1. Why bother with EBM? life before EBM what is EBM?
what was the problem?
what is EBM?
three principles
how to recognize an ebm practitioner
how to judge size of treatment effects
helping the patient decide

2. How did we make clinical decisions?
If the basis wasn’t evidence,
what was it?
expert recommendations

3. Thrombolytic Therapy Textbook/Review Recommendations Cumulative 0.5
1.0
2.0
Year
RCTs
Pts
1960
Experimental
Not Mentioned
Rare/Never
Routine
Specific
1965 21 5
1970 1 10 1 2
P<.01 2 8 7
1980 8 1 12
P<.001 M 8
1985 1 4 M 7 1 3 M
P<.00001 5 2 2 M 1 M 15 8 1
1990 M 6 1
Odds Ratio (Log Scale)
Favours Treatment
Favours Control

4. Prophylactic Lidocaine in MI
Outcome = death
Favors treatment
Favors placebo
Relative risk (CI)
Cumulative
Year # RCTs Subjects
Recommendations
Yes No Not mentioned
9 1 1
8 0 2
5 0 2
This slide shows a cumulative meta-analysis of the effect of prophylactic lidocaine in preventing death from myocardial infarction. As in the previous examples, this slide shows:
Expert opinion differs from available evidence
Expert opinion varies
8 0 3
4 2 1
[Gordon - it was not clear in your original slide when the 1st meta-analysis was published. I have identified Hine et al, Arch Intern Med 1989, is this correct?]
st meta-analysis published

5. Calcium Channel Blocker Post-MI
Outcome = death
Favors treatment
Favors placebo
Relative risk (CI)
Cumulative
Year # RCTs Subjects
Recommendations
Yes No Not mentioned
Recommendations can also go in the opposite direction to the evidence.
In the 1980s, calcium channel blockers were often recommended in textbooks and review articles as routine administration after a myocardial infarction, in the absence of evidence from randomized controlled trials.
Cumulative meta-analysis shows a a non-significant trend in favor of placebo but never in favor of calcium channel blockers.
Recommendations from review articles and textbooks show a wide variation in expert opinion.
st meta-analysis published

6. What do we mean by best evidence
evidence: observations in the world
clinical experience
open to bias
specious causal connections
vividness and immediacy
small samples
laboratory and physiological research
systematic but generalization dangerous
observational studies
non-comparable groups

7. Nature of Evidence HRT for reducing cardiovascular risk
anti-arrhythmic drugs
flecainide, encainide, class I agents
vasodilator/inotropes in heart failure
milrinone, vesnarinone, ibopamine, epoprostonol
beta blockers for heart failure

8. First principle, Hierarchies of Evidence: intervention
Individual RCT
Observational studies
patient-important outcomes
Basic research
test tube, animal, human physiology
Evidence from different sources can be categorized in a hierarchy:
Meta-analysis or systematic reviews are at the top of the hierarchy.
When summaries of the evidence are not available, individual randomized controlled trials provide the next best evidence.
Next are observational studies. We should try to find studies that focus on outcomes important to the patient.
If there are no clinical studies available we may look at basic scientific research, although caution must be used in extrapolating the results to the clinical setting.
Clinical experience is at the bottom of the hierarchy, either your own or that of colleagues or experts.
Clinical experience

9. Second principle
optimal clinical/health policy decision require systematic unbiased summaries of the all the best evidence
must avoid selection bias in evidence
can’t use favorite evidence (top journals)
why EBM so fond of systematic reviews
evidence regarding all outcomes important to patients
harm as well as benefit

10. Clinical decision-making
evidence is never enough
values and preferences
antibiotics and pneumococcal pneumonia
95 year-old demented, incontinent, contracted
daily value judgments
clopidigrel versus aspirin
most atrial fibrillation pts don’t receive warfarin

11. Model of evidence based clinical decisions
clinical circumstances
patient preference research evidence
Clinical expertise

12. Spotting an evidence-based clinician
should Mr. Jones receive a beta-blocker after myocardial infarction
sure, it works
which antibiotic should we use to treat Ms. Smith who presents with acute pyelonephritis

13. Spotting an evidence-based clinician
prospective studies suggest that Mr. Jones' risk of death in the first year after his infarct is 8%
a meta-analysis of rcts of beta-blockers after MI suggests a 25% risk reduction
must treat 50 such pts to prolong a life
given the relatively small expense, toxicity of generic beta-blockers, a trial of beta-blockers for Mr. Jones is clearly warranted

14. Spotting an evidence-based clinician
the relative benefit of a variety of antibiotics (an aminoglycoside, a cephalosporin, quinolone)
so, my recommendation that we administer ceftriaxone intravenously represents only one reasonable option
other antibiotic choices would be equally reasonable

15. How to recognize an EBP is old news
The Master said, "Yu, shall I tell you what it is to know? To say you know when you know, and to say you do not when you do not, that is knowledge."
Analects of Confucius
Chapter 2, Verse 17

16. Calibrating your enthusisam
It is Brazil, led by Pele, becomes – in a game played in Mexico City, the first country to win the world cup three times.
It is Brazil, in a game played in Rio, loses the world cup to Uruguai.

17. Interpreting the Evidence
willingness to fund mammography screening
program A reduces the rate of deaths from breast cancer by 34%
program B increases the rate of patients not dying from breast cancer from 99.82%to 99.88%.
program C means that 1600 women needed to be screened yearly for 7 years to prevent one death from breast cancer

18. Summarizing Evidence VA hypertension study
examined mortality after 5 years of treatment
Controls Treated RRR
DBP
20%

19. Relative risk reduction

20. Absolute risk reduction

21. Number needed to treat

22. Breast cancer breast cancer death rates RRR 0.18 - 0.12 / 0.18 = 34%
unscreened 0.18% (18 out of 10,000)
screen 0.12% (12 out of 10,000)
RRR / 0.18 = 34%
unscreened 0.18% means 99.82% don’t die
screened 0.12% means 99.88% don’t die
ARR = 0.06%
NNT 100/0.06 = 1,667

23. A patient/parent dilemma
3 year old
sore ear, low fever, irritable
examination shows otitis media
which of you:
treat kids with sore ears?
have been exposed to kids with sore ears?
who would administer/expect antibiotics?
what benefit can I expect?
what risks are there?

24. Glasziou, Cochrane, 2003 systematic review of RCTs question
patients: children with otitis media
intervention: antibiotics
outcome: resolution of symptoms
comprehensive search
8 high quality studies, 2,287 children
concealed randomization
blinding
complete follow-up

25. Antibiotics for Acute Otitis Media in Children
Pain at 24 hours

26. Antibiotics for Acute Otitis Media in Children
Pain at 2 – 7 days

27. Trade-off failure to resolve at 2 to 7 days absolute difference 7%
20% control
13% antibiotics
absolute difference 7%
NNT 15
other studies have addressed side effects
increase in vomiting, rash, diarrhea 5%
NNH 20

28. Why bother with EBM? without EBM we are helpless in the face of
misguided experts
overenthusiastic experts
drug company hype
without EBM our ability limited
to understand difficult tradeoffs
to help our patients make difficult decisions
with EBM comes
understanding and power
greater effectiveness in helping our patients