History

Cohort studies often are viewed as the gold standard in observational epidemiology, and the first large cohort study was conducted as early as 1913. Wilhelm Weinberg reported in the book Die Kinder der Tuberkuloesen (Children of the Tuberculous) on a 20-year follow-up of 18 212 exposed children whose parent died of tuberculosis and 7574 unexposed children to compare mortality and fertility rate. This early cohort study was ambidirectional and comprised both retrospective data collection of the parents’ death records to determine exposure and nonexposure of the child and prospective follow-up to determine the outcome.

This important early epidemiologic work set the stage for different types of cohort study designs. In a prospective cohort study, the investigator first determines the exposure in the population and follows up the defined population through time to determine the outcome. The design of the retrospective cohort study is similar, but historical data are used to ascertain exposure, follow-up, and outcome.

Measure of Disease Burden and Association

During the course of a cohort study, new cases arise during that given period in the specified group of people. This incidence of outcome frequency can be measured as cumulative incidence or incidence rate. The Beaver Dam Eye Study, conducted since 1988, provided United States population-based estimates of a high 25% cumulative incidence of loss of vision in people aged 75 years or older over a 15-year period, raising the need to address this substantial public health concern. To address loss to follow-up in cohort studies, incidence rate is based on person-time, taking into account the varying follow-up period of each individual. The Blue Mountains Eye Study, comprising 3654 white adults 49 years of age and older, identified the person-specific 10-year incidence rate of early and late age-related maculopathy as 2.8% and 10.8%, respectively, after age standardization. The incidence rate in cohort studies derived from the exposed and nonexposed group can lead to the derivation of the relative risk directly. This direct measure of risk cannot be calculated from case-control studies, which do not include incidence data. In case-control studies, the odds ratio, which is related to probability, approximates relative risk when the disease is rare, but not when the disease is common.

Measure of Disease Burden and Association

During the course of a cohort study, new cases arise during that given period in the specified group of people. This incidence of outcome frequency can be measured as cumulative incidence or incidence rate. The Beaver Dam Eye Study, conducted since 1988, provided United States population-based estimates of a high 25% cumulative incidence of loss of vision in people aged 75 years or older over a 15-year period, raising the need to address this substantial public health concern. To address loss to follow-up in cohort studies, incidence rate is based on person-time, taking into account the varying follow-up period of each individual. The Blue Mountains Eye Study, comprising 3654 white adults 49 years of age and older, identified the person-specific 10-year incidence rate of early and late age-related maculopathy as 2.8% and 10.8%, respectively, after age standardization. The incidence rate in cohort studies derived from the exposed and nonexposed group can lead to the derivation of the relative risk directly. This direct measure of risk cannot be calculated from case-control studies, which do not include incidence data. In case-control studies, the odds ratio, which is related to probability, approximates relative risk when the disease is rare, but not when the disease is common.

Temporality

The temporal sequence between exposure and disease can be elucidated clearly and is an important feature of cohort studies to establish causal associations. Lead time needs to be considered for an exposure such as dietary factors to have an effect on the outcome because of the long incubation period (lag phase) with the prolonged exposure. Outcomes in the first few years of the cohort may not be regarded as such because lag time needs to be considered. Misleading results also can occur in cohort studies that evaluate screening or treatment strategies. An adjustment is needed for the advancement of diagnosis by screening to ensure a common baseline for the time-to-event analysis. This takes into account the time between diagnosis by screening and diagnosis, which normally would have occurred through the usual course of medical care. In the Beaver Dam Eye Study, the 5-, 10-, and 15-year follow-up examinations determined that cigarette smoking, alcohol consumption, and extended sunlight exposure contribute to the incidence of age-related macular degeneration (AMD), cataract, and visual impairment. Because the exposures status could change over time, multiple time point measurement on the exposure with semiquantitative exposure variables incorporating exposed time information were used. Smoking status defined by total pack-years smoked found that current smokers had an increased risk of early AMD (odds ratio, 1.47; 95% confidence interval [CI], 1.08 to 1.99; P = .01) and progression (odds ratio, 1.43; 95% CI, 1.05 to 1.94; P = .02) in the recent 15-year follow-up, after adjusting for age, sex, and baseline AMD severity. In heavy alcohol drinkers who consumed 4 servings or more of alcoholic beverages daily, late AMD was 6.94 times more likely to develop. Extended exposure to sunlight was found to be a risk factor for the development of both AMD and cataract. In the Singapore Cohort study Of Risk factors for Myopia (SCORM) study, the risk factors related to myopia in a 10-year cohort of children with rapidly evolving refractive error were evaluated. Children with 2 myopic parents were found to be 1.55 times ( P = .002) more likely to experience myopia compared to those with no myopic parents, whereas lower intelligence quotient score in the third tertile was found to have a higher relative risk of 1.50 (95% CI, 1.19 to 1.89) of myopia development than first tertile intelligence quotient score. In contrast, the temporality of the associations cannot be documented in cross-sectional studies because it is unclear whether the exposure to the factor preceded outcome.

Multiple Outcomes

The potential to study multiple outcomes in relation to given exposure is unique in cohort studies. The Blue Mountains Eye Study of 3654 white adults aged 49 years and older assessed the incidence and associated risk factors such as cigarette smoking and visual impairment, cataract, AMD, glaucoma, and diabetic and other vascular retinopathy over a 15-year period since 1992. Nuclear cataract was more likely to develop in those who had ever smoked (relative risk, 1.41; 95% CI, 1.09 to 1.83) compared with those who had never smoked. Nuclear cataract further developed in current smokers at a slightly younger mean age of 65.2 years than in nonsmokers at 67.5 years of age ( P = .049). In addition, these current smokers were at a 4 times higher long-term risk of incident late AMD than never smokers. Higher mean intraocular pressure also was observed in current smokers (16.34 mm Hg) than in nonsmokers (16.04 mm Hg).