Evidence Based

MedicineDr. Mansij Biswas

Dept. of Pharmacology & TherapeuticsSeth GS Medical College & KEM

Hospital

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QUESTION:In patients with acute MI, does treatment with Aspirin/Streptokinase reduce mortality?

Evidence in 1988:Results of ISIS-2: ASA vs. placebo- significant 23% RR reduction in five-week cardiovascular mortality; ASA+STK vs. placebo- 42% RR reduction!

Application in 1997:463 patients in the ER with a definitive diagnosis of acute MI- Aspirin was NOT given to 55%!

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What is EBM?"A systematic approach to clinical problem solving by 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, et al. Users' Guides to the Medical Literature, 2002)

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Historical Evolution Traces of EBM’s origin in ancient Greek & 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 medicine” first appeared in the medical literature in 1992 in a paper by Guyatt et al.

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

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EBM in practice Took an “evidence cart” on rounds - 1995 Looked up 2-3 questions per patient Took 15-90 seconds to find evidence Changed about 1/3 decisions, rounds took longer!

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When… There is evidence that something works, is good and

benefits the patient- do it There is evidence that something does not work, is

harmful or does not benefit the patient- do not do it There is insufficient evidence, rely on individual clinical

expertise- be conservative

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Triad of EBM

Sackett DL et al. Evidence based medicine: what it is and what it isn’t. BMJ . 1996;312(7023):71-2.

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Misconceptions about EBM

×× It ignores clinical experience and clinical intuition.

×× Understanding of basic investigation and pathophysiology plays no part in it.

×× It ignores standard aspects of clinical training such as the history taking, physical examination etc.

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Why EBM?• Cost• Delay of "bench-to-bedside" research• Managing the literature• Counter misleading marketing• Dealing with conflicting results

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Cost

Many companies often use cost-cutting measures (such as treatment algorithms) under the name of EBM.

Increasing pressure to demonstrate effectiveness of interventions.

When cost is a barrier for a patient, it is important for clinicians to know when treatments are wholly ineffective and make decisions to utilize the most cost effective measures.

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Delay of "bench-to-bedside" research

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Secondary Research

Routine Clinical Practice

Primary Literature

“Lag period”≈ years to decades!!

Thrombolytics and Aspirin for acute MI: 6 years from the first Systematic Reviews of RCTs until most review articles, textbooks and expert opinions recommended their use.(Antman EM, Lau J, Kupelnick B, Mosteller F, Chalmers TC. A comparison of results of meta-analyses of randomized control trials and recommendations of clinical experts. Treatments for myocardial infarction. JAMA 1992; 268(2): 240-8.)

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Managing the literature

60,000 articles/year from 120 reputed journals worldwide.

More than 3800 biomedical journals in MEDLINE, more than 7300 citations added weekly

Just within their own fields, physicians would need to read 19 articles per day, 365 days per year, to keep up with research.

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

Thus EBM helps us to find the most appropriate article for a specific clinical question

CEBM (Centre for Evidence-Based Medicine), Oxford University, PubMed data for RCTs[Publication Type]

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Counter misleading marketing Pharmaceutical companies invest considerable resources

to promote products based on skewed or selective evidence or through direct-to-consumer advertising.

EBM provides tools to alert clinicians against potentially misleading marketing.

One such tool to detect publication bias is clinical trial registries, which also guard against data mining by "post hoc" statistical analysis.

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

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Dealing with conflicting results

A counter-intuitive result, demonstrating the inability to make accurate predictions based on physiologic reasoning, theoretical knowledge or results of studies which are biased or having poor methodological flaws.

Some examples:

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Beta-blockers were initially avoided after MI thinking that they would decrease compensatory sympathetic mechanisms.

Later shown to decrease hospitalization & death.

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

WHI trial showed that it actually increased the risk of MI, stroke, and venous thromboembolism.

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Need of EBM for clinical pharmacologists? Expert opinion regarding drug therapy during clinical

rounds Answering queries in drug information unit Formulating local guidelines Formulate hospital medication policy As a regulatory authority In pharmaceutical industry- identifying unmet medical

needs and developing the drug/device/diagnostic development program

Generating more sound evidences

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Principles of EBM① Construct a well-built clinical question and classify it

into one category (therapy, diagnosis, etiology, prognosis, prevention or cost)

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

⑤ Evaluate the whole process

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7 ‘A’s of EBM

Ask question

Acquire/Accessinformation

Appraise evidence

Apply findings

Analyze outcome

Assess the patientAdd knowledge

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Types of Questions:

Background questions

Asked for general knowledge about a disorder 

Has two essentials components: A question root (who, what, where, how, why) & a verb A particular disorder, test, treatment or other aspect of

health care.

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

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Foreground questions Asked for specific knowledge about managing patients

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

P - Patient/Population I - Intervention C - Comparison O - Outcome

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Patient / Population

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 whether

similar to the one in question or not?

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Intervention 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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Comparison 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.

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Outcome

What is the effect of the intervention? What do you hope to accomplish, measure,

improve, or affect with the intervention? What are you trying to do for the patient,

relieve or eliminate the symptoms, reduce side effects, reduce cost.

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What is pancytopenia?

What is the diagnostic test for meningitis?

Should a 70 year old pancytopenic patient with suspected meningitis receive platelets before undergoing a lumbar puncture?

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BACKGROUND

FOREGROUND

Type of Question

Clinical Experience

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SimplePatient/Population

Patients with common warts

Intervention Duct tape

Comparison Cryotherapy

Outcome Eliminating warts

Answerable clinical question:

In patients with common warts, is duct tape as effective as cryotherapy in eliminating warts?

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Patient/Population

In patients withacute MI

In womenwith suspectedcoronary artery

disease

does earlytreatment

with a statin

what is the accuracy of

exercise ECHO

compared to placebo

compared to exercise

ECG

decreasecardiovascular

mortality?

for diagnosingsignificant

CAD?

Components of Clinical Questions

Intervention Comparison Outcome

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Category of Question

Suggested best type of Study

Therapy RCT > cohort > case control > case series

Diagnosis Prospective, blind comparison to a gold standard

Etiology RCT > cohort > case control > case series

Prognosis Cohort > case control > case series

Prevention RCT > cohort > case control > case series

Cost Pharmaco-economic analysis

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Searching evidence“My students are dismayed when I say to them, half of what you are taught as medical students today, will have been shown to be wrong in 10 years, and the trouble is, none of us knows which half!”

≈ Dr. Sydney Burwell

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Primary Literature: articles and studies presented in peer-reviewed journals.

Secondary Literature: compiled by indexing and abstracting services that can be used to systematically locate various types of published literature through various databases like Medline (PubMed), Cochrane Library, Ovid, Embase etc.

Tertiary Literature: core knowledge established via primary literature or accepted as standard of practice within the medical community. The tertiary reference may consist of textbooks/handbooks/manuals on various drugs or disease topics (Harrison's Principles of Internal Medicine), compendia (Physician's Desk Reference) etc.

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Unfiltered

Expert Opinion

Filtered

More timeMore workMore evidence

Less timeLess workLess evidence

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Systematic ReviewCochrane reviews

Evidence based journals EBM, EBN, EBMH, ACP J club

Computerized Decision

Support System (CDSS)

5’S’ Information Resources: Information in top 4 are used

Original articles: BMJUpdates,

PubMed, Clinical Queries

Evidence based textbooks: UpTo Date, DynaMed, ACP

PIER, BMJ Clinical Evidence

Studies

Syntheses

Synopses

SummariesSystems

Haynes, R. (2006, November). Of studies, syntheses, synopses, summaries, and systems: the 5S evolution of information services for evidence-based health care decisions. ACP Journal Club, 145(3), A8-A9.

POCRaTs

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MA*

Systematic  Review

Double blinded RCTs (Ib)

Cohort studies (II)

Case Control studies (III)

Case

Series/Case

Reports (IV)

Ideas,

editorials, expert opinions

(V)

Ani

mal studies

In vitro research

The Evidence Pyramid *Meta-Analysis (Ia)

Bias

Bias

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Critically Appraise the Evidence Determine the appropriateness of some evidence for a

particular clinical situation.

Three main aspects to be appraised: V - I - A 1. Validity: (closeness to the truth) in the methodology section.

Internal validity:

Refers to the soundness of the research methodology.

External validity:

Refers to generalizability of the results.

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2. Importance: (usefulness) in the results section.

3. Applicability: (whether can be applied in clinical practice) in the discussion section.

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Apply the evidence to a particular patient

Compare the patient with those in the study from which evidence has been generated (similar disease state, similar baseline characteristics etc).

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

Consider the patient’s values, beliefs, concerns, affordability, compliance and readiness for the intervention.

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Evaluate the whole process

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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Benefits of adopting EBMMinimizes the error and optimizes the quality in

patient careReduces the cost of treatmentHelps in advancement of knowledge and keeping

pace with scientific progress

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Challenges in adopting EBM Technology and online information resources must be

available to the clinicians.

Understanding of the epidemiological study designs and concepts of biostatistics should be clear.

Attitude of the clinician- one must realize that clinical performance depends upon regularly updating knowledge and not merely on practical clinical experience.

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Conclusion: What EBM isNOT But it is

• "Cookbook" medicine

• Rigid adherence to clinical guidelines

• Managed care• Cost-cutting

measures

• A rigorously systematic way to evaluate the strength and appropriateness of available evidences for a particular clinical situation

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

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Conclusion: What EBM isNOT But it is

• The same thing as clinical epidemiology or biostatistics

• Limited to RCTs

• Build on concepts so we can better understand the strength of inferences from available evidence.

• A recognition that some study designs (esp. RCTs) are less susceptible to bias than others, and therefore less likely to mislead, but other evidences should also be used in clinical decision making as long as we understand their limitations.

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A lighter way to summarizeSeptember 03, 2015

https://www.youtube.com/watch?v=Ij8bPX8IINg

(“Some Studies That I Like To Quote”)

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