Final report for the technology evaluation of cefiderocol for treating severe aerobic Gram-negative bacterial infections

1.1. Background

The National Institute for Health and Care Excellence (NICE), NHS England and NHS Improvement are currently undertaking a project to assess the feasibility of innovative models that pay for antimicrobials (AMs) based on an evaluation of their value to the National Health Service (NHS) as opposed to the volumes used. Following the selection of two products considered to be of high public health importance, this project involves evaluation of the selected products to inform commercial discussions regarding contract value for a period of up to 10 years. The selection process was a formal procurement exercise and aimed to identify one new AM and one existing but “nearly new” AM. The products selected by this process were, respectively, cefiderocol (Fetcroja) which is manufactured by Shionogi; and ceftazidime with avibactam (Zavicefta), which is manufactured by Pfizer.

This report details the evaluation phase of this project for cefiderocol. Cefiderocol received a marketing authorisation in April 2020 for treating infections due to aerobic Gram-negative organisms in adults with limited treatment options.

1.2. Aim and objectives

The aim of this evaluation is to assess the value of cefiderocol to the NHS in England, for the treatment of severe aerobic Gram-negative bacterial (GNB) infections when used within its licensed indications.

Specific objectives are:

i. To identify two high value clinical scenarios (HVCSs), within its broad licensed indications, for which cefiderocol is expected to have a significant impact on patients’ outcomes in terms of reducing mortality risks and improving health-related quality of life (HRQoL).

ii. To undertake an ‘evidence mapping’ exercise and relevant systematic literature reviews to characterise the available clinical effectiveness evidence for the use of cefiderocol in the HVCSs.

iii. To establish an appropriate decision-analytic model to quantify the costs and health benefits of the use of cefiderocol under various usage scenarios compared with alternative treatments and management strategies (usage scenarios of other available AMs) in the HVCSs. The decisionanalytic model was required to estimate costs and health effects at both the individual level and the aggregate population level, providing population-level incremental net health effects (INHEs).

iv. Drawing on the systematic reviews and evidence synthesis, national-level data on health-care associated infections, and other sources as needed, to identify evidence to populate the decision-analytic models.

v. To use structured expert elicitation as necessary to supplement the available evidence to populate the decision-analytic models at the levels of both the individual patients and populations.

vi. To use available evidence and, where necessary, expert opinion quantitatively to extrapolate estimated population-level INHEs associated with cefiderocol in the HVCSs to other expected uses for the product beyond the HVCSs and within the product’s licensed indications.

1.3. Expected usage and high value clinical scenarios

The licensed indication for cefiderocol is broad. In practice, to control the spread of resistance to cefiderocol and to preserve its long-term viability as an effective treatment option against highly resistant pathogens, cefiderocol may be used in a more restricted group of patients than permitted by its license. Quantifying the health and cost implications of using cefiderocol across anticipated NHS usage, even within this restricted population, remains challenging, as use is expected in infections which differ in causative organism (pathogen, resistance mechanism), site of the infection, health care setting and other underlying features of the health status of the patient.

Using available evidence, this evaluation characterises the value of cefiderocol across its range of expected uses via a two-step approach. First, decision modelling is used quantitatively to assess the value of cefiderocol in a set of scenarios defined by features of the pathogen, site of infection, healthcare setting and other patient characteristics, considered to represent important uses of cefiderocol; referred to as the HVCSs. Secondly, rescaling is used to estimate how this evidence can be used to provide quantitative assessments of value in the overall population expected to receive cefiderocol, including patients who fall outside the HVCSs but whom are relevant to determining the overall value of cefiderocol to the English NHS.

The HVCSs were selected to reflect areas of clinical use where there is a current significant burden from resistant infections, and cefiderocol is expected to offer significant improvements over existing treatments in terms of efficacy and/or safety. The HVCSs were selected based on feedback from the manufacturer, clinical advisors to the Policy Research Unit in Economic Methods of Evaluation in Health and Social Care Interventions (EEPRU) and broader stakeholders involved in the NICE scoping process. The HVCSs focus on the following patient populations:

1) Empiric setting (ES): patients with an infection strongly suspected to be caused by metallobeta-lactamase (MBL) producing Enterobacterales or MBL-producing Pseudomonas aeruginosa (PA) in patients with hospital acquired pneumonia or ventilator associated pneumonia (HAP/VAP). In this patient group the pathogen, resistance mechanism and antibiotic susceptibility have not yet been established but treatment is initiated immediately due to the severity of the infection.

2) Microbiology-directed setting (MDS): patients with an infection confirmed to be caused by MBL Enterobacterales or MBL Pseudomonas aeruginosa, where antibiotic susceptibility testing results are available, and where the site of infection is HAP/VAP or complicated urinary tract infection (cUTI).

The resourcing for this project was equivalent to that of a diagnostic assessment review or multiple technology assessment for NICE, but the levels of analysis extend from the typical focus of those evaluations on a single type of patient for one indication and setting. In this evaluation, we also include population level health effects now and over time, and across several indications and settings. The objective is to use appropriate analyses of the available evidence at every level, but the detail in those analyses is inevitably constrained by the time and resources available for the project.