Section 1.3 Design of Experiments 23 Cohort studies In a cohort study, a group of subjects (the cohort) is studied to determine whether various factors of interest are associated with an outcome. In a prospective cohort study, the subjects are followed over time. One of the most famous prospective cohort studies is the Framingham Heart Study. This study began in 1948 with 5209 men and women from the town of Framingham, Massachusetts. Every two years, these subjects are given physical exams and lifestyle interviews, which are studied to discover factors that increase the risk of heart disease. Much of what is known about the effects of diet and exercise on heart disease is based on this study. Prospective studies are among the best observational studies. Because subjects are repeatedly examined, the quality of the data is often quite good. Information on potential confounders can be collected as well. Results from prospective studies are generally more reliable than those from other observational studies. The disadvantages of prospective studies are that they are expensive to run, and that it takes a long time to develop results. In a cross-sectional study, measurements are taken at one point in time. For example, in a study published in the Journal of the American Medical Association (300:1303–1310), I. Lang and colleagues studied the health effects of bisphenol A, a chemical found in the linings of food and beverage containers. They measured the levels of bisphenol A in urine samples from 1455 adults. They found that people with higher levels of bisphenol A were more likely to have heart disease and diabetes. Cross-sectional studies are relatively inexpensive, and results can be obtained quickly. The main disadvantage is that the exposure is measured at only one point in time, so there is little information about how past exposures may have contributed to the outcome. Another disadvantage is that because measurements are made at only one time, it is impossible to determine a time sequence of events. For example, in the bisphenol A study just described, it is possible that higher levels of bisphenol A cause heart disease and diabetes. But it is also possible that the onset of heart disease or diabetes causes levels of bisphenol A to increase. There is no way to determine which happened first. In a retrospective cohort study, subjects are sampled after the outcome has occurred. The investigators then look back over time to determine whether certain factors are related to the outcome. For example, in a study published in The New England Journal of Medicine (357:753–761), T. Adams and colleagues sampled 9949 people who had undergone gastric bypass surgery between 5 and 15 years previously, along with 9668 obese patients who had not had bypass surgery. They looked back in time to see which patients were still alive. They found that the survival rates for the surgery patients were greater than for those who had not undergone surgery. Retrospective cohort studies are less expensive than prospective cohort studies, and results can be obtained quickly. A disadvantage is that it is often impossible to obtain data on potential confounders. One serious limitation of all cohort studies is that they cannot be used to study rare diseases. Even in a large cohort, very few people will contract a particular rare disease. To study rare diseases, case-control studies must be used. Case-control studies In a case-control study, two samples are drawn. One sample consists of people who have the disease of interest (the cases), and the other consists of people who do not have the disease (the controls). The investigators look back in time to determine whether a particular factor of interest differs between the two groups. For example, S. S. Nielsen and colleagues conducted a case-control study to determine whether exposure to pesticides is related to brain cancer in children (Environmental Health Perspectives, 118:144–149 ). They sampled 201 children under the age of 10 who had been diagnosed with brain cancer, and 285 children who did not have brain cancer. They interviewed the parents of the children to estimate the extent to which the children had been exposed to pesticides. They did not find a clear relationship between pesticide exposure and brain cancer. This study could not have been conducted as a cohort study, because even in a large cohort of children, very fewwill get brain cancer.
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