CASE CONTROL STUDIES

Dr Manish Chandra PrabhakarMGIMS

Case control study= retrospective study=case referent study

Purpose:1- study the association between disease

and one or more exposure factors2- confirmation of new hypothesis

Design:

Two groups are compared 1- the group of cases, defined according to

the presence of the disease2- the group of controls defined according

to the absence of the disease

Cases: Defined as having the disease( the

working definition of the disease should be set)

Selected to represent all the population of cases in the community (inclusion of mild cases or severe cases only is not representative of the whole spectrum of the disease

Cases:

Should have some reasonable probability of having had their diseases induced by the exposure under study. Ex:

In studying the association between oral contraceptive (OC) and deep venous thrombosis (DVT), cases with post-operative DVT should not be included

Cases:

Should have been at potential risk of exposure to the factor under study:

ex.: unmarried , hyterectomized, or women with contraindications for OC are not eligible for the above study

Cases: Should better be newly diagnosed

(incident cases):

-To avoid to be missed in the selection as in short course diseases and diseases with high fatality

- To avoid recall bias- Ambiguity of temporal relationship

Cases:

Should have a reasonable probability of homogeneity of etiology:

Ex.: in studying lung cancer and smoking, squamous cell type (RR=30-40) is not homogenous with adenocarcinoma (RR=3-4)

Cases:

Source may be -the hospital-Disease registries-Records-Community survey

Controls:

Similar to cases in everything except the disease under the study

Must have a similar chance of exposure compared to cases

Source may be :general population, neighbors, friends of cases

Controls: Number of control per case- 1/1 when cases are easy to find at no

extra cost- >1/1 when the number of cases is

limited up to 4/1 Number of control groups- Usually one group- If the control group is suspected to

have a specific bias a second group might be used to increase validity

Controls: Matching may be used to ensure equal

distribution in the two groups of factors that might affect the studied relationship

Assessment of exposure is done in both groups (case and control) using the same maneuver

+E

-E retrospective assessment of exposure

+E -E

+Cases (D)

- Controls (D)

Analysis of case control studies:

total Non-exposed

exposed

A+B100

B20

A80

Cases (D +)

C+D100

D70

C30

Control (D -)

A+C+ B+D

200

B+D90

A+C110

total

Odds ratio (OR)

1- The probability that a case was exposed previously is estimated by

The case exposure probability= exposed cases all cases = A/A+B = 80/100

2-The probability that a case was not exposed previously is estimated by

cases not exposed all cases =B/A+B= 20/100

Odds ratio (OR)

The odds of exposure of cases = exposed cases cases not exposed

all cases all cases

= A/A+B =A/B= 80/20=4 B/A+B

The odds of exposure of controls =C/D= 30/70=0.4

Odds ratio (OR)

The odds ratio is the odds of exposure for cases divided by the odds of exposure for controls=

A/B = AD/BC= 70x80/20x30=56/6=9.3C/D

This represents the degree of association between the disease and exposure under investigation

Advantages of case- control studies

Feasibility: short time and costs Confirms a new hypothesis Most suitable for the studying of rare

diseases High statistical efficiency due to equal

groups

Problems: Misclassification: this is the placement

of a study subject in an improper cell in the 2x2 table

- misclassification of disease ex. Classify case as disease or the reverse will lead to underestimate the OR

Classification of exposure

Problems: Selection bias: this may be encountered in

either cases or controls:- Selection of cases from the hospital may

lead to:1- missing all cases that didn’t need hospital

care (mild cases)2- missing all cases that are not able to reach

the hospital( died – lack of money…)3- lack of representation of cases referred from

wide areas to a specialized center

- Selection of controls from the hospital lead to lack of representation because the hospital population is different from the general population (higher exposure to many risk factors)

Problems: Difficult in selection of proper control

group Recall bias Uncertainty of temporal relationship

between exposure and outcome specially in chronic diseases of insiduous onset