Evidence-Based Medicine

Francisco Javier Rodríguez-VeraDepartment of Internal MedicineHospital do Barlavento Algarvio

PortimãoPortugal. EU

Evidence Based Medicine: Evaluating and translating

evidence into clinical practice

Evidence Based Medicine: What it is?

Main Entry: 1ev·i·dence   Pronunciation: 'e-v&-d&n(t)s, -v&-"den(t)sFunction: noun1 a : an outward sign : INDICATION b : something that furnishes proof : TESTIMONY; specifically : something legally submitted to a tribunal to ascertain the truth of a matter2 : one who bears witness; especially : one who voluntarily confesses a crime and testifies for the prosecution against his accomplices

Consists in decision making according the state of the art of the medical knowledge

“Is the process of systematically reviewing, appraising and using clinical research findings to aid the delivery of optimum clinical care to patients”Rosenberg W, Donald A. Evidence-based Medicine: an approach to clinical problem solving. BMJ 1995; 310 (6987):1122-1126

Evidence Based Medicine: Why?

Evidence Based Medicine: Why?

Is a tool for the efficient management of the knowledge

Evidence Based Medicine

Where is evidence?

Personal experience

Reasoning and intuition

Colleagues

Bottom drawer

Published evidence

Where is evidence?

Personal experienceReasoning and intuitionColleaguesBottom drawer (pieces of paper in the office)Published evidence

Levels of evidenceI. Strong evidence from at least one systematic

review of multiple well designed randomised controlled trials.

II. Strong evidence from at least one properly designed randomised controlled trial of appropriate size.

III. Evidence from well designed trials such as non-randomised trials, cohort studies, time series matched case-controlled studies.

IV. Evidence from well-designed non-experimental studies from more than one centre or research group.

V. Opinions of respected authorities, based on clinical evidence, descriptive studies or reports of expert committees.

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Number of studies

Level of evidence

systematic review

randomised controlled trial

non-randomised trials, cohort studies, time series matched case-controlled studies.

non-experimental studies

Opinions

How to do Evidence Based Medicine. Steps.

1. Elaboration of a clinical question2. Searching the information3. Critical appraise.4. Application to our case

How to make a clinical question.

Questions in Evidence Based Medicine will have to be made in clear and well defined terms:oPerson or population in questionoIntervention givenoComparison (if appropriate)oOutcomes considered

The best question is that which can be answered with Yes or No

Patient or Problem Intervention Comparison Intervention OutcomeDescription of the patient or the target disorder of interest

Could include: •Exposure •Diagnostic test •Prognostic factor •Therapy •Patient perception etc.

Relevant most often when looking at therapy questions

Clinical outcome of interest to you and your patient

Questions

Therapy

Prognosis

Diagnosis

Harm/Etiology

You admit a 65 year old man with a stroke. On examination you find that he has mild weakness of the right arm and right leg and bilateral carotid bruits. You send the patient for carotid doppler ultrasonography and subsequently receive the report that he has moderate stenosis (50-69% by NASCET criteria) of the ipsilateral carotid artery. You want to now if aspirin will be indicated in this patient.

Therapy

Can ASA decrease the risk of stroke?

Patient or Problem Intervention Comparison Intervention Outcome65 year old man with a stroke and moderate carotid stenosis ASA Placebo Stroke

In a 65 year old man with a stroke and moderate carotid stenosis, can ASA decrease the risk of another stroke compared with no treatment?

You see a 70 year old man in your outpatient clinic 3 months after he was discharged from your service with an ischemic stroke. He is in sinus rhythm, has mild residual left-sided weakness but is otherwise well. His only medication is ASA and he has no allergies. He recently saw an article on the BMJ website describing the risk of seizure after a stroke and is concerned that this will happen to him.

Prognosis

Patient or Problem 70 year old manIntervention StrokeComparison InterventionOutcome SeizureQuestion In a 70 year old man does a history of stroke increase his risk for seizure?

In a 70 year old man does a history of stroke increase his risk for seizure?

Diagnosis

You admit a 75 year old woman with community-acquired pneumonia. She responds nicely to appropriate antibiotics but her hemoglobin remains at 10 g/dl with an MCV of 80. Her peripheral blood smear shows hypochromia, she is otherwise well and is on no incriminating medications. You contact her family physician and find out that her Hgb was 10.5 g/dl 6 months ago. She has never been investigated for anaemia. A ferritin has been ordered and comes back at 10 mmol/l. You admit to yourself that you're unsure how to interpret a ferritin result and aren't sure how precise and accurate it is.

Patient or Problem Elderly woman with anaemiaIntervention Ferritin

Iron deficiency anaemiaQuestion In an elderly woman with hypochromic, microcytic anaemia, can a low ferritin

diagnose iron deficiency anaemia?

Outcome

In an elderly woman with hypochromic, microcytic anaemia, can a low ferritin diagnose iron deficiency anaemia?

You see a 50 year old man who asks for a repeat prescription of sotalol which he has been taking for extrasystoles for several years. He has a remote history of an MI. You haven't seen him previously and are concerned about the proarrhythmic properties of sotalol given what is known about other antiarrhythmics.

Harm/Etiology

Patient or Problem Man with extrasystolesIntervention SotalolCompar Intervention PlaceboOutcome DeathQuestion In a man with extrasystoles and a remote history of MI, does treatment with sotalol increase his risk of death?

In a man with extrasystoles and a remote history of MI, does treatment with sotalol increase his risk of death?

How to do Evidence Based Medicine. Steps.

1. Elaboration of a clinical question2. Searching the information3. Critical appraise.4. Application to our case

Searching the information

• Background Resources:

• Give overview of a topic; print textbooks, electronic textbooks, narrative reviews in journals

1. Harrison’s Online 2. Scientific American Medicine Online 3. MD Consult 4. Medline (for narrative review articles)

a. Ovid b. PubMed

•Foreground Resources: (reports of original research or abstracts, summaries, syntheses of primary research)

• Secondary Sources-abstracts, summaries and syntheses of original research

1. Cochrane Database of Systematic Reviews- systematic review of a topic

•2. ACP Journal Club- review and commentary of an article

•3. Clinical Evidence -  summarizes evidence available for common clinical questions-includes Cochrane and ACP Journal Club report (direct)

4. Practice Guidelines

• Primary Sources-reports of original research 1. OVID Medline 2. PubMed Medline

It indexes nearly 9 million records representing articles from more than 3,600 biomedical journals published world-wide.

includes the full text of the regularly updated systematic reviews of the effects of healthcare interventions (therapy) prepared by The Cochrane Collaboration. http://www.cochrane.org

http://www.pubmed.org

PubMed

Created for the National Library of MedicineThree forms of presentation:

Full text (links to the journal)Abstracts (papers and original

articles)Title and Authors (Letters to

editor)

PubMed. Advantages and inconvenients

It accumulates the most relevant journalsFreeUpdated

Publications not included: grey literatureRequires learningFull text not avalaible in all pubblications

PubMed: an example of a search

"Myocardial Infarction/therapy"[MeSH]: 37326 artsLimits: arts with abstract: 20310 artsAdd limit Clinical Meta-analysis: 167 artschange limit: clinical practise guideline: 23 arts

Written in English and published in the last year: 4 arts

We want to know what´s the state of the art of the treatment of a myocardial infarction

Evidence Based medicine: After the efficient search

Depending the subject a search may give from 5 to 500 entries.Reading of abstracts and elimination of articles“After reading abstracts the search was limited to…”Reading of articles in full text “After the reading in full text, the search was limited to….articles”

The problem of obtaining articles

How would i get a full text article?

Official site of the journalAccumulatorsAsking the author for a copy of the articleSites with passwords to fulltext

Some articles are avalaible full text for free

http://intl.highwire.org/

http://ebro3.unizar.es:8080/rev/default.html

“Dear Dr …I´m researching on…., and in a search in PubMed I found the abstract of your study published in…, which I found extremely interesting. I would be pleased if you could provide my with a separata of your article.

Sincerely yours…”

Now, we have articles that may give an answer to our clinical question

Are these articles reliable?

I. Level of evidence provided by the article

II. Possibility of bias (internal coherence) of the article

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Number of studies

Level of evidence

systematic review

randomised controlled trial

non-randomised trials, cohort studies, time series matched case-controlled studies.

non-experimental studies

Opinions

Levels of evidence

Internal Coherence: The critical appraisal

-Consists in determining the possibility of bias of the study.-checklists

Critical appraisal. general

-Are the groups similar (homogeneity)?-Did it exist randomization?was it described?-Are the endpoints clearly defined?-Is the statistical study correct?-Are the conclusions according with the results?-Are the results of this study appliable to my patient(s)?

Are the results valid?1. Did the review address a clearly focused issue?2. Did the review describe: the population studied? the intervention given? the outcomes considered?

Critical appraisal. Review/Metanalysis

2. Did the authors select the right sort of studies for the review?

The right studies would:address the review's question

have an adequate study design

Critical appraisal. Review

3. Do you think the important, relevant studies were included?Look for: which bibliographic databases were used personal contact with experts search for unpublished as well as published studies search for non-English language studies

Critical appraisal. Review

4. Did the review's authors do enough to assess the quality of the included studies?

Did they use:description of randomization? rating scale?

Critical appraisal. Review

What are the results?5. Were the results similar from study to study? Are the results of all the included studies clearly displayed? Are the results from different studies similar? If not, are the reasons for variations between studiesdiscussed?

Critical appraisal. Review

6. What is the overall result of the review?Is there a clinical bottom-line?What is it?What is the numerical result?

Critical appraisal. Review

7. How precise are the results?Is there a confidence interval?

Critical appraisal. Review

Can I use the results to help my patient?8. Can I apply the results to my patient?Is this patient so different from those in the trial that the results don’t apply?

Critical appraisal. Review

9. Should I apply the results to my patient?how great would the benefit of therapy be for this particular patient? Is the intervention consistent with my patient's values andpreferences? Were all the clinically important outcomes considered? Are the benefits worth the harms and costs?

Critical appraisal. Review

Critical appraisal. Treatment.

Is the research valid?1a. Was the assignment of patients to treatments randomized?1b. Was the randomization list concealed?1c. Were subjects and clinicians ‘blind’ to which treatment was being received?

2a. Were all subjects who entered the trial accounted for at its conclusion?

2b. Were they analyzed in the groups to which they were

randomized?

Critical appraisal. Treatment.

3a. Aside from the experimental treatment, were the groups treated equally?

3b. Were the groups similar at the start of the trial?

Critical appraisal. Treatment.

Is the research important?RRR (Relative risk reduction)ARR (Absolute risk reduction)NNT (Number needed to treat)

Critical appraisal. Treatment.

Can I apply it to my patient?

4. Is this patient so different from those in the trial that the results don’t apply?

Critical appraisal. Treatment.

5a. How great would the benefit of therapy be for this particular patient?

5b. What is the event rate in my practice for patients like this one?

Critical appraisal. Treatment.

Is it consistent with the patients values and preferences?

6. Do I have a clear assessment of the patient’s values and preferences?

Critical appraisal. Treatment.

7. Do this intervention and its potential consequences meet them?

Critical appraisal. Treatment.

Critical appraisal. Diagnosis

Is the research valid?

1. Was there an independent, blind comparison with a reference ("gold") standard of diagnosis?

2. Was the diagnostic test evaluated in an appropriate spectrum of patients (like those in whom it would be used in practice)?

Critical appraisal. Diagnosis

3. Was the reference standard applied regardless of the diagnostic test result?

Critical appraisal. Diagnosis

Is the research important?

SensitivitySpecificity

Critical appraisal. Diagnosis

Can I apply it to my patient?

4. Is the diagnostic test available, affordable, accurate, and precise in your setting?

Critical appraisal. Diagnosis

5. Can you generate a clinically sensible estimate of your patient's pre-test probability (from practice data, from personal experience, from the report itself, or from clinical speculation?)

Critical appraisal. Diagnosis

6. Will the resulting post-test probabilities affect your management and help your patient? (Could it moveyou across a test-treatment threshold?)

Critical appraisal. Diagnosis

Critical appraisal. Prognosis/harm

Is the research valid?

1. Was a defined, representative sample of patients assembled at a common (usually early) point in the course of their disease?

2. Was patient follow-up sufficiently long and complete?

Critical appraisal. Prognosis/harm

3. Were objective outcome criteria applied in a "blind" fashion?

Critical appraisal. Prognosis/harm

4. If subgroups with different prognoses are identified, was there adjustment for important prognostic factors?

Critical appraisal. Prognosis/harm

5. Was there validation in an independent group ("test-set") of patients?

Critical appraisal. Prognosis/harm

Is the research important?

Outcome Rate (95% CI) Probability (95% CI)

Critical appraisal. Prognosis/harm

Can I apply it to my patient?6. Were the study patients similar to your own?

Critical appraisal. Prognosis/harm

7. Will this evidence make a clinically important impact on your conclusions about what to offer or tell your patient?

Critical appraisal. Prognosis/harm

After the critical appraisal you conclude that that article you´ve read has a low-moderate-high probabilities to be biased

Summary

After you make a clinical question, you formulate correctly that question, look for the information , obtain the appropriate articles and make an appropriate critical appraisal, you get the following answer:“there is a X level of evidence to assure that the answer to our question was yes/no”

frodriguezv14@hotmail.com

frodriguezv@sego.es