evidence based medicine: an introduction farhad hosseinpanah, m.d. obesity research center research...

Evidence Based Medicine: An Introduction

Farhad Hosseinpanah, M.D. Obesity Research Center

Research Institute for Endocrine sciencesShahid Beheshti Universityof Medical Sciences

Workshop objectives

• Problems of conventional medicine• Definition and philosophy of EBM/IM• Different concepts such as

– answerable question, systematic review, NNT,NNH,…

• Search methods • Most popular EBM data bases• Critical appraisal skills

Agenda

• Definitions: Definitions: Science and EBMScience and EBM

• Dimensions of the problemDimensions of the problem1. Information management (mastery)

2.2. Limitations of current clinical practiceLimitations of current clinical practice

3.3. Heuristic and errorsHeuristic and errors

4. Problems of communication

• EBM

Definition:• Science is devoted to formulating and

testing naturalistic explanations for natural phenomena. It is a process for systematically collecting and recording data about the physical world, then categorizing and studying the collected data in an effort to infer the principles of nature that best explain the observed phenomena.72 Nobel laureates. (From the Amicus Curiae presented in the US Supreme

Court Case of Edwards vs Agullard, 1986)

Trace back to the development of EBM.

• 1972:Archie Cochrane told about the role of randomized control trial in scientific medicine.

• 1980's: Dave Sackett

• 1990s :The term was generated by Gordon Guyatt from McMaster University

What evidence-based medicine is

• “The conscientious (careful), explicit (clear,

unambiguous) and judicious (sensible) , use of current best evidence in making clinical decisions about the care of individual patients.”

Sackett et al, 2000

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

• Patient’s values and expectations

Sackett DL, Rosenberg WMC, Gray JAM, Haynes RB, Richardson WS: Evidence based medicine:

what it is and what it isn’t. BMJ 1996;312:71-2.

I.Individual Clinical Expertise:

• Experience: Relates to what we’ve done and to knowledge.

• “An expert is a person who has made all the mistakes that can be made in a very narrow field” (Niels Bohr)

1. Clinical skills2. Clinical judgment3. Vital for determining whether the evidence applies

to the individual patient at all and, if so, how

Hypothesis generating

Confirms or denies hypothesis

Matches research result to specific patients

Clinical judgment

Outcomes research

Patient seen in practice

?

II. Best External Evidence:

• From real clinical research amongintact 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.

III. Patients’ Values & Expectations

• Have always played a central role in determining whether and which interventions take place

A model for evidence-based clinical A model for evidence-based clinical decisionsdecisionsSackett et al, 2000

Bayesian approach: background knowledge + evidence= decision making

Current bestCurrent best evidenceevidence

Conventional medicine

Expertise(intuition…)

Pathophysiology, references, tradition…

Patient value

Agenda

• Definitions: Definitions: Science and EBMScience and EBM

• Dimensions of the problemDimensions of the problem1. Information management (mastery)

2.2. Limitations of current clinical practiceLimitations of current clinical practice

3.3. Heuristic and errorsHeuristic and errors

4. Problems of communication

• EBM

• The database of the National Library of Medicine MEDLINE has approximately 6 million references from 4.000 journals with about 400.000 new entries added each year.

Why Is It So Hard to BeWhy Is It So Hard to BeUp-to-date?Up-to-date?

• Doubling time of biomedical Doubling time of biomedical science is about 20 months science is about 20 months in in 20012001

Increasing Knowledge

0

2000

4000

6000

8000

1966 1976 1986 1996

Number of articles on Hypertension cited in Medline by Year

Articles

How many original articles should a

specialist read each week to remain

up to date in his/her own field only ?

5 10 20 40 100

Dr.S.Naserimoghaddam

How many original articles should a specialist read each week to remain up to date in his/her own field only ?

5 10 20 40 100The story is different for a generalist: 17 /day!

Dr.S.Naserimoghaddam

RCT23 Patients

1960

1 20.5

Odds Ratio

Treatment Control

Thrombolytic Therapy & MI mortality

Antman EM, Lau J, Kupelnick B, Mosteller F, Chalmers TC: A comparison of results of meta-analyses of randomised control trials and recommendations of clinical experts. JAMA 1992;268:240-8

CumulativeYear RCTs Pts

1960

1965

1 20.5

1 232 653 1494 3167 1793

Odds Ratio

Treatment Control

Antman JAMA 92

Thrombolytic Therapy & MI mortality

CumulativeYear RCTs Pts

1960

1965

1970

1975

1980

1985

1990

1 20.5

1 232 653 1494 3167 179310 254411 265115 331117 392922 545223 576727 612533 657165 4718570 48154

Odds Ratio

Treatment Control

p < 0.01

p < 0.001

p < 0.00001

Antman JAMA 92

Thrombolytic Therapy & MI mortality

Thrombolytic Therapy & MI mortalityCumulative

Year RCTs

Pts1960

1965

1970

1975

1980

1985

1990

1 20.5

1 232 653 1494 3167 179310 254411 265115 331117 392922 545223 576727 612533 657165 4718570 48154

Odds Ratio

Treatment Control

p < 0.01

p < 0.001

p < 0.00001

Textbook Recommendations

Rout Specif Exp NOT

21 510 2 8 7 812 4 3 1 1

112

872

111281

515 6

Antman JAMA 92

Some parts of textbooks are out-of-date

• Fail to recommend Rx up to ten years after it’s been shown to be efficacious.

• Continue to recommend therapy up to ten years after it’s been shown to be useless.

• Different textbooks, different recommendations.

• Textbooks are fact or opinion?• Textbooks are appraisable?

Antman EM, Lau J, Kupelnick B, Mosteller F, Chalmers TC: A comparison of results of meta-analyses of randomised control trials and recommendations of clinical experts. JAMA 1992;268:240-8

Interesting ExampleInteresting Example

Dr Naserimoghaddam

182 Health authorities selected

2 Articles: 1 on cardiac rehabilitation 1 on breast Ca screening Results of each presented in 4 ways:

RRR (Relative Risk Reduction) ARR (Absolute Risk Reduction) PEFP (Proportion of Event Free Patients) NNT ( Number Needed to Treat)

Dr NaserimoghaddamEvidence based purchasing: understanding results of clinical trials and systematic reviews T Fahey, S Griffiths, T J Peters. BMJ 1995;311:1056-1059 (21 October)

They were told that these were the results of 4 articles on each topic

Question: According to which set of data you may choose to adopt the method as part of your regional practice policy?

Dr NaserimoghaddamEvidence based purchasing: understanding results of clinical trials and systematic reviews T Fahey, S Griffiths, T J Peters. BMJ 1995;311:1056-1059 (21 October)

Interesting Results !Interesting Results !

N=140N=140 MammographyMammographyCardiac Cardiac RehabilitationRehabilitation

RRRRRR 79%79% 76%76%

ARRARR 38%38% 56%56%

PEFPPEFP 38%38% 53%53%

NNTNNT 51%51% 62%62%

Dr NaserimoghaddamEvidence based purchasing: understanding results of clinical trials and systematic reviews T Fahey, S Griffiths, T J Peters. BMJ 1995;311:1056-1059 (21 October)

Only 3 noted that all 4 sets of data are the same!

None were clinicians!

Dr NaserimoghaddamEvidence based purchasing: understanding results of clinical trials and systematic reviews T Fahey, S Griffiths, T J Peters. BMJ 1995;311:1056-1059 (21 October)

Scientific illiteracy is a major failing

of medical education

• The The goal of information masterygoal of information mastery is to determine the information source with the is to determine the information source with the highest usefulness scorehighest usefulness score

A Useful Equation!A Useful Equation!

• We are looking for patient-oriented We are looking for patient-oriented evidenceevidence

• Not enough to find patient-oriented Not enough to find patient-oriented evidence, but we are truly seeking evidence, but we are truly seeking patient-patient-oriented evidence oriented evidence that mattersthat matters (POEM) (POEM)

• RelevancyRelevancy is based on the frequency that we are exposed to the clinical question in our practice and the type of evidence presented.  . 

Information Mastery (Relevancy)

• Articles

• POEM: Patient-oriented evidence that Matters – mortality, morbidity, quality of life

• DOE: Disease-oriented evidence– pathophysiology, pharmacology, etiology

Examples of Hypothetical DOE and Examples of Hypothetical DOE and POEM studiesPOEM studies

Drug A lowers cholesterol

Drug A lowers cardiovascular mortality

Drug A decreases overall mortality

HRT lowers cholesterol

HRT increase cardiovascular mortality

HRT do not decreases overall mortality!!

Fluoride increase osteoblastic activity Fluoride increase BMD Fluoride increase Fx!!

DOE POEM

Pathophysiologic reasoning

Agenda

• Definitions Definitions

• Dimensions of the problemDimensions of the problem1. Information management (mastery)

2.2. Limitations of current clinical practiceLimitations of current clinical practice

3.3. Heuristic and errorsHeuristic and errors

4. Problems of communication

• EBM

• A pervasive problem for primary care physicians attempting to appraise clinical information is the conflicting recommendations by experts.

Global judgment by expertsGlobal judgment by experts

Bloor M. Bishop Berkeley and the adenotonsillectomy enigma: anexploration of the social construction of medical disposals. Sociology1976; 10: 43–61. EVIDENCE-BASED PRACTICE 2000

Variation in current practiceVariation in current practice

Resident : So , which statin would you recommend ?

Attending : I prefer Atorvastatin , and the last time I sent someone over to the lipid clinic , that was Dr. x recommendation as well.

(Translation : Does it work? It does if Dr. Expert says so.)

Defer to authorityDefer to authority

Evidence Based Fallacy

Resident : So , which statin would you recommend ?

Attending : I don’t really like any of them. I have had good experience with diet and Cholestyramine, and I never prescribe 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors.

Results cannot be reproduced or verified. Studies, if any, are always so vaguely described that one can't figure out what was done or how it was done.

In My ExperienceIn My Experience

Evidence Based Fallacy

Pathophysiologic approachPathophysiologic approach

• Resident: Do you recommend HRT fore Resident: Do you recommend HRT fore high LDL in postmenopausal patients? high LDL in postmenopausal patients?

• Attending: Attending: YES because estrogen increase HDL and decrease LDL, Lpa,and ………..

Evidence Based Fallacy

Answering question

logic, mathematics, philosophy,

social science?

Empirical scienceMedicine…

Analyticthinking

Synthetic:Re/search,reading…

WHI: Invasive Breast Cancer

years 1 2 3 4 5 6 7

1%

2%

3%

WHI: Coronary Heart Disease

years 1 2 3 4 5 6

Does CME Work?

– Traditional CME in a nice place with pleasant after lecture diversions is, unfortunately, completely ineffective in changing our behavior.

Davis DA, Thompson MA, Oxman AD, Haynes RB: Changing physician performance. A systematic review of the effect of continuing medical education strategies. JAMA 1995;274:700-5.

The Slippery Slope

years since graduation

r = -0.54p<0.001

...

...

. ... . .... .

....

....

.....

...knowledgeof current best care

100%

0%

50%

Choudhry, Fletcher and Soumerai, Ann Intern Med 2005;142:260-73-94% of 62 studies found decreasing competence for at least some tasks, with increasing physician age.

Agenda

• Definitions: Definitions: Science and EBMScience and EBM

• Dimensions of the problemDimensions of the problem1. Information management (mastery)

2.2. Limitations of current clinical practiceLimitations of current clinical practice

3.3. Heuristic and errorsHeuristic and errors

4. Problems of communication

• EBM

A quick assessment

Consider the following list of words:

goiter ,weight loss, sweating, hair loss, proptosis, lid lag, dyspnea, wide pulse pressure, weakness, hyperphagia, staring, diarrhea ,anxiety

 Write down as many as you can remember…

A quick assessment:

• Did you include tremor or palpitation in the list of words you thought you heard?

• Results : based on nonrandom sampling (N=600), error proportion was 20% (unpublished!)

• What is the validity of the estimation of frequency (or other measures) of the clinical findings?

Heuristical errors

• Heuristic = rule of thumb; mental process used to learn, recall, or understand knowledge

• Some examples:– Recency– Rarity– “burned” by missing a case– Regression towards the mean– …

(Tversky& Kahneman, 1974)

Agenda

• Definitions Definitions

• Dimension of problemsDimension of problems1. Information management (mastery)

2.2. Limitations of current clinical practiceLimitations of current clinical practice

3.3. Heuristic and errorsHeuristic and errors

4. Problems of communication

• EBM

Probability estimates of various qualitative verbal expressions

Probable

Likely

Possible

Certain

Low probability

Suggests

High probability

Unlikely

Moderate probability

Pathognomonic

classic

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0Evidence-Based Medicine: A Framework for Clinical Practice by Friedland et. al

Why Evidence-based Medicine?

• Science is a process for systematically collecting and recording data

• Time not available to find and assimilate evidence into practice

• Doubling time of biomedical science is about oubling time of biomedical science is about 20 months in 200120 months in 2001– Medical Journals: too voluminous– Scientific chaos

Dr Naserimoghadam

Why Evidence-based Medicine?• Traditional sources of info:

– Textbooks :partially (10-30%) outdated before publication

– Experts:• Pathophysiologic approach

• Conflicting recommendations

• Biased towards their own works & knowledge

• Heuristic and errors• Problems of communication

– CME: ineffective

• Clinical judgment / diagnostic skills increase with time, but up-to-date clinical knowledge declines

Dr Naserimoghadam

Agenda

• Definitions: Definitions: Science and EBMScience and EBM

• Dimensions of the problemDimensions of the problem1. Information management (mastery)

2.2. Limitations of current clinical practiceLimitations of current clinical practice

3.3. Heuristic and errorsHeuristic and errors

4. Problems of communication

• EBM

Evidence Based

Medicine

EBM process

1. Ask

2. Search

3. Appraise

4. Apply

5. EvaluateEvidence-Based Medicine: How to Practice and Teach EBM by David Sackett

Ask

• We need it twice for every 3 outpatients and 2 times for every inpatient

• Questions are most likely to be about treatment

• Most of the questions generated in consultations go unanswered.

P: Among patients with NIDDM who are having MI

I: does tight control of their blood sugar

C: in comparison to conventional methods

O: reduce their risk of dying?"

EBM process

EBM process

1. Ask

2. Search

3. Appraise

4. Apply

5. Evaluate

EBM process

2Efficient track-down of the best evidence –Secondary (pre-appraised) sources e.g.,– Cochrane (systematic reviews)

– E-B Journals

–primary literature

Example of a search strategy

#1 RANDOMIZED-CONTROLLED-TRIAL in PT#2 CONTROLLED-CLINICAL-TRIAL in PT#3 RANDOMIZED-CONTROLLED-TRIALS#4 RANDOM-ALLOCATION#5 DOUBLE-BLIND-METHOD#6 SINGLE-BLIND-METHOD#7 #1 or #2 or #3 or #4 or #5 or #6#8 TG=ANIMAL not (TG=HUMAN andTG=ANIMAL)#9 #7 not #8#10 CLINICAL-TRIAL in PT#11 explode CLINICAL-TRIALS#12 (clin* near trial*) in TI#13 (clin* near trial*) in AB#14 (singl* or doubl* or trebl* or tripl*) near (blind*or mask*)#15 (#14 in TI) or (#14 in AB)#16 PLACEBOS#17 placebo* in TI#18 placebo* in AB#19 random* in TI#20 random* in AB

#21 RESEARCH-DESIGN#22 #10 or #11 or #12 or #13 or #15 or #16 or #17 or#18 or #19 or #20 or #21#23 TG=ANIMAL not (TG=HUMAN andTG=ANIMAL)#24 #22 not #23#25 #24 not #9#26 TG=COMPARATIVE-STUDY#27 explode EVALUATION-STUDIES#28 FOLLOW-UP-STUDIES#29 PROSPECTIVE-STUDIES#30 control* or prospectiv* or volunteer*#31 (#30 in TI) or (#30 in AB)#32 #26 or #27 or #28 or #29 or #31

#33 TG=ANIMAL not (TG=HUMAN andTG=ANIMAL)#34 #32 not #33#35 #34 not (#9 or #25)#36 #9 or #25 or #35

Validity: Find the Best Valid Evidence First

Cochrane Library

Specialty-specificPOEMs

Best Evidence

Clinical EvidenceClinical Inquiries

Textbooks, Up-to-Date, 5-Minute Clinical Consult

Use

fuln

ess

Medline

search for the best (prevalidated) database information first.

EBM process

1. Ask

2. Search

3. Appraise

4. Apply

5. Evaluate

EBM process

3-Critical appraisal of the evidence for its validity and clinical applicability

Level of evidence for treatmentLevel of evidence for treatment

A

B

C

D

EBM process

1. Ask

2. Search

3. Appraise

4. Apply

5. Evaluate

EBM process4 Integration of that critical appraisal

with clinical expertise and the patient’s unique biology and beliefs apply.

5 Evaluation: evaluating our effectiveness and efficiency in executing steps 1–4

Which doctor do you want?

William Osler, 1900 Smart young doctor

Which doctor do you want?

Wise & experienced smart young doctor

How we do actually practice EBM

• Doing mode (unstable angina)

• Using mode (aspirin overdose)

• Replicating mode (graft vs. host disease in BMT)

Even fully EB-trained clinicians work in all 3 modes

“Searching & appraising” mode for the problems I encounter daily.

“Searching only” mode among E-B resources for problems I encounter once a month.

“Replicating” the practice of experts mode for problems I encounter once a decade .

It’s what we’ve always done!

Epidemiology

• Types of design • Descriptive studies• Observationnal studies• Measures of association (RR,RRR,NNT,Odds Ratio..)• RCT• Biases (selection,information,…..)• Confounding• Causality (Hill criteria)• Surrogate vs clinical end point markers• Internal and external validity….

Statistics

• Hypothesis testing, p value• Confidence interval (CI)• Type 1 and type 2 error• Clinical significance vs statistical significance• Correlation and regression• Kappa statistic• Meta-analysis(test of homogenity,pooled

estimate,fixed vs randome effect model )……..

Reference based medicine?

• First, idea second, references

• Vague questions

• systematic search is not usual

• systematic critical appraisal is not usual

• Inadequate evaluation

It’s like pseudoscience, isn’t it?

What are the Challenges?

• Time

• Access

• Skill in critical appraisal

• language of research

• Sense of control over practice

• Environment/culture

• Applicability

Practicing EBM: New Developments

• New strategies for finding and evaluating evidence

• New tools:• Meta-analyses• Systematic reviews /Cochrane Collaboration

• Evidence-based journals of secondary publication

• Information systems bring info in seconds

Dr Naserimoghadam

A model for evidence-based clinical A model for evidence-based clinical decisionsdecisionsSackett et al, 2000

Current bestCurrent best evidenceevidence

Why Evidence Based Health Care?

• Too many patients

• Too many problems

• Too many journals

• Information overload

• No time to read

• I am out of date

• I may be causing harm

References• Cook DJ, Meade MO, Fink MP: How to keep up with the

critical care literature and avoid being buried alive. Crit Care Med 24:1757-1768, 1996

• Evidence-Based Medicine: A Framework for Clinical Practice by Friedland et. al

• Evidence-Based Medicine: How to Practice and Teach EBM by David Sackett

• How to Read a Paper: The Basics of evidence based medicine by Trisha Greenhalgh

• Studying a Study and Testing a Test by Richard Riegelman and Robert Hirsch

• Smith R: Where is the wisdom...? The poverty of medical evidence. BMJ 1991;303:798-9.

References• Antman EM, Lau J, Kupelnick B, Mosteller F, Chalmers TC: A comparison of

results of meta-analyses of randomised control trials and recommendations of clinical experts. JAMA 1992;268:240-8

• Bero L, Rennie D. The Cochrane Collaboration. JAMA 1995;274:1935–8. • Villanueva EV, Burrows EA, Fennessy PA, Rajendran M, Anderson JN. Improving

question formulation for use in evidence appraisal in a tertiary care setting: a randomised controlled trial. BMC Med Inform Decis Mak. 2001;1(1):4. Epub 2001 Nov 08.

• Booth A, O'Rourke AJ, Ford NJ. Structuring the pre-search reference interview: a useful technique for handling clinical questions. Bull Med Libr Assoc. 2000 Jul;88(3):239-46

• Haynes RB. Clinical review articles. BMJ. 1992;304:330-1.• Oxman AD, Cook DJ, Guyatt GH. Users’ guides to the medical literature. VI. How

to use an overview. Evidence-Based Medicine Working Group. JAMA. 1994;272:1367-71.

• Evidence-based Medicine Working Group. Evidence-based medicine: a new approach to teaching the practice of medicine. JAMA 1992;268:2420-5

• Guyatt GH, Rennie D. Users' guides to the medical literature. JAMA 1993;270:2096-7

• Oxman AD, Sackett DL, Guyatt GH. Users' guides to the medical literature. I. How to get started. JAMA 1993;270:2093-5.

• Evidence based purchasing: understanding results of clinical trials and systematic reviews T Fahey, S Griffiths, T J Peters. BMJ 1995;311:1056-1059 (21 October)

Further Reading

• Toshi A.Furukawa , Sharon strauss , Heiner C. Bucher and Gordon Guyatt , User Vs guide to medical literature, second edition ,Mac Graw Hill.

• Straus SE, Richardson WS, Glasziou P, Haynes RB. Evidence-Based Medicine: How to practice and teach EBM, Third edition. New York: Churchill Livingstone.

Thank you