Case Control Studies Case Control Studies

Dr Amna Rehana SiddiquiDepartment of Family and Community Medicine

October 17, 2010

Objectives

1. To understand the basic design features of case control study

2. To list the advantages and disadvantages of case control studies

3. To calculate the odds ratio as a measure of association in case control studies

Types of Study Designs

Design Study Type

Case report Observational - Descriptive

Case series Observational - Descriptive

Cross sectional Observational - Descriptive/Analytic

Case control Observational - Analytic

Cohort Observational - Analytic

Clinical trial Experimental - Analytic

3

Basic Question in Analytic Epidemiology

Are exposure and disease linked?

Direction of inquiry in case control studyDirection of inquiry in case control study

ExposureRisks e.gsmoking

Diseasee.g. Myocardial Infarction (MI)

Design of Case Control Study

The investigator selects cases with the diseasecases with the disease (MI) (MI)

and appropriate controls without the diseasecontrols without the disease

and obtains data regarding past exposure to possible etiologic factors (smoking & other ) in both groups then compares the frequency of exposure of the two groups.

Proportion of smoking in cases and controls

controlscases

Arrows show the extent of smoking among cases and controls

Smoking

Smoking

Proportion of exposure in cases and controls

controlscases

Arrows show the extent of factor among cases and controls

Saturated fatintake

Saturated fat intake

Study Design: Case Control Study Design: Case Control

-Exposure data collected retrospectively-Feasible where disease outcomes are rare -Case ascertainment system is present -More than one exposure can be studied -Control selection from the source population-Multiple controls possible; e.g. 2 controls/case) -Efficient in Cost and time

Study DesignStudy Design

Cases ControlsCases Controls

Myocardial infarction OTHER ILLNESS/ Free of any illness

EXPOSED

SMOKED

NOT EXPOSED

NEVER SMOKED

EXPOSED

SMOKED

NOT EXPOSED

NEVER SMOKED

Proportions of exposed and unexposed in cases and controls

Example Example MI Cases Controls

Smokers 110 150Never smokers 90 250

Total 200 400

% smokers 55% 37.5%If Cancer is related to smoking then more cases than

controls would be smokers

Selection of Cases Selection of Cases

• Source of cases / hospital based / other • Incident or prevalent • Representative• Homogenous criteria for case definition• Certainty of diagnosis

Selection of casesSelection of cases

Source population • Hospital• Physicians clinic• Registries • Community

Risk factors could be unique to any one particular source especially from a hospital/clinic

Selection of CasesSelection of Cases

• Incident cases; could take long time to wait to identify cases

• Early deaths before or after diagnosis may prevent determination of risk factors

• Prevalent cases; large pool of cases survival bias, change in exposures

Selection of ControlsSelection of Controls

Highly important for valid results Whether;• Controls be similar to cases in all aspects

except the occurrence of disease OR• Representative of all persons without the

disease in population from which the cases have arisen

Selection of ControlsSelection of Controls

Sources of Controls• Probability sample of a total population • Neighborhood controls • Sibling/ best friend control• Hospitalized controls

Measures of association• Odds ratio: A ratio of one odds to another

Odds of exposure in a case Odds of exposure in a case = probability of exposure (smoking)

probability of no exposure (not smoking)

Odds of exposure in a control Odds of exposure in a control = probability for exposure (smoking) probability for no exposure (not smoking)

Odds RatioOdds RatioIf any event takes place with a probability ‘p’ thenthe odds in the favor of event are ‘p/1-p’ to 1

If p=2/3 then the odds of event are 2/3 / 1/3 = 2 to1

=Prob (exposure|cases)/[1-prob(exposure|cases)] Prob(expsoure|controls)/[1-prob(exposure|controls)]

Odds Ratio is equivalent to Relative Risk (RR), onlyOdds Ratio is equivalent to Relative Risk (RR), onlywhen the disease is rare.when the disease is rare.

As incidence is not derived in case control studies then As incidence is not derived in case control studies then RR can not be derived from these studies.RR can not be derived from these studies.

Calculating Odds RatioCalculating Odds Ratio MI Cases Controls

Smokers 110 150Never smokers 90 250

Total 200 400

% smokers 55% 37.5%

Odds of exposure in cases=0.55/1-0.55 = 1.22Odds of smoking in controls=0.38/ 1-0.38 = 0.61

Odds Ratio= 1.22/0.61 = 2

Interpretation: Odds of smoking in cases are two times more than the odds of smoking in controls

Calculating Odds RatioCalculating Odds Ratio MI Cases Controls

Smokers 110 150Never smokers 90 250

Total 200 400

% smokers 55% 37.5%

Odds of exposure in cases=0.55/1-0.55 = 1.22Odds of smoking in controls=0.38/ 1-0.38 = 0.61

Odds Ratio= 1.22/0.61 = 2

Interpretation: Odds of smoking in cases are two times more than the odds of smoking in controls

ODDS RATIOODDS RATIO• Odds ratio ~ cross product ratio

Cases ControlsExposed 110 150

Not exposed 90 250

OR= a/b = 110/90 = ad/bc = [(110*250)/(150*90)] = 27500 = 2 c/d 150/250 13500

Odds of exposure in cases : two times compared to controls

Interpretation of (OR) odds ratioInterpretation of (OR) odds ratio> 1 means the exposure is a risk factor.

= 1 means the exposure is not associated with the disease.

< 1 means the exposure is protective

Factors considered in Design Factors considered in Design • Selection bias in selection of controls if selection is related to

exposure in any way; bias will occur • Recall bias; cases tend to recall more than controls; a high OR

could be a biased estimate

• Interviewer bias; interviewers would keenly interview cases to obtain information compared to controls

• Matching of cases and controls can be done on certain variables; e,g. age, gender, location, ethnicity

• Multiple controls increase the power of study as usually done on rare diseases and few cases are available during a specified time e.g. any cancer.

Advantages and Disadvantages

Advantages• Efficient in time & cost • Etiology of long latency

period can be studied e.g. chronic diseases • Multiple exposures could

be studied

Disadvantages• Errors in Case definitions

and in characterization of exposure

• Disease and exposure have already occurred and potential for bias remains

- selection - recall - interviewer

Example of Case Control Study Example of Case Control Study Toxic Shock SyndromeToxic Shock Syndrome

• Thirty-five patients were matched for age and menstruation to 105 controls:

• 34 of 35 cases (versus 80 of 105 controls) used tampons during every menstrual period;

• nine of 35 cases (versus 64 of 105 controls) practiced contraception.

• Make a two by two tables and• Calculate Odds Ratios