Evidence

Based
Medicine

Mehmet Ali Ergün, MD PhD Prof

Evidence Based Medicine Board

 EBM
• David Sackett and his collegues in 1990
bun vers tel len

• The definition of EBM as;

– integrating the best research evidence with
clinical expertise and patient values

• in order to achieve the best possible patient

management

Evidence Based Medicine Board

 EBM
• …is to improve the quality of the
information on which decisions are based
• …to help practitioners to avoid
‘information overload’
• …to find and apply the most useful
buggulamak
information

Evidence Based Medicine Board

Clinical decision making

I
(MEDULA)

Evidence Based Medicine Board

 Why do we need EBM?

ayr lle
• There is a large information gap between
research and clinical practice.
• As so much research is published all the
time, clinicians understandably are
unaware of most of it, or do not have the
b naber
‘tools’ to assess its quality.
Sdegerlend ned

Evidence Based Medicine Board

 Why do we need EBM?
• Researchers, on the other hand, do not
understand the information needs of clinicians
and continue to present their work in a way that
is not easily accessible to busy practitioners.
• In 1972, British epidemiologist Archie Cochrane
highlighted the fact that most treatment-related
decisions were based on
– information from the vast and variable quality
scientific literature, gen s
– on expert opinion,
– or, worse of all, on trial and error.
sderenetmmayor
Evidence Based Medicine Board
• Cochrane sonernek
proposed that researchers and
practitioners should collaborate internationally to
systematically review all the best clinical trials
(that is,randomised controlled trials, or RCTs),
specialty by specialty.
• This highlighted the gaps that existed between
research and clinical practice and started to
convince some doctors of the benefits of an
evidence based approach to bridge this gap.

Evidence Based Medicine Board

 The Cochrane Collaboration
S s b rl g
• Found in response to Cochrane’s call for
systematic, up-to-date reviews of all relevant
randomised controlled trials of health care.
• In the early 1990s, funds were provided by the
UK National Health Service to establish a
Cochrane Centre in Oxford.
• The approach was further outlined at an
international meeting organised by the New
York Academy of Sciences in 1993
• http://www.cochrane.org
Evidence Based Medicine Board
Evidence Based Medicine Board
 Corticosteroids for Preterm Birth
Premature
1972
t r lm outcomes
• improved ssony.l for preterm babies when mothers were given a
short course of corticosteroid before the birth.
1972-89
• Six more RCTs were published which all confirmed these fidings
Kad ndo5umuzman
• During this time, most obstetricians were still unaware that
corticosteroid treatment was so effective and so did not treat women
about to give birth early with corticosteroids.
1989
• First systematic review published
1989-91
• Seven more studies reported.
• Corticosteroid treatment reduces the odds of babies dying from
complications of immaturity by 30 to 50% but thousands of babies
have died or suffered unnecessarily since 1972 because doctors did
not know about the eff ectiveness of the treatment.

Evidence Based Medicine Board

 “flecainide”
• The history of the use of the drug flecainide to treat heart attacks in the
United States in the 1980s
• A dramatic example of the gap between research and clinical practice, and
the reliance on evidence of a mechanism rather than an outcome.
• A ‘safe g ven
and long-acting antiarrhythmic drug that protects against ventricular
fibrillation’ would save millions of lives.
• In response to this challenge, a paper was published in the New England
Journal of Medicine introducing a new drug called flecainide — a local
anaesthetic derivative that suppresses arrhythmia.
• The paper described a study in which patients who had just had heart
attacks randomly received placebo or flecainide and were then switched
from one to the other (a cross-over trial).
• The researchers counted the numberdeneme of preventricular contractions (PVCs)
as a measure of arrhythmias. The patients on flecainide had fewer PVCs
than the patients on placebo. When the flecainide patients were ‘crossed
over’ to the placebo, the PVCs increased again.

Evidence Based Medicine Board

Evidence Based Medicine Board
• “flecainide reduces arrythmias and arrythmias cause heart attacks”
• therefore, people who have had heart attacks should be given
flecainide.
• The results were published in the New England Journal of Medicine
and flecainide was approved by the United States Food and Drug
Adminstration and became fairly standard treatment for heart attack
in the United States (although it did not catch on in Europe or
Australia).
• Almost immediately after the first trials were complete, however,
other researchers had started gathering information on the survival
of the patients (the outcome) instead of the PVC rate (the
mechanism).
• This showed that over the 18 months following treatment, more than
10% of people who were given flecainide died, which was double
the rate of deaths among a placebo group.
• In other words, despite a perfectly good mechanism for the
usefulness of flecainide (it reduces arrhythmias), the drug was
clearly toxic and, overall, did much more harm than good.
Evidence Based Medicine Board
• Unfortunately, because the initial studies had been
widely published in medical texts, it was a long time
before doctors caught up with the subsequent poor
outcome data, which did not attract as much attention.
• Meanwhile, about 200,000 people were being treated
with flecainide in the United States by 1989. Based on
the trial evidence, this would have caused tens of
thousands of additional heart attack deaths due to the
use of flecainide.
• Although there was published information, doctors were
systematically killing people with flecainide because they
did not know about the good quality outcome-based
research.

Evidence Based Medicine Board

 What does the flecainide example
tell us?
• In the flecainide example, the initial
research was widely disseminated
because it was based on a traditional
mechanistic approach to medicine and
because it offered a ‘cure’.
• Doctors continued to prescribe flecainide
because they believed that it worked.
They did not know that they needed to
look for further information.
Evidence Based Medicine Board
 Overall…
• We need a better way to find information, even
when we do not know that we need it.
• In other words, up to-date, good-quality
research findings need to be available to all
medical practitioners on a routine basis.
• The type of research is important.
• We must move away from a traditional
mechanistic approach and look for empirical
evidence of effectiveness using a clinically
relevant outcome (eg survival, improved quality
of life).
Evidence Based Medicine Board
• ‘Kill as few patients as
possible’
• ‘Review the world literature
fortnightly-15 days’.

Evidence Based Medicine Board

 Advantages
• EBM helps doctors keep up to date across a very wide
spectrum of information.
• MEDLINE and similar databases have several
advantages.
• Patients like this empirical approach because it is easier
to understand and allows them to share in decision
making.
• Decision making can be shared between the doctor and
patient based on empirical evidence of risks and
benefits. This reduces the chances of future litigation.
• Electronic searching can reveal other useful information
that is of benefit to the patient.

Evidence Based Medicine Board

 The steps

Formulate an answerable question

Track down the best evidence

EBMT Szn sr
Rapid critical appraisal of controlled trials
degerlend me

Apply the evidence (clinical expertise and patient values)

Evaluate the effectiveness and efficiency of the process

Idegelend nek
Evidence Based Medicine Board
Evidence Based Medicine Board
• Patient-Who is the patient
• Intervention- Diagnostic tests
1 Medahale
• Control- Compare with…
• Outcome
Sonus

Evidence Based Medicine Board

Evidence Based Medicine Board
 The steps

Formulate an answerable question

Track down the best evidence

EBMT
Rapid critical appraisal of controlled trials

Apply the evidence (clinical expertise and patient values)

Evaluate the effectiveness and efficiency of the process

Evidence Based Medicine Board

 Search the databeses?
PubMed
• http://www.pubmed.com
E

Cochrane library
• http://www.cochrane.org

Evidence Based Medicine Board

 The steps

Formulate an answerable question

Track down the best evidence

EBMT
Rapid critical appraisal of controlled trials

Apply the evidence (clinical expertise and patient values)

Evaluate the effectiveness and efficiency of the process

Evidence Based Medicine Board

 Are the results are valid and
geger
clinically useful ?
• Were the groups of subjects
representative and comparable?
1 Hems la
• Was the outcome measurement accurate?
s dog v
• Was a placebo used?
• Could the results have been due to
chance?

Evidence Based Medicine Board

 The steps

Formulate an answerable question

Track down the best evidence

EBMT
Rapid critical appraisal of controlled trials

Apply the evidence (clinical expertise and patient

values)

Evaluate the effectiveness and efficiency of the process

Evidence Based Medicine Board

 Apply the evidence
• Is the treatment feasible in my setting?
1 m nk n
• Is my patient so different to those in the
study that the results cannot apply?
• What alternatives are available?
• Will the potential benefits of treatment
outweigh the potential harms of treatment
Is ag r basmall
for my patient?
• What does my patient think about it?
Evidence Based Medicine Board
Evidence Based Medicine Board
 The steps

Formulate an answerable question

Track down the best evidence

EBMT
Rapid critical appraisal of controlled trials

Apply the evidence (clinical expertise and patient values)

Evaluate the effectiveness and efficiency of the process

ter m l h
Evidence Based Medicine Board
• It is important to keeppdegerlend
records of ne
your clinical questions, research
results and critical appraisal of evidence, to follow up patients where
you have applied the results of your searches and to record and,
where appropriate, publish, outcomes.

• Are you asking any questions at all?

• What is your success rate in asking answerable questions?

• How is your searching going?

• Are you critically appraising your search results?

• Are you applying your evidence in clinical practice?

Evidence Based Medicine Board

 Pharmacogenetics

Grapefruit, inhibites
metabolism on CYP3A4
gene and also delays
clearance of some drugs
ten zlenne
Evidence Based Medicine Board
http://www.fda.gov/Drugs/ScienceResearch/ResearchAreas/Pharmacogenetics/ucm083378.htm
Evidence Based Medicine Board
 Dosages for CYP2D6
Drug PM (%) IM (%) EM (%) UM (%)

TAD amitryptiline 73 92 111 130

clomipramine 60 87 121 155
desipramine 42 83 125 167
doxepin 36 82 127 172
Tofranil (10- mg) imipramine 28 79 131 183
nortriptyline 53 96 119 142
trimipramine 32 76 141 206
SSRIs citalopram 98 100 101 102
Depreks, Fulsac,
fluoxetine 75 95 105 125
Prozac(20 mg), Zedprex
fluvoxamine 69 93 112 131
Seroxat (20 mg) paroxetine 66 90 114 138
sertraline 99 100 100 100
Evidence Based Medicine Board
 Warfarin
• Warfarin metabolism decreases in people carrying
CYP2C9*2 allel by 30-50 %, and carrying CYP2C9*3
allel by 90 %

• Patient dose has to be decreased !

• The promoter region of VKORC1 gene [-1639 G/A

polymorphism]
– AA genotypes have to use low dose of Warfarin with respect to
GA and GG

Evidence Based Medicine Board

1879 Flemming indicated their roles in mitosis
1888 Waldeyer named as “chromosome”
1905 X0 and XY have been identified
1912 47 for male and 48 for female
1923 Painter found 48 chromosomes in sperm
1930 Painter chromosome number was between 8 and 100
1930-1950 number of chromosomes was not so important
1950 techniques advanced

There were problems for harvesting chromosomes…

tophama Evidence Based Medicine Board
 l sk n
• Nature Genetics reported an article regarding a
novel mutation in an eplipsy family in 2003
• However, the original DNA was contaminated
with 3 DNAs
• The study group collected DNA from 10 of the
family members instead of 16 members as they
refused !!!
• Other studies did not reveal this mutation…
• In fact….

Evidence Based Medicine Board

 EBM and Cancer
• Retinoblastoma-RB1
• Li-Fraumeni syndrome (LFS)-TP53
• Familial Adenomatous Polyposis-APC
• Hereditary Nonpolyposis Colon Cancer-
MSH2/MLH1
• Inherited Breast Cancer-BRCA1&2
• Medullary thyroid carcinoma-RET

Evidence Based Medicine Board

 EBM and Cancer therapy
• In Non-small cell cancer patients
– if there is mutation in Exons 18,19 and 21 of
EGFR gene
• Tyrosine kinase inhibitor therapy can be applied
• In the patients that ALK gene
rearrangements have been detected
– ALK inhibitors can be applied

Evidence Based Medicine Board

 EBM and Cancer therapy-2
• In Colorectal cancer patients
– If the codons of 12,13 and 61 of KRAS gene
is wild type and
– No V600E mutation in BRAF gene
• anti-EGFR therapy can be (EGFR moAbs) applied

Evidence Based Medicine Board

 To do….
• CME
• E-Learning
• Web sites
• Open sources
• E-books

Evidence Based Medicine Board

 References
• Evidence-Based Medicine
http://www.evidence-basedmedicine.com
• Clinical Evidence
http://www.clinicalevidence.com

Evidence Based Medicine Board

EBM Practice
Term I
http://www.ncbi.nlm.nih.gov/pubmed/
www.pubmed.com
157.387
2.859.352
104.282
22.314
Meta
analyses
+
review
•5
years
6.139
5.526
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