case-control studies - university of...

Case-Control StudiesResearch Methods Mini-Course

July, 2005

Overview of study designs

Study designs

Descriptive Analytic

Randomized Non-randomized

Quasi-experiment

Cohort

Case-Control

Cross-sectional

Longitudinal

Other

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

Generic case-control study

Potentialstudy subjects



Sample according tooutcome status

Poor outcome(“case”)

Good outcome(“control”)



Sample according tooutcome status

Poor outcome(“case”)

Good outcome(“control”)

Exposedto riskfactor

Notexposedto riskfactor

Exposedto riskfactor

Notexposedto riskfactor

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)



Sample accordingto fatal injury

All fatalinjury cases

Sample of controls(without fatal injury)

Had usedstatins

Had notused statins

Had usedstatins

Had notused statins

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





� 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)

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



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



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



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


Statin

No statin

100



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


Statin

No statin

100 100



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


Statin 20

No statin 80

100 100



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


Statin 20 10

No statin 80 90

100 100



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


Statin 20 10

No statin 80 90

100 100

RR � OR

� 20 � 9010 � 80

� 2.25

Case-control sampling: 2 controls/case


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


Statin 20

No statin 80

100 200



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


Statin 20 20

No statin 80 180

100 200



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


Statin 20 20

No statin 80 180

100 200

RR � OR

� 20 � 18020 � 80

� 2.25

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)

Strengths and weaknesses of case-control studies

Strengths

� Efficient for rare ordelayed outcomes


Strengths


� Usually relativequick andinexpensive


Strengths



� Easy to study 2+different exposures


Strengths Weaknesses




� Cannot estimateincidence directly







� Choice ofappropriatecontrols can bedifficult







� Choice ofappropriatecontrols can bedifficult

� Recall biaspossible ifexposureself-reported

Broad categories of case-control studies

� Population-based

� Clinic-based

Population-based case-control study

� Cases: all (or a representative sample of)cases in a defined population—e.g.:



� Geopolitical area




� HMO enrollees




� HMO enrollees

� Previously defined study cohort (“nested”case-control study)




� HMO enrollees

� Previously defined study cohort (“nested”case-control study)

� Controls: sample of non-cases drawn fromthe same defined population

Clinic-based case-control study

� Cases: those captured through a particularsource of care



� Controls: ?



� Controls: ?

� Other patients receiving care from samesource?



� Controls: ?

� Other patients receiving care from samesource? (But their illnesses, too, may berelated to the exposure)



� Controls: ?


� Spouse / sib / other relative?



� Controls: ?


� Spouse / sib / other relative? (But mayshare the same exposure)



� Controls: ?



� Friends?



� Controls: ?



� Friends? (But may skew towardgregarious volunteers)

Case-control studies by UW physician fellows

Scholar Exposure Outcome

Ed Boyko Cigarettesmoking

Ulcerative colitis




Ulcerative colitis

Bruce Psaty “Non-cardiac”chest pain inpeople withhypertension

Myocardialinfarction




Ulcerative colitis



Ken Schellhase Screening forType 2 diabetes

End-organcomplications




Ulcerative colitis



Ken Schellhase Screening forType 2 diabetes

End-organcomplications

Heidi Blume Chorioamnionitis,fever

Neonatalencephalopathy

The end

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