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Case Control Study: An example
Depression and the Risk of
Out-of-hospital cardiac arrest
July, 2005
Background - OOH Cardiac Arrest
Sudden pulseless condition due to heart disease.
Critical confluence of chronic substrate & acute trigger
Chronic Acute
Accounts for up to 400,000 deaths annually in the US.
Theme of Research
How do common non-cardiac clinical
conditions and treatments influence the risk
of cardiac arrest?
Depression alters autonomic tone, increases
platelet aggregation, and affects health
behaviors and compliance with care.
Hypothesis
Depression is associated with an increased
risk of cardiac arrest.
Study Design?
Must consider the exposure, outcome,
and potential populations when choosing a
study design.
Randomized trial
Cohort Study
Case control
Study Design?
Exposure cannot be randomized.
Outcome is ~ 1/1000 person years
Randomized trial
Cohort Study
Case control
Exposure, Outcome, and Population
Exposure ascertainment
- De novo subject evaluation/interview
- Other informational resource
Exposure definition - Ideal versus practical
Exposure, Outcome, and Population
Exposure ascertainmentDe novo subject interview/evaluation
Medical record
Health Plan Enrollees
Definition – Medical record review - Clinical assessment, measures of severity
Exposure, Outcome, and Population
Outcome ascertainment - Emergency Medical Services Records - Death Records of the Health Plan
Outcome definition - Validation of a sample of events - Agreement between EMS and death records
Exposure, Outcome, and Population
Progress (definition and ascertainment)
Population- Health Plan Enrollees
Exposure- Medical record review
Outcome- EMS and death Records
Controls
The goal is to simulate a randomized trial to try
and best examine the exposure of interest.
If possible incorporate what is already known
about risk factors for the outcome and the
study’s goals when choosing controls.
Controls
Using a random sample would result in substantial confounding. Overcome confounding in the design and sampling stage.
Cardiac arrest risk factors
Older age ~ 65 years
Male gender ~67%
Clinical heart disease ~ 67%
Random sample of Enrollees
Age ~ 45 years
Male gender ~50%
Clinical heart disease ~ 15%
Controls
Cardiac arrest risk factors
Older age ~ 65 years
Male gender ~67%
Clinical heart disease ~ 67%
Selected sample of Enrollees
Match on age
Match on gender
Match on heart disease status
Planning data collection
Exposure- Temporal relationship to outcome- Dose response
Account for potential confounders - Specific type of heart disease- Established risk factors for cardiac arrest - Medication use
Study ProcessInterface and coordination with the Health Planand Emergency Medical Services
Study ProcessInterface and coordination with the Health Planand Emergency Medical Services
Funding
Study ProcessInterface and coordination with the Health Planand Emergency Medical Services
Funding
Human Subjects review and approval
Study ProcessInterface and coordination with the Health Planand Emergency Medical Services
Funding
Human Subjects review and approval
Case (and then) control identification
Study ProcessInterface and coordination with the Health Planand Emergency Medical Services
Funding
Human Subjects review and approval
Case (and then) control identification
Medical record review and abstraction
Study ProcessInterface and coordination with the Health Planand Emergency Medical Services
Funding
Human Subjects review and approval
Case (and then) control identification
Medical record review and abstraction
Data entry and cleaning
Study ProcessInterface and coordination with the Health Planand Emergency Medical Services
Funding
Human Subjects review and approval
Case (and then) control identification
Medical record review and abstraction
Data entry and cleaning
Data analysis
Study ProcessInterface and coordination with the Health Planand Emergency Medical Services
Funding
Human Subjects review and approval
Case (and then) control identification
Medical record review and abstraction
Data entry and cleaning
Data analysis
Draft manuscript - Interpretation
Study ProcessInterface and coordination with the Health Planand Emergency Medical ServicesFunding
Human Subjects review and approval
Case (and then) control identification
Medical record review and abstraction
Data entry and cleaning
Data analysis
Draft manuscript - Interpretation
Publication
Results
OutcomeExposed? Yes No
Yes
No
a b
c d
Data Layout
Cardiac ArrestDepression? Yes No
Yes
No
a b
c d
Results
Cardiac ArrestDepression? Yes No
Yes
No
300 327
1928 3837
Odds ratio = aXb/cXd = 300X3837/327X1928
Unadjusted odds ratio = 1.83
Adjusted odds ratio = 1.43
ResultsEvidence of dose response
Restriction and adjustment to account for confounding.
OR
No depress 1º Care Specialty Care
2
1.5
1
Strengths
Outcome is rare
Relatively quick and inexpensive
Study > 1 exposure
Weaknesses
Cannot estimate incidence directly
~2000 cases and 4000 controls
Choice of controls is challenging
Recall bias
Study Process
Research ideaInterface with HP/EMSFunding
Human Subjects
Subject identification
Medical record abstraction
Data entry and cleaning
Data analysis
Draft manuscript
Publication
Time line
Study Process
Research ideaInterface with HP/EMSFunding
Human Subjects
Subject identification
Medical record abstraction
Data entry and cleaning
Data analysis
Draft manuscript
Publication
Time line
6 months
Study Process
Research ideaInterface with HP/EMSFunding
Human Subjects
Subject identification
Medical record abstraction
Data entry and cleaning
Data analysis
Draft manuscript
Publication
Time line
6 months
24 months
Study Process
Research ideaInterface with HP/EMSFunding
Human Subjects
Subject identification
Medical record abstraction
Data entry and cleaning
Data analysis
Draft manuscript
Publication
Time line
6 months
24 months
30 months
Study Process
Research ideaInterface with HP/EMSFunding
Human Subjects
Subject identification
Medical record abstraction
Data entry and cleaning
Data analysis
Draft manuscript
Publication
Time line
6 months
24 months
30 months
36 months
Study Process
Research ideaInterface with HP/EMSFunding
Human Subjects
Subject identification
Medical record abstraction
Data entry and cleaning
Data analysis
Draft manuscript
Publication
Time line
6 months
24 months
30 months
36 months
48 months
Study Process
Research ideaInterface with HP/EMSFunding
Human Subjects
Subject identification
Medical record abstraction
Data entry and cleaning
Data analysis
Draft manuscript
Publication
Time line
6 months
24 months
30 months
54 months
36 months
48 months
Study Process
Research ideaInterface with HP/EMSFunding
Human Subjects
Subject identification
Medical record abstraction
Data entry and cleaning
Data analysis
Draft manuscript
Publication
Time line
6 months
24 months
30 months
54 months
57 months
36 months
48 months
Study Process
Research ideaInterface with HP/EMSFunding
Human Subjects
Subject identification
Medical record abstraction
Data entry and cleaning
Data analysis
Draft manuscript
Publication
Time line
6 months
24 months
30 months
54 months
57 months
60 months
36 months
48 months
Study Process
Research ideaInterface with HP/EMSFunding
Human Subjects
Subject identification
Medical record abstraction
Data entry and cleaning
Data analysis
Draft manuscript
Publication
Time line
6 months
24 months
30 months
54 months
57 months
60 months
72 months
36 months
48 months
Permutations of Study Process
Research ideaInterface with HP/EMSFunding
Human Subjects
Subject identification
Medical record abstraction
Data entry and cleaning
Data analysis
Draft manuscript
Publication
Time line
6 months
24 months
30 months
54 months
57 months
60 months
72 months
36 months
48 months
Permutations of Study Process
Research ideaInterface with HP/EMSFunding
Human Subjects
Subject identification
Medical record abstraction
Data entry and cleaning
Data analysis
Draft manuscript
Publication
Time line
6 months
24 months
30 months
54 months
15 months
18 months
30 months
36 months
48 months
Research accelerator
9 months
Permutations of Study Process
Research ideaInterface with HP/EMSFunding
Human Subjects
Subject identification
Medical record abstraction
Data entry and cleaning
Data analysis
Draft manuscript
Publication
Time line
6 months
24 months
30 months
54 months
15 months
18 months
30 months
36 months
48 months
9 months
Young investigatorFortunate investigator
Wise investigator
SummaryWhen choosing study design, consider issuesof exposure, outcome, and population.
Understand the strengths and weaknesses ofcase control studies and attempt to addressduring the design and then in analysis
Regardless of study design, recognize thehidden/logistic challenges and their timerequirements.
Thanks to David Siscovick, Bruce Psaty,
and Mickey Eisenberg
Contact information
Tom Rea
Division of General Internal Medicine
Box 359945
Pager 540-8048
E-mail [email protected]