Title: The effectiveness and acceptability of urine collection devices to reduce contaminated urine samples in women presenting with symptoms of urinary tract infection. A three arm trial in UK primary care
Funder: Department of Health and Social Care

Abstract: Background: Urinary tract infection (UTI) is one of the commonest bacterial infections managed in general practice, affecting about 10% of women every year1. The reference standard investigation is urine culture, and we estimate that 6 million samples are analysed each year from primary care in England and Wales. However, bacteria from the host s skin and vaginal secretions often contaminate samples, resulting in a mixed growth or equivocal result in up to 30% of cases2. This results in delay in diagnosis and increased use of inappropriate antibiotics in addition to increased resource use: if all contaminated specimens were repeated this would cost over &pound;14 million annually. Currently two readily available urine collection devices (UCDs) claim to reduce urine contamination rates: the Peezy and the Whizaway midstream . These devices use different mechanisms to funnel the midstream of the urine into a sterile container. The efficacy evidence supporting their use in primary care is contradictory. Adult women with symptoms attributable to a UTI are most likely to benefit, yet there has never been a pragmatic trial of these devices in symptomatic female patients in general practice. Despite this, these devices are being marketed for use in routine primary care and are already being used in some NHS trusts. Good quality evidence is required to guide general practitioners and commissioners in the optimal technique for collection of urine samples to avoid unnecessary contamination. Aims: To determine whether contamination rates in urine samples from women presenting to UK General Practice with symptoms that could be attributable to a UTI are reduced when UCDs are used compared to when samples are taken after standard advice. We also aim to assess the impact of UCDs on the performance of dipstick urinalysis in predicting infection, the acceptability of UCDs to patients and primary care professionals, and the cost effectiveness of UCDs. Study Plan: We propose a single blind, 3 arm, individually randomised controlled trial in women presenting to UK primary care with symptoms of UTI. Eligible patients will be randomised to provide a urine sample with either standardised usual care instructions, or a UCD and related instructions. Our primary outcome will be the proportion of contaminated samples: i.e. specimens reported as either mixed growth or a pure culture of a known contaminant by a central microbiology laboratory using national standard operating procedures. Secondary outcomes will include the sensitivity and specificity of dipstick results for true infection in each arm, acceptability to patients and primary care staff, and cost effectiveness. We estimate that a total sample size of 1191, with 397 patients per arm (&alpha; = 0.05 power = 0.9) will be required to detect a difference in contamination rates of 10%, allowing for 5% loss of specimens. We will assess baseline comparability of groups using descriptive statistics, and perform comparative analyses on an intention-to treat basis. A subset of patients from the UCD arms will contribute to a qualitative interview study exploring experiences of the UCD and confirming adherence to protocol, and a focus group study will assess acceptability and implementation with Primary Care professionals. Potential benefits to patients and the NHS: Urine samples reported as mixed growth are at best unhelpful to the clinician and, at worst, harmful to the patient since they are neither able to confirm nor exclude infection. They lead to increased patient distress through prolonged symptoms, untreated infection and inappropriate antibiotic choice, increased antimicrobial resistance, and increased NHS cost due to re-testing. The findings of this trial will offer primary healthcare teams and clinical commissioning groups nationwide much needed guidance on the optimal technique for sample collection.

Lay abstract: One in ten women visit their GP each year with symptoms that may be caused by urine infection. In order to confirm infection and guide prescription of the most appropriate antibiotic, GPs can send a urine sample to a laboratory. About 6 million urine samples are sent from primary care each year in England and Wales. However, up to 1 in 3 samples will be contaminated by bacteria from the patient s skin and secretions, leading to a result from the laboratory that is not helpful. Consequently, the patient may receive an antibiotic which does not target the correct infecting organism, so more than one course of treatment is required. This could result in up to 7 days of debilitating symptoms. Patients who take more courses of antibiotics are more likely to have an infection resistant to antibiotics in the future, which can be difficult to cure. Re-testing contaminated samples costs up to &pound;14 million a year, and uses additional valuable GP time. A urine collection device could reduce the likelihood of sample contamination, but this still needs to be assessed in women with symptoms of urine infection. We aim to compare the proportion of contaminated samples when obtained after usual instructions, to the proportion of contaminated samples when produced using two currently available urine collection devices (pictures in supplementary materials). The researchers analysing the specimens will not know which technique has been used. We will also assess the cost effectiveness of the devices and their acceptability to patients, GPs, and surgery staff. We will appoint a public advisory panel to assist us in patient recruitment, trial design, interpreting our findings and disseminating the trial results. Our group of researchers has excellent collective experience in running large trials in primary care infection research, assessing acceptability of devices and health economics.

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