Title: Water Assisted Sigmoidoscopy in NHS Bowel Scope Screening: a Randomised Multicentre Study (The WASH Study).
Funder: Department of Health and Social Care

Abstract: Background Bowel cancer is the second most common cause of cancer death in the UK, with over 40,000 new cases diagnosed every year(4). Recently, a large, UK randomised controlled trial (RCT) showed that screening 55-64 year olds with sigmoidoscopy reduced bowel cancer incidence and mortality in participants by 33% and 41% respectively(5). This is because sigmoidoscopy can detect and remove adenomas, the key cancer precursor, thereby preventing cancer development(3). Based on this trial, &ldquo;Bowel Scope Screening&rdquo; (BSS), comprising a one-off sigmoidoscopy at 55 years, began rollout in 2013. Sigmoidoscopy is invasive and can be painful due to bowel distension and scope &ldquo;looping&rdquo;. Data from a recent BSS patient-reported experience measure survey (43,378 patients) highlighted that 39% report moderate/severe pain(1). There is evidence that anticipation of pain represents an important barrier to public participation(2) - the current BSS sigmoidoscopy uptake rate is only 43.7% (BSS data, Mar 2016). Water-assisted colonoscopy is a recent technique which involves water infusion during scope insertion, instead of traditional CO2 insufflation. Water infusion requires a lower volume (under a litre) than CO2 infusion (10-20 litres), hence reducing distension and looping. Studies indicate this decreases procedural pain(6-10). Some studies also show increased adenoma detection rates (ADR)(9, 11, 12). However, no RCT has assessed water-assisted sigmoidoscopy (WAS), nor in UK practice. Aims We aim to investigate the effects of WAS on patient-reported procedural pain (primary, as guided by patient consultation). We hypothesise that WAS will decrease pain, when compared with CO2 insertion, improving patient experience. We also aim to investigate the effects of WAS on ADR, other aspects of patients experience and technical aspects of sigmoidoscopy. Research plan A multicentre, prospective, two-armed, randomised, single blinded study to evaluate performance of WAS in people referred for BSS screening. We aim to recruit 1100 patients (550 per study arm; 1:1 randomisation) over 18 months. The study is powered to detect a difference in the primary outcome of patient-reported procedural pain. Conventional CO2 sigmoidoscopy will be performed as per usual practice. The WAS technique involves disconnecting the CO2, and instilling water to achieve adequate luminal views, via the usual water irrigation system. In both arms, once maximal intubation has been achieved, CO2 insufflation will be reinstated for the inspection phase of the procedure, as per usual practice. Participants will rate their procedural pain on the standard BSS Likert scale prior to discharge. They will also rate maximal pain and overall pain using a validated visual analogue scale. A patient experience questionnaire will be completed the next day. Procedures will be performed by sigmoidoscopists trained in both CO2 and WAS techniques. Sigmoidoscopists will undergo a formal training package, comprising an educational session, video demonstrations, a live demo day, ongoing progress review and sign-off.(13) Potential benefits to patients and NHS If the trial shows that WAS either reduces pain or increases ADR, this may result in BCSP practice change to implement WAS, particularly considering it is cost-neutral. This will directly impact on the 256,000 people a year who will undergo BSS by 2020(14). We also anticipate that it would be introduced into non-BCSP endoscopic practice. A reduction in pain will benefit individual patients directly, reducing psychological harm and improving patient experience. Moreover, reduction in pain will increase screening test acceptability, potentially increasing screening uptake, preventing more cancers. An increase in adenoma detection is also likely to reduce cancer incidence &ndash; adenoma resection prevents cancer and recent studies have shown a strong inverse correlation between adenoma detection rate and post-colonoscopy colorectal cancer rate(13, 15). This will reduce the cost of treating bowel cancer, currently estimated at &pound;1.6 billion a year(16).

Lay abstract: Bowel cancer is the UK s second most common cause of cancer death. Over 1 in 20 people develop bowel cancer. To reduce this risk, the NHS Bowel Cancer Screening Programme (BCSP) invites 55 year olds for a sigmoidoscopy. This involves examining the lower bowel with a thin, flexible tube with a camera on it, via the back passage. The test can detect and remove warty growths called &ldquo;adenomas&rdquo;, which can progress to cancer if not removed. Research has shown that sigmoidoscopy reduces bowel cancer death by 41%. During the test, the bowel is inflated with carbon dioxide, to allow passage of the camera. The problem is that bowel distension can cause pain. National surveys show that over 1 in 3 patients report moderate or severe pain, leading us to conceive this trial. We plan to assess whether using water to minimise bowel distension, instead of gas, will make the procedure more comfortable. Early studies suggest this may be effective, but we need to know whether it works in UK practice. We hope that by reducing pain, people will have a better experience, which may increase public participation in screening. Currently only 43.7% of people participate &ndash; we can prevent more cancers if we increase participation. We wish to recruit 1100 people for the trial. Half will have normal sigmoidoscopy using carbon dioxide, and half will have sigmoidoscopy using water. We will then ask patients how comfortable they found the test, so that we know which is better. We will also measure which technique finds more adenomas. We have surveyed patients about this, leading to the trial being designed mainly around patient comfort. Results of the study will be published in an international journal and will be communicated to the BCSP and to patients and doctors internationally.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;4.4 POPULATION SCREENING
Health categories: CANCER AND NEOPLASMS