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Epidemiology in DiseaseEpidem
Control:
Screening

Lemessa Olira (MPH, PhD candidate)

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Screening

The early detection of

– disease
– precursors of disease
– susceptibility to disease
in individuals who do not show
any signs of disease
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Purpose of Screening
Aims to reduce morbidity and mortality from
disease among persons being screened
Is the application of a relatively simple,
inexpensive test, examinations or other
procedures to people who are asymptomatic,
– for the purpose of classifying them with respect to
their likelihood of having a particular disease
a means of identifying persons at increased
risk for the presence of disease, who warrant
further evaluation
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Screening for Disease Control

Examination of asymptomatic people

likely
Classification as
unlikely
….. to have a disease
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Screening for Disease Control

Unlikely” referred to next
screening cycle
“Likely” further testing for
diagnosis

yes no
referred to next
treatment screening cycle
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Diagnosis = Screening
Screening tests can also often be used as
diagnostic tests
Diagnosis involves confirmation of
presence or absence of disease in someone
suspected of or at risk for disease
Screening is generally in done among
individuals who are not suspected of
having disease
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Natural History of Disease

Detectable subclinical disease

Susceptible Subclinical Clinical Stage of Recovery,

Host Disease Disease Disability, or Death

Diagnosis
Point of sought
Exposure

Onset of
symptoms

Screening
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Screening Process
Population
(or target group)
Screening
Test Test
Negative Positive Clinical
Exam
Unaffected Affected

Re-screen Intervene
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Screening for Disease Control

Screening Objective: To lower morbidity

and mortality of the disease in a
population (control, rather than
elimination of disease).

Screening provides access to the

medical care system which is not an
actual goal of screening, but is a benefit.
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Screening for Disease Control

Screening is important because:

Diagnostic and therapeutic advances

are often slow, but screening may be a
“direct solution” to modify history of a
disease in a population.
It provides a model for studying disease
mechanisms and the natural history of a
disease.
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Screening for Disease Control

Primary requirements for screening:

Early detection of disease leads to a

more favorable prognosis due to early
treatment, as compared to delayed
treatment.

Pre-clinical disease left untreated

typically progresses to clinically-
evident disease (e.g. no spontaneous
regression).
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Screening for Disease Control

Primary requirements for screening:

The disease should be serious (relates

to cost effectiveness, ethics, and
prognosis).

Prevalence of pre-clinical disease

should be relatively high among those
screened.
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Natural History of Disease

Age of Individual
20 30 40 45 50 55 60

Birth Exposure Cells Screened Symptom Death

Neoplasia Exfoliate Diagnosis Diagnosis
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Natural History of Disease

Age of Individual
20 30 40 45 50 55 60

Birth Exposure Cells Screened Symptom Death

Neoplasia Exfoliate Diagnosis Diagnosis

Total Pre-Clinical Phase (TPCP)

TPCP: Begins at the initiation of disease; ends when the

disease is clinically manifested (25 years in this example)
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Natural History of Disease

Age of Individual
20 30 40 45 50 55 60

Birth Exposure Cells Screened Symptom Death

Neoplasia Exfoliate Diagnosis Diagnosis

Detectable Pre-Clinical Phase (DPCP)

DPCP: Begins when screening test is able to detect

disease; Ends when disease is clinically evident (10 years)
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Impact of ScreeningImpact of Scr

on Epi Measures

Prevalence of
clinical disease Steady state
(found by
either symptoms
or screening)
Screening

Time
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Impact of ScreeningImpact of Scr

on Epi Measures

Incidence of
clinical disease Steady state

Note incidence
rises, and then
drops sharply Screening
because the
“pool at risk” is
temporarily Time
depleted
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Validity of Screening Tests

Key Measures
Reliability
Sensitivity
Specificity
Yield (performance)
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Reliability of Screening Tests

RELIABILITY:

The extent to which the screening test will

produce the same or very similar results each
time it is administered.

--- A test must be reliable before it can be valid.

--- However, an invalid test can demonstrate

high reliability.
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Reliability of Screening Tests

Sources of variability that can affect the
reproducibility of results of a screening test:

Biological variation (e.g. blood pressure)

Reliability of the instrument itself
Intra-observer variability (differences in
repeated measurement by the same
screener)
Inter-observer variability (inconsistency in
the way different screeners apply or
interpret test results)
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Use of Multiple Screening Tests

Sequential (two-stage) testing:

A less expensive, less invasive, or less

uncomfortable test is performed first…

those who screen positive are referred for

further testing using a test which may have
greater sensitivity and specificity…

reduces false positives, hence an increase in net

specificity.
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Use of Multiple Screening Tests

Simultaneous testing:

Multiple tests are used simultaneously…

Person tests “positive” if there is a positive

result on any of the tests employed…

reduces false negatives, hence an increase in

sensitivity … but at the expense of decreased
specificity.
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Validity
Validity is analogous to accuracy

The validity of a screening test is how

well the given screening test reflects
another test of known greater
accuracy

Validity assumes that there is a gold

standard to which a test can be
compared
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Disease
PresentAbsent
a b
Screening

Positive a+b
Test

Negative c d c+d
N
a+c b+d
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Disease
Present Absent
True False
Screening

Positive positivespositives
Test

False True
Negative negatives
negatives
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Sensitivity
Proportion of individuals who have the
disease who test positive (a.k.a. true
positive rate)
tells us how well a test picks up disease
Disease
Screening

yes no a
a b a+b Sensitivity =
Test

+ a+c
- c d c+d
a+c b+d
N
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Specificity
Proportion of individuals who don t
have the disease who test negative
(a.k.a. true negative rate)
tell us how well a test detects no
disease
Disease
Screening

yes no d
a b a+b Specificity =
Test

+ b+d
- c d c+d
a+c b+d
N
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Screening Principles
Sensitivity
– the ability of a test to correctly identify
those who have a disease
a test with high sensitivity will have few false
negatives
Specificity
– the ability of a test to correctly identify
those who do not have the disease
a test that has high specificity will have few
false positives
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Predictive Value
Measures whether or not an individual
actually has the disease, given the results
of a screening test
Affected by
– specificity
– prevalence of preclinical disease
– Sensitivity
Prevalence = a+c
a+b+c+d
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Measuring the performanceMea

(yield) of a screening test
People with positive screening test
results will also test positive on the
diagnostic test:
Predictive Value Positive (PV+)
People with negative screening test
results are actually free of disease
Predictive Value Negative (PV-)

30
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Performance Yield
True Disease Status
+ -

Results of + a b
Screening
Test
- c d

Predictive value positive (PV+): The probability that a

person actually has the disease given that he or she
tests positive.

PV+ = a / (a + b)
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Performance Yield
True Disease Status
+ -

Results of + a b
Screening
Test
- c d

Predictive value negative (PV-): The probability that a

person is truly disease free given that he or she
tests negative.

PV- = d / (c + d)
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Performance Yield
True Disease Status
+ -

Results of + 400 995

Screening
Test
- 100 98905

Sensitivity: a / (a + c) = 400 / (400 + 100) = 80%

Specificity: d / (b + d) = 98905 / (995 + 98905) = 99%
PV+: a / (a + b) = 400 / (400 + 995) = 29%
PV-: d / (c + d) = 98905 / (100 + 98905) = 99%
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Performance Yield
True Disease Status
+ -

Results of + 400 995

Screening
Test
- 100 98905

PV+: a / (a + b) = 400 / (400 + 995) = 29%

Among persons who screen positive, 29% are found

to have the disease.
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Performance Yield
True Disease Status
+ -

Results of + 400 995

Screening
Test
- 100 98905

PV-: d / (c + d) = 98905 / (100 + 98905) = 99.9%

Among persons who screen negative, 99.9% are found

to be disease free.
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Performance Yield
Factors that influence PV+ and PV-

The more specific the test, the higher

the PV+

The higher the prevalence of preclinical

disease in the screened population, the
higher the PV+

The more sensitive the test, the higher

the PV-
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Performance Yield

Prevalence (%) Sensitivity Specificity PV+

0.1 90% 95% 1.8%

1.0 90% 95% 15.4%

5.0 90% 95% 48.6%

50.0 90% 95% 94.7%

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Performance Yield

Thus, the PV+ is maximized when used in “high

risk” populations since the prevalence of pre-
clinical disease is higher than in the general
population….

screening a total population for a relatively

infrequent disease can be very wasteful of
resources and may yield few previously
undetected cases.
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Effectiveness of Screening

Evaluating if the screening program reduced

morbidity and mortality from the disease:

Overall shift in severity of disease at the

time of diagnosis.

Compare cause-specific mortality from

among those whose disease was picked up
by screening versus those with a diagnosis
related to symptoms.
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Effectiveness of Screening

Evaluating if the screening program reduced

morbidity and mortality from the disease:

Reduction in disease-related
complications.

Improvement of quality of life in screened

individuals.
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Effectiveness of Screening
In reality, establishing the sensitivity and
specificity of screening tests may be difficult…

often times, data are only available on persons

who screen positive and are referred for
further testing.

a b Data are available for cells “a” and

“b” only.
c d
Permits calculation of PV+ only
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Effectiveness of Screening
Sources of bias in evaluating screening
programs:

Self-selection bias (volunteer bias)

Lead time bias

Length bias

Over-diagnosis bias
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Effectiveness of Screening

Self-selection bias (volunteer bias):

--- Volunteers for screening programs may be

healthier, on average, than persons who do
not participate in screening programs.

On the other hand….

--- The “worried well” may be more likely to
participate and may be at overall higher risk
due to family history or lifestyle
characteristics.
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Effectiveness of Screening
Lead time bias:

Lead time: The interval between “diagnosis” of

disease at screening and when it would have
been detected from clinical symptoms.

--- Survival may appear to be increased

among screen-detected cases simply
because diagnosis was made earlier in the
course of the disease.
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Lead time bias

Lead time: interval between the diagnosis of a

disease at screening and the usual time of
diagnosis (by symptoms)

Lead Time

Diagnosis Diagnosis
by screening via symptoms
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Bias in Screening:
Lead-Time Bias
Consider a condition where the natural history
allows for an earlier diagnosis, however,
survival does not improve despite identifying it
earlier
A screening program here will
– over-represent earlier diagnosed cases
– survival will appear to increase
but in reality, it is increased by exactly the
amount of time their diagnosis was advanced
by the screening program
– Thus there is no benefit to screening from a
survival standpoint.
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Lead time bias

Assumes survival is time between screen and
death
Does not take into account lead time between
diagnosis at screening and usual diagnosis.
Survival = 14 years

Diagnosis Death
by screening in 2008
in 1994
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Lead time bias

Survival = 14 years

True Survival = 10 years

Lead Time 4 years

DiagnosisUsual time of Death

by diagnosis in 2008
screeningvia symptoms
in 1994 in 1998
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Effectiveness of Screening
Length bias (prognostic selection):

---- The overrepresentation among screen-

detected cases of those with a long pre-
clinical phase, and thus a more favorable
prognosis.

--- Those with a long pre-clinical phase are

more readily detectable by screening than
more rapidly progressing cases with a
short pre-clinical phase.
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Bias in Screening:
Length Bias
Most chronic diseases, especially cancers, do
not progress at the same rate in everyone.
Any group of diseased people will include some
in whom the disease developed slowly and some
in whom it developed rapidly.
Screening will preferentially pick up slowly
developing disease (longer opportunity to be
screened) which usually has a better prognosis

Paneth
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O P Y D
Biological Disease Symptoms Death
onset of detectable Begin
disease via screening

Screening
Length bias

O P Y D
O P Y D
O P Y D
O P Y D
O P Y D
O P Y D
Time
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Effectiveness of Screening
Over-diagnosis bias:

---- Persons who screen positive and are truly

disease free (false positives), yet are
erroneously diagnosed as having the
disease.

--- Since these persons are truly disease

free, we expect a more favorable long-
term outcome – giving the appearance of
an effective screening program.
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Criteria for a SuccessfulCriteria

Screening Program
Disease
– present in population screened
– high morbidity or mortality; must
be an important public health
problem
– early detection and intervention
must improve outcome
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Criteria for a SuccessfulCriteria

Screening Program

Disease
– The natural history of the disease
should be understood, such that
the detectable sub-clinical disease
stage is known and identifiable
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Criteria for a SuccessfulCriteria

Screening Program
Screening Test
– should be relatively sensitive and
specific
– should be simple and inexpensive
– should be very safe
– must be acceptable to subjects and
providers
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Criteria for a SuccessfulCriteria

Screening Program
Have an Exit Strategy
– Facilities for diagnosis and appropriate
treatments should be available for
individuals who screen positive
– It is unethical to offer screening when
no services are available for
subsequent treatment
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Screening Strategies
High-Risk Strategy
Cost-effective
Intervention
appropriate to the
individual
Fails to deal with the
root causes of disease
Subjects motivated
Small chance of
reducing disease
incidence
Population Approach
Potential to alter the
root causes of disease
Large chance of
reducing disease
incidence
Small benefit to the
individual
Poor subject motivation
Problematic risk-benefit
ratio
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Screening is notScreeni
always free of risk
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In population screening .

False positives tend to swamp true

positives in populations, because most
diseases we test for are rare
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Risks of Screening
True Positives
– labeling effect (classified as diseased
from the time of the test forward)
False Positives
– anxiety
– fear of future tests
– monetary expense
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Risks of Screening

False Negatives
– delayed intervention
– disregard of early signs or symptoms
which may lead to delayed diagnosis
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Study Designs Used to EvaluateStudy D

Screening Programs
Study Designs Used to Evaluate Screening
Programs:

Ecological Studies

Observational Analytic Studies

Randomized Trials (infrequent and

difficult to carry out)