365–76.

    Article  PubMed  Google Scholar 

  31. Rein DB, et al. The cost-effectiveness, health benefits, and financial costs of new antiviral treatments for hepatitis C virus. Clin Infect Dis. 2015;61(2):157–68.

    Article  PubMed  Google Scholar 

  32. Tice JA, Ollendorf DA, Pearson SD. The comparative clinical effectiveness and value of simeprevir and sofosbuvir in the treatment of chronic hepatitis C infection: a technology assessment. Boston: Institute for Clinical and Economic Review; 2014. p. 118.

    Google Scholar 

  33. Hagan LM, Sulkowski MS, Schinazi RF. Cost analysis of sofosbuvir/ribavirin versus sofosbuvir/simeprevir for genotype 1 hepatitis C virus in interferon-ineligible/intolerant individuals. Hepatology. 2014;60(1):37–45.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Warren E, Wright A, Jones B. Cost-effectiveness of telaprevir in patients with genotype 1 hepatitis C in Australia. Value Health. 2014;17(8):792–800.

    Article  PubMed  Google Scholar 

  35. Vellopoulou A, et al. Cost utility of telaprevir–PR (peginterferon–ribavirin) versus boceprevir–PR and versus PR alone in chronic hepatitis C in the Netherlands. Appl Health Econ Health Policy. 2014;12(6):647–59.

    Article  PubMed  Google Scholar 

  36. Pitman R, et al. Dynamic transmission modeling: a report of the ISPOR–SMDM Modeling Good Research Practices Task Force–5. Value Health. 2012;15(6):828–34.

    Article  PubMed  Google Scholar 

  37. Chhatwal J, He T. Economic evaluations with agent-based modelling: an introduction. Pharmacoeconomics. 2015;33(5):423–33.

    Article  PubMed  Google Scholar 

  38. Liu S, et al. Sofosbuvir-based treatment regimens for chronic, genotype 1 hepatitis C virus infection in US incarcerated populations: a cost-effectiveness analysis. Ann Intern Med. 2014;161(8):546–53.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Cure S, Guerra I, Dusheiko G. Cost-effectiveness of sofosbuvir for the treatment of chronic hepatitis C-infected patients. J Viral Hepat. 2015;22(11):882–9.

    Article  CAS  PubMed  Google Scholar 

  40. Pfeil AM, et al. Cost-effectiveness analysis of sofosbuvir compared to current standard treatment in Swiss patients with chronic hepatitis C. PLoS One. 2015;10(5):e0126984.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Briggs AH, et al. Model parameter estimation and uncertainty analysis. Med Decis Making. 2012;32(5):722–32.

    Article  PubMed  Google Scholar 

  42. Hagan LM, et al. All-oral, interferon-free treatment for chronic hepatitis C: cost-effectiveness analyses. J Viral Hepat. 2013;20(12):847–57.

    Article  CAS  PubMed  Google Scholar 

  43. Athanasakis K, et al. Boceprevir for chronic genotype 1 hepatitis C virus in the current health care setting in Greece: a cost-effectiveness analysis. Clin Ther. 2015;37(7):1529–40.

    Article  CAS  PubMed  Google Scholar 

  44. Eddy DM, et al. Model transparency and validation: a report of the ISPOR–SMDM Modeling Good Research Practices Task Force–7. Med Decis Making. 2012;32(5):733–43.

    Article  PubMed  Google Scholar 

  45. Chan K, et al. Cost effectiveness of direct-acting antiviral therapy for treatment-naive patients with chronic HCV genotype 1 infection in the Veterans Health Administration. Clin Gastroenterol Hepatol. 2013;11(11):1503–10.

    Article  PubMed  Google Scholar 

  46. Camma C, et al. Cost-effectiveness of boceprevir or telaprevir for previously treated patients with genotype 1 chronic hepatitis C. J Hepatol. 2013;59(4):658–66.

    Article  PubMed  Google Scholar 

  47. San Miguel R, et al. Cost-effectiveness analysis of sofosbuvir-based regimens for chronic hepatitis C. Gut. 2015;64(8):1277–88.

    Article  PubMed  Google Scholar 

  48. Gimeno-Ballester V, Mar J, San Miguel R. Cost-effectiveness analysis of simeprevir with daclatasvir for non-cirrhotic genotype-1b-naive patients plus chronic hepatitis C. Expert Rev Pharmacoecon Outcomes Res (Epub 2015 Sep 1).

  49. Westerhout K, et al. A cost utility analysis of simeprevir used with peginterferon + ribavirin in the management of genotype 1 hepatitis C virus infection, from the perspective of the UK National Health Service. J Med Econ. 2015;18(10):838–49.

    Article  PubMed  Google Scholar 

  50. Younossi ZM, et al. Cost-effectiveness of all-oral ledipasvir/sofosbuvir regimens in patients with chronic hepatitis C virus genotype 1 infection. Aliment Pharmacol Ther. 2015;41(6):544–63.

    Article  CAS  PubMed  Google Scholar 

  51. Siebert U, et al. State-transition modeling: a report of the ISPOR–SMDM Modeling Good Research Practices Task Force. Med Decis Making. 2012;32(5):690–700.

    Article  PubMed  Google Scholar 

  52. Elbasha EH, Chhatwal J. Theoretical foundations and practical applications of within-cycle correction methods. Med Decis Making. 2016;36(1):115–31.

    Article  PubMed  Google Scholar 

  53. Elbasha EH, Chhatwal J. Theoretical foundations and practical applications of within-cycle correction methods. Med Decis Making. 2016;36(1):115–31.

    Article  PubMed  Google Scholar 

  54. Townsend R, et al. Structural frameworks and key model parameters in cost-effectiveness analyses for current and future treatments of chronic hepatitis C. Value Health. 2011;14(8):1068–77.

    Article  PubMed  Google Scholar 

  55. Takahashi K, et al. Regression of Hodgkin lymphoma in response to antiviral therapy for hepatitis C virus infection. Intern Med. 2012;51(19):2745–7.

    Article  PubMed  Google Scholar 

  56. Terrault N, et al. Treatment outcomes with 8, 12 and 24 week regimens of ledipasvir/sofosbuvir for the treatment of hepatitis C infection: analysis of a multicenter prospective, observational study. The Liver Meeting® 2015. American Association for the Study of Liver Diseases, San Fransisco; 13–17 Nov 2015.

  57. Liu S, et al. New protease inhibitors for the treatment of chronic hepatitis C: a cost-effectiveness analysis. Ann Intern Med. 2012;156(4):279–90.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Blazquez-Perez A, San Miguel R, Mar J. Cost-effectiveness analysis of triple therapy with protease inhibitors in treatment-naive hepatitis C patients. Pharmacoeconomics. 2013;31(10):919–31.

    Article  PubMed  Google Scholar 

  59. Chhatwal J, et al. Cost-effectiveness of boceprevir in patients previously treated for chronic hepatitis C genotype 1 infection in the United States. Value Health. 2013;16(6):973–86.

    Article  PubMed  Google Scholar 

  60. Elbasha EH, et al. Cost-effectiveness analysis of boceprevir for the treatment of chronic hepatitis C virus genotype 1 infection in Portugal. Appl Health Econ Health Policy. 2013;11(1):65–78.

    Article  PubMed  Google Scholar 

  61. Ferrante SA, et al. Boceprevir for previously untreated patients with chronic hepatitis C genotype 1 infection: a US-based cost-effectiveness modeling study. BMC Infect Dis. 2013;13:190.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Brogan AJ, et al. Cost-effectiveness of telaprevir combination therapy for chronic hepatitis C. PLoS One. 2014;9(3):e90295.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Dan YY, et al. Cost-effectiveness of boceprevir co-administration versus pegylated interferon α2b and ribavirin only for patients with hepatitis C genotype 1 in Singapore. Antivir Ther. 2015;20(2):209–16.

    Article  CAS  PubMed  Google Scholar 

  64. Saab S, et al. Cost-effectiveness analysis of sofosbuvir plus peginterferon/ribavirin in the treatment of chronic hepatitis C virus genotype 1 infection. Aliment Pharmacol Ther. 2014;40(6):657–75.

    Article  CAS  PubMed  Google Scholar 

  65. Leleu H, Blachier M, Rosa I. Cost-effectiveness of sofosbuvir in the treatment of patients with hepatitis C. J Viral Hepat. 2015;22(4):376–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Odhiambo R, et al. Economic evaluation of boceprevir for the treatment of patients with genotype 1 chronic hepatitis C virus infection in Hungary. J Health Econ Outcomes Res. 2012;15(7):A390.

    Google Scholar 

Download references

Acknowledgments

The authors thank Greg Pratt, DDS, MLS, for his help in creating the search strategy.

Author contributions

Jagpreet Chhatwal had full access to all of the data in the study and takes responsibility for the integrity and the accuracy of the data analysis.

Design and conduct of the study: Jagpreet Chhatwal, Tianhua He, Maria Lopez-Olivo.

Collection, management, analysis and interpretation of the data: Jagpreet Chhatwal, Tianhua He, Maria Lopez-Olivo.

Preparation, review or approval of the manuscript: Jagpreet Chhatwal, Tianhua He, Maria Lopez-Olivo.

Administrative, technical or material support: Jagpreet Chhatwal, Maria Lopez-Olivo.

Study supervision: Jagpreet Chhatwal.

Conflicts of interest

Jagpreet Chhatwal has received consulting fees from Merck, Gilead and Complete HEOR Solutions outside the scope of this work. Maria Lopez-Olivo has received consulting fees from Complete HEOR Solutions outside the scope of this work. Tianhua He has no conflicts of interest to report.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jagpreet Chhatwal.

Appendix: Medline search strategy [database(s): Ovid Medline® in-process and other non-indexed citations, and Ovid Medline®; searched on 9 Sep 2015]

Appendix: Medline search strategy [database(s): Ovid Medline® in-process and other non-indexed citations, and Ovid Medline®; searched on 9 Sep 2015]

#

Search

1

exp HEPATITIS C/

2

exp HEPACIVIRUS/

3

((hepatitis adj3 “C”) or hepacivir* or HCV).ti,ab

4

or/1–3

5

(telaprevir* or Incivek*).mp

6

(boceprevir* or Victrelis*).mp

7

(simeprevir* or Olysio* or TMC-435* or TMC435* or TMC-435350* or TMC435350*).mp

8

(paritaprevir* or Veruprevir*).mp

9

(asunaprevir* or BMS-650032* or BMS650032*).mp

10

(ledipasvir* or GS-5885* or GS5885*).mp

11

(ombitasvir* or ABT-267* or ABT267*).mp

12

(sofosbuvir* or Sovaldi* or GS-7977* or GS7977* or PSI-7977* or PSI7977*).mp

13

(dasabuvir* or ABT-333* or ABT333*).mp

14

(daclatasvir* or Daklinza*).mp

15

exp PROTEASE INHIBITORS/

16

(protease* adj3 inhibit*).mp

17

(direct* adj3 (anti-viral* or antiviral*)).mp

18

exp ANTIVIRAL AGENTS/and (direct* adj3 (act or acting)).ti,ab

19

or/5–18

20

4 and 19

21

limit 20 to English language

22

limit 21 to yr=“2011 -Current”

23

limit 22 to “review”

24

22 not 23

25

exp HEPATITIS C/ec

26

exp ANTIVIRAL AGENTS/ec

27

exp PROTEASE INHIBITORS/ec

28

exp MODELS, ECONOMIC/

29

exp ECONOMICS/

30

(cost or costs or costing or economi* or budget* or financ* or pharmacoeconom* or pharmacoeconom* or price* or pricing or expenditure* or affordab* or fee or fees or charg* or monetar*).ti,hw,kw

31

(economic* adj2 (burden* or barrier* or restriction* or resources)).ab

32

((cost or costs) adj3 (utilit* or effectiv* or benefit* or minimiz* or minimis* or model*)).ab

33

((decision* or cost*) adj3 (model* or analy*)).ti,ab,sh

34

or/25–33

35

24 and 34

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chhatwal, J., He, T. & Lopez-Olivo, M.A. Systematic Review of Modelling Approaches for the Cost Effectiveness of Hepatitis C Treatment with Direct-Acting Antivirals. PharmacoEconomics 34, 551–567 (2016). https://doi.org/10.1007/s40273-015-0373-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40273-015-0373-9

Keywords

Navigation