Clinical models for evaluating PREPs for tobacco users

描述(申请人提供)：在美国，香烟和无烟烟草(SLT)的使用每年造成超过40万人死亡和1000亿美元的损失。这些与烟草有关的死亡和医疗费用是由烟草带来的毒物，特别是致癌物质造成的。戒烟是减少毒物暴露的最有效方法，尽管复发率很高。高复发率和持续的烟草使用激发了继续使用烟草的人减少危害的兴趣。减少烟草使用者的危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造成的不利影响。烟草行业似乎接受了这种类型的减少危害，并为吸烟者和SLT使用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准备工作进行客观测试。目前还没有公认的测试方法，尽管我们已经成功地使用了一种短期临床模型来评估吸烟者的香烟样准备。这一短期模型可以改进，必须调整为评估SLT使用者和吸烟者的口腔准备。需要一个更长期的模型来衡量PREP诱导的致癌物暴露的减少。这项建议的具体目的是：(1)改进评估香烟样准备的短期临床模型，允许随意吸烟，以便可以测量吸烟行为引起的变化，并引入暴露前和暴露后的血液样本，以便评估准备尼古丁的释放。(2)调整短期临床模型，使其可以用于评估SLT使用者和/或吸烟者的口服产品，以及(3)开发评估Prep致癌物释放的长期临床模型。该项目的总体目标是建立一个临床模型，该模型可用于评估PREP对烟草使用者的营销主张和减少危害的潜力。该项目与NCI在2004年的癌症研究计划和优先事项是一致的：“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(PREPS)显著降低他们的疾病风险，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’是否是一个可行的公共卫生策略。”这项提案的临床模型可能会成为预测烟草使用者的准备是否增加、减少或未能改变烟草的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.