Cohort Study

Cohort studies also called :

follow-up studies, incidence studies, or prospective
studies.

1. Begin with a group of individuals free of the

disease(s) of interest

2. Determine the incidence rate (or mortality rate)

among the exposed and the unexposed

Cohort study designs evolved because of the need

for information on the length of survival and the
natural history of disease
 DZ

E
DZ
Healthy
People
DZ
E
-

DZ
 exposed

unexposed
 exposed

Incidence among
exposed

unexposed

Incidence among
unexposed
 Cohort Study
 Prospective (concurrent/longitudinal study):
Collect exposure information at the time the study
begins and follow for disease status that may occur in
the future
 Retrospective (historical):
Collect exposure information from some time in the
past and construct disease incidence (or mortality) from
then until the present
 Directionality

Longitudinal

1990 2000 2010

Retrospective Prospective

Retrospective Prospective
Cohort Study Cohort Study
 Time
Prospective: Onset of study
Onset of study
Retrospective:

Disease

Exposed
No disease

Eligible
subjects Disease
Unexposed

No disease

Direction of inquiry
PROSPECTIVE COHORT STUDY

2008 2011 Time

Onset of study

Disabled
Very low
Apgar score
No Disabled
Newborn
infants

Disabled
Higher
Apgar score
Not Disabled

Direction of inquiry
RETROSPECTIVE COHORT STUDY
2008 Onset of study
2009 2010 Time

Disabled
Very low
Apgar score
Newborn
infants
Not Disabled

Disabled
Higher
Apgar score
Not Disabled

Direction of inquiry
Comparison of retro- and prospective cohort study

Attribute Retrospective Prospective

approach approach
Information < complete > complete
< accurate > acurate
Expense Less costly More costly
Completion time Shorter Longer
 Outcome Definition
 Primary outcome
The main event that will be related to the
exposure

 Secondary outcomes
Other events that are of interest and may
corroborate the findings of the main outcome
Exercise 1.

Which of the following is a cohort study?

A. The risk of endometrial cancer in women with estrogen used
B. To investigate the risk of childhood cancer among those who had
received IM vitamin K
C. The occurrence of liver cirrhosis in 15 years and 20 years
alcohol consumption
D. Cholera carriers among residents of some villages with
different types of water supply
E. Exercise and the incidence of type 2 diabetes in impaired fasting
glucose group
 Advantages
 Direct calculation of risk ratio (relative risk)
 Clear temporal relationship between exposure and
disease
 Particularly efficient for study of rare exposures
 Ascertain incidence and natural history of disease
 Advantages (cont.)
 Can yield info on multiple outcomes of a particular
exposure
 Minimize bias
 Strongest observational design for establishing cause
and effect relationship
 Disadvantages
 Time consuming
 Often requires a large sample size
 Requires excellent follow-up
 Latency period
 Bias : selection bias, information bias
 Expensive
 Exposure can change
 Disadvantages (cont.)
 Not efficient for the study of rare diseases
 Losses to follow-up may diminish validity
 Changes over time in diagnostic methods may
lead to biased results
 Over long period, study procedures may influence
the behavior of the persons investigated in such a
way that the development of the disease may be
influenced accordingly
Exercise 2.

Which of the following statements are the advantages of a cohort

study?
A. Efficient for study of rare exposures
B. Can yield info on multiple outcomes of a particular exposure
C. Often requires a large sample size
D. Losses of follow-up may diminish validity
E. There is no bias in this type of study
Exercise 3.

What are the disadvantages of cohort study?

A. Often requires a large sample size
B. Particularly not efficient for study of rare exposures
C. Not efficient for the study of rare diseases
D. Exposed & unexposed groups must be free of the outcome of
interest at start of the study
E. There would be more biases compared with case control study
 Subject selection
 Selection of subjects for a cohort study is influenced
by various factors :
 The type of exposure under investigation

 Frequency of the exposure in the population

 Accessibility of subjects and the likelihood of their

continuing participation

 Exposed & unexposed groups must be free of the

outcome of interest at start of the study
 Subject selection (cont.)

 Exposed & unexposed groups must be similarly

eligible to develope the outcome of interest during
the course of study

 If some subjects already have the outcome of

interest at the onset of the study, the temporal
relationship between exposure and outcome will be
obscured.
 Subject selection (cont.)
Exposed Group
 Type of exposure under investigation is critical for

selection of the exposed group

 Feasibility (accessible and continuous
participation)
 Degree of exposure depends on the goals of the

study (exposed/unexposed, range of exposure

levels)
 Subject selection (cont.)
Unexposed (control) Group
 Feasibility issues same with exposed group

 Should yield a fair comparison with exposed group

 Unexposed persons should be sampled from the

same (or comparable) source population as the

exposed group
 Multiple comparison groups of unexposed subjects
chosen in different ways may reinforce the validity of
the findings
Exercise 4.

How is the subject selection in cohort study?

A. Assess the accessibility of subjects and the likelihood of their
continuing participation
B. Exposed group must be free of the outcome of interest at start of the
study
C. Exposed & unexposed groups must not be free of the outcome of
interest at start of the study
D. Unexposed group must be free of the outcome of interest at start of
the study
E. Unexposed persons should be sampled from the different source
population as the exposed group
 Data Collection

Exposure (Independent variable)

 Essential to define the exposure clearly

(intensity, duration, regularity, variability)

 A subject originally satisfies the criteria for
inclusion in cohort study should not
subsequently be excluded from the analysis due
to change in exposure status during follow-up
(avoid biased conclusion).
 Data Collection (cont.)
Exposure (Independent variable)
 Ex.

Use of anti nausea medication during pregnancy

& subsequent risk of spontaneous abortion.
The medication may be discontinued because of
early sign of abortion. Excluding this subject from
the analysis may result in an underestimateof the
true link between use of medication and risk of
abortion.
 Data Collection (cont.)

Exposure (Independent variable)

 It is possible that a change in exposure status may

indicate a change in outcome status

 Potential for changes in exposure status has
important implication for the frequency of follow-up
 Frequent reassessment of exposure and outcome

status required if exposure status changes over time

 Data Collection (cont.)

Response (Dependent variable)

 Before start of study, imperative that the subjects

do not have the outcome (disease) under

investigation (difficult if disease develops slowly,
insidious onset, asymptomatic till late stages)
 Same surveillance in exposed and unexposed

groups
 Data Collection (cont.)
Response (Dependent variable)
 Sources of outcome status

 Records of hospitals and physicians

 Periodic exams by investigators

 Accuracy and reliability of diagnosis same

between groups
 Standard diagnostic protocol
Exercise 5.

How is the data collection in cohort study?

A. It is essential to define the exposure clearly
B. Changes in exposure status has no important implicationfor the
frequency of follow-up
C. A change in exposure status may not indicate a change in outcome
status
D. Frequent reassessment of exposure and outcome status is not
required if exposure status changes over time
E. It is imperative that the subjects do not have the outcome under
investigation
ANALYSIS OF COHORT STUDIES

Outcome*
Death No death Total

Exposed A B A+B

Unexposed C D C+D

Total A+C B+D A+B+C+D

* Outcome : death/disease
 A = Exposed persons who later die
B = Exposed persons who do not die
C = Unexposed persons who later die
D = Unexposed persons who do not die

The total number of exposed persons = A + B

The total number of unexposed persons = C + D
 Among exposed persons, the RISK (R) of death is defined as :
Exposed persons who die A
R(exposed) = =
All exposed persons A+B

 Among unexposed persons, the RISK (R) of death is :

Unexposed persons who die C

R (unexposed) = =
All unexposed persons C+D

R (exposed) A / (A + B)
Relative Risk (RR) = =
R (unexposed) C / (C + D)
RR = A measure of the strength of association
between exposure and outcome

General interpretation of relative risk (RR)

RR > 1 : Positive association between disease and risk factor/

harmful
= 1 : No association
< 1 : Negative association /protective effect
e.g.

Relationship between 10-minute Apgar scores and risk of death in the

first year of life among children with birth weights of at least 2500 g.

Death No death Total

Apgar score
42 80 122
0-3
Apgar score 4
43 302 345
-6

Total 85 382 467

Nelson KB, Ellenberg JH : Apgar scores as predictors of chronic neurologic

Disability. Pediatrics 1981; 68-36
 R(exposed) = 42 / 122 = 0.344 = 34.4 %

R( less exposed) = 43/345 = 0.125 = 12.5 %

42 43
RR = = 2.8
122 345

The RR of 2.8 means that newborns at this birth weight with

very low 10 minute Apgar scores are almost 3 times more
likely to die in the first year of life
Thank you