TOAST-IBD: Treatment related Outcomes Associated with SToma in IBD: Developing core outcomes measures for intervention studies in patients with IBD who have stomas

Crohn’s Disease (CD) and Ulcerative Colitis (UC) are collectively known as Inflammatory Bowel Disease (IBD) and a small number of patients are diagnosed with IBD-Undetermined, where a distinction between the two conditions is not possible. They are both chronic relapsing-remitting diseases of the gastrointestinal tract, with peak age of onset in children and young adults. There is currently no cure, and the disease is associated lifelong morbidity. Recent decades have seen a steady rise in the incidence and prevalence of both UC and CD. In Scotland IBD prevalence increased by 4.3% p.a. between 2008-18 with all-age point prevalence of 1/125. Given the similarities (both genetic and environmental), there is reason to suspect a similar population prevalence in Ireland. Published data has shown a threefold increase in IBD incidence in children in Ireland in the last decade. This will lead to a significant expansion in prevalence in the adult population in the coming decades.

Patients with stomas are excluded from clinical trials of investigational medicinal products, primarily because of the difficulty in calculating disease activity scores such as Crohn’s Disease Activity Index (CDAI) and the Mayo Score for UC. Improvement in these disease activity indices (DAI) are typically used in determining the primary end points for clinical trials of drug therapies for IBD. Dedicated core outcome sets have recently been developed for fistulising peri-anal Crohn’s. A similar approach is needed in IBD patients with stomas, especially patients with Crohn’s disease, who often have treatment refractory disease, have failed medical therapies, and need access to new therapies. TOAST-IBD is a collaborative project established by INITIative (www.initiativeibd.ie) the IBD collaborative research network for Ireland to determine outcome measures that can be used to assess the clinical effectiveness of medical, surgical, nutritional, physical, and psychological treatment interventions for patients with IBD who have stomas.

The Core Outcome Measures in Effectiveness Trials (COMET; www.comet-initiative.org/initiative) initiative has improved understanding of outcome reporting and standardised outcome reporting through the development of core outcome sets (COS). COSs are the minimum outcomes that should be reported in every study of a given condition. They have usually been informed by a systematic review and developed through a Delphi consensus process with key stakeholders. COS are not restrictive; triallists may choose to investigate other outcomes but should always include the COS as a minimum within their study design.

Pragmatic trials are designed to assess whether an intervention is effective for routine clinical practice. However, focusing on physical health as a treatment target alone is insufficient for restoring health and quality of life. Outcomes therefore, need to be relevant to patients and clinicians. COS in IBD include validated measures of disease activity and PROs such as validated questionnaires. Industry sponsored trials in IBD utilize validated measures of disease activity such as the Mayo score (UC) and Crohn’s disease activity index (CDAI), as well as validated PROs including the IBDQ, SHS, EQ-5D, and SF-36. INITiative members have been involved in developing/validating several other outcome measures more suited to application in daily clinical practice. The DUBLIN score was developed because endoscopic scores of local severity don’t always reflect disease extent/burden. The DUBLIN score is a simple bedside clinical score that estimates inflammatory burden using disease severity and extent. INITIative investigators have pioneered the development/validation of novel PROM such as the Body Image Scale and the IBD-specific Male and Female Sexual Dysfunction Scales. Most industry sponsored studies exclude patients with perianal disease, stomas, limited proctitis and ileo-anal pouches. Future INITIative studies will focus on these understudied groups and development /validation of COS for these populations is now a priority. The Body Image Scale and IBD sexual dysfunction scales will likely form an important part of the COS for this sub-populations, as physical appearance can be altered by the cosmetic issues resulting from the underlying disease activity and surgical treatment.

Aims and Objectives

The overall aim is to achieve consensus on which clinical and patient reported outcomes are most representative of clinical effectiveness in patients with IBD with stomas receiving treatment/intervention.

1.To define how these outcomes are best measured and to develop and validate tools for measuring those outcomes ranked most important.

2.To verify the outcomes are responsive to effective treatment/interventions and thus to facilitate the inclusion of patients with IBD who have stomas in future clinical trials and intervention studies.

3.To improve the representation of patients with IBD who have stomas in trials and thus make future results more generalizable.

Inclusion Criteria

1.Patients over the age of 18 years with a confirmed diagnosis of IBD and a stoma (Phase 1)

2.Patients over the age of 18 years with a confirmed diagnosis of Crohn’s Disease and a stoma (Phase 3 only)

Exclusion Criteria

1.Patients under the age of 18 years

2.Patients without a stoma

3.Patients with ulcerative colitis or with a planned reversal of stoma in the next 3 months (phase 3 only)