Temporal Stability of Heavy Drinking Days and Drinking Reductions Among Heavy Drinkers in the COMBINE Study

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.

Reduced Drinking in Alcohol Dependence Treatment, What Is the Evidence?

“…However, other analyses found that the likelihood of maintaining moderate drinking was lower in severely dependent patients (more than 6 dependence criteria out of 9 [DSM-IIIR]) [44], which is consistent with several other studies showing that moderate drinking goals might be most appropriate for individuals with lower levels of AD severity [45,46,47]. Similarly, a recent secondary analysis of the COMBINE study data showed stability of no heavy drinking as an outcome within the first 4 months of treatment [48]. …”

A clinical remission study of low-severity alcohol use disorder, treated with nalmefene

“…In addition, they may be almost free of negative consequences of heavy drinking also in just 4 weeks of treatment, and maintain this almost absence of negative consequences throughout the 12 weeks of treatment. And this would be in accordance with a secondary analysis of the COMBINE study showing stability of no heavy drinking (Witkiewitz et al, 2017).…”

Who achieves low risk drinking during alcohol treatment? An analysis of patients in three alcohol clinical trials

“…Additionally, the treatment period for COMBINE was 16 weeks, however only the first 12 weeks of data were analyzed in the current paper. Recent work examining the COMBINE data has indicated that most changes in drinking occur during the first 2–3 months of treatment[50], which is reflected in the time-period analyzed in the current study. Nonetheless, future research examining the full 16 week treatment period could further help elucidate predictors of drinking patterns during treatment in the COMBINE study.…”