Case control study- Dr Monisha Mary P.pdf

The presentation aims to provide a clear and concise overview of the case-control study design, including its definition, key features, and steps involved. It serves as an educational resource for individuals seeking to understand the fundamentals of epidemiological research methods, particularly in the context of investigating associations between exposures and outcomes.

1. CASE CONTROL STUDY
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By Dr. Monisha Mary P
Post graduate in Community Medicine

2. LEARNING OBJECTIVES
❖ To know the Study design of epidemiological studies
❖ To define a Case-Control Study
❖ To describe the Basic steps of a case-control study
❖ To learn the bias involved in the Case-Control study
❖ To learn about advantages and disadvantages
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3. Formulation of a
clearly defined
hypothesis
“Retrospective”
study
Works backwards
Potential bias:
• Recall
• Selection
The starting point is the
outcome.
Basic steps in case-
control
Defining case groups
Defining control
groups
confounding factor
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4. EPIDEMIOLOGIC STUDIES
Experimental study Observational study
Random allocation
Comparison group
Randomised
control trial
Non
randomised
controlled
trial
Analytical study Descriptive study
COHORT STUDY CASE CONTROL STUDY
CROSS SECTIONAL
STUDY
Exposure to
outcome
Outcome to
exposure
Exposure and
outcome at the
same time
STUDY DESIGN
-
EPIDEMIOLOGICAL STUDIES
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5. DEFINITION OF CASE CONTROL STUDY
•The observational epidemiological study of people with the
disease of interest and a suitable control group of persons
without the disease.
•A case-control study involves two populations – cases and
controls.
•Also called a “retrospective study”.
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6. It has three distinct features
• Both exposure and outcome occurred before the start of the
study.
• The study proceeds backward from effect to cause.
• It uses a control or comparison group to support our
inference.
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7. •We identify Cases and Controls.
•We then determine what proportion of cases, controls were
exposed and what proportion of cases and controls were not
exposed.
•The hallmark of a Case-Control study is that it begins with
people with the disease and compares them to people without
the disease
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8. WHEN IS IT DESIRABLE TO CONDUCT A CASE CONTROL STUDY?
Exposure
management
is expensive
Disease is rare
Very little
understanding
of the disease
Many risk
factors can be
found out
Longer
duration(NCD)
Population is
dynamic
When Funds
are less
Carried out
quickly.
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9. DESIGN OF A CASE CONTROL STUDY
HAVE THE DISEASE
DO NOT HAVE THE DISEASE
WERE
EXPOSED
WERE NOT
EXPOSED
WERE EXPOSED
WERE NOT
EXPOSED
CASES CONTROLS
OUTCOMEEXPOSURE
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10. BASIC STEPS IN CASE CONTROL STUDY
❖SELECTION OF CASES AND CONTROLS
❖MATCHING
❖MEASUREMENT OF EXPOSURE
❖ANALYSIS AND INTERPRETATION
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11. Selection of cases
and controls
Matching
Measurement of
exposure
Analysis and
interpretation
BASIC STEPS IN CASE CONTROL STUDY
The
researcher
first comes up
with a
hypothesis
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12. SELECTION OF CASES & CONTROLS
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13. SELECTION OF CASES
•It involves defining the case and determining the source of cases.
•As the cause and effect have already occurred, the proper diagnosis
of the disease under investigation is necessary in the selection of a
case.
• Once the diagnostic criteria are established, they should not be
changed or altered till the end of the investigation.
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14. • Hospital patients, patients in physicians’ practices, or clinic patients.
•Many communities also maintain registers for certain diseases like
cancer.
•Using incident or prevalent cases-Incident cases are preferable to
prevalent cases for reducing
❖Recall bias and
❖Over-representation of cases of long duration.
•Old or advanced stages of the disease should preferably not be used
(prevalent cases).
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SOURCES OF CASES

15. SELECTION OF CONTROLS
•Controls should be selected from the same population
•the source population (i.e. study base).
❖ Non-hospitalized
•Neighbourhood control
•Best friend control
•Spouse or sibling control
❖ Hospitalized control
•All other patients admitted
•Specific ‘another diagnosis’
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16. Potential
controls
Neighbourhood
Population
Register
Door to
Door
Hospital
Relative
Friend
SOURCES OF CONTROLS
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17. CASES CONTROLS
TOTAL POPULATION
DEFINED POPULATION
SELECTION OF CASES AND CONTROLS
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18. USE OF MULTIPLE CONTROLS
•Matching 1:2,1:3 or 1:4 will increase the statistical power of our
study.
•Therefore many case-control studies will have more controls than
cases.
•These controls may be
❖Controls of the same type.
❖Controls of different types.
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19. MATCHING
•An important consideration is to ensure comparability within the
cases and controls.
•Matching is defined as the process of selecting the controls so
that they are similar to the cases .
•In certain characteristics such as age, race,sex, socioeconomic
status, and occupation.
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20. • If not adequately matched for comparability, it could distort or
confound the results of the study.
•Matching may be of two types:
❖Group matching (Frequency matching).
❖Individual matching(matched pairs).
THE NEED FOR MATCHING
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21. GROUP MATCHING
Consists of selecting the controls in such a manner that the
proportion of controls with a certain characteristic is identical to
the proportion of cases with the same characteristic.
INDIVIDUAL MATCHING
In this approach, for each case selected, a control is selected
who is similar to the case in terms of the specific variables of
concern.
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22. UNPLANNED MATCHING
Unplanned matching may inadvertently occur in case-control
studies, for example
Example:
•Neighborhood controls-we are in effect matching for
socioeconomic status as well as for cultural and other
characteristics of a neighborhood.
•Best friend controls-his or her best friend share many lifestyle
characteristics, which in effect produces a match for these
characteristics.
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EXAMPLE OF UNPLANNED MATCHING
Oral
contraceptive
Study of
cancer
best-friend
controls were
considered
study of oral
contraceptive
use and
cancer
Her best friend
would also be
likely to be an
oral
contraceptive
user
The result would be an unplanned matching of oral contraceptive use, so that
this variable could no longer be investigated in this study

24. PROBLEMS WITH MATCHING
Practical problems
If matching is done for
too many
characteristics,
difficult or impossible to
find an appropriate
control
Conceptual problem
Once matched controls to
cases according to a given
characteristic, we cannot
study that characteristic.
We do not match any
variable that we may wish
to explore in our study
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25. CONFOUNDING FACTOR
•The term “confounding factor” is defined as one which is
associated with both exposure and disease and is distributed
unequally in study and control groups.
• More specifically, a confounding factor is one that although
associated with exposure under investigation by itself,
independently of any such association, a risk factor for the
disease.
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26. •Let us suppose that we are interested in examining the
relationship between the current use of oral contraceptives and
ovarian cancer.
• In this example, it is appropriate to match age, since age is
associated with the exposure of interest (current oral
contraceptive use) and is an independent risk factor for ovarian
cancer.
•In other words, age is a confounding factor.
•Failure to match, or otherwise control, for age would result in a
biased assessment of the effect of oral contraceptive use.
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27. OVERMATCHING
•Unplanned matching on a variable strongly related to the
exposure being investigated in the study is called overmatching.
• The most serious type of overmatching occurs when one
matches on a factor that is both affected by exposure and a
cause of disease.
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28. MEASUREMENT OF EXPOSURE
•Information about the exposure should be obtained from both
the cases and controls in the same manner.
•This may be achieved by:
❖Interviews
❖Questionnaires
❖Studying past records like hospital or employment records etc
❖Medical records.
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29. ANALYSIS
•This is the final step in a case-control study, and it provides:
❖ Exposure rates among cases and controls to the suspected
factor.
❖ Estimation of disease risk associated with exposure.
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30. EXPOSURE RATES
•A case-control study directly estimates the exposure rates to a
suspected factor in disease and non-disease groups.
• The significance of measuring the exposure rates lies in
estimating the probability of associating the disease and the
factor under study.
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31. •Exposure Rates: Cases = a/(a+c) =65/100 =65%
Controls =b/(b+d) =40/200= 20%
•The frequency of obesity is definitely higher among
T2DM than those without T2DM.

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Diabetes + Diabetes -
Obesity+ 65
(a)
40
(b)
Obesity- 35
(c)
160
(d)
Total 100
(a + c)
200
(b + d)
CASE-CONTROL STUDY OF TYPE 2 DIABETES AND OBESITY

32. ODDS RATIO
•It is a measure of the strength of the association between risk
factor and outcome.
•It is closely related to relative risk.
•The determination of the odds ratio is based on 3 assumptions
❖The disease to be investigated must be relatively rare or a
chronic disease.
❖ The cases must be representative of those with the disease
and
❖ The controls must be representative of those without the
disease.
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33. ODDS OF AN EVENT
Can be defined as the ratio of the number of ways the event can
occur to the number of ways the event cannot occur.
ODDS RATIO (OR)
Compares the odds of exposure among those with the disease to
the odds of exposure among those without the disease.
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34. DETERMINE ASSOCIATION
CASES CONTROLS
EXPOSED a b
UNEXPOSED c d
•Assess whether exposure is distributed between the cases
and controls, which may indicate that the exposure is a risk
factor for the health outcome under study.
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35. ❖ Odds of a case being exposed = a:c or a/c
❖ Odds of control being exposed = b:d or b/d
❖ Odds ratio = odds that cases were exposed
/odds that controls were exposed
= ad/bc.
CASES CONTROLS
EXPOSED a b
UNEXPOSED c d
TOTAL (a + c) (b + d)
PROPORTIONS
EXPOSED
a/ (a + c) b/ (b + d)
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36. INTERPRETATION OF THE ODDS RATIO
•OR = 1: no association between outcome and exposure (same
odds of exposure in cases and controls = same odds of
disease in exposed vs. unexposed).
•OR >1: exposure is associated with increased risk for the
outcome (greater odds of exposure in cases than control
Harmful Effect.
•OR <1:exposure is associated with reduced risk for outcome
(lower odds of exposure in cases than controls =lower odds of
disease in exposed vs. unexposed) Protective Effect.
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37. CALCULATING ODDS RATIO IN AN UNMATCHED CASE CONTROL
STUDY
Odds Ratio=ad/bc
CALCULATING ODDS RATIO IN MATCHED PAIRS CASE -CONTROL
STUDY
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Concordant
pairs
Discordant
pairs
Pairs in which both case and control were exposed
Pairs in which neither the case nor the control was
exposed
Pairs in which the case was exposed but the control was
not
Pairs in which the control was exposed but the case was
not

38. •Calculation of the Odds ratio in such a matched pair study is
based on the discordant pairs only (b) and (c) .
•The concordant pairs are ignored as they do not contribute to
our knowledge of how many cases and controls differ in regard
to past history of exposure.
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Matched pairs odds ratio = b/c

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2 4
1 3
Exposed Non exposed
Control
Exposed
Not exposed
Case
Matched pairs Odds Ratio = b/c
= 4/1
=4

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Diabetes + Diabetes -
Obesity+ 65 40
Obesity- 35 160
Total 100 200
CASE-CONTROL STUDY OF TYPE 2 DIABETES AND OBESITY
Odds Ratio-ad/bc =65x160/40x35
=7.42
•How much higher is the odds of exposure in the cases as
compared to controls?
•In the above example, individuals with Diabetes are 7.42 times
more likely to be obese as compared to those without Diabetes.
•The odds ratio is a key parameter in case-control studies.

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a b
c d
a b
c d
Develop
disease
Do not
develop
disease
Exposed
Non
exposed
CASES CONTROLS
History of exposure
No history of
exposure
OR=odds that an exposed person
develops disease/odds that a nonexposed
person develops the disease.
=ad/bc
OR=odds that a case was exposed/odds that
control was exposed.
=ad/bc
a b
c d
Disease No Disease
Exposed
Non exposed
Odds Ratio(OR)
Cross product ratio
ad/bc

42. Diabetes + Diabetes -
Obesity+ 10 40
Obesity- 02 48
Odds of exposure among diseased10/2
Odds of exposure among non
diseased
40/48
Exposure Odds ratio 6.25
Odds of disease among exposed 10/40
Odds of disease among non exposed 2/48
Disease Odds ratio 6.25
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43. •Because epidemiology is always concerned with identifying
predictors of disease
•And odds ratio of exposure is same as odds ratio of disease
•Therefore even in case control studies , the Interpretation is
always prospective .
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44. BIAS
•Bias is any systematic error in the determination of the
association between exposure and the disease.
❖Selection bias
❖Information bias.
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45. SELECTION BIAS
•It refers to any error in selecting the study population
❖The people who are selected to participate in a study are not
representatives of the reference population.
❖Controls are not representative of the population which
produced the cases.
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46. Case-control study
to examine HTN in
women
OCP to be used as one
risk of factor of
interest
Women who take
OCP have regular
check ups
Than women with
who do not take
OCP
Women who take OCP
more likely to be
identified as having
HTN for study
EXAMPLE OF SELECTION BIAS IN THE SELECTION OF CASES
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We select as cases
those women who
have been
diagnosed as having
HTN in PHC

47. SELECTION
OF
CONTROLS
We want to
investigate risk
factors for liver
cirrhosis
Heavy alcohol use
will be a major risk
factor
We select cases
from hospital records
People admitted to
same hospital with
trauma as controls
People admitted to
hospital =heavy
users of alcohol
So less diff in
prevalence of risk
factor in case and
controls
EXAMPLE OF SELECTION BIAS IN SELECTION OF CONTROLS
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48. INFORMATION BIAS
RECALL BIAS
•When cases and controls are asked questions about their past
history, it may be more likely for the cases to recall the
existence of events than the controls who are healthy people.
•Cases may have a different recall of past events than controls.
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49. PROBLEMS OF RECALL
•A major problem in case control studies is that of recall of a
history of past exposure.
•Recall problems are of two types
❖Limitations in recall
❖Recall bias
•Recall bias is the main form of information bias in case control
study.
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50. LIMITATIONS OF RECALL
•Virtually all human beings are limited to varying degrees in their
ability to recall.
•Much of the information in case control involves collecting data
from subjects through interviews.
•People being interviewed may simply not have the information
being requested.
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51. EXAMPLE OF RECALL BIAS
A Mother who had a child
The child was born with a
birth defect
She may have forgotten
entirely
Mother tries to identify
some unusual effect
While mother of a child
without a brain defect
Which occurred during
her pregnancy
Such mother can recall
even a simple event
She wants to know why it
happened
Ernst Wynder called
Recall bias as
Rumination Bias
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52. Defined Cohort
Developed
disease Have not developed
disease
CASES
Subgroup selected as
CONTROLS
Years
Initial Data and/or
Serum, Urine, or Other
Specimens Obtained
Design of a case
-
control study initiated within a cohort

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53. DEFINED COHORT
DEVELOP
DISEASE
HAVE NOT DEVELOPED THE
DISEASE
TIME
I YEAR
2 YEARS
3 YEARS
4 YEARS
5 YEARS
CASE 1
CASE 2
CASE 3 AND 4
CONTROL 1
CONTROL 2
NESTED CASE CONTROL STUDY
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54. DEFINED COHORT
DEVELOP
DISEASE
TIME
I YEAR
2 YEARS
3 YEARS
4 YEARS
5 YEARS
CASE 1
CASE 2
CASE 3 AND 4
CASE 5
5 CASES
5 CONTROLS
CASE COHORT STUDY DESIGN
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55. CASE-CROSSOVER DESIGN
•The case-crossover design is used for studying the etiology of
acute outcomes such as myocardial infarctions or deaths.
•In this type of study, a case is identified (for example, a person
who has suffered a myocardial infarction) and the level of the
environmental exposure, is ascertained for a short time period
preceding the event (the at-risk period).
• This level is compared with the level of exposure in a control
time period.
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56. WHEN IS A CASE CONTROL STUDY
WARRANTED?
•At an early stage in our search for an etiology, we may suspect
any one of the several exposures, but we may not have
evidence.
•Using case control study we compare people with the
disease(cases) and people without the disease (controls).
•We can then explore the possible roles of a variety of
exposures or characteristics in curing the disease.
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57. ADVANTAGES
• Relatively easy to carry out.
• Rapid and inexpensive.
• Require comparatively few subjects.
• Particularly suitable to investigate rare diseases.
• No risk to subjects.
• Allows study of different etiological factors.
• Risk factors can be identified.
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58. DISADVANTAGES
•Problems of bias rely on memory or past records, the accuracy
of which may be uncertain; validation of information obtained is
difficult or sometimes impossible.
• Selection of an appropriate control group may be difficult.
• We cannot measure incidence, and can only estimate the
relative risk.
• Do not distinguish between causes and associated factors.
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59. POSITION IN HIERARCHY
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60. Cohort Case control study
Study group Exposed person Cases
Comparison group Non exposed person Controls
Measurement of risk Absolute risk
Relative risk
Odds ratio
Attributable risk
Odds ratio
Time for study Long Short
Cost of study Expensive Inexpensive
Best when Exposure is rare Disease is rare
Population size needed Relatively large Relatively small
Potential bias Assessment of outcome Assessment of exposure
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61. EXPOSED NOT EXPOSED
DISEASE
DEVELOPS
DISEASE
DOES NOT
DEVELOP
PEOPLE WITH THE
DISEASE
PEOPLE WITHOUT
THE DISEASE
COMPARING CASE CONTROL AND COHORT STUDIES
DISEASE
DEVELOPS
DISEASE
DOES NOT
DEVELOP
WERE
EXPOSED
WERE NOT
EXPOSED
WERE
EXPOSED
WERE NOT
EXPOSED
Start with
Then
follow
up for
Start with
CASES
CONTROLS
Then
determine the
exposure
history
COHORT STUDY
CASE CONTROL STUDY
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62. Defined
population
Disease
develop
Disease
does not
develop
Exposed
Non
Exposed
With disease Without disease
A
B
C
A
B
C
CASES CONTROLS
In a case-control study that starts by identifying cases and controls,
we can study multiple exposures but only one outcome.
In a cohort study that starts with a defined population, we can
study both multiple exposures and multiple outcomes.
CASE CONTROL AND COHORT STUDY DESIGN
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63. CASE CONTROL
OUTCOME TO
EXPOSURE
COHORT STUDIES
EXPOSURE TO OUTCOME
Ca Lung patients and non
patients
Follows a cohort of smokers and
non smokers without Ca Lung
Clarifies if it was smokers who
contributed to high Ca Lung
Smokers develop Ca Lung more
frequently
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PROSPECTIVE AND RETROSPECTIVE CASE CONTROL
AND COHORT
RETROSPECTIVE CASE CONTROL PROSPECTIVE
RETROSPECTIVE PROSPECTIVE
COHORT
OUTCOME
EXPOSURE
EXPOSURE
OUTCOME

67. REFERENCES
1.Park k . Textbook of preventive and social medicine.
Principles of epidemiology and epidemiologic methods. 26th
ed. Jabalpur: M/S Banarsidas bhanot publications; 2021.p.83-
88.
1.Gordis L., Celentano David D., Szklo Moyses. Gordis
Epidemiology.Observational Studies. 6th edition. Elsevier
Saunders; 2019.p. 178-186.
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