ebm for novice
DESCRIPTION
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 - PowerPoint PPT PresentationTRANSCRIPT
EBM for NoviceEBM for Novice
Maria Kwok, MD, MPHAssistant Clinical Professor
Section of Pediatric Emergency MedicineMorgan Stanley Children’s Hospital of New York
Presbyterian
OutlineOutline• 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
Why is EBM Important?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
Why is EBM Important?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)
Traditional ApproachesTraditional 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.
There is simply no way we There is simply no way we can keep up to date in can keep up to date in
medicine using traditional medicine using traditional approaches!approaches!
OutlineOutline• 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
Quiz: Define EBMQuiz: Define EBM
C) The conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients
A) A means of camouflaging biostatistics in medical training
B) An annoying and overused catch phrase
Research Evidence
Clinical Expertise Patient Preference
Decision MakingDecision Making
Evidence Based Medicine: A ProcessEvidence Based Medicine: A Process
Patients Ask Questions
SearchingAppraise
Validity Results Applicability
OutlineOutline• 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
What’s the difference between foreground and background questions?
Asking the Precise QuestionAsking 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
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?
Background or Foreground?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
OutlineOutline• 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
Structure of a Well-built QuestionStructure 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
Patient Intervention Comparison (if relevant)
Outcome
In patients with asthma discharged
home from the emergency department
does the use of both inhaled and oral corticosteroids
compared with oral steroids
alone
lead to a reduction in
asthma relapse?
Formulating the Clinical Question
PICO
Can You Identify PICO?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)?
Can You Form a PICO Question?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?
Searchable PICO QuestionSearchable PICO Question
P: Population I: Intervention/diagnostic test/risk factorC: ComparisonO: Outcome
In children with acute asthma exacerbation (P), will the addition of atrovent (I) to albuterol (C) decrease the rate of hospitalization (O)?
OutlineOutline• 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
Searching Superhero
Best Bets
The Evidence Pyramid
If your question is about… Look for a …
Intervention/Therapy • Randomized controlled trial
Diagnosis/Screening
To assess the accuracy of the test
To assess effect of test on health
outcome
• Cohort study
• Randomized controlled trial
Prognosis •Longitudinal cohort
Etiology/Risk factors • Randomized controlled trial• Cohort• Case-control
Pre-appraised ResourcesPre-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
Pre-appraised ResourcesPre-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
Primary Search EnginesPrimary Search Engines
• Pubmed
• Ovid
Primary Search EnginesPrimary Search Engines
• Both PubMed and Ovid
• Contains MEDLINE and other bibliographic databases (Cochrane, EMBASE, etc)
• Sells access to the databases to libraries
PubMed MEDLINE vs. Ovid MEDLINEPubMed 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
What is MEDLINE?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
Database ProducerDatabase Producer
Medline
EMBASE
CINAHL
VendorsVendors
Ovid
Pubmed
Dialog
LEXIS/NEXIS
Personal PC
Library PC
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)
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
OVIDOVID
• Most librarians favor this search engine
• Allow you to tailor your search
Design & Execute Search StrategyDesign & 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
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
More on Searching TipsMore 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
More on Searching Tips
• “Term.af”• Search all fields
• “..pg term”• Perge/delete
For More Searching TipsFor More Searching Tips
Ask your librarians!
OutlineOutline• 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
Appraise (Validity)Appraise (Validity)
• http://www.cebm.utoronto.ca/teach/materials/dx.htm
• http://www.cebm.utoronto.ca/teach/materials/therapy.htm
Validity of Therapy ArticlesValidity 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?
Validity: Validity: 1. Were the Subjects Randomized?1. Were the Subjects Randomized?
“Methods” section
Validity: 2. Were They Blinded?
“Methods” section
Validity: 3. Were the Subjects Similar at
the Start of the Trial?
“Results” section
Validity: 4. Were All Subjects Treated the Same except for the Treatment of Interest?
“Methods” section
Validity: Validity: 5. Were All Patients Accounted 5. Were All Patients Accounted
for at the End of the Trial?for at the End of the Trial?
“Results” section
Validity of the ArticleValidity 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?
OutlineOutline• 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
Step 4: Appraise “Therapy” StudyStep 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
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
Let’s Calculate NNT
CER EER ARR NNT
50% 20%
3% 2.5%
30% 25%
CER: Control Event Rate EER: Experimental Event Rate
ARR: Absolute Risk Reduction NNT: Number Needed to Treat
NNT=1/ARR
30% 3
0.5% 200
5% 20
Step 4: Appraise “Therapy” ArticlesStep 4: Appraise “Therapy” Articles
• ARR = CER – EER• NNT = 1/ARR
• ARR = 52.6-37.5 = 15.1
• NNT = 1/15.1 x 100 = 7
Step 5: Decision MakingStep 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.
OutlineOutline• 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
Appraise (Validity)Appraise (Validity)
• http://www.cebm.utoronto.ca/teach/materials/dx.htm
• http://www.cebm.utoronto.ca/teach/materials/therapy.htm
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 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?
Disease + Disease -
Test + A
True +
B
False +
Test - C
False -
D
True -
A + B
C + D
A + C B + D
Sensitivity & SpecificitySensitivity & Specificity
• SensitivityThe proportion of people with the target disorder (A+C) who have a positive test (A)
A/(A+C)
• SnNoutIf a test has a high sensitivity, a negative result rules out the disease
Disease +Disease + Disease -
Test +Test + AA
True +True +
B
False +
Test - C
False -
D
True -
A + B
C + D
A + CA + C B + D
Sensitivity & SpecificitySensitivity & 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
Disease + Disease -Disease -
Test + A
True +
B
False +
Test -Test - C
False -
DD
True -True -
A + B
C + D
A + C B + DB + D
Predictive ValuesPredictive 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)
Disease + Disease -
Test + AA
True +True +
B
False +
Test - C
False -
DD
True -True -
A + BA + B
C + DC + 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 RatioLikelihood 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
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.
Dis + Dis - Rate Dis +
Rate Dis -
LR
Result A a b
Result B c d
Total X 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?
a/X b/Y(a/X)
(b/Y)
c/X d/Y(c/X)
(d/Y)
Disease + Disease -
Test + A
True +
B
False +
Test - C
False -
D
True -
X = A + C Y = B + D
At what rate are Dis + patients identified by a “+ test” ?
At what rate are Dis – patients identified by a “+ test”?
What is the LR for a “positive” test result?
A/XA/X
B/YB/Y
(A/X) ÷ (B/Y)
Positive Likelihood Ratio (LR +)Positive Likelihood Ratio (LR +)
LR + = sensitivity/(1 – specificity)
= True pos rate/False pos rate
Disease + Disease -
Test + A
True +
B
False +
Test - C
False -
D
True -
X = A + C Y = B + D
At what rate are Dis + patients identified by a “- test” ?
At what rate are Dis – patients identified by a “- test”?
What is the LR for a “negative” test result?
C/XC/X
D/YD/Y
(C/X) ÷ (D/Y)
Negative Likelihood Ratio (LR-)Negative Likelihood Ratio (LR-)
LR - = (1 – sensitivity)/specificity
= False neg rate/True neg rate
LR+ LR-
1 – 2 V PoorV Poor 1 – 0.5
2 – 5 PoorPoor 0.5 – 0.2
5 – 10 FairFair 0.2 – 0.1
10 – 20 GoodGood 0.1 – 0.05
> 20 V. GoodV. Good < 0.05
Guide to Likelihood ratios
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 threshold
Treatment threshold
0% 100%
No test needed
Further testing needed
Testing completed;
treatment starts
Test & Treatment Thresholds in Test & Treatment Thresholds in the Diagnostic Processthe Diagnostic Process
Step 1: Pre-test ProbabilityStep 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 ProbabilityPre-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 LRStep 3: Calculate LR• Pretest probability is 30%
• LR+ = ?
Culture + Culture -
Test + 65 18
Test - 10 72
Total 75 90Rap
id S
trep
LR + = TP rate/FP rate = (65/75) (18/90) = 4.35
Am
ir, 1994
LR - = FN rate/TN rate = (10/75) (72/90) = 0.16
Fagan NomogramFagan Nomogram
Pre-test probability on the left hand column
LR in the middle
Post-test probability on the right hand column
TranslationTranslation
• 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%)
TranslationTranslation
• 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?
Test threshold
Treatment threshold
0% 100%
No test needed
Further testing needed
Testing completed;
treatment starts
Test & Treatment Thresholds in Test & Treatment Thresholds in the Diagnostic Processthe Diagnostic Process
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
OutlineOutline• 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
Knowledge is of two kinds; we know a subject ourselves; or we know where we can find information upon it.
- Samuel Johnson