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.
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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
PHCO 0502 Principles of Epidemiology (Schneider)
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)
PHCO 0502 Principles of Epidemiology (Schneider)
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
PHCO 0502 Principles of Epidemiology (Schneider)
Single Sample Cohort Study Design
TIME
Diseased
Exposed
Target
Population
Disease-Free
Cohort
Not Diseased
Diseased
Not Exposed
Not Diseased
PHCO 0502 Principles of Epidemiology (Schneider)
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
PHCO 0502 Principles of Epidemiology (Schneider)
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.
PHCO 0502 Principles of Epidemiology (Schneider)
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.
PHCO 0502 Principles of Epidemiology (Schneider)
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
PHCO 0502 Principles of Epidemiology (Schneider)
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
PHCO 0502 Principles of Epidemiology (Schneider)
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.
PHCO 0502 Principles of Epidemiology (Schneider)
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)
PHCO 0502 Principles of Epidemiology (Schneider)
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
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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
PHCO 0502 Principles of Epidemiology (Schneider)