Diagnostic Test - Ris 07 071107 PDF

STUDY OF DIAGNOSTIC TESTS
Modul Riset
www.kedokteran.dikampus.com
Laboratory study :
- Evaluation of diagnostic tests
- Experimental study : - In vitro
- In vivo
References:
- Pusponegoro HD, et al. Uji Diagnostik. In: S.
Sastroasmoro & S.Ismael (Ed.). Dasar-dasar
Metodologi penelitian klinis. Edisi ke-2.
Jakarta: CV Sagung Seto, 2002.
- Warren S, et al. Designing a New Study III:
Diagnostic Test. In: SB Hulley and SR
Cummings (Eds). Designing a Clinical Research
Baltimore: Williams and Wilkins, 1988.
QUESTIONS
• Is RT-PCR useful in the diagnosis of dengue infection?
• Among patients with hypertension, is a serum creatinin
level useful in the diagnosis of renovascular disease?
• How good USG can predict breast cancer in patients
with breast tumor?
How well a diagnostic test can differentiate presence or

absence of disease.
Purpose of diagnostic tests :
1. Diagnosis or exclusion of disease

- The tests must be : sensitive and specific
2. Screening of disease among asymptomatic persons.
Additional test will be needed to confirm early diagnosis.
The test are useful when:
- Prevalence of disease is “high”
- Significant morbidity/mortality without treatment
- Effective therapy is available
- Early treatment gives better outcome.
Purpose of diagnostic test (contd.)
3. Part of the treament

- To monitor disease/ treatment progress
- To identify complication
` - To monitor drug level
- Determine prognosis
- To confirm indeterminate tests.
- Characterization of causative microorganism
(e.g. drug resistance, genotype)
Important : reproducibility
4. Epidemiology study
Structure
They have :
- Predictor variable (the test results)
- Outcome variable (presence or absence of disease)
The test results as the predictor variable
- dichotomous (positive or negative)
- categorical (++++, +++, ++, + or -)
- continous ( …. Mg of glucose/ ml) --- cut off point
The disease as outcome variable

- Absence or presence of disease
- Determined by gold standard
2x2 table
Disease status
Test result Breast cancer benign nodule
Positif 65 30
Negative 35 70
Analysis with x2 p< 0.001 Statistically the positive result is

highly correlated with presence of disease.
But this test cannot well differentiate absence or presence of disease.
Sensitivity
= the proportion of subjects with the disease who have
positive test
Indicating how good a test is at identifying the diseased
Specificity
= the proportion of subjects without the disease who
have a negative test
Indicating how good a test is at indicating the
nondiseased
- The probability that a person with a positive result
actually has the disease.
------ Positive predictive value (PV+)
- The probability that a person with a negative result

actually doesn’t have the disease
------ Negative predictive value (PV-)
Disease status
Test result Breast cancer benign nodule
Positif 65 30
Negative 35 70
True positive : the test is positive & he has the disease

False positive : the test is positive & he doesn’t have the disease
True negative : The test is negative & doesn’t have the disease
False negative : The test is negative & he has the disease
DISEASE
YES NO TOTAL
TEST YES TRUE FALSE TP + FP

RESULT POSITIVE POSITIVE
NO FALSE TRUE FN + TN
NEGATIVE NEGATIVE
TOTAL TP + FN FP + TN TP + FP + FN +
TN
GOLD STANDARD
POSITIVE NEGATIVE TOTAL
TEST POSITIVE A B A+B

RESULT (45) (10) (55)
NEGATIVE C D C+D
(5) (40) (45)
TOTAL A+C B+D A+B+

(50) (50) C+D
Sensitivity = A : ( A+C) = 90%

Specivicity = D : (B + D) = 80%
Positive predictive value = A : (A + B) = 82%
Negative predictive value = D : (C + D) = 89%
Disease status
Test result Breast cancer benign nodule Total
Positif 70 25 95
Negative 30 75 105
Total 100 100 200
Sensitivity = ?
Specivicity = ?
PV+ = ?
PV- = ?
Disease status
Test result Breast cancer benign nodule Total
Positif 70 25 95
Negative 30 75 105
Total 100 100 200

PV+ = A : (A + B) = 73.7%
PV- = D : (C + D) = 71.4%
Steps in diagnostic test research
1. Identify why a new diagnostic test is necessary
- How good is the present available diagnostic test? Any
weakness?
Can a new method overcome the weakness of the old one?
2. Determine the main purpose of the new test.

- To screen? --- high sensitivity
- To confirm diagnosis? --- high sensitivity and specificity
- To exclude? ---- high specificity
3. Select subject population.

- Screening / Case finding/ Diagnosis
- Location
- Sample number
- Inclusion criteria
4. Select gold standard
- Best available diagnostic test
5. Do the test
- Blinded
6. Data analysis and report
- Sensitivity, Specificity, PV+, PV-.
With confidence interval
- ROC for continous data
GOLD STANDARD
- Standard method to determine presence or absence
of disease
- Ideally : always positive for diseased person, and
always negative for non-diseased person ---- rare, if
any ----- use the best method available
- One or combination of methods
- Its sensitivity and specificity should not lower than
the new method.
Cut Off
- When data are in ordinal (categorical) or numeral
(continous) We have to decide the point that
differentiate “normal” and “abnormal”.
- Depends on the purpose of the test, need high
sensitivity or high specificity.
- E.g : for screening : high sensitivity. To decide whether
a patient need a high-risk surgery : high specificity.
Receiver operator curve
A graph that show the “bargain” between sensitivity and specificity when
we determine a cut-off point.
Increase sensitivity - decrease specificity, vice versa.
Points closer to diagonal line – worse result
Selection of cut-off point depends on the purpose of the test.
x
1.0
x D
C
S
e 0.8
n
s x
B
i 0.6
t
i
v x
A
0.4
i
t
x
y 0.2
0 0.2 0.4 0.6 0.8 1.0

1 - Specificity
Receiver operator curve (ROC) for serum alanine aminotransferase (ALT)
Level (U/L) in the diagnosis of hepatitis
1.0
25
S 50
e 0.8
n
s
i 0.6 100
t
i x
v 0.4
200
i x
t
y 0.2 x 400
0 0.2 0.4 0.6 0.8 1.0

1 - Specificity
The value of diagnostic test also depends on prevalence of
the disease in the population being tested.
Prevalence decrease
less likely that someone with a positive test is
actually has the disease
the more specific a test must be in order to be
clinically useful.
GOLD STANDARD
TEST POSITIVE A B A+B

RESULT (45) (10) (55)
NEGATIVE C D C+D
(5) (40) (45)
TOTAL A+C B+D 100

(50) (50)
Prevalence = 50%
PV+ = A : (A + B) = 82%
PV- = D : (C + D) = 89%
GOLD STANDARD
TEST POSITIVE 18 16 34
RESULT
NEGATIVE 2 64 66
TOTAL 20 80 100
Prevalence = 20%
Specivisity = D : (B + D) = 80%
Nilai duga positif = A : (A + B) = 55%
Nilai duga negatif = D : (C + D) = 97%
Likelihood ratio
= the likelihood that a person with a disease would have

a particular test result devided by the likelihood that a
person without the disease would have that result.
-This especially useful when a test result categorical or

continous.
Positive Likelihood ratio =

a/(a+c) : b/(b+d) = sensitivity : (1-specificity)
Negative Likelihood ratio =

c/(a+c) : d/(b+d) = (1-sensitivity) : specificity
Limitations
1. Random error
- by chance
- quantifiable ---- confidence interval.
2. Systematic error
2.1. Sampling bias :
- When thestudy sample is not representative of the
target population in which test will be used.
2.2. Measurement bias :
- Increase when the person determine the test result
have already known the outcome of gold standard.
- borderline result --- determine in advance how to
treat this result.
2.3. Reporting bias
- Unpromising results usually go unreported.
------ enough samples, so negative results can be
meaningful and reported.
Summary
1. A diagnostic test study determines the usefulness of a
test in the diagnosis of a disease. Good tests are
those that distinguish the diseased from the non-
diseased, and are safe, quick, simple, painless, reliable,
and inexpensive.
Randomized blinded trial and usual clinical practice as
model is important in diagnostic test study.
2. In diagnostic test study there is a predictor variable
(test result) and an outcome variable (the disease,
determined by gold standard).
The goal is to describe how strong the association is,
in terms of its sensitivity and specificity.
3. The investigator should determine the sensitivity,
specificity, predictive value of positive test,
predictive value of negative test.
A cutoff point must be determined for calling a result
“positive”.
4. Studies of diagnostic tests are subject to several
biases; the most important are sampling bias,
measurement bias, and reporting bias.
5. Steps in planning diagnostic test study : a) Identify
why a new diagnostic test is necessary; b) Determine
the main purpose of the new test; c) Select subject
population; d) Select gold standard; e) Apply the test
and the gold standard bilndly; f) Analyse and report
data in terms of sensitivity, specificity and predictive
value.
Thank you

Diagnostic Test - Ris 07 071107 PDF

Transféré par

Informations du document

Titre original

Copyright

Formats disponibles

Partager ce document

Partager ou intégrer le document

Options de partage

Avez-vous trouvé ce document utile ?

Ce contenu est-il inapproprié ?

Droits d'auteur :

Formats disponibles

Diagnostic Test - Ris 07 071107 PDF

Transféré par

Droits d'auteur :

Formats disponibles

STUDY OF DIAGNOSTIC TESTS

How well a diagnostic test can differentiate presence or

1. Diagnosis or exclusion of disease

3. Part of the treament

The disease as outcome variable

Test result Breast cancer benign nodule

Analysis with x2 p< 0.001 Statistically the positive result is

- The probability that a person with a negative result

Test result Breast cancer benign nodule

True positive : the test is positive & he has the disease

TEST YES TRUE FALSE TP + FP

TEST POSITIVE A B A+B

TOTAL A+C B+D A+B+

Sensitivity = A : ( A+C) = 90%

Test result Breast cancer benign nodule Total

Total 100 100 200

Test result Breast cancer benign nodule Total

Total 100 100 200

Sensitivity = A : ( A+C) = 70%

2. Determine the main purpose of the new test.

3. Select subject population.

0 0.2 0.4 0.6 0.8 1.0

0 0.2 0.4 0.6 0.8 1.0

TEST POSITIVE A B A+B

TOTAL A+C B+D 100

= the likelihood that a person with a disease would have

-This especially useful when a test result categorical or

Positive Likelihood ratio =

Negative Likelihood ratio =

Vous aimerez peut-être aussi