Screening

Berhe Beyene (Email: berhebeyene200@gmail.com)

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What is screening?

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 Definition
 Search for unrecognized disease or defect by means
of rapidly applied tests, examinations or other
procedures in apparently healthy individuals.

 The goal is early detection and lifestyle changes or

surveillance, to reduce the risk of disease, or to
detect it early enough to treat it most effectively.

 A screening test is not intended to be diagnostic.

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 Screening Test Vs Diagnostic Test

 A screening test identifies asymptomatic individuals

who may have the disease.

„ A diagnostic test is used to determine the

presence or absence of a disease when a subject
shows signs or symptoms of the disease

 The diagnostic test is performed after a positive screening test to

establish a definitive diagnosis

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 Some Common Screening Tests
 „ Pap smear for cervical dysplasia or cervical cancer
 Fasting blood cholesterol for heart disease
 Fasting blood sugar for diabetes
 Blood pressure for hypertension
 „ Mammography for breast cancer
 PSA test for prostate cancer
 Fecal occult blood for colon cancer
 Ocular pressure for glaucoma
 PKU test for phenolketonuria in newborns
 Thyroid stimulating hormone(TSH) for hypothyroid and
hyperthyroid
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 Diseases Appropriate for Screening
1. Important public health problem – frequent or serious

2. Reasonably long, recognizable pre-symptomatic stage

3. Effective treatment exists and is available, or effective

ways of preventing spread

4. Treatment (or measures take to prevent spread) should

be more effective if initiated in the pre-symptomatic
stage than when initiated in symptomatic patients
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Diseases Appropriate for Screening cont’d

5. A suitable screening test or procedure should

be available and be:
I. Reliable
II. Sensitive and specific
III. Acceptable to the population screened
IV. Reasonably inexpensive and safe

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Criteria for instituting a screening programme

Disease -Serious
-High prevalence of preclinical stage
-Natural history understood
-Long period between first signs and overt disease
Diagnostic test -sensitive and specific
-Simple and cheap
-safe and acceptable
-Reliable
Diagnostic and -Facilities are adequate
treatment -Effective, acceptable, and safe treatment
available

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 WHO Criterion for Screening
 Is it a health problem?
 Is there treatment?
 Are there facilities in place?
 Is it detectable pre-clinically?
 Is there a suitable screening test?
 Is the screening test acceptable to people?
 Is the natural history of disease understood?
 Are the costs acceptable?

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 Types of screening
There are different types of screening, each
with specific aims
a) Mass screening – involves screening of the
whole population
b) Multiple or multiphase screening – involves a
variety of screening tests on the same
occasion.

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 Types of screening cont’d
c) Targeted screening of groups with specific
exposures – is often used in environmental
and occupational health
d) Case-finding or opportunistic screening – is
restricted to patients who consult a health
practitioner for some other purpose

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 Validity of a Screening Test
 Validity of a test is the ability to differentiate
accurately between those who have the disease and
those who do not(indicate which individuals have the
disease and which do not).
 Sensitivity and Specificity are two measures of the
validity of a screening test.
 Sensitivity and specificity can also be taken as
measures of validity for other tests which are applied
for diagnostic purposes.

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 Sensitivity
The ability of a test to correctly identify those
who have the disease

 The percentage of those who have the disease

and are proven to have the disease as
demonstrated by a test

The probability of a positive test in people

with the disease
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 Specificity
The ability of a test to correctly identify those
who do not have the disease

The probability of a negative test in people

without the disease

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Two-by –two table for the calculation of validity of screening
tests

Definitive Diagnosis

Screening Test Diseased Non Diseased Total

Positive TP(a) FP(b) TP+FP(a+b)

Negative FN(c) TN(d) FN+TN(c+d)

Total TP+FN(a+c) TN+FP(b+d) TP+FP+TN+FN

(a+b+C+d)

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 Validity cont’d

Sensitivity = TP X 100 a
TP+FN   100
=Pr(T+|D+)
ac

Specificity = TN X100
d
TN + FP   100
=Pr(T−|D−) bd
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 Validity cont’d
E.g. A group women aged 40-64 assigned into two
groups, i.e. screened vs. comparison. The women in
the screened group were offered an initial screening
examination for breast cancer (mammography and
physical examination) followed by three follow-up
examinations at yearly intervals. The women in the
comparison group were not offered the screening
examination but rather continued to receive their
usual care.

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 Validity cont’d
 Total of 64,810 screening examinations were performed
among the study populations. During the first 5 years of
observation, 132 breast cancers were diagnosed among
1,115 biopsies or aspirations that were recommended on
the basis of the results of the screening procedures.

 45 cases of breast cancer were detected among women

who screened negative but were diagnosed with the
disease during subsequent years. These women were
assumed to have been false negatives.

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 Group discussion
Group of 3 to 4 members
Prepare a two by two table and calculate
measures of validity of the test?

Time given: Ten minutes

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 Validity cont’d
Table 1: Sensitivity and specificity of breast cancer screening examination (Health Insurance
Plan of Great New York (HIP Program)

Breast cancer
Cancer cancer not Total
Confirmed confirmed

Screening test (Physical

Examination & mammography)
Positive 132 983 1115
Negative 45 63,650 63,695
Total 177 64,633 64,810
Sensitivity =132/177 = 74.6%
Specificity = 63,650/64,633 = 98.5%
PV+ = 132/1115 = 11.8 %
PV- = 63,650/63,695 = 99.9%

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 Validity cont’d
 Sensitivity: Among women diagnosed with breast
cancer during the study period, approximately 75 %
tested positive on the screening procedure

 Specificity: 98.5 % indicates that virtually all women

who did not have the disease tested negative

 A highly specific test will rarely be positive in the

absence of disease and will therefore result in a lower
proportion of persons without disease who are
incorrectly classified as test-positive
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(false positive). 21
 Validity cont…
 Obviously, it would be desirable to have a screening test that
has both highly sensitive and highly specific. Usually that is
not possible, and there is generally a trade off between the
sensitivity and specificity of a given screening test.

 Any decision regarding specific criteria for acceptable levels of

sensitivity and specificity in a given situation involves
weighing the consequences of leaving cases undetected (false
negative) against erroneously classifying healthy persons as
diseased (false positive).

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 Balance in choosing a screening test
• Disease serious & definitive • High risk with further
treatment exists diagnostic techniques

• Disease is highly • High cost with further

communicable diagnostic techniques

• Subsequent evaluation of • No definitive treatment exist

positives is not costly and has
minimal risk

Sensitivity Specificity

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Sensitivity and specificity at different levels
Cutoff points
Persons

A B C
True Negatives

Non True Positive

hypertensive
Hypertensive

50 80 120 Diastolic BP

False Negatives False Positive

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 Sensitivity and specificity...

 Set point at A; 100% sensitivity, FN=0 FP

increases, specificity decreases
 Set point at B; Sensitivity = 81.4%,
Specificity = 82.4%
 Set point at C; 100% specificity, FP = 0, FN =
increases, sensitivity decreases
NB: A highly Specific test is preferable when false
positive results might have negative (physical,
emotional or financial) consequences.

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Cut-points of sensitivities and specificities

• Different cut-points yield different sensitivities

and specificities
• „ The cut-point determines how many subjects
will be considered as having the disease
• „ The cut-point that identifies more true
negatives will also identify more false
negatives
• The cut-point that identifies more true
positives will also identify more false positives
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 Cut-points of sensitivities and specificities…
 „ If the diagnostic (confirmatory) test is expensive or
invasive:
 Minimize false positives or use a cut-point with high
specificity
 „ If the penalty for missing a case is high (e.g., the
disease is fatal and treatment exists, or disease
easily spreads):
 Maximize true positives. That is, use a cut-point with
high sensitivity
 „ Balance severity of false positives against false
negatives
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 Multi-stage testing
 One way of addressing the problem of the trade-off
between sensitivity and specificity is to use the
results of several screening tests together
 Commonly done in medical practice
 „ Choices depend on cost, invasiveness, volume of
test, presence and capability of lab infrastructure,
urgency, etc.

 These tests can be administered either in

parallel/simultaneous or in series/sequential.

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 Parallel testing
 When screening tests are given in parallel, all are
administered at the same time, and persons with
positive results on any test are considered positive.

 Parallel testing results in increased sensitivity

compared with that of each individual test
 It lower specificity because false positive diagnoses
are also more likely.

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 Sequential testing
When screening tests are given in series, an
initial screening test is administered, and only
persons with positive test are evaluated with
an additional screening procedure.

Testing in series results in an increase in

specificity compared with a single test

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Sequential testing: Re-screen the Positives
from the first test
Subject is disease positive when test positive
in both tests

Subject is disease negative when test negative

in either test

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 Predictive Value of a Screening Test
Predictive value is the ability of a test to predict the
presence or absence of disease from test results.
 1. Predictive Value of a Positive Test (PVPT) or
Positive Predictive Value
 probability that the person tested positive by this
specific test truly has the disease.

PVPT = TP X 100  a
TP+FP PV   100
ab
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 Predictive Value cont’d
2. Predictive Value of a Negative Test (PVNT) or
Negative Predictive Value

 The probability that an individual is truly

disease-free given a negative screening test
PVNT = TN X 100  d
TN+FN PV   100
cd

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 Predictive Value cont’d
Example: Refer table 1.
 PVPT = 11.8 % means the probability that a woman who tested
positive on the screen actually had breast cancer is 11.8%.
 PVNT = 99.9% means the probability that a woman who tested
negative truly did not have breast cancer is 99.9%.

 The ability to predict the presence or absence of diseases from

test results is dependent on the prevalence of the preclinical
disease in the population tested, as well as on the sensitivity and
specificity of the test.

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 Predictive Value cont’d
The higher the prevalence, the more likely it
is that a positive test is predictive of the
diseases i.e PVPT will be high.

The more sensitive a test, the less likely it is

that an individual with a negative test will
have the disease ( FN), and thus the greater
the predictive value negative.

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 Predictive Value cont’d
 The more specific the test, the less likely an
individual with a positive test will be free from the
disease ( FP) and the greater the predictive value
positive.

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Example 1 : The table below shows relation between results of liver
scan and diagnosis in 344 patients

Liver scan test Pathology Total

Abnormal Normal

Abnormal 231 32 263

Normal 27 54 81

Total 258 86 344

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Based on the given conditions in the table calculate:

a) Sensitivity?

b) Specificity?

c) Positive predictive value? and

d) Negative predictive value?

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Solutions

a) Sensitivity = No. of true positives X 100

Total number of diseased persons

= (231/258) x 100 = 89.5%

b) Specificity = No. of true negatives X 100

Total number of disease free persons

= (54/86) x 100 = 62.8%

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c) PV+ = True positives X 100

Total positives (TP + FP)

= (231/263) x 100 = 87.8%

d) PV- = True negatives X 100

Total negatives (TN + FN)

= (54/81) x 100 = 66.7%

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Example 2:

A hypothetical disease has a prevalence of 2%.

Sensitivity of a test being considered is 90% and the
specificity is 95%. The population being tested consists
of 1000 people.

Test result True disease status Total

Disease Non-disease
Positive 18 49 67
Negative 2 931 933
Total 20 980 1000
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Total disease -2/100 x 1000 = 20

Sensitivity = Tp/total disease

90% = Tp/20

Tp = 0.9 x 20

Tp = 18

FN = 20-18

=2
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 Specificity = TN/total non- disease
95% = TN/980
TN = 0.95 x 980
TN = 931
FP = 980-931
= 49
Predictive value a positive test-
(PV+) = 18/18+49 x 100
= 27%
Predictive value a negative test-
(PV-) = 931/2+931 x 100
= 99.8%%
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Example :

If the same test (having the same sensitivity & specificity)

if the prevalence of the disease is lowered to 1%.

Test result True disease state Total

Disease Non-disease

Positive 9 49 58

Negative 1 941 942

Total 10 990 1000

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Predictive value a positive test-

(PV+) = 9/9+49 x 100

= 15.5%

Predictive value a negative test-

(PV-) = 941/941+49 x 100

= 99.89%%

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Exercise 1:

A New diagnostic test for a certain disease was evaluated using a

group of 100 persons at high risk for the disease. Sixty of them were
found to be positive by the test. After the 100 people underwent
further clinical evaluation, the disease was confirmed in 50 people,
including in 40 who had been found positive by the test.

1. Show the results in the form of 2x2 table

2. Fill the marginal totals

3. How many TP, TN,FP,FN were there?

4. Calculate sensitivity and specificity

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 Exercise 2
 In a group of 500 children, 50 have a genuine hearing problem.
Of these, 45 fail the school hearing test, as do 30 of the children
with normal hearing (perhaps they had a cold on the day of the
test). Based on this scenario
 Develop the two- by-two table
 What percentage of children with a real hearing problem failed
the school test?
 What percentage of children with normal hearing passed the
school test?
 What percentage of children who failed the school hearing test
had a real hearing problem?
 What percentage of children who passed the school hearing test
really did have normal hearing?
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 Reliability(Precision)

 Reliability refers to the consistency of results when

repeated examinations are performed on the same
persons under the same condition.

 Measured using Percent agreement and Cohen’s

Kappa

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 1. Percent agreement
„
 Is the ability of a screening program to correctly classify
individuals either as truly affected or truly unaffected
 It is proportion of correctly categorizing of
individuals among the total tested individuals
 A perfect agreement occurs when:
 b=0
 c=0

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Percent agreement…

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 Reliability…
1. Cohen’s Kappa
 Difference between observed and expected
agreement expressed as a fraction of the
maximum difference and ranges between -1 to
1.
 Is an appropriate reliability measure (or
measure of agreement) for a screening test
which gives a categorical result
 It considers agreement that may occur by
chance alone
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Measures of Reliability - Kappa

Applies to categorical measures

Designed to take chance into account
• Defined as:

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 Cohen’s Kappa

• Po = a + d/P1 = proportion observed agreement

• Pe = P1.P2 + Q1.Q2 = proportion expected
agreement
• kappa = (Po - Pe)/(1 - Pe)

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Measures of Reliability – Kappa...
• Cohen’s kappa is thus the agreement adjusted for that expected by
chance
Self Interview Total
-administered Yes No
questionnaire Yes 61 2 63
No 6 25 31

an nt
Total 67 27 94

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 Measures of Reliability - Kappa

The range of Kappa is between -1 ( perfect

disagreement) through 0 ( agreement by
chance) and +1 (perfect agreement) .

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Reliability…..
 The source of variability that can affect the
reproducibility of results of screening test include:
 Biological variation –varies considerably for a given
individual with time and other
 Related to instrument- which relates to the reliability of
the instrument itself, such as standard mercury
sphygmomanometer for BP

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 Reliability…..
Intra-observer variability – differences in repeated
measurements by the same screener. The difference is due to
the changes (such as physiological, environmental, etc.)
occurring to that individual over that time period).

Inter-observer variation – in consistencies attributable to

differences in interpretation of measurement by different
screeners.
 The difference is due to the extent to which
observer(s) agree or disagree when interpreting the
same test result
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 Sources of variability cont’d
These variations can usually be reduced by:
1. Careful standardization of procedures
2. An intensive training period for all
observers (or interviewers)
3. Periodic checks on their work
4. The use of two or more observers making
independent observations.

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 Evaluation of screening program
 Two issues: Feasible and effective program . Both must be
considered carefully.

 No matter how effective a screening procedure is in

reducing subsequent morbidity and mortality, it will not be
accepted if it can not be conducted efficiently.

 The implementation of a screening program, no matter

how cost-effective, will not be warranted if it does not
accomplish its goal of reducing morbidity and mortality.

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 Feasibility
The feasibility of a screening program is
determined by a number of factors related to
program performance which measure:
 The acceptability of the program to the
potential screenees, measured by
number of persons examined
proportion of the target population that is
screened.

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 Feasibility cont’d
 cost-effectiveness
The costs of the screening program must be considered in terms
of
 total costs
resources expended per detected case of the disease.
 the subsequent diagnosis and treatment. Screening program must also
include provision for follow up of persons whose screening tests are
positive. This can be measured by:
 Proportions of those with positive tests who are followed, diagnosed, and treated.

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 Feasibility cont’d
The yield (number of cases detected by the
screening program).
Persons with the disease
Yield = detected by the test
X 100
Total screened
  TP
Yield = X 100
TP + FN + TN + FP
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 Strategies to Increase Yield of Screening
 Select a test with high specificity
– High sensitivity >> Low false - > > High PV-
– High specificity > > Low false + > > High PV+
 Select disease with high prevalence of pre-
clinical stage
Target high risk group for screening

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 Effectiveness
 Evaluation of effectiveness of a screening program
must be based on measures that reflect the impact
of a program on the course of a disease.

 An effective screening program should result in

reduction of morbidity, mortality and disability.

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 Study designs used to evaluate screening programs
1) Correlational studies
• Have been used to examine trends in disease
rates in relation to screening frequencies
within a population, or to compare the
relationship between the frequencies of
screening and disease rates for different
populations
• These studies can suggest the possibility of a
benefit of a screening program, but they can
not test that hypothesis
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 Study designs cont…
2) Case control studies
Individuals with and without the disease are
compared with respect to their past exposure
(screening)

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 Study designs cont…
3) Cohort studies
• the case-fatality rate of those who chose to be
screened is compared with the comparative rate
among those whose diagnoses were symptom-
related.
• is the most frequently used approach.
• in interpreting the results of such studies, the
potential effects of the self-selection of participants
as well as lead-time and length bias must be taken
into account.
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NB:
Lead-time bias: The period between when disease is
detected by screening and when it would have
become symptomatic and been diagnosed in the
usual way.

Length-time bias: When there is a screen for disease, it

is more likely to detect cases where the disease is
progressing slowly. Because rapidly developing
disease will come to clinical attention sooner and so
be more likely to be diagnosed outside a screening
programme.

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 Study designs cont…
4) Randomized trial
• Since no comparability of screened and symptom-
diagnosed cases is the chief threat to validate, the
optimal assessment of the efficacy of screening
program derives from randomized trials
• The screening program is allocated at random by the
investigators after individuals have agreed to
participate in the trial

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 Study designs cont…
• The Health Insurance Plan (HIP) breast cancer screening
project, New York, was a randomized trial designed to
evaluate whether periodic breast cancer screening with
mammography and physical examination would result in
reduced breast cancer mortality among women aged 40 to 64
years.

• After 9 years of follow up, there was an overall statistically

significant reduction in breast cancer mortality among
women who were offered screening compared with women
assigned to continuing to receive their usual medical care.

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Questions ?

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