a brief overview about how and why to practice evidence based medicine, its clinical application, what it is and what it is not? benefits and challenges

1. Evidence
Based
Medicine
Dr. Mansij Biswas
Dept. of Pharmacology & Therapeutics
Seth GS Medical College & KEM Hospital

2. 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%!
September 03, 20152

3. 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)
September 03, 20153

4. 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.
September 03, 20154

5. 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!
September 03, 20155

6. 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
September 03, 20156

7. Triad of EBM
Sackett DL et al. Evidence based medicine: what it is and what it isn’t. BMJ . 1996;312(7023):71-2.
September 03, 20157

8. 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.
September 03, 20158

9. Why EBM?
• Cost
• Delay of "bench-to-bedside" research
• Managing the literature
• Counter misleading marketing
• Dealing with conflicting results
September 03, 20159

10. 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.
September 03, 201510

11. Delay of "bench-to-bedside" research
September 03, 201511
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.)

12. 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]
September 03, 201512
0
2000
4000
6000
8000
10000
12000
14000
16000
18000
20000
1960 1970 1980 1990 2000 2010
RCTs
RCTs published over the last 50 years

13. 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.
September 03, 201513

14. 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:
September 03, 201514

15. September 03, 201515
Beta-blockers were initially avoided after MI thinking that
they would decrease compensatory sympathetic mechanisms.
Later shown to decrease hospitalization & death.

16. 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.
September 03, 201516

17. 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
September 03, 201517

18. Principles of EBM
① 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
September 03, 201518

19. 7 ‘A’s of EBM
Ask question
Acquire/Access
information
Appraise evidence
Apply findings
Analyze outcome
Assess the patientAdd knowledge
September 03, 201519

20. 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.
September 03, 201520

21. 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
September 03, 201521

22. 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?
September 03, 201522

23. 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.
23 September 03, 2015

24. 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.
24 September 03, 2015

25. 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.
25 September 03, 2015

26. 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?
September 03, 201526
BACKGROUND
FOREGROUND
Type of Question
Clinical Experience

27. Simple
Patient/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?
September 03, 201527

28. Patient/
Population
In patients with
acute MI
In women
with suspected
coronary artery
disease
does early
treatment
with a statin
what is the
accuracy of
exercise ECHO
compared to
placebo
compared to
exercise
ECG
decrease
cardiovascular
mortality?
for diagnosing
significant
CAD?
Components of Clinical Questions
Intervention Comparison Outcome
September 03, 201528

29. 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
September 03, 201529

30. 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
September 03, 201530

31.  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.
September 03, 201531

32. Unfiltered
Expert Opinion
Filtered
More time
More work
More evidence
Less time
Less work
Less evidence
September 03, 201532

33. September 03, 2015
Systematic Review
Cochrane 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
Summaries
Systems
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
33

34. September 03, 201534
MA*
Systematic
Review
Double blinded
RCTs (Ib)
Cohort studies (II)
Case Control studies (III)
Case Series/Case Reports (IV)
Ideas, editorials, expert opinions (V)
Animal studies
In vitro research
The Evidence Pyramid
*Meta-Analysis (Ia)
Bias
Bias

35. 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.
September 03, 201535

36. 2. Importance: (usefulness)  in the results
section.
3. Applicability: (whether can be applied in clinical
practice)  in the discussion section.
September 03, 201536

37. 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.
September 03, 201537

38. 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.
September 03, 201538

39. Benefits of adopting EBM
Minimizes the error and optimizes the quality in
patient care
Reduces the cost of treatment
Helps in advancement of knowledge and keeping
pace with scientific progress
September 03, 201539

40. 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.
September 03, 201540

41. Conclusion: What EBM is
NOT 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.
September 03, 201541

42. Conclusion: What EBM is
NOT 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.
September 03, 201542

43. A lighter way to summarize
September 03, 201543
https://www.youtube.com/watch?v=Ij8bPX
8IINg
(“Some Studies That I Like To Quote”)

44. September 03, 2015
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