Transcript Case Control and Cohort studies

Case Control and
Cohort studies
Dr. Hardeep Kaur
Associate Professor
University College of Nursing
Faridkot
Over view
- One of the most significant triumphs of the
case-control study was the demonstration of
the link between tobacco smoking and lung
cancer, by Sir Richard Doll
- Doll was able to show a statistically
significant association between the two in a
large case control study.
- Opponents argued (correctly) for many years
that this type of study cannot prove causation,
contd.
But the eventual results of cohort studies
confirmed the causal link which the casecontrol studies suggested, and it is now
accepted that tobacco smoking is the cause of
about 87% of all lung cancer mortality in the
US.
- Till now case control studies have been used
effectively for studies of many cancers, and
other serious conditions such as cirrhosis of
liver, lupus erythematous and congestive
heart failure.
Introduction
• For medical interventions,
the 'gold standard' is the double blind
randomized controlled trial, a specific type of
experiment. While such trials may be ideal for
testing the efficacy of (what are hoped to be)
beneficial interventions, such as surgeries or
drug treatments,
• There are many instances in which trials
would be impossible, impractical, and/or
unethical
Introduction
Studying infrequent events such as death
from cancer using randomized clinical trials
or other controlled prospective studies
requires that large populations be tracked for
lengthy
periods
to
observe
disease
development
So ideal way for studying such events is
case control studies.
Study design in epidemiology
Observational
study
individual
Case-control
study
intervention
population
Cohort
study
Ecological
study
DISTINCT FEATURES OF CASE
CONTROL STUDIES
The case control study has three distinct
features:
 Both exposure & outcome ( disease) have
occurred before the start of the study
 Study proceeds backwards from effect to
cause and
 It uses a control or comparison group to
support or refute an inference
Various types of case-control studies
１）a population-based case-control study
Both cases and controls are recruited from the
population.
２）a case-control study nested in a cohort
Both case and controls are members of the cohort.
３）a hospital-based case-control study
Both case and controls are patients who are
hospitalized or outpatients.
Controls with diseases associated with the exposure
of interest should be avoided.
FOUR BASIC STEPS IN CONDUCTING A
CASE CONTROL STUDY
SELECTION OF CASES & CONTROL
MATCHING
MEASUREMENT OF EXPOSURE
ANALYSIS AND INTERPRETATION
SELECTION OF CASES AND
CONTROLS
SELECTION OF CASES
 Definition of a Case
• Diagnostic criteria
• Eligibility criteria
 Sources Of Cases
• Hospitals
• General population
Who will be controls?
• Control
≠
non-case
– Controls are also at risk of the disease
in his(her) future.
– “Controls” are expected to be a
representative sample of the
catchment population from which the
case arise.
– In a case-control study of gastric
cancer, a person who has received the
gastrectomy cannot be a control since
he never develop gastric cancer .
MATCHING
Matching is defined as a process
by which we select controls in
such a way that they are similar
to cases with regard to certain
pertinent selected variables( e.g.
age) which are known to
influence the outcome of a
disease and which, if not
adequately
matched
for
comparability , could distort or
confound the results.
MATCHING CONTD……
• While matching it should be
kept in mind that suspected
etiological factors or the
variable we wish to measure
should not be matched.
• Matching procedures
- Group matching
- Pairing( Matched pairs)
MEASUREMENT OF EXPOSURE
• Definition & criteria about exposure are just as
important as those used to define cases & controls.
• Information about exposure should be obtained
by in precisely the same manner both for cases &
controls
• The information can be obtained by
- Interviews
- Questionnaire
- Studying past records
FLOW CHART
CASE CONTROL
CASES (DISEASE)
EXPOSED
CONTROLS (NO DISEASE)
NON EXPOSED EXPOSED NON EXPOSED
ANALYSIS
The final step is analysis to find out
- Exposure rates among cases & controls
to suspected factor
- Estimation of disease risk associated
with exposure ( odd ratio)
APPROXIMATING THE RATE
RATIO
EXPOSURE
NON
EXPOSURE
DISEASE
a
NO DISEASE TOTAL
b
M1
c
d
M2
N1
N2
T
N1- with disease
N2 – without disease
Two groups of subjects
you use to start project
in case control studies
Exposure Rate
Smoke
cigarettes
Do not
smoke
cigarettes
Develop
CHD
Do not
develop
CHD
Totals
Incidence
of disease
84
2916
3000
84/3000
87
4913
5000
87/5000
Cases = a/a+c = 84/84+87 = 49.1 %
Controls = b/b+d = 2916/ 2916+4913 = 37.2%
Odds Ratio
-In statistics, an odds of an event is the ratio of:
The probability that the event WILL occur to the
probability that the event will NOT occur
For example, in 100 births, the probability of a
delivery being a boy is 51% and being a girl is
49%
The odds of a delivery being a boy is 51/49 = 1.04
• In simpler term, an odds of an event can be calculated
as: Number of events divided by number of nonevents
APPROXIMATING THE RATE
RATIO
EXPOSURE
NON
EXPOSURE
DISEASE
a
NO DISEASE TOTAL
b
M1
c
d
M2
N1
N2
T
N1- with disease
N2 – without disease
Two groups of subjects
you use to start project
in case control studies
DISEASE ODD RATIO (OR)
OR = Odds of disease in
exposed group
Odds of disease in
non exposed
OR = a/b+c/d=a*d/b*c
Odds Ratio
Develop
Disease
Do no
develop
disease
Exposed
50
50
100
NonExposed
25
75
100
• Relative Risk = 50/75
______ = 2
50/25
• Odds Ratio = 50 x 75
______ = 3
50 x 25
Interpreting Odds Ratio of a Disease
• If OR = 1Exposure is not related to disease
• No association; independent
• If OR > 1Exposure is positively related to
disease
• Positive association; ? causal
• If OR < 1Exposure is negatively related to
disease
• Negative association; ? protective
Bias should be minimized
• Bias & Confounding
– Selection bias
– Detection bias
– Information bias (recall bias)
– Confounding
Confounding can be controlled
by statistical analyses but we
can do nothing about bias after
data collection.
PROS & CONS OF CASE
CONTROL STUDIES
- Relatively easy to carry out
- Rapid and inexpensive ( as
compared with cohort)
- Require comparatively few
subjects
- No risk to subjects
- No attrition problem is present
- Minimal ethical problems
On the other hand………
• Problem of bias relies on
memory or past records, the
accuracy of which may be
uncertain
• selection
of
appropriate
control group may be difficult
or sometimes impossible
• These
studies
donot
distinguish between cause &
associated factors
COHORT STUDIES
MEANING OF A COHORT
• Ancient
Roman
military unit, A band
of warriors.
• Persons
banded
together.
• Group of persons with
a common statistical
characteristic. [Latin]
E.g. age, birth date
INTRODUCTION
Cohort is another type of
analytical (observational) study
which is usually undertaken to
obtain additional evidence to
refute or support the existence of
an association between suspected
cause & disease.
- These studies are also called as
longitudinal studies, incidence
studies.
INTRODUCTION CONTD……..
• A major limitation of cross-sectional surveys and casecontrol studies is difficulty in determining if exposure or
risk factor preceded the disease or outcome.
• In Cohort study the Key Point is:
Presence or absence of risk
factor is determined before
outcome occurs.
INDICATION OF A COHORT
STUDY
• When there is good evidence of
exposure and disease.
• When exposure is rare but
incidence of disease is higher
among exposed
• When follow-up is easy, cohort
is stable
• When ample funds are available
THREE DISTINCT FEATURES OF
COHORT STUDIES INCLUDE………
• The cohorts are identified
prior to the appearance of the
disease under investigation
• The study groups, so defined
are observed over a period of
time
to
determine
the
frequency of disease among
them
• The study proceeds forward
from cause to effect.
Frame work of Cohort studies
Disease Status
Total
Exposure
Status
Yes
Yes
a+b
a
No
c+d
c
N
a+c
No
b
d
b+d
Study
cohort
Comparison
cohort
General consideration while selection
of cohorts

Both the cohorts are free of the disease.
 Both the groups should equally susceptible
to disease
 Both the groups should be comparable
 Diagnostic and eligibility criteria for the
disease should be defined well in advance.
Types of Cohort Study
Retrospective
(historical)
cohort study
Prospective
cohort study
Combination of
Retrospective
and Prospective
cohort study.
Elements of cohort study
Selection of study subjects
• General population
- Whole population in an area
- A representative sample
• Special group of population
– Select group
- occupation group / professional group (Dolls
study )
– Exposure groups
- Person having exposure to some physical,
chemical or biological agent (e.g. X-ray
exposure to radiologists)
Obtaining data on exposure
•
•
•
•
Personal interviews / mailed questionnaire
Reviews of records
Medical examination or special test
Environmental survey
By obtaining the data of
exposure we can classify cohorts
as Exposed and non exposed
and By degree exposure we can
sub classify cohorts
Selection of comparison group
• Internal comparison
- Only one cohort involved in study
• External comparison
- More than one cohort in the study for the
purpose of comparison
• Comparison with general population rates
– If no comparison group is available we can
compare the rates of study cohort with
general population.
Follow-up
• To obtain data about outcome to be
determined (morbidity or death)
 Mailed questionnaire, telephone calls,
personal interviews
 Periodic medical examination
 Reviewing records
 Surveillance of death records
 Follow up is the most critical part of the
study
• Some loss to follow up is inevitable due
to death change of address, migration,
change of occupation.
• Loss to follow-up is one of the draw-back
of the cohort study.
ANALYSIS
• Calculation of incidence rates
among exposed and non
exposed groups
• Estimation of risk
Incidence rates of outcome
Disease Status
Exposure
Status
Yes
No
Yes
No
Total
a
b
a+b
c
d
c+d
b+d
N
a+c
Study
cohort
Comparison
cohort
Incidence rate
• Incidence among exposed =
a
a+b
• Incidence among non-exposed
=
c
c+d
Estimation of risk
Relative Risk
incidence of disease
among exposed
RR =
__________________
Incidence of disease
among non-exposed
a/a+b
=
_________
c/c+d
Estimation of Risk Contd…….
• Attributable Risk
Incidence of disease among exposed
– incidence of disease among non
exposed
AR =
__________________________
Incidence of disease among
exposed
a/a+b – c/c+d
AR = _______________
a/a+b
Comparison of the study design
Case-control
Rare diseases
suitable
Number of disease
1
Sample size
relatively small
Control selection difficult
Study period
relatively short
Recall bias
yes
Risk difference
no available
Cohort
not suitable
1<
need to be large
easier
long
no
available
Cohort studies
Strengths
• We can find out
incidence rate and risk
• More than one disease
related to single
exposure
• can establish cause effect
• good when exposure is
rare
• minimizes selection and
information bias
•
•
•
•
•
•
Weaknesses
losses to follow-up
often requires large
sample
ineffective for rare
diseases
long time to complete
expensive
Ethical issues
THANK YOU
THANKS