Learning objectives
— Know the design of a ‘Cohort study’
— Know the design of ‘Prospective cohort study’
— Know the design of ‘Retrospective cohort study’
— Know the Advantages and Disadvantages of a cohort
study
— Know the potential issues if a cohort study
Cohort Studies
— One of the most useful observational study
— Individuals are divided on the basis of
presence or absence of risk factors
— Individuals are then followed over time to
determine if they develop a specific outcome
or disease
Cohort Studies
Also called:
— Longitudinal studies
— Follow-up studies
— Incidence Studies
What is a cohort?
— Group of individuals
— sharing same experience
— followed up for specific period of time
— Examples:
— Group of smokers
— Occupational cohort of chemical plant
workers
Cohort Studies
Cohort Studies
¨
Follow up
Follow up
Disease
develops
Disease
Does Not
Develop
Totals
Incidence
Exposed
A
B
A+B
A/A+B
Not exposed
C
D
C+D
C/ C+D
Incidences in the exposed group and
the not exposed group are calculated
Cohort Study of smoking and Coronary Heart
Disease (CHD)
Follow up
Follow up
CHD
develops
CHD Does Not
Develop
Totals
Incidence
/1000 per
year
Smoke cigarettes
84
2916
3000
28.0
Do not smoke
cigarettes
87
4913
5000
17.4
¨
¨
¨
¨
Select a group of 3,000 smokers (exposed) and 5,000
nonsmokers (not exposed)
All are free of heart disease at baseline
Both groups are followed for the development of CHD
Incidence in both groups is compared
Types of Cohort Studies
Ø PROSPECTIVE
Ø RETROSPECTIVE
Prospective Cohort Study
¨
¨
¨
¨
Initiation of study occurs before occurrence
of disease
Groups of exposed and unexposed
individuals are monitored over time to assess
the development of disease
The incidence of disease in both groups is
compared
Potential confounders documented
Prospective Cohort Study
Exposure
Disease
?
?
Exposure may have occurred at study entry
Outcome definitely has not occurred at study
entry
Prospective Cohort Study of smoking relationship
to lung cancer
¨
¨
¨
Identify a population of elementary school
students and follow them up
Identify those who smoke and those who do not
Observe who develop lung disease and who do
not in future
= Concurrent Cohort
= Longitudinal Study
Cohort Study: Lead level and Affective Disorders
Exposed group: One hundred children exposed
to high levels of lead were followed for 15 years;
40 developed an affective disorder
Non-exposed group: A similar group of 100
children not exposed to lead were followed. 5 of
these children developed an affective disorder
¨
What is the incidence of affective disorders
among those exposed to high lead levels?
exposed
not exposed
¨
¨
Affective Disorder
present
absent
40
60
5
95
What is the incidence of affective disorders
among those exposed to high lead levels?
40/100 = 40% or 0.40
What is the incidence of affective disorders
among those NOT exposed to high lead levels?
5/100 = 5% or 0.05
Retrospective Cohort Study
¨
¨
¨
¨
Initiation of study occurs after occurrence of
disease / outcome of interest
Allows investigators to complete study in less
time (saves money)
Subject to bias
Since they depend on exposure data
occurring previously, information can be
incomplete; information on confounders
may not be available
Retrospective Cohort Study
Exposure
Disease
?
?
Both exposure and disease have already occurred
Retrospective Cohort Study: Example
¨
¨
¨
In 1963, a group of asbestos workers was identified from
social security tax returns during 1948-1951
All deaths in the group 1948-1963 were investigated and
compared to deaths of a group of cotton textile workers
An excess lung cancer mortality was revealed among the
asbestos workers
= Non-concurrent Cohort
= Historical cohort Study
FAMOUS COHORT STUDIES
The Framingham Study
¨
¨
¨
¨
¨
One of the most important and best-known cohort of
cardiovascular disease – begun in 1948
Population – 30,000
Eligibility: age between 30 and 62 years of age
Many exposures: smoking, obesity, elevated blood
pressure, elevated cholesterol levels, low levels of
physical activity
New coronary events were identified by examining
the study population every 2 years and by daily
surveillance of hospitalizations at the only one
hospital in Framingham
The Framingham Study -hypotheses
§
§
§
§
The incidence of Coronary Heart Disease (CHD) increases with age. It occurs earlier
and more frequently in males
Persons with hypertension develop CHD at a greater rate than those who are
normotensive
Elevated blood cholesterol level is associated with an increased risk for 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 the development of CHD
§
An increased in body weight predisposes a person to the development of CHD
§
An increased rate of development of CHD occurs in patients with diabetes mellitus
Cohort studies of Special Exposures
¡ Atomic Bomb Causality Commission:
Hiroshima and Nagasaki survivors (effects of
radiation)
¡ Dutch famine survivors (effects of starvation)
Cohort studies – Childhood Health and Disease
¨
Ø
Ø
Ø
¨
Ø
Fetuses exposed to radiation from atomic bombs in Hiroshima
and Nagasaki during World War II
Followed-up for development of cancer and other health
problems resulting from intrauterine exposure to radiation
Exposure dose was calibrated for the survivors on the basis of
how far the person was from the point of bomb drop and the
nature of barriers were present
Determine the risk of adverse outcome to the radiation dose
that was received
Cohort pregnancies during Dutch Famine in World War II
Identify cohorts who were exposed to the severe famine at
different times in gestation and to compare them with each
other and with a non-exposed group
Advantages of Cohort Studies
— The temporal sequence between exposure and disease is
clearly established
— Well suited for assessing the effects of rare exposures
— Incidence of disease can be calculated
— Can examine multiple outcomes of a single exposure
— True estimate of risk can be calculated - RR
Disadvantages of Cohort Studies
— Time
— Money – expensive
— Subject to loss of follow up
When not to do a cohort study?
¡ No clear distinction between exposed and not exposed
¡ Rare disease
¡ Chronic disease: long gap between exposure and
outcome
¡ Bad records, unreliable data – for retrospective cohort
study
Steps in cohort study
— Choose the design
— Selection of exposed group
— Selection of comparison group
— Follow up
— Analysis and interpretation
Choice of Cohort Design
Depends on the study question
— Food handling and gastroenteritis: retrospective study design
— To investigate the association between hyperlipidemia and
coronary heart disease: prospective study design using
community cohort (Framingham Study)
Selection of the Exposed Population
¨ For diseases with common exposures: highly compliant
and motivated participants are chosen e.g. doctors,
nurses, union members, veterans
¨ For diseases with rare exposure: usually find high
exposure groups (uranium workers, Chernobyl
residents)
¨ The higher exposure should lead to relatively higher
incidence of the disease
Selection of the Comparison Group
The comparison group must be free from the
exposure, but otherwise similar to the case group
McMichael A. Mortality among rubber
workers: Relationship to specific jobs. J Occup.
Med 18:178,1976
— Rubber workers at a tire manufacturing plant in Akron,
Ohio were followed for development of disease and causes
of death
— Comparison group was from the general US population,
matched for age and sex
— All cause mortality for rubber workers was only 82%
compared to general population
— This is an example of the “Hawthorne effect”
Hawthorne Effect
— When individuals participating in a study change
behavior (mainly towards positive) for a temporary period
of time, due to the fact that they are being observed
— This can be addressed by using workers from the same
establishment who are not exposed to the risk factor, as
comparison group
— e.g. within the same company compare factory floor
workers (exposed) and office workers (not exposed)
Sources of Data
— Need accurate and readily available data, can be difficult
for retrospective cohort studies
— Usual sources e.g medical / death certificates,
interviews, questionnaires
— Exposure information: pre-existing records more
objective than patient interviews
Issues in a cohort study
— Bias
— Loss to follow up
— Non participation
Bias in cohort study
—
Bias is less of a concern in cohort studies than in casecontrol studies
— Recall bias rare, but misclassification and selection
bias can still occur
Lost to Follow –Up
— Since cohort studies follow people over a period of time,
participants can move or become non-compliant
— A study that loses > 25% of participants is flawed
— The study design should use stable, compliant individuals
who are committed
In 1945, a study was conducted to know the effects of exposure of Dutch
famine to the fetus and its association with childhood and adult illnesses.
500 pregnant women who were exposed to the famine were identified and
500 women who were not exposed to the famine were also studied. The
children born to both groups were followed. It was observed that more
number of children that were born to famine exposed women developed
early cardiovascular and respiratory diseases. What is the type of study that
was conducted?
— A. Prospective cohort study
— B. Retrospective cohort study
— C. Case-control study
— D. Case series study
— E. Clinical treatment trial
A study was conducted in 1998 to know the effects of exposure of Dutch
famine to the fetus and its association with childhood and adult illnesses.
Records were acquired from 1944. A total of 500 pregnant women who
were exposed to the famine were identified and 500 pregnant women who
were living in other areas and not exposed to famine were also studied.
From the hospital records, it was found that more number of children that
were born to famine exposed women developed early cardiovascular and
respiratory diseases. What is the type of study that was conducted?
— A. Prospective cohort study
— B. Retrospective cohort study
— C. Case-control study
— D. Case series study
— E. Clinical treatment trial