Dr.HARMANJIT SINGHDEPARTMENT OF PHARMACOLOGYGMC, PATIALA

DEFINITION AND HISTORY

NEED OF EBM

EVIDENCE PYRAMID

EBM PRINCIPLES

CONCLUSION2

Definitions:• "The integration of best research evidence with clinical

expertise and patient values” (David Sackett, et al. Evidence-based Medicine. How to Practice and Teach EBM, 2000)

• "The conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients..." (Gordon Guyatt, M.D., et al. Users' Guides to the Medical Literature, 2002)

What is EBM?

Traces of EBM`s origin in ancient Greece & Chinese medicine

Prof. Archie Cochrane, Scottish epidemiologist, through his book Effectiveness and Efficiency: Random Reflections on Health Services (1972), advocated concepts behind EBM.

“Evidence based" was first used in 1990 by David Eddy “Evidence-based medicine" first appeared in the medical

literature in 1992 in a paper by Guyatt et al

Methodologies used to determine "best evidence“, estb. by McMaster University Research Group led by David Sackett & Gordon Guyatt

Recently broadened interest due to information explosion that increased dramatically in the last decade.

Any practice that applies: - Up-to-date information from relevant &

valid research about usefulness of various diagnostic tests

- Predictive power of prognostic factors

- The beneficence of a particular treatment method

There is evidence that something works, is good and benefits the patient, do it

There is evidence that something does not work, is harmful, does not benefit the patient, do not do it

There is insufficient evidence, be conservative, relying on individual clinician expertise

X 1) Evidence-based medicine ignores clinical experience and clinical intuition.

X 2) Understanding of basic investigation and pathophysiology plays no part in evidence-based medicine.

X 3) Evidence-based medicine ignores standard aspects of clinical training such as the physical examination.

What is the need?• Cost• Delay of "bench-to-bedside" research• Managing the primary literature• Counter misleading marketing• Dealing with conflicting results

Why EBM?

What is the need?• Cost• Delay of "bench-to-bedside" research• Managing the primary literature• Counter misleading marketing• Dealing with conflicting results

Why EBM?

increasing pressure to

• demonstrate effectiveness of interventions

• utilize the most cost effective measures

How do you know what really works or is the most cost effective?

Delay of "bench-to-bedside" research:

Why EBM?

Secondary Research

Routine Clinical Practice

Primary Literature

Years-to-Decades

Delay of "bench-to-bedside" research:

Why EBM?

Secondary Research

Routine Clinical Practice

Primary Literature

Thrombolytic Drugs for acute MI:

6 years from the first Systematic Reviews of RCTs until most review articles and textbooks recommended their use.

(Antman, Lau, et al. JAMA 1992)

Delay of "bench-to-bedside" research:

Why EBM?

Secondary Research

Routine Clinical Practice

Primary Literature

Aspirin after acute MI:

Not recommended by expert opinion until 6 years after the first systematic review.

(Antman, Lau, et al. JAMA 1992)

Delay of "bench-to-bedside" research:

Why EBM?

Secondary Research

Routine Clinical Practice

Primary Literature "Life Cycle of Translational Research"

Median time from "initial discovery of a medical intervention" to a "highly cited article" was 24 years.

(Contopoulos-loannidis, Alexiou, et al. Science 2008)

Managing the primary literature

Why EBM?

•MEDLINE adds 4500 records daily.

•60,000 articles/yr from 120 journals

•Just within their own fields, physicians would need to read 19 articles per day, 365 days per year, to keep up with research. (Oxford Center for EBM)

•Not all (~10%) of these articles are considered high quality and clinically relevant. (Oxford)

EBM helps you find the most appropriate article for a specific clinical question.

• Counter misleading marketing

Why EBM?

Pharmaceutical companies invest considerable resources to promote products based on skewed or selective evidence (or emotion appeals through direct-to-consumer advertising). EBM provides tools to help alert clinicians to potentially misleading marketing.

(Glasziou, Hayes. The paths from research to improved health outcomes, Evidenced Based Nursing, 2005; 8(2):36-8.)

Dealing with conflicting results

Why EBM?

• Beta-blockers initially avoided after MI due to pathophysiologic reasoning that they would decrease compensatory sympathetic mechanisms

• Later shown to decrease hospitalization & death:

Dealing with conflicting results

Why EBM?

• Based on 16 cohort studies (and some physiologic reasoning) HRT used to be recommended for postmenopausal women to reduce the risk of CHD.

• Women’s Health Initiative show it actually increased the risk of MI, stroke, and venous thromboembolism:

Dealing with conflicting results

Why EBM?

• Since the 1960s, lidocaine was used for VF & VT prophylaxis in patients with acute MI.

• A meta-analysis showed some reduction in VF & VT, but a probably increase in actual mortality:

Need of EBM for clinical pharmacologists?

• Expert opinion regarding drug therapy during clinical rounds

• Answering queries in drug information unit

• Formulating local guidelines

• Hospital medication policy

• As a regulator

• In pharmaceutical industry- identifying unmet medical needs and developing the drug development program

• Devices/ diagnostics

• Generating evidence

Animal Research / Lab studies

Case Series/Case Reports

Case Control studies

Cohort studies

Randomized Controlled Trial

Systematic  Review

Meta-Analysis

1.  Construct a well-built clinical question

and classify it into one category (therapy,

diagnosis, etiology or prognosis)

2.  Find the evidence in health care literature

3.  Critically appraise or formally evaluate

for validity and usefulness

4.  Integrate the evidence with patient

factors to carry out the decision

5.  Evaluate the whole process

TYPES OF QUESTIONS

1. BACKGROUND QUESTIONS Asked for general knowledge about a disorder  Has two essentials components:

a question root ( who, what, where, how, why) with a verb

a disorder

Textbooks answer background questions, they contain collected & synthesized wisdom for topics that do not change often. 

2. FOREGROUND QUESTIONS Asked for specific knowledge about

managing patients with a disorder It has 4 components (PICO analysis):

P - Patient/Population

I - Intervention

C - Comparison

O - Outcome

 

Type of QuestionSuggested best type of Study

TherapyRCT>cohort > case control > case series

DiagnosisProspective, blind comparison to a gold standard

Etiology/HarmRCT > cohort > case control > case series

PrognosisCohort study > case control > case series

PreventionRCT>cohort study > case control > case series

Cost Economic analysis

What is the primary problem, disease or co-existing conditions

On what groups do you want information

   How would you describe a group of patients similar to the one in question

   Sometimes age or sex of a patient may be relevant and should be included.

What medical event do you want to study the effect of? 

  Which main intervention are you considering, prescribing a drug, ordering a test, ordering surgery.

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Compared to what?   Better or worse than no intervention at

all or than another intervention?   What is the main alternative to compare

with the intervention, are you trying to decide between two drugs, a drug and a placebo, or two diagnostic tests. 

Sometimes there is no comparison

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What is the effect of the intervention? 

What do you hope to accomplish, measure, improve, or affect with this intervention?

  What are you trying to do for the patient, relieve or eliminate the symptoms, reduce side effects, reduce cost

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2. SEARCHING EVIDENCE

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 us knows which half”

(Dr Sydney Burwell)

PRIMARY LITERATURE resources include articles and studies presented in peer-reviewed journals like NEJM, JAMA, Journal of Postgraduate Medicine, Lancet, BMJ, etc.

SECONDARY LITERATURE is compiled by indexing and abstracting services that can be used to systematically locate various types of published literature. Different formats of secondary literature are available in the form of various databases like Medline, Cochrane Library, PubMed, National Library of Medicine Gateway, International Pharmacy Abstracts, Current Contents, and Toxline. TERTIARY LITERATURE is core knowledge established via primary literature or accepted as standard of practice within the medical community. The tertiary reference may consist of textbooks on various drugs or disease topics (e.g. Harrison's Principles of Internal Medicine), compendia (a vast array of information about many drugs such as the Physician's Desk Reference).

Some websites often used

Evidence Based Medicines Review(www.ovid.com)Cochrane Library (update.cochrane.co.uk)MEDLINE (via www. ncbi.nlm.nih.gov/PubMed

3: CRITICALLY APPRAISE THE EVIDENCE"Critically appraise" refers to determining the appropriateness of a some evidence (usually a journal article) for a particular clinical situation.Internal validity: Refers to the soundness of the research methodology

• Does the study measure what it says it is measuring?• Related to efficacy: performance under ideal (or laboratory)

conditions.Randomization – done or not ?Method of Randomization – Mentioned or not ?Blinding – Done or not ?Concealment of randomization – Done or not ?Were the groups similar at the start of the trial ?Follow up done or not?Were all enrolled patients included in the conclusion of the study?Intention to treat analysis (ITT)- Done or not? Are the benefits worth the harm and cost?

External validity: Refers to generalizability of the results. Related to effectiveness: How meaningful are the results in

real life?

Will the results help your patient? Were the study patients similar to your patient?

Three broad questions are use to critically appraise an article:

1. Are the results valid?

2. What are the results?

3. How can I apply these results to my patient?

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• Compare the patient with those in the study (similar disease state and stage, similar baseline characteristics )

• Consider the patient’s baseline risk for the outcome of interest and other risks associated with therapy

• Consider the patient’s values, beliefs, concerns and readiness for the intervention:

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Once the therapy is administered, evaluate the following

- Did I formulate a focused question?- Did I use the most appropriate resource ?- Did the evidence work in my patient?- Reassess the strategy - Collaborate with your colleagues and professional

bodies in developing practice guidelines

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Assess the patient Clinical question that arises out of clinical examination

Ask the patient Construct a well-built clinical question from the findings in step 1

Access information

Appropriate resources need selected & searched for

Appraise evidence Information gathered in step 3 critically appraised

Apply findings Validated evidence integrated with clinical expertise & patient preferences

Assess outcomes Performance of the evidence with the patient needs to be evaluated

Add knowledge Information so gathered added to clinician’s knowledge base for future reference

Minimizes the error in patient care

Reduces the cost of treatment

Optimizes the quality of patient care

Helps in advancement of knowledge and keeping pace with scientific progress

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Technology and online information resources must be available to the clinicians

Understanding of the epidemiological study designs and concepts of biostatistics is must

Attitude of the clinician. One must realize that clinical performance depends upon regular updating of knowledge and not merely on the years of clinical experience

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Conclusion: What EBM is NOTThese are some of the criticisms you will sometimes hear about evidenced based medicine.

NOT... But it is...• "Cookbook" medicine• Rigid adherence to

clinical guidelines

• Managed care• Cost-cutting measures

A rigorously systematic way to:• Evaluate the strength of available evidence• Evaluate the appropriateness of available

evidence for a particular clinical situation

• A way to avoid waste by considering both the efficacy and effectiveness of a particular intervention in a particular clinical setting.

Conclusion: What EBM is NOTNOT... But it is...The same thing as• clinical epidemiology• biostatistics• study design

Build on these concepts so you can better understand the strength of inferences from available evidence.

Limited to Randomized Controlled Trials

Recognition that:• Some study designs (esp. RCTs) are less

susceptible to bias than others, and therefore less likely to mislead.

• RCTs are not always available (or are of poor quality) but other evidence can (and should) be used in clinical decision making as long as you understand its limitations.

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1. Sackeit DL. Evidence based medicine: what it is and what it isn't. BMJ 1996. Vol 312: 71-72.

2. Sackett DL, Haynes RB. 13 steps, 100 people, 1,000,000 thanks. Evid Based Med 1997;2:101–102.

3. Rajashekhar HB, Kodkany BS, Naik VA, Kotur PF, Goudar SS. Evidence Based Medicine And Its Impact On Medical Education. Indian J. Anaesth. 2002; 46 (2) : 96-103.

4. Giacomini MK, Cook DJ. Users’ guides to the medical literature: XXIII. Qualitative research in health care. A. Are the results of the study valid? Evidence-Based Medicine Working Group. JAMA 2000;284:357–362.

5. Selvaraj S, Kumar y, Elakiya M, Saraswathi C, Balaji D, Nagamani P, et al. Evidence-based medicine - a new approach to teach medicine: a basic review for beginners. Biology and Medicine 2010; Vol 2 (1): 1-5.

You are a second year resident posted in D.I.U. You receive a call from emergency medical department of your hospital. The resident there had received a case of organophosphate poisoning a day ago. The patient was critical at the time of admission. The resident tried her best and managed the patient with atropine and supportive measures. The patient did not survive. Their case will be discussed in a statistical meet. Their Unit is worried that the people from other units will criticize this management. She wants your help and needs to know what are the chances a timely use of pralidoxime could have saved the patient. 

Situation

What are the compounds causing organophosphorous poisoning?

What are the treatment options for OP? Etc ……

P- Any patient presenting with acute OP I- Pralidoxime treatment C- Placebo O – Mortality

THE QUESTION: Will pralidoxime treatment decrease the

mortality in patients presenting with acute organophosphorous poisoning?

Books Internet Resources

Pubmed Medline Google scholar MD Consult

235 patients were randomised to receive pralidoxime (121) or saline placebo (114). Pralidoxime produced substantial and moderate red cell acetylcholinesterase reactivation in patients poisoned by diethyl and dimethyl compounds, respectively. Mortality was higher in patients receiving pralidoxime: 30/121 (24.8%) receiving pralidoxime died, compared with 18/114 (15.8%) receiving placebo

Randomisation – done Method of Randomisation - Mentioned Concealment of randomisation – Done Blinding – Done Intention to treat analysis (ITT)- Done Reasons for withdrawal - none

EER= 30/121=.248 CER= 18/114= .158 RR= .248/.158=1.567 RRI= .248-.158/.158=.5696 ARI= .248-.158=.09 NNH= 1/.09=11

Out of every 11 patients treated with pralidoxime, 1 will die.

Hence the resident was right in not treating the OPP patient with pralidoxime.