Selection of Subjects for Cohort Studies
The selection of subjects for a study is primarily dictated by the research questions and by feasibility.
For relatively common exposures and health outcomes a general cohort, such as residents of Framingham, MA, can be enrolled. The Framingham Heart Study, which began in 1948, enrolled 5,209 men and women 30-62 years old. At the time little was known about the determinants of heart disease and stroke, devastating health problems that had steadily increased in frequency throughout the 20th century. The investigators gathered extensive baseline information with questionnaires, lab tests, and imaging studies. They then followed the subjects, and had them return to the study office every two years for a detailed medical history, physical examination, and repeat lab tests. The Framingham study has been enormously successful in providing information about the most important determinants of cardiovascular diseases (e.g., hypertension, high cholesterol, smoking, obesity, diabetes, and physical inactivity). Framingham investigators also collaborate with leading researchers throughout the world on studies of stroke and dementia, osteoporosis and arthritis, nutrition, diabetes, eye diseases, hearing disorders, lung diseases, and genetic patterns of common diseases.
The Nurses' Health Study and the Black Women's Health Study would also be considered general cohorts, because they both provide the opportunity to study many exposures and many health outcomes among residents with a wide variety of occupations and circumstances. These studies enable investigators to collect exposure information on many common exposures (e.g., high blood pressure, smoking, alcohol use, diet, exercise, etc.), and, after sufficient follow up time, many health outcomes can be studied. When conducting studies using data from a general cohort, the reference group comes from within the cohort, i.e., an internal comparison group. For example, when the Nurses' Health Study examined the association between exercise and heart disease, they carefully assessed physical activity and computed an overall "MET" score that takes into account the frequency, duration, and intensity of many activities. They then sorted them by MET score, divided the cohort into quintiles (i.e., five more or less equal numbers of subjects), and used the quintile with the lowest MET scores as the reference group against which they compared each of the other quintiles. [Manson JE, Hu FB, et al.: A prospective study of walking as compared with vigorous exercise in the prevention of coronary heart disease in women. N Engle J Med 1999;341:650-8].
For rare or unusual exposures the obvious choice would be a special cohort that provides a sufficient number of subjects with the exposure of interest. Examples might include occupational exposures (e.g., asbestos, radiation, and pesticides), unusual diets, drug exposures (e.g., pregnant women treated with diethylstilbesterol in the 1960s), or rare events (e.g., Hurricane Katrina, the bombing of Hiroshima, exposure of responders to the attack on the World Trade Center on 9/11). With special cohorts there is obviously a focus on a single exposure, but many potential health outcomes can be studied. Another major difference from general cohorts is that selection of an appropriate comparison group can be challenging.
A good example of a special cohort study is the US Air Force Health Study on the effects of exposure to dioxin. During the Vietnam War, the U.S. military sprayed the herbicide dioxin ("agent orange") over Vietnam to expose enemy supply lines and bases. Airmen were exposed during spraying flights, while loading the chemical and while performing maintenance on the planes that were used. After the war, combat veterans who had been in Vietnam complained of a variety of health problems. In 1979, the US Congress directed that an epidemiologic study be conducted to evaluate adverse health effects associated with exposure to dioxin and other herbicides used during the Vietnam conflict. The study (informally called the "Ranch Hand Study") enrolled a special cohort consisting of US Air Force pilots who had flown missions to spray dioxin. The comparison group consisted of Air Force flight crews and maintenance personnel who served in Southeast Asia but had not been involved in herbicide spraying operations. Subjects have been followed for many years, and several analyses have found increased all-cause mortality and cardiovascular mortality in those exposed to dioxan. There was also evidence of an association with obesity and possibly diabetes. There were conflicting reports regarding the association between dioxan and cancers.