Background & Aims
End points to determine the efficacy and safety of medical therapies for Crohn’s disease (CD) and ulcerative colitis (UC) are evolving. Given the heterogeneity in current outcome measures, harmonizing end points in a core outcome set for randomized controlled trials is a priority for drug development in inflammatory bowel disease.
Methods
Candidate outcome domains and outcome measures were generated from systematic literature reviews and patient engagement surveys and interviews. An iterative Delphi process was conducted to establish consensus: panelists anonymously voted on items using a 9-point Likert scale, and feedback was incorporated between rounds to refine statements. Consensus meetings were held to ratify the outcome domains and core outcome measures. Stakeholders were recruited internationally, and included gastroenterologists, colorectal surgeons, methodologists, and clinical trialists.
Results
A total of 235 patients and 53 experts participated. Patient-reported outcomes, quality of life, endoscopy, biomarkers, and safety were considered core domains; histopathology was an additional domain for UC. In CD, there was consensus to use the 2-item patient-reported outcome (ie, abdominal pain and stool frequency), Crohn’s Disease Activity Index, Simple Endoscopic Score for Crohn’s Disease, C-reactive protein, fecal calprotectin, and co-primary end points of symptomatic remission and endoscopic response. In UC, there was consensus to use the 9-point Mayo Clinic Score, fecal urgency, Robarts Histopathology Index or Geboes Score, fecal calprotectin, and a composite primary end point including both symptomatic and endoscopic remission. Safety outcomes should be reported using the Medical Dictionary for Regulatory Activities.
Conclusions
This multidisciplinary collaboration involving patients and clinical experts has produced the first core outcome set that can be applied to randomized controlled trials of CD and UC.
The aim was to develop the first international consensus-based COS for use in Crohn’s disease and ulcerative colitis RCTs.
ContributorsThe CORE-IBD Collaborators: Christopher Ma, Jurij Hanzel, Remo Panaccione, William J. Sandborn, Geert R. D’Haens, Vineet Ahuja, Raja Atreya, Charles N. Bernstein, Peter Bossuyt, Brian Bressler, Robert V. Bryant, Benjamin Cohen, Jean-Frederic Colombel, Silvio Danese, Axel Dignass, Marla C. Dubinsky, Phillip R. Fleshner, Richard B. Gearry, Stephen B. Hanauer, Ailsa Hart, Paulo Gustavo Kotze, Torsten Kucharzik, Peter L. Lakatos, Rupert W. Leong, Fernando Magro, Julian Panés, Laurent Peyrin-Biroulet, Zhihua Ran, Miguel Regueiro, Siddharth Singh, Antonino Spinelli, A. Hillary Steinhart, Simon P. Travis, C. Janneke van der Woude, Bruce Yacyshyn, Takayuki Yamamoto, Matthieu Allez, Willem A. Bemelman, Amy L. Lightner, Edouard Louis, David T. Rubin, Ellen J. Scherl, Corey A. Siegel, Mark S. Silverberg, Severine Vermeire, Claire E. Parker, Stefanie C. McFarlane, Leonardo Guizzetti, Michelle I. Smith, Niels Vande Casteele, Brian G. Feagan, and Vipul Jairath
Disease Category: Gastroenterology
Disease Name: Inflammatory bowel disease (IBD)
Age Range: 18
Sex: Either
Nature of Intervention: Non-surgical
- Clinical experts
- Consumers (patients)
- Methodologists
- Researchers
- COS for clinical trials or clinical research
- Consensus meeting
- Delphi process
- Interview
- Survey
- Systematic review
Phase 1: Outcome identification through systematic review. Phase 2: Patient engagement surveys and interviews. Phase 3: 2-round Delphi survey. Phase 4: Consensus meetings.