Skip to main content
SpringerLink
Log in

Cost Effectiveness of Tenofovir Disoproxil Fumarate for the Treatment of Chronic Hepatitis B from a Canadian Public Payer Perspective

  • Original Research Article
  • Cost Effectiveness of Tenofovir for Chronic Hepatitis B
  • Published:
PharmacoEconomics Aims and scope Submit manuscript

Abstract

Introduction: Previous research has demonstrated that tenofovir disoproxil fumarate (DF) is the most cost-effective nucleos(t)ide treatment for chronic hepatitis B (CHB) in the UK, Spain, Italy and France. However, to our knowledge, no published studies have yet evaluated the cost effectiveness of any treatments for CHB in a Canadian setting, where relative prices and management of CHB differ from those in Europe.

Aim: Our objective was to determine the cost effectiveness of tenofovir DF compared with other nucleos(t)ide therapies licensed for CHB in Canada from the perspective of publicly funded healthcare payers.

Methods: A Markov model was used to calculate the costs and benefits of nucleos(t)ide therapy in three groups of patients with hepatitis B e antigen (HBeAg)-positive and -negative CHB: nucleos(t)ide-naive patients without cirrhosis; nucleos(t)ide-naive patients with compensated cirrhosis; and lamivudine- resistant patients. Disease progression was modelled as annual transitions between 18 disease states. Transition probabilities, quality of life and costs were based on published studies. Health benefits were measured in QALYs. The reference year for costs was 2007 and costs and outcomes were discounted at 5% per annum.

Results: First-line tenofovir DF was the most effective nucleos(t)ide strategy for managing CHB, generating 6.85–9.39 QALYs per patient. First-line tenofovir DF was also the most cost-effective strategy in all patient subgroups investigated, costing between $Can43 758 and $Can48 015 per QALY gained compared with lamivudine then tenofovir. First-line tenofovir DF strongly dominated first-line entecavir. Giving tenofovir DF monotherapy immediately after lamivudine resistance developed was less costly and more effective than any other active treatment strategy investigated for lamivudine-resistant CHB, including second-line use of adefovir or adefovir + lamivudine. Probabilistic sensitivity analysis demonstrated 50% confidence that first-line tenofovir DF is the most cost-effective nucleos(t)ide strategy for treatmentnaive patients with CHB, at a $Can50 000 per QALY threshold, and confirmed that first-line tenofovir DF has the highest expected net benefits.

Conclusions: First-line tenofovir DF appears to be the most cost-effective nucleos(t)ide treatment for both cirrhotic and non-cirrhotic CHB patients in Canada, providing that society is willing to pay at least $Can48 015 per QALY gained, although sensitivity analyses highlighted uncertainty around the results.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Table I
Table II
Fig. 1
Table III
Table IV
Table V
Table VI
Fig. 2
Fig. 3

Similar content being viewed by others

Notes

  1. Expert opinion was provided by MS, SF and seven other members of the Gilead Canada National Hepatitis B Advisory Board, who validated assumptions, identified and validated the choice of treatment strategies included in the analysis and provided specific epidemiological estimates during face-to-face meetings or by e-mail or telephone.

References

  1. WHO. Fact sheet no. 204: hepatitis B. Geneva: WHO, 2008 Aug [online]. Available from URL: http://www.who.int/mediacentre/factsheets/fs204/en/ [Accessed 2011 Sep 7]

    Google Scholar 

  2. Wright TL. Introduction to chronic hepatitis B infection. Am J Gastroenterol 2006; 101 Suppl.1: S1–6

    Article  Google Scholar 

  3. Sherman M, Shafran S, Burak K, et al. Management of chronic hepatitis B: consensus guidelines. Can J Gastroenterol 2007; 21 Suppl. C: 5–24C

    Google Scholar 

  4. Hoffmann-La Roche Limited. Product monograph: pegasys peginterferon alfa-2a injection (pre-filled syringes: 180 mcg/0.5 mL, single use vials 180 mcg/1 mL) [online]. Available from URL: http://www.rochecanada.com/gear/glossary/servlet/staticfilesServlet?type=data&communityId=re753001&id=static/attachedfile/re7300002/re77300002/AttachedFile_08765.pdf [Accessed 2011 Sep 7]

  5. Marcellin P, Lau GK, Bonino F, et al. Peginterferon alfa-2a alone, lamivudine alone, and the two in combination in patients with HBeAg-negative chronic hepatitis B. N Engl J Med 2004; 351: 1206–17

    Article  PubMed  CAS  Google Scholar 

  6. Wong DK, Cheung AM, O’Rourke K, et al. Effect of alphainterferon treatment in patients with hepatitis B e antigenpositive chronic hepatitis B: a meta-analysis. Ann Intern Med 1993; 119: 312–23

    PubMed  CAS  Google Scholar 

  7. European Association for the Study of the Liver. EASL clinical practice guidelines: management of chronic hepatitis B. J Hepatol 2009; 50: 227–42

    Article  Google Scholar 

  8. Lai CL, Dienstag J, Schiff E, et al. Prevalence and clinical correlates of YMDD variants during lamivudine therapy for patients with chronic hepatitis B. Clin Infect Dis 2003; 36: 687–96

    Article  PubMed  CAS  Google Scholar 

  9. Lok AS, Lai CL, Leung N, et al. Long-term safety of lamivudine treatment in patients with chronic hepatitis B. Gastroenterology 2003; 125: 1714–22

    Article  PubMed  CAS  Google Scholar 

  10. Snow-Lampart A, Chappell B, Curtis M, et al. Week 96 resistance surveillance for HBeAg positive and negative subjects with chronic HBV infection randomised to receive tenofovir DF 300 mg QD [poster]. The 59th Annual Meeting of the American Association for the Study of Liver Disease; 2008 Oct 31-Nov 4; San Francisco (CA)

    Google Scholar 

  11. Khungar V, Han SH. A systematic review of side effects of nucleoside and nucleotide drugs used for treatment of chronic hepatitis B. Curr Hepat Rep 2010; 9: 75–90

    Article  PubMed  Google Scholar 

  12. Tenney DJ, Rose RE, Baldick CJ, et al. Long-term monitoring shows hepatitis B virus resistance to entecavir in nucleoside-naive patients is rare through 5 years of therapy. Hepatology 2009; 49: 1503–14

    Article  PubMed  CAS  Google Scholar 

  13. Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, et al. Long-term therapy with adefovir dipivoxil for HBeAgnegative chronic hepatitis B for up to 5 years. Gastroenterology 2006; 131: 1743–51

    Article  PubMed  CAS  Google Scholar 

  14. Dakin H, Fidler C, Harper C. Mixed treatment comparison meta-analysis evaluating the relative efficacy of nucleos(t)ides for treatment of chronic hepatitis B. Value Health 2010; 13 (8): 934–45

    Article  PubMed  Google Scholar 

  15. Chang TT, Gish RG, de Man R, et al. A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. N Engl J Med 2006; 354: 1001–10

    Article  PubMed  CAS  Google Scholar 

  16. National Institute for Health and Clinical Excellence. Bristol-Myers Squibb Pharmaceuticals Ltd. Entecavir (baraclude®) for the treatment of chronic hepatitis B single technology appraisal submission to the National Institute forHealth and Clinical Excellence. London: NICE, 2007 Nov

    Google Scholar 

  17. Marcellin P, Heathcote EJ, Buti M, et al. Tenofovir disoproxil fumarate versus adefovir dipivoxil for chronic hepatitis B. N Eng J Med 2008; 359: 2442–55

    Article  CAS  Google Scholar 

  18. Ontario Drug Benefit. eFormulary. Prices effective 2008 Aug 28 [online]. Available from URL: http://www.healthinfo.moh.gov.on.ca/formulary/index.jsp [Accessed 2008 Sep 17]

  19. RAMQ formulary. 17th ed. 2008 Jun 2 [online]. Available from URL: http://www.prod.ramq.gouv.qc.ca/DPI/PO/Commun/PDF/Liste_Med/Liste_Med/liste_med_2008_06_02_en.pdf [Accessed 2011 Sep 6]

  20. Woo G, Tomlinson G, Nishikawa Y, et al. Tenofovir and entecavir are the most effective antiviral agents for chronic hepatitis B: a systematic review and Bayesian metaanalyses. Gastroenterology 2010; 139: 1218–29

    Article  PubMed  CAS  Google Scholar 

  21. Dakin H, Bentley A, Dusheiko G. Cost-utility analysis of tenofovir disoproxil fumarate in the treatment of chronic hepatitis B. Value Health 2010 Dec; 13 (8): 922–33

    Article  PubMed  Google Scholar 

  22. Buti M, Brosa M, Casado MA, et al. Modeling the costeffectiveness of different oral antiviral therapies in patients with chronic hepatitis B. J Hepatol 2009; 51 (4): 640–6

    Article  PubMed  CAS  Google Scholar 

  23. Deniz B, Buti M, Brosa M, et al. Cost-effectiveness simulation analysis of tenofovir disoproxil fumarate (tenofovir), lamivudine, adefovir dipivoxil (adefovir) and entecavir of HBeAg negative (-) patients with chronic hepatitis-B (CHB) in Spain [abstract 557]. J Hepatol 2008; 48 Suppl. 2: S209

    Article  Google Scholar 

  24. Deniz B, Everhard F. Cost-effectiveness simulation analysis of tenofovir disoproxil fumarate (tenofovir) in HBeAg negative (-) patients with chronic hepatitis-B (CHB) in Italy and France [abstract 559]. J Hepatol 2008; 48 Suppl. 2: S210

    Article  Google Scholar 

  25. Product monograph: hepsera® adefovir dipivoxil tablets (10 mg). Antiviral agent. Date of revision: 2009 May 25. Foster City (CA): Gilead Sciences, Inc. [online]. Available from URL: http://www.gilead.ca/pdf/ca/hepsera_pm_english.pdf [Accessed 2010 Jun 17]

  26. Baraclude® (entecavir) tablets 0.5 mg, oral solution 0.05 mg/mL. Antiviral: product monograph. Bristol-Myers Squibb Canada [online]. Available from URL: http://www.bmscanada.ca/static/products/en/pm_pdf/Baraclude_E_19%20Nov%202010_PM_DIST_CLN.pdf [Accessed 2011 Sep 6]

  27. Viread® (tenofovir disoproxil fumarate tablets) 300 mg antiretroviral agent: product monograph. Gilead Sciences, Inc. [online]. Available from URL: http://www.gilead.ca/pdf/ca/viread_pm_english.pdf [Accessed 2011 Sep 6]

  28. Canadian Coordinating Office for Health Technology Assessment. CEDAC final recommendation on reconsideration and reasons for recommendation: tenofovir (Viread® - Gilead Sciences Canda, Inc.) 2006 Mar 15 [online]. Available from URL: http://www.cadth.ca/media/cdr/complete/cdr_complete_Viread_Resubmission_march2006.pdf [Accessed 2011 Sep 6]

    Google Scholar 

  29. Canadian Agency for Drugs and Technologies in Health. CEDAC final recommendation and reasons for recommendation: tenofovir/emtricitabine/efavirenz (Atripla ™- Bristol-Myers Squibb Canada andGilead Sciences Canada, Inc.) 2008 Apr 17 [online]. Available from URL: http://www.cadth.ca/media/cdr/complete/cdr_complete_Atripla_April-17-2008.pdf [Accessed 2011 Sep 6]

    Google Scholar 

  30. Fung SK, Wong FS, Wong DK, et al. Hepatitis B virus genotypes, precore and core promoter variants among predominantly Asian patients with chronic HBV infection in a Canadian center. Liver Int 2006; 26: 796–804

    Article  PubMed  CAS  Google Scholar 

  31. Gagnon YM, Levy AR, Iloeje UH, et al. Treatment costs in Canada of health conditions resulting from chronic hepatitis B infection. J Clin Gastroenterol 2004; 38: S179–86

    Article  Google Scholar 

  32. Levy AR, Kowdley KV, Iloeje U, et al. The impact of chronic hepatitis B on quality of life: a multinational study of utilities from infected and uninfected persons. Value Health 2008; 11: 527–38

    Article  PubMed  Google Scholar 

  33. de Franchis R, Hadengue A, Lau G, et al. EASL International Consensus Conference on Hepatitis B. 13-14 September, 2002 Geneva, Switzerland. Consensus statement (long version). J Hepatol 2003; 39 Suppl. 1: S3–25

    Google Scholar 

  34. Fung SK, Mazzulli T, El-Kashab M, et al. Lamivudineresistant mutation detected among treatment-naive hepatitis B patients is common and may be associated with treatment failure [poster]. 59th Annual meeting of the American Association for the Study of Liver Disease; 2008 Oct 31-Nov 4; San Francisco (CA)

    Google Scholar 

  35. Statistics Canada. Table 102-0218: life expectancy, abridged life table, by age group and sex, three-year average, Canada, provinces, territories, health regions and peer groups, occasional (years) [online]. Available from URL: http://www5.statcan.gc.ca/cansim/a05?id=1020218&pattern=Life+expectancy%2C+abridged+life+table&stByVal=1&paSer=&lang=eng [Accessed 2011 Sep 6]

  36. Canadian Agency for Drugs and Technologies in Health. Guidelines for the economic evaluation of health technologies: Canada. 3rd edition. Ottawa (ON): CADTH, 2006 [online]. Available from URL: http://www.cadth.ca/media/pdf/186_EconomicGuidelines_e.pdf [Accessed 2011 Sep 6]

    Google Scholar 

  37. Canadian Agency for Drugs and Technologies in Health. CEDAC final recommendation on reconsideration and reasons for recommendation: telbivudine (Sebivo™ - Novartis Pharmaceuticals Canada Inc.) 2007 Sep 26 [online]. Available from URL: http://www.cadth.ca/media/cdr/complete/cdr_complete_Sebivo_September-26-2007.pdf [Accessed 2011 Sep 6]

    Google Scholar 

  38. Canadian Agency for Drugs and Technologies in Health. CEDAC final recommendation on reconsideration and reasons for recommendation: entecavir (baraclude™ - Bristol-Myers Squibb Canada). 2007 Nov 28 [online]. Available from URL: http://www.cadth.ca/media/cdr/complete/cdr_complete_Baracude_November-28-2007.pdf [Accessed 2011 Sep 6]

    Google Scholar 

  39. Gilead Sciences. Study GS-US-174-0106 week 48 clinical study report: tenofovir disoproxil fumarate (DF and emtricitabine/ tenofovir DF fixed-dose combination). Data on file, 2008

  40. Berg T, Marcellin P, Zoulim F, et al. Tenofovir is effective alone or with emtricitabine in adefovir-treated patients with chronic-hepatitis B virus infection. Gastroenterology 2010; 139: 1207–17

    Article  PubMed  CAS  Google Scholar 

  41. van Bommel F, Zollner B, Sarrazin C, et al. Tenofovir for patients with lamivudine-resistant hepatitis B virus (HBV) infection and high HBV DNA level during adefovir therapy. Hepatology 2006; 44: 318–25

    Article  PubMed  Google Scholar 

  42. Buti M, Hadziyannis S, Mathurin P, et al. Tenofovir disoproxil fumarate (TDF) is highly active for treatment of chronic hepatitis B in subjects with cirrhosis [podium presentation #1352]. 43rd Annual Meeting of the European Association for the Study of the Liver; 2008 Apr 23-27; Milan

    Google Scholar 

  43. Crowley S, Tognarini D, Desmond P, et al. Introduction of lamivudine for the treatment of chronic hepatitis B: expected clinical and economic outcomes based on 4-year clinical trial data. J Gastroenterol Hepatol 2002; 17: 153–64

    Article  PubMed  CAS  Google Scholar 

  44. Crowley SJ, Tognarini D, Desmond PV, et al. Costeffectiveness analysis of lamivudine for the treatment of chronic hepatitis B. Pharmacoeconomics 2000; 17 (5): 409–27

    Article  PubMed  CAS  Google Scholar 

  45. Fattovich G, Brollo L, Giustina G, et al. Natural history and prognostic factors for chronic hepatitis type B. Gut 1991; 32: 294–8

    Article  PubMed  CAS  Google Scholar 

  46. Liaw YF, Tai DI, Chu CM, et al. The development of cirrhosis in patients with chronic type B hepatitis: a prospective study. Hepatology 1988; 8: 493–6

    Article  PubMed  CAS  Google Scholar 

  47. Sung JJ, Lai JY, Zeuzem S, et al. Lamivudine compared with lamivudine and adefovir dipivoxil for the treatment of HBeAg-positive chronic hepatitis B. J Hepatol 2008; 48: 728–35

    Article  PubMed  CAS  Google Scholar 

  48. Lai CL, Leung N, Teo EK, et al. A 1-year trial of telbivudine, lamivudine, and the combination in patients with hepatitis B e antigen-positive chronic hepatitis B. Gastroenterology 2005; 129: 528–36

    PubMed  CAS  Google Scholar 

  49. Heathcote J, George J, Gordon S, et al. Tenofovir disoproxil fumarate (TDF) for the treatment of HBeAg-positive chronic hepatitis B: week 72 TDF data and week 24 adefovir dipivoxil switch data (study 103). 43rd Annual Meeting of the European Association for the Study of the Liver; 2008 Apr 23-27; Milan

    Google Scholar 

  50. Reijnders JG, Pas SD, Schutten M, et al. Entecavir shows limited efficacy in HBeAg-positive hepatitis B patients with a partial virologic response to adefovir therapy. J Hepatol 2009; 50: 674–83

    Article  PubMed  CAS  Google Scholar 

  51. Kind P, Hardman G, Macran S. UK population norms for EQ-5D. York: Centre for Health Economics, 1999 Nov

    Google Scholar 

  52. Wong JB, Koff RS, Tine F, et al. Cost-effectiveness of interferon-alpha 2b treatment for hepatitis B e antigen-positive chronic hepatitis B. Ann Intern Med 1995; 122: 664–75

    PubMed  CAS  Google Scholar 

  53. Statistics Canada. Table 326-0021. Consumer price index (CPI), 2005 basket, annual (2002=100 unless otherwise noted), CANSIMdatabase. Based on Canadian geographical region and healthcare commodity group [online]. Available from URL: http://www5.statcan.gc.ca/cansim/pick-choisir?lang=eng&searchTypeByValue=1&id=3260021 [Accessed 2011 Sep 6]

  54. Zethraeus N, Johannesson M, Jonsson B, et al. Advantages of using the net-benefit approach for analysing uncertainty in economic evaluation studies.Pharmacoeconomics 2003; 21 (1): 39–48

    Article  PubMed  Google Scholar 

  55. Stinnett AA, Mullahy J. Net health benefits: a new framework for the analysis of uncertainty in cost-effectiveness analysis. Med Decis Making 1998; 18: S68–80

    Article  Google Scholar 

  56. McGuire A. Chapter 1: theoretical concepts in the economic evaluation of health care. In: Drummond M, McGuire A, editors. Economic evaluation in health care: merging theory with practice. Oxford: Oxford University Press, 2001

    Google Scholar 

  57. Briggs AH. Handling uncertainty in cost-effectiveness models. Pharmacoeconomics 2000; 17 (5): 479–500

    Article  PubMed  CAS  Google Scholar 

  58. Briggs AH, Goeree R, Blackhouse G, et al. Probabilistic analysis of cost-effectiveness models: choosing between treatment strategies for gastroesophageal reflux disease. Med Decis Making 2002; 22: 290–308

    PubMed  Google Scholar 

  59. Claxton K. The irrelevance of inference: a decision-making approach to the stochastic evaluation of health care technologies. J Health Econ 1999; 18: 341–64

    Article  PubMed  CAS  Google Scholar 

  60. Kamal A, Gerson L, Ahmed A. Cost-effectiveness of new treatment paradigms for e-Ag negative chronic hepatitis B [abstract no. 987]. 58th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD); 2007 Nov 2-6; Boston (MA)

    Google Scholar 

  61. Kanwal F, Gralnek IM, Martin P, et al. Treatment alternatives for chronic hepatitis B virus infection: a costeffectiveness analysis. Ann Intern Med 2005; 142: 821–31

    PubMed  CAS  Google Scholar 

  62. Shepherd J, Jones J, Takeda A, et al. Adefovir dipivoxil and pegylated interferon alfa-2a for the treatment of chronic hepatitis B: a systematic review and economic evaluation. Health Technol Assess 2006; 10: iii-iv, xi-xiv, 1–183

    Google Scholar 

  63. Lai CL, Gane E, Liaw YF, et al. Telbivudine versus lamivudine in patients with chronic hepatitis B. N Engl J Med 2007; 357: 2576–88

    Article  PubMed  CAS  Google Scholar 

  64. Drummond MF, O’Brien B, Stoddart GL, et al. Methods for the economic evaluation of health care programmes. Oxford: Oxford Medical Publications, 1997

    Google Scholar 

  65. National Institute for Health and Clinical Excellence. Guide to the methods of technology appraisal. London: NICE, 2008 Jun [online]. Available from URL: http://www.nice.org.uk/media/B52/A7/TAMethodsGuideUpdatedJune2008.pdf [Accessed 2010 Jun 17]

    Google Scholar 

  66. Minuk G, Uhanova J. Chronic hepatitis B infection in Canada. Can J Infect Dis 2001; 12: 351–6

    PubMed  CAS  Google Scholar 

  67. Gish RG, Gadano AC. Chronic hepatitis B: current epidemiology in the Americas and implications formanagement. J Viral Hepat 2006; 13: 787–98

    Article  PubMed  CAS  Google Scholar 

  68. Zhang J, Zou S, Giulivi A. Epidemiology of hepatitis B in Canada. Can J Infect Dis 2001; 12: 345–50

    PubMed  CAS  Google Scholar 

  69. Yang H, Qi X, Sabogal A, et al. Cross-resistance testing of next-generation nucleoside and nucleotide analogues against lamivudine-resistant HBV. Antivir Ther 2005; 10: 625–33

    PubMed  CAS  Google Scholar 

  70. Novartis Pharmaceuticals Canada Inc. Prescribing information: Sebivo® (telbivudine). Tablets (film-coated) 600 mg. Antiviral agent. Dorval (QC): Novartis Pharmaceuticals Canada Inc., 2006 [online]. Available from URL: http://www.sebivo.com.ua/files/sebivo_scrip_e.pdf [Accessed 2008 Apr 30]

    Google Scholar 

  71. Dore GJ, Cooper DA, Pozniak AL, et al. Efficacy of tenofovir disoproxil fumarate in antiretroviral therapy-naive and -experienced patients coinfected with HIV-1 and hepatitis B virus. J Infect Dis 2004; 189: 1185–92

    Article  PubMed  CAS  Google Scholar 

  72. Curtis M, Harris J, Borroto Esoda K, et al. Tenofovir is equally active in vitro against wild-type HBV clinical isolates of genotypes A-H [abstract]. Hepatology 2008; 48: 735A

    Google Scholar 

Download references

Acknowledgements

The authors thank Christie Harper for design advice and editing assistance and Gilead Canada for funding the research.

Helen Dakin, Anthony Bentley and Carrie Fidler have undertaken consultation for Gilead Sciences as employees of Abacus International. Dr Fung has received research support and is on the Speaker’s Bureau for Gilead Sciences Canada. Morris Sherman has received honoraria from the manufacturers of tenofovir and entecavir for sitting on an advisory board and for speaking engagements.

Author information

Authors and Affiliations

  1. Abacus International, 6 Talisman Road, Bicester, Oxfordshire, OX26 6HR, UK

    Helen Dakin, Carrie Fidler & Anthony Bentley

  2. Health Economics Research Centre, Department of Public Health, University of Oxford, Oxford, UK

    Helen Dakin

  3. Department of Medicine, University of Toronto and University Health Network, Toronto, ON, Canada

    Morris Sherman & Scott Fung

Authors
  1. Helen Dakin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Morris Sherman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Scott Fung
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Carrie Fidler
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Anthony Bentley
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Helen Dakin.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dakin, H., Sherman, M., Fung, S. et al. Cost Effectiveness of Tenofovir Disoproxil Fumarate for the Treatment of Chronic Hepatitis B from a Canadian Public Payer Perspective. Pharmacoeconomics 29, 1075–1091 (2011). https://doi.org/10.2165/11589260-000000000-00000

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/11589260-000000000-00000

Keywords

Search

Navigation