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

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

Thrombolytic Therapy Textbook/Review Recommendations Cumulative 0.5 1.0 2.0 Year RCTs Pts 1 23 1960 Experimental Not Mentioned Rare/Never Routine Specific 2 65 1965 3 149 21 4 316 5 1970 7 1793 1 10 10 2544 1 2 11 2651 P<.01 15 3311 2 8 17 3929 22 5452 7 23 5767 1980 8 1 27 6125 12 P<.001 30 6346 M 8 1985 1 4 33 6571 M 7 43 21 059 1 3 M 54 22 051 P<.00001 5 2 2 65 47 185 M 1 67 47 531 M 15 8 1 1990 70 48 154 M 6 1 Odds Ratio (Log Scale) Favours Treatment Favours Control

Prophylactic Lidocaine in MI Outcome = death Favors treatment Favors placebo Relative risk (CI) Cumulative Year # RCTs Subjects 0.5 1 1.5 2 Recommendations Yes No Not mentioned 1970 2 304 9 1 1 1974 9 1451 8 0 2 1976 11 1686 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 1978 12 1986 8 0 3 1985 14 8412 14 4 6 1988 15 8745 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?] 1989 - 1st meta-analysis published

Calcium Channel Blocker Post-MI Outcome = death Favors treatment Favors placebo Relative risk (CI) Cumulative Year # RCTs Subjects 0.5 1 1.5 2 Recommendations Yes No Not mentioned 1984 4 486 2 3 8 1985 7 587 2 3 6 1986 11 5857 2 2 6 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. 1987 12 5879 7 10 7 1988 16 6420 0 5 2 1988 - 1st meta-analysis published

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

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

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

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

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

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

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

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

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

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

Calibrating your enthusisam It is 1970. Brazil, led by Pele, becomes – in a game played in Mexico City, the first country to win the world cup three times. It is 1950. Brazil, in a game played in Rio, loses the world cup to Uruguai.

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

Summarizing Evidence VA hypertension study examined mortality after 5 years of treatment Controls Treated RRR DBP .074 .059 0.074 - 0.059 90 - 104 0.074 20%

Relative risk reduction

Absolute risk reduction

Number needed to treat

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 - 0.12 / 0.18 = 34% unscreened 0.18% means 99.82% don’t die screened 0.12% means 99.88% don’t die ARR 0.18 - 0.12 = 0.06% NNT 100/0.06 = 1,667

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?

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

Antibiotics for Acute Otitis Media in Children Pain at 24 hours

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

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

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