Non-Cigarette Tobacco Products as Harm Reduction Tools in Smokers Who Failed to Quit With Traditional Methods

摘要 大多数吸烟者每年都试图戒烟，而且大多数戒烟尝试都以失败告终，即使最有效的戒烟方法 使用FDA批准的药物疗法。不可燃烟草产品排放的有害化学物质较少 因此，对于无法戒烟的吸烟者来说，完全改用危害较小的产品 可能会改善他们的健康。对于那些用传统方法戒烟失败的吸烟者，尝试改用 一种危害较小的产品可能更有可能帮助他们戒烟，而不是试图完全戒烟 反复使用药物治疗。拟议的试验评估了非香烟烟草产品的潜力。 作为当前吸烟者的减害工具，这些吸烟者已经尝试使用传统戒烟方法戒烟，但失败了 方法：研究方法。过去一年内未使用FDA批准的药物治疗戒烟的现有吸烟者(N=225) 将被随机分配到1)完全切换到非香烟烟草产品(切换组， N=150)，或2)尝试再次使用药物治疗戒烟(MEDS组，n=75)。参与者将在以下选项中进行选择 他们想要接受的产品或药物的有限菜单(最大化外部有效性)并选择 确定他们将戒烟的换烟/戒烟日期。Switch Group的参与者将在 两种提供足够尼古丁并吸引成年吸烟者的非香烟产品：电子烟、 最常用的非香烟烟草产品，或加热烟草产品，一种新型烟草产品 最近被FDA批准销售，与香烟相比，这是修改后的风险暴露。这两个产品类别，而 不安全，与香烟相比，释放的有害化学物质更少。MEDS小组的参与者将选择 在现有的两种最有效的药物疗法之间：varenicline或联合透皮尼古丁 替代疗法和短效尼古丁含片。Switch或MEDS组的参与者将收到 9周供应；细分为：1周在继续吸烟时临时使用，8周用作 在目标切换或退出日期之后进行说明。主要结果是生物化学证实的禁欲。 在6个月的随访中减少吸烟，次要结果包括吸烟减少50%， 最长戒烟尝试持续时间、尼古丁、烟雾和毒物暴露的生物标志物，以及呼吸变化 症状。拟议的试验使用严格的设计解决了一个非常重要的研究问题，并 由一支强大的调查团队提供支持。该试验符合NOT-OD-22-023中的优先顺序，包括 减少研究涉及从可燃卷烟转向末端[或加热烟草产品]。

Abstract The majority of smokers try to quit each year, and the majority of quit attempts fail, even when the most effective FDA-approved pharmacotherapies are used. Non-combustible tobacco products emit fewer harmful chemicals than cigarettes, and thus for smokers who cannot quit smoking, switching completely to a less harmful product is likely to improve their health. For smokers who have failed to quit with traditional methods, trying to switch to a less harmful product may be more likely to help them stop smoking than trying to quit using tobacco altogether repeatedly with pharmacotherapy. The proposed trial evaluates the potential of non-cigarette tobacco products to serve as harm reduction tools for current smokers who have already tried, and failed, to quit with traditional methods. Current smokers who failed to quit with FDA-approved pharmacotherapy within the past year (N=225) will be randomly assigned to either 1) switch completely to a non-cigarette tobacco product (Switch Group, n=150), or 2) try to quit again using pharmacotherapy (Meds Group, n=75). Participants will choose among a limited menu of products or medications they would like to receive (maximizing external validity) and select a Target Switch / Quit Date on which they will stop smoking. Participants in the Switch Group will choose between two non-cigarette products that deliver sufficient nicotine and are appealing to adult smokers: e-cigarettes, the most commonly used non-cigarette tobacco product, or heated tobacco products, a novel tobacco product recently approved for sale by FDA as modified risk exposure compared to cigarettes. Both product classes, while not safe, emit fewer harmful chemicals compared to cigarettes. Participants in the Meds Group will choose between the two most effective pharmacotherapies available: varenicline or combination transdermal nicotine replacement therapy and short-acting nicotine lozenge. Participants in the Switch or Meds groups will receive a 9-week supply; broken down as: 1-week to use ad libitum while continuing to smoke, and 8-weeks to use as instructed following a Target Switch or Quit Date. The primary outcome is biochemically-confirmed abstinence from cigarette smoking at the 6-month follow-up, and secondary outcomes include smoking reduction > 50%, longest quit attempt duration, biomarkers of nicotine, smoke, and toxicant exposure, and changes in respiratory symptoms. The proposed trial addresses a highly significant research question using a rigorous design and is supported by a strong investigative team. The trial is in line with priorities within NOT-OD-22-023 including “Harm reduction studies that involve switching from combustible cigarettes to ENDS [or heated tobacco products].”