Case Control Study: An example

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 ascertainmentDe novo subject interview/evaluation

Medical record

Health Plan Enrollees

Definition – Medical record review - Clinical assessment, measures of severity


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


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%


Controls

Cardiac arrest risk factors

Older age ~ 65 years

Male gender ~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


Funding


Funding

Human Subjects review and approval


Funding


Case (and then) control identification


Funding



Medical record review and abstraction


Funding




Data entry and cleaning


Funding





Data analysis


Funding





Data analysis

Draft manuscript - Interpretation

Study ProcessInterface and coordination with the Health Planand Emergency Medical ServicesFunding





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 analysis

Draft manuscript

Publication

Time line

Study Process


Human Subjects




Data analysis

Draft manuscript

Publication

Time line

6 months

Study Process


Human Subjects




Data analysis

Draft manuscript

Publication

Time line

6 months

24 months

Study Process


Human Subjects




Data analysis

Draft manuscript

Publication

Time line

6 months

24 months

30 months

Study Process


Human Subjects




Data analysis

Draft manuscript

Publication

Time line

6 months

24 months

30 months

36 months

Study Process


Human Subjects




Data analysis

Draft manuscript

Publication

Time line

6 months

24 months

30 months

36 months

48 months

Study Process


Human Subjects




Data analysis

Draft manuscript

Publication

Time line

6 months

24 months

30 months

54 months

36 months

48 months

Study Process


Human Subjects




Data analysis

Draft manuscript

Publication

Time line

6 months

24 months

30 months

54 months

57 months

36 months

48 months

Study Process


Human Subjects




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


Human Subjects




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


Human Subjects




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



Human Subjects




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



Human Subjects




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]

Case Control Study: An example

Documents

Transcript of Case Control Study: An example