Design and Analysis of Clinical Study
6. Case-control Study
Dr. Tuan V. Nguyen
Garvan Institute of Medical Research
Sydney, Australia
What is Case-Control ?
• Traditional view: compare
- people who get the disease
- people who do not get the disease
• “Controls” a misnomer, derived from faulty analogy to
controls in experiment
• Modern conceptualization: controls are a “window” into the
“study base”
Case – Control Study
• Grouping studied: "cases" vs. "Control" group(s).
• Measurements analyzed: past "exposures.“
• Case-selection usually clinic- or hospital-based.
• Controls may also be clinic- or hospital-based, or
population-sampled.
• Controls may be unmatched, group-matched, or
individually matched.
Case-Control Study
Yes
Cases
No
Yes
Controls
No
Population at risk
Case-Control Study
Aspirin
use
Cases
No Aspirin
use
Aspirin
use
Controls
No Aspirin
use
Population at risk
Steps in Designing Case-control Studies
• Selection of cases
–
–
–
–
Precise definition of ‘case’.
Inclusion / Exclusion criteria.
Are cases to be ‘incident’ or ‘prevalent’?
How are cases to be identified? How recruited?
Steps in Designing Case-control Studies
• Selection of Controls
– Source ( hospital patients without disease; neighbourhood
controls; random sample of population; sibs).
– Inclusion / exclusion criteria.
– Match to cases?
Steps in Designing Case-control Studies
• Collection of information
– Identify risk factor of interest
– Method of collection of information ( questionnaire; medical
records; employment records)
– Same procedure to be used for cases and controls
– Interviewer should be unaware who is a case and who a
control.
Two Methods of Selection
• Select new cases
(i.e.incident) as they come
up. Controls are selected
from those in the same
setting at the same time.
• Select existing cases
(prevalent) from a defined
population. From the same
population a larger number
of controls are identified.
The Incident type of case-control study is stronger because diagnosis
of cases and ascertainment of exposure is being done by the
researcher.
Results of a Case-Control Study
Disease
Risk factor
Yes (cases)
No (controls)
Aspirin Use
a
c
No Aspirin Use
b
d
N1
N2
Total
N1 and N2 are fixed numbers
Nested Case-Control Study
• Case-control studies within a cohort study
• In ARIC (Atherosclerosis Risk in Communities) study, a cohort
of 16 thousand men, all men provided serum samples at the
outset which were saved.
• The cohort is observed for CHD.
• After 5 years we have 246 cases of CHD.
• We randomly choose 500 participants to be controls.
• We only measure Chlamydia antibody in the stored sera from
these 246 + 500 subjects.
• We compare the cases (CHD) to the controls (no CHD) with
regard to the presence of exposure (Chlamydia) which
preceded the outcome
Matched Case-Control Studies
Cases
cases
Non-cases
cases
Non-cases
Controls
Cases
Controls
All cases or
random sample
Random sample
of non-cases
All cases or
random sample
Matched
controls
Effects of Beta-blocker on Hip Fracture
• Select a hip fracture case
• Note the patient’s age, sex, weight, bone mineral density
(BMD)
• Select a sample of controls
• Randomly selected k controls who have the same age,
weight, and BMD as the case
Potential Biases
• A knowledge of the patient's disease status may
influence:
– Both the intensity and outcome of a search for
exposure to the putative cause
• A late look at those exposed (or affected) early will
miss:
– Fatal and other short episodes, plus mild or silent
cases and cases in which evidence of exposure
disappears with disease onset
COHORT VS. CASE-CONTROL STUDIES OF CHD VS. CHOLESTEREMIA
AMONG MEN
UPPER QUARTILE SERUM CHOLESTEROL
COHORT STUDY
CHD BY EXAM 6
YES
NO
TOTAL
YES
85
462
547
NO
116
1511 1627
TOTAL 201
1973 2174
ODDS RATIO = 2.40
CASE-CONTROL STUDY
CHD BY EXAM 6
YES
NO
TOTAL
38
34
72
113
117
230
151
151
302
ODDS RATIO = 1.16
Sample Size Calculation
• Power : probability of detecting a real effect (eg b = 0.20)
• Alpha level : probability of detecting a false effect (eg a =
0.05)
• P0 : probability of exposure in controls
• P1 : probability of exposure in case subjects
• R : odds ratio of exposures between cases and controls
• m : number of control subjects per case subject
Sample Size Calculation
• The estimated sample size is:
Website for Sample Size Calculation
http://www.sph.emory.edu/~cdckms/sample%20size%202%20grps%
20case%20control.html
Advantages and Disadvantages of Case-control
Studies
Advantages
• Relatively cheap compared
to cohort studies
• Relatively quick
• Useful for study of rare
diseases.
• No ethical problems
• Useful for diseases with long
latent period.
Disadvantages
• Estimate of disease
incidence cannot be done
• At times difficult to measure
exposure accurately
• Open to selection bias.
• Difficult to interpret.
Self-evaluation Questions
• Q2: Suppose that in a case-control study using incident cases of colon
cancer you found that 80% of the cases were married. Does this
demonstrate that being married increases the risk of developing cancer?
• Q2: In the same case-control study above, assume that 90% of the
control group group are married. If there are 200 cases and 200
controls, estimate the risk of colon cancer for single men. Constuct a 2x2
table and determine and interpret the exposure odds ratio.