Designing clinical trials to address alcohol use and alcohol-associated liver disease: an expert panel Consensus Statement.
Brian P. Lee
(1)
,
Katie Witkiewitz
(2)
,
Jessica Mellinger
(3)
,
Frank A. Anania
(4)
,
Ramon Bataller
(5)
,
Thomas G. Cotter
(6)
,
Brenda Curtis
(7)
,
Srinivasan Dasarathy
(8)
,
Kelly S. Demartini
(9)
,
Ivan Diamond
,
Nancy Diazgranados
(10)
,
Andrea F. Dimartini
(11)
,
Daniel E. Falk
(10)
,
Anne C. Fernandez
(3)
,
Margarita N. German
(12)
,
Patrick S. Kamath
(13)
,
Kelley M. Kidwell
(14)
,
Lorenzo Leggio
(7)
,
Raye Litten
(7)
,
Alexandre Louvet
(15, 16)
,
Michael R. Lucey
(12)
,
Mary E. Mccaul
(17)
,
Arun J. Sanyal
(18)
,
Ashwani K. Singal
(19, 20)
,
Norman L. Sussman
(21, 22)
,
Norah A. Terrault
(1)
,
Mark R. Thursz
(23)
,
Elizabeth C. Verna
(24)
,
Svetlana Radaeva
(10)
,
Laura E. Nagy
(8)
,
Mack C. Mitchell
(6)
1
UCLA -
University of California [Los Angeles]
2 The University of New Mexico [Albuquerque]
3 University of Michigan Medical School [Ann Arbor]
4 FDA - U.S. Food and Drug Administration
5 IDIBAPS - Institut d'Investigacions Biomèdiques August Pi i Sunyer
6 University of Texas Southwestern Medical Center [Dallas]
7 NIDA - National Institute on Drug Abuse [NIH, Bethesda, USA]
8 Cleveland Clinic
9 YSM - Yale School of Medicine [New Haven, Connecticut]
10 NIAAA - National Institute on Alcohol Abuse and Alcoholism [Bethesda, MD, USA]
11 PITT - University of Pittsburgh
12 University of Wisconsin School of Medicine and Public Health
13 Mayo Clinic [Rochester]
14 University of Michigan [Ann Arbor]
15 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
16 INFINITE - Institute for Translational Research in Inflammation - U 1286
17 JHU - Johns Hopkins University
18 VCU - Virginia Commonwealth University
19 University of Louisville School of Medicine [Louisville]
20 Robley Rex Veterans Affairs Medical Center
21 DURECT Corporation
22 BCM - Baylor College of Medicine
23 Imperial College London
24 Columbia University [New York]
2 The University of New Mexico [Albuquerque]
3 University of Michigan Medical School [Ann Arbor]
4 FDA - U.S. Food and Drug Administration
5 IDIBAPS - Institut d'Investigacions Biomèdiques August Pi i Sunyer
6 University of Texas Southwestern Medical Center [Dallas]
7 NIDA - National Institute on Drug Abuse [NIH, Bethesda, USA]
8 Cleveland Clinic
9 YSM - Yale School of Medicine [New Haven, Connecticut]
10 NIAAA - National Institute on Alcohol Abuse and Alcoholism [Bethesda, MD, USA]
11 PITT - University of Pittsburgh
12 University of Wisconsin School of Medicine and Public Health
13 Mayo Clinic [Rochester]
14 University of Michigan [Ann Arbor]
15 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
16 INFINITE - Institute for Translational Research in Inflammation - U 1286
17 JHU - Johns Hopkins University
18 VCU - Virginia Commonwealth University
19 University of Louisville School of Medicine [Louisville]
20 Robley Rex Veterans Affairs Medical Center
21 DURECT Corporation
22 BCM - Baylor College of Medicine
23 Imperial College London
24 Columbia University [New York]
Résumé
Most patients with alcohol-associated liver disease (ALD) engage in heavy drinking defined as 4 or more drinks per day (56 g) or 8 (112 g) or more drinks per week for women and 5 or more drinks per day (70 g) or 15 (210 g) or more drinks per week for men. Although abstinence from alcohol after diagnosis of ALD improves life expectancy and reduces the risk of decompensation of liver disease, few studies have evaluated whether treatment of alcohol use disorders will reduce progression of liver disease and improve liver-related outcomes. In November 2021, the National Institute of Alcohol Abuse and Alcoholism commissioned a task force that included hepatologists, addiction medicine specialists, statisticians, clinical trialists and members of regulatory agencies to develop recommendations for the design and conduct of clinical trials to evaluate the effect of alcohol use, particularly treatment to reduce or eliminate alcohol use in patients with ALD. The task force conducted extensive reviews of relevant literature on alcohol use disorders and ALD. Findings were presented at one in-person meeting and discussed over the next 16 months to develop the final recommendations. As few clinical trials directly address this topic, the 28 recommendations approved by all members of the task force represent a consensus of expert opinions.