A Translational Randomized Clinical Trial of Varenicline Sampling to Promote Smoking Cessation and Scalable Treatment Dissemination

摘要：吸烟是可预防的发病率和死亡率以及戒烟的主要危险因素。 仍然是以人口为基础的烟草和癌症控制的主要目标。许多吸烟者缺乏资源来 启动并维持成功的退出尝试。在过去的十年里，我们一直在测试创新的方法 提供药物治疗，允许吸烟者尝试循证戒烟药物和自我 确定他们的目标和戒烟的步伐。用药抽样是一种简短、具体和易于理解的方法 经常导致态度转变支持戒烟的运动，更重要的是促进戒烟 尝试和实际停止。药物抽样也受到医疗保健提供者的青睐，增加了他们的 根据临床指南提供的简短建议。我们已经进行了三次尼古丁替代疗法(NRT)的试验 抽样(N=157,849,1245)，所有这些都是远程的，其中一些已经在医疗领域应用 设置。每项试验都显示出戒烟行为的增加。我们之前在NRT采样方面的工作创建了一个 令人信服的问题是，Varenicline抽样是否会有类似或可能更好的效果。 Varenicline无疑是目前可用的最有效的单一戒烟药物，优于其他 单一疗法选项。作为处方药，varenicline是否适合用于抽样尚不清楚，但 值得在经验上进行测试。一方面，非结构化的使用在很短的时间内可能不能产生足够的效果 药理上的好处。处方递送遇到了广泛传播的自身障碍(这可能是 克服)。另一方面，与NRT抽样非常相似，它可以提供切实的行动线索，从而提供 心理投入(动机、信心、自主性)以维持随后的使用并最终 加强停顿。Varenicline抽样试验不仅是NRT试验的常规扩展，而且 考虑到其独特好处的证据，其意义甚至更加令人信服。因此，我们建议一项 随机临床试验，主要目的是确定1)使用，2)后果(停药)，3) 瓦伦尼克林的抽样机制。将招募648名吸烟者的不同人口统计学样本 在整个南卡罗来纳州，随机(2：1：1)接受i)四周的varenicline样本，ii)四周的供应 NRT，或者III)什么都没有。因此，我们的设计得到了积极和不积极的对照组的加强。 结果将通过6个月的随访进行评估。我们在移动医疗领域采用创新技术 加强方法严谨性的技术，包括对吸烟的远程生物核查 行为。如果varenicline抽样在这次和未来的试验中显示出希望，这将提供很好的机会。 传播对医生、戒毒线等很有吸引力，就像我们的NRT工作一样，varenicline抽样可以 作为一种务实的策略，让更多的吸烟者更快地接受更好的治疗。归根结底，人口 药物/varenicline抽样的影响可能是深远的，提供了一个重要的和可衡量的机会 减少烟草对公众健康的影响，降低癌症的风险、发病率和死亡率。

Abstract: Smoking is the leading risk factor for preventable morbidity and mortality, and smoking cessation remains the primary goal for population-based tobacco and cancer control. Many smokers lack resources to initiate and sustain a successful quit attempt. For the last decade we have been testing innovative approaches for delivery of pharmacotherapies that allow smokers to try evidence-based cessation medications and self- determine their goals and pace for cessation. Medication sampling is a brief, concrete, and easily understood exercise that often induces attitudinal shifts in favor of quitting smoking, and more importantly promotes quit attempts and actual cessation. Medication sampling is also favored by healthcare providers, augmenting their brief advice as per clinical guidelines. We have conducted three trials of nicotine replacement therapy (NRT) sampling (N=157, 849, 1245), all of which were remote, and some of which have been applied within medical settings. Each trial demonstrated increases in cessation behavior. Our prior work on NRT sampling creates a compelling question as to whether varenicline sampling would have similar, or potentially better, effects. Varenicline is inarguably the most effective single cessation medication available, superior to other monotherapy options. As a prescription medication, whether varenicline is suitable for sampling is unclear but worth testing empirically. On one hand, unstructured use, over a brief time, may not deliver sufficient pharmacologic benefit. Prescription delivery incurs its own barriers to widespread dissemination (which can be overcome). On the other hand, much like NRT sampling, it could provide a tangible cue to action that provides psychological engagement (motivation, confidence, autonomy) to sustain subsequent use and ultimately enhance cessation. A trial of varenicline sampling is not merely a routine extension of NRT trials, yet the significance is even more compelling given evidence of its unique benefits. We therefore propose a randomized clinical trial with primary aims to determine the 1) use, 2) consequences (on cessation), and 3) mechanisms of varenicline sampling. A demographically diverse sample of 648 smokers will be recruited across South Carolina and randomized (2:1:1) to receive I) a 4-week sample of varenicline, II) a 4-week supply of NRT, or III) nothing. Thus, our design is strengthened by both active and inactive comparison groups. Outcomes will be assessed through 6 months of follow-up. We employ innovations in mobile health technologies throughout to enhance methodological rigor, including remote biological verification of smoking behavior. If varenicline sampling were to show promise through this and future trials, this would offer great dissemination appeal to physicians, quitlines, etc in that, much like our NRT work, varenicline sampling could be a pragmatic strategy to engage more smokers in better treatments, sooner. Ultimately, the population impact of medication/varenicline sampling could be profound, offering a significant and measurable opportunity to lessen the impact of tobacco on public health and to reduce the risk, incidence and mortality of cancer.