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.
Palak Trivedi, 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).
Disease Category: Gastroenterology
Disease Name: Primary Sclerosing Cholangitis (PSC)
Age Range: 8 - 80
Sex: Either
Nature of Intervention: Drug, Surgery
- Charities
- Clinical experts
- Consumers (patients)
- Economists
- Epidemiologists
- Methodologists
- Patient/ support group representatives
- Pharmaceutical industry representatives
- Policy makers
- Regulatory agency representatives
- Researchers
- Statisticians
- COS for clinical trials or clinical research
- COS for practice
- 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.