Freedman L S, Schatzkin A
Division of Cancer Prevention and Control, National Cancer Institute, Bethesda, MD 20892.
Am J Epidemiol. 1992 Nov 1;136(9):1148-59. doi: 10.1093/oxfordjournals.aje.a116581.
An intermediate endpoint is a biologic event or marker that is a precursor to a given health outcome. Examples of potential intermediate endpoints include serum cholesterol for coronary heart disease, endogenous steroid hormones for breast cancer, and CD4 count for acquired immunodeficiency syndrome. When one is studying a potential intermediate endpoint in the context of an intervention trial, five types of questions may be investigated: 1) Does the intervention affect the intermediate endpoint? 2) Is the intermediate endpoint associated with prognostic or risk factors? 3) Is the intermediate endpoint associated with the main outcome? 4) Is the intervention effect on the main outcome mediated by the intermediate endpoint? 5) Are the prognostic or risk factor effects mediated by the intermediate endpoint? In this paper, the authors show that each of these questions had different sample size requirements, and they illustrate their point with a discussion of an ancillary study of large bowel epithelial proliferation in the National Cancer Institute's Polyp Prevention Trial. The same methods may be used in an observational study, in which case questions 2, 3, and 5 are relevant. However, much larger numbers than those used in the Polyp Prevention Trial example will be required when the main outcome is rare.
中间终点是一种生物事件或标志物，是特定健康结局的先兆。潜在中间终点的例子包括冠心病的血清胆固醇、乳腺癌的内源性甾体激素以及获得性免疫缺陷综合征的CD4计数。当在干预试验的背景下研究潜在的中间终点时，可以研究五种类型的问题：1）干预是否影响中间终点？2）中间终点是否与预后或风险因素相关？3）中间终点是否与主要结局相关？4）干预对主要结局的效应是否由中间终点介导？5）预后或风险因素的效应是否由中间终点介导？在本文中，作者表明这些问题中的每一个都有不同的样本量要求，并且他们通过讨论美国国立癌症研究所息肉预防试验中大肠上皮增殖的一项辅助研究来说明这一点。相同的方法可用于观察性研究，在这种情况下，问题2、3和5是相关的。然而，当主要结局罕见时，所需的样本量将比息肉预防试验示例中使用的样本量多得多。
