Case Control Study For Medic

Epidemiological studies
Populations Ecologic/correlational
Descriptive Case report/Case-series

Individuals
Cross-sectional
Case-control
Observational
Prospective
Cohort
Analytical Retrospective
Intervention Clinical trials

1
Prof. Alemayehu Bayray (PhD) 11/27/22
Case-Control Study design
 Subjects are selected with respect to presence or absence of out come of
interest (e.g. disease), and then inquiries are made about past exposure to
factors of interest.
 Those who have the outcome of interest are termed as “cases”, and those
who do not have the outcome of interest are termed as “controls”.
 The exposure histories of cases and controls are then obtained and
compared.
 Thus, the central feature of case control study is the comparison of the
cases’ and controls’ exposure histories. Case control study is usually
retrospective in nature.
2 Prof. Alemayehu Bayray (PhD) 11/27/22
Case-Control Cont’d
Advantage of case control study:

 Optimal for the evaluation of rare disease.
 Suitable for diseases with long induction period.
 Can examine multiple etiologic factors for a single disease.
 Quick and inexpensive in comparison with cohort study.
 Requires comparatively few subjects and Often no risk to subjects
 Existing records can occasionally be used

Case-Control Cont’d
Disadvantage of case control study:

 Inefficient for the evaluation of rare exposures.
 It is restricted to single outcome.
 Liable to “recall bias”
 Liable to “survivor bias”
 Liable to “selection bias”

Case-Control cont’d
Selection of Cases:
 The starting point of most case-control studies is the
identification of cases.
 Thisrequires a suitable case definition. A case definition is

usually based on a combination of signs and symptoms,
physical and pathological examinations, and results of
diagnostic tests.
 It
is best to use all available evidence to define with as
much accuracy as possible the true cases of the disease.

Selection of controls:
 Controls are those who have not developed the outcome of interest
and are a sample of the population that produced the cases.
1. Controls must come from the same base population as the cases
(the control resemble the case except in outcome status),
2. Comparability of controls with cases, (comparability is more
important than representativeness)
3. Controls must be sampled independently of exposure status
(exposed and unexposed controls should have the same
probability of selection)
4. Outcome ascertainment criteria should be the same for cases and
controls.

 Control selection is usually achieved through matching.
 Matching is the process of selecting controls so that they are

similar to the cases in regard to certain characteristics.
 Hence, we should identify matching variables (e.g. age), and

develop matching criteria (e.g. control must be within the same 5
year age group) in advance.
 Here it is important to note that controls can be individually

matched or frequency matched.
 Individual matching: For a case search for one (or more) controls who
have the required matching criteria.
 Frequency (group) matching: Select a population of controls such that

the overall characteristics of the group match the overall characteristics
of the cases (i.e. based on matching variables).
 During the matching process it is important to avoid “Over matching”

i.e. match only on factors known to be causes of the outcome of interest.
 The power of study can be increased by matching a case with multiple

(usually <4) controls. There is no further gain of power above four
controls per case.

Epidemiologists use several sources for identifying controls
in case control studies. They may sample:
 Individuals from the general population
 Individuals attending a hospital or clinic
 Friends or relatives identified by the cases

Population control:
Population controls are typically selected when cases are identified from
a well defined population such as residents of a geographic area. These
controls are usually identified using available registration system.
Advantage of population controls:

 They are more likely to be comparable to the cases with respect to
socio-demographic and other important variables.

Disadvantage of population controls:
 Time consuming and expensive to identify them.
 Do not have the same level of interest in participating as do cases,
 Because they are generally healthy, their recall may be less accurate
than that of cases
Hospital/clinic controls:
 The guiding principles in selection of controls from health
institutions are:
1. The illnesses/disease in the control group should

be unrelated to the exposure under study.
2. The controls should be comparable with cases

(type of hospital, severity of illness etc).

Advantage of hospital/clinic controls:
 They are easy to identify and are less expensive
 Usually they have good participation rates
 Their recall of prior exposures will be similar to the
cases’ recall, because they are also ill.
Disadvantage of hospital/clinic controls:

 Difficulty in determining appropriate illness for
inclusion.

Special Controls:
 In rare circumstances, “special” controls can be considered.
A friend, spouse, or relative (usually a sibling) can

be nominated by a case to serve as his or her
control.
 These “special” controls are used because they are

likely to share the cases’ socioeconomic status, race,
age, educational level, and genetic characteristics, if
they are related to the cases.
Ascertainment of exposure
 Ascertainment of exposure should attempt to obtain sufficiently detailed
information on the nature, frequency, and duration of these exposures.
 Sources available for obtaining exposure data include:-

 in-person interviews
 self-administered questionnaires
 preexisting medical registry
 employment record
 environmental records
 physical examination
 biological specimens
 Imaging
 Accuracy of exposure data is a particular concern in case control studies as it
is collected retrospectively.
Major findings revealed by case control studies:
 Few of the major scientific association discovered by case
control studies include:
Cigarette smoking and lung cancer,
Post-menopausal estrogens exposure and
endometrial cancer,
Aspirin and Reyes syndrome,
Tampon use and toxic shock syndrome,
AIDS and sexual practices,
Assessment of different vaccines effectiveness.

Design of a Case-Control Study cont’d
FIRST: Select
CASES CONTROLS
(With Disease) (Without Disease)
THEN: Were exposed a b

Measure
Exposure Were not exposed c d

TOTALS a+c b+d
Proportions a b
Exposed a+c b+d

Case-Control Study formula to calculate Odds Ratio (OR)
a
c ad
Odds Ratio = =
b bc
d Case Control
E+ a b
E- c d

Matching in Case-Control Designs
what is matching?
 The process of making a study group and a comparison group
comparable with respect to extraneous factors.
 In case-control studies, we match to make cases and controls as similar

as possible with regard to potentially important confounding factors.
 Matching addresses issues of confounding in the DESIGN stage of a

study as opposed to the analysis phase
 A means of providing a more efficient stratified analysis rather than

a direct means of preventing confounding, by increasing precision of
estimates (reduction in SE)
Types of matching
1. Individual (paired) matching: for each case, one (or
more) controls with the relevant characteristics matching
the case are chosen
 For continuous variables such as age or weight,
controls may be selected if they are within a specified
range of the control value
 Example: Age ± 2 years
 Example: Weight ± 5 pounds

Types of matching…
2. Frequency (Group) matching: Controls are selected such that
the distribution of the relevant characteristic in the controls is
similar to the distribution in the cases
Ex. 1
 If 30% of cases are smokers, then select a control group in
such a way that 30% of controls are smokers
Ex. 2
 Frequency matching on age and sex. If 20% of cases are 50-54
year old females, then controls are selected in such a way that
20% are also 50-54 years old and females.
Advantages of Matching
 May be the best way to control for a strong confounder when
there is little overlap of the confounder between the cases
and controls
 Example: If the cases tend to be older (CHD, prostate cancer) and a
random sample of controls would result in a much younger control
group, then there may not be much overlap of age between cases and
controls
 When the confounder is strong, matching increases the

efficiency of the study (by decreasing the width of the
confidence intervals around an estimate).

Advantages of Matching…
 Matching can be a useful method of sampling controls
when cases and controls are identified from a reference
population for which there is no available sampling frame
(list).
 Example: Reference population is patients at a clinic or

hospital

Disadvantages of Matching
 It may be difficult (and expensive) to identify a matched

control
 When you match on a characteristic, you create an equal

distribution in the cases and controls. Therefore, you
cannot examine the association between the matched
characteristic and the outcome

Disadvantages of Matching…
 You cannot assess additive interaction between the

matching variable and the exposure of interest
 You must account for matching in the data analysis
 You may create groups that are no longer representative of

the reference population, thus decreasing your ability to
generalize your findings

Disadvantages of Matching…
 If you match on a characteristic that is a weak confounder, you may
decrease the statistical power of your study
 If you match on a characteristic that is strongly correlated with the

exposure of interest, you may overmatch
 If you categorize continuous variables too broadly, you may still

have residual confounding
N.B.
 Sample size in unmatched study is number of cases and controls
 Sample size in matched study is number of matched pairs (or triplets,
etc).
Overmatching
 Overmatching occurs when you match on a variable that is
strongly correlated with the exposure of interest
 By setting the distribution of the matching variable to be

equal between cases and controls, you are effectively
setting the distribution of the exposure variable to be equal
between cases and controls
 In doing so, you will be unable to detect a difference in

exposure between cases and controls

Residual confounding
 Occurs when you categorize continuous variables
 Ex. Create age categories for matching

20-25
25-30
30-35
For each case between 20 and 25, select a control who is
also between 20 and 25
 Now your cases and controls are comparable with respect

to age right?
Residual confounding…

Analysis of matched data
 Rationale is to control at the design stage for potential
confounders
 Unit of Analysis is the matched case-control pair
 Mantel-Haenszel OR
 If we pair-match cases and controls, we keep them in pairs

for the calculation of the odds ratio
 What combinations will be possible with regard to

exposure?
Analysis of matched data…
 Concordant pairs:
 Both case and control are exposed
 Neither case nor control are exposed
 Discordant pairs
 Case is exposed, control is not
 Control is exposed, case is not
 What do the concordant pairs tell us?

 Nothing
 We are interested in the discordant pairs

How do you interpret the MH OR? Just as usual.


Multivariable analysis of matched data
 Conditional logistic regression
 Use when you have individual matching

 Analogous to logistic regression, but the model takes into
account the pairing of cases and controls
 Logistic regression
 Use when you have frequency (group) matching

 Simply include the matching variables in the model

Interpreting odds ratios
An odds ratio of :
 1.0 (or close to 1.0) indicates that the odds of exposure among case-patients
are the same as, or similar to, the odds of exposure among controls.
 The exposure is not associated with the disease.
 Greater than 1.0 indicates that the odds of exposure among case-patients are
greater than the odds of exposure among controls.
 The exposure might be a risk factor for the disease.
 Less than 1.0 indicates that the odds of exposure among case-patients are
lower than the odds of exposure among controls.
 The exposure might be a protective factor against the disease.

The Difference Between "Probability" and "Odds"?
•The probability that an event will occur is the fraction of
times you expect to see that event in many trials.

•Probabilities always range between 0 and 1.
•The odds are defined as the probability that the event will
occur divided by the probability that the event will not occur.
•If the probability of an event occurring is Y, then the

probability of the event not occurring is 1-Y. (Example: If the
probability of an event is 0.80 (80%), then the probability that
the event will not occur is 1-0.80 = 0.20, or 20%.
The Difference Between "Probability" and "Odds"?...
 The odds of an event represent the ratio of the (probability that
the event will occur) / (probability that the event will not occur).
This could be expressed as follows:
 Odds of event = Y / (1-Y)
 So, in this example, if the probability of the event occurring = 0.80,

then the odds are 0.80 / (1-0.80) = 0.80/0.20 = 4 (i.e., 4 to 1).

Exercise on case control studies I
 A case-control study was conducted to evaluate the relationship
between artificial sweeteners and bladder cancer. 3,000 cases
and 3,000 controls were enrolled in the study. Amongst the
cases, 1,293 had used artificial sweeteners in the past, while
1,707 had never used artificial sweeteners. Among the controls,
855 had used sweeteners and 2,145 had not.
1. Construct a 2X2 table and

2. Compute the appropriate measure of association, that is the
Odds Ratio (OR).
3. What does your result suggest

Exercise on case control studies II
A study was conducted in men aged 40-70 in order to determine
whether exercising for 2 or more hours per week decreases the
likelihood of heart attack. The cases were 1,000 men who had recently
had a heart attack; of these, 236 reported that they had regularly
exercised for two or more hours per week prior to their heart attack.
1,000 controls were also selected for the study; of these, 379 reported
that they exercised regularly.
1. Construct a 2X2 table
2. Calculate the magnitude of association between regular exercise
and heart attack.
3. What does your calculation suggest?

Exercise on case control studies III
 In a study it was identified that 100 patients with newly diagnosed
squamous-cell carcinomas of the head and neck. The comparison group
consisted of 200 patients without a history of cancer who were seen for
benign conditions. Among the 100 subjects with oropharyngeal cancer 62
reported no tooth loss and 38 reported complete tooth loss. Among the 200
subjects without oropharyngeal cancer 163 reported no tooth loss, 37
reported complete tooth loss.

2. What is the odds ratio for complete tooth loss compared to no tooth loss?
3. What does it mean?

Exercise on case control studies IV
 An estimated 200 persons attended a dinner ceremony in Hargeisa restaurant;
55 attendees became ill. Thirty-three of 55 case-patients and 21 of 145 controls
reported eating a sweet cake in their dinner.

2. What is the odds ratio ?
3. What does it mean?

Thank you

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Epidemiological studies

Descriptive Case report/Case-series

Intervention Clinical trials

Advantage of case control study:

 Existing records can occasionally be used

3 Prof. Alemayehu Bayray (PhD) 11/27/22

Disadvantage of case control study:

4 Prof. Alemayehu Bayray (PhD) 11/27/22

 Thisrequires a suitable case definition. A case definition is

5 Prof. Alemayehu Bayray (PhD) 11/27/22

6 Prof. Alemayehu Bayray (PhD) 11/27/22

 Matching is the process of selecting controls so that they are

 Hence, we should identify matching variables (e.g. age), and

 Here it is important to note that controls can be individually

 Frequency (group) matching: Select a population of controls such that

 During the matching process it is important to avoid “Over matching”

 The power of study can be increased by matching a case with multiple

8 Prof. Alemayehu Bayray (PhD) 11/27/22

 Individuals from the general population

 Individuals attending a hospital or clinic

 Friends or relatives identified by the cases

9 Prof. Alemayehu Bayray (PhD) 11/27/22

Advantage of population controls:

1. The illnesses/disease in the control group should

2. The controls should be comparable with cases

11 Prof. Alemayehu Bayray (PhD) 11/27/22

Disadvantage of hospital/clinic controls:

12 Prof. Alemayehu Bayray (PhD) 11/27/22

A friend, spouse, or relative (usually a sibling) can

 These “special” controls are used because they are

 Sources available for obtaining exposure data include:-

15 Prof. Alemayehu Bayray (PhD) 11/27/22

THEN: Were exposed a b

Exposure Were not exposed c d

16 Prof. Alemayehu Bayray (PhD) 11/27/22

17 Prof. Alemayehu Bayray (PhD) 11/27/22

 In case-control studies, we match to make cases and controls as similar

 Matching addresses issues of confounding in the DESIGN stage of a

 A means of providing a more efficient stratified analysis rather than

 Example: Age ± 2 years

 Example: Weight ± 5 pounds

19 Prof. Alemayehu Bayray (PhD) 11/27/22

 When the confounder is strong, matching increases the

21 Prof. Alemayehu Bayray (PhD) 11/27/22

 Example: Reference population is patients at a clinic or

22 Prof. Alemayehu Bayray (PhD) 11/27/22

 It may be difficult (and expensive) to identify a matched

 When you match on a characteristic, you create an equal

23 Prof. Alemayehu Bayray (PhD) 11/27/22

 You cannot assess additive interaction between the

 You must account for matching in the data analysis

 You may create groups that are no longer representative of

24 Prof. Alemayehu Bayray (PhD) 11/27/22

 If you match on a characteristic that is strongly correlated with the

 If you categorize continuous variables too broadly, you may still

 By setting the distribution of the matching variable to be

 In doing so, you will be unable to detect a difference in

26 Prof. Alemayehu Bayray (PhD) 11/27/22

 Ex. Create age categories for matching

 Now your cases and controls are comparable with respect

28 Prof. Alemayehu Bayray (PhD) 11/27/22

 Unit of Analysis is the matched case-control pair