Evaluation of Oral Tobacco as a Harm Reduction Method for Smokers

描述（由申请人提供）：与其他可能减少暴露的产品相比，口服非燃烧烟草制品具有最大的减少危害的可能性（Gray et al., 2005; Hatsukami & Hecht, 2005）。烟草公司一直在开发和销售口服烟草产品，以吸引吸烟者作为香烟的“替代品”。一些公共卫生研究人员认为，让吸烟者改用口服烟草将大大降低死亡率和发病率，并指出数据显示，与吸烟相比，使用无烟烟草的健康风险要小得多。然而，很少有研究调查美国的吸烟者是否会觉得口服烟草产品作为戒烟辅助品是美味的，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进行评估），以及使用这些产品是否会导致显着的戒烟率，特别是与FDA批准的戒烟产品（如药用尼古丁）相比。本提案描述了两项研究，这将是解决这些问题的第一次系统努力。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中测试的产品提供信息。吸烟者将获得四种品牌的口服烟草，这些品牌的烟草特有亚硝胺含量都很低，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对这些产品进行抽样，并在抽样期结束时选择他们在随后的四周戒烟期间想要使用的产品。主要的结果测量将是确定最优选的产品，然后将在随后的临床试验中使用。其他结果测量包括产品使用模式、对产品的主观和生理反应、产品戒断症状以及接触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功效。受试者将被随机分配到研究1中确定的最喜欢的口服烟草产品或尼古丁口香糖中，为期12周。随访将在26周和52周进行。主要结果变量是两种产品的戒断率，非戒断者减少吸烟的程度以及治疗结束后产品的继续使用。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与药用尼古丁相似或超过药用尼古丁，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制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.