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Hepatology. 2016 Apr;63(4):1357-67. doi: 10.1002/hep.28256. Epub 2015 Dec 23.

Surrogate endpoints for clinical trials in primary sclerosing cholangitis: Review and results from an International PSC Study Group consensus process.

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Department of Gastroenterology & Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
Department of Gastroenterology & Hepatology, John Radcliffe Hospital, Headington, Oxford, United Kingdom.
AP-HP, Hôpital Saint-Antoine, Service d'Hépatologie and Sorbonne Universités, UPMC Univ Paris, France.
Center for Liver Research and NIHR Biomedical Research Unit University of Birmingham, Birmingham, United Kingdom.
Norwegian PSC Research Center, Oslo University Hospital, Oslo, Norway.
Department of Medicine, University Medical Center Hamburg, Eppendorf, Germany.
Division of Medicine, University College London, UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, United Kingdom.
Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN.


Primary sclerosing cholangitis (PSC) is a rare, but serious, cholestatic disease for which, to date, no effective therapy exists to halt disease progression toward end-stage liver disease. Clinical trial design to study drugs that improve prognosis is hampered by the relatively low event rate of clinically relevant endpoints. To overcome this shortcoming, there is an urgent need to identify appropriate surrogate endpoints. At present, there are no established surrogate endpoints. This article provides a critical review and describes the results of a consensus process initiated by the International PSC Study Group to delineate appropriate candidate surrogate endpoints at present for clinical trials in this frequently dismal disease. The consensus process resulted in a shortlist of five candidates as surrogate endpoints for measuring disease progression: alkaline phosphatase (ALP); transient elastography (TE); histology; combination of ALP+histology; and bilirubin. Of these, histology, ALP, and TE came out as the most promising. However, the expert panel concluded that no biomarker currently exceeds level 3 validation. Combining multiple endpoints is advisable.


At present, there are insufficient data to support level 2 validation for any surrogate endpoint in PSC. Concerted efforts by all stakeholders are highly needed. Novel, promising noninvasive biomarkers are under study and should be incorporated as exploratory endpoints in clinical trials.

[Indexed for MEDLINE]

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