Harnan, S. orcid.org/0000-0002-9318-9206, Kearns, B. orcid.org/0000-0001-7730-668X, Scope, A. orcid.org/0000-0003-1604-1758 et al. (11 more authors) (2024) Ceftazidime with avibactam for treating severe aerobic Gram-negative bacterial infections: technology evaluation to inform a novel subscription-style payment model. Health Technology Assessment, 28 (73). ISSN 1366-5278
Abstract
Background
To limit the use of antimicrobials without disincentivising the development of novel antimicrobials, there is interest in establishing innovative models that fund antimicrobials based on an evaluation of their value as opposed to the volumes used. The aim of this project was to evaluate the population-level health benefit of ceftazidime-avibactam in the NHS in England, for the treatment of severe aerobic Gram-negative bacterial infections when used within its licensed indications. The results were used to inform National Institute for Health and Care Excellence guidance in support of commercial discussions regarding contract value between the manufacturer and NHS England.
Methods
The health benefit of ceftazidime-avibactam was first derived for a series of high-value clinical scenarios. These represented uses that were expected to have a significant impact on patients’ mortality risks and health-related quality of life. Patient-level costs and health-related quality of life of ceftazidime-avibactam under various usage scenarios compared with alternative management strategies in the high-value clinical scenarios were quantified using decision modelling. Results were reported as incremental net health effects expressed in quality-adjusted life-years, which were scaled to 20-year population in quality-adjusted life-years using infection number forecasts based on data from Public Health England. The outcomes estimated for the high-value clinical scenarios were extrapolated to other expected uses for ceftazidime-avibactam.
Results
The clinical effectiveness of ceftazidime-avibactam relative to its comparators was estimated by synthesising evidence on susceptibility of the pathogens of interest to the antimicrobials in a network meta-analysis. In the base case, ceftazidime-avibactam was associated with a statistically significantly higher susceptibility relative to colistin (odds ratio 7.24, 95% credible interval 2.58 to 20.94). The remainder of the treatments were associated with lower susceptibility than colistin (odds ratio < 1). The results were sensitive to the definition of resistance and the studies included in the analysis.
In the base case, patient-level benefit of ceftazidime-avibactam was between 0.08 and 0.16 quality-adjusted life-years, depending on the site of infection and the usage scenario. There was a high degree of uncertainty surrounding the benefits of ceftazidime-avibactam across all subgroups, and the results were sensitive to assumptions in the meta-analysis used to estimate susceptibility. There was substantial uncertainty in the number of infections that are suitable for treatment with ceftazidime-avibactam, so population-level results are presented for a range of scenarios for the current infection numbers, the expected increases in infections over time, and rates of emergence of resistance. The population-level benefit varied substantially across the scenarios, from 531 to 2342 quality-adjusted life-years over 20 years.
Conclusion
This work has provided quantitative estimates of the value of ceftazidime-avibactam within its areas of expected usage within the NHS.
Limitations
Given existing evidence, the estimates of the value of ceftazidime-avibactam are highly uncertain.
Future work
Future evaluations of antimicrobials would benefit from improvements to NHS data linkages, research to support appropriate synthesis of susceptibility studies, and application of routine data and decision modelling to assess enablement value.
Study registration
No registration of this study was undertaken.
Funding
This award was funded by the National Institute for Health and Care Research (NIHR) Policy Research Programme (NIHR award ref: NIHR135592), conducted through the Policy Research Unit in Economic Methods of Evaluation in Health and Social Care Interventions, PR-PRU-1217-20401, and is published in full in Health Technology Assessment; Vol. 28, No. 73. See the NIHR Funding and Awards website for further award information.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2024 Harnan et al. This work was produced by Harnan et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This is an Open Access publication distributed under the terms of the Creative Commons Attribution CC BY 4.0 licence, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. See: https://creativecommons.org/licenses/by/4.0/. For attribution the title, original author(s), the publication source – NIHR Journals Library, and the DOI of the publication must be cited. |
Keywords: | anti-bacterial agents; bacterial; ceftazidime-avibactam; colistin; cost-effectiveness analysis; drug resistance; expert testimony; gram-negative bacterial infections; microbial sensitivity tests; network meta-analysis; oxacillinase; quality-adjusted life-years; systematic review; Ceftazidime; Azabicyclo Compounds; Humans; Anti-Bacterial Agents; Quality-Adjusted Life Years; Cost-Benefit Analysis; Drug Combinations; Gram-Negative Bacterial Infections; Technology Assessment, Biomedical; England; State Medicine; Quality of Life; Male; Female |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine and Population Health |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 05 Nov 2024 15:21 |
Last Modified: | 05 Nov 2024 15:21 |
Status: | Published |
Publisher: | National Institute for Health and Care Research |
Refereed: | Yes |
Identification Number: | 10.3310/yapl9347 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:219289 |