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

翻译后摘要：吸烟是可预防的发病率和死亡率的主要危险因素，戒烟 仍然是基于人口的烟草和癌症控制的主要目标。许多吸烟者缺乏资源， 发起并维持成功的戒烟尝试。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，让吸烟者尝试循证戒烟药物， 确定他们的目标和停止的速度。药物取样是一种简单、具体和容易理解的方法。 运动，往往诱导态度转变，有利于戒烟，更重要的是促进戒烟 尝试和实际停止。药物采样也受到医疗保健提供者的青睐， 根据临床指南提供简短建议。我们进行了三项尼古丁替代疗法（NRT）的试验 抽样（N=157，849，1245），所有这些都是远程的，其中一些已应用于医疗 设置.每一项试验都证明了戒烟行为的增加。我们之前在NRT采样方面的工作创建了一个 关于伐尼克兰取样是否会有类似或潜在更好的效果，这是一个令人信服的问题。 伐尼克兰无疑是最有效的单一戒烟药物，上级于其他 单一疗法选择。作为一种处方药，伐尼克兰是否适合采样尚不清楚， 值得进行实证检验。一方面，在短时间内，非结构化的使用可能无法提供足够的 药理学益处处方交付本身就存在广泛传播的障碍（这可能是 克服）。另一方面，就像NRT采样一样，它可以提供一个有形的行动线索， 心理参与（动机，信心，自主性），以维持随后的使用，并最终 加强戒断。伐尼克兰取样试验不仅仅是NRT试验的常规扩展， 鉴于其独特的好处，其重要性甚至更加引人注目。因此，我们建议 随机临床试验，主要目的是确定1）使用，2）后果（停止），和3） 伐尼克兰取样的机制。将招募648名吸烟者的人口统计学多样性样本 横跨南卡罗来纳州，随机（2：1：1）接受I）4周伐尼克兰样品，II）4周供应 NRT，或III）无。因此，我们的设计得到了活性和非活性对照组的加强。 将通过6个月的随访评估结局。我们采用移动的医疗创新 技术，以提高方法的严谨性，包括远程生物验证吸烟 行为如果伐伦克林取样通过这次和未来的试验显示出希望，这将提供巨大的 传播对医生、戒烟热线等有吸引力，因为就像我们的NRT工作一样，伐伦克林采样可以 这是一个务实的策略，让更多的吸烟者更快地接受更好的治疗。最终，人口 药物/伐尼克兰采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.