generally use old cases in a defined cohort that has been followed long enough for sufficient outcome events to have occurred but only a random sample of cohort members who were eligible to become cases but had not developed the disease or died at the time the corresponding cases were diagnosed. Controls are often matched to cases on 1 or more potential confounders (e.g., age, sex, and smoking status) that the investigator does not wish to study. An individual selected as a control may become a case if the disease of interest develops. Nested case-control studies can be designed to have almost as much statistical power as the cohort study from which they are derived because of tighter experimental control, and they can be used to derive better inferences on exposure-disease associations. These studies may also be substantially more economical if the determination of exposure of the controls can be limited to a sample.

Case-cohort Studies

In this design, a random sample of the total cohort is drawn and taken to represent the exposure experience of the cohort. When the cohort has been followed long enough to accrue sufficient cases for analysis, the exposure experience of this subcohort is compared with that of the cases (who arise from the total cohort and might or might not be individuals in the subcohort who become cases). This design also provides economies in obtaining exposure data compared with a cohort study, but surveillance of the total cohort is still needed to identify the cases that occur.

Special Considerations

Many epidemiologic studies explore the relation between risk factors and health outcomes, often examining the relation between a single exposure and a single factor or disease. In environmental epidemiology, however, both exposures and outcomes are usually multiple. Many of the risk factors of interest derive from large-scale data sets on environmental pollution that involve continuous variables, as well as a variety of clinical health indicators. Much of cancer epidemiology has focused on studying specific anatomic sites of cancer and delineating important contributors to specific types of cancer, such as the link between occupational exposure to benzene and leukemia or that between asbestos and mesothelioma. Similarly, much of cardiovascular epidemiology has involved prospective cohort studies that concentrate on identifying a few specific risk factors.

Cross-Sectional Designs

Many environmental-epidemiology studies are cross-sectional. In such designs, the relations between contemporaneous assessments of out-



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