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SCREENING
Dr. Vineeta
Shukla
st
Outline
 Definition and Concept
 Iceberg Phenomenon of Disease
 Screening vs Diagnosis
 Concept of Lead Time
 Examples of Screening
 Types of Screening
 Characteristics of a Screening Test
 Evaluating a Screening Test
 Baye’s Theorem
 Screening in Series and Parallel
 Problem of the Borderline
 Kappa Statistics
 ROC Curve
Definition
 Defined as “ the search for
unrecognized disease or defect
by means of rapidly applied tests,
examinations or other procedures
in apparently healthy individuals.”
Iceberg Phenomenon of
Disease
•Biggest Challenge in Preventive Medicine
Screening : A form of
Secondary Prevention
•Earlier done to conserve physician’s time for
diagnosis , administer inexpensive lab tests etc
•Now-a-days Screening is
considered a form of
Secondary prevention
•It detects disease in its early
Asymptomatic phase whereby
early treatment can be given and
disease can be cured or its
progression can be delayed
SCREENING DIAGNOSIS
Done on Apparently healthy Done on Cases
Applied on Population groups Applied on individual basis
Test result is finalDiagnosis and
confirmation
Diagnostic Test result is not final
Based on one criterion or cut off
point
Based on Signs and Symptoms
Less accurate More accurate
Less expensive More expensive
Rapid test,faster Time Consuming
Not a basis for Treatment Basis for Treatment
Initiative comes from the
investigator
Initiative comes from patient
Concept of Lead time
How much we are ‘leading’ the
time of detection of the disease (
The Advantage gained by
Screening)
Examples of Screening
SCREENING TEST(S) DISEASE SCREENED
VIA , Pap Smear Cervical Cancer
Breast Self Examination(BSE) Breast Cancer
Mammography Breast Cancer
Bimanual Oral Palpation Oral Cancer
ELISA HIV
Urine for Sugar , RBS Diabetes mellitus
AFP ( Alpha Feto Protein) Developmental anomalies in
fetus
Prostate Specific
Antigen(PSE)
Prostate Cancer
Fecal Occult Blood Test Colorectal Cancer
Uses of Screening
1. CASE DETECTION : Presumptive Screening
“ Presumptive identification of unrecognized
disease
which does not arise from a patient’s request
.”
Example : Neonatal Screening
The people are screened
primarily for their own
benefit.
2. CONTROL OF DISEASE : Prospective
Screening
People are examined for the Benefit of others
Example :
-Screening of Immigrants to protect home population
-Screening for HIV,
STIs etc
3. RESEARCH PURPOSES :
•To know the Natural History of Chronic diseases
4. EDUCATIONAL OPPORTUNITIES :
-Acquisition of Information of Public Health
relevance
-Providing opportunities for creating Public
awareness
-For educating Health Professionals
Types of Screening
1. MASS SCREENING :
Applied generally on large unselected
populations regardless of the probability
of having the disease or condition.
Example :
-Visual defects in all school children
-Chest Xray in elderly
for detection of
Lung Cancer
-Mammography
For breast cancer
Among women
2. HIGH RISK/SELECTIVE
SCREENING : Applied on high risk groups.
Example :
-Screening for HIV in commercial sex workers.
-Screening fetus for Down’s Syndrome in a
mother who has already had a Down’s
Syndrome baby in the past
-Screening for Ca Cervix
In low SE status women
3. MULTIPHASIC SCREENING :
Various Screening tests are applied during
the same screening program.
Example :
-Annual Health Check up(DM, Lipid
profile, LFT, KFT)
4. MULTIPURPOSE SCREENING :
When >1 Test is applied simultaneously to
detect >1 Disease.
Example :
-Screening of Pregnant women for VDRL ,
HIV , HBV by serological tests
5. OPPORTUNISTIC SCREENING :
Example – Screening for Rheumatic
Heart disease in school children
CRITERIA FOR SCREENING
 Before initiating a Screening
Programme , a decision must be
made whether it abides to all the
ethical, scientific and financial
justification.
 The priniciples that should govern a
Screening Programme were first
enunciated by Wilson and
Jugner(1968)
 Criteria based on – The Disease
Wilson and Jugner Criteria(1968)
A : The Disease
 Knowledge of the Disease
(i)The condition should be important
(ii)There must be a recognisable latent or
early symptomatic stage
(iii)Natural course of condition,including
development from latent to declared
disease, should be adequately
understood
 Knowledge of Test
(iv)Suitable test or examination
(v)Test acceptable to population
(vi)Case finding should be continuous , not
just ‘once and for all’ project
 Treatment for Disease
(vii)Accepted treatment for patients with
recognised disease
(viii)Facilities for diagnosis and treatment
available
(ix)Agreed policy concerning whom to
treat as patients
 Cost Considerations
(x) Cost of case finding should be
economically balanced in relation to
possible expenditure on medical care as
a whole
B : The Screening Test
 Simple
 Acceptable to Subjects and Providers
 Reliable : Precision, Reproducible,
Repeatability – Observer Variation
Biological Variation
Technical error
 Valid : Accuracy
 Safe
 Cost effective
 Yielding : the amount of previously
unrecognized disease that is
diagnosed and brought to treatment
as a result of the screening programme.
Components of Validity
 Sensitivity
 Specificity
 Predictive Accuracy
Result of a Screening Test
DISEASE
PRESENT
DISEASE
ABSENT
TOTAL
Screening Test
POSITIVE
True Positive
( TP) (a)
False
Positive (FP)
(b)
Total Positive
by Test = a +
b
Screening Test
NEGATIVE
False
Negative
(FN) (c)
True
Negative
(TN) (d)
Total
Negative by
Test = c + d
Total
Diseased = a
+ c
Total Non-
diseased =
b + d
Total
population=
a+b+c+d
Sensitivity
 Ability of a Test to identify correctly all
those who have the disease ( True
Positive)
 Also called as Positivity in Disease
X 100
=
X 100
X 100
Specificity
 Ability of a Test to identify correctly those
who do not have the disease( True
Negative)
X
100
=
=
X 100
X 100
Example :
Q : ELISA was used as a Screening Test for HIV
among 1000 healthy blood donors. The results of
the test are as follows. Calculate Sensitivity and
Specificity
HIV Positive HIV Negative
ELISA
Positive
95 (a) 45 (b) a + b = 140
ELISA
Negative
5 (c) 855 (d) c + d = 860
a + c = 100 b + d = 900
Sensitivity =
= (95 / 100) x 100
= 95%
Specificity =
= (855/900) x 100
= 95%
X 100
X 100
Problems with FP and FN
 False Positives :
-Further testing with long , expensive tests
-Discomfort , inconvenience , anxiety
-Burden on health facilities
-Emotional trauma
-Difficulty in de-labelling
 False Negatives :
-False Reassurance
-Ignores any disease signs and symptoms
-Postponement of treatment
-Detrimental to overall health
Positive Predictive Value
 Ability of a Screening Test to identify
correctly all those who have the
disease , out of all those who test
positive on a screening test
 Also called Post Test Probability
PPV = [a /(a+b) ] x 100
X 100
Negative Predictive Value
 Ability of a Screening Test to identify
correctly all those who do not have the
disease , out of all those who test
negative on a screening test
NPV = [ d/(c+d) ] x 100
X 100
Calculate PPV and NPV
HIV Positive HIV Negative
ELISA
Positive
95 (a) 45 (b) a + b = 140
ELISA
Negative
5 (c) 855 (d) c + d = 860
a + c = 100 b + d = 900
PPV =
= (95/140) x 100
= 68 %
NPV =
= (855/860) x 100
= 99 %
Problems with PPV and NPV :
 While Sensitivity and Specificity of a
particular Screening test are constant
PPV and NPV are largely dependent on
the Prevalence of the disease in the
Population
 Example :
Q:The sensitivity and specificity of ELISA
in diagnosing HIV infection is 99% and
90% respectively, prevalence of HIV =
40%. Total Population (Commercial sex
workers) is 10,000.Calculate PPV and
Prevalence = 40%
Total HIV positive = (40/100) X 10,000=
4000.
and HIV negative = 10,000 - 4,000 = 6000.
Sensitivity of ELISA is 99%
TP : (99 /100) x 4000 = 3960
FN : 4000 - 3960 = 40
Specificity is 90%, it will correctly call, as
negative,
TN : (90/100) of 6000= 5400
FP : 6000 - 5400 = 600
HIV Positive HIV Negative
ELISA
Positive
3960 (a) 600 (b) a + b =
4560
ELISA
Negative
40 (c) 5400 (d) c + d =
5440
Total = 4000 Total = 6000
 PPV = [ a /(a+b)] x 100
= (3960/4560) x100
= 0.86 x 100 = 86%
 NPV = [ d/(c+d)] x 100
= (5400/5440) x 100
= 0.99 x 100 = 99%
Baye’s Theorem
 If the test results are +ve , what is the
probability that the patient has the
disease?
 If the test is negative , what is the
probability that the person doesn’t
have the disease?
 Baye’s Theorem provides answer
 It was first described by Clergyman
Formula :
Baye’s Theorem
Relationship between PPV of a Screening Test
and Sensitivity, Specificity and Prevalence of
disease in a population:
PPV
NPV [ ]
[ ]
Likelihood Ratio
 Incorporates both the Sensitivity and
Specificity of the test and provides a
direct estimate of how much a test
result will change the chances of
having a disease
 Sensitivity (TP) = 1- FN
or FN = 1 – Sensitivity
 Specificity (TN) = 1- FP
or FP = 1 - Specificity
Likelihood Ratio Positive (LR
+)
Example : If the sensitivity of ELISA is 99% (i.e.
0.99) and specificity is 90% (i.e. 0.90), then
A positive result on ELISA for HIV is 9.9 times
more likely to occur in a subject with HIV infection
as compared to a subject who does not have HIV
infection
Likelihood Ratio Negative (LR
-)
Example : If the sensitivity of ELISA is 99%
(i.e. 0.99 and specificity is 90% (i.e. 0.90),
then
The interpretation is that a negative result is only
one
hundredth times likely to occur in a person who
really has HIV infection as compared to a person
Tests in Series and Parallel
• SERIES : One Test after Another
2nd Test is applied only after 1st Test is
Positive
• PARALLEL : Both Tests are applied together
Series Parallel
Sensitivity Decreases Increases
Specificity Increases Decreases
PPV Increases Decreases
NPV Decreases Increases
 STa( Sn= 90%) in 100 patients
+ve in 90/100 patients
STb( Sn=90%) in 90 patients
+ve in 90% of 90 = 81
patients
STa STb
90/100 90/100
+ve cases +ve cases
So, Sensitivity Increases in Parallel
In Series :
 Combined Sensitivity of 2 Tests A & B
in series = Sn(A) x Sn(B)
 Combined Specificity of 2 Tests A & B
in series = [ Sp(A) + Sp(B)] – [Sp (A) x
Sp(B)]
In Parallel :
 Combined Sensitivity of 2 tests A & B in
Parallel = [ Sn(A) + Sn(B)] – [Sn (A) x
Sn(B)]
 Combined Specificity of 2 Tests A & B in
Parallel = Sp(A) x Sp(B)
Unimodal & Bimodal Distribution
(problem of the borderline)
Problem of the Borderline
Which of the two Qualities ( Sensitivity or
Specificity) is more important in Screening?
Kappa Statistics
 Reliability can be statistically assessed
by estimating the degree of agreement
between two measurements
 Example : Consider a study on
pulmonary TB, with AFB positivity on
sputum smear as the method of
measurement. For assessing the inter -
observer reliability,(between the
microbiologist and Lab technician), we
took 200 stained slides and each slide
was examined by both of them.The
results are given as :
POSITIVE NEGATIVE TOTAL
TECHNICIAN’s
DIAGNOSIS
POSITIVE 13 (a) 7 (b) 20 (p1)
NEGATIVE 24 (c) 156 (d) 180 (q1)
TOTAL 37 (p2) 163 (q2) n=200
MICROBIOLOGIST’S DIAGNOSIS
 K
O : Observed Agreement
E : Expected Agreement(expected in
chance)
 O = (a+d) / n
= (13 + 156) / 200 = 169/200 = 0.85
 E = [(20 x 37) + (180 x 163)] /
(200x200)
= (740 + 29340)/40000
= 30080/40000=0.75
 K =
= (0.85 – 0.75) / (1 – 0.75)
=0.10/0.25
= 0.40
Kappa Coefficient
 Value between 0 and 1
 0 : The 2 measurements agree simply
because of chance
 1 : The 2 measurements agree perfectly
irrespective of chance
 Nearer the K to 1 better the agreement
 K between
0 - 0.25 : Mild agreement
0.25 - 0.50 : Moderately strong
0.50 - 0.75 :Strong agreement
0.75 – 1.00 : Very strong / excellent
Interpretation :
 Moderately Strong agreement
 Kappa coeff is 0.4 means that the
observed agreement between the 2
observers of assessing AFB positivity is
0.40
or 40% of the way between a
coincidental
agreement purely by chance and a
perfect
Bias in Screening
1.Lead Time Bias :
-Over estimation of survival duration due to
earlier detection by screening than clinical
presentation
2. Length Bias
-Over estimation of survival duration due to the
relative excess of cases detected that are
slowly progressing
3. Self Selection Bias
-If the groups which are offered screening are
not constituted by random allocation but
Receiver Operator
Characteristic Curve
(Relationship between
Sensitivity & Specificity)
History
 The name ‘ Receiver Operator
Characteristic’ came from “ Signal
Detection Theory” developed during
World War II for analysis of Radar
Images
 Radar operators had to decide whether
a blip on the screen
represented an enemy
target, a friendly ship
or just noise
 True Positive: Correct early warning of
enemy ships crossing the English Channel
 False Positive : When Radar operator sent
out an alarm but no enemy ships appeared
 False Negative: When enemy ships
appeared without previous warning from the
radar operator
More the area of the Curve , Better the Test
Area Under ROC Curve
Perfect = 1 Random = 0.5
Conclusion
 Screening , despite its flaws is a major
Public health determinant
 Establishing appropriate criteria
requires considerable knowledge of
the Natural history of disease,
adequate facilities for follow up and
treatment
 It is necessary to ensure that the
program is continuously monitored to
confirm that effectiveness is
maintained (benefits>cost)
ThankYou 

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Screening of Diseases

  • 2. Outline  Definition and Concept  Iceberg Phenomenon of Disease  Screening vs Diagnosis  Concept of Lead Time  Examples of Screening  Types of Screening  Characteristics of a Screening Test  Evaluating a Screening Test  Baye’s Theorem  Screening in Series and Parallel  Problem of the Borderline  Kappa Statistics  ROC Curve
  • 3. Definition  Defined as “ the search for unrecognized disease or defect by means of rapidly applied tests, examinations or other procedures in apparently healthy individuals.”
  • 4. Iceberg Phenomenon of Disease •Biggest Challenge in Preventive Medicine
  • 5. Screening : A form of Secondary Prevention •Earlier done to conserve physician’s time for diagnosis , administer inexpensive lab tests etc •Now-a-days Screening is considered a form of Secondary prevention •It detects disease in its early Asymptomatic phase whereby early treatment can be given and disease can be cured or its progression can be delayed
  • 6. SCREENING DIAGNOSIS Done on Apparently healthy Done on Cases Applied on Population groups Applied on individual basis Test result is finalDiagnosis and confirmation Diagnostic Test result is not final Based on one criterion or cut off point Based on Signs and Symptoms Less accurate More accurate Less expensive More expensive Rapid test,faster Time Consuming Not a basis for Treatment Basis for Treatment Initiative comes from the investigator Initiative comes from patient
  • 8. How much we are ‘leading’ the time of detection of the disease ( The Advantage gained by Screening)
  • 9. Examples of Screening SCREENING TEST(S) DISEASE SCREENED VIA , Pap Smear Cervical Cancer Breast Self Examination(BSE) Breast Cancer Mammography Breast Cancer Bimanual Oral Palpation Oral Cancer ELISA HIV Urine for Sugar , RBS Diabetes mellitus AFP ( Alpha Feto Protein) Developmental anomalies in fetus Prostate Specific Antigen(PSE) Prostate Cancer Fecal Occult Blood Test Colorectal Cancer
  • 10.
  • 11.
  • 12. Uses of Screening 1. CASE DETECTION : Presumptive Screening “ Presumptive identification of unrecognized disease which does not arise from a patient’s request .” Example : Neonatal Screening The people are screened primarily for their own benefit.
  • 13. 2. CONTROL OF DISEASE : Prospective Screening People are examined for the Benefit of others Example : -Screening of Immigrants to protect home population -Screening for HIV, STIs etc
  • 14. 3. RESEARCH PURPOSES : •To know the Natural History of Chronic diseases
  • 15. 4. EDUCATIONAL OPPORTUNITIES : -Acquisition of Information of Public Health relevance -Providing opportunities for creating Public awareness -For educating Health Professionals
  • 16. Types of Screening 1. MASS SCREENING : Applied generally on large unselected populations regardless of the probability of having the disease or condition. Example : -Visual defects in all school children -Chest Xray in elderly for detection of Lung Cancer -Mammography For breast cancer Among women
  • 17. 2. HIGH RISK/SELECTIVE SCREENING : Applied on high risk groups. Example : -Screening for HIV in commercial sex workers. -Screening fetus for Down’s Syndrome in a mother who has already had a Down’s Syndrome baby in the past -Screening for Ca Cervix In low SE status women
  • 18. 3. MULTIPHASIC SCREENING : Various Screening tests are applied during the same screening program. Example : -Annual Health Check up(DM, Lipid profile, LFT, KFT) 4. MULTIPURPOSE SCREENING : When >1 Test is applied simultaneously to detect >1 Disease. Example : -Screening of Pregnant women for VDRL , HIV , HBV by serological tests
  • 19. 5. OPPORTUNISTIC SCREENING : Example – Screening for Rheumatic Heart disease in school children
  • 20. CRITERIA FOR SCREENING  Before initiating a Screening Programme , a decision must be made whether it abides to all the ethical, scientific and financial justification.  The priniciples that should govern a Screening Programme were first enunciated by Wilson and Jugner(1968)  Criteria based on – The Disease
  • 21. Wilson and Jugner Criteria(1968) A : The Disease  Knowledge of the Disease (i)The condition should be important (ii)There must be a recognisable latent or early symptomatic stage (iii)Natural course of condition,including development from latent to declared disease, should be adequately understood  Knowledge of Test (iv)Suitable test or examination (v)Test acceptable to population (vi)Case finding should be continuous , not just ‘once and for all’ project
  • 22.  Treatment for Disease (vii)Accepted treatment for patients with recognised disease (viii)Facilities for diagnosis and treatment available (ix)Agreed policy concerning whom to treat as patients  Cost Considerations (x) Cost of case finding should be economically balanced in relation to possible expenditure on medical care as a whole
  • 23. B : The Screening Test  Simple  Acceptable to Subjects and Providers  Reliable : Precision, Reproducible, Repeatability – Observer Variation Biological Variation Technical error  Valid : Accuracy  Safe  Cost effective  Yielding : the amount of previously unrecognized disease that is diagnosed and brought to treatment as a result of the screening programme.
  • 24.
  • 25. Components of Validity  Sensitivity  Specificity  Predictive Accuracy
  • 26. Result of a Screening Test DISEASE PRESENT DISEASE ABSENT TOTAL Screening Test POSITIVE True Positive ( TP) (a) False Positive (FP) (b) Total Positive by Test = a + b Screening Test NEGATIVE False Negative (FN) (c) True Negative (TN) (d) Total Negative by Test = c + d Total Diseased = a + c Total Non- diseased = b + d Total population= a+b+c+d
  • 27. Sensitivity  Ability of a Test to identify correctly all those who have the disease ( True Positive)  Also called as Positivity in Disease X 100 = X 100 X 100
  • 28. Specificity  Ability of a Test to identify correctly those who do not have the disease( True Negative) X 100 = = X 100 X 100
  • 29. Example : Q : ELISA was used as a Screening Test for HIV among 1000 healthy blood donors. The results of the test are as follows. Calculate Sensitivity and Specificity HIV Positive HIV Negative ELISA Positive 95 (a) 45 (b) a + b = 140 ELISA Negative 5 (c) 855 (d) c + d = 860 a + c = 100 b + d = 900
  • 30. Sensitivity = = (95 / 100) x 100 = 95% Specificity = = (855/900) x 100 = 95% X 100 X 100
  • 31. Problems with FP and FN  False Positives : -Further testing with long , expensive tests -Discomfort , inconvenience , anxiety -Burden on health facilities -Emotional trauma -Difficulty in de-labelling  False Negatives : -False Reassurance -Ignores any disease signs and symptoms -Postponement of treatment -Detrimental to overall health
  • 32. Positive Predictive Value  Ability of a Screening Test to identify correctly all those who have the disease , out of all those who test positive on a screening test  Also called Post Test Probability PPV = [a /(a+b) ] x 100 X 100
  • 33. Negative Predictive Value  Ability of a Screening Test to identify correctly all those who do not have the disease , out of all those who test negative on a screening test NPV = [ d/(c+d) ] x 100 X 100
  • 34. Calculate PPV and NPV HIV Positive HIV Negative ELISA Positive 95 (a) 45 (b) a + b = 140 ELISA Negative 5 (c) 855 (d) c + d = 860 a + c = 100 b + d = 900
  • 35. PPV = = (95/140) x 100 = 68 % NPV = = (855/860) x 100 = 99 %
  • 36. Problems with PPV and NPV :  While Sensitivity and Specificity of a particular Screening test are constant PPV and NPV are largely dependent on the Prevalence of the disease in the Population  Example : Q:The sensitivity and specificity of ELISA in diagnosing HIV infection is 99% and 90% respectively, prevalence of HIV = 40%. Total Population (Commercial sex workers) is 10,000.Calculate PPV and
  • 37. Prevalence = 40% Total HIV positive = (40/100) X 10,000= 4000. and HIV negative = 10,000 - 4,000 = 6000. Sensitivity of ELISA is 99% TP : (99 /100) x 4000 = 3960 FN : 4000 - 3960 = 40 Specificity is 90%, it will correctly call, as negative, TN : (90/100) of 6000= 5400 FP : 6000 - 5400 = 600
  • 38. HIV Positive HIV Negative ELISA Positive 3960 (a) 600 (b) a + b = 4560 ELISA Negative 40 (c) 5400 (d) c + d = 5440 Total = 4000 Total = 6000  PPV = [ a /(a+b)] x 100 = (3960/4560) x100 = 0.86 x 100 = 86%  NPV = [ d/(c+d)] x 100 = (5400/5440) x 100 = 0.99 x 100 = 99%
  • 39. Baye’s Theorem  If the test results are +ve , what is the probability that the patient has the disease?  If the test is negative , what is the probability that the person doesn’t have the disease?  Baye’s Theorem provides answer  It was first described by Clergyman
  • 41. Baye’s Theorem Relationship between PPV of a Screening Test and Sensitivity, Specificity and Prevalence of disease in a population: PPV NPV [ ] [ ]
  • 42. Likelihood Ratio  Incorporates both the Sensitivity and Specificity of the test and provides a direct estimate of how much a test result will change the chances of having a disease  Sensitivity (TP) = 1- FN or FN = 1 – Sensitivity  Specificity (TN) = 1- FP or FP = 1 - Specificity
  • 43. Likelihood Ratio Positive (LR +) Example : If the sensitivity of ELISA is 99% (i.e. 0.99) and specificity is 90% (i.e. 0.90), then A positive result on ELISA for HIV is 9.9 times more likely to occur in a subject with HIV infection as compared to a subject who does not have HIV infection
  • 44. Likelihood Ratio Negative (LR -) Example : If the sensitivity of ELISA is 99% (i.e. 0.99 and specificity is 90% (i.e. 0.90), then The interpretation is that a negative result is only one hundredth times likely to occur in a person who really has HIV infection as compared to a person
  • 45. Tests in Series and Parallel • SERIES : One Test after Another 2nd Test is applied only after 1st Test is Positive • PARALLEL : Both Tests are applied together Series Parallel Sensitivity Decreases Increases Specificity Increases Decreases PPV Increases Decreases NPV Decreases Increases
  • 46.  STa( Sn= 90%) in 100 patients +ve in 90/100 patients STb( Sn=90%) in 90 patients +ve in 90% of 90 = 81 patients
  • 47. STa STb 90/100 90/100 +ve cases +ve cases So, Sensitivity Increases in Parallel
  • 48. In Series :  Combined Sensitivity of 2 Tests A & B in series = Sn(A) x Sn(B)  Combined Specificity of 2 Tests A & B in series = [ Sp(A) + Sp(B)] – [Sp (A) x Sp(B)]
  • 49. In Parallel :  Combined Sensitivity of 2 tests A & B in Parallel = [ Sn(A) + Sn(B)] – [Sn (A) x Sn(B)]  Combined Specificity of 2 Tests A & B in Parallel = Sp(A) x Sp(B)
  • 50. Unimodal & Bimodal Distribution (problem of the borderline)
  • 51. Problem of the Borderline Which of the two Qualities ( Sensitivity or Specificity) is more important in Screening?
  • 52.
  • 53.
  • 54.
  • 55.
  • 56. Kappa Statistics  Reliability can be statistically assessed by estimating the degree of agreement between two measurements  Example : Consider a study on pulmonary TB, with AFB positivity on sputum smear as the method of measurement. For assessing the inter - observer reliability,(between the microbiologist and Lab technician), we took 200 stained slides and each slide was examined by both of them.The results are given as :
  • 57. POSITIVE NEGATIVE TOTAL TECHNICIAN’s DIAGNOSIS POSITIVE 13 (a) 7 (b) 20 (p1) NEGATIVE 24 (c) 156 (d) 180 (q1) TOTAL 37 (p2) 163 (q2) n=200 MICROBIOLOGIST’S DIAGNOSIS
  • 58.  K O : Observed Agreement E : Expected Agreement(expected in chance)
  • 59.  O = (a+d) / n = (13 + 156) / 200 = 169/200 = 0.85  E = [(20 x 37) + (180 x 163)] / (200x200) = (740 + 29340)/40000 = 30080/40000=0.75  K = = (0.85 – 0.75) / (1 – 0.75) =0.10/0.25 = 0.40
  • 60. Kappa Coefficient  Value between 0 and 1  0 : The 2 measurements agree simply because of chance  1 : The 2 measurements agree perfectly irrespective of chance  Nearer the K to 1 better the agreement  K between 0 - 0.25 : Mild agreement 0.25 - 0.50 : Moderately strong 0.50 - 0.75 :Strong agreement 0.75 – 1.00 : Very strong / excellent
  • 61. Interpretation :  Moderately Strong agreement  Kappa coeff is 0.4 means that the observed agreement between the 2 observers of assessing AFB positivity is 0.40 or 40% of the way between a coincidental agreement purely by chance and a perfect
  • 62. Bias in Screening 1.Lead Time Bias : -Over estimation of survival duration due to earlier detection by screening than clinical presentation 2. Length Bias -Over estimation of survival duration due to the relative excess of cases detected that are slowly progressing 3. Self Selection Bias -If the groups which are offered screening are not constituted by random allocation but
  • 63. Receiver Operator Characteristic Curve (Relationship between Sensitivity & Specificity)
  • 64. History  The name ‘ Receiver Operator Characteristic’ came from “ Signal Detection Theory” developed during World War II for analysis of Radar Images  Radar operators had to decide whether a blip on the screen represented an enemy target, a friendly ship or just noise
  • 65.  True Positive: Correct early warning of enemy ships crossing the English Channel  False Positive : When Radar operator sent out an alarm but no enemy ships appeared  False Negative: When enemy ships appeared without previous warning from the radar operator
  • 66.
  • 67.
  • 68.
  • 69. More the area of the Curve , Better the Test
  • 70.
  • 71. Area Under ROC Curve Perfect = 1 Random = 0.5
  • 72. Conclusion  Screening , despite its flaws is a major Public health determinant  Establishing appropriate criteria requires considerable knowledge of the Natural history of disease, adequate facilities for follow up and treatment  It is necessary to ensure that the program is continuously monitored to confirm that effectiveness is maintained (benefits>cost)