Cohort Studies
Compare
incidence
Cohort
Study
• Follow up studies
• Longitudinal studies
• Incidence studies
Identify non-diseased people;
group by risk factor status
Compare
past exposures
Compare their
past exposures.
X
X
X
X
Follow longitudinally to
compare incidence.
X X XX Case –
XXX X Control
Study
Find cases with disease
& non-disease controls.
Key Features of
Cohort Studies
• Start with non-diseased people.
• Group by exposure status.
• Compare incidence of disease.
X
Exposed
Non-diseased
initially
Not Exposed
X
Time passes
X
X
Compare
Incidence
In prospective cohort studies conception, design, &
enrollment occur before anyone develops the outcome.
Enroll non-diseased subjects;
collect baseline exposure data
Obese
X
X
X
Compare incidence
X
Follow up at intervals to get
accurate outcome data.
Lean
Identify a cohort retrospectively,
e.g. employees at a tire factory.
Exposed
to chemicals
Non-exposed
office workers
Determine what then
happened to them.
X
X
X
Compare incidence
X
A randomized clinical trial is similar
to a prospective cohort study.
The investigators assign subjects to a treatment or
intervention.
Aspirin
X
Compare incidence over time
Placebo
X
X
X
Club Members
Had factor
Didn’t have
factor
Kiddy Pool
No Kiddy Pool
Compare
Incidence
Start
of Study
Past
During the short time course of this study fairly reliable
data was collected by interviews with club members.
Employees of tire
manufacturer
Had factor
Didn’t have
factor
Tire makers
Clerical staff
Compare
Incidence
of Death
Start
of Study
Past
During the long time course of this occupational study
data on exposure was from employee records and there
was little information on other confounding factors.
Patients with
ankylosing spondylitis
Had factor
Didn’t have
factor
X-Ray therapy
Other therapy
Compare
Incidence
of Cancer
Start
of Study
Past
During the long time course
of this medical study accurate
data on exposure was obtained from medical records, but
accurate information about smoking, alcohol consumption,
BMI, & occupational exposures was missing.
Data Sources for
Retrospective Cohort Studies
Retrospective cohort studies are useful for unusual
exposures and they are efficient for diseases with long
latent periods (time between exposure & disease).
•
•
•
Questionnaires
Employee records
Medical records
However, accurate information on the main exposure and
confounding factors is often missing because the data source
was not designed for the purpose of conducting the study.
Similar in Design &
Analysis
• Retrospective Cohort
• Prospective Cohort
• Clinical Trial
• You can collect data in a spreadsheet.
• Organize findings in a 2x2 table (or R x C).
• Calculate RR, RD, AR%
• Test for significance with chi square.
• Compute 95% confidence interval for RR.
Recording the data for analysis:
A table with subjects in rows. Exposures
and outcomes are listed in columns.
Analysis of Retrospective
Cohort Studies
Given the assumption that exposure status is
fixed and the lack of periodic follow up, it
makes sense to compare cumulative incidence.
Got Giardiasis
Yes
Cumulative
Incidence
No
In kiddy pool
Yes
16
108
124
12.9%
Not exposed
No
14
341
355
3.9%
12.9%
Relative Risk =
= 3.3 ( 1.7-6.5)
3.9%
P value = 0.0003
Prospective Cohort Study
The Cohort
117,000 Nurses
without cancer or CVD
Have risk factor
obese
Don’t have it
lean
Start
of Study
Compare
Incidence
of disease
Follow-up
Future
A major advantage of prospective cohort studies is that they
are carefully designed with specific goals in mind. Therefore,
information on baseline exposures can be carefully collected
on all subjects before anyone has an “event”.
Potential Sources of Data in
a Prospective Cohort Study
•
Interviews
•
Questionnaires
•
Biological specimens (blood, urine, toenails,
hair)
•
Imaging studies (x-ray, ultrasound, CT, etc.)
•
Medical records (verifying outcomes such as
myocardial infarction, stroke, cancer, etc.)
Data collected specifically for a prospective cohort
study will be of higher quality than that obtained
from pre-existing records, but it is more expensive
to do a large, prospective cohort study.
Potential Problems
•
Loss to follow up.
If follow up is over many years, subjects
may loose interest and quit.
•
Exposure status may change.
What if some women lost or gained a
substantial amount of weight during the
period of study? What if smokers quit?
These problems can be overcome by taken steps to
minimize loss to follow-up and by careful periodic
follow up with re-assessment of exposure status.
Incidence Rate For Variable Followup in A Prospective Cohort Study
Subject
ABCDEFGHIJKL81
82
x= when they
got disease
Time
at Risk
8.3
11.0
x
14.0
14.0
10.2
3.0
x
12.0
7.0
10.0
3.0
9.0
6.2
x
83
84
85
86
87 88
89
90
91
92
93
94
95
Incidence (IR) = 3/107.7 = .028/ person-yr Total time at risk =107.7
= 28/1000 p-yrs
person-yrs
Nurses Health Study
Is obesity associated with an
increased risk of heart disease?
BMI:
<21
MI Rate per
# MIs
person-years 100,000 P-Yrs Relative
(non-fatal) of observation (incidence)
Risk
41
177,356
23.1
1.0
21-<23
57
194,243
29.3
1.3
23-<25
56
155,717
36.0
1.6
25-<29
67
148,541
45.1
2.0
>29
85
99,573
85.4
3.7
Risk difference = 62.3 excess cases /100,000 P-Yrs
Another Unusual Risk Factor
Agent Orange
Veterans’ Problems after Viet Nam:
• Skin rashes
• Psychological problems
• Infertility
• Liver abnormalities
• Cancers
Goals of the Agent
Orange Study
Look at a single, unusual exposure.
Look at multiple possible effects.
An Ambi-directional Cohort Study
The “Ranch Hand” study looked at effects of Agent Orange
»1,264 pilots who sprayed dioxin in Vietnam
»1,264 pilots who flew only cargo missions in Vietnam
Prospective part
Retrospective part
Incidence
of cancer?
Exposed
Unexposed
Incidence of
skin rash?
Start of Study
Why were pilots flying only cargo missions
an appropriate comparison groups?
A cohort study can look at multiple effects
of a single exposure.
Yes
Skin Disease
Abnormalities
Yes LiverNo
Problems
Yes Psychological
No
Cancer
Yes
No
139
Agent
Orange
119
Yes
No
169
No
239
217
10,820
227
10,807
3
98
138
Subjects grouped
by risk factor status
Conclusions from the Ranch Hand Study
Exposure to dioxin was associated with a
significant increase in risk of soft tissue
sarcoma, non-Hodgkin's lymphoma, and
Hodgkin's disease.
There was suggestive, but not statistically
significant evidence of an association with
respiratory cancers, prostate cancer, and
multiple myeloma.
Selecting Subjects for
a Cohort Study
Common risk factors (obesity, HBP):
• A cohort from the general population:
(e.g., Framingham Heart Study)
• A special study group: doctors, nurses
(e.g. The Nurse’s Health Study)
Unusual risk factors:
• A special exposure group:
(e.g., tire manufacturing, dioxin, asbestos)
The Comparison Group
1) As similar as possible with respect to
other factors that could influence outcome.
2) Comparable & accurate information.
Where does the comparison group come from?
Ideally, from within the cohort (internal
controls), but this is not always possible.
Problems with the Comparison Group
Subjects may switch
exposure status or become
lost to follow up (quit)
An Open Cohort
Employees of tire
manufacturer
Had factor
Didn’t have
factor
Tire makers
Clerical staff
Compare
Incidence
of Death
Start
of Study
Past
What are the strengths and weaknesses of using
clerical employees as the comparison group?
Problems with the Comparison Group
Subjects may switch
exposure status or become
lost to follow up (quit)
An Open Cohort
Employees of tire
manufacturer
Had factor
Didn’t have
factor
Tire makers
Clerical staff
Compare
Incidence
of Death
Start
of Study
Past
The clerical staff may be much less exposed to the chemicals, but there
may be important differences in confounding factors such as gender, age,
socioeconomic status, education, diet, smoking, alcohol consumption, etc.
Internal Control Group
Heaviest
Incidence of
heart disease?
Nurses
Leanest
The best comparison group is an unexposed
or “least exposed” subset of the study cohort.
General Population Control
General Population
The general population is often used in
occupational studies of mortality, since
data is readily available, and they are mostly
unexposed. Some data sets allow adjustment
for age, gender, SES, and race.
vs.
Rubber
Workers
Mortality
Rates?
The main disadvantage is bias by the “healthy worker
effect.” The employed work force (mostly healthy)
generally has lower rates of mortality and disease than
the general population (with healthy & ill people).
A Comparison Cohort
Rayon
Exposed Factory
to disulfide Workers
Incidence of
vs.
heart disease?
No disulfide
exposure
Paper
Mill
Workers
Both groups consist of blue collar workers, minimizing differences in SES,
education, etc. The “healthy worker effect” is also not a factor. However,
the paper mill workers may have other exposures that affect heart disease.
A strength is that cohort studies are
efficient for unusual exposures.
•
Suspicion that occupational exposure to chemicals
in tire manufacturing increase risk of death.
•
Viet Nam veterans with a variety of health problems.
Was Agent Orange responsible?
•
Does x-ray treatment of ankylosing spondylitis (back
problem) increase the risk of cancer?
•
The need for a better understanding of behavior
modifications that can prevent cancer & heart
disease (e.g., smoking & obesity).
However, cohort studies also provide high quality
information for examining common exposures as well.
Bias From Loss To Follow-up
If subjects in one of the exposure groups are more likely
to be lost to follow up if they develop the outcome, then
the estimate of association will be biased.
OC Users
Example:
True incidence of thromboembolism: 20/10,000
Subjects lost to follow up:
Subjects with TE lost to follow up:
Apparent incidence of TE:
True RR = 2.0
Non-OC users
10/10,000
4,012
4,008
12
8/5,988
2
8/5,992
Apparent RR = 1.0
Can occur in cohort studies & intervention trials.
Effects: over- or under- estimate of association.
Maintain Follow Up
•
•
•
•
•
Choose subjects who are motivated
Choose subjects who are easy to track
(professionals)
Keep them interested: newsletters,
incentives, part of the “family”
Frequent phone calls
Make questionnaires easy to fill out
Both Retrospective
& Prospective:
Advantages of Cohort Studies:
•
•
•
•
Temporal sequence between exposure & disease
is clear (e.g., obesity preceded CHD)
Can directly calculate incidence, RR, RD, AR%
Efficient for looking at rare exposures or unusual
risk factors (e.g. agent orange).
Can evaluate multiple effects of a single exposure.
Retrospective cohort studies:
• Efficient for diseases with
long latent period (time from
exposure to development of
disease).
Prospective cohort studies:
• Provide better information on
exposures.
• Are less vulnerable to bias
because exposure status is
determined before outcomes.
Enroll non-diseased subjects;
collect baseline exposure data
Obese
Follow up at intervals to get
accurate outcome data.
Lean
Compare incidence over time
X
X
X
X
• Better information on exposures.
• Less vulnerable to bias because exposure
status is determined before outcomes.
Exposed
Not
Exposed
Identify a cohort retrospectively
(e.g. tire manufacturing workers
vs. desk employees. Look at what
subsequently happened to them.
Compare incidence
X
X
X
• EfficientXwith long latent
period from exposure to
development of disease).
Disadvantages of Cohort Studies
•
Inefficient for rare outcomes (both).
Retrospective Cohort Study
• Poor information on exposures
& confounding factors.
• More vulnerable to bias. Prospective Cohort Study
• May need large numbers of
subjects for long periods of time.
• Can be expensive and time
consuming.
• Inefficient for diseases with long
latent periods.
• Loss to follow up can bias
results.
Enroll non-diseased subjects;
collect baseline exposure data
Obese
Follow up at intervals to get
accurate outcome data.
Lean
Compare incidence over time
X
X
X
X
• Expensive and time consuming.
• Inefficient for diseases with long latency.
• Loss to follow up can bias results.
Exposed
Not
Exposed
Identify a cohort retrospectively
(e.g. tire manufacturing workers
vs. desk employees. Look at what
subsequently happened to them.
X
X
X
• Poor information on exposures
X
& confounding factors.
Compare incidence
• More vulnerable to bias.
When reading a cohort study, consider…
• How were the study groups selected or defined?
• Did they differ in other ways that could affect the outcome?
• Data collection:
 Accurate?
 Comparable for all groups?
• How complete was the follow-up?