1. Dr.HARMANJIT SINGH
DEPARTMENT OF PHARMACOLOGY
GMC, PATIALA

2.  DEFINITION AND HISTORY
 NEED OF EBM
 EVIDENCE PYRAMID
 EBM PRINCIPLES
 CONCLUSION
2

3. 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?

4.  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.

5. 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

6.  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

7. 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.

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

10. 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?

11. Delay of "bench-to-bedside" research:
Why EBM?
Secondary Research
Routine Clinical Practice
Primary Literature
Years-to-Decades

12. 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)

13. 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)

14. 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)

15. 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.

16. • 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.)

17. 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:

18. 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:

19. 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:

20. 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

21. Animal Research / Lab studies
Case Series/Case Reports
Case Control studies
Cohort studies
Randomized Controlled
Trial
Systematic
Review
Meta-
Analysis

22. 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

23. 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.

24. 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

25. Type of Question
Suggested best type
of Study
Therapy
RCT>cohort > case control >
case series
Diagnosis
Prospective, blind
comparison to a gold
standard
Etiology/Harm
RCT > cohort > case control
> case series
Prognosis
Cohort study > case control
> case series
Prevention
RCT>cohort study > case
control > case series
Cost Economic analysis

26.  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.

27.  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.
27

28.  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
28

29.  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
29

30. 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)

31. 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).

32. 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

33. 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?

34.  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?
34

35. • 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:
35

36.  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
36

37. 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

38.  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
38

39.  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
39

40. Conclusion: What EBM is NOT
These 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.

41. Conclusion: What EBM is NOT
NOT... 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.

42. 42

43. 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.

44. 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

45.  What are the compounds causing
organophosphorous poisoning?
 What are the treatment options for OP?
 Etc ……

46.  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?

47.  Books
 Internet Resources
 Pubmed
 Medline
 Google scholar
 MD Consult

48.  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

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

50.  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

51.  Out of every 11 patients treated with
pralidoxime, 1 will die.
 Hence the resident was right in not treating the
OPP patient with pralidoxime.