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To examine the possible relation of an

exposure to a certain disease, we


identify a group of individuals with that
disease
(called
cases)
and,
for
purposes of comparison, a group of
people without that disease (called
controls).

We determine what proportion of the


cases
were
exposed
and
what
proportion were not.
We also determine what proportion of
the controls were exposed and what
proportion were not.

CASES

CONTROLS

Selection of Cases

In a case-control study, cases can be selected


from
a
variety of sources, including hospital patients,
patients
in physicians' practices, or clinic patients.

Several problems must be kept in mind in


selecting cases for a case-control study.

Selection of Controls

Controls
may
be
selected
from
nonhospitalized
persons living in the community or from
hospitalized patients admitted for diseases
other
than
that
for
which the cases were admitted.

Selection of Controls

Nonhospitalized Persons as Controls

Nonhospitalized controls may be selected from


several sources in the community.
Other sources include school rosters, selective
service lists, and insurance company lists.
Another option is to select, as a control for each
case, a resident of a defined area, such as the
neighborhood in which the case lives.
Another approach to control selection is to use a
best friend control.

Selection of Controls

Hospitalized Persons as Controls

Hospital inpatients are often selected as controls


because of the extent to which they are a "captive
population" and are clearly identified; it should
therefore be relatively more economical to carry
out a study using such 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.
Matching may be of two types:

group matching
individual matching.

Group Matching

Group matching (or frequency 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 for


the study, a control is selected who is
similar to the case in terms of the specific
variable or variables of concern.

The problems with matching are of two


types:

Practical

Conceptual

Practical Problems with Matching:

If an attempt is made to match according


to too many characteristics, it may prove
difficult or impossible to identify an
appropriate control.

Conceptual Problems with Matching:

Once we have matched controls to cases


according
to a given characteristic, we cannot study
that
characteristic.
We do not want to match on any variable
that
we
may wish to explore in our study.

A major problem in case-control studies


is that of recall.
Recall problems are of two types:

Limitations in recall

Recall bias

Limitations in Recall

Virtually all human beings are limited to varying


degrees in their ability to recall information,
limitations in recall are an important issue in
such studies.
If a limitation of recall regarding exposure affects
all subjects in a study to the same extent,
regardless
of whether they are cases or controls, a
misclassification of exposure status may result.

Recall Bias

A more serious potential problem in casecontrol


studies is that of recall bias.
The small number of examples available could
reflect infrequent occurrence of such bias, but
the
possibility for such bias must always be kept in
mind.

The odds ratio (OR) is used as an effect


measure for association.

Confidence of the effect estimates is


given by a confidence interval, usually at
a 95% level. The confidence interval
covers the unknown effect measure with
95% probability.

The data can be displayed in a 2 X 2


contingency table.

The exposed subjects (b + d), d will be


classified as ill or affected. The odds for
being ill consequently is d/(b + d) divided
by b/(b + d) or d/b, which is the same as
the probability of being ill divided by the
probability of not being ill.
In the group of the (a + c) non-exposed, c
are counted as ill or affected and a as
healthy. The odds for being ill versus
healthy is c/a.

The odds ratio is a comparison of these


two groups by dividing the odds for
both groups,
d b giving:
ad
OR

ca

bc

The odds ratio is an effect measure


that tells us how much larger the odds
are for the exposed to be ill than for
the nonexposed.

The main advantage of casecontrol


studies is that they are relatively simple to
carry out
Inexpensive
Reasonably rapid
Suited to infrequent conditions
Permit examining large numbers of
possible risk factors
May be organized as multicentre studies

The major disadvantage of the casecontrol study


is the inverse direction of the data on exposure,
which is collected after the patient has become a
case.
Systematic error or errors that affect results in a
certain direction are called bias.
The inverse time aspect is a major problem in
interpreting the results of retrospective or case
control studies.
To avoid these types of systematic errors, one must
establish examination procedures that reduce the
possibility of clinical disease affecting the answers.

Case Control
Studies

Cohort Studies

Population

Start with affected


subjects

Start with healthy


subjects

Incidence

No

Yes

Prevalence

No

No

Association

Odds ratio

Relative risk

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