Endpoints and patient stratification in clinical trials for alcoholic hepatitis.


Journal

Journal of hepatology
ISSN: 1600-0641
Titre abrégé: J Hepatol
Pays: Netherlands
ID NLM: 8503886

Informations de publication

Date de publication:
02 2019
Historique:
received: 01 11 2018
revised: 07 11 2018
accepted: 08 11 2018
entrez: 20 1 2019
pubmed: 20 1 2019
medline: 20 6 2020
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 30658732
pii: S0168-8278(18)32537-6
doi: 10.1016/j.jhep.2018.11.005
pii:
doi:

Substances chimiques

Adrenal Cortex Hormones 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

314-318

Subventions

Organisme : Department of Health
ID : 08/14/44
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R014019/1
Pays : United Kingdom

Informations de copyright

Copyright © 2018 European Association for the Study of the Liver. All rights reserved.

Auteurs

Philippe Mathurin (P)

Service des Maladies de l'Appareil Digestif, PU-PH, Hôpital Claude Huriez, 1er étage- Aile Est, Rue Michel Polonovski, 59037 Lille Cedex, France.

Mark Thursz (M)

Digestive Diseases Division, Department of Surgery & Cancer, Imperial College, London W2 1NY, United Kingdom. Electronic address: m.thursz@imperial.ac.uk.

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Classifications MeSH