Interpretation of results
Sensitivity and specificity
Predictive values positive and negative
Sep 2007
P I D E M I C A L E R T
Laboratory Training for FieldEEpidemiologists
A N D
R E S P O N S E
Outline
•
Intrinsic characteristics of a test
– Sensitivity
– Specificity
•
Performance of a test in a population
– Predictive value of a positive test
– Predictive value of a negative test
P I D E M I C A L E R T
Laboratory Training for FieldEEpidemiologists
A N D
R E S P O N S E
Sensitivity
The sensitivity of a test in the ability of the test to identify
correctly affected individuals
Proportion of persons testing positive among affected individuals
Affected persons
(Positive by gold standard)
Persons testing positive
(True positives)
Persons testing negative
(False negatives)
Sensitivity = True positives / Affected persons
Estimate the 95% confidence interval
P I D E M I C A L E R T
Laboratory Training for FieldEEpidemiologists
A N D
R E S P O N S E
Estimating the sensitivity of a test
•
Identify affected individuals with a gold standard
•
Obtain a wide panel of samples that are representative of the
population of affected individuals
– Recent and old cases
– Severe and mild cases
– Various ages and sexes
•
Test the affected individuals
•
Estimate the proportion of affected individuals that are
positive with the test
P I D E M I C A L E R T
Laboratory Training for FieldEEpidemiologists
A N D
R E S P O N S E
Estimating the sensitivity of a rapid test
for leishmaniasis
•
Identify persons with leishmaniasis with a gold standard
– Parasitologically proven infection
•
Obtain a wide panel of samples that are representative of the
population of individuals with leishmaniasis
– Recent and old cases
– Severe and asymptomatic cases
– Various ages and sexes
•
Test the persons with leishmaniasis
•
Estimate the proportion of persons with leishmaniasis that
are positive with the rapid test
P I D E M I C A L E R T
Laboratory Training for FieldEEpidemiologists
A N D
R E S P O N S E
Sensitivity of a rapid test for
leishmaniasis
Patients with
leishmaniasis
Rapid test
True positive
148
False negative
2
150
Sensitivity = 148 / (150) = 98%
95% confidence interval: 94%-99%
P I D E M I C A L E R T
Laboratory Training for FieldEEpidemiologists
A N D
R E S P O N S E
What factors influence
the sensitivity of a test?
•
Characteristics of the affected persons?
 YES: Antigenic characteristics of the pathogen in the area
(e.g., if the test was not prepared with antigens reflecting the
population of pathogens in the area, it will not pick up infected
persons in the area)
•
Characteristics of the non-affected persons?
 NO: The sensitivity is estimated on a population of affected persons
•
Prevalence of the disease?
 NO: The sensitivity is estimated on a population of affected persons
Sensitivity is an INTRINSIC characteristic of the test
P I D E M I C A L E R T
Laboratory Training for FieldEEpidemiologists
A N D
R E S P O N S E
Specificity
The specificity of a test in the ability of the test to identify
correctly non-affected individuals
Proportion of person testing negative among non affected individuals
Non-affected persons
(Negative by gold standard)
Persons testing negative
(True negatives)
Persons testing positive
(False positives)
Specificity = True negatives / Non-affected persons
Estimate the 95% confidence interval
P I D E M I C A L E R T
Laboratory Training for FieldEEpidemiologists
A N D
R E S P O N S E
Estimating the specificity of a test
•
Identify non affected individuals
– Negative with a gold standard
– Unlikely to be infected
•
Obtain a wide panel of samples that are representative of the
population of non-affected individuals
– Diverse unaffected population: Difficult to find. Ideally, those
individuals that would need to be tested but not infected
•
Test the non-affected individuals
•
Estimate the proportion of non-affected individuals that are
negative with the test
P I D E M I C A L E R T
Laboratory Training for FieldEEpidemiologists
A N D
R E S P O N S E
Estimating the specificity of a rapid test
for leishmaniasis
•
Identify persons without leishmaniasis
– Persons without sign and symptoms of the infection
– Persons at low risk of infection, negative with gold standard
•
Obtain a wide panel of samples that are representative of the
population of individuals without leishmaniasis
– Persons from neighbouring villages having similar characteristics
but with no transmission and no infections
•
Test the persons without leishmaniasis
•
Estimate the proportion of persons without leishmaniasis
that are negative with the rapid test
P I D E M I C A L E R T
Laboratory Training for FieldEEpidemiologists
A N D
R E S P O N S E
Specificity of a rapid test for
leishmaniasis
Individuals
without
leishmaniasis
Test
False positive
12
True negative
188
200
Specificity = 188 / 200 = 94%
95% confidence interval: 90%-96%
P I D E M I C A L E R T
Laboratory Training for FieldEEpidemiologists
A N D
R E S P O N S E
What factors influence
the specificity of a test?
•
Characteristics of the affected persons?
 NO: The specificity is estimated on a population of non affected
•
Characteristics of the non-affected persons?
 YES: The diversity of antibodies to various other antigens in the
population may affect cross reactivity (e.g., If malaria is endemic,
polyclonal hyper gammaglobulinemia may increase the proportion
of false positives)
•
Prevalence of the disease?
 NO: The specificity is estimated on a population of non affected
Specificity is an INTRINSIC characteristic of the test
P I D E M I C A L E R T
Laboratory Training for FieldEEpidemiologists
A N D
R E S P O N S E
Identifying the cut-off to use with a test
on the basis of panel analysis: Ideal case
Number of tests
25
Cut-off
20
15
Sick
10
Well
5
0
1
2
3
4
5
6
7
8
9 10 11 12 13 14
Possible values of the test
P I D E M I C A L E R T
Laboratory Training for FieldEEpidemiologists
A N D
R E S P O N S E
Identifying the cut-off to use with a test
on the basis of panel analysis: Real case
Number of tests
25
Cut-off
20
15
10
False
negatives
False
positives
True
negatives
Sick
Well
True
positives
5
0
1
2
3
4
5
6
7
8
9 10 11 12 13 14
Possible values of the test
P I D E M I C A L E R T
Laboratory Training for FieldEEpidemiologists
A N D
R E S P O N S E
To whom sensitivity and specificity
matters most?
•
Look at denominators!
– Panels of affected individuals
– Panels of negative individuals
•
To laboratory specialists!
P I D E M I C A L E R T
Laboratory Training for FieldEEpidemiologists
A N D
R E S P O N S E
Outline
•
Intrinsic characteristics of a test
– Sensitivity
– Specificity
•
Performance of a test in a population
– Predictive value of a positive test
– Predictive value of a negative test
P I D E M I C A L E R T
Laboratory Training for FieldEEpidemiologists
A N D
R E S P O N S E
How is the test doing in a real population?
•
The test is now used in a real population
•
This population is made of
– Affected individuals
– Non-affected individuals
•
The proportion of affected individuals is the prevalence
Status of persons
Test
Affected
Non-affected
Positive
True +
False +
A+B
Negative
False -
True -
C+D
A+C
B+D
A+C+B+D
P I D E M I C A L E R T
Laboratory Training for FieldEEpidemiologists
A N D
R E S P O N S E
Predictive value of a positive test
The predictive value of a positive test is the probability that
an individual testing positive is truly affected
Proportion of affected persons among those testing positive
Persons testing positive
(Positive by test)
Persons affected
(True positives)
Persons not affected
(False positives)
Predictive value of a positive test =
True positives / Persons testing positive
Estimate the 95% confidence interval
P I D E M I C A L E R T
Laboratory Training for FieldEEpidemiologists
A N D
R E S P O N S E
Predictive value of a positive test
Status of persons
Test
Affected
Non-affected
Positive
A
B
A+B
Negative
C
D
C+D
A+C
B+D
A+C+B+D
PVP = A / (A+B)
This is only valid for the sample of specimens tested
P I D E M I C A L E R T
Laboratory Training for FieldEEpidemiologists
A N D
R E S P O N S E
What factors influence
the predictive value positive of a test?
•
Sensitivity?
 YES: To some extend.
•
Specificity?
 YES: The more the test is specific, the more it will be negative for
non affected persons. Thus, when the test is positive, it is probably
truly positive (All non affected were correctly identified as testing
negative).
•
Prevalence of the disease?
 YES: Low prevalence: The test will pick up more false positives
 YES: High prevalence: The test will pick up more true positives
P I D E M I C A L E R T
Laboratory Training for FieldEEpidemiologists
A N D
R E S P O N S E
Predictive value positive of a test
according to prevalence and specificity
Specificity
Prevalence (%)
P I D E M I C A L E R T
Laboratory Training for FieldEEpidemiologists
A N D
R E S P O N S E
0
10
90
80
70
60
50
40
30
70%
80%
90%
95%
20
0
10
10 0
90
80
PVP % 70
60
50
40
30
20
10
0
Predictive value of a negative test
The predictive value of a negative test is the probability that
an individual testing negative is truly non-affected
Proportion of non-affected persons among those testing negative
Persons testing negative
(Negative by test)
Persons non affected
(True negatives)
Persons affected
(False negatives)
Predictive value of a negative test =
True negatives / Persons testing negative
Estimate the 95% confidence interval
P I D E M I C A L E R T
Laboratory Training for FieldEEpidemiologists
A N D
R E S P O N S E
Predictive value of a negative test
Status of persons
Test
Affected
Non-affected
Positive
A
B
A+B
Negative
C
D
C+D
A+C
B+D
A+C+B+D
PVN = D / (C+D)
This is only valid for the sample of specimens tested
P I D E M I C A L E R T
Laboratory Training for FieldEEpidemiologists
A N D
R E S P O N S E
What factors influence
the predictive value negative of a test?
•
Sensitivity?
 YES: The more the test is sensitive, the more it captures affected
persons. Thus, when the test is negative, it is probably truly
negative (all affected were captured among the positive).
•
Specificity?
 YES: But to a lesser extend.
•
Prevalence of the disease?
 YES: Low prevalence: The test will pick up more true negatives
 YES: High prevalence: The test will pick up more false negatives
P I D E M I C A L E R T
Laboratory Training for FieldEEpidemiologists
A N D
R E S P O N S E
Predictive value negative of a test
according to prevalence and sensitivity
100
90
80
70
60
PVN % 50
40
30
20
10
0
0
Sensitivity
70%
80%
90%
95%
10
20
30
40
50
60
70
80
90 100
Prevalence (%)
P I D E M I C A L E R T
Laboratory Training for FieldEEpidemiologists
A N D
R E S P O N S E

Relation between predictive values and
(1) sensitivity and (2) specificity
Se.P
PVP 
Se.P  (1  Sp)(1  P)
Sp(1- P)
PVN 
Sp(1- P)  (1 Se).P
P I D E M I C A L E R T
Laboratory Training for FieldEEpidemiologists
A N D
R E S P O N S E
Positive (PPV) and negative (NPV) predictive
values of a test according to the prevalence
(95% sensitivity and specificity)
Predictive value (%)
100
80
PVN
60
40
20
PVP
0
0
50
25
75
Prevalence (%)
P I D E M I C A L E R T
Laboratory Training for FieldEEpidemiologists
A N D
R E S P O N S E
100
To whom predictive values matters most?
•
Look at denominators!
– Persons testing positive
– Persons testing negative
•
To clinicians and epidemiologists!
P I D E M I C A L E R T
Laboratory Training for FieldEEpidemiologists
A N D
R E S P O N S E
Summary
•
Sensitivity and specificity matter to laboratory specialists
– Studied on panels of positives and negatives
– Look into the intrinsic characteristics of the test:
• Capacity to pick affected
• Capacity to pick non affected
•
Predictive values matter to clinicians and epidemiologists
– Studied on homogeneous populations
– Look into the performance of the test in real life:
• What to make of a positive test
• What to make of a negative test
P I D E M I C A L E R T
Laboratory Training for FieldEEpidemiologists
A N D
R E S P O N S E
Interpretation of results
Developed by:
The Department of Epidemic and Pandemic Alert
and Response of the World Health Organization
with the assistance of:
European Program for Field Epidemiology
Training
Canadian Field Epidemiology Programme
Thailand Ministry of Health
Institut Pasteur
P I D E M I C A L E R T
Laboratory Training for FieldEEpidemiologists
A N D
R E S P O N S E