Case-Control Studies
Dr. Prasanna Mithra P. MD, DNB
Associate Professor
Dept. of Community Medicine
Kasturba Medical College (Manipal
University), Mangalore
Case Control Study
It is an observational, analytical epidemiological study
Subjects selected on the basis of whether they do (Cases) or do
not (controls) have a particular disease/condition/outcome under
study
Used to test a hypothesis
The groups are compared with respect to the proportion having
history of an exposure or characteristic of interest
Case-control studies - most frequently undertaken analytical
epidemiological studies
Only practical approach for identifying risk factors for chronic
& rare diseases
Best suited to the study of diseases for which medical care is
sought, such as cancers, cirrhosis, SLE, CCF
Case Control Study Design
Exposed
Diseased
(Cases) Not Exposed
Target
Population Exposed
Not Diseased
(Controls) Not Exposed
Distinct Features
Both exposure and outcome have occurred before start of
disease
Study proceeds backward - from effect to cause (Retrospective
study)
Uses comparison group to support or refute an inference
Example of Case Control Study
Chewers of
tobacco
Cases of Oral
Cancer
Non chewers
of tobacco
Chewers of
tobacco
Controls
Non chewers
of tobacco
Basic Steps
1. Selection of cases and controls
2. Matching
3. Measurement of exposure
4. Analysis, interpretation
Selecting Cases
Diagnostic criteria and definition of the disease and stage of
disease to be clearly established
Once established diagnostic criteria should not be changed
Study cases should be representative of all cases
Sources – Hospital or General Population
Selecting Cases (Cont.)
Eligibility criteria
Incident cases are preferable to prevalent cases for reducing
(a) Recall bias
(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
Controls estimate the exposure rate to be expected in cases if there
were no association between exposure and disease
Sources of Controls
Hospital
Relatives How many controls?
1:1 to maximum of 1:4 (Case : Control)
Neighborhood
Beyond that there is no added advantage
General population
Multiple types of controls
Matching
It is a process by which controls are selected so that they are
similar to cases with regarding to certain pertinent variables which
are known to influence the outcome of the disease
If not matched adequately for comparability, it could distract or
confound the result
Cases and controls should be as similar as possible except for the
presence of outcome of interest
Group matching
Individual matching
Examples of Confounders
Age
OCP CA BREAST
ALCOHOL CA. ESOPHAGUS
Smokin
g
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
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
Analysis & Interpretation
Cases Controls
(Disease (Disease
present) absent)
Risk Present a b
factor Absent c d
a+c b+d
Level of risk factors among Cases = a / (a+c) x 100
Level of risk factors among controls= b / (b+d) x 100
Odds Ratio (OR)
A ratio that measures the odds of exposure for cases compared to
controls
It describes the risk of developing a disease in the presence of a
risk factor as compared to its absence
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
Cases Controls
(CHD) (No CHD)
Exposu Smokers 112 176
re Non-smokers 88 224
Status 200 400
AD 112 x 224
Odds Ratio = = = 1.62
BC 176 x 88
Interpreting the Odds Ratio
The odds of exposure for cases are 1.62 times the odds of
exposure for controls or
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
When is the odds ratio a good approximation
of the relative risk in the population?
When the cases studied are representative, with regard to history
of exposure, of all people with the disease in the population
When the controls studied are representative, with regard to
history of exposure, of all people without the disease in the
population
When the disease being studied does not occur frequently
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
Suitable when the disease being studied occurs rarely, e.g. -
cancer of a specific organ
Relatively efficient, requiring a smaller sample than a cohort
study
No attrition problems
Sometimes the earliest practical observational strategy for
determining an association
For e.g. - use of diethyl stilboesterol and clear cell
adenocarcinoma of vagina in daughters
Disadvantages of Case-Control Studies
Uncertainty of exposure - disease time relationship
Cannot measure incidence
Inability to provide a direct estimate of risk
Not efficient for studying rare exposures
Subject to biases (recall & selection bias)
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
