Cost Effectiveness of Inhaled Mannitol (Bronchitol®) in Patients with Cystic Fibrosis
Inhaled mannitol (Bronchitol®) is licensed in Australia as a safe and efficacious addition to best supportive care in patients with cystic fibrosis.
The objective of this study was to assess the cost effectiveness of inhaled mannitol (in addition to best supportive care) in the Australian setting from the perspective of a government-funded national healthcare system.
A probabilistic patient-level simulation Markov model estimated life-time costs and outcomes of mannitol when added to best supportive care, compared with best supportive care alone in patients aged 6 years and older. We estimated treatment-related inputs (initial change in percentage of predicted forced expiratory volume, relative reduction in severe pulmonary exacerbations, and treatment discontinuations) from two phase III trials. Longer term natural history rates of predicted forced expiratory volume decline over time and severe pulmonary exacerbation rates for best supportive care were taken from Australian CF registries. The utility value for the cystic fibrosis health state was as measured in the trials using the Health Utility Index, whereas the impact of pulmonary exacerbations and lung transplantation on utility was ascertained from the published literature. The underlying cost of managing cystic fibrosis, and the cost associated with pulmonary exacerbations and transplantations was taken from published Australian sources.
The addition of inhaled mannitol to best supportive care resulted in a discounted cost per quality-adjusted life-year of AU$39,165. The result was robust with 77% of probabilistic sensitivity analysis samples below a willingness-to-pay threshold of AU$45,000/quality-adjusted life-year.
Benchmarked against an implicit Australian willingness-to-pay threshold for life-threatening diseases, our model suggests inhaled mannitol provides a cost-effective addition to best supportive care in patients with cystic fibrosis, irrespective of concomitant dornase alfa use.
The authors gratefully acknowledge Jo Prior (Pharmaxis Ltd.) for helpful discussions and providing clinical context; and John Miller (Pharmaxis Ltd.) for medical input and Brent Carryer (Pharmaxis Ltd.) for conducting the statistical analysis of the clinical trials.
Emma Warren conducted the Australian economic analysis and drafted the manuscript. Kristen Morgan was responsible for the conception and management of the project. Joanna Leadbetter directed the statistical analysis of clinical trial data. Toby J. Toward and Matthias Schwenkglenks were responsible for the original development of the TreeAge model. All authors reviewed and critically revised the manuscript and approved the final version.
Compliance with Ethical Standards
This article/research was funded by Pharmaxis Ltd.
Conflict of interest
Emma Warren and Toby Toward have received consulting fees from Pharmaxis Ltd. Matthias Schwenkglenks has received research funding via an employment institution from Pharmaxis Ltd. Joanna Leadbetter and Kristen Morgan are employees of Pharmaxis Ltd.
Several datasets were used for this analysis (CF-301/CF-302). The patient-level data are not publicly available, but the results of the trials have been presented in several publications. Model inputs are described within the article. The model was developed in TreeAge Pro 2017, and is not publicly available, but is available from the authors upon reasonable request, with authorisation from Pharmaxis Ltd. and receipt of a signed confidentially agreement.
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