Developing IBD outcome effect size thresholds to inform research, guidelines and clinical decisions

Abstract

Background
When designing clinical trials, interpreting trial outcomes for guideline development or sharing decisions with patients in clinical practice, the clinical outcomes used and the implicit choices on what constitutes a clinically significant finding can vary greatly. This can lead to diversity or even inequity in care offered to patients with inflammatory bowel disease. The GRADE approach to guideline development has proposed a process to address this prospectively to solve these issues, but this has never been used inflammatory bowel disease (IBD). We aimed to develop the first international consensus set of outcome thresholds to establish their use in Crohn’s disease and ulcerative colitis.

Methods
A Delphi methodology was used to develop a consensus. An online survey was conducted by inviting stakeholders from the British Society of Gastroenterology (BSG) through a two-phase process. Participants were asked to select important clinically relevant outcomes and were asked about what magnitude of the effect they consider large, moderate, small, or trivial for each clinical trial outcome in line with the GRADE guidance. The results were fedback to all participants to ensure consensus agreement. Then, further surveys were sent to Europe and North America to ensure validity and international triangulation of the data set. Data are presented as mean percentages with standard deviation (SD).

Results
131 clinical stakeholders participated including clinicians, IBD nurses and a small number of patients with IBD. Clinical remission and serious adverse events were considered the most critical outcomes for Crohn’s disease while clinical remission and endoscopic remission were for ulcerative colitis. The consensus results for thresholds of small, moderate and large outcome effects size were agreed with as follows: clinical remission 11 (SD 6), 20 (8) and 31 (13), endoscopic remission 9 (5), 17 (9) and 28 (14), and serious adverse events 6 (6), 11 (9) and 17 (12) respectively. No significant differences were observed for responses for each condition.

Conclusion
This is the first study to develop a consensus on magnitude thresholds for outcomes in IBD. These thresholds have been used in the development of the 2024 BSG guidelines for the management of IBD but can and should also be used by study designers and mostly importantly for clinicians when discussing evidence with patients as part of shared decision making. Future work to validate these findings globally and with other groups, including patients, is needed