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association. Because all studies are susceptible to bias, a goal is to minimize bias or to adjust the observed value of an association by using special methods to correct for bias. Two kinds of bias may compromise the results of an investigation: selection bias and information bias.

  • Selection bias occurs when the participants in a study are not representative of the general population. The study participants differ from nonparticipants in characteristics that cannot be observed, that is, groups differ in measured or unmeasured baseline characteristics because of how participants were selected or assigned.

  • Information bias results from the manner in which data are collected and can result in measurement errors, imprecise measurement, and misdiagnosis. Those types of errors may be uniform in an entire study population or may affect some parts of the population more than others. Bias may result from misclassification of study subjects with respect to the outcome variable. Other common sources of information bias are the inability of study subjects to recall accurately the circumstances of their exposure (recall bias) and the likelihood that one group more frequently reports what it remembers than another group (reporting bias). Information bias is especially harmful in interpreting study results when it affects one comparison group more than another.


Many of the studies reviewed failed to control for potential confounders. For many of the outcomes of interest, there are several well-known risk factors that were not taken into consideration; these include smoking, diet, other lifestyle factors, and preexisting illness. In some studies, the lack of control was a result of the study design; for example, ecologic studies, such as the residential studies in which exposure is determined solely by geographic proximity to an exposure source, by design cannot take individual-level factors into account. Retrospective cohort studies can only be analyzed on the basis of the data available; often, information on other risk factors was not collected, either because they were not known risk factors at the time or because collection of such information was not routine.


Interaction, or synergism, occurs when combined exposure to two or more chemicals is more likely to produce an adverse health outcome than exposure to the chemicals individually. Epidemiologic studies are typically unable to partition data on exposures to multiple chemicals quantitatively and even less likely to be

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