Screening tests

Natural history of disease

prepathogenesis pathogenesis
X

 Stage of prepathogenesis when there

are no symptoms of the disease

 Stage of pathogenesis, when the

disease manifests itself by certain
symptoms and signs which bring the
patient to the physician
 There are two types of tests:
Screening tests & diagnostic tests

Purpose of screening tests:

 To detect individuals with risk factors that

predispose to disease development, thus
preventive interventions could be done
(primary prevention)
 To identify persons with early or
asymptomatic ( latent disease) that can be
effectively treated leading to better
outcome (secondary prevention)
Examples

 Overt carcinoma of the cervix is preceded by a stage when

cancer cells are localized called carcinoma in situ, if detected
prevent the development of the disease

 Senile keratosis of the skin ( benign lesion) has a great

probability of transformation to malignancy, so its detection and
removal is a preventive measure

 Thus detection in the prepathogenic state or early stages of the

disease requires the examination of symptomless or apparently
healthy individuals which means
Purpose of diagnostic tests

 It is to move the estimated probability of disease toward either

end of the probability scale. When the estimated probability of
the disease is close to Zero, the disease can be ruled out, when
the estimated likelihood of a disease is close to 100, the disease
is confirmed

disease probability scale

Zero probability 100% probability

(The test is used to measure the probability of an outcome(

Screening vs. diagnostic tests
- Screening test is done in the
prepathogenic state
- Persons who are positive
are more likely to have the
disease, and who are
negative are more likely not
to have the disease
- Applied to a pop. with low
probability of the risk factor
or disease prevalence
relative to those with
symptoms
- Diagnostic test is done in the
pathogenic state
-Persons may be positive or
negative for the disease
- Applied to a pop. with high
probability of risk factor or
disease prevalence relative
to those with no symptoms
Criteria of the successful screening program

The disease:
 The disease should be common enough (high
prevalence) to warrant a search for its risk factors or
latent stages, because screening for rare disease
leads to unacceptable cost- benefit ratios

 The morbidity or mortality of the untreated condition

must be substantial (potential of screening)

 An effective preventive intervention or therapy should

exist and should have a more beneficial outcome
when applied to the prepathogenic than the
pathogenic state
Criteria for a successful screening program:

The disease:
- Early detection and intervention must improve
disease outcome

- The natural history of the disease should be

understood, such that the detectable prepathogenic
stage is known and identifiable

- Facilities for diagnosis and appropriate treatments

should be available for individuals who screen
positive
The screening test

 It must be suitable to the population and suitable for

routine application

 Maintenance of test accuracy over time and freedom

from screening related adverse effects

 A combination of the objective and subjective criteria

must be present
 Criteria of screening tests

 objective criteria  Subjective criteria

 Operating characteristics  Individual and public

( sensitivity + specificity acceptability
= validity)
( rapid, simple, painless,
with no complications)
 Predictive value ( positive &
negative)
 Financing ( inexpensive )

 Cost effectiveness
 Screening test
will divide examined apparently
healthy population

 Healthy  With abnormality

Being rapid and simple, screening test is subjected to many
errors, so a confirmatory test must be done to evaluate its
results. This will be applied for both healthy and people with
abnormality as revealed by the screening test:

confirmatory test

Healthy With abnormality

 The test done to this group
will help to assure that none
of them has the disease
 By this test some of the
healthy will be fined to have
the disease (false negative),
and others will be negative
for it ( true negative)
 The test done to this group
will help to assure that all of
them really have the disease
and none of them is negative
for it
 So, by this test some of the
population proved before to
have the disease will be
negative for it (false positive)
and others will be proved to
be positive for it ( true
positive)
Screening Confirmatory test total
test +ve -ve
+ve a b a+b
-ve c d c+d
a+b+c+d
Total a+c b+d
 a) Individuals positive by the screening test are also
positive by the confirmatory test (true positives)
 b) Individuals positive by the screening test , but
negative by the confirmatory test ( false positives)
 c) Individuals negative by the screening test , but
positive by the confirmatory test (false negatives)
 d) Individuals negative by the screening test and
negative by the confirmatory test ( true negatives)
The overall validity =
a+b+c+d
zero validity
 A 100% valid test is one that
has no false positives (b) or
false negatives (c) results
 Which means that its results
agree 100% with
confirmatory test
 So, this screening test could
be considered a diagnostic
test
(screening test= diagnostic test)
a+d %
100% validity
X
 A Zero % valid screening
test doesn’t give any true
positives (a) or true
negatives (d)
 Which means that its results
agree zero% with the
confirmatory test
( this test must be rejected)
 Sensitivity
 Definition: It is the ability of the test to give positive results in
diseased population .It is the percentage of persons with the
disease of interest who have +ve test results= a/a+c x100,(by
relating the true positives by the screening test to all positives
by the confirmatory test

 The greater the sensitivity of the test, the more likely that the
test will detect persons with the disease of interest

 Tests of high sensitivity are important to rule out the disease,

that is a –ve result would virtually exclude the possibility that
the patient has the disease of interest
 specificity
 Definition : It is the ability of the test to give negative results in free
population. It is the percentage of persons without the disease of
interest who have –ve test results = d/ d+b x 100, ( by relating the
true negatives by the screening test to all negatives by the
confirmatory tests

 The greater the specificity, the more likely that persons without the
disease of interest will be excluded by the test. Very specific tests are
used to confirm the presence of the disease

 If the test is highly specific, a positive test result would strongly

implicate the disease of interest
The effect of false positives:

- False positives tend to swamp true positives in

population, because most diseases we test for are rare

 The effect of false negatives:

- Delayed intervention

- disregard of early signs and symptoms which may

lead to delayed diagnosis
 Risks of screening:

 Labeling effect: individuals truly diagnosed to have

the disease will be positive for the disease to the end.

 Some of the individuals who were finally truly diagnosed

as not having the disease may be diagnosed as having
the disease by the screening test (false positives), these
may path through psychic trauma, spent unexpected
money to reach the final diagnosis of being healthy
Relation between sensitivity and specificity:
sensitivity and specificity are inversely
related
+ve -ve total +ve -ve total

+ve 14 8 22 +ve 10 12 22
(a) (b)
-ve 1 91 92 -ve 5 87 92
total 15 99 114 (c ) (d)
total 15 99 114
Sensitivity=a/a+cx100=14/15x Sensitivity=a/a+cx100=10/15x
100=93% 100=66.6%
Specificity= Specificity=
d/d+bx100= 91/99x100 = 92% d/d+bx100=87/99x100=87.8%
Predictive values

 Whereas the operating criteria of a test are of major

help in selecting a screening test, the predictive value
of a test is a major aid in interpretation of results.

 The operating criteria of a test are descriptors of

accuracy of a test, the predictive values are
estimations of disease probability
+ve predictive value:
 It is the probability of the presence of the
disease given the test result is positive. It is
the percentage of persons with +ve test
results who actually have the disease of
interest =(a/a+b)x100

-ve predictive value:

 It is the probability of the absence of the
disease given the test result is negative. It is
the percentage of persons with –ve test
results who actually have not the disease of
interest= (d/d+c)x100
Relation between predictive values and
disease prevalence:
screening in women with no breast mass screening in women with breast mass

+ve -ve total +ve -ve total

+ve 14 8 22 +ve 113 15 128
-ve 1 91 92 -ve 8 181 189
total 15 99 114 total 121 196 317
Prevalence=15/114x100= 13% Prevalence=121/317x100=38%
Sensitivity =14/15x100=93% Sensitivity=113/121x100=93%
Specificity=91/99x100=92% Specificity= 181/196x100=92%
+pv=14/22x100=64% +pv= 113/128x100=88%
-pv=91/92x100=99% -pv=181/189x100=96%
Sources of bias in the evaluation of a
screening program:

 Lead time bias

 Length bias
 Volunteer bias
Lead time bias:
 Lead time: it is the interval between the diagnosis of
a disease at screening and the usual time of
diagnosis by symptoms

lead time

I I

diagnosis diagnosis
by screening by symptoms
Lead time bias:

 Consider a condition where the natural history allows

for an earlier diagnosis, however survival does not
improve despite identifying it earlier

- The 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 of screening from the survival
standpoint
Lead time bias:

 Assume survival is the time between screen and

death
 Does not into account the lead time between
diagnosis at screening and usual diagnosis
survival=14 years

I I
diagnosis death
by screening in 2008
in 1994
Lead time bias

survival=14 years

I I
true survival=10 years

lead time 4 years

I I I
diagnosis usual time of death
by diagnosis in 2008
screening via symptoms
in 1994 in 1998
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 the disease developed rapidly

 Screening will preferentially pick up slowly developing

disease (longer opportunity to be screened) which
usually has a better prognosis
O P Y D
biological disease symptoms death
onset of detectable begin
disease via screening

Screening
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
Volunteer bias:

 This occurs when those accept to participate are

different from the others

 Volunteers tend to have:

- better health
- lower mortality
- likely to adhere to prescribed medical regimens
Screening in breast cancer

 There is an evidence of effectiveness that breast physical

ex.& breast mamography done annually to women above
50years will reduce mortality of breast cancer
 Risks :
 Each rad of radiation delivered to the breast increases
woman’s chance to develop breast cancer by
6/1000.000/year. This increases for developing breast
cancer by less than 1% each time
 False positive results occur in 1.5% of examination, which
leads to biopsies that are unnecessary.
 cost effectiveness: is measured by comparing the reduction
in mortality achieved with the financial costs of screening
*2/3 of the effectiveness of breast cancer screening program
can be achieved by screening with physical examination only

* Adding mammography increases the effectiveness more

than 50% but increases the cost

*The cost of increasing life expectancy by reducing mortality

from cancer= 5000$ for physical ex.

* Adding annual mamography gains additional year of life

expectancy at a cost of 25000$
 Conclusion

 Sensitivity will determine the number of diseased people that will be

missed (false -ve) and this increases when sensitivity decreases.

 Specificity will determine the number of well people wrongly

included as diseased ( false positive) and this increases when
specificity decreases.

 A test with false positives gives false alarm and psychological

trauma

 A test with false negatives gives a false sense of security and the
disease may progress to non-curable stage

 High disease prevalence will increase the + pv and decrease the - pv