Meta-Analysis Systematic and Design Errors: Alcohol Use and Disease Outcomes

6.项目摘要/摘要 本申请涉及广泛的挑战领域(05)比较有效性研究(CER)和 具体挑战主题，05-AA-101对现有临床数据集的创新分析。 这项为期24个月的项目的重点是检验关于酒精与酒精之间假设联系的假说。 消费和疾病后果的风险来自三种类型的流行病学 研究设计：队列研究、人群病例对照研究和医院病例对照研究。这个 总体目标是检验关于流行病学研究中可能出现的系统性错误的假设。Meta- 分析将被用来确定这些研究中的不同方法和设计是否会不适当地偏向 结果是：(1)对某些疾病产生明显的防止酒精使用的保护；(2)掩盖 潜在的具有统计意义的关联；(Iii)造成了不明确的“好坏参半”的结果 决议；以及(Iv)影响已建立的酒精疾病协会的规模和意义。全 已知的流行病学研究，如果适用，分别评估了酒精使用和缺血性 中风、痴呆症/阿尔茨海默氏症、出血性中风和结直肠癌将被比较。 将检验以下假设：i)系统性的错误分类错误，即‘弃权者’群体 错误地包括那些由于年龄增加或健康不佳而减少或停止饮酒的人，有偏见 发现“轻度/适度”饮酒“预防”某些疾病；ii)使用 预期设计更容易出现系统性错误分类错误，因此更有可能显示J- 形状曲线(即保护作用)，而病例对照研究不太可能受到系统性 错误分类错误，因此更有可能显示出正的线性关联；iii)控制设计 在一系列不同的研究中，可能增加系统性错误分类错误的特征将 使研究结果更接近一致(例如，控制酒精摄入量的接近程度 疾病发病率，在对照组中排除有既往疾病的受试者)；四)系统性 错误的分类错误会降低酒精与酒精之间的正线性关联的大小和重要性 消费和疾病。 该项目将促进对酒精对一系列慢性疾病的贡献的理解，并 改进对酒精所致死亡率和发病率的估计。它应该澄清证据基础， 从临床实践中获得建议，并为国家和国际战略提供理解，以减少 酒精饮料的危害。

6. Project Summary/Abstract This application addresses broad challenge Area (05) Comparative Effectiveness Research (CER) and specific challenge topic, 05-AA-101 Innovative Analyses of Existing Clinical Datasets. The focus of this 24 month project is to test hypotheses regarding postulated associations between alcohol consumption and the risk of disease outcomes that have emanated from three types of epidemiological research designs: cohort studies, population case-control studies and hospital case-control studies. The general aim is to test hypotheses regarding possible systematic errors in epidemiological studies. Meta- analyses will be used to determine whether different methods and designs in these studies can unduly bias results towards: (i) creating apparent protection from alcohol use against some diseases; (ii) masking potentially statistically significant associations; (iii) contributing to 'mixed' outcomes that defy a clear resolution; and (iv) influencing the size and significance for established alcohol-disease associations. All known epidemiological studies, if applicable, that have evaluated alcohol use and, respectively, ischemic stroke, dementia/Alzheimer's, hemorrhagic stroke, and colorectal cancer will be compared. The following hypotheses will be tested: i) Systematic misclassification error, whereby 'abstainer' groups erroneously include people who had reduced or stopped drinking due to increasing age or ill-health, biases towards finding that 'light/moderate' use of alcohol 'protects' against certain disease; ii) Studies employing prospective designs are more prone to systematic misclassification error and hence more likely to show J- shape curves (i.e. protective effects), whereas case-control studies are less likely to suffer from systematic misclassification error and hence more likely to show positive linear associations; iii) Controlling for design characteristics likely to increase systematic misclassification error across a range of different studies will bring study outcomes into closer agreement (e.g. control for proximity of the measure of alcohol consumption to disease incidence, exclusion of subjects with pre-existing illness in comparison groups); iv) Systematic misclassification error will reduce the size and significance of positive linear associations between alcohol consumption and disease. The project will advance the understanding of alcohol's contribution to a range of chronic diseases and improve estimates of alcohol-attributable mortality and morbidity. It should clarify the evidentiary basis for advice from clinical practice and contribute understanding to national and international strategies to reduce the harm from alcoholic beverages.