Coeliac disease affects approximately 1% of the population. A lifelong gluten-free diet remains the only established treatment, yet it is burdensome and does not resolve symptoms or intestinal damage in all patients. Several non-dietary therapies have entered clinical trials, but studies have used different outcomes, definitions and measurement tools. This limits comparison between trials and may have contributed to failed or inconclusive endpoint assessment. Existing recommendations, including the 2018 Tampere recommendations, were largely developed through expert consensus with limited direct patient involvement.
This study will develop an international, patient-informed core outcome set: the minimum outcomes that should be measured and reported in all adult coeliac disease treatment trials. The work will follow COMET and COS-STAD standards. First, a systematic review will identify outcomes, definitions, instruments and timepoints reported in treatment studies. Semi-structured interviews with adults living with coeliac disease will identify outcomes that may be absent from trials. These sources will form a plain-language longlist mapped to the COMET outcome taxonomy. Patients, healthcare professionals, researchers and trialists will then prioritise outcomes through an international Delphi survey. A patient pre-consensus meeting and independently chaired consensus meeting will use anonymous voting to agree the final set.
The project will produce a transparent, implementable outcome standard for dietary, pharmacological and adjunctive treatment trials. It will improve consistency, reduce selective outcome reporting and ensure future trials measure outcomes that matter to patients as well as clinicians and regulators.
Principal investigator: Dr Mohamed Shiha, University of Sheffield, UK
Contributors:
Professor David Sanders, University of Sheffield, UK
Dr Merel Kimman, Maastricht UMC+, the Netherlands
Pip Divall, University Hospitals of Leicester, UK
Dr Rose-Marie Satherley, University of Surrey, UK
Coeliac UK & the Association of European Coeliac Societies
Professor Jason Tye-Din, University of Melbourne, Australia
Professor Jonas F. Ludvigsson, Karolinska Institute, Sweden
Professor Daniel Keszthelyi, Maastricht UMC+, The Netherlands
Dr Sadé Assmann, Maastricht UMC+, The Netherlands
Dr Luca Elli, University of Milano, Italy
Dr Juha Taavela, Tampere University, Finland
Dr Hugo Penny, Sheffield Teaching Hospitals, UK
Nick Trott, Sheffield Teaching Hospitals, UK
Disease Category: Gastroenterology
Disease Name: Coeliac disease
Age Range: 18 - 80
Sex: Either
Nature of Intervention: Any
- Charities
- Clinical experts
- Consumers (patients)
- Epidemiologists
- Journal editors
- Methodologists
- Patient/ support group representatives
- Researchers
- COS for clinical trials or clinical research
- Consensus meeting
- Delphi process
- Interview
- Systematic review
This international mixed-methods study will follow the COMET Handbook, COS-STAD and COS-STAP standards. Five linked work packages are planned.
WP1 – Systematic review
A systematic review will identify outcomes reported in randomised and non-randomised interventional studies, protocols and trial registries evaluating treatments for adults with established coeliac disease. MEDLINE, Embase and CENTRAL will be searched alongside relevant clinical trial registries. Two reviewers will independently screen full texts. We will extract reported outcomes, definitions, instruments, metrics and assessment timepoints.
WP2 – Patient interviews
Approximately 15–25 adults with coeliac disease will participate in semi-structured online or telephone interviews. Purposive sampling will seek variation in demographics, disease duration, symptoms and treatment burden. Recruitment will be guided by information power and outcome-concept saturation. Inductive qualitative content analysis, within a qualitative descriptive approach, will identify patient-important outcomes that may be absent from previous trials.
WP3 – Outcome longlist
Outcomes identified through the systematic review and interviews will be combined, deduplicated and mapped to the COMET outcome taxonomy. Measurement instruments and timepoints will be recorded separately. Patient partners will review the plain-language wording and pilot the Delphi questionnaire. All decisions to merge, exclude or reword outcomes will be documented.
WP4 – International Delphi survey
Patients and patient representatives, healthcare professionals, and researchers or trialists will prioritise candidate outcomes through two rounds of an international online Delphi survey, with an optional third round if substantial uncertainty remains. Participants will use the nine-point GRADE/COMET importance scale and receive their previous scores and stakeholder-specific feedback before rescoring.
Consensus-in will require at least 70% of participants in each stakeholder group to score an outcome 7–9, with fewer than 15% scoring 1–3. Consensus-out will use the inverse rule. Outcomes prioritised by patients but not other groups will receive protected discussion. Attrition will be reported by stakeholder group, and missing scores will not be imputed.
WP5 – Final consensus
A patient pre-consensus meeting will review the Delphi findings and clarify patient priorities. The final international online consensus meeting will include representatives from each stakeholder group, selected using prespecified criteria. An independent facilitator will chair structured discussions, followed by anonymous voting. Unresolved outcomes will enter the final COS only if at least 70% of voting participants within each key stakeholder group support inclusion. Conflicts of interest will be declared, industry-affiliated results reported separately and reasons for excluding patient-priority outcomes documented.
Ethical approval will be obtained before participant recruitment. The final COS will be reported in accordance with COS-STAR.