Endpoints and patient stratification in clinical trials for alcoholic hepatitis

JOURNAL OF HEPATOLOGY

卷:70

Review

Mathurin, Philippe¹  Thursz, Mark² 

[1] Hop Claude Huriez, Serv Malad Appareil Digestif, 1er Etage Aile Est,Rue Michel Polonovski, F-59037 Lille, France

[2] Imperial Coll, Digest Dis Div, Dept Surg & Canc, London W2 1NY, England

关键词: Surrogate endpoints;    MELD;    ABIC;    GAHS;    Infection;   

DOI  :  10.1016/j.jhep.2018.11.005

来源: Elsevier

【 摘 要 】

In some areas of medicine the clinical development pathway through phase II and III clinical trials has been well mapped out and refined through extensive experience. In contrast, a number of key questions remain unanswered in the development of novel therapeutics for alcoholic hepatitis. The use of mortality as an endpoint in phase II clinical trials will potentially restrict the appeal of this therapeutic area for pharmaceutical companies, as the number of patients required for adequately powered clinical trials becomes impractical. Herein, we discuss alternative endpoints and conclude that dynamic assessment of liver function is the most pragmatic option in early stage studies. Stratification based on disease severity should be applied to avoid uneven distribution of patients with substantially differing mortality risks. Consensus on early phase trial design would help to facilitate new therapeutic development in this area of high unmet medical need. (C) 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

【 授权许可】

Free