ago. Consequently, epidemiologists often rely on job classification as a surrogate means of documenting dose. Reliance on job classification introduces the possibility of misclassification bias because the classification may not be a good proxy for the actual exposure or dose. Another problem is incompleteness of records, not only in determining job classification but especially in determining whether potential confounding exposures, such as cigarette smoking by individual workers, are present. Bias, introduced by misclassification and confounding, can systematically alter study results by diluting or enhancing associations (see discussion later in this chapter).

Case-control studies. The case-control study is useful for testing hypotheses about the relationships between exposure to specific agents and disease. It is especially useful for studying the etiology of rare diseases. When health outcomes are infrequent or rare, longitudinal or cross-sectional studies must be large enough and of sufficiently long duration to accumulate enough adverse events to accurately estimate the risk of a particular agent. In case-control studies, subjects (or cases) are selected on the basis of having a disease; controls are selected on the basis of not having the disease. Cases and controls are then asked about their past exposures to specific agents. Cases and controls are matched with regard to characteristics such as age, gender, and socioeconomic status, so as to eliminate these characteristics as the cause of observed differences in past exposure. The odds of exposure to the agent among the cases are then compared with the odds of exposure among controls. The comparison generates an odds ratio,7 a statistic that depicts the odds of having a disease among those exposed to the agent of concern relative to the odds of the disease for an unexposed comparison group. An odds ratio greater than 1 indicates that there is a potential association between exposure to the agent and the disease. The greater the odds ratio, the greater is the association. Thus, in a case-control study, subjects are selected on the basis of disease presence; prior exposure is then ascertained.

Case-control studies have the advantages of ease, speed, and relatively low cost. They are also advantageous for their ability to probe multiple exposures or risk factors. However, case-control studies are vulnerable to several types of bias, including recall bias. Other problems are identifying representative groups of cases, choosing suitable controls, and collecting comparable information about exposures on both cases and controls. These problems may lead to unidentified confounding variables that differentially influence the selection of cases or control subjects or the detection of exposure. For these reasons case-control studies are often the first, yet not the definitive, approach to testing a hypothesis.

Cross-sectional studies. In a cross-sectional study, the population of interest is surveyed at one point in time. Information is collected simultaneously about their health conditions and exposures to various agents, either present or


The odds ratio is a good estimate of relative risk when the disease under study is rare.

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