dividing the rate of the effect in the exposed group by the rate in the unexposed group. An RR greater than 1 suggests a positive association between an exposure and an outcome, and a value less than 1 suggests a protective association. The farther the RR is from 1.0 (in either direction), the stronger the association.

One major advantage of a cohort study is the ability of the investigator to define the exposure classification of subjects at the beginning of the study. Because participants are followed over time, it avoids problems with the temporal sequence between an exposure and an outcome; that is, it avoids the problem of effect–cause associations. Classification of exposure in prospective cohort studies is not influenced by the presence of a health effect, because the health effect has yet to occur, and this reduces an important source of potential bias known as misclassification bias (see later discussion). The disadvantages of cohort studies are the high costs associated with the use of a large study population, the long periods needed for followup (especially if the effect is rare), attrition of study subjects, and delay in obtaining results.

A prospective cohort study selects subjects on the basis of exposure (or lack of it) and follows the cohort to some date to determine whether and at what rate the outcome develops. A retrospective (or historical) cohort study differs from a prospective study temporally in that the investigator traces back in time to classify past exposures in the cohort and then tracks the cohort forward to the present to ascertain the rate of the outcome. The investigator often focuses on mortality from the outcome because of the relative ease of determining vital status of people and the availability of death certificates to determine the cause of death.

Standardized Mortality Studies

For comparison purposes, some cohort studies use mortality or morbidity rates in the general population because it might be difficult to identify a suitable group of unexposed people, especially if the outcome is rare. An example of this is the standardized mortality ratio (SMR), which is the ratio of the observed number of deaths in a cohort (from a specific cause, such as TBI) to the expected number of deaths in a reference population. An SMR greater than 1.0 generally suggests an increased risk of death in the exposed group. Such measures can also be used to examine morbidity, such as cancer.

The major problem in comparing rates in the general population with rates in military cohorts is the “healthy-warrior effect.” That effect arises when a military population experiences a lower mortality or morbidity rate than the general population, which consists of a mixture of healthy and unhealthy people. Inasmuch as military personnel must meet physical-health criteria when they enter the military and while they are on active duty, the group’s health status is usually better than that of the general population of the same age and sex. Since military personnel are at overall lower risk of adverse health outcomes compared to the general population, any excess risk associated with an exposure they experience must be large enough to overcome their inherent advantage in order to be detectable by such methods as SMR.

Case–Control Studies

In a case–control study, subjects (cases) are selected on the basis of having the outcome of interest; controls are selected on the basis of not having the outcome of interest. Investigators seek information on specific exposures. Cases and controls can be matched or not in the selection process with regard to such characteristics as age, sex, and socioeconomic status to suppress the influence of confounding variables in any observed differences. The odds of exposure to the

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