COMPARING

DIAGNOSTIC TEST

DR. Siswo Poerwanto, MPH, MSc

GOAL
• Rule out disease when the probability of
its present is low (Choose: greatest sens.)
• Rule in disease when the probability of its
present is high (Choose: greatest spec.)
• Assess prognosis a disease by repeating
the test to monitor its progression
• Detect disease in the absence of
symptoms (Screening)
Basic Design

Series of patients

Index test

Reference (Gold) standard

Cross-classification (2x2 table)

Diagnostic accuracy studies
• Results from the index test are compared
with the results obtained with the
reference standard on the same subjects
• Accuracy refers to the degree of
agreement between the results of the
index test and those from the reference
standard
Anatomy of diagnostic study

• Target population: population or patient

• Index test: Lab Test
• Target condition: disease
• Final diagnosis (reference standard): gold
standard diagnosis
• Cross classification
• Conclusion
Our example

Patients of Fe-deficiency anemia

Serum ferritin measurement

Clinical diagnosis

Cross-classification (2x2 table)

Measures of diagnostic accuracy

• Sensitivity and specificity

• Positive and negative predictive values
• Likelihood ratios
• Diagnostic odds ratio
Example: clinical problem
• Diagnostic value of B type natriuretic protein
(BNP) measurement

• Does BNP measurement distinguish between

those with and without left ventricular
dysfunction (LVSD) in the elderly?

• Smith et al. BMJ 2000; 320: 906.

Sens & spec not directly affected
by prevalence. Why?
• sensitivity
11 / 12 = 92% < Pr(T+|D+) >
• specificity
93 / 143 = 65% < Pr(T-|D-) >

LVSD
Present Absent

>=18.7 11 50 61
BNP
<18.7 1 93 94

12 143 155
PV values directly affected by
prevalence. Why?
• positive predictive value
11 / 61 = 18% < Pr(D+|T+) >
• negative predictive value
93 / 94 = 99% < Pr(D-|T-) >
LVSD
Present Absent

>=18.7 11 50 61
BNP
<18.7 1 93 94

12 143 155
Why Likelihood Ratios (LR)?

• Applicable in situations with more than 2

test outcomes to choose the best test for
rule in or rule out a disease
• LR of a +test shows how well a +test by
comparing its performance when the
disease is present compared when it is
absent.
Likelihood Ratio of positive test
• How more often a positive test result
occurs in persons with the disease
compared to those without the target
condition
Pr(T  | D )
LR  
Pr(T  | D )
Formula: LR +test
• LR+ ratio=(Sens/100%-spec) or

Pr(T  | D  ) 11 / 12
LR     2.6
Pr(T  | D ) 50 / 143
LVSD
Present Absent

>=18.7 11 50 61
BNP
<18.7 1 93 94

12 143 155
Interpret value of LR+
• The best test to use for ruling in disease,
choose the largest LR+ value.
• LR+ = 1, the test does not provide any
additional information for ruling in disease,
that is, it doesn’t change the pretest
probability of a disease.
Likelihood ratios of
a negative test
• Likelihood ratio of a negative test result
Pr(T  | D  )
LR  
Pr(T  | D )
• How less likely a negative test result is
in persons with the target condition
compared to those without the target
condition
Formula: LR -test

Pr(T  | D ) 1 / 12
LR     0.13
Pr(T  | D ) 93 / 143

LVSD
Present Absent

>=18.7 11 50 61
BNP
<18.7 1 93 94

12 143 155
Interpret value of LR -test
• The best test to use for ruling out disease,
choose the smallest LR -value.The smaller
the more information is provided.
• LR- = 1, the test does not provide any
additional information for ruling out
disease, that is, it doesn’t change the
pretest probability of a disease.
Interpreting likelihood ratios
• A LR=1 indicates no diagnostic value

• LR+ >10 are usually regarded as a ‘strong’

positive test result to rule in disease
• LR- <0.1 are usually regarded as a strong
negative test result to rule out disease

• But it depends on what change in probability is

needed to make a diagnosis or prognosis
 92%
LR+ = 10

55%
10%

50%
Confidence intervals
• Sample uncertainty should be described for all
statistics, using confidence intervals
+ gives upper limit
- gives lower limit

  
Standard
95% CI  ˆ  z / 2  se ˆ error of
estimate

estimate of
Normal deviate
effect
(1.96 for 95% CI)
Confidence Intervals for
Proportions
• Sensitivity, specificity, positive
and negative predictive values, r
and overall accuracy are all pˆ 
proportions n

pˆ (1  pˆ )
se pˆ  
n
Take home exercise!
Disease
• Calculate measures of
Present Absent

+ 400 2850 3250

performance test for
Test 1 test 1 and test 2!
- 100 6650 6750

500 9500 10000

• Interpret the results!
Disease
• Which test is better to
Present Absent rule in disease?
+ 425 4750 5175 • Which test is better to
Test 2
- 75 4750 4825 rule out disease?
500 9500 10000