1. DR. Sudhira Kumar Parida.

2. OVERVIEW
 Introduction.
 Design of a Case-Control Study.
 Hallmark.
 Selection of cases.
 Selection of controls.
 Problems in control selection.
 Multiple control.
 Matching.
 When warranted?
 Case-Control Study based in a defined cohort.
 Measurement of exposure.
 Analysis & Interpretation.
 Bias
 Adv & disadv.
 Examples

3. INTRODUCTION
Epidemiological Studies
 Observational studies  Experimental studies
A.Descriptive studies A.RCT/ Clinical trials
B.Analytical studies B.Field trials/ Community
1.Ecological/ intervention studies
Correlational
C.Community trials.
2.Cross-sectional/
Prevalence
3.Case-control/ Case-
reference
4.Cohort/ Follow-up

4. DESIGN OF A CASE-CONTROL
STUDY
First Select
CASES CONTROLS
(with disease) (without ds)
THEN MEASURE PAST EXPOSURE
Were Exposed a b
Were Not exposed c d
Total a+c b+d
Proportions Exposed a b
a+c b+d

5. HALLMARK
 It begins with people with the disease(CASES) &
COMPARES them to people without the
ds(CONTROLS).

6. SELECTION OF CASES
 Definition of a CASE:
i)diagnostic criteria & stage of the ds ,if any.
ii)eligibility criteria-preferably incident cases.
 Sources:
1.hospital-based
2.population-based
 Case verification
 Exclusion criteria

7. SELECTION OF CONTROLS
 Who is a CONTROL
 Sources:
1.hospital-based
2.population-based
i)school rosters
ii)selective service lists
iii)insurance company lists
iv)neighbourhood
v)best friend
vi)spouse/ sibling
vii)dead

8. USE OF MULTIPLE CONTROLS
 Same types:
-increases the power of the study(only upto
1case:4control)
 Different types:
-for exploring alternate hypotheses
-for taking account possible potential biases like recall
bias.

9. MATCHING
 Def: The process of selecting the controls so that they are similar
to cases in certain characteristics ,such as age,race,sex,socio-eco.
status & occupation.
 Types:
1.Group/ Frequency
2.Individual/ Matched pairs.
 Problems:
a)practical-difficulty in finding a control
b)conceptual-cannot study that characteristic
c)unplanned matching
d)overmatching

10. WHEN A CASE-CONTROL STUDY
IS WARRANTED
 Often the 1st step in determining whether an exposure
is linked to an increased risk of ds.
 Rare ds.

11. CASE-CONTROL STUDIES BASED IN
A DEFINED COHORT
Defined Initial Data &/or Sr.,Urine or
Cohort Other specimens
YEARS
Develop
Disease Have Not developed
disease
Sub-gr
CASES selected as
CONTROL

12.  Nested Case-Control Studies:
-controls are a sample of individuals who are at risk for the
ds at the time of each case of the ds develops.
-cases & controls are matched on calendar time & length
of follow-up.
 Case-Cohort Studies:
-controls are randomly chosen.
-Adv: possible to study different diseases.

13. ADVANTAGES OF EMBEDDING A
CASE-CONTROL STUDY IN A
DEFINED COHORT
 Recall bias-eliminated.
 Abnormalities in biologic characteristics like lab
values –risk factors.
 More economical.
 Less lab burden.
 Greater comparability b/w cases & controls.

14. MEASUREMENT OF EXPOSURE
( IN PRICESLY THE SAME MANNER BOTH FOR
CASES & CONTROLS .)
 Interviews
 Questionnaires
 Past records of cases
-hospital records
-employment records etc.

15. ANALYSIS
 Exposure rates among cases & controls to suspected
factor.
 Estimation of ds risk asso. With exposure( ODDS
RATIO).

16. EXPOSURE RATES:
 Direct estimation.
A Case-Control Study of Smoking &Lung cancer.
Cases Controls
(with Lung cancer) (without lung cancer)
Smokers(<5 cigarettes/d) 33 (a) 55 (b)
Non-smokers 2 (c) 27 (d)
Total 35 (a+c) 82 (b+d)
Exposure rates:
. Cases= a/a+c= 33/35 =94.2%
. Controls= b/b+d =55/82 =67%.

17. ODDS RATIO
(RELATIVE ODDS/ CROSS-PRODUCTS RATIO.)
 A measure of the Strength of the association b/w risk
factor & ds.
 Def:
OR= Odds that a case was exposed
Odds that a control was exposed
=
a/c
=
b/d
ad
bc
=
Product of 2 cells that SUPPORT the hypothesis
Product of 2 cells that NEGATE the hypothesis

18.  Interpretation:
OR=1 (exposure is not related to the ds)
>1 (+ly related)
<1 (- ly related).
 OR is a good approximation of RR when:
-cases studied are representative of those with the ds.
-controls studied are representative of those without the
ds.
-ds being studied does not occur frequently.

19.  CALCULATING ‘OR’ IN AN UNMATCHED CASE-
CONTROL STUDY:
OR= ad
bc
 CALCULATING ‘OR’ IN A MATCHED PAIRS CASE-
CONTROL STUDY:
CONTROL
Exposed Not exposed
C Exposed p q
A
S
Not exposed r s
E
OR=Ratio of discordant pairs=q/r.

20. BIAS
 Bias due to confounding.
 Recall bias.
 Selection bias.
 Berkesonian bias.
 Interviewer’s bias.

21. ADVANTAGES
 Relatively easy.
 Rapid & inexpensive.
 Rare ds.
 No risk to subjects.
 Allows study of several different aetiological factors.
 Risk factors can be identified-----
rational prevention & control programme
 No attrition problems.
 Minimal ethical problem.

22. DISVANTAGES
 Recall bias.
 Selection of appropriate control gr. –may be difficult.
 Cannot measure incidence.
 Cannot distinguish b/w causes & asso. Factors.
 Not suited to evaluation of Tt/ Px of ds.
 Concern about representativeness of cases & controls.

23. EXAMPLES
MATERNAL DES THERAPY & ADENOCARCINOMA
OF VAGINA IN FEMALE OFFSPRINGS:
CASES CONTROLS SIGNIFICANCE
(8) (32) LEVEL
Maternal age 26.1 29.3 n.s.
Maternal smoking 7 21 n.s.
Antenatal radiology 1 4 n.s.
Oestrogen exposure 7 -- P< 0.00001

24. OCP & THROMBOEMBOLIC DISEASE:
CASES(Venous CONTROLS
thrombosis &
pul.embolism)
(84) (168)
% who used OCP 50 14
THALIDOMIDE TRAGEDY:
CASES(46) CONTROLS(300)
Thalidomide exposure in 41 --
early pregnancy

25. REFERENCES
 Leon Gordis,4th ed.
 Silman, Macfarane ,2nd ed.
 Park,20th ed.

26. THANK YOU.