Endpoints and patient stratification in clinical trials for alcoholic hepatitis

J Hepatol. 2019 Feb;70(2):314-318. doi: 10.1016/j.jhep.2018.11.005.

Abstract

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.

Keywords: ABIC; GAHS; Infection; MELD; Surrogate endpoints.

Publication types

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

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Clinical Trials as Topic*
  • Drug Discovery / methods
  • Endpoint Determination*
  • Hepatitis, Alcoholic / drug therapy*
  • Hepatitis, Alcoholic / mortality*
  • Humans
  • Patient Selection
  • Prognosis
  • Risk Factors
  • Severity of Illness Index

Substances

  • Adrenal Cortex Hormones