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You are on page 1of 28

The Probability of Disease

Prof. Bhisma Murti

Department of Public Health,

Faculty of Medicine, Universitas Sebelas Maret

The Clinical Epidemiology/ Evidence Based Medicine Series

As a medical student you learn to make a diagnosis of

your patient by the following methods:

1. History Taking (Anamnesis)

2. Physical Examination

Both exercises are known as Clinical

Examination (Pemeriksaan Klinis)

3. Diagnostic Test

the prevalence of disease in the population from which

your patient originates. Evidence of high prevalence of the

disease in the population will support your current diagnosis

for Diagnosis ?

Clinical examination is far more powerful than laboratory

evaluation. By careful history taking and physical examination

in most cases you have got 73% of the correct diagnosis!

Establishing Diagnosis

Percent*)

History Taking

56%

Percent*)

73%

2

Physical Examination

Diagnostic test

17%

27%

*) Sandler G (1980). The importance of the history in the medical clinic and the

cost of unnecessary tests. American Heart Journal 100(Part 1):928.

methods, clinical epidemiology aims to help

clinicians to improve the accuracy of

diagnosis and prognosis, and to choose the

correct treatment, i.e. one that does more

good than harm

Probability

After history taking and physical examination, you can

make a diagnosis of the disease in question, but with

some uncertainty. Then you need to list some differential

diagnoses each with its probability. The probability of

correct diagnosis before using a diagnostic test is called

pretest probability.

Differential Diagnosis

Pretest Probability

(value from 0 to 1)

1. ____________________

_____

2. ____________________

_____

3. ____________________

_____

4. ____________________

_____

Disease Probability

Numerical Probability

No disease is certain

Disease Possible

0.25

0.50

Disease probable

0.75

Disease certain

to Improve Diagnosis

Many clinicians do not understand how the

results of diagnostic tests change the likelihood

of a particular diagnosis.

The information from a diagnostic test can be

used to refine the probability of diagnosis. The

probability of correct diagnosis after using a

diagnostic test is called posttest probability.

Given that a diagnostic test accounts for

only about 27% for diagnosing a disease,

you need to select a diagnostic test that is

CLINICALLY USEFUL.

A clinically useful diagnostic test is one that

is ACCURATE for diagnosing the disease,

therefore will give valuable additional

information to the clinicain so as to reduce

uncertainty in making diagnosis.

What are the measures of accuracy for a

diagnostic test?

The Basic Format

Myocardial Infarction

Positive

(>=80IU)

Present

Absent

True Positive

False Positive

Creatinine

Kinase (CK) Test Negative

Results

(<80IU)

a b

c d

False Negative

True Negative

Sensitivity = the proportion of patients with the disease who

have a positive test result

= a / (a+c)

Specificity = the proportion of patients without the disease who

have a negative test result

= d / (b+d)

Positive Predictive Value (PPV) = the proportion of patients with a

positive test result who have the disease

= a / (a+b)

Negative Predictive Value (NPV) = the proportion of patients with a

negative test result who do not have the disease

= d / (c+d)

The more sensitive a diagnostic test, the more likely you will

classify individuals with the disease as positive.

Its a good test, isnt it? Yes, it is because you had a few false

negative. But it is only partially good. Why? Because you might

have made some false positive.

The more specific a diagnostic test, the more likely you will classify

individuals without the disease as negative.

For a diagnostic test to be accurate, it should be BOTH sensitive

and specific. Then you can trust this diagnostic test.

Results from A Study Assessing The Clinical Values of a Diagnostic Test

Myocardial Infarction

Positive

(>=80IU)

CK Test

Results

Present

Absent

215

16

231

a+b

c+d

114

129

b+d

a+b+c+d

130

360

Negative

(<80IU)

15

a+c

230

An Example

a

215

Sensitivity

93%

a c 230

The more sensitive a diagnostic test, the more

likely it will give you true positive result, the less

likely it will give you false negative result

d

114

Specificity

88%

b d 130

The more specific a diagnostic test, the more

likely it will give you true negative result, the less

likely it will give you false positive result

ROC depicts the relation between sensitivity and

specificity (see the next slide). ROC relates sensitivity in

the x axis and 1-specifity in the y axis.

Figure A shows that with a cut-off point of CK>=280 IU,

sensitivity is slightly low while as agak rendah dan

spesififitas tinggi. Gambar B menunjukan bahwa dengan

cut-off point >=80 IU, sensitivitas dan spesifisitas tinggi.

Gambar C menunjukkan bahwa dengan cut-off point

>=40 IU, sensitivitas tinggi dan spesifisitas agak rendah.

Intinya, cut-off point yang dipilih menentukan

sensitivitas dan spesififitas tes.

Ketepatan (akurasi) keseluruhan tes diagnostik dapat

diterangkan oleh luasnya area di bawah kurva ROC;

makin luas area makin bertambah baik hasil tesnya

(terbaik adalah area ROC pada Gambar B).

Cut Off Point CK untuk Diagnosis Infark Otot Jantung

Area under ROC curve = 0.9179

Area under ROC curve = 0.7997

1.00

1.00

CK>=80

0.75

Sensitivity

Sensitivity

0.75

CK >=280

0.50

0.25

0.25

0.00

0.00

0.00

0.25

0.50

1 - Speci fi ci ty

0.75

1.00

1.00

CK>=40

0.75

Sensitivity

0.50

0.50

0.25

0.00

0.00

0.25

0.50

1 - Speci fi ci ty

0.75

1.00

0.00

0.25

0.50

1 - Speci fi ci ty

0.75

1.00

Titik batas

(cut off

point) CK

(IU)

Sensitivitas

Spesifisitas

False

Positive

Rate

>=40

98%

63%

32%

>=80

93%

88%

12%

>=280

64%

96%

1%

An ideal test is highly sensitive and specific. However, since

both sensitivity and specificity are framed in a 2 by 2

contingency table, a rise in sensitivity would lead to a fall in

specificity, vice versa.

Choose a highly sensitive test if effective treatment is

available for a true positive finding (e.g. tuberculosis,

syphillis, etc.). In addition to being effective, this treatment

may be inexpensive, and non-expansive, resulting negligible

side effects.

On the other hand, a false negative finding would

disadvantage the patient and a larger community and place

them at high risk for an illness since they are untreated with

the available effective treatment.

Choose a highly specific test if the test is invasive, expensive,

and resulting in much adverse effects (e.g. chemotherapy for

cancers) for a true negative finding, while a false positive

finding would stigmatize patient (e.g. HV/AIDS).

As the name suggests, it measures how well your diagnostic test

predicts the disease.

High PPV means high probability that those individuals

with a positive test will actually have the disease

a

215

PPV

93%

a b 231

Likewise, high NPV means high probability that those

individuals with a negative test will actually NOT have

the disease

d

114

NPV

88%

c d 129

Value, Sensitivity, Specificity, and Prevalence?

Predictive value of a diagnostic test is based on its sensitivity

and specificity.

That is, the more sensitive and specific your diagnostic test has,

the higher predictive value, meaning the more likely that your

patients classified as positive will actually have the disease, or

classified as negative will actually NOT have the disease.

But predictive value also depends on the prevalence of the

target disease in the population.

The higher prevalence of a disease, the higher predictive value

you will get! The lower prevalence of a disease, the lower

predictive value, even if sensitivity and specificity are high!

As I mentioned before, PPV refers to how likely an

individual classified as positive by your diagnostic test will

actually have the disease.

Since PPV indicates the probability of having the

disease AFTER you use the diagnostic test, it is also

called as POSTTEST PROBABILITY, or POSTERIOR

PROBABILITY.

Recall PRETEST PROBABILITY or PRIOR

PROBABILITY refers to the likelihood that your patient

has the disease, BASED on HISTORY TAKING AND

PHYSICAL EXAMINATION. That is, BEFORE YOU USE A

DIAGNOSTIC TEST.

A diagnostic test helps us to refine our pretest probability

into posttest probability.

A test can increase or decrease our pretest probability of

a disease into posttest probability:

= Posttest probability

By rule of thumb, posttest probability > 80% is sufficiently

high that we are certain enough to start working our patient

up for causes of the target disorder.

Likelihood Ratio

As the name suggests, a likelihood ratio is a ratio of likelihoods:

The probability of test positive in someone with disease relative

to someone without disease.

Likelihood of test positive in someone

WITH disease

a/(a+c)

b/(b+d)

WITHOUT disease

sensitivity

LR(+)= -----------------1 - specificity

1- sensitivity

LR(-)= ------------------specificity

Results from A Study Assessing The Clinical Values of a Diagnostic Test

Myocardial Infarction

Positive

(>=80IU)

CK Test

Results

Present

Absent

215

16

231

a+b

c+d

114

129

b+d

a+b+c+d

130

360

Negative

(<80IU)

15

a+c

230

LR: An Example

215/230

LR (+) = ------------- = 7.59 = 8

16/130

times as likely to occur in a patient with

myocardial infarction than in someone without

myocardial infarction - this is called the

likelihood ratio for a positive test.

Probability

Likelihood Ratio

No disease

0.1

Lower

Unchanged

10

Higher

Disease certain

The probability of something to occur

Odds = ----------------------------------------------------------The probability of something not to occur

p

Odds = -----------1-p

Odds

Probability = ----------------Odds + 1

Probability

1-p

Posttest Probability

Pretest Probability

Pretest Odds

Likelihood Ratio

Posttest Odds

high that we are certain enough to start working our

patient up for causes of the target disorder.

When probability is not low enough (i.e. 0.10),

odd will be greater than probability, so that odd is

not a good substitute for probability

But when probability is low (i.e. <0.10), odd will

get closer to probability, so that they can be used

interchangably

When the probability is 0.5, the odds are 1.

Probability is limited to values between 0 and 1,

whereas odds range from 0 to +

Conclusions

Pretest Probability = (a+c)/(a+b+c+d) =230/360 = 0.64.

Pretest Odds = p/(1-p) = 0.64/ (1-0.64)= 1.78

LR = 8

Posttest Odds = pretest odds x LR = 1.78 x 8 = 14.22

Posttest Probability = odds/(odds+1) = 14.22/(14.22+1)= 0.93

on our patient's serum creatine kinase, it is very

likely that he has myocardial infarction (posttest

probability > 80%) and that our posttest probability is

sufficiently high that we would want to work our

patient up for causes of this target disorder.

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