Core Outcome Measures in Effectiveness Trials

Development of Core Outcomes Measures for Clinical Trials in Primary Sclerosing Cholangitis (PSC)

General Information

Summary:
Primary sclerosing cholangitis (PSC) is an immune-mediated liver disease leading to inflammation and progressive stricturing of the bile ducts. Presently, there is no medical therapy consistently proven to slow disease progression; and liver transplantation is the only life-extending intervention for PSC.

However, at least 28 interventional studies have been published in the literature targeting the drivers of cholestasis, leukocyte recruitment, and tissue fibrosis. In parallel, a paradigm shift in the treatment targets for PSC has occurred, with a move away from serum liver biochemistry to a more objective assessment of liver disease severity and bile duct injury. Equally, in recognition of the need to accurately measure the patient experience with PSC, the US Food and Drug Administration (FDA) has advocated the measurement of patient-reported outcomes (PROs).

Insufficient attention has been paid to the standardized assessment of outcome measures for PSC trials. Notably, no formalized consensus exists regarding what to measure, how to measure and when to measure selected efficacy and safety outcomes. Given the evolving landscape of PSC therapeutics and development of study endpoints, international consensus agreements on core outcomes for use in future PSC trials are of critical importance.

Aim:
This programme of work aims to develop a core outcome set for application to clinical trials in the immune-mediated liver disease Primary Sclerosing Cholangitis (PSC). These will be developed initially for adult clinical trials but subsequently also for pediatric trials.

Contributors:
Principal Investigator:
- Chief Investigator for UK-PSC
- Clinician Scientist; NIHR Birmingham BRC, University of Birmingham (UK)
- Consultant Hepatologist; University Hospitals Birmingham (UK)

Contributors:
- Institute of Immunology and Immunotherapy, University of Birmingham
- Institute of Applied Health Research, University of Birmingham
- UK-PSC Study Group
- Toronto Centre for Liver Disease, University Health Network, University of Toronto, Toronto, Canada
- Division of Gastroenterology and Hepatology, University of Calgary, Calgary, Alberta, Canada.
- Robarts Clinical Trials, Western University, London, Ontario, Canada.
- Department of Biostatistics, University of Liverpool
- PSC Support (UK patient support charity).

Further Study Information

Current Stage:
Ongoing
Date:
October 2018 - October 2022
Funding source(s):
Institutional Support funding through the National Institute for Health Research Research (NIHR) Birmingham Biomedical Research Centre (BRC) currently in place. Developmental Grant application submitted. Fellowship application in progress.

Health Area

Disease Category
Gastroenterology

Disease Name
Primary Sclerosing Cholangitis (PSC)

Target Population

Age Range
8 - 80

Sex
Either


Nature / type of Intervention
Drug
Surgery

Method(s)

Consensus conference
Consensus meeting
Delphi process
Focus group(s)
Literature review
Semi structured discussion
Systematic review

1) To conduct a systematic review to produce a comprehensive list of outcome measures reported in clinical trials of PSC. Trials covered in existing meta-analysis, systematic reviews and Cochrane reviews would be also studied. This would generate a list of clinical, laboratory, endoscopic, radiological, histological, healthcare economic and patient reported outcomes. Additionally, as PSC is a rare disease with limited current therapeutic options, outcome measures studied in observational cohort studies within the last 20 years will also be studied.

2) To augment this list with additional items generated through semi-structured interviews of patients with PSC, clinicians, specialist nurses, industry, FDA and EMA representatives and outcome methodologists.

3) Use Delphi methodology to refine this outcome list into a core outcome set for clinical trials.

4) To host consensus meetings with stakeholders in order to discuss disagreements, ratify the core outcome set and support dissemination of the findings.


Stakeholders Involved

Charities
Clinical experts
Consumers (patients)
Economists
Epidemiologists
Methodologists
Patient/ support group representatives
Pharmaceutical industry representatives
Policy makers
Regulatory agency representatives
Researchers
Statisticians

Study Type

COS for clinical trials or clinical research
COS for practice

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