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Case-Control StudiesResearch Methods Mini-Course
July, 2005
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Overview of study designs
Study designs
Descriptive Analytic
Randomized Non-randomized
Quasi-experiment
Cohort
Case-Control
Cross-sectional
Longitudinal
Other
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Data layout common to many analytic studies
Outcome
Exposed? Bad Good
Yes a b
No c d
where a, b, c, d are number ofstudy subjects in each cell
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Generic case-control study
Potentialstudy subjects
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Generic case-control study
Potentialstudy subjects
Sample according tooutcome status
Poor outcome(“case”)
Good outcome(“control”)
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Generic case-control study
Potentialstudy subjects
Sample according tooutcome status
Poor outcome(“case”)
Good outcome(“control”)
Exposedto riskfactor
Notexposedto riskfactor
Exposedto riskfactor
Notexposedto riskfactor
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Case-control study of statins and fatal injury
Source populationfollowed � 1 year
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Case-control study of statins and fatal injury
Source populationfollowed � 1 year
Sample accordingto fatal injury
All fatalinjury cases
Sample of controls(without fatal injury)
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Case-control study of statins and fatal injury
Source populationfollowed � 1 year
Sample accordingto fatal injury
All fatalinjury cases
Sample of controls(without fatal injury)
Had usedstatins
Had notused statins
Had usedstatins
Had notused statins
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Key features of a case-control study
� Relative sizes of case and control groups usually donot reflect frequency of outcome in the sourcepopulation. Typically:
� All available cases included
� Only a sample of many non-cases included
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Key features of a case-control study
� Relative sizes of case and control groups usually donot reflect frequency of outcome in the sourcepopulation. Typically:
� All available cases included
� Only a sample of many non-cases included
� Hence cannot directly estimate incidence fromcase-control data
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Key features of a case-control study
� Relative sizes of case and control groups usually donot reflect frequency of outcome in the sourcepopulation. Typically:
� All available cases included
� Only a sample of many non-cases included
� Hence cannot directly estimate incidence fromcase-control data
� Nonetheless, can nearly always estimate ratio ofincidence in exposed to that in non-exposed (i.e.,relative risk):
RR � Odds Ratio = ad/bc
(To be explained in EPI 512/513)
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Case-control sampling: 1 control/case
Full population (unobserved):
Fatal injury?
Yes No
Statin 20 1,000 1,020
No statin 80 9,000 9,080
100 10,000 10,100
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Case-control sampling: 1 control/case
Full population (unobserved):
Fatal injury?
Yes No
Statin 20 1,000 1,020
No statin 80 9,000 9,080
100 10,000 10,100
RR � 20
�
1,02080
�
9,080
� 2.23
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Case-control sampling: 1 control/case
Full population (unobserved):
Fatal injury?
Yes No
Statin 20 1,000 1,020
No statin 80 9,000 9,080
100 10,000 10,100
RR � 20
�
1,02080
�
9,080
� 2.23
Case-control sampling:
Statin
No statin
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Case-control sampling: 1 control/case
Full population (unobserved):
Fatal injury?
Yes No
Statin 20 1,000 1,020
No statin 80 9,000 9,080
100 10,000 10,100
RR � 20
�
1,02080
�
9,080
� 2.23
Case-control sampling:
Statin
No statin
100
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Case-control sampling: 1 control/case
Full population (unobserved):
Fatal injury?
Yes No
Statin 20 1,000 1,020
No statin 80 9,000 9,080
100 10,000 10,100
RR � 20
�
1,02080
�
9,080
� 2.23
Case-control sampling:
Statin
No statin
100 100
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Case-control sampling: 1 control/case
Full population (unobserved):
Fatal injury?
Yes No
Statin 20 1,000 1,020
No statin 80 9,000 9,080
100 10,000 10,100
RR � 20
�
1,02080
�
9,080
� 2.23
Case-control sampling:
Statin 20
No statin 80
100 100
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Case-control sampling: 1 control/case
Full population (unobserved):
Fatal injury?
Yes No
Statin 20 1,000 1,020
No statin 80 9,000 9,080
100 10,000 10,100
RR � 20
�
1,02080
�
9,080
� 2.23
Case-control sampling:
Statin 20 10
No statin 80 90
100 100
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Case-control sampling: 1 control/case
Full population (unobserved):
Fatal injury?
Yes No
Statin 20 1,000 1,020
No statin 80 9,000 9,080
100 10,000 10,100
RR � 20
�
1,02080
�
9,080
� 2.23
Case-control sampling:
Statin 20 10
No statin 80 90
100 100
RR � OR
� 20 � 9010 � 80
� 2.25
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Case-control sampling: 2 controls/case
Full population (unobserved):
Fatal injury?
Yes No
Statin 20 1,000 1,020
No statin 80 9,000 9,080
100 10,000 10,100
RR � 20
�
1,02080
�
9,080
� 2.23
Case-control sampling:
Statin 20
No statin 80
100 200
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Case-control sampling: 2 controls/case
Full population (unobserved):
Fatal injury?
Yes No
Statin 20 1,000 1,020
No statin 80 9,000 9,080
100 10,000 10,100
RR � 20
�
1,02080
�
9,080
� 2.23
Case-control sampling:
Statin 20 20
No statin 80 180
100 200
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Case-control sampling: 2 controls/case
Full population (unobserved):
Fatal injury?
Yes No
Statin 20 1,000 1,020
No statin 80 9,000 9,080
100 10,000 10,100
RR � 20
�
1,02080
�
9,080
� 2.23
Case-control sampling:
Statin 20 20
No statin 80 180
100 200
RR � OR
� 20 � 18020 � 80
� 2.25
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How many controls?
0 2 4 6 8 10
0.0
0.2
0.4
0.6
0.8
1.0
Control:case ratio
Pow
er No. cases = 100 20% of cases exposed 10% of controls exposed alpha = .05 (2−tailed)
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Strengths and weaknesses of case-control studies
Strengths
� Efficient for rare ordelayed outcomes
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Strengths and weaknesses of case-control studies
Strengths
� Efficient for rare ordelayed outcomes
� Usually relativequick andinexpensive
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Strengths and weaknesses of case-control studies
Strengths
� Efficient for rare ordelayed outcomes
� Usually relativequick andinexpensive
� Easy to study 2+different exposures
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Strengths and weaknesses of case-control studies
Strengths Weaknesses
� Efficient for rare ordelayed outcomes
� Usually relativequick andinexpensive
� Easy to study 2+different exposures
� Cannot estimateincidence directly
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Strengths and weaknesses of case-control studies
Strengths Weaknesses
� Efficient for rare ordelayed outcomes
� Usually relativequick andinexpensive
� Easy to study 2+different exposures
� Cannot estimateincidence directly
� Choice ofappropriatecontrols can bedifficult
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Strengths and weaknesses of case-control studies
Strengths Weaknesses
� Efficient for rare ordelayed outcomes
� Usually relativequick andinexpensive
� Easy to study 2+different exposures
� Cannot estimateincidence directly
� Choice ofappropriatecontrols can bedifficult
� Recall biaspossible ifexposureself-reported
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Broad categories of case-control studies
� Population-based
� Clinic-based
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Population-based case-control study
� Cases: all (or a representative sample of)cases in a defined population—e.g.:
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Population-based case-control study
� Cases: all (or a representative sample of)cases in a defined population—e.g.:
� Geopolitical area
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Population-based case-control study
� Cases: all (or a representative sample of)cases in a defined population—e.g.:
� Geopolitical area
� HMO enrollees
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Population-based case-control study
� Cases: all (or a representative sample of)cases in a defined population—e.g.:
� Geopolitical area
� HMO enrollees
� Previously defined study cohort (“nested”case-control study)
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Population-based case-control study
� Cases: all (or a representative sample of)cases in a defined population—e.g.:
� Geopolitical area
� HMO enrollees
� Previously defined study cohort (“nested”case-control study)
� Controls: sample of non-cases drawn fromthe same defined population
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Clinic-based case-control study
� Cases: those captured through a particularsource of care
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Clinic-based case-control study
� Cases: those captured through a particularsource of care
� Controls: ?
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Clinic-based case-control study
� Cases: those captured through a particularsource of care
� Controls: ?
� Other patients receiving care from samesource?
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Clinic-based case-control study
� Cases: those captured through a particularsource of care
� Controls: ?
� Other patients receiving care from samesource? (But their illnesses, too, may berelated to the exposure)
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Clinic-based case-control study
� Cases: those captured through a particularsource of care
� Controls: ?
� Other patients receiving care from samesource? (But their illnesses, too, may berelated to the exposure)
� Spouse / sib / other relative?
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Clinic-based case-control study
� Cases: those captured through a particularsource of care
� Controls: ?
� Other patients receiving care from samesource? (But their illnesses, too, may berelated to the exposure)
� Spouse / sib / other relative? (But mayshare the same exposure)
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Clinic-based case-control study
� Cases: those captured through a particularsource of care
� Controls: ?
� Other patients receiving care from samesource? (But their illnesses, too, may berelated to the exposure)
� Spouse / sib / other relative? (But mayshare the same exposure)
� Friends?
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Clinic-based case-control study
� Cases: those captured through a particularsource of care
� Controls: ?
� Other patients receiving care from samesource? (But their illnesses, too, may berelated to the exposure)
� Spouse / sib / other relative? (But mayshare the same exposure)
� Friends? (But may skew towardgregarious volunteers)
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Case-control studies by UW physician fellows
Scholar Exposure Outcome
Ed Boyko Cigarettesmoking
Ulcerative colitis
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Case-control studies by UW physician fellows
Scholar Exposure Outcome
Ed Boyko Cigarettesmoking
Ulcerative colitis
Bruce Psaty “Non-cardiac”chest pain inpeople withhypertension
Myocardialinfarction
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Case-control studies by UW physician fellows
Scholar Exposure Outcome
Ed Boyko Cigarettesmoking
Ulcerative colitis
Bruce Psaty “Non-cardiac”chest pain inpeople withhypertension
Myocardialinfarction
Ken Schellhase Screening forType 2 diabetes
End-organcomplications
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Case-control studies by UW physician fellows
Scholar Exposure Outcome
Ed Boyko Cigarettesmoking
Ulcerative colitis
Bruce Psaty “Non-cardiac”chest pain inpeople withhypertension
Myocardialinfarction
Ken Schellhase Screening forType 2 diabetes
End-organcomplications
Heidi Blume Chorioamnionitis,fever
Neonatalencephalopathy
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The end