6.1 - Rationale & Design
6.1 - Rationale & DesignCohort studies are useful for estimating disease risk, incidence rates, and/or relative risks. Non-cases may be enrolled from a well-defined population, their current exposure status (at t0) determined, and their disease onset observed over time. Disease status at t1 can be compared to exposure status at t0.
There are two main types of cohort studies: prospective and retrospective. In general, the descriptor, 'prospective' or 'retrospective', indicates when the cohort is identified relative to the initiation of the study.
Sometimes investigators enter into an ongoing prospective cohort study before the cases are determined. An investigator may pose a new question during an intermediate time period of an ongoing study. The cohort is already determined.
Exposure and case status information is available from the beginning of the ongoing study; subjects can be followed forward to collect cases. For example, suppose genotyping is performed in a cohort study. Later, an investigator may decide to use these data and subsequent case status to consider the relationship of a genetic factor to a particular disease. The investigator may wish to follow the subjects for several more years to ascertain more cases. This would be a mixture of a prospective and retrospective cohort.
Prospective Cohort Design (concurrent; longitudinal study)
In a prospective cohort study, the investigators identify the study population at the beginning of the study and accompanies the subjects through time. When proposing a prospective cohort study, the investigator first identifies the characteristics of the group of people he/she wishes to study. The investigator then determines the present case status of individuals, selecting only non-cases to follow forward in time. Exposure status is determined at the beginning of the study. A member of the cohort reaches the endpoint either by dying, becoming a case, or reaching the end of the study period. A subject can also be lost to follow-up over the course of the study.
Challenges:
- loss to follow up;
- differential nonresponse;
- loss of funding support;
- continually improving methods for detecting exposure (leading to greater misclassification than would be expected in current practice)
An advantage of a well-run cohort study is the multiple outcomes that can be considered. A group well-characterized and followed over a long period of time provides much useful information. For example, the Framingham study has studied 3 generations and added to our understanding of the roles of obesity, HDL lipids, and hypertension in heart disease and stroke as well as contributing an algorithm for predicting CHD risk and identifying 8 genetic loci associated with hypertension. The use of sub-cohorts for specific purposes can minimize cost and the length of a study.
Retrospective Cohort Study (Historical cohort; Non-concurrent Prospective Cohort)
An investigator accesses a historical roster of all exposed and non-exposed persons and then determines their current case/non-case status. The investigator initiates the study when the disease is already established in the cohort of individuals, long after the original measurement of exposure. Doing a retrospective cohort study requires good data on exposure status for both cases and non-cases at a designated earlier time point.
Stop and Think!
Both types of studies identify present cases and non-cases.
The case-control study identifies the cases and then selects appropriate controls. An entire cohort is not used. If you were investigating an environmentally-related cancer among university students with a case-control study, you would identify students within certain years who met the case definition for the cancer. You would select controls among students who were not a case of cancer, but matched on characteristics such as age, gender, and graduation year, then determine their exposure status (perhaps the proximity of their campus address to the identified toxin) and compare exposures between cases and non-cases.
A retrospective cohort study uses the entire cohort; all cases and non-cases within the identified group. A retrospective cohort design might designate the cohort to be students enrolled at the university over a 5 year time span. The present case status of all these students is determined and historical data about their exposure status accessed, in order to assess the relationship between being a case of the cancer with the exposure.
Examples of Cohort Studies
Examples of large prospective cohort studies that have been ongoing for an extended period of time are provided in this section.
Research is still being conducted with these established cohorts.
- Suicide Attempts in the US Army During the Wars in Afghanistan and Iraq, 2004 to 2009.
- Association Between Vaccination and Acute Myocardial Infarction and Ischemic Stroke After COVID-19 Infection | Acute Coronary Syndromes | JAMA | JAMA Network
- Prenatal acetaminophen use linked to sleep, attention problems in preschoolers | Penn State University (psu.edu)