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The Cost Effectiveness of Dry Powder Antibiotics for the Treatment of Pseudomonas aeruginosa in Patients with Cystic Fibrosis

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Abstract

Background

Cystic fibrosis (CF) affects over 9,000 people in the UK and limits life expectancy. CF patients are susceptible to lung infections, most commonly Pseudomonas aeruginosa. Once infection is established, patients require lifetime treatment using nebulised antibiotics. Newer dry powder formulations of antibiotics may reduce treatment burden and improve compliance.

Objective

Our objective was to evaluate the cost effectiveness of (i) colistimethate sodium dry powder for inhalation (DPI) and (ii) tobramycin DPI versus nebulised tobramycin for the treatment of chronic P. aeruginosa lung infection in patients with CF from the perspective of the National Health Service (NHS) and Personal Social Services (PSS).

Methods

We developed a state transition model based on transitions between three strata of lung function measured in terms of forced expiratory volume in 1 second (FEV1) % predicted. Additional health states representing post-lung transplantation and dead are also modelled. The model structure was informed by systematic reviews of evidence concerning the plausibility of potential relationships between intermediate endpoints and final outcomes. The model assumes that treatment impacts on FEV1 trajectory, which manifest as changes in health-related quality of life. No survival benefit is assumed due to the absence of robust quantifiable evidence. Model parameters were informed by patient-level and aggregate data from two randomised controlled trials together with the best available evidence from the literature. Resource use and costs associated with drug acquisition, the management of exacerbations and reduced nebuliser maintenance were drawn from reference sources and expert opinion. Costs were valued at 2011/2012 prices. Costs and health outcomes were discounted at a rate of 3.5 %. Simple and probabilistic sensitivity analyses were undertaken, including additional analyses of Patient Access Scheme (PAS) price discounts offered by the manufacturers of both DPI products.

Results

Colistimethate sodium DPI is expected to produce fewer quality-adjusted life-years (QALYs) than nebulised tobramycin. Based on its list price, colistimethate sodium DPI is expected to be dominated by nebulised tobramycin. When the PAS is incorporated, the incremental cost-effectiveness ratio (ICER) for colistimethate sodium DPI versus nebulised tobramycin is expected to be approximately £288,600 saved per QALY lost. Based on its current list price, the ICER for tobramycin DPI versus nebulised tobramycin is expected to be approximately £124,000 per QALY gained. When the proposed PAS is included, tobramycin DPI is expected to dominate nebulised tobramycin.

Conclusions

Under their list prices, neither DPI product is likely to represent good value for money for the NHS given current cost-effectiveness thresholds. The PAS discounts have a significant impact upon the economic attractiveness of both DPI products compared against nebulised tobramycin. The clinical effectiveness and cost effectiveness of the DPIs against other nebulised antibiotics, such as aztreonam and inhaled colistimethate sodium, remains unclear.

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Acknowledgments

This study was funded by the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Programme to inform the National Institute for Health and Care Excellence Technology Appraisal Programme (project number 10/1801). The authors would like to thank Forest Laboratories and Novartis Pharmaceuticals for providing additional data requested throughout the course of the appraisal.

Contribution of authors

Paul Tappenden and Matthew Mildred developed the health economic model. Anna Cantrell developed the electronic search strategies. Sue Harnan and Lesley Uttley undertook a related review of clinical effectiveness and inputted into the design of the model. Keith Brownlee, Martin Walshaw and Chris Taylor provided considerable clinical input into the design of the model. All authors contributed to the drafting of the manuscript.

Conflicts of interest

Keith Brownlee has attended a Novartis Advisory board on future developments in CF in 2010 and received a fee and travel expenses for a lecture given at the East Anglia Cystic Fibrosis Club in 2010 from Forest Laboratories. None of the other authors have any conflicts of interest to declare.

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Authors and Affiliations

  1. ScHARR, University of Sheffield, Regent Court, 30 Regent Street, Sheffield, S1 4DA, England

    Paul Tappenden, Sue Harnan, Lesley Uttley & Matthew Mildred

  2. Liverpool Heart and Chest Hospital NHS Foundation Trust, Thomas Drive, Liverpool, L14 3PE, England

    Martin Walshaw

  3. Sheffield Children’s NHS Foundation Trust, Western Bank, Sheffield, S10 2TH, England

    Christopher Taylor

  4. Leeds Regional Paediatric Respiratory and Cystic Fibrosis Centre, Leeds Children’s Hospital, Leeds General Infirmary, A Floor, Clarendon Wing, Leeds, LS1 3EX, England

    Keith Brownlee

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  1. Paul Tappenden
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  2. Sue Harnan
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  4. Matthew Mildred
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  5. Martin Walshaw
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  7. Keith Brownlee
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Corresponding author

Correspondence to Paul Tappenden.

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Tappenden, P., Harnan, S., Uttley, L. et al. The Cost Effectiveness of Dry Powder Antibiotics for the Treatment of Pseudomonas aeruginosa in Patients with Cystic Fibrosis. PharmacoEconomics 32, 159–172 (2014). https://doi.org/10.1007/s40273-013-0122-x

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  • DOI: https://doi.org/10.1007/s40273-013-0122-x

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