An Effectiveness Trial of Maintenance Therapy for Nicotine Dependence

描述（由申请人提供）：透皮尼古丁贴片是美国和欧洲使用最广泛的烟草依赖治疗形式。然而，贴片治疗后的戒断率在6个月时只有约20%，在12个月时只有约9%。越来越多的人认识到尼古丁依赖是一种慢性病，就像哮喘或糖尿病一样，需要维持治疗。虽然美国国土安全部公共卫生服务（PHS）制定的现行指南建议经皮尼古丁治疗的持续时间为8周，但对这一建议的支持有限。在最近的一项随机安慰剂对照疗效试验中，比较标准（8周）和延长（24周）尼古丁贴片治疗，我们发现，在24周时，24周组的点流行戒断率为30%，标准治疗组为20% (p < 0.05)；然而，在第52周，即延长治疗组停止治疗6个月后，戒烟率在治疗组之间是相等的。这是第一个临床试验，表明透皮尼古丁延长治疗的益处在很大程度上取决于积极治疗的继续。然而，作为一项疗效试验，本研究在高度控制的条件下进行，有严格的纳入/排除标准，以提高内部效度。如果要正式修改尼古丁贴片治疗持续时间的建议，以鼓励维持治疗，这些发现必须在“现实环境”的有效性试验中得到复制和扩展。此外，正如在支持使用美沙酮维持治疗阿片类药物依赖的临床试验中所做的那样，重复性研究必须包括在整个试验期间（52周）接受维持治疗的治疗组。因此，我们建议进行一项随机有效性试验，以评估透皮尼古丁贴片维持治疗对戒烟的益处。具体来说，660名吸烟者将接受简短的咨询，并将随机分为：标准（8周）、延长（24周）或维持（52周）透皮尼古丁治疗。主要结果将是生物化学验证的第52周的7天点流行禁欲。其他研究目的包括评估：1)整个研究组的治疗副作用；2)各治疗组复发和恢复的纵向模式；3)治疗效果的中介和调节因子；4)成本效益。总的来说，试验结果将为未来PHS审查透皮尼古丁维持治疗的后续治疗指南提供关键数据；第三方付款人评估维持性透皮尼古丁作为承保福利；个别吸烟者决定通过非处方途径使用透皮尼古丁。反过来，这项研究可能有助于实现2010年健康人群的目标，即降低美国的烟草使用率。公共卫生相关性：透皮尼古丁贴片是美国和欧洲最广泛使用的烟草依赖治疗形式，但大多数吸烟者无法通过这种治疗方式成功戒烟。在很大程度上，对这种治疗没有反应可能是由于尼古丁贴片只使用了8周，即推荐的治疗时间。我们在一项随机对照临床试验中发现，使用尼古丁贴片24周可以显著提高戒烟率。我们在此建议进行一项临床试验，将这些结果复制并扩展到现实世界的社区环境中，使用与临床试验相同的研究设计来证明美沙酮维持治疗对阿片类药物依赖的有效性。具体来说，660名吸烟者将接受咨询和标准（8周）、延长（24周）或维持（52周）的透皮尼古丁贴片治疗。主要的结果是在第52周的生物化学验证戒烟。还将评估透皮尼古丁维持疗法的成本效益、安全性和作用机制（例如，促进失效后的恢复）。研究结果可能会改变我们使用透皮尼古丁治疗尼古丁依赖的方法。

DESCRIPTION (provided by applicant): The transdermal nicotine patch is the most widely used form of tobacco dependence treatment in the US and Europe. Yet, abstinence rates following patch treatment are only ~20% at 6-months and ~9% at 12-months. There is a growing recognition that nicotine dependence is a chronic disease, like asthma or diabetes, which requires maintenance therapy. While current guidelines established by the US DHHS's Public Health Service (PHS) recommend 8-week duration for transdermal nicotine therapy, support for this recommendation is limited. In a recent randomized placebo-controlled efficacy trial comparing standard (8-week) vs. extended (24- weeks) treatment with nicotine patches, we found that, at 24 weeks, point-prevalence abstinence rates were 30% in the 24-week arm vs. 20% in the standard therapy arm (p < .05); however, by week 52, 6 months after treatment was discontinued for the extended treatment arm, the quit rates were equivalent across the treatment arms. This was the first clinical trial to suggest that the benefits of extended treatment with transdermal nicotine are largely dependent on the continuation of active treatment. However, as an efficacy trial, this study was conducted under highly-controlled conditions with strict inclusion/exclusion criteria to enhance internal validity. If recommendations for the duration of nicotine patch therapy are to be formally revised to encourage maintenance therapy, these findings must be replicated and extended under "real-world circumstances" in an effectiveness trial. In addition, as done in clinical trials to support the use of methadone maintenance for opiate dependence, a replication study must include a treatment arm that receives maintenance therapy throughout the duration of the trial (52 weeks). Thus, we propose to conduct a randomized effectiveness trial to evaluate the benefits of maintenance therapy with transdermal nicotine patches for smoking cessation. Specifically, 660 smokers will receive brief counseling and will be randomized to: standard (8-weeks), extended (24-weeks), or maintenance (52 weeks) transdermal nicotine therapy. The primary outcome will be bio-chemically verified 7-day point prevalence abstinence at week 52. Additional study aims include assessing: 1) treatment side effects across study arms; 2) longitudinal patterns of relapse and recovery across treatment arms; 3) mediators and moderators of treatment effects; and 4) cost-effectiveness. Overall, the trial findings will provide critical data for future PHS reviews of maintenance therapy with transdermal nicotine for subsequent treatment guidelines; for third-party payer assessments of maintenance transdermal nicotine as a covered benefit; and for individual smokers' decisions to use maintenance transdermal nicotine through over-the-counter access. In turn, this study may help to attain the Healthy People 2010 goals of reducing the US rate of tobacco use. PUBLIC HEALTH RELEVANCE: The transdermal nicotine patch is the most widely used form of tobacco dependence treatment in the US and Europe, but most smokers are unable to successfully quit with this form of treatment. Failure to respond to this treatment may, to a large extent, be due to the use of nicotine patches for only 8 weeks, the recommended treatment duration. We have found in a controlled randomized clinical trial that using the nicotine patch for 24 weeks can increase quit rates significantly. We propose here a clinical trial to replicate and extend these results to a community setting in the real-world, using the same research design utilized in clinical trials to demonstrate the effectiveness of methadone maintenance therapy for opiate dependence. Specifically, 660 smokers will receive counseling and standard (8-weeks), extended (24-weeks), or maintenance (52 weeks) therapy with transdermal nicotine patches. The main outcome is bio-chemically verified smoking cessation at week 52. The cost-effectiveness, safety, and mechanism of effect (e.g., promotion of recovery following a lapse) for maintenance therapy with transdermal nicotine will also be assessed. The study results may change how we treat nicotine dependence with transdermal nicotine.