Cefiderocol for treating severe aerobic Gram-negative bacterial infections: technology evaluation to inform a novel subscription-style payment model

Beth Woods, Laetitia Helene Marie Schmitt, Dina Jankovic, Benjamin Kearns, Alison Scope, Ren Shijie (Kate), Tushar Srivastava, Chu Chang Ku, Jean Hamilton, Claire Rothery, Laura Bojke, Mark Sculpher, Susan Harnan

Research output: Contribution to journalArticlepeer-review

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 cefiderocol 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 the 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 cefiderocol 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. The clinical effectiveness of cefiderocol relative to its comparators was estimated by synthesising evidence on susceptibility of the pathogens of interest to the antimicrobials in a network meta-analysis. Patient-level costs and health outcomes of cefiderocol under various usage scenarios compared with alternative management strategies 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 values 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 cefiderocol. Results: Among Enterobacterales isolates with the metallo-beta-lactamase resistance mechanism, the base-case network meta-analysis found that cefiderocol was associated with a lower susceptibility relative to colistin (odds ratio 0.32, 95% credible intervals 0.04 to 2.47), but the result was not statistically significant. The other treatments were also associated with lower susceptibility than colistin, but the results were not statistically significant. In the metallo-beta-lactamase Pseudomonas aeruginosa base-case network meta-analysis, cefiderocol was associated with a lower susceptibility relative to colistin (odds ratio 0.44, 95% credible intervals 0.03 to 3.94), but the result was not statistically significant. The other treatments were associated with no susceptibility. In the base case, patient-level benefit of cefiderocol was between 0.02 and 0.15 quality-adjusted life-years, depending on the site of infection, the pathogen and the usage scenario. There was a high degree of uncertainty surrounding the benefits of cefiderocol across all subgroups. There was substantial uncertainty in the number of infections that are suitable for treatment with cefiderocol, 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 benefits varied substantially across the base-case scenarios, from 896 to 3559 quality-adjusted life-years over 20 years. Conclusion: This work has provided quantitative estimates of the value of cefiderocol within its areas of expected usage within the NHS. Limitations: Given existing evidence, the estimates of the value of cefiderocol 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) Health Technology Assessment Policy Research Programme (NIHR award ref: NIHR135591), 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. 28. See the NIHR Funding and Awards website for further award information.

Original languageEnglish
Pages (from-to)1-238
Number of pages238
JournalHealth technology assessment
Volume28
Issue number28
DOIs
Publication statusPublished - 1 Jun 2024

Bibliographical note

We have been asked to do the following by the journal: At this time, you can upload a ‘closed’ submission of the accepted report to your University repository site and cite the report as ‘in press’. You can make the report ‘open’ following publication. Please note the report is subject to change during the production process, therefore please ensure the submission reflects the current version up to the point of publication.

Keywords

  • ANTIBACTERIAL AGENTS
  • BACTERIAL
  • BETA-LACTAMASES
  • CEFIDEROCOL
  • COLISTIN
  • COST-EFFECTIVENESS ANALYSIS
  • COST–BENEFIT ANALYSIS
  • DRUG RESISTANCE
  • EXPERT ELICITATION
  • GRAM-NEGATIVE BACTERIAL INFECTIONS
  • MICROBIAL SENSITIVITY TESTS
  • NETWORK META-ANALYSIS
  • OXACILLINASE
  • PSEUDOMONAS AERUGINOSA
  • QUALITY-ADJUSTED LIFE-YEARS
  • SYSTEMATIC REVIEW

Cite this