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UNLABELLED: 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. CONCLUSION: 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.

Original publication

DOI

10.1002/hep.28256

Type

Journal article

Journal

Hepatology

Publication Date

04/2016

Volume

63

Pages

1357 - 1367

Keywords

Biomarkers, Cholangitis, Sclerosing, Clinical Trials, Phase II as Topic, Clinical Trials, Phase III as Topic, Consensus, Disease Progression, End Stage Liver Disease, Evidence-Based Medicine, Female, Humans, Internationality, Liver Transplantation, Male, Needs Assessment, Practice Guidelines as Topic, Rare Diseases, Risk Assessment, Survival Rate, Treatment Outcome