Bài giảng Bài 1: Dẫn nhập y hoc (EBM) /y tế công cộng (EBPH) dựa vào chứng cứ

BÀI 1. DẪN NHẬP Y HOC ( EBM) / Y TẾ CÔNG CỘNG ( EBPH) DỰA VÀO CHỨNG CỨ

GS TS BS LÊ HOÀNG NINH

Nội dung cốt lõi

• Tại sao y hoc chứng cứ là quan trọng • Y học chứng cứ là gì ? • Phân biệt foreground vs. background

questions

• Đặt câu hỏi dạng PICO • Tìm nguồn tư liệu • Giá trị của một bào báo khoa học y học / sức

khoẻ

• Đánh giá các dạng bài báo : can thiệp điều trị / dự phòng; chẩn đoán/ sàng lọc; nguyên nhân…

Tại sao EBM là quan trọng?

• MEDLINE

• To keep up-to-date

– 400,000 new entries added each year

– Need to read 6,000 articles each day

Tại sao EBM là quan trọng?

sự chậm trễ “ từ lúc biết cho tới lúc áp dụng” – 13 years for thrombolytic therapy – 10 years for corticosteroids for

acceleration of fetal lung maturity

(Antman EM, JAMA, 1992)

Traditional Approaches

60 min. none 10 min. 45 min.

Self-reported reading time per week. (University setting) – Medical students – Interns – Senior residents – Fellows – Attendings graduating

• Post 1975 • Pre 1975 60 min. 30 min.

There is simply no way we can keep up to date in medicine using traditional approaches!

Nội dung cốt lõi

• 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

Research Evidence

Decision Making

Patient Preference

Clinical Expertise

Qui trình y học chứng cứ / y tế công cộng

Patients

Ask Questions

Appraise

Searching

Validity Results Applicability

Nội dung cốt lõi

• 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 Question

• Background questions • Basic aspect of a

• Foreground questions • Specific knowledge • Have 4 parts:

•Patient/problem

•Intervention disease • Pathophysiology • Etiology • Basic treatment

• Who, what, when, how •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?

• 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

Nội dung cốt lõi

• 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 Question • Patient or population

• Be specific to capture the group you want • Ex: Children w/ asthma

• Intervention • Be specific

• Compare to standard therapy or test

• Comparison group (if any)

• Be precise • What are the outcome of interest

• Outcome

Formulating the Clinical Question

PICO

Patient

Intervention

Outcome

Comparison (if relevant)

compared with oral steroids alone

lead to a reduction in asthma relapse?

does the use of both inhaled and oral corticosteroids

In patients with asthma discharged home from the emergency department

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?

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 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)?

Nội dung cốt lõi

• 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

• Cohort study

• Randomized controlled trial

To assess effect of test on health outcome

Prognosis

•Longitudinal cohort

Etiology/Risk factors

• Randomized controlled trial • Cohort • Case-control

Pre-appraised Resources

– http://www.cochrane.org/cochrane/revabstr/mainindex.htm – Very high quality reviews – Mostly questions of therapy

• Cochrane

– http://www.guideline.gov/ – Guidelines of varying levels of quality – Do broad searches

• National Guideline Clearinghouse

– http://researchinpem.homestead.com/homepage.html – Not pre-appraised

• PEM database

Pre-appraised Resources

• Best Evidence Topics – http://www.bestbets.org – Developed in the ED of Manchester Royal

• Clinical Evidence (CE Concise) – http://www.clinicalevidence.com – From UK – Focus mostly on therapy – Free

Infirmary in UK – Usually EM topics – Free

Primary Search Engines

• Pubmed

• Ovid

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

PubMed: Clinical Queries

• Pre-filtered searching • Search on questions of

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

• Or, search for Systematic Reviews

– Therapy – Diagnosis – Etiology – Prognosis

OVID

• Most librarians favor this search engine

• Allow you to tailor your search

Nội dung cốt lõi

• 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)

• http://www.cebm.utoronto.ca/teach/mate

rials/dx.htm

• http://www.cebm.utoronto.ca/teach/mate

rials/therapy.htm

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?

Validity: 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: 5. Were All Patients Accounted for at the End of the Trial?

“Results” section

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?

Nội dung cốt lõi

• 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” 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

Let’s Calculate NNT

CER EER ARR NNT

50% 20% 30% 3

3% 2.5% 0.5% 200

30% 25% 5% 20

CER: Control Event Rate

EER: Experimental Event Rate

ARR: Absolute Risk Reduction

NNT: Number Needed to Treat

NNT=1/ARR

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

Step 5: Decision Making

Atrovent – Low cost medication – Minimal to no side effects

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

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

Appraise (Validity)

• http://www.cebm.utoronto.ca/teach/mate

rials/dx.htm

• http://www.cebm.utoronto.ca/teach/mate

rials/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 + B

A True + B False +

Test -

C + D C False - D True -

A + C B + D

Sensitivity & Specificity

• Sensitivity

The proportion of people with the target disorder (A+C) who have a positive test (A)

• SnNout

A/(A+C)

If a test has a high sensitivity, a negative result rules out the disease

Disease + Disease -

Test +

A + B

A True + B False +

Test -

C + D C False - D True -

A + C B + D

Sensitivity & Specificity

• Specificity

• SpPin

The proportion of people without the disease (B+D) who have a negative test (D) D/(B+D)

When a test has a high specificity, a positive result rules IN the diagnosis

Disease + Disease -

Test +

A + B

A True + B False +

Test -

C + D C False - D True -

A + C B + D

Predictive Values

• Positive Predictive Value

Proportion of people with a positive test (A+B) who have the target disorder

• Negative Predictive Value

A/(A+B)

Proportion of people with a negative test (C+D) who are free of the disease (D)

D/(C+D)

Disease + Disease -

Test +

A + B

A True + B False +

Test -

C + D C False - D True -

A + C B + D

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 (LR) of 1 means

• LR >1

 The test result identifies patients w/ the disorder at the same rate as identifying patients w/o the disorders

 The test result identifies patients w/ the

• LR <1

disorder at a faster rate; likelihood goes 

 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 - LR

Rate Dis + Rate Dis -

Result A a b

a/X b/Y

(a/X) (b/Y)

Result B c d

c/X d/Y

(c/X) (d/Y)

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?

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” ?

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 +)

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” ?

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-)

LR - = (1 – sensitivity)/specificity

= False neg rate/True neg rate

Guide to Likelihood ratios

LR+ LR-

1 – 2 V Poor 1 – 0.5

2 – 5 Poor 0.5 – 0.2

5 – 10 Fair 0.2 – 0.1

10 – 20 Good 0.1 – 0.05

> 20 V. Good < 0.05

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

Treatment threshold Test threshold

0%

100%

Testing completed; treatment starts

No test needed

Further testing needed

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

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

• Pretest probability is 30% • LR+ = ?

Culture + Culture -

A m

i r , 1 9 9 4

Test + Test - Total 65 10 75 18 72 90

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

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

Fagan Nomogram

Pre-test probability on the left hand column

LR in the middle

Post-test probability on the right hand column

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%)

Translation

• Your patient rapid strep is positive • You calculated the LR + to be 4.35 • You determined the post-test