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EBM for Novice. Maria Kwok, MD, MPH Assistant Clinical Professor Section of Pediatric Emergency Medicine Morgan Stanley Children’s Hospital of New York Presbyterian. Outline. Why is EBM important? What is EBM Understand foreground vs. background questions Formulate PICO questions

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ebm for novice

EBM for Novice

Maria Kwok, MD, MPH

Assistant Clinical Professor

Section of Pediatric Emergency Medicine

Morgan Stanley Children’s Hospital of New York Presbyterian

outline
Outline
  • Why is EBM important?
  • What is EBM
  • Understand foreground vs. background questions
  • Formulate PICO questions
  • Find resources, do searches
  • Validity of an article
  • Appraise “Therapy” articles
  • Appraise “Diagnostic” articles
slide3

Why is EBM Important?

  • MEDLINE
    • 400,000 new entries added each year
  • To keep up-to-date
    • Need to read 6,000 articles each day
slide4

Why is EBM Important?

Lag time from time of “knowing” to time of “implementation”

  • 13 years for thrombolytic therapy
  • 10 years for corticosteroids for acceleration of fetal lung maturity

(Antman EM, JAMA, 1992)

slide5

Traditional Approaches

Self-reported reading time per week. (University setting)

  • Medical students 60 min.
  • Interns none
  • Senior residents 10 min.
  • Fellows 45 min.
  • Attendings graduating
    • Post 1975 60 min.
    • Pre 1975 30 min.
slide7

Outline

  • Why is EBM important?
  • What is EBM?
  • Understand foreground vs. background questions
  • Formulate PICO questions
  • Find resources, do searches
  • Validity of an article
  • Appraise “Therapy” articles
  • Appraise “Diagnostic” articles
slide8

Quiz: Define EBM

A) A means of camouflaging biostatistics in medical training

B) An annoying and overused catch phrase

C) The conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients

slide9

Research Evidence

Decision Making

Patient Preference

Clinical Expertise

slide10

Evidence Based Medicine: A Process

Patients

Ask Questions

Appraise

Searching

slide12

Outline

  • Why is EBM important?
  • What is EBM
  • Understand foreground vs. background questions
  • Formulate PICO questions
  • Find resources, do searches
  • Validity of an article
  • Appraise “Therapy” articles
  • Appraise “Diagnostic” articles
slide14

Asking the Precise Question

  • Background questions
  • Basic aspect of a disease
    • Pathophysiology
    • Etiology
    • Basic treatment
  • Who, what, when, how
  • Foreground questions
  • Specific knowledge
  • Have 4 parts:
  • Patient/problem
  • Intervention
  • Comparison intervention
  • Clinical outcomes
slide15

Background or Foreground?

  • What is asthma?
  • Is prednisone helpful in asthma?
  • What are the newest medication for asthma?
  • Does atrovent used acutely make you feel better?
slide16

Background or Foreground?

  • What is asthma? (B)
  • What are the newest medication for asthma? (B)
  • Does atrovent used acutely make you feel better? (F)
  • Is prednisone helpful in asthma? (F or B)
    • Foreground if compare to other drugs
    • Background if interested in how it works
slide17

Outline

  • Why is EBM important?
  • What is EBM
  • Understand foreground vs. background questions
  • Formulate PICO questions
  • Find resources, do searches
  • Validity of an article
  • Appraise “Therapy” articles
  • Appraise “Diagnostic” articles
slide18

Structure of a Well-built Question

  • Patient or population
    • Be specific to capture the group you want
    • Ex: Children w/ asthma
  • Intervention
    • Be specific
  • Comparison group (if any)
    • Compare to standard therapy or test
  • Outcome
    • Be precise
    • What are the outcome of interest
slide20

Can You Identify PICO?

  • In children under 6 months, how does sleeping on back compared to sleeping on the stomach in terms of risk of SIDS?
  • In children under 6 months (P), how does sleeping on back (I) compared to sleeping on the stomach (C) in terms of risk of SIDS (O)?
slide21

Can You Form a PICO Question?

Clinical scenario:

5 yo with moderate persistent asthma now in severe acute asthma exacerbation. Intern gave 2 albuterol and orapred with minimal improvement. Intern asks why how good is atrovent?

slide22

Searchable PICO Question

P: Population

I: Intervention/diagnostic test/risk

factor

C: Comparison

O: Outcome

In children with acute asthma exacerbation (P), will the addition of atrovent (I) to albuterol (C) decrease the rate of hospitalization (O)?

slide23

Outline

  • Why is EBM important?
  • What is EBM
  • Understand foreground vs. background questions
  • Formulate PICO questions
  • Find resources, do searches
  • Validity of an article
  • Appraise “Therapy” articles
  • Appraise “Diagnostic” articles
slide27

Pre-appraised Resources

  • Cochrane
    • http://www.cochrane.org/cochrane/revabstr/mainindex.htm
    • Very high quality reviews
    • Mostly questions of therapy
  • National Guideline Clearinghouse
    • http://www.guideline.gov/
    • Guidelines of varying levels of quality
    • Do broad searches
  • PEM database
    • http://researchinpem.homestead.com/homepage.html
    • Not pre-appraised
slide28

Pre-appraised Resources

  • Best Evidence Topics
    • http://www.bestbets.org
    • Developed in the ED of Manchester Royal Infirmary in UK
    • Usually EM topics
    • Free
  • Clinical Evidence (CE Concise)
    • http://www.clinicalevidence.com
    • From UK
    • Focus mostly on therapy
    • Free
slide30

Primary Search Engines

  • Both PubMed and Ovid
  • Contains MEDLINE and other bibliographic databases (Cochrane, EMBASE, etc)
  • Sells access to the databases to libraries
slide31

PubMed MEDLINE vs. Ovid MEDLINE

  • Same DATABASE
  • Different SEARCH ENGINES
    • Searching differently may get you slightly different results
    • If you search both databases EXACTLY the same, your results will be the same
slide32

What is MEDLINE?

  • MEDLINE is a DATABASE
    • MEDLINE is produced by the National Library of Medicine
    • MEDLINE is available free via Pubmed
    • MEDLINE is sold to many vendors, like Ovid, who search the DATA in MEDLINE through different search engines
slide33

Database Producer

Vendors

Medline

EMBASE

CINAHL

Ovid

Pubmed

Dialog

LEXIS/NEXIS

Personal PC

Library PC

slide34

PubMed: Clinical Queries

  • Pre-filtered searching
  • Search on questions of
    • Therapy
    • Diagnosis
    • Etiology
    • Prognosis
  • Or, search for Systematic Reviews

Limit any of the categories to sensitivity (broad) or specificity (narrow)

slide38

Sensitivity vs. Specificity

  • SPECIFICITY
  • Narrower search
  • More relevant items
  • Possibility of losing some useful citations
  • LESS information to weed through
  • SENSITIVITY
  • Broader search
  • More irrelevant items
  • Less chance of losing useful citations
  • MORE information to weed through
slide43

OVID

  • Most librarians favor this search engine
  • Allow you to tailor your search
slide45

Design & Execute Search Strategy

  • MeSH terms
    • How articles are indexed
    • Predefined categories from the National Library of Medicine
  • Explode
    • MeSH + all items underneath
  • Focus
    • MeSH only
slide46

Design & Execute Search Strategy

  • Limiters
    • Limit by languages, human, age, etc
  • Hedges
    • “Clinical trials” for therapy
    • “Sensitivity” & “Specificity” for diagnostic tests
    • “Cohort studies” for prognosis
slide47

More on Searching Tips

  • “Term$”
    • Search engines will look for occurrences of the word with any combination of letters following. (Ex: “Hospital$” will include hospitalization, hospitals, hospitalized)
  • “Exp” for “explode”
  • “Term.tw.”
    • Allow search engine to look in the titles and abstract
slide48

More on Searching Tips

  • “Term.af”
    • Search all fields
  • “..pg term”
    • Perge/delete
slide49

For More Searching Tips

Ask your librarians!

slide50

Outline

  • Why is EBM important?
  • What is EBM
  • Understand foreground vs. background questions
  • Formulate PICO questions
  • Find resources, do searches
  • Validity of an article
  • Appraise “Therapy” articles
  • Appraise “Diagnostic” articles
slide51

Appraise (Validity)

  • http://www.cebm.utoronto.ca/teach/materials/dx.htm
  • http://www.cebm.utoronto.ca/teach/materials/therapy.htm
slide52

Validity of Therapy Articles

  • Randomized?
  • Blinded?
  • Were the subjects similar at the start of the trial?
  • Were all subjects treated the same except for the treatment of interest?
  • Were all patients accounted for at the end of the trial?
slide54

Validity: 2. Were They Blinded?

“Methods” section

slide56

Validity: 4. Were All Subjects Treated the Same except for the Treatment of Interest?

“Methods” section

slide58

Validity of the Article

  • Was the study randomized?
  • Were the subjects blinded?
  • Were the subjects similar at the start of the trial?
  • Were all subjects treated the same except for the treatment of interest?
  • Were all patients accounted for at the end of the trial?
slide59

Outline

  • Why is EBM important?
  • What is EBM
  • Understand foreground vs. background questions
  • Formulate PICO questions
  • Find resources, do searches
  • Validity of an article
  • Appraise “Therapy” articles
  • Appraise “Diagnostic” articles
slide60

Step 4: Appraise “Therapy” Study

  • Therapy study
    • Number Needed to Treat (NNT) to prevent an adverse outcome
  • Mathematically
    • NNT= 1/ARR (absolute risk reduction)
  • ARR = Risk of adverse outcome in the control group (CER) – those in the experimental group (EER)
    • ARR* = CER** – EER***

*ARR: Absolute risk reduction

**CER: control event rate

***EER: experimental event rate

slide61

More on NNT

  • Variables must be dichotomous
    • Cannot calculate NNT from continuous variables
  • For NNT to be meaningful, the difference between the 2 groups must be significant
slide62

Let’s Calculate NNT

30%

3

0.5%

200

5%

20

CER: Control Event Rate EER: Experimental Event Rate

ARR: Absolute Risk Reduction NNT: Number Needed to Treat

NNT=1/ARR

slide63

Step 4: Appraise “Therapy” Articles

  • ARR = CER – EER
  • NNT = 1/ARR
  • ARR = 52.6-37.5 = 15.1
  • NNT = 1/15.1 x 100 = 7
slide64

Step 5: Decision Making

Atrovent

  • Low cost medication
  • Minimal to no side effects
  • Every 7 children with severe asthma exacerbation, 1 hospitalization will be prevented

The benefits outweigh the risks. Therefore it would be worth treating the child with Atrovent in the emergency department.

slide65

Outline

  • Why is EBM important?
  • What is EBM
  • Understand foreground vs. background questions
  • Formulate PICO questions
  • Find resources, do searches
  • Validity of an article
  • Appraise “Therapy” articles
  • Appraise “Diagnostic” articles
slide66

Appraise (Validity)

  • http://www.cebm.utoronto.ca/teach/materials/dx.htm
  • http://www.cebm.utoronto.ca/teach/materials/therapy.htm
validity of diagnostic articles
Validity of Diagnostic Articles
  • Was there an independent, blind comparison with a reference (“gold”) standard of diagnosis?
  • Was the diagnostic test evaluated in an appropriate spectrum of patients (like those in whom it would be used in practice)?
validity of diagnostic articles68
Validity of Diagnostic Articles
  • Was the reference standard applied regardless of the diagnostic test result?
  • Was the test (or cluster of tests) validated in a second, independent group of patients?
slide69

A + B

C + D

A + C

B + D

sensitivity specificity
Sensitivity & Specificity
  • Sensitivity
  • The proportion of people with the target disorder (A+C) who have a positive test (A)
  • A/(A+C)
  • SnNout
  • If a test has a high sensitivity, a negative result rules out the disease
slide71

A + B

C + D

A + C

B + D

sensitivity specificity72
Sensitivity & Specificity
  • Specificity
  • The proportion of people without the disease (B+D) who have a negative test (D)
  • D/(B+D)
  • SpPin
  • When a test has a high specificity, a positive result rules IN the diagnosis
slide73

A + B

C + D

A + C

B + D

predictive values
Predictive Values
  • Positive Predictive Value
  • Proportion of people with a positive test (A+B) who have the target disorder
  • A/(A+B)
  • Negative Predictive Value
  • Proportion of people with a negative test (C+D) who are free of the disease (D)
  • D/(C+D)
slide75

A + B

C + D

A + C

B + D

what is likelihood ratio
What is Likelihood Ratio?

A likelihood that a given test result would be expected in a patient w/ the target disorder compared w/ the likelihood that the same result would be expected in a patient w/o the target disorder

likelihood ratio
Likelihood Ratio
  • Likelihood ratio (LR) of 1 means
    • The test result identifies patients w/ the disorder at the same rate as identifying patients w/o the disorders
  • LR >1
    • The test result identifies patients w/ the disorder at a faster rate; likelihood goes 
  • LR <1
    • The test result identifies patients w/ the disorder at a slower rate; likelihood goes 
slide78

LR of 3 means:

The result is 3 times more likely to occur in a patient w/ the target disease than in a patient without.

In general, the LR for a test result is the percentage of “disease +” patients identified by that result divided by the percentage of “disease –” patients so identified.

slide79

(a/X)

(b/Y)

a/X

b/Y

(c/X)

(d/Y)

c/X

d/Y

What rate are Dis + patients identified by Result A?

What rate are Dis - patients identified by Result A?

What is the LR for Result A?

slide80

X = A + C

Y = B + D

At what rate are Dis + patients identified by a “+ test” ?

A/X

At what rate are Dis – patients identified by a “+ test”?

B/Y

What is the LR for a “positive” test result?

(A/X) ÷ (B/Y)

positive likelihood ratio lr
Positive Likelihood Ratio (LR +)

LR + = sensitivity/(1 – specificity)

= True pos rate/False pos rate

slide82

X = A + C

Y = B + D

At what rate are Dis + patients identified by a “- test” ?

C/X

At what rate are Dis – patients identified by a “- test”?

D/Y

What is the LR for a “negative” test result?

(C/X) ÷ (D/Y)

negative likelihood ratio lr
Negative Likelihood Ratio (LR-)

LR - = (1 – sensitivity)/specificity

= False neg rate/True neg rate

why do we care about lr
Why Do We Care About LR?

Allow us to think about pre-test and post-test probabilities so that we can personalize the test to our patients

test treatment thresholds in the diagnostic process
Test & Treatment Thresholds in the Diagnostic Process

Test

threshold

Treatment threshold

0%

100%

Testing completed; treatment starts

No test needed

Furthertesting needed

step 1 pre test probability
Step 1: Pre-test Probability
  • Prevalence

The number of events (instances of a given disease or other condition) in a given population at a designated time.

It is not a rate.

It is used as pre-test probability

It is the number of “disease +” patients to the “total”

pre test probability
Pre-test Probability

5 sources to determine this:

  • Clinical experience
  • Regional or national prevalence statistics
  • Practice databases
  • Original report on accuracy of the test
  • Studies that calculate pre-test probability
step 3 calculate lr
Step 3: Calculate LR
  • Pretest probability is 30%
  • LR+ = ?

Amir, 1994

Rapid Strep

LR + = TP rate/FP rate = (65/75)  (18/90) = 4.35

LR - = FN rate/TN rate = (10/75)  (72/90) = 0.16

slide90

Fagan Nomogram

Pre-test probability on the left hand column

LR in the middle

Post-test probability on the right hand column

translation
Translation
  • You see a 4 yo child who comes in c/o sorethroat, no other complaints
  • Your pre-test probability is that she has a 30% chance of having strep throat
  • You wonder how good is rapid strep
  • You look up an article (Amir, 1994) and find its sensitivity (86.5%) and specificity (80%)
translation92
Translation
  • Your patient rapid strep is positive
  • You calculated the LR + to be 4.35
  • You determined the post-test probability to be 66%
  • Is that enough of a threshold for you to treat or would you rather do more test?
slide93

Test & Treatment Thresholds in the Diagnostic Process

Test

threshold

Treatment threshold

0%

100%

Testing completed; treatment starts

No test needed

Furthertesting needed

a different article showed
A Different Article Showed…
  • What if the LR+ is 12?
  • What is the post-test probability?
diagnostic summary
“Diagnostic” Summary…
  • Use the 2 x 2 table to determine likelihood ratio (LR)
    • LR + = True pos rate/False pos rate
    • LR - = False neg rate/True neg rate
  • Use Fagan Nomogram
slide97

Outline

  • Why is EBM important?
  • What is EBM
  • Understand foreground vs. background questions
  • Formulate PICO questions
  • Find resources, do searches
  • Validity of an article
  • Appraise “Therapy” articles
  • Appraise “Diagnostic” articles
slide98

Knowledge is of two kinds; we know

a subject ourselves; or we know

where we can find information upon it.

- Samuel Johnson