Heterogeneity in Definitions of Endpoints for Clinical Trials of Ulcerative Colitis: A Systematic Review for Development of a Core Outcome Set

Christopher Ma; Remo Panaccione; Richard N Fedorak; Claire E Parker; Tran M Nguyen; Reena Khanna; Corey A Siegel; Laurent Peyrin-Biroulet; Geert D'Haens; William J Sandborn; Brian G Feagan; Vipul Jairath

doi:10.1016/j.cgh.2017.08.025

Heterogeneity in Definitions of Endpoints for Clinical Trials of Ulcerative Colitis: A Systematic Review for Development of a Core Outcome Set

Clin Gastroenterol Hepatol. 2018 May;16(5):637-647.e13. doi: 10.1016/j.cgh.2017.08.025. Epub 2017 Aug 24.

Authors

Affiliations

¹ Division of Gastroenterology and Hepatology, University of Calgary, Calgary, Alberta, Canada.
² Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada.
³ Robarts Clinical Trials, Western University, London, Ontario, Canada.
⁴ Robarts Clinical Trials, Western University, London, Ontario, Canada; Department of Medicine, Western University, London, Ontario, Canada.
⁵ Section of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire.
⁶ Department of Gastroenterology and Inserm U954, Nancy University Hospital, Lorraine University, Nancy, France.
⁷ Robarts Clinical Trials, Western University, London, Ontario, Canada; Inflammatory Bowel Disease Centre, Academic Medical Centre, Amsterdam, the Netherlands.
⁸ Robarts Clinical Trials, Western University, London, Ontario, Canada; Division of Gastroenterology, University of California, San Diego, La Jolla, California.
⁹ Robarts Clinical Trials, Western University, London, Ontario, Canada; Department of Medicine, Western University, London, Ontario, Canada; Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada.
¹⁰ Robarts Clinical Trials, Western University, London, Ontario, Canada; Department of Medicine, Western University, London, Ontario, Canada; Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada. Electronic address: vjairath@uwo.ca.

PMID: 28843356
DOI: 10.1016/j.cgh.2017.08.025

Abstract

Background & aims: Advances in development of therapeutic agents for ulcerative colitis (UC) have been paralleled by innovations in trial design. It would be useful to identify a core outcome set, to standardize outcome definitions for efficacy and safety in clinical trials. We performed a systematic review of efficacy and safety outcomes reported in placebo-controlled randomized controlled trials of patients with UC.

Methods: We searched MEDLINE, EMBASE, and the Cochrane Library from inception through March 1, 2017, for placebo-controlled randomized controlled trials of adult patients with UC treated with aminosalicylates, immunosuppressants, corticosteroids, biologics, and oral small molecules. We collected information on efficacy and safety outcomes, definitions, and measurement tools, stratified by decade of publication.

Results: We analyzed data from 83 randomized controlled trials (68 induction and 15 maintenance) comprising 17,737 patients. Clinical or composite-clinical efficacy outcomes were reported in all trials; the UC Disease Activity Index and Mayo Clinic Score were frequently used to determine clinical response or remission. We found substantial variation in definitions of clinical or composite-clinical endpoints, with more than 50 definitions of response or remission. Endoscopic factors, histologic features, and fecal or serum biomarkers were used to determine outcomes in 83.1% (69 of 83), 24.1% (20 of 83), and 24.1% (20 of 83) of trials, respectively. A greater proportion of trials published after 2007 reported objective outcomes (96.5% endoscopic, 26.3% histologic, and 36.8% biomarker outcomes), but no standardized definitions of histologic or biomarker endpoints were found. Patient-reported efficacy and quality-of-life outcomes were described in 25 trials (30.1%) and safety outcomes were reported in 77 trials (92.8%).

Conclusion: In a systematic review, we found that despite recent advances in clinical trials methods, there is a great deal of variation in definitions of endpoints, including response and remission, in randomized controlled trials of patients with UC. Researchers should identify a core set of outcomes to standardize efficacy and safety reporting in UC clinical trials.

Keywords: COS; IBD; MCS; RCT; UCDAI.

Publication types

Systematic Review

MeSH terms

Colitis, Ulcerative / pathology*
Colitis, Ulcerative / therapy*
Gastrointestinal Agents / adverse effects*
Gastrointestinal Agents / therapeutic use*
Humans
Randomized Controlled Trials as Topic / standards*
Treatment Outcome

Substances

Gastrointestinal Agents