Case-Control Studies
Abdualziz BinSaeed
Case-Control Studies
• Type of analytic study
• Unit of observation and analysis: Individual
(not group)
Case-Control Studies
• Definition:
It is a type of observational analytic epidemiologic
investigation in which subjects are selected on the basis
of whether they do or do not have a particular disease
under study.
• Importance of case-control studies
∂ (drawback of cohort study “large population”)
∂ Achieving the same goals of cohort study efficiently
Case-Control Studies
• Case-control studies are the most frequently undertaken
analytical epidemiological studies
• They are the only practical approach for identifying risk
factors for rare diseases
• They are best suited to the study of diseases for which
medical care is sought, such as cancers or hip fracture
Design
• At baseline:
– Selection of cases (disease) and controls (no disease)
based on disease status
– Exposure status is unknown
• Retrospective design – lacks temporality!
Case Control Study Design
Exposed
Diseased
)Cases(
Not Exposed
Target
Population
Exposed
Not Diseased
)Controls(
Not Exposed
Selecting Cases
• Select cases after the diagnostic criteria and
definition of the disease is clearly
established
• Study cases should be representative of all
cases
Selecting Cases (cont.)
• The study need not include all cases in the
population
• Cases may be located from hospitals, clinics,
disease registries, screenings, etc.
Selecting Cases (cont.)
• Incident cases are preferable to prevalent
cases for reducing (a) recall bias and (b) over-
representation of cases of long duration
• The most desirable way to obtain cases is to
include all incident cases in a defined
population over a specified period of time
Selecting Controls
• Controls should come from the same
population at risk for the disease as the cases
• Controls should be representative of the
target population
Selecting Controls (cont.)
• Controls estimate the exposure rate to be
expected in cases if there were no
association between exposure and disease
Selecting Controls (cont.)
• Multiple controls can be used to help add
statistical power when cases are unduly
difficult to obtain
• Using more than one control group lends
credibility to the results
• More than 3 controls for a case is usually not
cost-efficient
Sources of cases and controls
CASES CONTROLS
All cases diagnosed in the Sample of general population
community
All cases diagnosed in a Non-cases in a sample of the
sample of the population population
All cases diagnosed in all Sample of patients in all
hospitals hospitals who do not have the
disease
All cases diagnosed in a
Sample of patients in the same
single hospital
hospital who do not have the
disease
Any of the above methods Spouses, siblings or associates
of cases
Assessing Exposure
• Exposure is usually an estimate unless past
measurements are available
– It has to be assumed that the exposure incurred
at the time the disease process began (this may
not be valid)
Assessing Exposure (cont.)
• Exposure estimates are subject to recall bias and
interviewer bias
– Some protection may be afforded by blinding
interviewers and carefully phrasing interview
questions
• Potential confounders need to be accurately
assessed in order to be controlled in the analysis
Odds Ratio (OR)
• A ratio that measures the odds of exposure for
cases compared to controls
• Odds of exposure = number exposed number
unexposed
• OR Numerator: Odds of exposure for cases
• OR Denominator: Odds of exposure for controls
Calculating the Odds Ratio
Disease Status
CHD cases No CHD
)Cases( )Controls(
Exposure Smoker 112 176
Status Non- 88 224
smoker
Total 200 400
AD x 112
Odds Ratio = = 224 = 1.6
BC x 88 176 2
OR<1 OR=1 OR>1
Odds of exposure Odds of Odds of exposure
Odds exposure are for cases are
for cases are less
comparison equal among greater than the
than the odds of
between cases cases and odds of exposure
exposure for
and controls controls for controls
controls
Exposure
Exposure
Exposure as a reduces Particular
increases
risk factor for disease risk exposure is not
disease risk
?the disease Protective( a risk factor
(Risk factor)
)factor
Interpreting the Odds Ratio
The odds of exposure for cases are 1.62 times
the odds of exposure for controls.
Interpreting the Odds Ratio
Those with CHD are 1.62 times more likely to be
smokers than those without CHD
or
Those with CHD are 62% more likely to be
smokers than those without CHD
Possible Sources of Bias and Error
• Information on the potential risk factor
(exposure) may not be available either from
records or the study subjects’ memories
• Information on potentially important
confounding variables may not be available
either from records or the study subjects’
memories
Possible Sources of Bias and Error
(cont.)
• Cases may search for a cause for their
disease and thereby be more likely to report
an exposure than controls (recall bias)
• The investigator may be unable to determine
with certainty whether the suspected agent
caused the disease or whether the
occurrence of the disease caused the person
to be exposed to the agent
Possible Sources of Bias and Error
(cont.)
• Identifying and assembling a case group
representative of all cases may be unduly
difficult
• Identifying and assembling an appropriate
control group may be unduly difficult
Nested Case-Control Study
Initial Data and/or
Population
Serum, Urine, or Other
Specimens Obtained
Years
Do Not
Develop
Develop
Disease
Disease
Subgroup
”Cases” Selected as
”Controls“
CASE-CONTROL STUDY
ORs, P-Values and 95% CIs for Case-Control
Study with 3 Different Sample Sizes
Sample Size
Parameter
n=500 n=50 n=20
Computed
2.0 2.0 2.0 OR
0.001 0.200 0.500 p-value
1.5, 2.6 0.9, 4.7 0.5, 7.7 95% CIs
Advantages of Case-Control
Studies
• Quick and easy to complete, cost effective
• Most efficient design for rare diseases
• Usually requires a smaller study population
than a cohort study
Disadvantages of Case-Control Studies
• Uncertainty of exposure-disease time
relationship
• Inability to provide a direct estimate of risk
• Not efficient for studying rare exposures
• Subject to biases (recall & selection bias)
