Introduction to Evidence-Based Medicine (EBM)

Prof. dr. Mohammad Hakimi, SpOG(K), PhD. Department of Obstetrics & Gynecology Gadjah Mada University Faculty of Medicine

EBM what we would like to achieve?

Not to discourage and not to bore you! To present:

Introduction to EBM Asking answerable questions How to find current best evidence

To interest you in EBM

Hormone Replacement Therapy and Cardiovascular Disease

Cardiovascular Disease: Incidence differs significantly between men and women In part because of differences in risk factors and hormones The incidence of atherosclerotic diseases is low in pre-menopausal women, rises in post-menopausal women, and is reduced to premenopausal levels in postmenopausal women who receive estrogen therapy

Atheroprotective Effects of Estrogen (1/2)

Until recently were attributed principally to the hormones effects on serum lipid concentrations However, estrogen-induced alterations in serum lipids account for only approximately one third of the observed clinical benefits of estrogen

Atheroprotective Effects of Estrogen (2/2)

Reviews of the data suggest that the direct actions of estrogen on blood vessels contribute substantially to the cardiovascular protective effects of estrogen The vasculature, like the reproductive tissues, bone, liver, and brain, is now recognized as an important target of estrogens action

(Mendelsohn and Karas, 1999)

Postmenopausal estrogen therapy and cardiovascular disease. Ten-year follow-up from the nurses' health study. (Stampfer et al., 1991)

Method:

Up to 10 year follow up of 48,470 post-menopausal women, 30 to 63 years old, who did not have a history of cardiovascular disease at baseline After adjustment of age and other risk factors, the relative risk of coronary heart disease in women currently taking estrogen was 0.56 (90% C.I. 0.40-0.80)

Result:

Estrogens for Prevention of Coronary Heart Disease

(Rossouw, 1996)

Eighty-two percent of 1383 cardiologists, internists, family doctors, and general practitioners surveyed by the National Heart, Lung, and Blood Institute (NHLBI) reported that they prescribe hormone replacement therapy Of those who prescribe it, 93% do so for relief of menopausal symptoms and 91% for osteoporosis However, 41% also prescribe it for high blood cholesterol, and 66% prescribe it for coronary heart disease

Risks and benefits of estrogen plus progestin in healthy postmenopausal women (Womens Health Initiative
Investigators, 2002)

Design:
Randomized controlled trial of 16,608 postmenopausal women aged 50-79 years with an intact uterus at baseline

Result:
Estimated hazard ratios for CHD = 1.29 (90% C.I. 1.02-1.63)

Gabriel-Sanchez R, Carmona L, Roque M, Sanchez-Gomez LM, Bonfill X. Hormone replacement therapy for preventing cardiovascular disease in post-menopausal women. The Cochrane Database of Systematic Reviews 2005,

No protective effect of HRT was seen for any of the cardiovascular outcomes assessed: all cause mortality, cardiovascular death, non-fatal MI, venous thrombo-emboli or stroke. Higher risks of venous thrombo-embolic events (Relative risk (RR) 2.15, 95% CI 1.61 to 2.86), pulmonary embolus (RR 2.15, 95% CI 1.41 to 3.28), and stroke (RR 1.44, 95% CI 1.10 to 1.89) was found in those randomized to HRT compared with placebo.

Treatments should be given not because they ought to work, but because they do work Treatments should be avoided not because they ought to cause harm, but because they do cause harm

Paradigm Shift: Evidence-based Medicine

De-emphasizes intuition, unsystematic clinical experience, and pathophysiologic rationale as sufficient grounds for clinical decision making Stresses the examination of evidence from clinical research Requires new skills of the physician, including efficient literature searching and the application of formal rules of evidence evaluating the clinical literature

What evidence-based medicine is:

The practice of EBM is the integration of individual clinical expertise with the best available external clinical evidence from systematic research and patients values and expectations

I. Individual Clinical Expertise

Clinical skills and clinical judgement Vital for determining whether the evidence (or guideline) applies to the individual patient at all and, if so, how

II. Best External Evidence

From real clinical research among intact patients Has a short doubling-time (10 years) Replaces currently accepted diagnostic tests and treatments with new ones that are more powerful, more accurate, more efficacious, and safer

My students are dismayed when I say to them

Half of what you are taught as medical students will in 10 years have been shown to be wrong. And the trouble is, none of your teachers knows which half.
(Dr. Sydney Burwell, Dean of Harvard Medical School).

Hierarchy of evidence
Quality Type of evidence
1a (best) 1b Systematic review of randomized controlled trials Individual randomized controlled trials with narrow confidence interval

1c
2a 2b 2c 3a 3b 4

All or none case series (when all patients died before a new therapy was introduced, but patients receiving the new therapy now survive)
Systematic review of cohort studies Individual cohort study or randomized controlled trials with <80% follow up Outcome research; ecological studies Systematic review of case-control studies Individual case-control study Case series

5 (worst)

Expert opinion

Strength of Recommendation
A B Strong evidence of efficacy and substantial clinical benefit support a recommendation for use Moderate evidence of efficacy or strong evidence of efficacy but limited clinical benefit support a recommendation for use

D
E

Insufficient evidence to support a recommendation for or against use, or evidence of efficacy might not outweigh adverse consequences or alternative approaches Moderate evidence of lack of efficacy or of adverse outcome support a recommendation against use
Good evidence of lack of efficacy or of adverse outcome supports a recommendation against use

III. Patients Values & Expectations

Have always played a central role in determining whether and which interventions take place Were getting better at quantifying and integrating them

A model for evidence-based clinical decisions

Another formulation of Evidence-based Medicine

Health care professionals always made and will make decisions based on expertise, values, and evidence There is a hierarchy of evidence Assessment of evidence requires separate set of skills and understanding of a specific language

EBM: Evidence Based Medicine

It is about providing optimal patient care It is about using this process (carefully and judiciously) the best available evidence It is about decision making

Odds Ratio (Log Scale)

Experimental 1 1 4 2
Not Mentioned

0.5 1960 1965 1970 1975 1980 1985

14 15 8412 8745 6 8 9 11 12
2 5 304 647 850 1239 1451

1.0

2.0
Rare/Never Specofic 17 4 7 3 8 4 2 8 6 5 2 9 3 Routine

2
1 4 4 5 3 4 5 1
Favors Ctrl

4 1 1 2 2 1 1 2 3 3 6 1

1686 1986

1990

p=NS

Favors Tx

Lidocaine in the treatment of myocardial infarction

Odds Ratio (Log Scale)

Experimental
Not Mentioned

0.5
1
23 65
143

1.0

2.0
Rare/Never Specific Routine

1960 1965 1970 1975 1980 1985

2 3 4 7 10 11 15 17 22 23 27 30 33 43 54 65 67 67

316

1783 2544 2651 3311 3929 5452 5767 6125 6346 6571

p < 0.01

1 1 2
p < 0.001 p < 0.0001 5 15 6
Favors Tx Favors Ctrl

1990

21059 22051 47185 47531 48154

1 1 1 2 8 1

8 7 2

21 5 10 2 8 7 8 12 4 3 1 6

Thrombolytic in the treatment of myocardial infarction

Barriers to practicing EBM

Topic threatening if critical appraisal skills poor Basic knowledge and skills needed Evidence often poor or none Lack of evidence is anxiety provoking Cookbook medicine has its appeal

Achieving EB Practice: Original concept

Reference to the original literature Critical appraisal exercise

Precise definition of the clinical problem (population, intervention, outcome) Searching literature Evaluating the strength of evidence Extracting the information Arriving at the bottom line Applying information to patient care Summarizing information for future use

Achieving EB Practice: Original concept

Nothing wrong with the concept! But it does not work! For most people (>95%) - no time, no skills, not a priority to learn!

EBM solutions
Pre-digested presentation of data (ACP Journal Club, Best Evidence) Coordinated effort in producing valid summary data (Cochrane Collaboration, Clinical Evidence) Production of EBM oriented textbooks (UpToDate)

Achieving evidence based practice Current concept

Do it all yourself

Searching, assessing validity, extracting data, drawing conclusions

Do nothing yourself

Follow EBM practice developed by others From asking question to applying answer Resembles expert-based way, only experts are different Saving time
Use EBM-related materials Searching, appraising, and extracting data much easier (done by others)

Get help from others

Achieving evidence based practice Current concept

Evidence-based practice (medicine) is here One can be an excellent health care professional without having all the EBM related skills, but Some skills essential for:

People producing evidence (researchers) People distributing evidence (editors) People telling others what to do (authors of practice guidelines, managers, decision makers, pharmaceutical representatives) Clinical teachers and supervisors Anybody who wants to make independent decisions

Obstacles to practicing EBM in developing countries

Limited access to literature databases Limited access to adequate library facilities Questionable applicability of journal articles that are eventually retrieved

Obstacles to teaching EBM in developing countries

Inexperience in small-group learning Lack of time to attend workshops Lack of role models for practicing EBM

Closing Remarks
Medicine is not just a scienceit is a human activity. It entails ritual, custom, and the expectations of doctors, patients, and society. To safeguard against ineffective or harmful health care we need doctors who:

want to do the best they can for their patients, are willing to continually question their own managements, and have readily available sources of information about what does work.