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Diagnostic Testing
Ethan Cowan, MD, MS
Department of Emergency Medicine
Jacobi Medical Center
Department of Epidemiology and Population Health
Albert Einstein College of Medicine
The Provider Dilemma
A
26 year old pregnant female presents after
twisting her ankle. She has no abdominal or
urinary complaints. The nurse sends a UA
and uricult dipslide prior to you seeing the
patient. What should you do with the
results of these tests?
The Provider Dilemma

Should a provider give
antibiotics if either one
or both of these tests
come back positive?
Why Order a Diagnostic Test?
When the diagnosis is
uncertain
 Incorrect diagnosis
leads to clinically
significant morbidity
or mortality
 Diagnostic test result
changes management
 Test is cost effective

Clinician Thought Process
Clinician derives patient
prior prob. of disease:
H & P
 Literature
 Experience
 “Index of Suspicion”
 0% - 100%
 “Low, Med., High”

Threshold Approach to
Diagnostic Testing
Probability of Disease
0%
100%
Testing Zone
P(-)
P(+)
P < P(-)
Dx testing & therapy not indicated
 P(-) < P < P(+) Dx testing needed prior to therapy
 P > P(+)
Only intervention needed

Pauker and Kassirer, 1980, Gallagher, 1998
Threshold Approach to
Diagnostic Testing
Probability of Disease
0%
100%
Testing Zone
P(-)

P(+)
Width of testing zone depends on:
 Test properties
 Risk of excess morbidity/mortality attributable to the test
 Risk/benefit ratio of available therapies for the Dx
Pauker and Kassirer, 1980, Gallagher, 1998
Test Characteristics

Reliability
 Inter observer
 Intra observer
 Correlation
 B&A Plot
 Simple Agreement
 Kappa Statistics

Validity
 Sensitivity
 Specificity
 NPV
 PPV
 ROC Curves
Reliability

The extent to which
results obtained with a
test are reproducible.
Reliability
Not Reliable
Reliable
Intra rater reliability
 Extent
to which a
measure produces
the same result at
different times for
the same subjects
Inter rater reliability

Extent to which a
measure produces the
same result on each
subject regardless of
who makes the
observation
Correlation (r)
For continuous data
r=1
perfect
r=0
none

O1
O1 = O2
O2
Bland & Altman, 1986
Correlation (r)
Measures relation
strength, not
O1
agreement
 Problem: even near
perfect correlation
may indicate
significant differences
between observations

r = 0.8
O1 = O2
O2
Bland & Altman, 1986
Bland & Altman Plot
O1 – O 2
For continuous data
 Plot of observation
differences versus the
means
 Data that are evenly
distributed around 0
and are within 2 STDs
exhibit good
agreement

10
0
-10
[O1 + O2] / 2
Bland & Altman, 1986
Simple Agreement
Rater 1
+
total
 Extent
Rater 2
+
a
b
c
d
a+c b+d
total
a+b
c+d
N
to which two or more raters agree on the
classifications of all subjects
 % of concordance in the 2 x 2 table (a + d) / N
 Not ideal, subjects may fall on diagonal by chance
Kappa
Rater 1
+
total
 The
Rater 2
+
a
b
c
d
a+c b+d
total
a+b
c+d
N
proportion of the best possible improvement in
agreement beyond chance obtained by the observers
 K = (pa – p0)/(1-p0)
 Pa = (a+d)/N (prop. of subjects along the main diagonal)
 Po = [(a + b)(a+c) + (c+d)(b+d)]/N2 (expected prop.)
Interpreting Kappa Values
K=1
K > 0.80
0.60 < K < 0.80
0.40 < K < 0.60
0 < K < 0.40
K=0
K<0
Perfect
Excellent
Good
Fair
Poor
Chance (pa = p0)
Less than chance
Weighted Kappa
Rater 1
1
2
.
.
C
total
Rater 2
1
2
n11
n12
n21
n22
.
.
.
.
nC1
nC2
n.1
n.2
...
...
...
...
...
...
...
C
n1C
n2C
.
.
nCC
n.C
total
n1.
n2.
.
.
nC.
N
Used for more than 2 observers or categories
 Perfect agreement on the main diagonal weighted
more than partial agreement off of it.

Validity
The degree to which a
test correctly diagnoses
people as having or not
having a condition
 Internal Validity
 External Validity

Validity
Valid, not reliable
Reliable and Valid
Internal Validity
Performance Characteristics
 Sensitivity
 Specificity
 NPV
 PPV
 ROC Curves

2 x 2 Table
Disease Status
Test
Result
+
total
cases
noncases
TP
FN
FP
TN
cases
noncases
TP = True Positives
FP = False Positives
total
positives
negatives
N
TN = True Negatives
FN = False Negatives
Gold Standard
 Definitive
test used
to identify cases
 Example:
traditional agar
culture
 The dipstick and
dipslide are
measured against
the gold standard
Sensitivity (SN)
Disease Status
Test
Result
+
total
cases
noncases
TP
FN
FP
TN
cases
noncases
total
positives
negatives
N
 Probability
of correctly identifying a true case
 TP/(TP + FN) = TP/ cases
 High SN, Negative test result rules out Dx (SnNout)
Sackett & Straus, 1998
Specificity (SP)
Disease Status
Test
Result
+
total
cases
noncases
TP
FN
FP
TN
cases
noncases
total
positives
negatives
N
 Probability
of correctly identifying a true noncase
 TN/(TN + FP) = TN/ noncases
 High SP, Positive test result rules in Dx (SpPin)
Sackett & Straus, 1998
Problems with
Sensitivity and Specificity
 Remain
constant over patient populations
 But, SN and SP convey how likely a test
result is positive or negative given the
patient does or does not have disease
 Paradoxical inversion of clinical logic
 Prior knowledge of disease status obviates
need of the diagnostic test
Gallagher, 1998
Positive Predictive Value (PPV)
Disease Status
Test
Result
+
total
cases
noncases
TP
FN
FP
TN
cases
noncases
total
positives
negatives
N
 Probability
that a labeled (+) is a true case
 TP/(TP + FP) = TP/ total positives
 High SP corresponds to very high PPV (SpPin)
Sackett & Straus, 1998
Negative Predictive Value (NPV)
Disease Status
Test
Result
+
total
cases
noncases
TP
FN
FP
TN
cases
noncases
total
positives
negatives
N
 Probability
that a labeled (-) is a true noncase
 TN/(TN + FN) = TP/ total negatives
 High SN corresponds to very high NPV (SnNout)
Sackett & Straus, 1998
Predictive Value Problems
 Vulnerable
to Disease Prevalence (P) Shifts
 Do not remain constant over patient populations
 As P
PPV
NPV
 As P
PPV
NPV
Gallagher, 1998
Flipping a Coin to Dx AMI for
People with Chest Pain
ED AMI Prevalence 6%
AMI
No AMI
Heads (+) 3
47
50
Tails (-) 3
47
50
6
94
100
SN = 3 / 6 = 50%
SP = 47 / 94 = 50%
PPV= 3 / 50 = 6%
NPV = 47 / 50 = 94%
Worster, 2002
Flipping a Coin to Dx AMI for
People with Chest Pain
CCU AMI Prevalence 90%
AMI
No AMI
Heads (+) 45
5
50
Tails (-) 45
5
50
10
100
90
SN = 45 / 90 = 50%
SP = 5 / 10 = 50%
PPV= 45 / 50 = 90%
NPV = 5 / 50 = 10%
Worster, 2002
Receiver Operator Curve
1.0
Sensitivity
(TPR)
0.0
0.0 1-Specificity (FPR) 1.0
Allows consideration of test performance across a
range of threshold values
 Well suited for continuous variable Dx Tests

Receiver Operator Curve
 Avoids
the “single
cutoff trap”
Sepsis
No Effect Effect
WBC Count
Gallagher, 1998
Area Under the Curve (θ)
1.0
Sensitivity
(TPR)
0.0
0.0 1-Specificity (FPR) 1.0
 Measure
of test accuracy
 (θ) 0.5 – 0.7 no to low discriminatory power
 (θ) 0.7 – 0.9 moderate discriminatory power
 (θ) > 0.9
high discriminatory power
Gryzybowski, 1997
Problem with ROC curves
 Same
problems as SN and SP “Reverse
Logic”
 Mainly used to describe Dx test
performance
Appendicitis Example
Study design:
 Prospective cohort
 Gold standard:
 Pathology report from
appendectomy or CT
finding (negatives)
 Diagnostic Test:
 Total WBC

Physical Exam
+
OR
+
Appy
CT Scan
-
No Appy
Cardall, 2004
Appendicitis Example
WBC
Appy
Not Appy Total
> 10,000
66
89
155
< 10,000
21
98
119
Total
87
187
274
SN 76% (65%-84%)
SP 52% (45%-60%)
PPV 42% (35%-51%)
NPV 82% (74%-89%)
Cardall, 2004
Appendicitis Example
Patient WBC:
 13,000
 Management:
 Get CT with PO & IV
Contrast

Physical Exam
+
OR
+
Appy
CT Scan
-
No Appy
Cardall, 2004
Abdominal CT
Follow UP
 CT
result: acute
appendicitis
 Patient taken to
OR for
appendectomy
But, was WBC necessary?
Answer given in talk on Likelihood Ratios