The Abuse Liability of a Novel Heated Tobacco Product (IQOS) and Its Feasibility as a Menthol Cigarette Substitute.

项目总结/摘要 FDA提议禁止薄荷卷烟的公共卫生成功取决于薄荷是否 无法戒烟的吸烟者转向非薄荷醇香烟（没有公共健康收益）或 潜在的低危害替代品，如加热烟草产品（HTP）。2019年，FDA批准了一项名为HTP的 “IQOS”及其烟草和薄荷味的“HeatSticks”（HS）作为改良风险烟草产品（MRTP）。 与FDA未来有关IQOS的行动相关的一个问题是“某些口味是否以及如何帮助 成年吸烟者减少吸烟，转而使用潜在危害较小的产品”（FDA，2018）。 了解像IQOS这样的HTPs减少香烟健康负担的潜力需要有针对性地 一项研究调查了香料的可用性对薄荷醇吸烟者转向HTPs的重要程度。 对于一种烟草产品替代另一种烟草产品，它们的滥用责任应该是一致的。经验证的临床 现有的实验室方法通过表征烟草制品的尼古丁释放曲线来比较烟草制品的滥用倾向 (via血浆尼古丁和喷烟形貌）和增强功效（通过主观和行为测量）。 自然评估可以验证临床实验室关于使用模式和产品替代的结果。 目前的研究包括一项两组、为期两周的平行组试验。第一周是自有品牌（OB） 薄荷醇香烟基线，在此期间，每天使用生态瞬时 评估（EMA）。周一和周五，参与者将完成临床实验室课程，包括使用 OB香烟和对主观测量和实验烟草市场（ETM）任务的响应 该研究评估了用包括IQOS在内的一系列烟草产品替代薄荷醇香烟的意愿。 在接下来的一周里，参与者将被随机分配接受IQOS-薄荷醇（n=25）或IQOS-烟草 （n=25）;将重复进行EMA和临床实验室访视。目标1评估IQOS在临床实验室中的滥用责任 设置.结果包括血浆尼古丁水平，吸烟行为，对主观影响的反应， ETM任务的产品替代。目标2衡量自然环境中的烟草使用模式， 参与者将通过EMA报告每日OB和IQOS使用结果。最重要的假设是， 对于OB，IQOS-薄荷醇的滥用倾向性特征与IQOS-烟草的差异较小，这表明薄荷醇 吸烟者将更有可能取代HTP可燃薄荷香烟时，薄荷味 HTP可用。研究结果将加深我们对HTPs和政策的公共卫生影响的理解， 可能会限制薄荷味的MRT。此外，该应用程序描述了一项出色的研究 在具有相关专门知识的协作指导小组的支持下， 因此，申请人将学习烟草制品临床实验室评估的新技能， 药理学、临床试验和转化研究、成瘾医学和专业发展。 这种培训将是非常宝贵的对申请人的目标，成为一个独立的医生/科学家。

PROJECT SUMMARY/ABSTRACT The public health success of FDA’s proposed ban on menthol cigarettes hinges upon whether menthol smokers who are unable to quit smoking switch to non-menthol cigarettes (no public health gain) or to potentially lower harm alternatives like heated tobacco products (HTP). In 2019, FDA authorized an HTP called “IQOS” and its tobacco- and menthol-flavored “HeatSticks” (HS) as a modified risk tobacco product (MRTP). One issue relevant to FDA’s future action regarding IQOS will be “whether and how certain flavors may help adult cigarette smokers reduce cigarette use and switch to potentially less harmful products” (FDA, 2018). Understanding the potential for HTPs like IQOS to reduce the health burden of cigarettes requires targeted research investigating the extent to which flavor availability is important for menthol smokers to switch to HTPs. For one tobacco product to substitute for another, their abuse liabilities should be congruent. Validated clinical lab methods exist for comparing tobacco product abuse liability by characterizing their nicotine delivery profiles (via plasma nicotine and puff topography) and reinforcing efficacy (via subjective and behavioral measures). Naturalistic assessment can validate clinical lab results regarding use patterns and product substitution. The current study involves a two-arm, two-week, parallel group trial. The first week is an own brand (OB) menthol cigarette baseline, during which tobacco use will be assessed daily using ecological momentary assessment (EMA). On Monday and Friday, participants will complete clinical lab sessions that involve using OB cigarettes and responding to subjective measures and an Experimental Tobacco Marketplace (ETM) task that assesses willingness to substitute menthol cigarettes with an array of tobacco products including IQOS. During the next week, participants will be randomized to receive IQOS-menthol (n=25) or IQOS-tobacco (n=25); EMA and clinical lab visits will be repeated. Aim 1 assesses IQOS’ abuse liability in a clinical lab setting. Outcomes include plasma nicotine levels, puffing behavior, responses about subjective effects, and product substitution from the ETM task. Aim 2 measures tobacco use patterns in naturalistic settings where participants will report daily OB and IQOS use outcomes via EMA. The overarching hypothesis is that, relative to OB, IQOS-menthol’s abuse liability profile will differ less than IQOS-tobacco’s, suggesting that menthol smokers will be more likely to substitute an HTP for combustible menthol cigarettes when a menthol-flavored HTP is available. Results will deepen our understanding of the public health impact of HTPs and policies that might restrict access to menthol-flavored MRTPs. Moreover, this application describes an excellent research environment for the proposed work, supported by a collaborative mentorship team with relevant expertise. Resultantly, the applicant will learn new skills in clinical lab assessments of tobacco products, behavioral pharmacology, clinical trials and translational research, addiction medicine, and professional development. This training will be invaluable towards the applicant’s goal of becoming an independent physician/scientist.