title: 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 end points in the development of medications for alcohol use disorder to include either abstinence from alcohol or a nonabstinent 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 nonabstinent drinking outcome. However, few alcohol clinical trials have examined the stability of nonheavy drinking during and after treatment.
  
  
  METHODS
  In a secondary analysis of the COMBINE study data (n = 1,383), 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 afterward (months 13 through 16) using latent variable mixture models.
  
  
  RESULTS
  Heavy drinking and nonheavy drinking were relatively stable in consecutive months (minimum agreement [kappa] = 0.64 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 4 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 end points.
authors.affiliation: Department of Psychology and Center on Alcoholism, Substance Abuse, and Addictions, University of New Mexico, Albuquerque, New Mexico.
authors.forename: Katie
authors.identifier: http://orcid.org/0000-0002-1086-3067
authors.initials: K
authors.lastname: Witkiewitz
authors.affiliation: Department of Psychology and Center on Alcoholism, Substance Abuse, and Addictions, University of New Mexico, Albuquerque, New Mexico.
authors.forename: Adam D
authors.initials: AD
authors.lastname: Wilson
authors.affiliation: Department of Psychology and Center on Alcoholism, Substance Abuse, and Addictions, University of New Mexico, Albuquerque, New Mexico.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Pearson
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington.
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Hallgren
authors.affiliation: National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Falk
authors.affiliation: National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland.
authors.forename: Raye Z
authors.initials: RZ
authors.lastname: Litten
authors.affiliation: Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Henry R
authors.initials: HR
authors.lastname: Kranzler
authors.affiliation: Central Institute of Mental Health, Mannheim, Germany.
authors.forename: Karl F
authors.initials: KF
authors.lastname: Mann
authors.affiliation: Departments of Psychiatry and Epidemiology, Columbia University, New York City, New York.
authors.forename: Deborah S
authors.initials: DS
authors.lastname: Hasin
authors.affiliation: Department of Psychiatry, Yale University, New Haven, Connecticut.
authors.forename: Stephanie S
authors.initials: SS
authors.lastname: O'Malley
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Raymond F
authors.identifier: http://orcid.org/0000-0003-3417-6576
authors.initials: RF
authors.lastname: Anton
mesh_terms: D000428:Alcohol Drinking / Q000453:epidemiology* / Q000628:therapy*; D000435:Alcoholic Intoxication / Q000175:diagnosis / Q000453:epidemiology* / Q000628:therapy*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D013997:Time Factors
keywords: Alcohol Clinical Trials; Alcohol Treatment; Alcohol Use Disorder; Heavy Drinking Days; Primary End Points for Alcohol Medications