Developing IBD Outcome Effect Size Thresholds to Inform Research, Guidelines, and Clinical Decisions.

backgroundWhen 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 (IBD). The GRADE approach to guideline development has proposed a process to address this prospectively to solve these issues, but this has never been used in IBD. We aimed to develop the first international consensus set of outcome thresholds to establish their use in Crohn's disease and ulcerative colitis.

methodsA Delphi methodology was used to develop a consensus. An online survey was conducted by inviting stakeholders from the British Society of Gastroenterology through a 2-phase process. Participants were asked to select important clinically relevant outcomes and were asked about what magnitude of the effect that they consider large, moderate, small, or trivial for each clinical trial outcome in line with the GRADE guidance. The results were fed back 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 dataset. Data are presented as mean ± SD.

resultsA total of 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 considered the most critical outcomes for ulcerative colitis. The consensus results for thresholds of small, moderate, and large outcome effect sizes were agreed on as follows: clinical remission, 11 ± 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.

conclusionsThis 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 British Society of Gastroenterology guidelines for the management of IBD but can and should also be used by study designers and, most importantly, by 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.