Metagenomic sequencing (mNGS) has the potential to transform the diagnosis and management of lower respiratory tract infections (LRTIs) and bloodstream infections (BSIs), but its value depends not only on diagnostic performance, but also on which patients are tested, when testing occurs along the clinical pathway, and whether clinicians act on the results [1]. This project will develop an integrated modelling framework to identify how metagenomic sequencing can deliver the greatest clinical and economic benefit while informing the development of mNGS testing procedures and associated implementation strategies [4].

The student will first develop epidemiological and decision-analytic health-economic models to identify which patient populations, and at which points in the clinical pathway, metagenomic sequencing is expected to provide the greatest health gains and be cost-effective across different healthcare settings[3]. Initial analyses will focus on the UK and US healthcare systems, recognising differences in clinical pathways, reimbursement mechanisms, antimicrobial stewardship practices and health technology assessment frameworks.

A key innovation will be the integration of behavioural modelling using discrete choice experiments to quantify how clinicians respond to metagenomic sequencing results [2]. These experiments will generate a quantitative dataset of approx. 1000 responses from prescribers in the UK and US. Diagnostic information alone does not necessarily lead to changes in antibiotic prescribing, and the student will estimate how test characteristics, turnaround time, diagnostic certainty and implementation strategies influence prescribing decisions. These behavioural predictions will be incorporated into the epidemiological and health-economic models to produce realistic estimates of clinical impact, antimicrobial use and resistance outcomes and cost-effectiveness[3,4].

Finally, the project will integrate these findings to develop evidence-based Target Product Profiles (TPPs) and accompanying implementation strategies for metagenomic diagnostics. The TPPs will define the technical, clinical and operational characteristics required for tests to be acceptable to clinicians, achieve meaningful changes in prescribing behaviour, and deliver value for money in different healthcare systems. The project will provide a quantitative framework for guiding diagnostic developers, healthcare providers and policy-makers on how metagenomic sequencing should be designed, implemented and evaluated to maximise patient and population health benefits.