Planning Grant for a Multi Center RCT of Moderate Alcohol Use on Chronic Disease

说明(由申请人提供)：中等或低风险饮酒(NIAAA定义为任何一天喝d4酒，男性每周喝d14酒，非怀孕妇女每周喝d7酒)--尽管其名称是--与最大进口的各种健康后果有关。与不饮酒或很少饮酒的人相比，适度饮酒的人冠心病、充血性心力衰竭、缺血性中风、糖尿病和胆石症的发病率较低，但乳腺癌和可能的其他癌症的发病率较高；与骨折的关系不太确定，尽管有证据表明，适度饮酒可能同时增加创伤风险和提高骨密度。也许最令人信服的是，适度饮酒与全因死亡率的低风险相关，主要反映了它与心血管死亡率的负相关。然而，重要的限制会影响这一证据。虽然已经进行了大量和一致的流行病学研究，但仍然存在对健康状况和寻求健康行为的残留混淆的强烈担忧。现有的酒精实验研究规模小而短，虽然证明了适度饮酒可以降低心脏代谢风险的合理机制，但绝经后雌激素治疗的类似研究与随机的妇女健康倡议临床试验之间缺乏一致性，只会加剧这一担忧。鉴于酒精的广泛使用，过度使用的明显风险和成本，适度使用的风险和好处的不确定平衡，以及完全缺乏明确的临床试验数据，迫切需要进行适度酒精摄入量的临床试验，这一点毋庸置疑。在这项临床试验中 根据规划合作协议(U34)的申请，我们提议开发一项多中心、国际、长期、务实的适度饮酒随机临床试验，研究与适度饮酒相关的关键临床结果-心血管疾病、癌症、糖尿病、创伤、事故、死亡率以及进展为重度或高风险饮酒。在北美、亚洲、欧洲和非洲拥有临床试验和/或酒精专业知识的成熟研究人员和现场中心(大多数情况下)的团队的基础上，我们打算制定临床试验方案，招募更多的现场中心，建立数据管理网络，并概述跨不同环境的招募、干预、监测和结果确定的实用战略。我们将重点关注心血管风险较高的成年人，以最大限度地提高效率，我们将与NIAAA合作开发一项权威的临床试验，为世界各地的患者和临床医生提供关于适度饮酒在慢性病预防中的有效性的黄金标准建议。

DESCRIPTION (provided by applicant): Moderate or low-risk alcohol consumption (defined by NIAAA as d4 drinks on any single day AND d14 drinks per week for men or d3 drinks on any single day AND d7 drinks per week for non-pregnant women) has been associated - despite its appellation - with a wide variety of health outcomes of the greatest import. Compared with abstainers or rare drinkers, moderate drinkers have been observed to have lower rates of coronary heart disease, congestive heart failure, ischemic stroke, diabetes, and cholelithiasis but higher rates of breast and possibly other cancers; relationships with fractures are less certain, although evidence suggests that moderate alcohol may simultaneously raise risk of trauma yet improve bone density. Perhaps most compellingly, moderate alcohol intake has been associated with a lower risk of all-cause mortality, chiefly reflecting its inverse associatio with cardiovascular mortality. Important limitations affect this body of evidence, however. Although large and consistent epidemiological studies have been conducted, strong concerns about residual confounding by both health status and health- seeking behavior exist. The existing experimental studies of alcohol are small and short and, while demonstrating plausible mechanisms by which moderate drinking would lower cardiometabolic risk, the lack of correspondence between similar studies of postmenopausal estrogen treatment and the randomized Women's Health Initiative clinical trial only heightens this concern. Given the widespread use of alcohol, the clear risks and costs of its overuse, the uncertain balance of risks and benefits of moderate use, and the complete lack of definitive clinical trial data, the urgent need for a clinical trial of moderate alcohol intake is unmistakable. In this Clinical Trial Planning Cooperative Agreement (U34) application, we propose to develop a multi-center, international, long-term, pragmatic randomized clinical trial of moderate drinking on the key clinical outcomes with which it has been associated - cardiovascular disease, cancer, diabetes, trauma, accidents, mortality, and progression to heavy or at-risk drinking. Building upon a team of established investigators and field centers with clinical trial and/or alcohol expertise (both i most cases) in North America, Asia, Europe, and Africa, we intend to develop a clinical trial protocol, recruit additional field centers, establish a data management network, and outline practical strategies for recruitment, intervention, monitoring, and outcome ascertainment across diverse settings. With a focus upon adults at higher cardiovascular risk to maximize efficiency, we will partner with NIAAA to develop a definitive clinical trial that can provide patients and clinicians worldwide with gold- standard advice about the effectiveness of moderate drinking in chronic disease prevention.