Probabilities in Clinical Medicine

Mohammad Saifur Rohman, MD. PhD.

Interventional Cardiologist

Department of Cardiology and Vascular Medicine

Faculty of Medicine, Brawijaya University/dr. Saiful Anwar
Hospital, Malang
 Evidence based Medicine

The integration of:

 Best Research Evidence with
 Clinical Expertise and
 Patient Values

Sackett et al., 2000

 Evidences
Research Evidence: clinically relevant
research, sometimes from basic sciences,
often from clinical research studies
examining
Diagnostic tests
Markers of prognosis
Safety and efficacy of treatment
Rehabilitative or preventive regimens
 Patient oriented
Patient Values: the unique concerns,
expectations and preferences each
patient brings to that particular clinical
encounter.
Incorporate these into clinical-
decision making as part of our
collaborative treatment with the
patient.
 Skills
Clinical Expertise: using our clinical skills
and past experience to identify health
states, diagnosis, risks and benefits for
individual patients,

and integrate their …

 Reasoning Under Uncertainty Example:
Medical Diagnosis

• Uncertainty is inherent to medical reasoning

– Relation of diseases to clinical and laboratory
findings is probabilistic
– Patient data itself is often uncertain with respect
to value and time
– Patient preferences regarding outcomes vary
– Cost of interventions and therapy can change
 An Example: Chest pain
• pressure, tightness, or heaviness, strangling,
constricting, or compression
• burning
• Indigestion, belching, dyspnea
• Angina : A syndrome resulting from myocardial
ischemia. Demand and supply imbalance
• Careful history taking; mode of onset, location,
quality of pain, duration, precipitating factors,
pattern of disappearance, risk factor,
Troponin in AMI, relative to onset and
Disease Severity
 Patient preference to outcomes

• Overestimate
• Underestimate
• Hopeful
• Hopeless
 Cost Effective Treatment

• Correct diagnosis
• Proper patient
• Best choice
• Feasible
• Risk/benefit
 What is Diagnosis?

“The anatomic, biochemical, physiologic,

or psychologic derangement”

Labeling
DIAGNOSIS
Pathology
 What is Diagnosis?

“Diagnosis is the term which names the primary

dysfunction toward which the physical therapist
directs treatment” (Sahrmann, 1989)

Planning
DIAGNOSIS
Treatment
 Three Strategies of Clinical Diagnosis

• Pattern recognition
• Complete history and physical
examination
• Hypothetico-deductive strategy
 Pattern Recognition

• Instantaneous realization that the patient

conforms to a previously learned pattern of
disease
• Usually reflexive, not reflective
• Usually cannot be explained to others
• Argued to be “learned” on patients and not
“taught” in lecture halls
Complete History and Physical (Exhaustion)

• The pain-staking search for (but paying no

immediate attention to) all the facts about a
patient.
• Method of a novice
• Impractical and inefficient
 Hypothetico-Deductive Method
• The formulation, from the earliest clues of a
“short list” of potential diagnoses.
• Subsequent tests are performed which will
most likely reduce the length of the list.
• Requires an understanding of probability.
Gathering Diagnostic Data for a Hypothesis-
Driven Approach

• Complete versus exhaustive data gathering

• Must know what is good data
• The importance of confirmatory and
disconfirmatory data
• Rarely is one test sufficient
Appraising the Literature Regarding Diagnostic Tests

• The effectiveness of a hypothesis-driven

approach hinges on appropriate selection
and interpretation of diagnostic tests.
• The clinician must be able to appraise the
literature regarding diagnostic tests.
 Appraising the Literature Regarding
Diagnostic Tests

Condition Present Condition Absent

Test Positive
True Positive False Positive
Test Negative

False Negative True Negative

 Appraising the Literature Regarding
Diagnostic Tests

• Characteristics of Good Studies:

– Independent Gold Standard
– Operational Definitions
– Representative Subjects
 Condition Present Condition Absent

Test Positive

True Positive False Positive

B
Test Negative A

False Negative True Negative

C D

SENSITIVITY SPECIFICITY
A/(A+C) D/(B+D)
Sensitivity (True Positive Rate)

– Proportion of patients with the condition who

have a positive test result
– Tests with high sensitivity have few false
negatives, therefore a negative result rules out
the condition
Specificity (True Negative Rate)

– Proportion of patients without the condition

who have a negative test result
– Tests with high specificity have few false
positives, therefore a positive result rules in
the condition. (SpPin)
Appraising the Literature Regarding Diagnostic
Tests

• Likelihood ratios combine the information

contained in sensitivity and specificity
values.
• Permits comparisons among competing
tests.
Appraising the Literature Regarding Diagnostic
Tests

• Positive Likelihood Ratio: Expresses the

change in odds favoring the disorder given
a positive test.
 (Sensitivity/(1-Specificity))
• Negative Likelihood Ratio: Expresses the
change in odds favoring the disorder given
a negative test.
 ((1-Sensitivity) /Specificity)
Appraising the Literature Regarding Diagnostic
Tests

• What characterizes a good test?

– Large +LR (>5.0)
• change the odds favoring the diagnosis given a +
test
• helpful for ruling in the condition.
– Small -LR (<0.30)
• reduce the odds favoring the diagnosis
given a - test
• . helpful for ruling out the condition.
 Pre-Test Likelihood Post-TestProbability
Ratio Probability
X =

50% (1:1) X 5.0 = 83% (5:1)

50% (1:1) X 0.30 = 23% (.3:1)

 An Example from the Literature

• All tests had higher specificity than sensitivity,

therefore each is better as a rule in test.
• The posterior drawer test has a high +LR, and
small -LR, making it an excellent diagnostic test
Test Sens. Spec. + LR - LR
Signs (2+) 41% 79% 1.9 0.75

Symptoms (3+) 50% 81% 2.6 0.62

Signs+Symptoms (3+) 64% 62% 1.7 0.59

 Another Example

• None of the tests demonstrated good LRs

• None of the tests would function well as a
screening tool
 Integrating Diagnostic Information into
Practice

If Data Exists FIND IT!!

If Data Does
Not Exist COLLECT
IT!!
 Integrating Diagnostic Information into
Practice

• What You Need To Do:

– Decide what you are diagnosing
– List all possible variables
– Decide on the “gold standard”
– Measure Everyone !!
 An Example

You are in charge of screening residents of a

long-term care facility for those who need
therapy due to increased risk of falling.
 What are you diagnosing - Risk of falling
 What are the possible predictors?
 What will be the gold standard of fall risk?
 Follow-up everyone
 Test Characteristics
Disease Disease Disease Total
Test result present absent
True False TP+FP
Positive positive positive
(TP) (FP)
False True FN+TN
Negative negative negative
(FN) (TN)
TP+FN FP+TN
 Test Performance Measures
• The gold standard test: the procedure that defines presence or
absence of a disease (often, very costly)
• The index test: The test whose performance is examined
• True positive rate (TPR) = Sensitivity:
– P(Test is positive|patient has disease) = P(T+|D+)
– Ratio of number of diseased patients with positive tests to total
number of patient: TP/(TP+FN)
• True negative rate (TNR) = Specificity
– P(Test is negative|patient has no disease) = P(T-|D-)
– Ratio of number of nondiseased patients with negative tests to
total number of patients: TN/(TN+FP)
 Test Predictive Values

• Positive predictive value (PV+) = P(D|T+) =

TP/(TP+FP)
• Negative predictive value (PV-) = P(D-|T-) =
TN/(TN+FN)
 The Cut-off Value Trade off
• Sensitivity and specificity depend on the cut off value
between what we define as normal and abnormal
• Assume high test values are abnormal; then, moving
the cut-off value to a higher one increases FN results
and decreases FP results (i.e. more specific) and vice
versa
• There is always a trade off in setting the cut-off point
Receiver Operating Characteristic (ROC)
Curves: Examples
 Bayesian Diagnostic System Example:
de Dombal’s Abdominal-Pain System (1972)
• Domain: Acute abdominal pain (7 possible diagnoses)
• Input: Signs and symptoms of patient
• Output: Probability distribution of diagnoses
• Method: Naïve Bayesian classification
• Evaluation: an eight-center study involving 250 physicians and
16,737 patients
• Results:
– Diagnostic accuracy rose from 46 to 65%
– The negative laparotomy rate fell by almost half
– Perforation rate among patients with appendicitis fell by half
– Mortality rate fell by 22%
• Results using survey data consistently better than the clinicians’
opinions and even the results using human probability estimates!
 Belief Networks
(Bayesian/Causal Probabilistic/Probabilistic Networks, etc)
Influence diagrams without decision and utility nodes

Disease Gender

Sinusitis
Fever

Runny nose Headache

Thank You