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

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Surrogate endpoints for clinical trials in primary sclerosing cholangitis: Review and results from an International PSC Study Group consensus process. / Ponsioen, Cyriel Y; Chapman, Roger W; Chazouillères, Olivier; Hirschfield, Gideon M; Karlsen, Tom H; Lohse, Ansgar W; Pinzani, Massimo; Schrumpf, Erik; Trauner, Michael; Gores, Gregory J.

In: HEPATOLOGY, Vol. 63, No. 4, 04.2016, p. 1357-67.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Ponsioen, CY, Chapman, RW, Chazouillères, O, Hirschfield, GM, Karlsen, TH, Lohse, AW, Pinzani, M, Schrumpf, E, Trauner, M & Gores, GJ 2016, 'Surrogate endpoints for clinical trials in primary sclerosing cholangitis: Review and results from an International PSC Study Group consensus process', HEPATOLOGY, vol. 63, no. 4, pp. 1357-67. https://doi.org/10.1002/hep.28256

APA

Ponsioen, C. Y., Chapman, R. W., Chazouillères, O., Hirschfield, G. M., Karlsen, T. H., Lohse, A. W., Pinzani, M., Schrumpf, E., Trauner, M., & Gores, G. J. (2016). Surrogate endpoints for clinical trials in primary sclerosing cholangitis: Review and results from an International PSC Study Group consensus process. HEPATOLOGY, 63(4), 1357-67. https://doi.org/10.1002/hep.28256

Vancouver

Ponsioen CY, Chapman RW, Chazouillères O, Hirschfield GM, Karlsen TH, Lohse AW et al. Surrogate endpoints for clinical trials in primary sclerosing cholangitis: Review and results from an International PSC Study Group consensus process. HEPATOLOGY. 2016 Apr;63(4):1357-67. https://doi.org/10.1002/hep.28256

Bibtex

@article{c0d56c5e3902406fb3598408b8150a50,
title = "Surrogate endpoints for clinical trials in primary sclerosing cholangitis: Review and results from an International PSC Study Group consensus process",
abstract = "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.",
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, Journal Article, Research Support, Non-U.S. Gov't, Review",
author = "Ponsioen, {Cyriel Y} and Chapman, {Roger W} and Olivier Chazouill{\`e}res and Hirschfield, {Gideon M} and Karlsen, {Tom H} and Lohse, {Ansgar W} and Massimo Pinzani and Erik Schrumpf and Michael Trauner and Gores, {Gregory J}",
note = "{\textcopyright} 2015 by the American Association for the Study of Liver Diseases.",
year = "2016",
month = apr,
doi = "10.1002/hep.28256",
language = "English",
volume = "63",
pages = "1357--67",
journal = "HEPATOLOGY",
issn = "0270-9139",
publisher = "John Wiley and Sons Ltd",
number = "4",

}

RIS

TY - JOUR

T1 - Surrogate endpoints for clinical trials in primary sclerosing cholangitis: Review and results from an International PSC Study Group consensus process

AU - Ponsioen, Cyriel Y

AU - Chapman, Roger W

AU - Chazouillères, Olivier

AU - Hirschfield, Gideon M

AU - Karlsen, Tom H

AU - Lohse, Ansgar W

AU - Pinzani, Massimo

AU - Schrumpf, Erik

AU - Trauner, Michael

AU - Gores, Gregory J

N1 - © 2015 by the American Association for the Study of Liver Diseases.

PY - 2016/4

Y1 - 2016/4

N2 - 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.

AB - 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.

KW - Biomarkers

KW - Cholangitis, Sclerosing

KW - Clinical Trials, Phase II as Topic

KW - Clinical Trials, Phase III as Topic

KW - Consensus

KW - Disease Progression

KW - End Stage Liver Disease

KW - Evidence-Based Medicine

KW - Female

KW - Humans

KW - Internationality

KW - Liver Transplantation

KW - Male

KW - Needs Assessment

KW - Practice Guidelines as Topic

KW - Rare Diseases

KW - Risk Assessment

KW - Survival Rate

KW - Treatment Outcome

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

KW - Review

U2 - 10.1002/hep.28256

DO - 10.1002/hep.28256

M3 - SCORING: Journal article

C2 - 26418478

VL - 63

SP - 1357

EP - 1367

JO - HEPATOLOGY

JF - HEPATOLOGY

SN - 0270-9139

IS - 4

ER -