Development of a core outcome set for clinical trials in inflammatory bowel disease: study protocol for a systematic review of the literature and identification of a core outcome set using a Delphi survey
Open Access
- 9 June 2017
- Vol. 7 (6), e016146
- https://doi.org/10.1136/bmjopen-2017-016146
Abstract
Introduction Crohn’s disease (CD) and ulcerative colitis (UC), the main forms of inflammatory bowel disease (IBD), are chronic, progressive and disabling disorders of the gastrointestinal tract. Although data from randomised controlled trials (RCTs) provide the foundation of evidence that validates medical therapy for IBD, considerable heterogeneity exists in the measured outcomes used in these studies. Furthermore, in recent years, there has been a paradigm shift in IBD treatment targets, moving from symptom-based scoring to improvement or normalisation of objective measures of inflammation such as endoscopic appearance, inflammatory biomarkers and histological and radiographic end points. The abundance of new treatment options and evolving end points poses opportunities and challenges for all stakeholders involved in drug development. Accordingly, there exists a need to harmonise measures used in clinical trials through the development of a core outcome set (COS). Methods and analysis The development of an IBD-specific COS includes four steps. First, a systematic literature review is performed to identify outcomes previously used in IBD RCTs. Second, semistructured qualitative interviews are conducted with key stakeholders, including patients, clinicians, researchers, pharmaceutical industry representatives, healthcare payers and regulators to identify additional outcomes of importance. Using the outcomes generated from literature review and stakeholder interviews, an international two-round Delphi survey is conducted to prioritise outcomes for inclusion in the COS. Finally, a consensus meeting is held to ratify the COS and disseminate findings for application in future IBD trials. Ethics and dissemination Given that over 30 novel therapeutic compounds are in development for IBD treatment, the design of robust clinical trials measuring relevant and standardised outcomes is crucial. Standardising outcomes through a COS will reduce heterogeneity in trial reporting, facilitate valid comparisons of new therapies and improve clinical trial quality.Keywords
This publication has 43 references indexed in Scilit:
- Vedolizumab as Induction and Maintenance Therapy for Crohn's DiseaseThe New England Journal of Medicine, 2013
- Vedolizumab as Induction and Maintenance Therapy for Ulcerative ColitisThe New England Journal of Medicine, 2013
- Developing core outcome sets for clinical trials: issues to considerTrials, 2012
- Adalimumab Induces and Maintains Clinical Remission in Patients With Moderate-to-Severe Ulcerative ColitisGastroenterology, 2012
- Using the Delphi Technique to Determine Which Outcomes to Measure in Clinical Trials: Recommendations for the Future Based on a Systematic Review of Existing StudiesPLoS Medicine, 2010
- The COSMIN checklist for evaluating the methodological quality of studies on measurement properties: A clarification of its contentBMC Medical Research Methodology, 2010
- Direct Health Care Costs of Crohn's Disease and Ulcerative Colitis in US Children and AdultsGastroenterology, 2008
- The Direct and Indirect Cost Burden of Crohn's Disease and Ulcerative ColitisJournal of Occupational and Environmental Medicine, 2008
- Infliximab for Induction and Maintenance Therapy for Ulcerative ColitisThe New England Journal of Medicine, 2005
- Coated Oral 5-Aminosalicylic Acid Therapy for Mildly to Moderately Active Ulcerative ColitisThe New England Journal of Medicine, 1987