Transcript Cohort Study

WARM-UP
Cohort Study
Kaijuan Wang
2008.11
Cohort Study
Wenjie Yang
[email protected]
2004.12
Concept Map
Descriptive
Epidemiology
Hypothesis
Cross-Sectional Survey
Judging
Causality
Prevention
Strategies
Analytical
Epidemiology
Cohort Study
Case-control study
Experimental
Epidemiology
Cohort Study
★Postulate of Cohort Study
★Designing of Cohort Study
★Analysis of Cohort Study
★Postulate of Cohort study
Definition of cohort
Cohort: A group of people who share
a common experience or condition.
e.g. A cohort of smoker;
A cohort of drug addict
A cohort of A type behavior
Cohort study: people who are free of
disease are classified into two (or more)
groups according to whether they are expose
to a suspected factor or not(or different
levels of the exposure) , and are followed
over a period of time, the association
between exposure and disease is evaluated by
the difference of incidence rates of the
two(or more) groups.
smokers
Lung cancer
diseased
exposed
Ie=
Follow-up
diseased
Unexposed
I0=
Types of cohort study
Prospective Cohort Study
Retrospective Cohort Study
Ambispective Cohort Study
Prospective Cohort Study
diseased
exposed
nondiseased
Initiation of study
d
unexposed
now
future
nd
Retrospective Cohort Study
diseased
exposed
nondiseased
last
Initiation of Study
d
now
unexposed
nd
Ambispective Cohort Study
diseased
exposed
nondiseased
Initiation of Study
now
unexposed
Last
d
future
nd
Comparison
Prospective cohort study
surveyed personally
Retrospective cohort study
collected from historical
records
higher authenticity
lower authenticity
time-consuming
time-saving
expensive
economic
★ Design of cohort study
1 Ascertain the research goal
2 Define the exposure and fix on the
measure method
3 Ascertain the research type
4 Ascertain a proper sample size

Z
N

2PQ  Z  P1Q1  P2Q2
( P1  P2 )
2

2
An example
A cohort study is to conducted to
reveal the association between X-ray
and leukaemia.We have know that:
1. the incidence rate of leukaemia in
general population is 1 per 10 thousand
approximately;
2. the incidence rate of leukaemia in
X-ray exposed population is10 per 10
thousand approximately;
Required:α=0.05 β=0.10 (Zα =1.96 Z
β=1.28)
N1  N 2 
( Z  2 PQ  Z  P1Q1  P2 Q2 ) 2
P1  P2
P
2
( P1  P2 ) 2
Q  1 P
P1 = 0.0001, Q1=1-0.0001=0.9999
P2 = 0.001, Q2=1-0.001=0.999
N=14247
5 Select research subject
5.1 Select the exposed group
(1) From particular group
A population that have a high
level of exposure.
ionic radiation
leukemia
radiologist
uranium miner
Atomic-bomb survivor
1) exposure is rare in general
population,but relates to particular
occupations , locations,life styles or
experiences.
2) less time and less expense needed

(2) From general population:
1) Exposure is relatively common .
E.g. Smoking
Tea drinking
2) Interested in the effect of
moderate or low level of exposure

5.2 Selection of the comparison group
Principle:
Comparison group do not have
exposure and should be as similar as
possible with the exposed group except
for the exposure .
(1) internal comparison
exposed
inhomogeneous
unexposed
(2)external comparison
exposed
exposed
Sampling
inhomogeneous
unexposed
6 Screen the subjects and collect
the baseline data
Screening of the subjects:
exclude the subjects who have had
the disease of interest
collection of the baseline data:
The exposure status
Other risk factor status
7 Follow-up
(1) Beginning of follow-up
Latency period: the period
between the initiation of exposure
and the ascertainment of outcome
(disease of interest)
(2) Period of follow-up
Depend on Strength of the
association between exposure and
disease
(3)interval of follow-up
Depend on stability of exposure
status and the span of minimum
latency period and maximum latency
period
(4) Task of follow-up
exposure status
outcome
other risk factor exposure status
(5) Main Methods of follow-up :
① Utilize varied routine record
② family interview
③ telephone or correspond inquiry
★Analysis of Cohort Study

1 Measures of disease frequency
(1) In fixed cohort(the status of
participants is changeless)
CI(cumulative incidence): The proportion
of individuals who become diseased during
a specified time period.
CI=
number of new cases of a disease
during the follow-up period
number of participants at the
initiation of follow-up

In a study of oral contraceptive use and
bacteriauria, a total of 2400 women aged
from 16 to 49 years were identified who
were free from bacteriauria. Of these,
400 were OC users at the initiation. 3
years later,20 of the OC users had
developed bacteriauria.
3-year
period CI=20/400=5.0%

(2) in dynamic population(the status of
participants is protean)
ID(incidence density) :when the denominator is
sum of person-time at risk, the incidence rate
is called as ~.
ID=
number of new cases of a disease
during the follow-up period
total person-time of observation
Jan, July, Jan, July Jan, July, Jan, July person
1998 1998 1999 1999 2000 2000 2001 2001 time
A
2
B
2.5
C
2
D
3.5
Total person-time
10
Exposed
population
General
population
Unexposed
population
Measures of association
1 RR (Relative Risk)
ratio of the risk (i.e., incidence
rate) in an exposed population to the
risk in an unexposed, but otherwise
similar, population.
Incidence（exposed）
RR=
Incidence（unexposed）
indicator of the strength (biological
significance) of an association between
an expose and disease.
RR>1
Research factor is a risk factor
(Positive association)
RR<1
Research factor is a protective
factor
(Negative association )
RR=1
No association between the factor
and the disease.
Incidence（exposed）
RR=
Incidence（unexposed）
strength
no
low
middle
high
More higher
For example, a relative risk of 2
associated with a risk factor means
that persons with that risk factor
have a doubled risk of having a
specified outcome compared to
persons without that risk factor.
Breast
Cancer
Alcohol
70
No alcohol
50
No Breast
Cancer
2,930
2,950
Total
3,000
3,000
RR using Cumulative Incidence (CI):
70 / 3,000
RR
=
50 / 3,000
= 1.4
Smoking
population
Infinite population
Non-smoking
population
samples
Statistics: p-value
indicates the likelihood that a
study’s findings are due to chance in
data analysis,
RR =2.6, p=0.001
0.1% probability that the observed
RR was a chance finding
RR =2.6
p=0.001
RR 95% CI（confidence interval): 1.8 -3.7
there is 95% probability that the true
population RR lies between 1.8 and 3.7.
Factor A
RR=2
Disease a Factor B
RR=5
Disease b
Factor A
RR=2
Disease a Factor B
RR=5
Disease b
2 AR (Attributable risk)
Numbers of cases among the
exposed that could be eliminated if
the exposure were removed.
AR=Ie-I0
AR is an estimate of the amount of
risk that is attributable to the risk
factor after all other known causes
of the disease have been taken into
account
RR & AR of different diseases
among smokers and unsmokers
Disease
Smoker
（1/100000PY）
Lung cancer
Cardio
-vascular
Unsmoker RR
(1/100000PY）
AR
（1/100000PY）
48.33
4.49
10.8
43.84
294.67
169.54
1.7
125.13
3 ARP (AR%) (attributable risk percent)
Proportion of disease in the exposed
population that could be eliminated if
exposure were removed.
Ie  Io
ARP 
100%
Ie
E
UE
E UE
Among the E group ,what percentage
of the total risk for disease is due
to the exposure

PAR (Population Attributable Risk)
Numbers of cases among the general
population that could be eliminated if
the exposure were removed.
PAR=It-I0
G
UE
G
UE

PARP (PAR%) (population attributable
risk percent)
Proportion of disease in the study
population that could be eliminated
if exposure were removed.
It  Io
PARP 
100%
It
E
UE
RR
E
NE
AR
E
NE
E
=AR%
G
NE
PAR
G
NE
G
=PAR%
3 SMR : (standardized morbidity
/mortality ratio, ）
When the polulations under study is
small and the incidence is low
SMR=O/E
O: actual number of diseased or
dead subjects
E: Expect number of diseased or
dead subjects
In a factory,there are 500 workers
with aged 20~24. 1 of them died from
lung cancer in 2001. We have known
that the incidence of lung cancer in
general population aged 20~24 is
1.8‰ . Try to evaluate the risk level
of lung cancer among 20~24 years-old
workers in the factory。
O＝1，E＝500×1.8 ‰＝0.9
SMR＝1/0.9=1.11
In
a study of oral contraceptive use
and bacteriauria, a total of 2400 women
aged from 16 to 49 years were
identified as free from bacteriauria.Of
these, 400 were OC users at the
initiation. 3 years later,20 of the OC
users had developed bacteriauria, 50 of
the non-OC users had developed
bacteriauria. Based on data above, try
to evaluate the association between OC
and bacteriauria.
Ie( 3-year period CI )=(20/400) ×100%=5.0%
Io( 3-year period CI )=(50/2000) ×100%=2.5%
RR=Ie/Io=2
contraceptive use is a risk factor to
bacteriauria
AR=Ie-Io=2.5%
Ie-Io
ARP=
×100%=
Ie
5%-2.5%
5%
=50%
(20+50)
It =
×100%=2.9 %
2400
PAR=It-Io=2.9%-2.5%=0.4%
It-Io
PARP =
×100%=13.8%
It
Advantaged of cohort studies
Unbiased assessment of exposure
assessment before outcome
 Ability to examine rare exposures
appropriate selection of exposed
populations
 Opportunity to study multiple outcomes

Disadvantaged of cohort
studies
Expensive and time-consuming
prospective cohorts
 Need to consider changes in exposure
status during follow-up
 Selection bias
losses to follow-up
 Information bias
ascertainment of outcome related to
exposure status

a
expoure
b
c
unexposure
d
a / (a+b)
RR=
c/(c+d)
≈
a/b
c/d
a﹡d
=
b﹡c
a/c
=
b/d
a
exposed
b
c
unexposed
d
a
Case
b
c
Control
d
Case Control Study: Subjects are
selected on the basis of whether they
have a particular disease or not . The
association between the exposure and
the disease is evaluated by compared
the two groups with respect to the
proportion having a history of an
exposure of interest.