A Naturalistic Nationwide Randomized Study of e-Cigarette Uptake and Consequences

到目前为止，电子烟是不可燃烟草市场中增长最快的部分。 可供吸烟者使用。大多数对电子烟的研究都是基于实验室的药代动力学研究或 毒物暴露2)流行率和使用预测因素的横断面研究，或者，更罕见的，3) 不受控制的队列研究。到目前为止，这三项随机研究都是在美国以外的地方进行的，都是戒烟-- 聚焦，因此对吸烟者使用电子烟的自然过程以及如何使用电子烟只字不提 这样的收养改变了吸烟行为。对自然主义的、自主使用的研究对 了解电子烟对现实世界的影响。现有的许多研究都受到方法学问题的限制。 这限制了解释：由于自我选择的用户与非用户的比较而导致的选择偏差， 抑制因果推断的回顾或横断面设计，没有暴露的生物标志物， 和/或样本量不足。缺乏前瞻性的、随机的、但仍然是生态学的研究是一个明显的问题 文献中的遗漏。事实上，还没有一项研究表明，a)吸烟者随机选择电子烟，而不是 不是，b)专注于实时发生的自然主义结果，c)是预期的，并有足够的后续行动 持续时间，d)提供尼古丁/烟草暴露的数据，e)有足够的样本量，f)是美国的， 考虑到即将到来的监管变化，这是一个重要的考虑因素。据我们所知，还没有发表过的研究甚至有两项 这些标准。 我们提出了一项全国性的随机临床试验，其中吸烟者(N=660)被随机接受 电子烟的样品与不是。随机化将是2：1，以提高摄取结果的精确度(目标1)。 将在当地招募一组吸烟者(n=120)，以评估电子烟的使用对 暴露(目标2)。最后，尽管我们的研究不是戒烟研究，但如果我们不这样做，我们将错失机会 跟踪停药结果(目标3)或充分支持试验，以检测出现的差异。因此，我们的 这项研究的设计和支持是为了解决三个主题的一系列综合结果：1)吸收 和使用模式，2)暴露的生物标志物，以及3)吸烟的变化。重要的是，这些都是动态的 更改将在它们自然展开时被实时捕获。 我们相信，这将是迄今为止对电子烟对自然主义人口影响的最好测试。方法是 加强了1)大样本(最大的电子烟RCT)，2)全国范围内的招聘，3)本地 招募子集来评估生物标记物，以及4)结果的多个衡量标准。强大的调查团队， 再加上我们在使用类似方法的先前研究中取得的成功，共同提高了 成功实现赠款目标。我们相信，这项研究将为电子烟的发展做出重要贡献 文献，并为烟草控制提供了相当大的影响，包括对监管的重要信息 FDA等机构。

Electronic (e-)cigarettes are by far the fastest growing segment of the non-combustible tobacco market available to smokers. Most studies of e-cigarettes are 1) lab-based studies of either pharmacokinetics or toxicant exposure 2) cross-sectional studies of prevalence and predictors of use or, more rarely, 3) uncontrolled cohort studies. The three randomized studies to date, all based outside the US, are cessation- focused and thus do not say anything about the natural process by which smokers adopt e-cigarettes, and how such adoption changes smoking behavior. Studies of naturalistic, self-determined used are important to understand real-world impact of e-cigarettes. Many of the existing studies are limited by methodological issues that constrain interpretation: selection bias resulting from comparisons of self-selected users vs. non-users, retrospective or cross-sectional designs that inhibit causal inferences, absence of biomarkers of exposure, and/or insufficient sample size. The absence of prospective, randomized but still ecological studies is a glaring omission in the literature. In fact, there has yet to be a study that a) randomizes smokers to e-cigarettes vs. not, b) is focused on naturalistic outcomes that occur in real time, c) is prospective, with sufficient follow-up duration, d) provides data on nicotine/tobacco exposure, e) is of sufficient sample size, and f) is US-based, an important consideration given upcoming regulatory changes. We know of no published study with even two of these criteria. We propose a nationwide randomized clinical trial in which smokers (N=660) are randomized to receive samples of e-cigarettes vs. not. Randomization will be 2:1 to increase precision of uptake outcomes (Aim 1). A subset of smokers (n=120) will be recruited locally, to assess the impact of e-cigarette use on biomarkers of exposure (Aim 2). Finally, though ours is not a cessation study, it would be a missed opportunity if we did not track cessation outcomes (Aim 3) or sufficiently power the trial to detect differences if they emerge. Thus, our study is designed and powered to address a comprehensive set of outcomes along three themes: 1) uptake and patterns of use, 2) biomarkers of exposure, and 3) changes in smoking. Importantly, these, dynamic changes will be captured in real time as they naturally unfold. We believe this will be the best test to date of the naturalistic population impact of e-cigarettes. Methods are strengthened by 1) large sample size (the largest e-cigarette RCT), 2) nationwide recruitment, with 3) locally recruited subset to assess biomarkers, and 4) multiple measures of outcome. The strong investigative team, coupled with our success in prior studies using similar methodology, collectively enhances the probability of success in achieving grant aims. We believe this study will offer an important contribution to the e-cigarette literature, and offer considerable implications for tobacco control, including vital information for regulatory agencies such as the FDA.