Title: DEVELOPMENT OF A UK EVIDENCE-BASED PATHWAY FOR THE MANAGEMENT OF CHRONIC CONSTIPATION IN ADULTS
Funder: Department of Health and Social Care

Abstract: Aims and objectives The aim of this programme is to answer the important research questions relevant to an NHS evidence-based management of chronic constipation (CC) in adults and derive an appropriate and cost-effective pathway of care. Background and rationale CC - defined as more than 6 months of symptoms that are unresponsive to laxative therapy affects up to 10% of the population and is especially prevalent in women. CC leads to significantly impaired QOL and is a major consumer of healthcare resource. While many new treatments are emerging, there is almost no agreement (or published NHS guidance) as to which are most effective, what investigations are warranted, or in what order such investigations and interventions should be offered. The overall rationale of the programme is to develop an evidence base for CC management through a series of interlinked work packages (WPs) that answer these important questions. Research environment & team expertise The research team comprises leading UK clinicians in bowel management (primary care, gastroenterology, surgery, colorectal nursing, radiology, physiology, psychology and urogynaecology) together with broad methodological expertise. Trials will be managed by the Pragmatic Clinical Trials Unit at Barts Health NHS Trust and Queen Mary University of London. Research plan In WP1, national recruitment from primary care networks and approx. 10 specialist centres in England will provide (over 2.5 years) a large selected cohort of approximately 1000 well-defined patients for subsequent studies within parallel WPs. This cohort will be profiled at baseline for characteristics of interest per se and which may serve as outcome predictors. In WP2, 600 patients will be randomly allocated to 2 groups on the basis of whether they receive (INVEST: n=200) or do not receive (NO-INVEST: n=400) specialist radio-physiological investigations. A nested randomised trial of the 400 NO-INVEST patients will determine whether a more complex and expensive intervention (biofeedback with habit training) is more effective than a less complex one (habit training alone) in unselected CC patients. A comparison of these outcomes with those from the INVEST-stratified treatment arm will determine the added value of extensive investigation. In WP3, patients who have failed behavioral training will be recruited to a waiting list RCT of anal irrigation. Non-responders to anal irrigation will be eligible for waiting list RCTs of surgical interventions (WP4). These RCTs will determine short-term effectiveness of interventions and also response predictors that might target future treatment (by longitudinal follow up). All WPs will use a common, standardised outcome framework to assess the value of treatments, with a validated patient reported outcome score (PAC-QOL) providing the primary clinical outcome. Together, the WPs will generate real-life evidence using pragmatic studies to inform patient outcomes, acceptability and cost. In WP5, findings will be assimilated and synthesised with previous research, and a national working group convened to develop a new treatment pathway for management of CC in adults. The working group will identify best practice, remaining controversies and mechanisms for promoting the uptake of findings by the NHS. Project outputs and dissemination plans Summative findings will be disseminated as guidance to the NHS, promoting a new treatment pathway for the management of CC in adults (a NICE guideline for the management of CC in adults does not currently exist). While it is accepted that the programme will be conducted in secondary and tertiary settings, such guidance will directly affect primary care management by informing timely referral for further hospital-based investigations or treatment. A detailed plan at professional, patient and public levels will ensure broad dissemination of the programme findings. All scientific findings will be published in peer-reviewed academic journals and we will seek to engage with patients, public and media to raise awareness of attitudes, problems and solutions for adult CC. Justification of costs A total research cost of &pound;1,997,327 provides for full CTU programme management; dedicated research staff, qualitative research costs (approx. 100 interviews and analysis); evidence synthesis and health economic evaluations as well as directly incurred costs to institutions for the applicant team; UK travel and subsistence for trial managers and research nurses, patients and programme steering committee (PSC); PPI management and some equipment / consumables. Management and governance A PSC will be comprised of an independent chair, 3 independent members including PPI representation, the Chief Investigator, WP leads, and relevant co-investigators. An independent data monitoring committee will assist the PSC according to standard clinical trial protocol. A defined schedule of meetings and interim reporting will ensure that recruitment milestones are met and that the overall programme is delivered to time and cost. Patient and public involvement A constipation research advisory group will be formed as part of a well-developed PPI strategy at QMUL (in close association with the Charity Bowel and Cancer Research). This advisory group will participate in development of all patient interface documents and two members will serve on the programme steering committee.

Lay abstract: Some degree of constipation affects nearly everyone at some stage in their life. However, some people suffer chronic symptoms that seriously impair their quality of life and which require medical intervention. Chronic constipation describes patients who have a longer duration of symptoms (more than 6 months) and who fail to respond to basic measures e.g. exercise, increased fluid intake, simple diet changes and laxatives. This problem may affect about 1 in 10 people, especially women, with about 1 in 50 people seeking specialist hospital management. Chronic constipation can be remarkably difficult to treat effectively, even in specialist units, resulting in a significant and sometimes severe impact on quality of life. Current approaches include laxatives and newer drugs, nurse-led bowel retraining programmes, bowel (anal) irrigation, and a variety of surgical operations that may have variable, and sometimes very poor, results. While there is current optimism that the situation for such patients will improve with several new treatments being developed (drugs and medical devices), there is a lack of evidence about which treatments should be offered to patients and when, and practice varies widely between centres. Further, the value of certain specialist (expensive and invasive) investigations which may help to understand the underlying cause of the constipation is also unclear. In a resource-constrained NHS, doctors and patients need to have confidence that new and sometimes expensive therapies are cost-effective and that the old ones actually work. The aim of this programme of research is to recruit a large number of adult patients (about 1000 in total) with chronic constipation (from primary care and secondary specialist centres in England over 2-3 years) who will then participate in several important trials of the main current non-drug therapies. These treatments will include two types of specialist nurse-led bowel retraining, anal irrigation and surgery. For each treatment, we will collect detailed data on the effectiveness in reducing symptoms, patient acceptability and NHS cost. We will also determine the value of particular specialist investigations in being able to successfully guide treatment. Patients failing one treatment will be able to move onto the next. Subsequently, we will synthesise our new evidence and published research findings to develop a guidance document for the NHS, which can be used nationally as a treatment pathway to provide effective care to patients in a timely fashion.

Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING;8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: ORAL AND GASTROINTESTINAL