Clinical models for evaluating PREPs for tobacco users

描述（由申请人提供）：在美国使用香烟和无烟烟草（烟草）每年花费超过40万人的生命和1000亿美元。这些与烟草有关的死亡和卫生保健费用是由于烟草提供的有毒物质，特别是致癌物质。戒烟是减少有毒物质暴露的最有效方法，尽管复发率很高。高复吸率和持续使用烟草引起了人们对减少继续使用烟草的人的危害的兴趣。减少烟草使用者的伤害可以包括通过减少毒物暴露来降低持续使用烟草对健康的总体不利后果。烟草行业似乎接受这种类型的危害减少，并为吸烟者和非吸烟者销售几种潜在的减少暴露产品（PREP）。国家癌症研究所和医学研究所主张对这些PREP进行客观测试。没有公认的测试方法存在，虽然我们已经成功地使用短期临床模型来评估吸烟者的吸烟样PREP。这种短期模型可以改进，必须适应于评估口服PREPs的吸毒者和吸烟者。一个长期的模型是必要的，以衡量PREP引起的致癌物暴露的减少。该提案的具体目的是：（1）通过允许随意抽吸，改善用于评估尼古丁样PREP的短期临床模型，以便可以测量PREP诱导的吸烟行为变化，并引入暴露前和暴露后血液采样，以便可以评估PREP尼古丁递送。(2)调整短期临床模型，使其可用于评价预期用于吸烟者和/或吸烟者的口服产品，以及（3）开发用于评价PREP致癌物递送的长期临床模型。该项目的总体目标是建立一个临床模型，可用于评估PREP对烟草使用者的营销宣传和降低危害的潜力。该项目与2004年NCI的癌症研究计划和优先事项一致：“吸烟者可能会有一种错误的安全感，认为他们可以通过使用这些新产品[PREP]来显着降低疾病风险，而没有数据表明它们实际上危害较小。科学家必须检查这些产品的毒性，并评估“减少危害”是否是一种可行的公共卫生策略。“该提案的临床模型可能是预测烟草使用者的PREP是否增加、减少或未能改变烟草健康风险的综合方法的重要组成部分。

DESCRIPTION (provided by applicant): Use of cigarettes and smokeless tobacco (SLT) in the U.S. costs over 400,000 lives and $100 billion annually. These tobacco-related deaths and health care costs are due to tobacco-delivered toxicants, especially carcinogens. Tobacco cessation is the most effective way of reducing toxicant exposure, though relapse rates are high. High relapse rates and continued tobacco use have provoked interest in harm reduction for people who continue to use tobacco. Harm reduction for tobacco users can involve lowering the total adverse health consequences of continued tobacco use by reducing toxicant exposure. The tobacco industry appears to embrace this type of harm reduction, and markets several potential reduced exposure products (PREPs) for smokers and SLT users. The National Cancer Institute and Institute of Medicine argue for objective testing of these PREPs. No accepted testing method exists, though we have had success using a short-term clinical model for evaluating cigarette-like PREPs for smokers. This short-term model could be improved and must be adapted to evaluate oral PREPs for SLT users and smokers. A longer-term model is necessary to measure PREP-induced reductions in carcinogen exposure. The specific aims of this proposal are to: (1) Improve the short-term clinical model for evaluating cigarette-like PREPs by allowing ad libitum puffing so that PREP-induced changes in smoking behavior can be measured, and introducing pre- and post-exposure blood sampling so that PREP nicotine delivery can be assessed. (2) Adapt the short-term clinical model so that it can be used to evaluate oral products intended for SLT users and/or smokers, and (3) Develop a longer-term clinical model for evaluating PREP carcinogen delivery. This project's overarching goal is to establish a clinical model that can be used to evaluate the marketing claims and harm reduction potential of PREPs for tobacco users. The project is consistent with NCI's Plans and Priorities for Cancer Research in 2004: "Smokers may feel a false sense of security that they can significantly reduce their risk of disease by using these new products [PREPs], when no data exists to suggest that they are in fact less harmful. Scientists must examine the toxicity of these products as well as evaluate whether or not 'harm reduction' is a viable public health strategy." This proposal's clinical model will likely be an important component of a comprehensive approach to predict if PREPs for tobacco users increase, decrease, or fail to change tobacco's health risks.