This document provides an overview of case-control and cohort study designs. It defines the basic elements and steps of each design, including selection of cases and controls, measurement of exposure, and analysis. It discusses biases that can occur in each design such as selection, recall, and confounding bias. Advantages and disadvantages of each design are presented, such as the ability of cohort studies to measure incidence but susceptibility to loss to follow up. Analytical studies like case-control and cohort designs are used to test hypotheses about associations between exposures and diseases.

1. Dr. Sonal Kale
PG 1st yr 1

2. ◦ Analytical study
◦ Case-control study
◦ Basic steps
◦ Bias in case control study
◦ Advantages and disadvantages of case-control study
◦ Cohort study
◦ Types of cohort study
◦ Elements of cohort study
◦ Biases in cohort study
◦ Advantages and disadvantages of cohort study
◦ Conclusion
◦ References
2

3.  The objective of analytical study is to test the hypothesis.
 2 types of analytical study are-
◦ Case control study
◦ Cohort study
 Help to determine -Whether statistical association exists
between a disease and a suspected
factor.
- If exists then what is the strength of
the association.
3

4.  Also called as retrospective studies.
 First approach to test causal hypothesis.
 Features are-
◦ Exposure and outcome have occurred before the start of the
study.
◦ The study proceeds backward cause effect
 Subjects are grouped based upon presence or absence
of disease and then their prior exposure status is
determined.
4

5. Cases
Not
Exposed
Exposed
Control
Exposed
Not
Exposed
With disease
Without disease
5

6.  It begins with individuals with the disease(CASES) &
compares them to individuals without the
disease(CONTROLS).
 Patients with the disease in question (cases) are enquired
for all the details of their exposure to the suspected cause.
 The new cases, which are similar clinically,
histologically, pathologically and in their duration of
exposure (stage) are chosen to avoid any error and for
better comparison.
6

7. RISK
FACTORS
CASES
(Disease
Present)
CONTORLS
(Disease
Absent)
PRESENT
a b
ABSENT c d
Total a+c b+d
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8. 1. Selection of cases and controls.
2. Matching
3. Measurement of exposure
4. Analysis and interpretation.
8

9. Definition of case: prior definition of what constitutes case is
crucial in case-control study.
It involve two specifications-
(i) Diagnostic criteria : diagnostic criteria and stage of the
disease should be specified prior the study is undertaken.
(ii) Eligibility criteria : It is always advisable to take the newly
diagnosed cases since the prevalent cases may change their
exposure status due to medical advice.
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10. Sources of cases-
1. Hospitals
◦ Convenient
◦ Cases drawn from single hospital or network of hospital
2. General population
◦ All cases of the study disease occurring within a defined
geographic area during a specified period of time are
selected.
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11.  Controls must be similar to the cases except for the disease under
study.
 Difficulty in selection of control- when disease of interest occurs
in subclinical form whose diagnosis is difficult.
 Selection of proper control necessary- against this group
comparisons are made and inferences are drawn.
Sources of controls:
 Hospital controls Proxy respondents
 General population Neighborhood
 Relatives
 Friend

11

12. Hospital controls-
 Can be selected from same hospital as from cases.
 Controls selected should have different disease other than the
study disease.
Ex-Cases- oral cancer, Control- digestive tract cancer/ non
cancerous lesions.
Disadvantage- hospital patients may have disease which are
influenced by factors under study.
 Ex-Cases- oral cancer( relationship between smoking and oral
cancer)
Controls- lung cancer
In selecting such type of control the relationship between smoking
and oral cancer cannot be demonstrated because- smoking is a
risk factor for lung cancer also.
12

13. Relatives- spouse, siblings.
Siblings as control should not be used when genetic conditions are
under study.
Neighborhood
- people living in same locality as cases.
- Same factory
- Same school children
Friend
 They can be selected from a list of friends or associates obtained
from the case.
 As the case and friend control will have similar socioeconomic
status, the biases due to social class are reduced.
13

14. Proxy respondent control
 Interviews with proxy respondents are often used when
subjects die before being interviewed, too sick to
answer questions or for subjects with cognitive
disorders.
 Spouses and children provide accurate responses for
broad categories of exposure information but detailed
information is less reliable.
14

15. General population-
Can be obtained from defined geographic area by taking
random sample of individuals free from disease of
interest.
15

16. Number of controls-
 In large study- one control for each case
 Small study group(50)-2,3,4 controls for each subject.
 In case of hospital study- more than one control group
with different disease condition.
16

17.  Defined as the process by which we select controls in such a
way that they are similar to cases with regards to certain
pertinent selected variables (e g. age, sex, occupation, social
status) which are known to influence the outcome of the
disease and which not adequately matched can distort the
results.
 Types of matching
1. Group matching- done by assigning cases to sub
categories(strata) based on their characteristics like age,
occupation social class.
2. Pair matching- for each case a control matching closely is
selected. Eg-40 yr old male with disease- 40 yr old male
without disease.( same sex and age)
17

18.  Information about the exposure should be obtained in
precisely the same manner for both cases and controls.
 This may be obtained by
◦ Interviews
◦ Questionnaires
◦ By studying past records of cases such as hospital records,
employment records
◦ Clinical or laboratory examination
18

19. The final step is Analysis:
Exposure rate among cases and controls to suspected
factors.
Estimation of the Disease risk associated with exposure
(Odds ratio).
 Exposure rate-provides direct estimation of exposure
rates(frequency of exposure) to a suspected factor in
case and control group.
19

20. CASES
(WITH ORAL CANCER)
CONTROLS
(WITHOUT ORAL
CANCER)
TOBACCO CHEWERS 33(a) 55(b)
NON CHEWERS 2(c ) 27 (d)
TOTAL 35 (a + c) 82( b + d)
20

21. 1.Exposure rates:
Cases= a/a + c
= 33/35
= 94.2%.
Controls = b/b + d
= 55/82
= 67.0%
 This shows frequency rate of oral cancer is definitely higher
among tobacco chewers than among non chewers.
21

22.  Measure of strength of association between risk
factors and outcome.
 The odds ratio is also known as the cross-products
ratio.
 Based on 3 assumption:
o Disease being investigated must be relatively rare
o The cases must be representative of those with the disease.
o The controls must be representative of those without the
disease.
22

23.  Odds Ratio = ad/ bc
=33 X 27/55 X 2
= 8.1
 In this example risk of oral cancer is 8.1 times greater
in individuals who chewed tobacco than in those who
did not.
23

24. 1.Selection Bias- the cases and controls may not be
representative of cases and controls in general
population.
2. Berksonian Bias – This type of bias arises because of the
different rate of admission to hospital for different diseases.
3. Memory Bias- Cases who are suffering from a disease are
likely to recall much more as regards their exposure when
compared to controls.
Example – myocardial infarction and past habits.
Bias due to Confounding – occurs due to counfounding
factor which is associated both with exposure and disease
and is distributed unequally in study and control groups.
24

25.  Combines the advantages of a cohort and a case control
study.
 It is a hybrid study design in which case control study
is nested in a cohort study.
25
Population
Develop
disease
Do not
develop
disease
Cases Controls
Initial data collection
Years

26.  Firstly a population is identified.
 Then followed over a period of time.
 At the time the population is identified->
baseline data is collected ( via interviews,
blood, urine tests).
 From this population small % of participants
will manifest disease while most will not.
 Now at this time case-control study is carried
out in participants who developed disease
and who did not.
26

27. 1.Elimination of recall bias-Interviews are performed at
beginning(years before) so data obtained is before the
disease has developed. So recall bias is eliminated.
2.Identifies risk factor- as the specimens are obtained years
back before development of disease so if abnormalities in
biologic characteristics are found, it is more likely that
these findings represent risk factor or other premorbid
characteristics than a manifestation of disease.
 When such biologic abnormalities are found in traditional
case-control study we cannot know whether they preceded
the disease or were manifestation/result of the disease.
27

28. Why nested case-control over cohort study?
 More economic.
 In cohort study (of 10,000 people) laboratory analyses of all the
specimens obtained would have to be carried out to define
exposed and non-exposed. This becomes were expensive.
 But in nested case control specimens obtained are frozen/stored.
 Only after the disease develops in some subjects case control
study begins and then the specimens from small number of
people in the case-control study are analyzed.
 Thus reducing the laboratory cost dramatically.
28

29. 
Efficient for the study of rare and chronic
diseases

Tend to require a smaller sample size than
other designs

Less expensive than cohort study

No attrition problem(no follow up required)

May be completed more rapidly than
alternative designs.

Allows to study several different etiological
factors.
29

30. 
Incidence cannot be measured

Problem of recall bias (relies on memory).

More susceptible to selection bias

Information on exposure may be less
accurate
30

31.  Forward looking ,incidence , longitudinal, prospective study.
 Cohort = Group of people who share a common characteristic or
experience within a defined time period(age, occupation,
exposure etc).
 Group of people born on same day/period of time- Birth cohort
 People exposed to common drug- Exposure cohort
 Features of cohort study-
◦ The cohorts are identified prior to the appearance of a disease under
investigation.
◦ The study groups –observed over a period of time to determine the
frequency of disease among them.
◦ Study proceeds forward cause effect
31

32.  Cohorts must be free from the disease under study.
 Both the groups must be comparable in respect to all
the possible variables which may influence the
frequency of the disease.
 The diagnostic and eligibility criteria of the disease
must be defined before starting the study.
Groups are then followed , under the same identical
conditions, over a period of time to determine the
outcome of the exposure.
32

33. 1. Prospective cohort study
2. Retrospective cohort study
3. Ambispective ( combination of prospective
and retrospective)
33

34.  Outcome has not occurred at the time when investigation
begins.
 Population of study identified->follow up done till exposure
group identified-> follow up till disease is developed.
34
Defined
population
Exposed Non-exposed
Disease
No
Disease
Disease
No
Disease
2016
2026
2036

35.  Outcome has occurred before the investigation begins.
 Investigator goes back in time-> exposed, non-exposed group
selected-> records traced forward through time (upto present
to see if disease developed or not). No future follow-up is
done.
35
Defined
population
Exposed Non-exposed
Disease
No
Disease
Disease
No
Disease
1996
2006
2016

36.  The cohort is identified from past records.
The same cohort is followed up prospectively
into future for further outcomes.
36
Defined
population
Exposed Non-exposed
Disease
No
Disease
Disease
No
Disease
1996
2006
2016
2016
2026
2036

37.  Selection of study subjects
 Obtaining data on exposure
 Selection of comparison groups
 Follow-up
 Analysis
37

38.  General population- Cohort defined on basis of
geographical or administrative boundaries (e.g.
people living in a given state or district).
 Special group-select group-e.g. specific
profession. All registered doctors, lawyers,
teachers, civil servants).
 Special Exposure Groups – group of people
exposed to physical, chemical and other disease
agent(e.g. radiologists for studies on effect of
radiation).
38

39.  Through interviews or mailed questionnaires.
 Through review records.
 Through medical examination or special
tests.
 Through environmental surveys.
39

40.  Internal Comparison
Single cohort selected- classified into several
comparison groups according to degree of exposure
to risk
 External comparison
When information on degree of exposure is not
available, another group, another cohort is chosen
(smokers and non smokers)
40

41.  General population- If none of the mentioned
comparison is available then the mortality experience
of the exposed group is compared with the mortality
experience of the general population in the same
geographic area as the exposed people.
 E.g. comparison of frequency of cancer among
uranium mine workers with the rate in general
population in same geographic area
41

42.  Regular follow up is necessary in cohort study
and method should be decided regarding the
same depending on the outcome(morbidity or
death)
Procedures used-
 Periodic medical examination of each member of
the cohort.
 Routine surveillance of death records.
 Mailed questionnaires, telephone calls, periodic
home visits.
 Reviewing physician and hospital records
42

43.  DATA IS ANALYSED IN TERMS OF
a) Incidence rates of outcome among exposed and non-
exposed.
b) Estimation of risk.
(i) relative risk
(ii) attributable risk
43

44. Tobacco
(risk
factor)
Developed
oral
cancer
Did not
develop
Total Incidence
Present
(chewers)
45
(a)
9955
(b) 10000
(a + b )
45/1000
0
=4.5 per
1000
Absent
(non-
chewers)
5
(c)
9995
(d) 10000
(c +d)
5/10000
=0.5per
1000
44

45. It is the ratio of incidence of disease among exposed and
incidence of disease among non-exposed.
R. R = incidence of disease (or Death) among exposed
incidence of disease (or Death) among non- exposed
RR= a/a+b = 45/10000
c/c+d 5/10000
=4.5/0.5
=9
9 times higher risk of developing oral cancer in tobacco chewers
compared to non-chewers.
45

46.  RR=1 = No association between exposure and disease
incidence rates are identical between groups
 RR=> 1 = Positive association exposed group has higher
incidence than non-exposed group
 RR=< 1 = Negative association or protective effect.
46

47.  It is the difference in incidence rates of disease
between exposed and non-exposed group.
◦ Formula-
Incidence of disease rate among exposed- incidence of
disease rate among non-exposed
Incidence rate among exposed
=4.5-0.5 x 100
4.5
=88.9%
It means out of total risk of development of oral cancer in
chewers, 88.9% is attributed to tobacco chewing.
47

48.  Selection bias- group studied does not reflect the
same distribution characteristics occurring in the
general population.
 Information bias- if the quality and extent of
information obtained is different for exposed and
non-exposed, this bias is introduced.
 Confounding bias- this bias occurs because of
confounding factors and when these factors are
not equally distributed in both the groups.
48

49.  Incidence can be calculated
 Several possible outcomes related to exposure can be
studied simultaneously.
 Cohort studies provide a direct estimate of Relative
risk.
 Dose – response ratio can also be calculated.
49

50.  Large number of population required.
 Very lengthy- takes very long time to complete.
 Certain administrative.
◦ Loss of experienced staff.
◦ Loss of funding.
◦ Extensive record keeping.
 There may be changes in study methods or Diagnostic
Criteria of the Disease over the prolonged period.
 Cohort studies are expensive.
 The study may itself alter the patients Behavior.
50

51. 51
CASE CONTROL STUDY
1. Proceeds from effect to cause.
2. Starts with the disease.
3. Tests whether the suspected
cause occurs more frequently in
those with the disease than
among those without the
disease.
4. Usually the first approach to the
testing of a hypothesis, but also
useful for exploratory studies.
5. Involves fewer number of
subjects.
COHORT STUDY
1. Proceeds from cause to effect.
2. Starts with people exposed to
risk factor or suspected cause.
3. Tests whether disease occurs
more frequently in those
exposed, than in those not
similarly exposed.
4. Reserved for testing of precisely
formed hypothesis.
5.Involves large number of
subjects.

52. CASE CONTROL STUDY
6. Yields relatively quick results.
7. Suitable for the study of rare
disease.
8. Generally yields only estimate
of RR(odds ratio).
9. Cannot yield information about
diseases other than that selected
for study.
10. Relatively inexpensive.
COHORT STUDY
6. Long follow-up period often
needed, involving delayed
results.
7. Inappropriate when the disease
or exposure under
investigation is rare.
8. Yields incidence rates, RR as
well as AR.
9. Can yield information about
more than one disease
outcome.
10. Expensive.
52

53.  The purpose of case-control and cohort
study is to identify association between
exposure and disease.
 Care should be taken in selecting study/case
and control group because any bias in this
will lead to unreliable results.
53

54.  Peter S. General epidemiology. Essentials of preventive and
community dentistry, 4th edition. New delhi, Arya
publication. 2009;42-82
 Gordis L. Cohort studies. Epidemiology, 3rd edition.
Elsevier. 2004;149-148
 Gordis L. Case-control and cross-sectional studies.
Epidemiology, 3rd edition. Elsevier. 2004;159-176
 Park K. analytical epidemiology.Textbook of Preventive
and Social Medicine. 23rd ed. Bhanot Publishers. Pg
no.62-73
54

55. THANK YOU
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