Evaluation of Oral Tobacco as a Harm Reduction Method for Smokers

描述（由申请人提供）：与其他潜在的减少暴露产品相比，口服非燃烧烟草产品最有可能导致危害减少（Gray等人，2005; Hatsukami & Hecht，2005）。烟草公司一直在开发和销售吸引吸烟者的口服烟草产品，作为香烟的“替代品”。一些公共卫生研究人员认为，吸烟者改用口服烟草将导致死亡率和发病率显著降低，并指出数据显示，与吸烟相比，使用无烟烟草的健康风险显著降低。然而，很少有研究检查美国的吸烟者是否会发现口服烟草产品作为戒烟辅助剂是可口的，这些产品与香烟相比的毒性（通过人体暴露和毒性的生物标志物评估），以及使用这些产品是否会导致显著的戒烟率，特别是与FDA批准的戒烟产品（如药用尼古丁）相比。 本提案介绍了两项研究，这将是解决这些问题的首次系统努力。第一项研究将确定吸烟者对各种口服非燃烧烟草产品的适口性和偏好，这将为研究2中待测产品提供信息。吸烟者将获得四种品牌的口服烟草，这些烟草的亚硝胺含量都很低，但尼古丁含量和产品类型各不相同。受试者将按照随机顺序依次对这些产品进行采样，并在采样期结束时选择他们希望在随后4周戒烟期间使用的产品。主要结局指标将确定最首选的产品，然后将其用于后续临床试验。其他结局指标包括产品使用模式、对产品的主观和生理反应、产品的戒断症状以及暴露和毒性的生物标志物。第二项研究将是一项随机临床试验，比较口服烟草产品与药用尼古丁产品对希望戒烟的吸烟者的疗效。受试者将随机接受研究1中确定的最首选口服烟草产品或尼古丁口香糖，持续12周。将在第26周和第52周进行随访。主要结果变量是两种产品的戒烟率，非戒烟者的吸烟减少程度和治疗结束后继续使用产品。其他结果变量与第一项研究相似。如果口服烟草产品的戒烟率类似于或超过药用尼古丁的戒烟率，则将进行成本分析。这些研究的结果将有助于确定使用口服烟草产品作为戒烟辅助手段和降低吸烟者个人健康风险的方法的效果和可行性。

DESCRIPTION (provided by applicant): Oral non-combusted tobacco products have the greatest likelihood of leading to harm reduction compared to other potential reduced exposure products (Gray et al., 2005; Hatsukami & Hecht, 2005). Tobacco companies have been developing and marketing oral tobacco products that appeal to cigarette smokers as a "substitute" for cigarettes. Some public health researchers believe that switching smokers to oral tobacco would lead to a significant reduction in mortality and morbidity and point to data showing significantly less health risk with smokeless tobacco use compared to cigarette smoking. However, very little research has examined if smokers in the US will find oral tobacco products palatable as a cessation aid, the toxicity of these products compared to cigarettes as assessed by biomarkers of exposure and toxicity in humans, and whether or not use of these products will result in significant smoking cessation rates, particularly compared to FDA approved cessation products, such as medicinal nicotine. This proposal describes two studies which will be the first systematic effort to address these questions. The first study will determine the palatability and preference of various oral non-combusted tobacco products in cigarette smokers, which will inform the product to be tested in Study 2. Smokers will be presented with four brands of oral tobacco that are all low in tobacco specific nitrosamine levels but vary in nicotine content and product type. Subjects will sequentially, and in randomized order, sample each of these products and at the end of the sampling period, choose which product that they would like to use during a subsequent 4-week abstinence from smoking. The main outcome measure will be determining the product that is most preferred, which will then be used in the subsequent clinical trial. Other outcome measures include pattern of product use, subjective and physiological responses to the product, withdrawal symptoms from the product and biomarkers of exposure and toxicity. The second study will be a randomized clinical trial comparing the efficacy of an oral tobacco product compared to a medicinal nicotine product for smokers wishing to quit. Subjects will be randomized to either the most preferred oral tobacco product determined in Study 1 or nicotine gum for a period of 12 weeks. Follow-up will occur at 26 and 52 weeks. The primary outcome variables are abstinence rates across the two products, extent of cigarette reduction in non-abstainers and continued product use after the end of treatment. Other outcome variables are similar to the first study. A cost analysis will be conducted if the oral tobacco product is similar to or exceeds the cessation rates of medicinal nicotine. The results from these studies will help determine the effects and feasibility of using oral tobacco products as both a cessation aid and a method to reduce individual health risk in cigarette smokers.