Surrogate endpoints for clinical trials in primary sclerosing cholangitis; review and results from an International PSC Study Group consensus process

Cyriel Y Ponsioen, Roger W Chapman, Olivier Chazouillères, Gideon M Hirschfield, Tom H Karlsen, Ansgar W Lohse, Massimo Pinzani, Erik Schrumpf, Michael Trauner, Gregory J Gores

Research output: Contribution to journalArticlepeer-review

89 Citations (Scopus)

Abstract

Primary sclerosing cholangitis (PSC) is a rare but serious cholestatic disease for which to date no effective therapy exists to halt disease progression towards 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, transient elastography, histology, combination of alkaline phosphatase + histology, and bilirubin. Of these, histology, alkaline phosphatase, and transient elastography came out as most promising. However, the expert panel concluded that no biomarker currently exceeds level 3 validation. Combining multiple endpoints is advisable.

CONCLUSION: At present, there is insufficient data to support level 2 validation for any surrogate endpoint in PSC. Concerted efforts by all stakeholders are highly needed. Novel promising non-invasive biomarkers are under study and should be incorporated as exploratory endpoints in clinical trials. This article is protected by copyright. All rights reserved.

Original languageEnglish
JournalHepatology
Early online date29 Sept 2015
DOIs
Publication statusPublished - Apr 2016

Bibliographical note

© 2015 by the American Association for the Study of Liver Diseases.

Keywords

  • Surrogate endpoint
  • primary sclerosing cholangitis

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