Protocol for the development of a core outcome set for clinical trials in primary sclerosing cholangitis
Martine Walmsley,
Vipul Jairath,
Christoph Schramm,
Michael Trauner,
Christopher Ma,
Gideon Hirschfield,
Palak J Trivedi,
Nasir Hussain,
Olalekan Lee Aiyegbusi,
Mette Vesterhus,
Kris Kowdley,
Cyriel Ponsioen,
Annika Bergquist,
Paula Hanford,
Cynthia Levy,
David Assis,
Christopher Bowlus
Affiliations
Martine Walmsley
5 PSC Support, Oxford, UK
Vipul Jairath
19 Department of Medicine, Division of Gastroenterology, Western University, London, Ontario, Canada
Christoph Schramm
13 First Department of Medicine, Martin Zeitz Centre for Rare Disease and Hamburg Centre of Translational Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Michael Trauner
16 Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Wien, Austria
Christopher Ma
3 Department of Medicine and Community Health Sciences, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada
Gideon Hirschfield
4 Toronto Centre for Liver Disease, Division of Gastroenterology and Hepatology, University of Toronto, Toronto, Ontario, Canada
Palak J Trivedi
1 NIHR Birmingham Biomedical Research Centre, Birmingham, UK
Nasir Hussain
1 NIHR Birmingham Biomedical Research Centre, Birmingham, UK
Olalekan Lee Aiyegbusi
18 NIHR Birmingham Biomedical Research Centre, University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, University of Birmingham, Birmingham, UK
Mette Vesterhus
6 Norwegian PSC Research Centre, Department of Transplantation Medicine, Division of Surgery, Oslo University Hospital, Oslo, Norway
Kris Kowdley
8 Liver Care Network and Organ Care Research, Swedish Medical Center, Seattle, Washington, USA
Cyriel Ponsioen
10 Department of Gastroenterology and Hepatology, Academic Medical Centre, Amsterdam University Medical Centres, Amsterdam, The Netherlands
Annika Bergquist
9 Department of Gastroenterology and Hepatology, Karolinska University Hospital, Stockholm, Sweden
Paula Hanford
5 PSC Support, Oxford, UK
Cynthia Levy
11 Miller School of Medicine, University of Miami, Miami, Florida, USA
David Assis
12 Department of Medicine, Section of Digestive Disease, Yale School of Medicine, New Haven, Connecticut, USA
Christopher Bowlus
15 Department of Internal Medicine, University of California Davis, Davis, California, USA
Background Primary sclerosing cholangitis (PSC) is a progressive immune-mediated liver disease, for which no medical therapy has been shown to slow disease progression. However, the horizon for new therapies is encouraging, with several innovative clinical trials in progress. Despite these advancements, there is considerable heterogeneity in the outcomes studied, with lack of consensus as to what outcomes to measure, when to measure and how to measure. Furthermore, there has been a paradigm shift in PSC treatment targets over recent years, moving from biochemistry-based endpoints to histological assessment of liver fibrosis, imaging-based biomarkers and patient-reported outcome measures. The abundance of new interventional trials and evolving endpoints pose opportunities for all stakeholders involved in evaluating novel therapies. To this effect, there is a need to harmonise measures used in clinical trials through the development of a core outcome set (COS).Methods and analysis Synthesis of a PSC-specific COS will be conducted in four stages. Initially, a systematic literature review will be performed to identify outcomes previously used in PSC trials, followed by semistructured qualitative interviews conducted with key stakeholders. The latter may include patients, clinicians, researchers, pharmaceutical industry representatives and healthcare payers and regulatory agencies, to identify additional outcomes of importance. Using the outcomes generated from the literature review and stakeholder interviews, an international two-round Delphi survey will be conducted to prioritise outcomes for inclusion in the COS. Finally, a consensus meeting will be convened to ratify the COS and disseminate findings for application in future PSC trials.Ethics and dissemination Ethical approval has been granted by the East Midlands—Leicester Central Research Ethics Committee (Ref: 24/EM/0126) for this study. The COS from this study will be widely disseminated including publication in peer-reviewed journals, international conferences, promotion through patient-support groups and made available on the Core Outcomes Measurement in Effectiveness Trials (COMET) database.Trial registration number 1239.
