Title: Rapid respiratory microbiological point-of-care-testing in primary care: a randomised controlled trial with internal pilot and qualitative and quantitative investigation of microbial, behavioural and antibiotic mechanisms (the RAPID-TEST RCT)
Funder: Medical Research Council

Abstract: Every year, millions of people seek help for coughs, colds, chest infections, sore throats and earaches (‘respiratory infections’). On average, GPs and nurses (‘clinicians’) give antibiotics to half of these patients. This is more than is necessary and leads to antibiotic resistance, but they don’t always know who needs them, so often give them ‘just in case’. _x000D_ _x000D_ We know most respiratory infections are caused by viruses, and that antibiotics only work on bacteria. If clinicians knew which were which, they could target antibiotics better. Clinicians could send swabs to hospitals, but laboratory testing takes 3 days, by which time most patients are improving and it is clear antibiotics are not needed._x000D_ _x000D_ The UK government thinks getting swab results more quickly is critical to improving antibiotic use. Manufacturers are developing ‘point-of-care tests’ (POCTs) that can detect multiple viruses on swabs in 45 minutes - quick enough to make decisions the same day. _x000D_ _x000D_ It might seem obvious that POCTs should be used, but for four things. First, the technology is developing, and the price of the machines and tests is high, respectively £40,000 and £100 for one system, plus the NHS time to run and interpret them._x000D_ _x000D_ Second, current machines test mainly for viruses, like the ones causing common colds, ‘flu and COVID. But when a virus is detected, it does not mean it is causing the infection, because viruses can live harmlessly in our noses and throats. So, the clinician must still use their judgment about whether a bacterial infection is present. _x000D_ _x000D_ Third, no test is 100% accurate. It might say ‘no virus’ when an important virus is present. This means patients could be given harmful advice or treatment._x000D_ _x000D_ Finally, we know that the clinician’s decision to prescribe and the patient’s decision to take an antibiotic are influenced by the patient-clinician interaction and the patient’s expectations for antibiotics. So, knowing how a POCT works is not as simple as ‘presence of virus = antibiotic not necessary’._x000D_ _x000D_ POCT prices will fall, but we will still need to know if spending NHS resources on them is sensible. If POCTs improved how patients feel and reduced antibiotic prescribing at a reasonable price in routine care, we would say they were ‘cost-effective’. _x000D_ _x000D_ But there is no point in checking cost-effectiveness if POCTs don’t reduce antibiotic prescribing or help patients feel better. No study like that has been done. To date, two small studies have shown that clinicians like and would use POCTs. _x000D_ _x000D_ We did one of these, and the results helped us design the present study, which aims to see if POCTs can reduce antibiotic prescribing and if so how. It will also see if POCTs help patients feel better quicker. If we get positive answers to these questions, a future study will check cost-effectiveness._x000D_ _x000D_ We will invite people with respiratory infections seeking help from their GP. We will divide them into two groups at random (so they are similar) with the clinicians of one group receiving POCT results and the other continuing with usual care. Clinicians will prescribe antibiotics as they see fit, and participants followed up to see how long symptoms last._x000D_ _x000D_ Our PPI advisory group said getting antibiotics to the people who need them most is important and provided practical considerations for recruitment and follow up during COVID. One member has joined as a co-applicant and has been integral to the design and drafting of this application.

Lay abstract: RESEARCH QUESTIONS_x000D_ Clinical: can the use of a rapid respiratory microbiological point-of-care-test reduce same-day antibiotic prescribing in children and adults presenting to primary care with acute respiratory infections in whom there is uncertainty about antibiotic treatment?_x000D_ _x000D_ Mechanistic: are there overall (test use vs. no use) and differential (virus detected vs. not detected) effects of test results with respect to clinician beliefs that ‘antibiotics are necessary for this infection’ and thereby antibiotic prescribing?_x000D_ _x000D_ BACKGROUND_x000D_ Primary care is responsible for 75-80% of NHS antibiotic prescribing, mostly for respiratory infections, despite good evidence of little benefit, driving antimicrobial resistance. ‘Just-in-case’ prescribing is attributed to uncertainty about the microbiological diagnosis and patient prognosis._x000D_ _x000D_ Point-of-care-tests (POCTs) are promoted as ‘game-changing’ stewardship tools. Manufacturers are investing heavily, particularly in respiratory microbiological POCTs with current technology providing virus results, including SARS-CoV-2, in 45-120 minutes. Our feasibility study demonstrates primary care clinician acceptability, but there is no evidence regarding safety, efficacy or mechanisms. _x000D_ _x000D_ METHODS_x000D_ Design: ‘COVID compliant’ individually randomised controlled trial with mixed-methods investigation of microbial, behavioural and antibiotic mechanisms._x000D_ _x000D_ Patients eligible: =/>12 months and presenting with a respiratory infection for which the clinician and/or patient is uncertain and/or disagree about treatment. After consent and baseline data all participants (self-)take throat and nasal swabs. Study champion randomises participants to POCT or no POCT and advises clinician. Clinicians contact participants to finalise treatment: immediately in control group; after POCT result for intervention group. Participants invited to complete: a symptom diary recording duration and severity of symptoms until resolution or 28 days; and questionnaires at 2 and 6 months about beliefs and intention to consult for similar future illnesses. GP notes reviewed at 6 months for infection consultations, antibiotic prescribing, and hospital admissions._x000D_ _x000D_ After the trial, qualitative interviews will be conducted with clinicians (n=20) and participants (n=30) to understand changes in beliefs and behaviour resulting from the POCT and generate attributes for clinician and patient discrete choice experiments (DCEs). Patient DCE will explore trade-offs made when choosing to visit the GP and the extent POCTs would change this behaviour; clinician DCE will explore trade-offs when deciding about whether and when to use POCT._x000D_ _x000D_ 514 patients will be randomised to achieve 90% power with 5% significance to detect a 15% absolute reduction in prescribing from 60% in the control group, accounting for 5% attrition. _x000D_ _x000D_ TIMELINES FOR DELIVERY_x000D_ Months 1 – 6 Trial set-up and approvals; Months 7 – 30 Participant recruitment; Month 15 Assessment of internal pilot; Month 32 Follow-up of last participant; Months 33 – 38 Data cleaning, analysis and final report._x000D_ _x000D_ ANTICIPATED IMPACT AND DISSEMINATION_x000D_ Comprehensive plan co-produced with PPI to ensure outputs widely disseminated. Results expected to influence public, patient, clinician, manufacturer and policy-maker views, particularly if no advantage to POCTs. Positive results to inform a future pragmatic trial.

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