• There is a outbreak of endopthalmitis in
patients undergone surgery in the camp held
by District hospital
• how will you investigate?
• Which study design will you used investigate?

Study designs
Quantitative
Observational
Descriptive
Case report
Case series
Cross sectional
longitudinal
Experimental
Analytical
Case control
cohort
Cross sectional
Qualitative
Field
expt Clinical
trial
Community
trial

Case Control Study
Dr Suvarna Joshi

Case Control Study
Dr Suvarna Joshi
Associate Professor Microbiology
Grant Govt Medical College & JJ group
of hospitals Mumbai

SLO
• Indications
• Layouts of typical case control study
• Steps
• Interpretation of odds ratio & other statistics
emerging out of case control study
• Possible biases and their resolution
• Comparison with cohort studies

Indications
• Investigating outbreak
• Evaluating effectiveness of new vaccine
• Evaluation of treatment & program efficacy
• Genetic epidemiology
• Occupational health research
• Evaluation of screening
• Outbreak investigations

Case Control study design

General characteristics
• Observational epidemiological study
• Analytical type
• Testing hype
• Hypothesis – association type
• Two groups-case , control
• Retrospective –
going back from outcome(disease) to exposure
• Also called Flashback study

Steps
• Sample size estimation
• Selection of cases
• Control matching
• Collection of data
• Applying statistics

Selection of cases
Definition of cases
• Individuals with the disease entity under
investigation (as per standard definition)
• Based on standard diagnostic criteria
• These criteria should be
objective, valid, reproducible

Selection of Cases
• Source-
Hospital , workplace, community/general
population
Time (eligibility)-
New cases- incident cases within specified
time
Old cases- prevalent cases -derived from
cross sectional survey
Selection usually done from the available cases

Selection of controls
• Control- One who does not have disease
under investigation
• Need not be healthy
• Control and cases should be from same study
base(source) if cases selected from hospital
then controls also from same hospital

Sources for Control
• Hospital, relatives, neighbors, occupational
associates, general population
d) Neighbors
(i) walk (door to door)
(ii) Phone (random digit dialing)
(iii) Letter carrier routes
e) Friends or associates of cases
f) Siblings, spouses or other relatives
g) Other

Matching
• Done for confounding factors to ensure the
comparability
• Eg age, sex, occupation, education, social
status
• Individual/frequency matching
• Overmatching: do not match for risk factor
under study
• Increase power of study; increasing no. of
controls per case

Matching…
• Control >4 per case will just increase the cost
• Disadvantage of matching
• Time consuming
• Costly
• Exact match may not be found
• Multiple controls per case
• (one from hospital and one from general
population per case)

Bias
• Recall bias
Selection bias
Information bias
Non-response bias
Analysis bias

Recall bias
• eg A case control study on adults which
gathered information relating to
hospitalization prior to the age of 16 was
concerned about poor recall
• Recall bias (cases may remember
their exposure with a higher or
lower accuracy than controls do)

Overcoming recall bias
• In subsample of both cases and controls,
medical records were examined to determine
evidence of for difference in recall between
cases and control

Selection bias
• Case control study on duodenal ulcer and
smoking
• Cases- patients attending gastroenterology
clinic (likely to be severe cases)
• Any risk factor derived from those cases may
represent risk factors for severity rather than
ulcer susceptibility per se
• Referal practice

Information/interviewer’s bias
• Case control study on possible link between
febrile illness and subsequent early pregnancy
loss
• Greater care in introducing questions to the case
mothers, the study coordinator was concerned
that the interviewer might have probed more
closely for history of fever in the cases
• It was found that interviewer was taking 10 min
more than normal pregnant controls

Case Control Design
Time
Direction of Inquiry
Population
Cases with
the Disease
Controls without
the disease
Exposed
Exposed
Not Exposed
Not Exposed

Case-Control Studies: Methodology
Then measure,
post-exposure
First Select the Cases
and Controls
Cases
(with
disease)
Control
(without
disease)
Were Exposed A B
Not Exposed C D
A+C B+D
Population
Exposed
A/A+C B./B+D

Figure 1 (continued)
a
c ad
Odds Ratio = =
b bc
d
Risk = a
a + b
= c
c + d
a b
c d
Case Control
E+
E-

Kidney stone
present
Kidney stone
absent
Total
Drinking hard
water
90 (a) 20 (b) 110
Not drinking
hard water
10 (c) 80 (d) 90
total 100 100 200
Exposure rate in cases = a/a+c = 90/90+10= 90%
Exposure rate in control = b/+d= 20/20+80= 20%
Odds ratio= ad/bc = 90x80/20x10=7200/200=36

• Odd ‘s ratio =1 no association
• > 1 positive association
• < 1 protective effect

Strength of Association
Relative Risk;(Prevalence); Odds Ratio Strength of Association
0.83-1.00 1.0-1.2 None
0.67-0.83 1.2-1.5 Weak
0.33-0.67 1.5-3.0 Moderate
0.10-0.33 3.0-10.00 Strong
<0.01 >10.0 Approaching
Infinity

Nested Case-Control Studies
Figure 3
Study Population
TIME 1
YEARS
TIME 2
Develop
Disease
Do Not
Develop
Disease
CASES CONTROLS
CASE-CONTROL STUDY
Obtain
interviews,
bloods,
urines, etc.

A. Advantages of Nested Case-Control Studies
1. Possibility of recall bias is eliminated, since data
on exposure are obtained before disease
develops.
2. Exposure data are more likely to represent the
pre-illness state since they are obtained years
before clinical illness is diagnosed.
3. Costs are reduced compared to those of a
prospective study, since laboratory tests need to
be done only on specimens from subjects who
are later chosen as cases or as controls.

• A major limitation of cross-sectional surveys
and case-control studies is difficulty in
determining if exposure or risk factor
preceded the disease or outcome.
to overcome this problem ?

Cohort study

WHAT IS COHORT
• Ancient Roman military
unit, A band of warriors.
• Persons banded
together.
• Group of persons with a
common statistical
characteristic. [Latin]
• E.g. age, birth date,

Indication
• When a good evidence of association between
exposure and disease
• When exposure is rare but incidence of
disease in exposed is high
• When follow up is easy and cohort is relatively
stable
• Ample funds available

Elements of cohort study
• Selection of study subjects
• Obtaining data on exposure
• Selection of comparison group
• Follow up
• Analysis

Selection of subject
• Group of people exposed to suspected cause
• Eg cohort group who drink hard water (study
cohort)
• And cohort who don’t drink hard
water(control cohort)
• Comparison group are in built based on
gradation of exposure

• Cohort must be free from disease under study
• Both cohort should be equally susceptible to
the disease under study
• Both cohort should be comparable
• Diagnostic & eligibility criteria must be
defined before study commences

Characteristic of Cohort study
 Longitudinal
 Prospective studies
 Forward looking study
 Incidence study
 starts with people free of disease
 assesses exposure at “baseline”
 assesses disease status at “follow-up”

b+d
Frame work of Cohort studies
c
c+d
a
a+b
Total Yes
Disease Status
Yes
No
Exposure
Status
b
d
a+c
N
No
Study
cohort
Comparison
cohort

Selection of study subjects
• General population
– Whole population in an area
– A representative sample
• Special group of population
– Select group
• occupation group / professional group (Dolls study )
– Exposure groups
• Person having exposure to some physical, chemical or biological
agent
– e.g. X-ray exposure to radiologists

Obtaining data on exposure
• Personal interviews / mailed questionnaire
• Reviews of records
– Dose of drug, radiation, type of surgery etc
• Medical examination or special test
– Blood pressure, serum cholesterol
• Environmental survey
• By obtaining the data of exposure we can classify
cohorts as
– Exposed and non exposed and
– By degree exposure we can sub classify cohorts

Selection of comparison group
• Internal comparison
– Only one cohort involved in study
– Sub classified and internal comparison done
• External comparison
– More than one cohort in the study for the purpose of
comparison
– e.g. Cohort of radiologist compared with ophthalmologists
• Comparison with general population rates
– If no comparison group is available we can compare the
rates of study cohort with general population.
– Cancer rate of uranium miners with cancer in general
population

Follow-up
• To obtain data about outcome to be determined
(morbidity or death)
– Mailed questionnaire, telephone calls, personal interviews
– Periodic medical examination
– Reviewing records
– Surveillance of death records
– Follow up is the most critical part of the study
• Some loss to follow up is inevitable due to death
change of address, migration, change of occupation.
• Loss to follow-up is one of the draw-back of the
cohort study.

ANALYSIS
• Calculation of incidence rates among exposed
and non exposed groups
• Estimation of risk

Incidence rates of outcome
N
d
c
b
a
Yes No
Disease Status
Yes
No
Exposure
Status
a+b
c+d
b+d
a+c
Total
Study
cohort
Comparison
cohort

Incidence rate
• Incidence among exposed =
a
a+b
• Incidence among non-exposed =
c
c+d

Estimation of risk
• Relative Risk
incidence of disease among exposed
RR = ______________________________
Incidence of disease among non-exposed
a/a+b
= _________
c/c+d

Estimation of Risk
• Attributable Risk
Incidence of disease among exposed –
incidence of disease among non exposed
AR = _______________________________
Incidence of disease among exposed
a/a+b – c/c+d
AR = _______________
a/a+b

Smoking Lung cancer Total
YES NO
YES 70 6930 7000
NO 3 2997 3000
73 9927 10000
Find out RR and AR for above data

• Incidence of lung cancer among smokers
70/7000 = 10 per 1000
• Incidence of lung cancer among non-smokers
3/3000 = 1 per thousand
RR = 10 / 1 = 10
(lung cancer is 10 times more common among
smokers than non smokers)
AR = 10 – 1 / 10 X 100
= 90 %
(90% of the cases of lung cancer among smokers are
attributed to their habit of smoking)

Types of Cohort Study
• Prospective cohort study
• Retrospective (historical) cohort study
• Combination of Retrospective and Prospective
cohort study.

Cohort studies
Strengths
• We can find out
incidence rate and risk
• More than one disease
related to single
exposure
• can establish cause -
effect
• good when exposure is
rare
• minimizes selection and
information bias
Weaknesses
• losses to follow-up
• often requires large
sample
• ineffective for rare
diseases
• long time to complete
• expensive
• Ethical issues

Comparison between Case control & Cohort
Case control
• Proceed from effect to
cause
• Involves few subjects
,quick ,less expensive
• Yields only estimate of
relative risk by virtue of
odds ratio
• Sampling bias
• Measuremnet bias
Cohort
• Proceed from cause to
effect
• Involves large no. prolong
duration, expensive
• Yield incidence
rate,relative risk,
attributable risk
• No sampling bias
• No information bias

Thank U