Citation

Witkiewitz K, Wilson AD, Pearson MR, Hallgren KA, Falk DE, Litten RZ, Kranzler HR, Mann KF, Hasin DS, O'Malley SS, Anton RF. Alcohol Clin. Exp. Res. 2017; 41(5): 1054-1062.

Affiliation

Medical University of South Carolina.

Copyright

(Copyright © 2017, John Wiley and Sons)

DOI

10.1111/acer.13371

PMID

28295414

Abstract

BACKGROUND: Recently, the Food and Drug Administration (FDA) proposed to expand the options for primary endpoints in the development of medications for alcohol use disorder (AUD) to include either abstinence from alcohol or a non-abstinent outcome: no heavy drinking days (with a heavy drinking day defined as more than 3 drinks per day for women and more than 4 drinks per day for men [>3/>4 cutoff]). The FDA also suggested that 6 months would be the most appropriate length for a clinical trial to demonstrate the stability of this non-abstinent drinking outcome. However, few alcohol clinical trials have examined the stability of non-heavy drinking during and after treatment.

METHODS: In a secondary analysis of the COMBINE study data (n=1383), we examined transitions in heavy drinking days during the course of treatment (months 1 through 4), during the transition out of treatment (months 4 through 7), and up to 12 months afterwards (months 13 through 16) using latent variable mixture models.

RESULTS: Heavy drinking and non-heavy drinking were relatively stable in consecutive months (minimum agreement (kappa) =.64 for months 1 to 2). Most individuals were stable low-risk drinkers/abstainers or heavy drinkers by the end of treatment, as characterized by a 10% probability (or less) of transitioning out of either a no heavy drinking state or a heavy drinking state. More than two-thirds of the heavy drinkers who exceeded the heavy drinking threshold during treatment reported, on average, a 64% reduction in drinking frequency and a 38% reduction in drinking intensity from pretreatment drinking levels.

CONCLUSIONS: The results show stability of no heavy drinking as an outcome within the first four months of treatment and that the >3/>4 drink cutoff may mask substantial reductions in alcohol consumption among some patients. Future studies should explore the clinical utility of reduction endpoints. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Language: en

Keywords

alcohol clinical trials; alcohol treatment; alcohol use disorder; heavy drinking days; primary endpoints for alcohol medications