Protocol for the development of a core outcome set for clinical trials in primary sclerosing cholangitis

TY - JOUR

T1 - Protocol for the development of a core outcome set for clinical trials in primary sclerosing cholangitis

AU - Hussain, Nasir

AU - Ma, Christopher

AU - Hirschfield, Gideon

AU - Walmsley, Martine

AU - Hanford, Paula

AU - Vesterhus, Mette

AU - Kowdley, Kris

AU - Bergquist, Annika

AU - Ponsioen, Cyriel

AU - Levy, Cynthia

AU - Assis, David

AU - Schramm, Christoph

AU - Bowlus, Christopher

AU - Trauner, Michael

AU - Aiyegbusi, Olalekan Lee

AU - Jairath, Vipul

AU - Trivedi, Palak J

N1 - © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

PY - 2024/6/26

Y1 - 2024/6/26

N2 - 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.

AB - 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.

KW - Humans

KW - Cholangitis, Sclerosing/therapy

KW - Research Design

KW - Clinical Trials as Topic

KW - Delphi Technique

KW - Outcome Assessment, Health Care

KW - Endpoint Determination

KW - Systematic Reviews as Topic

U2 - 10.1136/bmjopen-2023-080143

DO - 10.1136/bmjopen-2023-080143

M3 - SCORING: Journal article

C2 - 38926149

VL - 14

SP - e080143

JO - BMJ OPEN

JF - BMJ OPEN

SN - 2044-6055

IS - 6

ER -