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The case control study
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The case control study
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Case control studies
E+
Disease
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No disease
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Case control studies
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Disease
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No disease
E- Disease No
disease
Exposed a b
Not Exposed c d
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Case control studies
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Disease
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No disease
E- Disease No
disease
Exposed a b
Not Exposed c d
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Case control studies
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Disease
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No disease
E- Disease No
disease
Exposed a b
Not Exposed c d
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Case control studies
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Disease
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No disease
E- Disease No
disease
Exposed a b
Not Exposed c d
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Case control studies
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Disease
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No disease
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Disease No
disease
Exposed a b
Not Exposed c d
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Case control studies
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Disease
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No disease
E- Disease No
disease
Exposed a b
Not Exposed c d
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Principles of case control studies
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Case control study design
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Issues in selecting cases
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Aside...about prevalent cases
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Where do cases come from?
Population-based cases
Complete sample of all cases arising in a well-defined
population (time and place)
Hospital-based cases
Patients admitted to one of several hospitals within a given
population or area
Other sources
Patients of a medical group, persons enrolled through a
screening program, etc.
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Issues in selecting controls
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Where do controls come from?
Population-based controls
A random sample of all the disease-free population from
where cases came
If cases are within subgroups, then that subgroup is the
population from where controls must come
Neighborhood controls
Similar to cases on some, perhaps not other, factors
Dead people
Problematic if exposure in any way leads to death (i.e.,
exposure associated with control selection)
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Special case: hospitalized controls
Patients hospitalized for disease unrelated to exposure of interest
Only valid if cases/controls come from same population
(demographically and geographically)
e.g., if controls are patients with myocardial infarction, do not select
controls from pathologies (e.g., bronchitis) that may also be associated
with smoking
Problem is that sometimes we do not know that a particular disease is
associated with outcome; hence frequent use of orthopedic cases
Advantages of hospital-based controls: convenient, may be
representative of population from which cases are selected, may be
assessed in much the same way as cases
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Advantages of case control studies
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Disadvantages of case control studies
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An example
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Study findings
140
E+
Disease 180
E- 40
E+ 370
No disease 604
E- 234
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2x2 table
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What measure of associations can we
calculate?
We cannot calculate either risks or rates since we do not
have a complete population to be denominator for risk nor a
complete person time population for rate calculation
But we can calculate odds; calculation of odds depends
only on numbers of cases and numbers of controls
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And...
140
Odds of brain cancer among smokers =
370
40
Odds of brain cancer among non − smokers =
234
140* 234
Odds ratio of brain cancer = = 2.2
370* 40
Therefore, the odds of brain cancer is 2.2 times higher
among smokers vs. non - smokers
28
Cell phones and cancer: hype or
hazard?
There has been persistent concern about the potential carcinogenic
effects of electromagnetic radiofrequency fields emitted by cellular
phones
The vast majority of studies do not show an association between cell
phone use and development of tumors
Most studies neglect to look at long term users
A research group in Israel published results of a population-based
case control study to describe the association between cell phone use
and parotid gland tumors
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Sadetzki et al. Cellular phone use and risk of benign and malignant parotid gland tumors-a nationwide case-control study. Am J Epidemiol. 2007; 167:457-467
Cell phone study: set up
Controls: People who do not have PTG and are listed in the
National Population Registry in Israel
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Sadetzki et al. Cellular phone use and risk of benign and malignant parotid gland tumors-a nationwide case-control study. Am J Epidemiol. 2007; 167:457-467
Cell phone study: measuring exposure
• Number of calls?
• Duration of calls?
• Use of headsets?
Regular User • Which side of the
(exposed) head was phone held
FOR CASES AND on?
CONTROLS: • Urban or rural
location?
Has the participant
used a cell phone
more than 1x/week
for at least 6 months
(ever)? Not a regular
user
(unexposed)
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Sadetzki et al. Cellular phone use and risk of benign and malignant parotid gland tumors-a nationwide case-control study. Am J Epidemiol. 2007; 167:457-467
Cell phone study: findings
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Sadetzki et al. Cellular phone use and risk of benign and malignant parotid gland tumors-a nationwide case-control study. Am J Epidemiol. 2007; 167:457-467
It is helpful to think of all case control studies as
nested within a population cohort
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Cell phone study: set up
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Disease cases
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Incidence density sampling
For every case we select a control from the population risk set during
the same follow-up period in which the cases are identified
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Therefore, in incidence density sampling
a c Disease Time
Not Exposed c To
aim is to select controls so that
Total a+c T1+To
if b is exposed and d is unexposed
b PT1 b d d PT0
= or = or =
d PT0 PT1 PT0 b PT1 so, OR is an unbiased
estimate of the IRR in
therefore
incidence density sampling
a
PT1 a PT0 a d
IRR = = * = * = OR
c c PT1 c b
PT0
39
Case-cohort sampling
Not
c d PYOexp c+d
exposed
controls
are
selected
from those
who are no
longer
cases at
the end of
the study
Here we are overestimating the risk ratio because, at end of study, the proportion of exposure among
those who are controls is less than population (assuming a positive exposure-disease association)
When disease is “rare”, this is not much of an issue since there are very few cases so the proportion
of exposure among controls approximates population anyway
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Sampling fractions
Target population
Exposed Unexposed
a b c d
Cases Non-cases Cases Non-cases
F1 F2 F3 F4
Cases Controls
Sample 44
Case control study as sampling from a
cohort study
a * F1 * d * F4 ad *( F1 * F4 )
Case control OR = =
c * F3 * b * F2 cb *( F3 * F2 )
F1 * F4
Case control OR = Cohort OR *
F3 * F2 Disease
No
Total
disease
F1 * F4
Case control OR = Cohort OR if =1
F3 * F2
Exposed a b a+b
Not
c d c+d
exposed
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The “underlying cohort”, 2x2 table
No smoking 40 35,060
46
And...
140
IR of brain cancer among smokers =
55,360
40
IR of brain cancer among non − smokers =
35, 060
140
Odds ratio of brain cancer = 55,360 = 2.2
40
35, 060
Therefore, the incidence rate ratio of brain cancer is 2.2 times higher
among smokers vs. non - smokers
Therefore, when controls are sampled from person time of observation of
population, IRR = OR
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A note about number of controls
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Special topic: Exchangeability of odds ratio
a
a
odds of being a case among exp osed = a + b = Disease No disease Total
a b
1−
a+b Exposed a b a+b
c
Not Exposed c d c+d
c
odds of being a case among un exp osed = c + d =
c d
1- Total a+c b+d a+b+c+d
c+d
a
a* d
relative odds of being a case, comparing exp to un exp = b =
c b* c
d
a
a
odds of being exposed among cases = a + c =
a c
1−
a+c
b
b
odds of being exposed among controls = b + d =
b d
1−
b+d
a
a* d
relative odds of being exp osed , comparing cases to controls = c =
b b* c 49
d
Comparing cohort and case control studies
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