Transcript Evidence-based medicine

Introduction to EvidenceBased Medicine: Part 1
Prof. Dr. R. Erol Sezer
Evidence-based medicine (EBM)
has been defined as “the
conscientious, explicit, and
judicious use of the best evidence
in making decisions about the
care of individual patients”
http://ebm.mcmaster.ca/documents/
how to teach ebcp workshop brochure 2009.pdf
“EBM requires the integration of
the best research evidence with our
clinical expertise and
our patient’s unique values and
circumstances.”
Straus SE, Glasziou P, Richardson WS ,Haynes RB. Evidence-based
medicine: how to practice and teach it. Fourth Edition 2011. Churchill
Livingstone Elsevier.
Evidence means grounds for belief .
By best evidence we mean research
findings from clinically relevant
research, especially from patientcentered (or patient oriented)
research.
(Not from disease oriented research)
The flecainide story:
Glasziou P, Del Mar C, Salisbury J. Evidence-based
Practice Workbook. BMJ Books, Blackwell Publishing,
2007.
“..In 1979 the developer of the
defibrilator, Bernard Lown, pointed out
in an address to the American College
of Cardiology that one of the biggest
causes of death was heart attack,
particularly among young and
Middle-aged men (20-64 year olds).
People had a heart attack, developed
arrythmia, and died from arrythmia..
He suggested that a safe and long
acting antiarrythmic drug that
protects against ventricular fibrilation
would save millions of lives.”
In fact in an article published in 1977
ventricular premature depolarizations
were reported to be a risk factor for
sudden death and nonsudden cardiac
death after myocardial infarction.
Ruberman et al. Ventricular premature beats and mortality after myocardial
infarction. NEJM 1977;297:750-757
In response to the challenge
expressed by Albert Lown, a
paper was published in 1981 in
the NEJM introducing a new drug
called flecainide.
(Anderson JL. Oral flecainide acetate for
treatment of ventricular arrhythmia. NEJM
1981;305:473-477)
The paper described a study in
which patients who had just had
heart attack were randomly
assigned to groups to receive
either a placebo or flecainide
and were then switched from
one group to the other (a crossover trial).
..The researchers counted the
number of premature ventricular
contractions (PVCs) as a measure
of arrythmia.”
The results can be seen in the
following figure:
PVCs/12 hours
Effects of flecainide and placebo on number
of premature ventricular contractions (PVCs)
among nine patients who had just had heart
attack (Each line represents one patient)
Anderson JL. Oral flecainide acetate for treatment of ventricular arrhythmia.
NEJM 1981;305:473-477
The patients on flecainide had
fewer PVCs than patients on
placebo. When the flecainide
patients were ‘crossed over’ to the
placebo treatment, the PVCs
increased again.
Conclusion was straightforward:
flecainide reduces arrythmias
(PVCs). Therefore people who have
had heart attack should be given
flecainide.
After the results were published
flecainide was approved by the
US Food and Drug Administration
and became fairly standard
treatment for heart attack.
Several years later
The Cardiac Arrhythmia
Suppression Trial (CAST)
designed to test whether the
suppression of asymptomatic or
mildly symptomatic ventricular
arrhythmia with the drug
flecainide after myocardial
infarction would reduce
mortality started to recruit
patients in june 1987.
It was a multicenter ,
randomized, placebo controlled
clinical trial
(or briefly a randomized control
trial – RCT)
Recruitment of study subjects
(inclusion and exclusion criteria )
was described in the study protocol:
“..patients were eligible for
enrolment six days to two years after
myocardial infarction if they had an
average of six or more ventricular
pramature depolarizations per hour
on ambulatory electrocardiographic
monitoring of at least 18 hours
duration……”
All of the following rules for a valid
RCT study were implemented
1. Was the assignment of patients to
treatments randomised?
2. Was the randomization concealed ?
3. Were the groups similar at the start
of the trial?
4. Was follow-up of patiens sufficiently
long and complete?
5.Were all patients analyzed in the
groups to which they were
randomized?
6.Were patients, clinicians and
study personnel kept blind to
treatment?
7.Were the groups treated equally,
apart from the experimental
therapy?
Recruitment was planned to
last three years from June
1987 to June 1990
“ However, in April 1989
the Data Monitoring Committee (DMC)
— sometimes called “Data and Safety
Monitoring Board” (DSMB)
terminated the flecainide trial.
(An independent group of experts who
monitor patient safety and treatment
efficacy data while a clinical trial is
ongoing.There are typically three reasons a
DMC might recommend termination of the
study: safety concerns, outstanding benefit,
and futility.)
Because:
% Alive
Cardiac arrhythmia suppression trial
Gün
Echt DS et al. Mortality and morbidity in patients receiving
encainide, flecainide, or placebo. Cardiac Arrhythimia Supression
Trial. NEJM 1991;324:781-788.
Over the 18 months following
treatment, more than 10% of
people who were given flecainide
died, which was almost triple the
rate of deaths among the
placebo group.
A book tells this story in detail.
“A deadly Medicine” by Moore TJ -1995, Simon
and Schuster, Newyork
Despite a perfectly good mechanism for
the usefulness of flecainide (it reduces
arrhythmias), the drug was clearly toxic
and, overall, did more harm than good.
By the time results of this trial were
published, at least 100 000 such
patients had been taking this drug.
We can not rely on pathophysiologic
(mechanistic) reasoning and evidence.
This type of evidence is also described
as disease oriented evidence (DOEs).
Best evidence regarding
interventions comes from
randomized controlled trials
focusing on patient-centered (or
patient oriented) outcomes such
as mortality, quality of life ,
survival, cure. This type of
evidence is also described patient
oriented evidence that matters
(POEMs)
It was showed that many widely
used therapies that had been
adopted based on lower form of
evidence (coming from expert
opinion and/or pathophysiologic
reasoning) proved to be useless
when subjected to randomized
trials.
Jeremy howick states in his book (The philosophy
of evidence-based medicine. 2011, Blackwell
Publishing Ltd)
“The EBM philosophy of evidence is
best expressed in the EBM
hierarchies… The idea behind the
many different hierarchies can be
summed up quite simply with three
central claims:
1. Randomized trials or
systematic reviews of many
randomized trials generally offer
stronger evidential support than
observational studies.
2. Comparative clinical studies in
general including both randomized
clinical trials and observational
studies offer stronger evidential
support than mechanistic
reasoning (pathophysiologic
rationale) from more basic
sciences.
3. Comparative clinical studies in
general including both randomized
clinical trials and observational
studies offer stronger evidential
support than expert clinical
judgement”
“..By clinical expertise we mean the
ability to use our clinical skills and
past experience to rapidly identify
each patient’s unique health state and
diagnosis, their individual risks and
benefits of potential interventions, and
personal values and expectations.”
Straus SE, Glasziou P, Richardson WS ,Haynes RB. Evidencebased medicine: how to practice and teach it. Fourth Edition
2011. Churchill Livingstone Elsevier.
“…By patient values we mean the
unique preferences, concerns and
expectations each patient brings to
a clinical encounter and which must
be integrated into clinical decisions
if they are to serve the patient.”
Straus SE, Glasziou P, Richardson WS ,Haynes RB. Evidencebased medicine: how to practice and teach it. Fourth Edition
2011. Churchill Livingstone Elsevier.
“…By patient circumstances we
mean their individual clinical state
and the clinical setting.”
Straus SE, Glasziou P, Richardson WS ,Haynes RB.
Evidence-based medicine: how to practice and teach it.
Fourth Edition 2011. Churchill Livingstone Elsevier.
The complete practice of EBM
comprises five steps:
Step 1-Formulating an answerable
clinical question:
Converting the need for information
(about prevention, diagnosis,
prognosis, therapy, causation) into
an answerable question.
Step 2- Searching the available
evidence :
Tracking down the best
evidence with which to answer
that question.
Step 3: Critically appraising that
evidence for its validity (closeness
to the truth), impact (size of the
effect), and applicability (usefulness
in our clinical practice)
Step 4: Integrating the critical
appraisal with our clinical expertise
and with our patient’s unique
biology, values and circumstances.
Step 5: Evaluating our effectiveness
and efficiency in executing steps 1-4
and seeking ways to improve them
both for the next time.
EBM practice begins and
ends with patients.
It is a new paradigm to
provide the best possible
care to patients
It is a new paradigm for
lifelong learning in medicine
Evidence-based medicine (EBM) is
also called evidence-based health
care (EBHC) or evidence-based
practice (EBP) to broaden its
application from medicine to
the allied health professions.
“Evidence-based health service” is
the practice of evidence-based
medicine at the organizational or
institutional level.
Step 1
Formulating a clinical question
Example 1: Ayşe Hanım is a 56 year
old woman and quite often goes to
Ankara by bus to visit her university
student son. It takes 7 hours for her
to get to Ankara. She tends to get
swollen legs on this trips and is
worried about her risk of developing
deep vein thrombosis. Because she
has read quite a bit about this in
newspapers lately, she asks you if
she should wear elastic stockings
on her next trip to reduce her risk of
this.
A clinical question you have in
mind during a patient encounter
can be divided into four
components. Dissecting the
question into its component parts
and restructuring it so that it is
easy to find the answers is an
essential first step in EBP. This
restructured problem is called a
PICO (pee-co) question.
Population and clinical Problem: P
Intervention
(or indicator or Index test):
I
Comparator/Control
C
Outcome:
O
Population and clinical problem” or P
shows who the relevant people are in
relation to the clinical problem that
you have in mind.
Intervention (or indicator or index test)
shows the management strategy or
exposure or test you want to find out
Intervention: A procedure (such as
drug treatment, surgery, diet)
Indicator: exposure to an harmful
agent or a factor that might affect a
health outcome
Index test: A diagnostic test or a
screening test
Comparator: This shows an
alternative or control strategy,
exposure or test foe comparison
with the one you are interested in.
Outcome: This shows what you are
most concerned about happening
(or stopping happening AND/OR
what the patient is most
concerned about.
The “6S” hierarchy of organization of
pre-appraised evidence
1. Systems: Computerized decision support
2. Summaries: Evidence-based digital
textbooks (eg, UpToDate, ACP Med, CE,
PIER, UTD, Dynamed)
3. Synopses of syntheses: Evidence-based
journal abstracts (eg, ACPJC, EBM, EBN,
DARE)
4. Syntheses: Systematic reviews (eg,
ACPJC, EvidenceUpdates, Cochrane)
5. Synopses of studies: Evidence-based
journal abstracts
6. Studies: Original journal articles (eg,
ACPJC,EvidenceUpdates)
Evidence-based digital textbooks:
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ACP Med: American College Of
Physicians Medicine
CE: Clinical Evidence
PIER: Physicians Education and
Information Resource
UpToDate
ACP Journal Club
Database of Reviews of Evidence
Evidence-Based Medicine
Evidence-Based Nursing