Percentage of Subjects With No Heavy Drinking Days: Evaluation as an Efficacy Endpoint for Alcohol Clinical Trials
Percentage of Subjects With No Heavy Drinking Days: Evaluation as an Efficacy Endpoint for Alcohol Clinical Trials
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DOI：
10.1111/j.1530-0277.2010.01290.x
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发表时间：
2010-12-01
影响因子：
3.2
通讯作者：
Litten, Raye Z.
中科院分区：
文献类型：
--
作者：
Falk, Daniel;Wang, Xin Qun;Litten, Raye Z.
背景资料：没有大量饮酒日（PSNHDD）的受试者百分比，这是食品和药物管理局推荐的疗效终点，认为戒酒个体或从事低风险饮酒行为的个体是治疗的成功应答者。由于PSNHDD已很少在以前的酒精临床试验中使用，我们评估的实用性和有效性的PSNHDD的结果措施在2大酒精clinical trials.Methods：数据集从2酒精试验，联合收割机和多站点托吡酯试验，被用来分析PSNHDD和其他传统的终点托吡酯，纳曲酮，阿坎酸，安慰剂组。PSNHDD的效应量是根据每个月的积极治疗和不同的宽限期（试验早期，分析中不考虑结果）确定的，并与其他传统的结果指标进行比较。长期的结果进行了比较，没有大量饮酒的日子与那些有大量饮酒的日子在积极treatment.Results：PSNHDD效应大小都托吡酯（0.34和0.25在第2个月和第3个月，分别）和纳曲酮（0.24和0.26在第3个月和第4个月，分别）显着。考虑到纳洛酮的2个月宽限期，PSNHDD的效应量与使用传统结局指标的效应量相当。托吡酯有1个月的宽限期，它大于大多数传统的结局指标。允许1天、2天或3天的大量饮酒作为终点，几乎没有什么好处。受试者在治疗过程中没有硬盘表现出更好的比那些有一些硬盘饮酒的结果和酒精相关的后果在1年follow-up.Conclusions：PSNHDD似乎是一个临床信息的终点措施，特别是当使用的宽限期，是敏感的最传统的结果措施，在检测药物和安慰剂组之间的差异。尽管如此，这些发现应该在其他临床数据集中复制，特别是通过不同机制发挥作用的药物。
Background: Percent subjects with no heavy drinking days (PSNHDDs), an efficacy end point recommended by the Food and Drug Administration, considers abstinent individuals or those engaging in low-risk drinking behavior as successful responders to treatment. As PSNHDD has been used infrequently in previous alcohol clinical trials, we evaluated the utility and validity of the PSNHDD outcome measure in 2 large alcohol clinical trials.Methods: Data sets from 2 alcohol trials, COMBINE and a multisite topiramate trial, were used to analyze PSNHDDs and other traditional end points for the topiramate, naltrexone, acamprosate, and placebo groups. Effect sizes of PSNHDDs were determined for each month of active treatment and by varying grace periods-early periods in the trial where outcome is not considered in the analysis-and were compared with that of other traditional outcome measures. Longterm outcomes were compared for groups that had no heavy drinking days versus those that had heavy drinking days during active treatment.Results: PSNHDD effect sizes were significant for both topiramate (0.34 and 0.25 at months 2 and 3, respectively) and naltrexone (0.24 and 0.26 at months 3 and 4, respectively). Given a 2-month grace period for naltrexone, the effect size of PSNHDDs was comparable to the effect sizes using traditional outcome measures. With a 1-month grace period for topiramate, it was greater than the majority of traditional outcome measures. Little is gained by allowing up to 1, 2, or 3 heavy drinking days as an end point. Subjects with no HDDs during treatment fared better than those with some HDDs on drinking outcomes and alcohol-related consequences during a 1-year follow-up.Conclusions: PSNHDD appears to be a clinically informative end point measure, especially when used with a grace period, and is as sensitive as most traditional outcome measures in detecting differences between the medication and placebo groups. Nonetheless, these findings should be replicated in other clinical data sets, particularly with medications that work via different mechanisms.