Transcript Cohort Studies Principles of Epidemiology Lecture 9 Dona Schneider, PhD, MPH, FACE Cohort Studies  Type of Analytic study  Unit of observation and analysis: Individual (not group)  Also.

Cohort Studies
Principles of Epidemiology
Lecture 9
Dona Schneider, PhD, MPH, FACE
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
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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)
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)
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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
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Single Sample Cohort Study Design
TIME
Diseased
Exposed
Target
Population
Disease-Free
Cohort
Not Diseased
Diseased
Not Exposed
Not Diseased
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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
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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.
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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 (1948-1952)

Cohort was examined every 2 years and by
daily surveillance of hospitalizations at
Framingham Hospital
PHCO 0502 Principles of Epidemiology (Schneider)
The Framingham Study

Exposures included:

Smoking

Alcohol use

Obesity

Elevated blood pressure

Elevated cholesterol levels

Low levels of physical activity, etc.
PHCO 0502 Principles of Epidemiology (Schneider)
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

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.
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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
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Multi-Sample Cohort Study Design
TIME
Diseased
Study
Cohort
Exposed
Not Diseased
Diseased
Control
Cohort
Not Exposed
PHCO 0502 Principles of Epidemiology (Schneider)
Not Diseased
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
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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?
PHCO 0502 Principles of Epidemiology (Schneider)
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?
PHCO 0502 Principles of Epidemiology (Schneider)
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
PHCO 0502 Principles of Epidemiology (Schneider)
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 selfreports, telephone surveys or calendar sheets
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
PHCO 0502 Principles of Epidemiology (Schneider)
Example: Calculating the Relative Risk
Disease Status
CHD cases No CHD
(Cases)
Exposure
Status
(Controls) TOTAL
Smoker
112
176
288
Nonsmoker
88
224
312
Relative Risk
=
A/(A+B)
B/(C+D)
PHCO 0502 Principles of Epidemiology (Schneider)
=
112 / 288
88 / 312
= 1.38
Example: Interpreting the Relative Risk
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.
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Risk
comparison
between
exposed and
unexposed
Exposure as a
risk factor for
the disease?
RR<1
Risk for
disease is
lower in the
exposed than
in the
unexposed
Exposure reduces
disease risk
(Protective
factor)
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RR=1
RR>1
Risk of disease
is equal for
exposed and
unexposed
Risk for disease
is higher in the
exposed than in
the unexposed
Particular
exposure is not
a risk factor
Exposure
increases
disease risk
(Risk factor)



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:

Exposure baseline in the past

Follow-up period: past to present to future
PHCO 0502 Principles of Epidemiology (Schneider)
Cohort study data collection (pg. 221)
DESIGN
PAST
Prospective
PRESENT
FUTURE
E
D
Retrospective
E
D
Historical prospective
E
E
PHCO 0502 Principles of Epidemiology (Schneider)
D
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
PHCO 0502 Principles of Epidemiology (Schneider)
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
PHCO 0502 Principles of Epidemiology (Schneider)
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
PHCO 0502 Principles of Epidemiology (Schneider)
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
PHCO 0502 Principles of Epidemiology (Schneider)
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
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