Department of Statistics, Università degli Studi di Milano-Bicocca, Milan, Italy.
Stat Med. 2010 Nov 20;29(26):2679-87. doi: 10.1002/sim.4041.
A fundamental challenge in meta-analyses of published epidemiological dose-response data is the estimate of the function describing how the risk of disease varies across different levels of a given exposure. Issues in trend estimate include within studies variability, between studies heterogeneity, and nonlinear trend components. We present a method, based on a two-step process, that addresses simultaneously these issues. First, two-term fractional polynomial models are fitted within each study included in the meta-analysis, taking into account the correlation between the reported estimates for different exposure levels. Second, the pooled dose-response relationship is estimated considering the between studies heterogeneity, using a bivariate random-effects model. This method is illustrated by a meta-analysis aimed to estimate the shape of the dose-response curve between alcohol consumption and esophageal squamous cell carcinoma (SCC). Overall, 14 case-control studies and one cohort study, including 3000 cases of esophageal SCC, were included. The meta-analysis provided evidence that ethanol intake was related to esophageal SCC risk in a nonlinear fashion. High levels of alcohol consumption resulted in a substantial risk of esophageal SCC as compared to nondrinkers. However, a statistically significant excess risk for moderate and intermediate doses of alcohol was also observed, with no evidence of a threshold effect.
在对已发表的流行病学剂量-反应数据进行荟萃分析时，一个基本的挑战是估计描述疾病风险在给定暴露水平下变化的函数。趋势估计中的问题包括研究内的变异性、研究间的异质性和非线性趋势成分。我们提出了一种基于两步过程的方法，同时解决了这些问题。首先，在荟萃分析中包含的每个研究中拟合两项分数多项式模型，考虑到不同暴露水平下报告的估计值之间的相关性。其次，考虑研究间异质性，使用双变量随机效应模型来估计汇总的剂量-反应关系。通过对酒精摄入与食管鳞状细胞癌（SCC）之间的剂量-反应曲线进行的荟萃分析来说明该方法，该分析共纳入了 14 项病例对照研究和一项队列研究，包括 3000 例食管 SCC 病例。荟萃分析提供的证据表明，乙醇摄入与食管 SCC 风险呈非线性关系。与不饮酒者相比，高饮酒量会导致食管 SCC 的风险显著增加。然而，也观察到中等和中等剂量的酒精具有显著的超额风险，没有证据表明存在阈值效应。
