BÀI 1. DẪN NHẬPY HOC ( EBM) / Y TẾ CÔNG CỘNG( EBPH) DỰA VÀO CHỨNG CỨBÀI 1. DẪN NHẬPY HOC ( EBM) / Y TẾ CÔNG CỘNG( EBPH) DỰA VÀO CHỨNG CỨ
GS TS BS LÊ HOÀNG NINH
Nội dung cốt lõiNội dung cốt lõi
•Tại sao y hoc chứng cứ là quan trọng
•Y học chứng cứ là gì ?
•Phân biệt foreground vs. backgroundquestions
•Đặt câu hỏi dạng PICO
•Tìm nguồn tư liệu
•Giá trị của một bào báo khoa học y học / sứckhoẻ
•Đánh giá các dạng bài báo : can thiệp điều trị/ dự phòng; chẩn đoán/ sàng lọc; nguyênnhân…
Tại sao EBM là quan trọng?Tại sao EBM là quan trọng?
•MEDLINE
–400,000 new entries added each year
•To keep up-to-date
–Need to read 6,000 articles each day
Tại sao EBM là quan trọng?Tại sao EBM là quan trọng?
sự chậm trễ “ từ lúc biết cho tới lúcáp dụng”
–13 years for thrombolytic therapy
–10 years for corticosteroids foracceleration of fetal lung maturity
(Antman EM, JAMA, 1992)
Traditional ApproachesTraditional Approaches
Self-reported reading time per week.(University setting)
–Medical students60 min.
–Internsnone
–Senior residents10 min.
–Fellows45 min.
–Attendings graduating
•Post 197560 min.
•Pre 197530 min.
There is simply no way wecan keep up to date inmedicine using traditionalapproaches!There is simply no way wecan keep up to date inmedicine using traditionalapproaches!
Nội dung cốt lõiNội dung cốt lõi
•Why is EBM important?
•What is EBM?
•Understand foreground vs. backgroundquestions
•Formulate PICO questions
•Find resources, do searches
•Validity of an article
•Appraise “Therapy” articles
•Appraise “Diagnostic” articles
Research Evidence
Clinical Expertise
Patient Preference
Decision MakingDecision Making
Qui trìnhQui trình
y học chứng cứ / y tế công cộngy học chứng cứ / y tế công cộng
Patients
Ask Questions
Searching
Appraise
Validity Results Applicability
Nội dung cốt lõiNội dung cốt lõi
•Why is EBM important?
•What is EBM
•Understand foreground vs. backgroundquestions
•Formulate PICO questions
•Find resources, do searches
•Validity of an article
•Appraise “Therapy” articles
•Appraise “Diagnostic” articles
What’s the differencebetween foreground andbackground questions?
Asking the Precise QuestionAsking the Precise Question
•Background questions
•Basic aspect of adisease
•Pathophysiology
•Etiology
•Basic treatment
•Who, what, when, how
•Foreground questions
•Specific knowledge
•Have 4 parts:
•Patient/problem
•Intervention
•Comparisonintervention
•Clinical outcomes
Background or Foreground?
•What is asthma?
•Is prednisone helpful in asthma?
•What are the newest medication forasthma?
•Does atrovent used acutely make youfeel 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 feelbetter? (F)
•Is prednisone helpful in asthma? (F or B)
•Foreground if compare to other drugs
•Background if interested in how it works
Nội dung cốt lõiNội dung cốt lõi
•Why is EBM important?
•What is EBM
•Understand foreground vs. backgroundquestions
•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
Formulating the Clinical Question
PICO
Can You Identify PICO?Can You Identify PICO?
•In children under 6 months, how doessleeping on back compared to sleeping onthe stomach in terms of risk of SIDS?
•In children under 6 months (P), how doessleeping on back (I) compared to sleeping onthe 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 persistentasthma now in severe acute asthmaexacerbation. Intern gave 2 albuteroland orapred with minimalimprovement. Intern asks why howgood is atrovent?
Searchable PICO QuestionSearchable 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) toalbuterol (C) decrease the rate ofhospitalization (O)?
Nội dung cốt lõiNội dung cốt lõi
•Why is EBM important?
•What is EBM
•Understand foreground vs. backgroundquestions
•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
–Very high quality reviews
–Mostly questions of therapy
•National Guideline Clearinghouse
–Guidelines of varying levels of quality
–Do broad searches
•PEM database
–Not pre-appraised
Pre-appraised ResourcesPre-appraised Resources
•Best Evidence Topics
–Developed in the ED of Manchester RoyalInfirmary in UK
–Usually EM topics
–Free
•Clinical Evidence (CE Concise)
–From UK
–Focus mostly on therapy
–Free
Primary Search EnginesPrimary Search Engines
•Pubmed
•Ovid
What is MEDLINE?What is MEDLINE?
•MEDLINE is a DATABASE
•MEDLINE is produced by the NationalLibrary of Medicine
•MEDLINE is available free via Pubmed
•MEDLINE is sold to many vendors, likeOvid, who search the DATA in MEDLINEthrough different search engines
PubMed: Clinical Queries
•Pre-filtered searching
•Search on questions of
–Therapy
–Diagnosis
–Etiology
–Prognosis
•Or, search for Systematic Reviews
Limit any of the categories tosensitivity (broad) or specificity(narrow)
OVIDOVID
•Most librarians favor this search engine
•Allow you to tailor your search
Nội dung cốt lõiNội dung cốt lõi
•Why is EBM important?
•What is EBM
•Understand foreground vs. backgroundquestions
•Formulate PICO questions
•Find resources, do searches
•Validity of an article
•Appraise “Therapy” articles
•Appraise “Diagnostic” articles
Appraise (Validity)Appraise (Validity)
Validity of Therapy ArticlesValidity of Therapy Articles
•Randomized?
•Blinded?
•Were the subjects similar at the start ofthe trial?
•Were all subjects treated the sameexcept for the treatment of interest?
•Were all patients accounted for at theend of the trial?
Validity:1. Were the Subjects Randomized?Validity:1. Were the Subjects Randomized?
“Methods” section
Validity:2. Were They Blinded?
“Methods” section
Validity:3. Were the Subjects Similar atthe Start of the Trial?
“Results” section
Validity:4. Were All Subjects Treated the Sameexcept for the Treatment of Interest?
“Methods” section
Validity:5. Were All Patients Accountedfor at the End of the Trial?Validity:5. Were All Patients Accountedfor 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 ofthe trial?
•Were all subjects treated the same exceptfor the treatment of interest?
•Were all patients accounted for at the endof the trial?
Nội dung cốt lõiNội dung cốt lõi
•Why is EBM important?
•What is EBM
•Understand foreground vs. backgroundquestions
•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 anadverse outcome
•Mathematically
–NNT = 1/ARR (absolute risk reduction)
•ARR = Risk of adverse outcome in the controlgroup (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 continuousvariables
•For NNT to be meaningful, thedifference between the 2 groupsmust be significant
Let’s Calculate NNT
CER
EER
ARR
NNT
50%
20%
3%
2.5%
30%
25%
CER: Control Event RateEER: 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
The benefits outweigh the risks. Thereforeit would be worth treating the child withAtrovent in the emergency department.
OutlineOutline
•Why is EBM important?
•What is EBM
•Understand foreground vs. backgroundquestions
•Formulate PICO questions
•Find resources, do searches
•Validity of an article
•Appraise “Therapy” articles
•Appraise “Diagnostic” articles
Appraise (Validity)Appraise (Validity)
Validity of Diagnostic Articles
•Was there an independent, blindcomparison with a reference (“gold”)standard of diagnosis?
•Was the diagnostic test evaluated in anappropriate spectrum of patients (likethose in whom it would be used inpractice)?
Validity of Diagnostic Articles
•Was the reference standard appliedregardless of the diagnostic testresult?
•Was the test (or cluster of tests)validated in a second, independentgroup 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
•Sensitivity
The proportion of people with the targetdisorder (A+C) who have a positive test (A)
A/(A+C)
• SnNout
If a test has a high sensitivity, a negativeresult 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 thedisease (B+D) who have a negative test (D)
D/(B+D)
•SpPin
When a test has a high specificity, a positiveresult 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 resultwould be expected in a patient w/the target disorder compared w/the likelihood that the same resultwould be expected in a patient w/othe target disorder
Likelihood RatioLikelihood Ratio
•Likelihood ratio (LR) of 1 means
The test result identifies patients w/ thedisorder at the same rate as identifyingpatients w/o the disorders
•LR >1
The test result identifies patients w/ thedisorder at a faster rate; likelihood goes
•LR <1
The test result identifies patients w/ thedisorder at a slower rate; likelihood goes
LR of 3 means:
The result is 3 times more likely tooccur in a patient w/ the target diseasethan in a patient without.
In general, the LR for a test result isthe percentage of “disease +” patientsidentified by that result divided by thepercentage of “disease –” patients soidentified.
Dis +
Dis -
RateDis +
RateDis -
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 canpersonalize the test to our patients
Test
threshold
Treatmentthreshold
0%
100%
No testneeded
Further testingneeded
Testing completed;treatment starts
Test & Treatment Thresholds inthe Diagnostic ProcessTest & Treatment Thresholds inthe Diagnostic Process
Step 1: Pre-test ProbabilityStep 1: Pre-test Probability
•Prevalence
The number of events (instances of a givendisease or other condition) in a givenpopulation 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
90
Rapid Strep
LR + = TP rate/FP rate = (65/75) (18/90) = 4.35
Amir, 1994
LR - = FN rate/TN rate = (10/75) (72/90) = 0.16
Fagan NomogramFagan Nomogram
Pre-test probabilityon the left handcolumn
LR in the middle
Post-test probabilityon the right handcolumn
TranslationTranslation
•You see a 4 yo child who comes in c/osorethroat, no other complaints
•Your pre-test probability is that she hasa 30% chance of having strep throat
•You wonder how good is rapid strep
•You look up an article (Amir, 1994) andfind its sensitivity (86.5%) andspecificity (80%)
TranslationTranslation
•Your patient rapid strep is positive
•You calculated the LR + to be 4.35
•You determined the post-testprobability to be 66%
•Is that enough of a threshold for you totreat or would you rather do more test?
Test
threshold
Treatmentthreshold
0%
100%
No testneeded
Further testingneeded
Testing completed;treatment starts
Test & Treatment Thresholds inthe Diagnostic ProcessTest & Treatment Thresholds inthe 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 determinelikelihood ratio (LR)
•LR + = True pos rate/False pos rate
•LR - = False neg rate/True neg rate
•Use Fagan Nomogram