Case Control Study

Dr. Ashry Gad MohamedMB, ChB, MPH, Dr.P.H.

Prof. Of Epidemiology

Descriptive Analytical

Case report

Case series

Cross section

Ecological

Case control

Cohort

Observational Experimental

Study Designs

Animal Experiment

HumanInterventionClinical trial

Case control study

-Observational study

-Analytical study

-Unit of observation and

analysis: individual

Target population

Cases

Controls

Exposed

Not exposed

Exposed

Not exposed

Selection of cases

• Definition of cases is first task of the investigator in case control studies.

• The definition may be

Simple e.g. cleft lip.

Complex e. g. hypertension

• A variety of methods may be used alone or in combination to establish the presence of the disease.

• It is often recommended to choose incident (newly diagnosed) cases

1-Exposure is recent and easy to recall.

2-The etiological milieu of incident cases is relatively homogeneous.

3-To avoid the possibility that in long term survivors the exposure may occur after the onset of the disease.

Sources of cases

• Cases admitted to or discharged from a hospital, clinic or any health care facility.

• Cases reported or diagnosed during a survey or surveillance system

• Incident cases in a going cohort study • Death certificates with recorded cause of

death.• Employment records.• Institutional records

Selection of controls

• It is crucial to set up control group (s) of people who do not have the specified disease condition in order to obtain estimates of the frequency of the attribute or risk factor for comparison with its frequency among cases.

Methods for selecting controls

A-Through matching for relevant criteria • Pair-wise matching For each case, a specific comparison

subject (s) with similar values of the matching factors is (are) selected.

• Frequency matching The overall distribution of matching

factors parallels the distribution in case group.

Advantages of matching

• In some situations there are natural partners for comparison e.g. identical twins.

• Matching may account for extraneous variables

• Matching may improve the statistical precision of study results

Disadvantages of matching

• when there are a large number of matching variables, it may be difficult to find suitable controls.

• Unmatched cases and controls cannot be analyzed.

• Overmatching may lead to an underestimation of study effect.

• Matching may increase the costs of the study.

B-Through random or stratified sampling.

• No restriction.

• No matching.

• Allow confounders to act.

Sources of control

• 1-Hospital controls Advantages of hospital controls• Subjects are easily accessible.• Patients usually have time to participate.• Patients are often motivated to cooperate

with investigators.• Controls and cases may be drawn from

similar social and geographical environment.• Differential recalls of prior exposure is likely

to be minimized.

Disadvantages of hospital controls

• Differential hospitalization patterns may introduce selection bias.

• Difficult to blind disease status from cases and controls.

• An underestimate of the study effect may be obtained if control’s disease is etiologically similar to cases’ disease.

2-Community controls

• A probability sample of a defined population, if cases do belong to that population or a sample of relatives or associates of cases or neighborhood controls.

Advantages of community controls• Reduction of selection bias.• Generalization of study results is more valid.• May provide convenient control of

extraneous variables.

Disadvantages of community controls

• Time and money consuming.

• May suffer low participation rate.

• Cases and control may exhibit differential recall of prior exposures.

How many controls per case?

• Ideal : 1 : 1

• In case of Rare Cases Increase Controls.

1 : 4

• More than 4 controls add little to study power

4 91.5

5 92.4

6 93.0

7 93.4

Collection of data• Self reported (self administered

questionnaire) or by interview.

• Revision of records (medical or occupational).

• Biological markers (lab.records).

Quality control in case control study.• Standardization of methods and

circumstances of data collection.

• Observers are better to collect the data blindly.

• Observations should be objective.

Analysis of case control study

• Because population at risk is absent we can not calculate relative risk as it is based on incidence, however it can be estimated by means of odds ratio (OR) which is the ratio of odds of exposure among diseased to the odds of exposure among controls.

Exposure for each case and control

Disease status

Cases Controls

Exposure Yes

NO

AB

CD

A+CB+D

• Calculating Odds (number exposed number unexposed)

Odds (Cases) = A/C

Odds (controls) = B/D

Odds Ratio = (A/C) / (B/D) = AD/BC

OR=1OR<1OR>1

Odds comparison between cases and controls

Odds of exposure are equal among

cases and controls

Odds of exposure for

cases are less than the odds of

exposure for controls

Odds of exposure

for cases are greater than the

odds of exposure for

controls

Exposure as a risk factor for the

disease?

Particular exposure is not a

risk factor

Exposure reduces disease

risk

(Protectivefactor)

Exposure increases

disease risk(Risk factor)

Disease Status

CHD

)Cases(

No CHD

)Controls(

112176

88224

200400

Smoker

Non smoker

Total

Odds Ratio=

AD

BC

= 112 X 224

176 X 88

= 1.62

Example

Odds Ratio = 1.62

• The risk of CHD is 62% higher among smokers

• 95% CI = 1.13 – 2.31 Sig.

Advantages of case control study• Efficient sampling of rare diseases.

• Rapid evaluation of chronic diseases.

• Requires less money and personnel

• Little problem of attrition

Disadvantages of case control study

• Not practical for rare exposures.

• Historical information often can not be validated.

• Relevant cofactors may be difficult to control.

• Temporality may be obscured.

• Selective survival may bias the comparison.