Witkiewitz Katie, Wilson Adam D, Pearson Matthew R, Hallgren Kevin A, Falk Daniel E, Litten Raye Z, Kranzler Henry R, Mann Karl F, Hasin Deborah S, O'Malley Stephanie S, Anton Raymond F
Department of Psychology and Center on Alcoholism, Substance Abuse, and Addictions, University of New Mexico, Albuquerque, New Mexico.
Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington.
Alcohol Clin Exp Res. 2017 May;41(5):1054-1062. doi: 10.1111/acer.13371. Epub 2017 Apr 5.
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.
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.
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.
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.
最近，美国食品药品监督管理局（FDA）提议扩大酒精使用障碍药物研发中主要终点的选择范围，将戒酒或非戒酒结果纳入其中：无重度饮酒日（重度饮酒日定义为女性每天饮酒超过3杯，男性每天饮酒超过4杯[>3/>4临界值]）。FDA还建议，6个月是证明这种非戒酒饮酒结果稳定性的临床试验最合适的时长。然而，很少有酒精临床试验研究治疗期间及治疗后非重度饮酒的稳定性。
在对联合研究数据（n = 1383）的二次分析中，我们使用潜在变量混合模型研究了治疗期间（第1至4个月）、治疗过渡期间（第4至7个月）以及之后长达12个月（第13至16个月）重度饮酒日的转变情况。
连续几个月中，重度饮酒和非重度饮酒情况相对稳定（第1至2个月的最小一致性[kappa] = 0.64）。到治疗结束时，大多数个体为稳定的低风险饮酒者/戒酒者或重度饮酒者，其特征是从无重度饮酒状态或重度饮酒状态转变的概率为10%（或更低）。在治疗期间超过重度饮酒阈值的重度饮酒者中，超过三分之二的人报告称，与治疗前饮酒水平相比，饮酒频率平均降低了64%，饮酒强度降低了38%。
结果表明，在治疗的前4个月内，无重度饮酒作为一种结果具有稳定性，并且>3/>4杯的临界值可能掩盖了一些患者酒精消费量的大幅减少。未来的研究应探索减少终点的临床效用。
