, Volume 24, Issue 9, pp 903–915 | Cite as

Public Funding of Bosentan for the Treatment of Pulmonary Artery Hypertension in Australia

Cost Effectiveness and Risk Sharing
  • John H. Wlodarczyk
  • Leslie G. Cleland
  • Anne M. Keogh
  • Keith D. McNeil
  • Kate Perl
  • Robert G. Weintraub
  • Trevor J. Williams
Original Research Article


Objectives: In Australia, no therapeutic agents were subsidised for the treatment of idiopathic pulmonary artery hypertension (iPAH), a rare progressive and severe disease with short life expectancy, until 1 March 2004, when bosentan (a dual endothelin receptor antagonist of high cost) was listed on the Pharmaceutical Benefits Scheme (PBS). Bosentan, in addition to conventional therapy, has been shown to slow iPAH progression and improve clinical and haemodynamic status and symptomatology, compared with placebo and conventional therapy. The objective of this paper is to describe the process of the Australian Pharmaceutical Benefits Scheme listing for bosentan (Tracleer®), which included a health economic model assessing the cost effectiveness of bosentan from a healthcare payer perspective, and a risk-sharing arrangement based on the establishment of a patient registry.

Methods: The health economic model predicted the cost, hospitalisation and mortality rates of a population of iPAH patients treated with either the conventional therapy regimen used in Australia or bosentan plus the conventional therapy regimen. The model was implemented as a first-order Monte Carlo simulation with mortality modelled directly as the main clinical outcome. The impacts of proposed continuation criteria, restricting the ongoing use of the drug, were evaluated. Costs and outcomes were discounted at 5% and a sensitivity analysis examined the robustness of the key assumptions.

Results: The model predicted that after 5, 10 and 15 years, the difference in average cumulative costs between bosentan plus conventional therapy and conventional therapy alone would be 116 929 Australian dollars ($A), $A181 808 and $A216 331 for each patient, respectively. There would be an associated increase in average life expectancy of 1.39, 2.93 and 3.87 years at 5, 10 and 15 years, respectively, with an incremental cost-effectiveness ratio at 15 years of $A55 927 for each life-year gained. Removing the continuation criteria from the model increased the incremental cost-effectiveness ratio to $A62 267 (1996–2002 values).

Conclusions: Economic modelling based on improved survival suggests bosentan to be a potentially cost-effective treatment for iPAH. However, the structure of the model and its inputs should be reviewed and updated as more data become available.


Pulmonary Arterial Hypertension Bosentan Epoprostenol Pharmaceutical Benefit Scheme Pulmonary Arterial Hypertension Patient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



All submissions to the PBAC were funded by Actelion Pharmaceuticals Australia. The Manuscript was compiled with financial support from Actelion Pharmaceuticals Australia.

John Wlodarczyk is a consultant to Actelion Pharmaceuticals Australia. Les Cleland has acted as a consultant to Actelion Pharmaceuticals Australia and the Pharmaceutical Benefits Scheme (PBS). Anne Keogh has participated in clinical trials with Actelion Pharmaceuticals Australia, Myogen, Encysive, Pfizer, Roche, Novartis and Ventracor. She has acted as a consultant to Actelion Pharmaceuticals Australia, Pfizer, Roche, Wyeth and Novartis. Keith McNeil has served on advisory boards for Actelion Pharmaceuticals Australia and GSK. Kate Perl acted as a consultant to Actelion Pharmaceuticals Australia. Trevor J. Williams is an investigator for Actelion Pharmaceuticals Australia, Pfizer, Novartis and GSK funded studies. He is also on the Advisory Board for Actelion Pharmaceuticals Australia and GSK. Andrew Mitchell, Director, Pharmaceutical Evaluation Section, Australian Department of Health and Ageing and David Kwasha, Managing Director of Actelion Pharmaceuticals Australia reviewed and commented on an earlier draft of this paper.

All authors were part of an advisory board convened by Actelion Pharmaceuticals Australia, which contributed to the development of the model and risk sharing arrangement.

The manuscript and the economic model were prepared by John Wlodarczyk. Anne Keogh, Les Cleland, Keith McNeil, Kate Perl, Robert Weintraub and Trevor Williams reviewed drafts of the paper.


  1. 1.
    Rubin LJ. Primary pulmonary hypertension. Chest 1993; 104 (1): 236–250PubMedCrossRefGoogle Scholar
  2. 2.
    Rubin LJ, Badesch DB, Barst RJ, et al. Bosentan therapy for pulmonary arterial hypertension. N Engl J Med 2002; 346 (12): 896–903PubMedCrossRefGoogle Scholar
  3. 3.
    D’Alonzo GE, Barst RJ, Ayres SM, et al. Survival in patients with primary pulmonary hypertension: results from a national prospective registry. Ann Intern Med 1991; 115 (5): 343–349PubMedGoogle Scholar
  4. 4.
    Koh ET, Lee P, Gladman DD, et al. Pulmonary hypertension in systemic sclerosis: an analysis of 17 patients. Br J Rheumatol 1996; 35 (10): 989–993PubMedCrossRefGoogle Scholar
  5. 5.
    Sulica R, Poon M. Current medical treatment of pulmonary artery hypertension. Mt Sinai J Med 2004; 71 (2): 103–114PubMedGoogle Scholar
  6. 6.
    Channick RN, Simonneau G, Sitbon O, et al. Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study. Lancet 2001; 358 (9288): 1119–1123PubMedCrossRefGoogle Scholar
  7. 7.
    McLaughlin V, Sitbon O, Rubin L, et al. The effect of first line bosentan on survival of patients with primary pulmonary hypertension. Am J Respir Crit Care Med 2003; 167 (7): A441Google Scholar
  8. 8.
    Highland KB, Strange C, Mazur J, et al. Treatment of pulmonary arterial hypertension. Chest 2003; 124 (6): 2087–2092PubMedCrossRefGoogle Scholar
  9. 9.
    Commonwealth Department of Health and Ageing. Guidelines for the pharmaceutical industry on preparation of submission to the pharmaceutical benefits advisory committee. Canberra (ACT): Comm Dept of Health and Ageing, 2002Google Scholar
  10. 10.
    Therapeutic Goods Administration. Drugs designated as orphan drugs [online]. Available from URL: [Accessed 2005 Dec 4]Google Scholar
  11. 11.
    Commonwealth Department of Health and Ageing. The orphan drug programme and improving community access to effective drugs for rare diseases. Canberra (ACT): Comm Dept of Health and Ageing, 2001Google Scholar
  12. 12.
    Pharmaceutical Benefits Advisory Committee. Other relevant factors and the “rule of rescue” [online]. Available from URL: /internet/wcms/publishing.nsf/Content/health-pbs-general-pubs-pharmpac-relevant.htm -copy3 [Accessed 2005 Apr 3]Google Scholar
  13. 13.
    Hadorn DC. The Oregon priority-setting exercise: quality of life and public policy. Hastings Cent Rep 1991; 21 (3): S11–S16PubMedCrossRefGoogle Scholar
  14. 14.
    Conner L. The rule of rescue. Ala Med 1991; 60 (10): 2, 5-6PubMedGoogle Scholar
  15. 15.
    Roux S, Kobrin I, Rainisio M, et al. Long-term open-label study in patients with pulmonary hypertension who participated in controlled clinical studies with bosentan (interim study report — protocol AC-052-354). Actelion Pharmaceuticals US, Inc., 2001 Oct 3Google Scholar
  16. 16.
    Therapeutic Guidelines Ltd. Cardiovascular. In. Version 4 ed. Melbourne (SA): Therapeutic Guidelines Ltd, 2003: Pulmonary Hypertension SectionGoogle Scholar
  17. 17.
    Medicare Australia. Physician’s guide: a guide to prescribing bosentan monohydrate and iloprost trometamol within the PBS section 100 of the National Health Act 1953: restriction criteria [online]. Available from URL: [Accessed 2006 Mar 3]Google Scholar
  18. 18.
    Commonwealth of Australia. Bosentan monohydrate. In: Schedule of pharmaceutical benefits for approved pharmacists and medical practitioners. Fyshwick (ACT): National Capital Printing, 2004: 309–318Google Scholar
  19. 19.
    Keogh A, MacDonald P, Williams T, et al. Tracleer (bosentan), a dual endothelin receptor antagonist (ERA), for the treatment of pulmonary arterial hypertension (PAH): interim results of an Australian multicentre study. Cardiac Society of Australia and New Zealand (CSANZ) Congress; 2003 Aug 10–13; Adelaide (SA)Google Scholar
  20. 20.
    Policy Analysis Inc. Exploratory analyses of data from BREATHE-1 on measures of potential pharmacoeconomic significance. Brookline (MA): Policy Analysis Inc., 2001Google Scholar
  21. 21.
    Sandoval J, Bauerle O, Palomar A, et al. Survival in primary pulmonary hypertension. Validation of a prognostic equation. Circulation 1994; 89 (4): 1733–1744PubMedCrossRefGoogle Scholar
  22. 22.
    Kapoor A, Sheppard R, Panyon J, et al. Clinical outcome comparison in pulmonary artery hypertension patients treated with epoprostenol and bosentan [poster]. American Heart Association Scientific Sessions; 2003 Nov 9–12; Orlando (FL)Google Scholar
  23. 23.
    McLaughlin VV, Sitbon O, Badesch DB, et al. Survival with first-line bosentan in patients with primary pulmonary hypertension. Eur Respir J 2005; 25 (2): 244–249PubMedCrossRefGoogle Scholar
  24. 24.
    AHTAC. Superspecialty service guidelines for lung transplantation services. Canberra (ACT): Australian Health Technology Advisory Committee, 1998Google Scholar
  25. 25.
    Mendeloff EN, Meyers BF, Sundt TM, et al. Lung transplantation for pulmonary vascular disease. Ann Thorac Surg 2002; 73: 209–219PubMedCrossRefGoogle Scholar
  26. 26.
    Keogh A, Wlodarczyk J. Idiopathic- and scleroderma-related pulmonary arterial hypertension: outcomes and QoL on bosentan. Expert Rev Pharmacoeconomics Outcomes Res 2004; 4 (5): 505–513CrossRefGoogle Scholar
  27. 27.
    Schedule of Pharmaceutical Benefits. Fyshwick (ACT): Australian Government, Department of Health and Ageing, 2002 AugGoogle Scholar
  28. 28.
    Medicare Benefits Schedule. Fyshwick (ACT): Australian Government, Department of Health and Ageing, 2001 NovGoogle Scholar
  29. 29.
    NHCDC. Australian refined diagnosis related groups [AR-DRG]. Canberra (ACT): Commonwealth of Australia, 1999–2000Google Scholar
  30. 30.
    Barst RJ, Rubin LJ, McGoon MD, et al. Survival in primary pulmonary hypertension with long-term continuous intravenous prostacyclin. Ann Intern Med 1994; 121: 409–415PubMedGoogle Scholar
  31. 31.
    Zolessi R. Epoprostenol (Flolan®). J Pharmacy Society Wisconsin 2001 Nov/Dec: 25–29Google Scholar
  32. 32.
    Keogh A, Macdonald P, Williams T, et al. Tracleer (bosentan), for the treatment of pulmonary arterial hypertension (PAH): six month quality of life data [abstract]. J Heart Lung Transplant 2004; 23 (2S): S54CrossRefGoogle Scholar
  33. 33.
    Keogh A, Wlodarczyk J. Idiopathic- and scleroderma-related pulmonary arterial hypertension: outcomes and QoL on bosentan. Expert Rev Pharmacoeconomics Outcomes Res 2004; 4 (5): 505–513CrossRefGoogle Scholar
  34. 34.
    Kawut SM, Taichman DB, Archer-Chicko CL, et al. Haemodynamics and survival in patients with pulmonary arterial hypertension related to systemic sclerosis. Chest 2003; 123: 344–350PubMedCrossRefGoogle Scholar
  35. 35.
    Barst RJ, Maislin G, Fishman AP. Vasodilator therapy for primary pulmonary hypertension in children. Circulation 1999; 99: 1197–1208PubMedCrossRefGoogle Scholar
  36. 36.
    Commonwealth Department of Health and Ageing. Schedule of pharmaceutical benefits. Fyshwick (ACT): National Capital Printing, 2005Google Scholar
  37. 37.
    George B, Harris A, Mitchell A. Cost-effectiveness analysis and the consistency of decision making: evidence from pharmaceutical reimbursement in Australia (1991 to 1996). Pharmacoeconomics 2001; 19 (11): 1103–1109PubMedCrossRefGoogle Scholar
  38. 38.
    Sudlow CL, Counsell CE. Problems with UK government’s risk sharing scheme for assessing drugs for multiple sclerosis. BMJ 2003; 326: 388–392PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2006

Authors and Affiliations

  • John H. Wlodarczyk
    • 1
  • Leslie G. Cleland
    • 2
  • Anne M. Keogh
    • 3
  • Keith D. McNeil
    • 4
  • Kate Perl
    • 5
  • Robert G. Weintraub
    • 6
  • Trevor J. Williams
    • 7
  1. 1.John Wlodarczyk Consulting ServicesNew LambtonAustralia
  2. 2.Royal Adelaide HospitalAdelaideAustralia
  3. 3.St Vincent’s HospitalDarlinghurstAustralia
  4. 4.Prince Charles HospitalChermsideAustralia
  5. 5.Nitecs Pty LimitedFrenchs ForestAustralia
  6. 6.Royal Children’s HospitalMelbourneAustralia
  7. 7.Department of Allergy, Immunology and Respiratory MedicineAlfred Hospital/Monash UniversityMelbourneAustralia

Personalised recommendations