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

电子烟是目前不燃烟草市场增长最快的部分 提供给吸烟者。大多数关于电子烟的研究都是1）基于实验室的药代动力学研究， 毒物暴露2）流行率和使用预测因素的横断面研究，或更罕见的情况下，3） 非对照队列研究。到目前为止，三项随机研究都是在美国以外进行的，都是关于戒烟的。 重点，因此没有说任何关于吸烟者采用电子烟的自然过程，以及如何 这种采用改变了吸烟行为。研究自然主义，自我决定的使用是重要的， 了解电子烟的现实影响。许多现有的研究受到方法问题的限制 限制解释：自我选择的用户与非用户的比较导致的选择偏差， 抑制因果推断的回顾性或横断面设计，缺乏暴露的生物标志物， 和/或样本量不足。缺乏前瞻性的，随机的，但仍然生态研究是一个引人注目的问题。 文学中的省略。事实上，还没有一项研究表明：a）将吸烟者随机分为电子烟和吸烟者。 不，B）关注在真实的时间内发生的自然结果，c）是前瞻性的，有足够的随访 持续时间，d）提供尼古丁/烟草暴露数据，e）样本量充足，f）基于美国， 考虑到即将到来的监管变化。据我们所知，还没有发表过研究， 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 电子烟与非电子烟随机化比例为2：1，以提高摄取结局的精确度（目标1）。 将在当地招募一个吸烟者子集（n=120），以评估电子烟使用对以下生物标志物的影响： 暴露（目标2）。最后，尽管我们不是一个戒烟研究，但如果我们不这样做，我们将失去一个机会。 跟踪戒烟结果（目标3），或在出现差异时充分加强试验以检测差异。所以我们 研究的设计和动力是为了解决一系列全面的结果，沿着三个主题：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，这些动态 变化将在真实的时间内自然展开。 我们相信，这将是迄今为止对电子烟自然人口影响的最佳测试。方法 通过1）大样本量（最大的电子烟RCT），2）全国范围内招募，3）当地 招募亚组以评估生物标志物，和4）多种结果测量。强大的调查团队， 再加上我们在以前使用类似方法的研究中取得的成功，共同提高了 成功实现目标。我们相信这项研究将为电子烟做出重要贡献。 文献，并提供了相当大的影响，烟草控制，包括重要的信息， 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.