Diagnosis: EBM Approach

Michael Brown MD

Grand Rapids MERC/ Michigan State

University

Scenario

1 day colicky pain with nausea diffuse to RLQ mild tenderness, T 37

Step 1: Clinical Question

In the patient presenting to the ED with suspected appendicitis, what is the accuracy of helical CT ?

Step 2: Search

MeSH Browser– appendicitis AND– computerized tomography AND– sensitivity and specificity

Clinical Query– diagnosis

Step 3: Critical Appraisal

Internal Validity Results (focus today)

– even if critical appraisal not your bag

External Validity

Evidenced-based Medicine

stresses methodology de-emphasizes statistics simplify: NNT, LR

Likelihood Ratio: How to use

How to calculate

Examples

Appendicitis Pulmonary embolism

– JAMA series– current slant

Threshold Approach to Clinical Decision Making

Treatment threshold– if above, start therapy

Test threshold– if below, no further testing

Pauker NEJM 1980

Diagnostic Testing

Treatment threshold for PE?– If above: heparin

Test threshold for PE?– If below: discharge home

If between?– Further testing

Test/Treatment Threshold

prior probability

post-test probLR

(prevalence) (predictive value)

Test/Treatment Threshold

Pretest Probability

experience in your setting– patient population

prevalence of condition in literature– Oxford web site

scoring systems

Estimate Pretest Probability for PE

history risk factors physical exam initial screening tests

Estimate Pretest Probability for PE

Not exact science– usually a range 40-60%– low, intermediate, high

done daily in clinical practice clinical prediction rules

– physicians estimate very close

Wicki 2001

Bayesian Analysis?

Thomas Bayes 1702-1761 English clergyman Doctrine of Chances

Bayesian Analysis

pretest probability– prevalence

LR for diagnostic test result post-test probability

– predictive value

Interpretation

convert pretest prob to odds odds x LR = post-test odds convert odds back to prob

Interpretation

convert pretest prob to odds odds x LR = post-test odds convert odds back to prob

Fagan Nomogram

Effect on pretest probability:

>10 or <0.1 large changes 5-10 and 0.1-0.2 moderate approach 1 no effect

Advantages of LR:

combines sensitivity and specificity interpret test result on individual patient multiple cut-offs sequential testing

Shortcut: LR for + test =

sensitivity

1 - specificity

Calculate: LR=

prob (test result) with disease

prob (test result) without disease

2 x 2 Table

Target Disorder Totals

Present Absent

DiagnosticTest Result

Positive a b a+b

Negative c d c+d

Totals a+c b+d a+b+c+d

CT and Appendicitis

Target Disorder Totals

Present Absent

DiagnosticTest Result

Positive 29 4 33

Negative 1 66 67

Totals 30 70 100

Funaki et al

CT and Appendicitis

probability of + CT with appendicitis

29/30 = .97

CT and Appendicitis

Target Disorder Totals

Present Absent

DiagnosticTest Result

Positive 29 4 33

Negative 1 66 67

Totals 30 70 100

CT and Appendicitis

Likelihood of + CT with appendicitis

29/30 = .97 Likelihood of +CT without appendicitis

4/70 = .057 LR for + CT = 17

Effect on pretest probability:

>10 or <0.1 large changes 5-10 and 0.1-0.2 moderate approach 1 no effect

Scenario

1 day colicky pain with nausea diffuse to RLQ mild tenderness, T 37

Pretest probability 30% – range 20 - 40%

Helical CT

Helical CT

Helical CT

Effect on pretest probability:

>10 or <0.1 large changes 5-10 and 0.1-0.2 moderate approach 1 no effect

Advantages of LR:

combines sensitivity and specificity interpret test result on individual patient multiple cut-offs

– don’t have to lump!

sequential testing

Multiple cut-offs

appendicitis No disease Total

CT positive

CT equivocal a b

CT negative

Total x y

Calculate: LR=

prob equivocal CT with disease

prob equivocal CT without disease

Multiple cut-offs

appendicitis No disease Total

CT positive

CT equivocal a b

CT negative

Total x y

Multiple cut-offs: V/Q scan

normal low prob intermediate prob high prob

LR 0.1

LR 0.4

LR 1

LR 18

JAMA series

Sequential Testing

post-test probability 1st test new pretest probability for 2nd test assume independence

Helical CT : Diagnosis of PE

CT +

CT -

LR 8

LR .2

Rathbun, 2000

ELISA D-dimer: Diagnosis of PE

> 500

<500

LR 2

LR .1

Brown, Bermingham 2001

Helical CT

D-dimer

Test/Treatment Threshold

Questions?

Scenario

1 day colicky pain with nausea diffuse to RLQ mild tenderness, T 37

Pretest probability 30%

Discussion: CT and appy

Internal Validity Results External Validity

CT and Appendicitis

Flaws?– Minor– Major– Fatal

CT and Appendicitis (Rao)

Target Disorder

Totals

Present Absent

Diagnostic Test Result

Positive

52 1 53

Negative

1 46 47

Totals 53 47 100

Rao et al

+LR = .98/.02 = 46-LR = .019/.98= .02

CT and Appendicitis (Funaki)

Target Disorder Totals

Present Absent

DiagnosticTest Result

Positive 29 4 33

Negative 1 66 67

Totals 30 70 100

Funaki et al

CT and Appendicitis

Likelihood of + CT with appendicitis

29/30 = .97 Likelihood of +CT without appendicitis

4/70 = .057 LR for + CT = 17

Funaki: CT and Appendicitis

LR for a positive CT 17 LR for a negative CT 0.03

CT and Appendicitis

Likelihood of + CT with appendicitis

29/30 = .97 Likelihood of +CT without appendicitis

4/70 = .057 LR for + CT = 17

Helical CT

Sources of LR:

PE: + CT LR = 8 - CT LR = .2

– meta-analysis: Rathbun et al Pharyngitis: neg rapid strep

- LR = 0.2– hosptial data

Alcoholism: CAGE >3 LR = 250

– web

Combinations (LRxLR)

D-dimer <500, CT - LR .02