UK Cohort study to Investigate the prevention of Parastomal Hernia (CIPHER)

DESIGN: Our proposed research project has two components: Phase A: Phase A will comprise preliminary work to establish the key surgical steps that may influence parastomal hernia (PSH) formation and test patient reported outcome measures (PROs) for symptomatic PSH to use in Phase B. Phase B: Phase B will be the main multi-centre pragmatic cohort study. It will identify key technical surgical factors, defined during Phase A, that are associated with PSH. Participants will be recruited at the time of surgery. SETTING: 50+ acute hospital Trusts in the UK POPULATION: Adults (18+ yrs) undergoing planned surgery with the intention to form a stoma. Inclusion: Surgery requiring formation of ileostomy or colostomy. Exclusion: Emergency surgery; double-barrelled stoma; urostomy formation; previous abdominal wall stoma; life expectancy <12 months. SURGICAL TECHNIQUES OF INTEREST: Surgical techniques [estimated use] of stoma formation; a) creation of stoma trephine in abdominal wall (location within or without the rectus sheath); b) use of mesh/type (none [80%] vs biologic [10%] vs synthetic [10%]); c) mesh position (intra-abdominal [15%] vs sublay/ retrorectus [80%] vs onlay [<5%]); d) trephine shape in the mesh (circle [30%] vs cross [60%] vs slit AND none [10%](Sugarbaker)). These techniques will be defined in Phase A. COSTS: Cost-utility of different surgical methods of stoma formation with respect to the risk of PSH will be estimated using data collected from participants and from routine sources. It will consider the costs of in-theatre, in-hospital, community care and social service resources, time off work, and personal out-of-pocket expenditure. Cost-utility will be estimated from NHS and societal perspectives. HES data will describe hospital resource use and the NHS Central Register will provide vital status. OUTCOME MEASURES: The primary outcome will be PSH incidence in the 2-years following surgery, defined as symptomatic PSH (participant-reported quarterly) with radiological (CT) confirmation. Symptoms of PSH include difficulties with stoma appliances or discomfort/pain. A defined pre-agreed threshold will be used. Clinical and radiological protocols will be used to confirm PSH. Secondary outcomes will include hospital stay, surgical site infection and other complications, PSH repair and generic (EQ-5D-5L, SF12) and disease specific patient-reported outcomes. Follow up will be optimised using post/web/social media/SMS. RECRUITMENT: About 13,000 stoma-related procedures were recorded in HES in 2012-13, excluding loop ileostomies. We estimate that 50 Trusts will carry out about stoma forming procedures eligible for CIPHER on about 4,000 patients/year and that 50% will consent; this gives a sample of 4,000 in 2 years, each centre recruiting about 4 patients/month. SAMPLE SIZE: The incidence of PSH is unknown; we assume that it is 30-40% by 2 years. Surgical techniques of interest are used with varying frequencies. Considering extremes, i.e. ratios of 1:2 and 1:20, the study will have 90% power to detect adjusted hazard ratios between 1.2 and 1.9 at the 5% significance level (2-sided). ANALYSES: Survival multilevel model of time to PSH, estimating hazards of key predictors (see Surgical techniques) after adjusting for important procedure, patient and surgeon confounding factors. Follow-up will be censored if bowel function is restored or participants die. STUDY UPDATE: Recruitment was reviewed by the Study Steering Committee (SSC) in April 2021, when advising about a request to the funder for a costed contract variation. In addition to slower than expected recruitment of sites and participants since the outset, recruitment to the study was paused at most sites from March 2020 due to the COVID-19 pandemic, and only 443 participants were recruited between then and May 2021. The total number recruited at 22nd May was 2440. After discussion with the SSC, the CIPHER study team applied to the NIHR to end recruitment on 30th June 2021. The main reason for making this recommendation was that CIPHER was primarily designed to inform the future research agenda for preventing PSH, rather than to provide definitive estimates of the effects of particular surgical steps. The current sample is sufficient to do this. The NIHR agreed with this decision and to a funded extension to allow continued follow up the existing cohort for a further 15 months from 1st July 2021.