Title: A Single-use Device for the Diagnosis of Influenza and Other Respiratory Pathogens at the Point-of-Care.
Funder: Department of Health and Social Care

Abstract: The overall aim of this project is to design and manufacture a fully-functional prototype device for rapid diagnosis of respiratory pathogens (including Influenza, RSV, Rhinovirus and others) at the point-of-care and perform feasibility trials to demonstrate clinical proof-of-concept and commercial viability. Our detailed project plan (see Gantt Chart) comprises seven interconnected work packages with defined objectives, activities and deliverables, and five key milestones. WP1. Product Specification: We will conduct activities to support creation of a product requirements specification including specification of the pathogen panel, integrating input from multiple stakeholders, including clinicians, patients and public in an iterative design process (WP3). Key deliverables (D1.1-D1.3) include industrial design concepts. MILESTONE 1: PRODUCT SPECIFICATION User, Market, Commercial, Functional and Regulatory requirements fully defined. WP2. Product Concept: We will refine device designs through evaluation and testing of technology options and define engineering specifications before manufacturing non-functioning (no diagnostic capability) handling models of multiple designs for user preference and human factors studies (WP3) to enable selection of a final concept using a concept selection matrix. Key deliverables (D2.1-D2.6) include 3D CAD designs and handling models. WP3. User Research/Human Factors: User research, comprising stakeholder and clinical pathway analysis, focus groups and expert interviews will inform design specifications including selection of the final pathogen panel (WP1). Handling models (WP2) will be tested in user preference and formative human factors studies including a user Failure Mode Effect Analysis. A second pre-validation human factors study with functional prototypes will be integrated with the clinical Performance Evaluation study (WP6). Key deliverables (D3.1-D3.4) include the reports of the user/human factors studies. MILESTONE 2: PRODUCT CONCEPT Final product concept selected that meets product requirement specifications; engineering specifications defined. WP4. Proof-of-Prototype: Informed by the results of work packages 1-3 we will proceed with detailed iteration of the device design for manufacture, procure injection mould tools, build devices and test functional prototypes ready for clinical feasibility testing. Supporting documentation for the clinical trials will be created. Key deliverables (D4.1-D4.10) include batches of devices for clinical testing in the laboratory and then in patients (WP6). MILESTONE 3: PROOF-OF-PROTOTYPE Product prototype built using representative processes and tested to prove safety and conformance to engineering and product specifications. WP5. Bioprocess Development: We will evaluate multiplex SENSE assays for alternative respiratory pathogen panels in the context of expert clinical review (A3.2) to define final assay reagents. We will then establish processes for production, purification and stabilisation of these reagents and develop methods for aseptic integration into functional prototypes (WP4). Key deliverables (D5.1-D5.2) include non-cGMP batches of bioreagents integrated into device prototypes (WP4) for clinical testing (WP6). WP6. Clinical Feasibility Testing: The overall objective of the clinical testing is to inform the design of a subsequent pivotal study. We will evaluate the performance of functional prototypes firstly in a laboratory study with characterised samples to assess strain coverage, analytical sensitivity and specificity, followed by a prospective study (50-100 patients) to evaluate performance versus standard-of-care (PCR) with clinical end users. Key deliverables (D6.1-D6.2) include data and reports from clinical studies. MILESTONE 4: CLINICAL FEASIBILITY Demonstration that the prototype is safe and effective for clinical diagnosis in line with specified performance requirements. WP7. Translational Activities: In order to support the case for further development we will perform a regulatory review and a preliminary health economic study integrating analysis of healthcare costs and utility based on common measures (e.g. QALY) to establish commercial viability. A detailed development plan will be prepared. Key deliverables (D7.1-D7.3) include regulatory and health economics reports and a development plan. MILESTONE 5: COMMERCIAL VIABILITY Health economics analysis supports commercial viability.

Lay abstract: Infections that affect patients breathing, such as influenza, are behind 1 in every 30 admissions to hospitals and 15% of deaths across England and Wales. Typically, it is older adults, young children and people who have long-standing illnesses who are worst affected. In the winter months of 2014/15, there was a sharp rise in excess winter deaths to 49,300 of which a very large number were due to this type of infection. This was made worse because the influenza vaccine did not work well proving that we cannot rely on vaccination alone to reduce deaths. Instead there is a need to focus on better diagnosis and treatment of respiratory illnesses including cutting the use of antibiotics when they are not required. Two very different tests to diagnose influenza are available. Laboratory tests, used by the NHS, are very accurate but results take a long time which is highly problematic when decisions about treatment need to be made quickly. Rapid influenza diagnostic tests, similar to a pregnancy test, are cheap and convenient but miss many cases of infection and so are not used by the NHS. We have developed a new technology combining the performance of laboratory tests with the speed, low cost and ease of rapid tests. In this project, we will design and manufacture a device for hospital use, and conduct a clinical feasibility study in patients with suspected influenza. We will coordinate patient and public involvement through ‘flu-and-you.org’, a dedicated engagement resource used to recruit advisors, form a design focus group and conduct regular consultation and communication. The NHS would benefit from our test through improved treatment of patients, fewer hospitalisations, better use of antibiotics, fewer deaths and significantly lower overall costs. Future use by GPs and nursing homes would also enable more effective prevention and infection control.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION