1. Principles of Epidemiology Lecture 9 Dona Schneider, PhD, MPH, FACE
Cohort Studies
Principles of Epidemiology
Lecture 9
Dona Schneider, PhD, MPH, FACE

2. Cohort Studies Type of Analytic study
Unit of observation and analysis: Individual (not group)
Also called follow-up studies, incidence studies, panel studies, longitudinal studies, or prospective studies

3. Assembling a Cohort Cohorts may be chosen because they represent
The general population (i.e., the outcome of interest has a high incidence rate)
Special exposure groups (e.g., smokers, uranium miners or asbestos workers with high levels of specific exposures)
Special resource groups (e.g., alumni, physicians, nurses)
Geographically or facility-defined groups (e.g., Three Mile Island, hospitals with specialized maternity care)

4. Design At baseline (1st observation point):
Subjects are all disease free
Exposure is used to classify subjects into exposed or unexposed groups
Subjects are followed to document incidence (2nd observation point)

5. Assembling the Cohort
Before beginning the study, determine who is susceptible and who is immune to the outcome of interest
You may need to do this with diagnostic tests or medical histories

6. Single Sample Cohort Study Design
TIME
Diseased
Disease-Free
Cohort
Exposed
Not Diseased
Target Population
Diseased
Not Exposed
Not Diseased

7. The Framingham Study
Since 1948, samples of residents of Framingham, Massachusetts, have been subjects of investigations of risk factors in relation to the occurrence of heart disease and other outcomes

8. The Framingham Study Hypotheses:
Persons with hypertension develop CHD at a greater rate than those who are normotensive.
Elevated blood cholesterol levels are associated with an increased risk of CHD.
Tobacco smoking and habitual use of alcohol are associated with an increased incidence of CHD.
Increased physical activity is associated with a decrease in development of CHD.
An increase in body weight predisposes a person to CHD.

9. The Framingham Study
Study population consisted of 5,127 men and women between ages 30 and 62 years and were at the time of entry free of cardiovascular disease ( )
Cohort was examined every 2 years and by daily surveillance of hospitalizations at Framingham Hospital

10. The Framingham Study Exposures included: Smoking Alcohol use Obesity
Elevated blood pressure
Elevated cholesterol levels
Low levels of physical activity, etc.

11. Comparison (Control) Groups
With a one-sample (population-based) cohort, exposure is unknown until after the first period of observation
Example:
Select the cohort (all residents of Framingham)
All members of the cohort are given questionnaires, and/or clinical examinations, and/or testing to determine exposure status
The cohort is then divided into exposure categories based on those results
The nonexposed become the internal controls
For continuous variables, such as caloric intake or amount of exercise, multiple levels of exposure are constructed
It is common to break exposure into quantiles (equally ordered subgroups) and to use the extremes as the comparison (referent) group

12. Question
How does the design of a cohort study change if everybody in the cohort is exposed (special exposure cohort)?
Example: All persons exposed to radiation from the Chernobyl accident.

13. Answer
You need to select a separate control cohort people as similar as possible to the exposed cohort (income, age, gender, employment) but with no exposure
If you cannot find a comparison group, you may use available population incidence rates under certain circumstances

14. Multi-Sample Cohort Study Design
TIME
Diseased
Study Cohort
Exposed
Not Diseased
Diseased
Control Cohort
Not Exposed
Not Diseased

15. Selecting Comparison (Control) Groups
If the cohort is the general population, subjects are selected based on exposure and the comparison group is internal - from the same sample - who do not have the exposure
If the cohort is based on a high risk population selected on the basis of a given exposure (e.g., Chernobyl residents, asbestos workers), external controls must be sought
Sometimes both comparison groups are sought
This eliminates the healthy worker effect and confounding for etiologic agents other than the exposure of interest

16. Selecting Comparison Groups (cont.)
If a comparison group cannot be assembled, known population rates for outcomes may be acceptable but only if they are adjusted for the exposure
Lung cancer rates are based on the population but should not be used for comparison to compare to populations with high smoking rates, such as miners. WHY?
Leukemia rates from the general population can be used to compare rates to Three Mile Island residents. WHY?

17. Determining Exposure Valid means of determining exposure include:
Questionnaires
Laboratory tests
Physical measurements
Special procedures
Medical records
What if the exposure is chronic, such as radon or smoking?

18. Measuring Disease
You must determine endpoints in a similar manner for both the exposed and the non-exposed
That is, procedures for disease identification must be the same for the exposed and the non-exposed
Define the outcomes of interest (set diagnostic criteria)
If you are looking for multiple outcomes, each must be defined

19. Measuring Disease (cont.)
Mortality may be ascertained from medical records, autopsy records, death certificates, physician records, or next-of-kin
Using mortality records does not allow for multiple outcomes
Hospital records can be scanned for specific types of admissions
Health records of employers and schools can be monitored
Reportable diseases may be ascertained from state registries
Absenteeism may be monitored with work records, self reporting, school records or household surveys
Common ailments that do not usually require medical care may be monitored through self-reports, telephone surveys or calendar sheets

20. Relative Risk (RR)
A ratio that measures the risk of disease among the exposed to the risk among the unexposed
RR Numerator: Incidence rate in the exposed
RR Denominator: Incidence rate in the unexposed

21. Example: Calculating the Relative Risk
Disease Status
CHD cases
(Cases)
No CHD
(Controls)
TOTAL
Exposure Status
Smoker
112
176
288
Non-smoker 88
224
312
A/(A+B)
112 / 288
Relative Risk = = =
1.38
B/(C+D)
88 / 312

22. Example: Interpreting the Relative Risk=
1.38
The risk of developing CHD is 1.38 times higher for a smoker than for a nonsmoker. or
The risk of developing CHD is 38% higher for a smoker than for a nonsmoker.

23. Risk comparison between exposed and unexposed
RR<1
RR=1
RR>1
Risk comparison between exposed and unexposed
Risk for disease is lower in the exposed than in the unexposed
Risk of disease is equal for exposed and unexposed
Risk for disease is higher in the exposed than in the unexposed
Exposure as a risk factor for the disease?
Exposure reduces disease risk
(Protective factor)
Particular exposure is not a risk factor
Exposure increases disease risk (Risk factor)

24. Types of Cohort Studies
Prospective
Exposure baseline in the present
Follow-up period: present to future
Retrospective:
Exposure baseline in the past
Follow-up period: past to present
Historical prospective or ambispective:
Follow-up period: past to present to future

25. Cohort study data collection (pg. 221)
DESIGN
PAST
PRESENT
FUTURE
Prospective E D
Retrospective E D
Historical prospective E E D

26. Types of Cohort Studies (cont.)
You may also NEST a case-control study within a cohort study
Example:
Begin with a cohort of 10,000 individuals without rheumatoid arthritis
Test for the presence of RA antigen
Assume those with RA antigen are the exposed and those without the controls
Follow for 10 years and determine the incidence of disease among both cohorts
This reduces the cost of testing

27. Outcome Measures Incidence in the exposed Incidence in the unexposed
Relative risk
Attributable risk (risk difference)
Population attributable risk
Attributable risk percent
Population attributable risk percent
Standardized mortality ratio

28. Advantages of Cohort Studies
Temporality: Exposure precedes outcome because the cohort is disease free at baseline
Efficient for studying rare exposures
May be used to study multiple outcomes
Allows for calculation of incidence of diseases in exposed and unexposed individuals
Minimizes recall bias

29. Disadvantages of Cohort Studies
Tend to be expensive (large sample size) and time consuming (long follow-up period)
Loss to follow-up
When multiple outcomes or specific disease incidence is the outcome of interest, bias can be a serious problem
Inefficient to study rare diseases

30. Disadvantages of Cohort Studies (cont.)
Nonparticipation (selection bias) – it cannot be assumed that those who chose to participate had the same prevalence of exposures nor incidence of disease as those who did not participate
A difference in prevalence of exposure in nonparticipants will not bias the results
A difference in rate of disease among nonparticipants will bias the results