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Screening

Advance Epidemiology
Lecture 8
Dr. Ridwan Amiruddin, MSc.PH.
Principles Underlying Screening
Programs
 Validity – the ability to predict who has the
disease and who does not
 Sensitivity – the ability of a test to correctly
identify those who have the 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
Principles Underlying Screening
Programs (cont.)
 An ideal screening test would be 100%
sensitive and 100% specific – that is there
would be no false positives and no false
negatives
 In practice these are usually inversely related
 It is possible to vary the sensitivity and
specificity by varying the level at which
the test is considered positive
Calculating Measures of Validity

True Diagnosis
Test Result Disease No Disease Total

Positive a b a+b
Negative c d c+d
Total a+c b+d a+b+c+d
Note the Following Screening Relationships
 Specificity + false positive rate = 1
d/(b+d) + b/(b+d) = 1
 If the specificity is increased, the false positive rate is
decreased
 If the specificity is decreased, the false positive rate is
increased

 Sensitivity + false negative rate = 1


a/(a+c) + c/(a+c) = 1
 If the sensitivity is increased, the false negative rate is
decreased
 If the sensitivity is decreased, the false negative rate is
increased
Probability of Disease

 Pre-test probability of disease =


disease prevalence
 Post-test probability of disease =
 If normal, c/(c+d)
 If negative, a/(a+b)
Interrelationship Between Sensitivity
and Specificity
Sensitivity and Specificity of a
Blood Glucose Level
Sensitivity and Specificity of a Blood Glucose Level of 110
mg/100 ml for Presumptive Determination of Diabetes Status
Blood Glucose Level Diabetics Nondiabetics
(mg/100 ml) (Percent) (Percent)
All those with level over 92.9 51.6
110 mg/100 ml are (false positives)
classified as diabetics (true positives)

All those with level under 7.1 48.4


110 mg/100 ml are (false negatives) (true negatives)
classified as nondiabetics

100.0 100.0
Adjusting
Sensitivity and
Specificity by
Adjusting Cut
Points
Which is Preferred: High Sensitivity or
High Specificity?
 If you have a fatal disease with no
treatment (such as for early cases of
AIDS), optimize specificity
 If you are screening to prevent
transmission of a preventable disease
(such as screening for HIV in blood
donors), optimize sensitivity
Remember….
 Sensitivity and specificity are functions
of the screening test
 If you use a given screening test on a low
prevalence population, you will have a
low positive predictive value and
potentially many false positives
Translated into Real Life…..
Elisa is about 90% sensitive and 99% specific
Population Prevalence of HIV PV+ PV-

NJ (7 million) 1.5% 58% 99.8%

Disease Yes Disease No Total


Test + 94,500 68,950 163,450
Test - 10,500 6,826,050 6,836,550
Total 105,000 6,895,000 7 million
Efficiency of test = (TP + TN)/Total tested = 98.9%
But, 10,500 people who are HIV+ think they are disease free
Another 68,950 are frightened into believing they have the
disease and require more testing
If You Change To a High Risk Population,
You Get Better Results….
Population Prevalence of HIV PV+ PV-
IV Drug User 50% 98.9% 90.8%
Disease Yes Disease No Total
Test + 3,150 35 3,185
Test - 350 3,465 3,185
Total 3,500 3,500 7,000
Efficiency of test = (TP + TN)/Total tested = 94.5%
Now 350 people who are HIV+ think they are disease free
But only 35 are frightened into believing they have the
disease and require more testing
Suppose You Have a Very High
Prevalence?

 HIV seropositivity is 90% among IV


drug users in Newark
PV+ = 99.9%
PV- = 52%
 But, why bother to screen?
Example: Breast Cancer Screening

Breast Cancer
Mammogram
Disease No Disease Total
Results

Positive 132 983 1,115


Negative 45 63,650 63,695
Total 177 64,633 64,810
Example: Disease X (prevalence = 2%)

True Diagnosis of Disease X

Test Results Disease No Disease Total

Positive 18 49 67
Negative 2 931 933
Total 20 980 1000
Example: Disease X (prevalence = 1%)

True Diagnosis of Disease X

Test Results Disease No Disease Total

Positive 9 49.5 58.5


Negative 1 940.5 941.5
Total 10 980 1000

To increase positive predictive value increase


prevalence by screening high risk populations
Importance of Prevalence in Screening
Assume we have a test for AIDS which has a sensitivity of 100% and
a specificity of 99.995%. We wish to apply it to female blood donors
who have an HIV prevalence of 0.01% and we wish to apply it to male
homosexuals in San Francisco, in whom the prevalence is 50%. For
every 100,000 screened we find:

Female Donors True Diagnosis of HIV


Test Results Disease No Disease Total
Positive 10 5 15
Negative 0 99,985 99,985
Total 10 99.990 100,000
PV+ = 0.66667
True Diagnosis of HIV
Male Homosexuals Disease No Disease Total
Positive 50,000 3 50,003
Negative 0 49,997 49,997
Total 50,000 50,000 100,000
PV+ = 0.99994
Relationship of Specificity to Predictive Value
Disease Disease
+ - + -
+ 250 250 500
500 + 100 400
Test Test
- 250 250 - 400 500
500 100
500 500 1,000 200 800 1,000
Prev = 50%, Sens = 50%, Spec = 50%, Prev = 20%, Sens = 50%, Spec = 50%,
PV = 250/500 = 50% PV = 100/500 = 20%
Disease Disease
+ - + -
+ 400 580 + 100 80 180
Test 180 Test
400 420 - 100 720 820
- 20
200 800 1,000 200 800 1,000
Prev = 20%, Sens = 90%, Spec = 50%, Prev = 20%, Sens = 50%, Spec = 90%,
PV = 180/520 = 31% PV = 100/180 = 56%
Suppose You Are Faced With the
Following Brain Teaser
 In a given population of 1,000 persons,
the prevalence of Disease X is 10%. You
have a screening test that is 95%
sensitive and 90% specific.
 What is the positive predictive value?
 What is the efficiency of the test?
Suppose You Are Faced With the
Following Brain Teaser (cont.)
1) Set up a 2x2 table
True Diagnosis of Disease X

Test Results Disease No Disease Total


Positive True Positive False Positive

Negative False Negative True Negative

Total 100 900 1000


Suppose You Are Faced With the
Following Brain Teaser (cont.)

True Diagnosis of Disease X

Test Results Disease No Disease Total

Positive 95 90 185

Negative 5 810 815

Total 100 900 1000


Principles Underlying Screening Programs
 Reliability – the ability of a test to give consistent
results when performed more than once on the same
individual under the same conditions
 Variation in the method due to variability of test
chemicals or fluctuation in the item measured (e.g.,
diurnal variation in body temperature or in relation to
meals)
 Standardize fluctuating variables
 Use standards in laboratory tests, run multiple samples
whenever possible
 Observer variation
 Train observers
 Use more than one observer and have them check each other
Principles Underlying Screening Programs
 Yield – the amount of previously unrecognized disease
that is diagnosed and brought to treatment as a result
of the screening program
 Sensitivity
 You must detect a sufficient population of disease to be useful

 Prevalence of unrecognized disease


 Screen high risk populations

 Frequency of screening
 Screening on a one time basis does not allow for the natural history
of the disease, differences in individual risk, or differences in onset
 Diseases have lead time

 Participation and follow-up


 Tests unacceptable to those targeted for screening will not be
utilized
Conditions for Establishing Screening Programs
 The condition should be an important health problem
 There should be an accepted treatment for patients with
recognized disease
 If there is no treatment, it is premature to institute
screening
 Facilities for diagnosis and treatment should be available
 It is unethical to screen without providing possibilities
for follow-up
 There should be a recognizable latent or early
symptomatic stage
 If early detection does not improve survival, there is
no benefit from screening
Conditions for Establishing
Screening Programs (cont.)
 There should be a suitable test for
examination, with sufficient sensitivity and
specificity to be of use in identifying new cases
 The test should be acceptable to the
population
 The natural history of the condition, including
development from latent to declared disease,
should be adequately understood
 There should be an agreed-upon policy
concerning whom to treat as patients
Conditions for Establishing
Screening Programs (cont.)
 The cost of case-finding should be
economically balanced in relation to
possible expenditure on medical care as
a whole

 Case-finding should be in a continuing


process and not a one-time project
Biases in Screening
 Referral Bias (volunteer bias)
 Length Bias
 Screening selectively identifies those
with a long preclinical and clinical
phase (i.e., those who would have a
better prognosis regardless of the
screening program)
Biases in Screening (cont.)
 Lead Time Bias
 The apparently better survival that is
observed for those screened is not
because these patients are actually
living longer, but instead because
diagnosis is being made at an earlier
point in the natural history of the
disease
Biases in Screening (cont.)
 Overdiagnosis Bias (a misclassification bias)
 Enthusiasm for a new screening program
may result in a higher rate of false
positives and give false impression of
increased rates of diagnosis and detection
 Also, false positives would result in
unrealistically favorable outcomes in
persons thought to have the disease