Evidence Based Diagnosis

When a Patient Has a ProblemWhen a Patient Has a Problem

The doctor reaches a diagnosis by:The doctor reaches a diagnosis by:

• Clinical dataClinical data

• Diagnostic toolsDiagnostic tools

Increasing use of Diagnostic Increasing use of Diagnostic tests:tests:

- Availability.- The urge to make use of new technology.

The evaluation of diagnostic techniques is less advanced than that

of treatments (NO phase I, II, III, IV).

New Diagnostic testsNew Diagnostic tests

RelevanceRelevance

• First, the test should be one that is feasible for you in your community

• Example: brain biopsy is an accurate test for diagnosing dementia, it’s not practical for my (living) patients!

• Can I apply the test to my patients? (Availability, Cost) e.g MRI

ValidityValidity

The degree to which the results of a study are likely to be true and free from bias.

• It should be compared to a gold reference standard

CautionCaution

• reference standard used should be acceptable (e.g HSG vs DL)

• Both reference standard and test should be applied to all patients

IndependentIndependent

• the decision to perform the reference standard should ideally be independent of the results of the test being studied.

Ask yourselfAsk yourself

• the patient sample should include an appropriate spectrum of patients to whom the diagnostic test will be applied in clinical practice

Rule of ThumbRule of Thumb

• at least 100 participants to ensure an appropriate "spectrum" of disease

22 x 2 tablex 2 table comparing the results of a diagnostic test with a reference standard

reference standard

diseaseno disease

test abnormaltrue pos. [a]false pos. [b]

test normalfalse neg. [c]true neg. [d]

sensitivitysensitivity

• probability of a positive test among patients with disease

• i.e Ability to diagnose

specificityspecificity

• probability of a negative test among patients without disease

• i.e Ability to exclude

22 X 2 TableX 2 Table

a(true positive)

b(false positive)

c(false negative)

d(true negative)

Keep in MindKeep in Mind

• sensitivity and specificity by themselves are only useful when either is very high (over typically, 95% or higher).

Who wants whatWho wants what? ?

main interest

Methodologistsensitivity

specificity

Doctoraccuracy

PatientProbability

Likelihood RatioLikelihood Ratio

The "positive likelihood ratio" (LR+) tells us how much to increase the probability of disease if the test is positive

The "negative likelihood ratio" (LR-) tells us how much to decrease it if the test is negative

Likelihood RatioLikelihood RatioLR=+

probability of a +ve test in those who have the disease___probability of a +ve test in those who do not have the disease

=   sensitivity         1-specificity

LR=- probability of a -ve test in those who have the disease___

probability of a -ve test in those who do not have the disease

=   1-sensitivity     specificity

LRInterpretationInterpretation >10

Large and often conclusive increase in the likelihood of disease

5 - 10Moderate increase in the likelihood of disease

2 - 5Small increase in the likelihood of disease

1 - 2Minimal increase in the likelihood of disease

1No change in the likelihood of disease

0.5 - 1.0

Minimal decrease in the likelihood of disease

0.2 - 0.5

Small decrease in the likelihood of disease

0.1 - 0.2

Moderate decrease in the likelihood of disease

<0.1Large and often conclusive decrease in the likelihood of

disease

Why LR

• The LR+ corresponds to the clinical concept of "ruling-in disease"

• The LR- corresponds to the clinical concept of "ruling-out disease“

Patient oriented!!!!!!!

• Your 45 year old patient has a mammogram. The study is interpreted as "suspicious for malignancy" by your radiologist.

• Your patient asks you:"Does this mean I have cancer?", and you (correctly) answer "No, we have todo further testing."  

• Your patient then asks, "OK, I understand that the mammogram isn't the final answer, but given what we know now, what are the chances that I have breast cancer?".

Is it Easy!!!

• Assume that the overall risk of breast cancer in any 45 year old woman,

regardless of mammogram result, is1%. Assume also that mammography is 90% sensitive and 95% specific. Then,

select your answer below:

1%    15%      60%      85%    95%

If you know that the risk of breast cancer in any 45 year old woman is 1% and that mammography is 90% sensitive and 95% specific.

What do you think your patient’s probability of having breast cancer is?

LR+=Sens/100-Spec

=90/5=18

Diseaseruled IN

Disease ruled OUT

Disease not

ruled in or out

Above this point,treat

Below this point,no further testing

Determined by:Complications of untreated disease

Risks of therapyComplications of tests

Cost

ROC curve is simply a graph of sensitivity vs (1-specificity)

ScoreSystematic Collaboration of Ovarian Reserve Evaluation

systematic reviews of Diagnostic tests

THANK YOU