Title: Evaluating the impact of a molecular point-of-care test and treat strategy for influenza in hospitalised adults
Funder: Department of Health and Social Care

Abstract: Background: The influenza virus causes annual seasonal epidemics leading to many hospitalisations and around 10,000 excess deaths in the UK. The rate of hospitalisation can be over 1000 per 100,000 in the elderly despite high levels of vaccination in this group. 10-30% of adult hospitalised with influenza require critical care support and 3-15% will die. Treatment with the neuraminidase inhibitors (NAI) oseltamivir and zanamivir is recommended by national guidelines for all hospitalised patients with influenza and a recent meta-analysis has demonstrated reductions in mortality in hospitalised adults treated with oseltamivir, further strengthening this position. In current UK practice hospitalised adults with acute respiratory illness are not routinely tested for influenza even during peak periods of transmission, leading to under-diagnosis and missed opportunities for NAI treatment. When testing is performed laboratory PCR is used which takes 24-48 hours to generate a result, leading to delays in appropriate treatment and isolation. New rapid molecular testing platforms for influenza have been developed which are as accurate as laboratory PCR but can generate a result in 1 hour making them deployable as a point-of-care test (POCT). Potential benefits of POCT for influenza and other respiratory viruses include the early appropriate use of NAIs in addition to improved use of hospital side rooms and a reduction in inappropriate antibiotic use. Aims: To evaluate the clinical and health economic impact of a molecular POCT for influenza, followed by directed NAI use, in adults presenting to hospital with acute respiratory illness. Objectives: 1. To evaluate the impact of POCT on the clinical management of influenza, including; the speed and appropriateness of neuraminidase inhibitor use and the use of antibiotics. 2. To evaluate the impact of POCT on clinical effectiveness (including; proportion of case of influenza detected, duration of illness, duration of hospitalisation, critical care admission, mortality, adverse events, and patient satisfaction). 3. To evaluate the impact of POCT on healthcare resource use and costs including; the duration of hospital stay, the use of diagnostic testing and procedures, the use of isolation facilities, the use of NAIs and antibiotics, critical care admission, post discharge GP visits and readmissions to hospital. Design and methods: Parallel-group randomised controlled trial with a 1:1 allocation to the intervention and control group with an economic analysis alongside. Adults with acute respiratory illness will be identified in the emergency department and medical admission unit within 24 hours of presentation, during the winter months, over two consecutive years. Patients randomised to the intervention will have a nose and throat swab taken and immediately tested for influenza and other viruses using the FilmArray platform. The patient and responsible clinical team will be notified of the results as soon as available (1 hour). Patients with influenza detected will be offered NAI treatment. Data will be collected following discharge from hospital on; NAI use, antibiotic use, side room use, duration of hospitalisation, critical care admission, mortality, readmission and GP visits post discharge, patient satisfaction scores and turnaround time of diagnostic testing. Analysis will be by intention-to-treat and groups will be compared for the above outcome measures. Expected outcomes: We hypothesise that a point-of-care test and treat strategy for influenza, using the FilmArray platform, followed by directed NAI treatment will improve the appropriate use of neuraminidase inhibitors, antibiotics and hospital isolation facilities, will reduce the length of hospital stay and economic cost, is safe and associated with improved patient satisfaction, compared to routine clinical care. Results will be presented at national and international conferences and published in high impact journals. If our hypothesis is supported then POCT for respiratory viruses in adults will become part of routine clinical care.

Lay abstract: Aims: This fellowship aims to train the applicant and develop their skills so that they are able to design and run clinical studies in the future without needing help from more senior researchers. This is done by helping the applicant to plan and carry out a clinical study whilst doing some specific training courses and being supported and supervised by more senior researchers. The care of patients with influenza in hospital needs to be improved. The study within this fellowship will see whether using a new rapid test for influenza in adults admitted to hospital can improve their care compared to the usual way that patients are tested and treated. Background: Influenza causes thousands of people to become unwell and be admitted to hospital every year. There is a vaccine available to prevent influenza but not everybody receives it and some of those who do still catch influenza and become unwell. There are antiviral drugs available to treat influenza but they are not used as often as they should be. This is because patients admitted to hospital with influenza are not always tested for it and when they are, the standard test takes 24-48 hours to give a result. Recent studies have shown that antiviral drugs are very helpful in unwell patients admitted to hospital with influenza and so we must find a way to improve the numbers of patients who are diagnosed with influenza and treated with antivirals. We have a new test which is very accurate, gives results within 1 hour and can be used at the bedside as soon as patients come into hospital. We think that by using this test in patients admitted to hospital we may improve the number of cases of influenza diagnosed and increase the number given antivirals. Design and methods: Patients will be put into one of two groups. One group will have the new test performed as soon as they come into hospital and the results given to the doctors and the patient. Patients with a positive test for influenza will be offered antiviral medicines in accordance with UK guidelines. The other group will be managed in the standard way where doctors will decide whether or not to send a test to the laboratory and then whether to offer antiviral medicines. The two groups will be compared to see if having the new rapid test made any difference to their care or outcome. To allow the applicant to become more skilled in running studies and analysing the results of trials they will have specific training classes during the fellowship and will also have help and support from local experts in statistics and health economics (studying whether new treatments are good value for money). Patient and public involvement: We asked patients how their care and experience could have been improved when they were admitted to hospital with possible influenza and their answers have helped to design this research study. Patients preferred to have the rapid tests as they got their results sooner. Patients said that having a named virus as the cause of their symptoms was reassuring compared to being told it was 'probably a viral illness'. Patients also said that they wanted to be part of any decision making about using antiviral treatment rather than having this decision made for them. Dissemination: The results of the study within this fellowship may change the way in which patients are routinely tested and treated for influenza. The results of the study will be presented at medical conferences and published in well respected scientific journals. Members of the public helping with this study will also help to inform the wider general public of the results both locally and nationally.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION