David Sackett

-B a s e d
i d e n c e
n t o E v l
d u ct io p p ra is a
In t ro t i ca l A
n d C ri
ic i n e a
Me d
nada a
a B a g us Sub Health, , Denpasa
r
Id hi ld it al
a rt m ent of C Sanglah Hosp
Dep l-
e d ic a l Schoo
M
a s Udayana
sit
Univer
 David Sackett

What is Evidence-Based
Medicice (EBM) ?
“EBM is the conscientious, explicit, and
judicious use of current best evidence in
making decisions about the care of individual
patients” David Sackett, McMaster University; 2001

ATAU
ATAU
“kerangka
“kerangka untuk
untuk menerapkan
menerapkan bukti
bukti mutakhir
mutakhir
yang sahih dalam tata laksana pasien”
Sastroasmoro
Sastroasmoro S.
S. Evidence-based
Evidence-based Medicine.
Medicine. Jakarta:
Jakarta: Sagung
Sagung Seto;
Seto; 2014.
2014.
 David Sackett

What is Evidence-Based
Medicice (EBM) ?
“Evidence‐based medicine is the use of
mathematical estimates of the risk of benefit
and harm, derived from high‐quality
research on population samples, to inform
clinical decision‐making in the diagnosis,
investigation or management of individual
patients”
Greenhalgh
Greenhalgh T.
T. How
How to
to Read
Read aa Paper.
Paper. The
The Basic
Basic of
of Evidence-Based
Evidence-Based
Medicine
Medicine and
and Healthcare.
Healthcare. 66th ed.
th
ed. Oxford:
Oxford: Wiley
Wiley Blackwell;
Blackwell; 2019
2019
 David Sackett

The term:
Clinical Epidemiology
‘Evidence-Based Medicine’

Referred to

Evidence-Based Practice (EBP)

 David Sackett

British epidemiologist ARCHIE COCHRANE:

The fact that the most treatment-related decisions
were not based on a systematic review of clinical
research.
But based on :
1. Variable quality scientific literature
2. Expert opinion
3. Trial and error
 David Sackett

Corticosteroid for preterm birth

1972
An RCT was published : improved outcomes for preterm babies when
mother given a short course of corticosteroid
1972-1989
6 more were published, all confirming the 1972 finding
But during this time, most obstetrician were still unaware did not treat
women who have a preterm birth
1989
The 1st Systematic review of corticosteroid treatment was published.
1989-1991
Seven more studies were published
 David Sackett

Conclusion
o Corticosteroid reduces the odds babies dying from
complications of immaturity by 30-50%.
o Thousands of babies have died or suffered
unnecessarily since 1972 because doctor did not
know about the effectiveness of the treatment in
1972 trial.
TEXTBOOKS ARE ALWAYS ABOUT
5-10 YEARS OUT OF DATE
 David Sackett
“Evidence-Based Medicine is the integration
of best research evidence with clinical
expertise and patient values”
David Sackett, McMaster University; 2001
Penggabungan
Penggabungan dari:dari:
1.
1. Bukti-bukti
Bukti-bukti yg
yg sahih
sahih dari
dari penelitian.
penelitian.
2.
2. Kompetensi
Kompetensi dokter
dokter sebagai
sebagai pemberi
pemberi jasa
jasa pelayanan
pelayanan
kesehatan.
kesehatan.
3.
3. Nilai-nilai
Nilai-nilai dan
dan pilihan
pilihan pasien
pasien (ketersediaan
(ketersediaan obat,
obat,
fasilitas
fasilitas medis
medis dan
dan penunjang
penunjang yg yg diperlukan,
diperlukan, dan
dan
biaya).
biaya).
Sastroasmoro
Sastroasmoro S.
S. Evidence-based
Evidence-based Medicine.
Medicine. Jakarta:
Jakarta: Sagung
Sagung Seto;
Seto;
 David Sackett
“Evidence-Based Medicine is the integration
of best research evidence with clinical
expertise and patient values”

Clinical
Clinical expertise
expertise

EBM
EBM
Best
Best research
research evidence
evidence Patient
Patient values
values

Diagram
Diagram Venn
Venn of
of
EBM
EBM
David
David Sackett,
Sackett, McMaster
McMaster University;
University; 2001
2001
 David Sackett

Why do we need EBM ?

There is a large though variable gap

between what we know from research
and what we do in clinical practice.

Because so much research is published –

some valid and some invalid – clinicians
understandably are unaware of most of
it, or do not have the ‘tools’ to assess its
quality.
Glasziou P, et al. EBP workbook. 2nd ed. Oxford: Blackwell; 2007
 David Sackett

The amount of medical

Glasziou P, et research
al. EBP workbook. 2nd ed. Oxford: Blackwell; 2007
 David Sackett
Review the World Literature Fortnightly*
5,000?
2500000
per
Medical Articles per Year

2000000
day

1500000 1,400
55 per
1000000
per day
500000 day

0
Trials MEDLINE BioMedical
Finding the high quality evidence is like trying to sip pure water
from a hose pumping dirty water or looking for rare pearl
 David Sackett

Doctor’s
knowledge Patient
of evidence, values,
Clinical decisions concerns,
skills,
attitude expectations

Health system
access rules Concern about
(PBS, Medicare, litigation
funding, etc)
 David Sackett

How did EBM help ?

1. EBM can help you find information you need.

2. EBM helped because the empirical data were easy for

the patient to understand and he could participate in
the clinical decision

3. EBM can help to reduce litigation

4. EBM helps doctors keep up to date across a very

wide spectrum of information
 David Sackett

Case study : dog bite

Case:
A patient came to the clinic with a fresh dog bite. It
looked clean. The GP & patient wondered
whether it was necessary to give prophylactic
antibiotic.
Searched MEDLINE
Meta-analysis:
Indicating that the average infection rate for dog bites
was 14%
 David Sackett

Empirical measures of outcome

Outcome measured as:

Absolute Risk Reduction (ARR)
Relative Risk (RR )
Number Needed to Treat (NNT)
 David Sackett

The risk of infection after dog bite without Antibiotics = 14%

(0,14)

The risk of infection after dog bite with Antibiotics =7% (0,07)
ARR for Antibiotics:
14% - 7%= 7%
(7 people in every 100 treated will be saved from infection)

NNT = 100/7 = 14
(Need to treat 14 dog bite patients with AB to prevent 1 infection)

RR of infection with AB compared to without AB

RR = 0,07 / 0,14 = 0.5
 David Sackett

STEPS IN EBM
1. Formulate an answerable question

2. Track down the best evidence of outcomes available

3. Critically appraise the evidence (find out how good it is

and what it means)

4. Apply the evidence : integrate the results with clinical

expertise and patient values

5. Evaluate our performance

 David Sackett

EBM step 1 : Formulate an answerable

question
 David Sackett

Gap between “das Sollen” and “das

Sein”

Problem

Problem solving: formulate an answerable

question
The “PICO” (pronounced “pee-co”)
principle
P : Patient/ population/
I problem
: Intervention/ indicator/ index
C text
: Comparator/ control
O : Outcome
 Exampl
David e
Sackett
Julie is pregnant for the second time. She had her first baby when she was 33
and had amniocentesis to find out if the baby had Down syndrome. The test
was negative but it was not a good experience, because she did not get the
result until she was 18 weeks pregnant. She is now 35 and 1 month pregnant,
and ask if she can have a test that would give her an earlier result. The local
hospital offers serum biochemistry plus nuchal translucency ultrasound
screening as a first trimester test for Down syndrome. You wonder if this
combination of test is as reliable as conventional amniocentesis.

PICO principle
P Population/problem: pregnant women (first trimester)
I Index test : serum biochemistry plus nuchal
translucency ultrasound screening
C Comparator/control : conventional amniocentesis
O Outcome : accurate diagnosis (sensitivity and
specificity) of Down syndrome
Glasziou P, et al. EBP workbook. 2nd ed. Oxford: Blackwell;
 David Sackett

Clinical
question:
For pregnant women, is serum
biochemistry plus nuchal
translucency ultrasound screening
testing in the first trimester as
accurate (equal or better sensitivity
and specificity) as conventional
amniocentesis for diagnosing Down
syndrome?
Glasziou P, et al. EBP workbook. 2nd ed. Oxford: Blackwell; 2007
 David Sackett

Question Best study designs

Intervention RCT
Aetiology and risk RCT, Cohort, Case-
factors control
Frequency and rate Cohort, Cross-sectional
Diagnosis Cross-sectional with
random or consecutive
sample
Prognosis and prediction Cohort/survival study

Straus SE, et al. EBM, 3 rd ed. London: Elsevier; 2005

 David Sackett

Question Question type Best Study design

What should I do about this
condition or problem?
What causes the problem?
How common is the
problem?
INTERVENTION RCT
AETIOLOGY AND RISK RCT, Cohort study, Case-
FACTORS control study
FREQUENCY AND RATE Cohort study, Cross-
sectional study

Does this person have the DIAGNOSIS Cross-sectional study

condition or problem with random or
consecutive sample

Who will get the condition PROGNOSIS AND Cohort/survival study

or problem PREDICTION
 David Sackett
Clinical
For pregnant
question: women, is serum
biochemistry plus nuchal translucency
ultrasound screening testing in the first
trimester as accurate (equal or better
sensitivity and specificity) as conventional
amniocentesis for diagnosing Down
Step 2:Track down the best evidence
syndrome?
(searching of article)

Step 3 and 4: Critically appraise and

apply the evidence
Step
Step 5:
5: Evaluate
Evaluate our
our performance
performance
 David Sackett

EBM step 2 : Track down the best evidence

oo What
What study
study designs
designs should
should you
you look
look for
for
(interventions,
(interventions, aetiology
aetiology and
and risk
risk factors,
factors, diagnosis,
diagnosis,
prognosis,
prognosis, frequency,
frequency, and
and rate)?
rate)?

oo How
How to
to recognize
recognize different
different study
study types
types [experimental,
[experimental,
observational
observational (cohort,
(cohort, case-control,
case-control, cross-sectional
cross-sectional
studies,
studies, case
case report,
report, case
case series),
series), analytical,
analytical,
descriptive]?
descriptive]?
 David Sackett

oo Where
Where to
to search
search (PubMed,
(PubMed, The
The Cochrane
Cochrane Library,
Library, and
and
others)?
others)?

oo Searching
Searching tips
tips and
and tactics
tactics [AND,
[AND, OR,
OR, NEAR,
NEAR, NOT,
NOT,
parentheses,
parentheses, ** (truncation),
(truncation), ti,
ti, so]
so]
 David Sackett

EBM Step 3 : Critically appraise the evidence

A careful look at the study or studies

and decide how good they are for
answering the clinical question.
 David Sackett

Principles of critical
appraisal – primary research

1. What is the PICO of the study, and is it close

enough to your PICO?
2. How well was the study done?
3. What do the results mean and could they have
been due to chance?
 David Sackett

1. Is the PICO of the study close enough to your

PICO?
oo When
When you
you find
find aa study
study that
that you
you think
think will
will help
help to
to
answer
answer your
your clinical
clinical question,
question, the
the first
first thing
thing to
to look
look at
at
is
is whether
whether the
the PICO
PICO of
of the
the study
study matches
matches the the PICO
PICO of
of
your
your question.
question.

oo Quickly
Quickly decided
decided ifif you
you want
want to
to appraise
appraise itit further
further or
or
not.
not.
 David Sackett

2. How well was the study done?

R Recruitment :
were the subjects representative of the target population?
Allocation or Adjustment :
A Was the treatment allocation concealed before randomization and were
the groups comparable at the start of the trial?

M Maintenance :
Was the comparable status of the study groups maintained through equal
management and adequate follow-up?

M Measurement :
Were the outcomes measured with :

b blinded subjects and assessor and/or

o objective outcomes?
 David Sackett
Study question Study design Aim Study methods Critical
Appraisal
Source
Source
P Fair recruitment
Subjects
Recruit a large
enough sample R
representative of the PLUS recruit subject
Subjects target population randomly OR recruit
Subjects consecutive patient

I Fair allocation Allocate randomly to

groups A
Comparable study OR
groups Adjust for
confounding

C Fair Maintenance Manage groups

equally M
Follow up all subjects
and assess relevant
II C
C
outcomes in the
starting groups
+
+
O Fair Measurement
Valid and unbiased
Measure outcomes
with: blinded subjects M
outcome measures and assessors and/or
-- objective measures b
o
 David Sackett

3. What do the results mean?

P-values (hypothesis testing)

Measure the probability that a result is purely due to

chance
P < 0,05 ~ statistically significant

Confidence intervals (CI ~ estimation)

An estimate of the range of values that are likely to

include the real value
Usually CI are quoted as 95% CI
 Outcome measures for binary outcomes
Measure
Relative Risk (RR)
= risk of outcome in the
treatment group/risk of
event in the control group
Absolute risk reduction
(ARR)
= risk of event in the control
group – risk of event in the
treatment group
Relative risk reduction
(RRR)
= ARR/risk of event in
control group
(or 1 – RR)
Number needed to treat
(NNT)
= 1/ARR
Meaning Example
David Sackett
RR tells us how many times more likely it is that an RR = 0,1/0,15 = 0,67
event will occur in the treatment group relative to the
control group Since this RR < 1 , the treatment
RR = 1 means that there is no difference between decreases the risk of death
the 2 groups
RR < 1 means that the treatment reduces the risk of
the event
RR> 1 means that the treatment increases the risk
of the event
ARR tells us the absolute difference in the rates of ARR = 0,15 – 0,10 = 0,05 (5%)
events between the two groups and given an
indication of the baseline risk and treatment effect The absolute benefit of treatment
ARR = O means that there is no difference between is a 5% reduction in the death
two groups rate
ARR positive means that the treatment is beneficial
ARR negative means that the treatment is harmful
RRR tells us the reduction in rate of the event in the RRR = 0,05/0,15 = 0,33 (33%)
treatment group relative to the rate in the control OR
group 1 – 0,67 = 0,33 (33%)
RRR is probably the most commonly reported
measure of treatment effects
NNT tells us the number of patients we need to treat NNT = 1/0,05 = 20
in order to prevent 1 bad event We would need to treat 20
people for 2 years in order to
prevent 1 death
 Statistically
Statistically Clinically
Clinically
significant
significant important
important

= confidence interval

= point estimate OR
effect size

Minimum clinical
Important difference

Null hypothesis
(no effect)
(a) (b) (c) (d)
(a) Difference is clinically important and statistically significant
(b) Difference is clinically important but not statistically significant
(c) Difference is not clinically important but statistically significant
(d) Difference is not clinically important and not statistically significant
 David Sackett

RAMMbo
INTERVENTION PROGNOSTIC DIAGNOSTIC FREQUENCY

R R R R

A = allocation A = adjustment (-) (-)

M M M M

M M M M

b b b b

o o o o
 David Sackett

EBM Step 4 : Apply the evidence : integrate the

results with clinical expertise and patient
values
The
The questions
questions that
that you
you should
should ask
ask before
before you
you decide
decide
to
to apply
apply the
the results
results ofof the
the study
study toto your
your patient
patient
are:
are:
1.
1. IsIs the
the instrument
instrument or or test
test are
are feasible
feasible in
in my
my
setting?
setting?
2.
2. What
What else
else do
do II need
need to
to apply
apply this
this evidence?
evidence?
3.
3. What
What alternatives
alternatives are
are available?
available?
 David Sackett

EBM Step 4: Apply the evidence : integrate the

results with clinical expertise and patient
values

4.
4. Is
Is my
my patient
patient so
so different
different to
to those
those inin the
the study
study
that
that the
the result
result can
can not
not apply
apply at
at all?
all?
5.
5. Will
Will the
the potential
potential benefits
benefits of
of treatment
treatment outweigh
outweigh
the
the potential
potential harms
harms of of treatment
treatment forfor my
my patient?
patient?
6.
6. What
What does
does my
my patient
patient think
think about
about it?
it?
(%
(%
))

David Sackett
BB Lower
Lower risk
risk patients
patients Higher
Higher risk
risk patients
patients
ee
nn
ee 88
ff
ii Trial
Trial patients
patients Note:
Note:
tt
Benefit
Benefit
oo 66
ff Harm
Harm
Threshold
Threshold
tt
rr 44
ee
aa
tt
m
m 22
ee
nn
tt
00
00 55 10
10 15
15
Risk
Risk of
of outcome
outcome (%)
(%)
 David Sackett

The “f method” for estimating your

patient’s risk:
● If your patient is twice as susceptible as
those in trial, f = 2
● If your patient is half as susceptible as
those in the trial, f = 0.5

The NNT for your patient = NNT (trial)/f

 David Sackett

EBM Step: Evaluate our performance

1.
1. Informal:
Informal: evaluate
evaluate the
the outcome
outcome ofof EBM
EBM practice
practice in
in
each
each patient.
patient.
2.
2. Formal
Formal :: evaluate
evaluate the
the input,
input, process,
process, and
and outcome
outcome
 David Sackett

Pasien
Pasien dg
dg
masalah
masalah

Terapkan
Terapkan Formulasikan
Formulasikan
“evidence”
“evidence” permasalahan
permasalahan
klinis
klinis

Telaah
Telaah kritis
kritis Cari
Cari
“evidence”
“evidence” “evidence”
“evidence”

Gambar.
Gambar. Siklus
Siklus EBM
EBM
 David Sackett

Level of evidence
LEVEL INTERVENTION DIAGNOSIS PROGNOSIS AETIOLOGY
I Systematic review of Systematic review of Systematic Systematic
level II studies level II studies review of level II review of level II
studies studies

II RCT Cross-sectional - Inception cohort Prospective

consecutive study cohort study
III One of the following: One of the following: One of the One of the
•Non-randomized •Cross-sectional – following: following:
experimental study non-consecutive •Untreated •Retrospective
•Cohort study, case- •Diagnostic case- control – RCT cohort study
control study control •Retrospectively •Case-control
cohort study study

IV Case series Case series Case series, Cross-sectional

cohort study at
different stages
of disease
 Level of evidence
Level of Therapy/prevention/etiology/ harm
evidence
1a Systematic review of homogeneity of RCTs
1b Individual RCT with narrow CI
1c All or none
2a Systematic review (with homogeneity) of cohort
studies
2b Individual cohort study (including low-quality RCT;
e.g. <80% f-up)
3a Systematic review (with homogeneity) of case-
control study
3b Individual case-control study
4 Case series (and poor quality cohort and case-
control study)
5 Expert opinion
 Grade of recommendation
A Consistent level 1 studies

B Consistent level 2 or 3 studies OR extrapolations from levels 1

studies

C Level 4 studies OR extrapolations from level 2 or 3 studies

D Level 5 evidence OR troublingly inconsistent OR inconclusive

studies at any level

Straus SE, et al. EBM, 3 rd ed. London: Elsevier; 2005

 David Sackett

References

1. Glasziou P, et al. EBP workbook. 2nd ed. Oxford: Blackwell; 2007

2.
2. Sastroasmoro
Sastroasmoro S.
S. Evidence-based
Evidence-based Medicine.
Medicine. Jakarta:
Jakarta: Sagung
Sagung Seto;
Seto;
2014.
2014.

3.
3. Greenhalgh
Greenhalgh T.T. How
How to
to Read
Read aa Paper.
Paper. The
The Basic
Basic of
of Evidence-Based
Evidence-Based
Medicine
Medicine and
and Healthcare.
Healthcare. 66th ed.
th
ed. Oxford:
Oxford: Wiley
Wiley Blackwell;
Blackwell; 2019
2019

4.
4. Straus
Straus SE,
SE, et
et al.
al. Evidence-Based
Evidence-Based Medicine.
Medicine. How
How to
to Practice
Practice and
and Teach
Teach
EBM.
EBM. 55th ed.
th
ed. Edinburgh:
Edinburgh: Elsevier;
Elsevier; 2019
2019
David Sackett
David Sackett
 David Sackett

Latihan
Latihan
Skenario
Skenario 1
1
Kita
Kita menghadapi
menghadapi anak
anak dg
dg defisiensi
defisiensi growth
growth
hormone
hormone (GH),
(GH), apakah
apakah pemberian
pemberian terapi
terapi GH
GH
eksogen
eksogen dapat
dapat memacu
memacu pertumbuhan
pertumbuhan anakanak
tersebut?
tersebut?

Buat
Buat pertanyaan
pertanyaan klinis
klinis berdasarkan
berdasarkan prinsip
prinsip
PICO
PICO !!!!!
!!!!!
 David Sackett

Latihan
Latihan
Skenario
Skenario 22
Kita
Kita menghadapi
menghadapi perempuan
perempuan mudamuda yang
yang telah
telah
didiagnosis
didiagnosis dengan
dengan lupus
lupus eritematosus
eritematosus sistemik.
sistemik.
Pasien
Pasien tersebut
tersebut pernah
pernah mengalami
mengalami komplikasi
komplikasi
gagal
gagal jantung
jantung 22 bulan
bulan yang
yang lalu.
lalu. Kita
Kita ditanya
ditanya oleh
oleh
keluarga
keluarga tentang
tentang harapan
harapan kesembuhan
kesembuhan pasien
pasien
tersebut
tersebut

Buat
Buat pertanyaan
pertanyaan klinis
klinis berdasarkan
berdasarkan prinsip
prinsip
PICO
PICO !!!!!
!!!!!
 David Sackett

Latihan
Latihan

Skenario
Skenario 3
3
Pada
Pada suatu
suatu studi
studi kohort
kohort ditemukan
ditemukan insidens
insidens batuk
batuk
kronik
kronik berulang
berulang (BKB)
(BKB) pada
pada pekerja
pekerja pabrik
pabrik tekstil
tekstil
sebesar
sebesar 16%,
16%, sedangkan
sedangkan pada
pada pekerja
pekerja pabrik
pabrik
minuman
minuman sebesar
sebesar 6%.
6%. Risiko
Risiko relatif
relatif (RR)
(RR) yang
yang
didapat
didapat adalah
adalah 2,67
2,67 (IK95%
(IK95% 1,8
1,8 sampai
sampai 4,4).
4,4).

1.
1. Bagaimana
Bagaimana interpretasi
interpretasi dari
dari nilai
nilai RR
RR tersebut
tersebut ??
2.
2. Apakah
Apakah nilai
nilai RR
RR tersebut
tersebut penting
penting secara
secara klinis
klinis ??
3.
3. Bagaimana
Bagaimana presisi
presisi estimasinya?
estimasinya?
 David Sackett

Latihan
Latihan

Skenario
Skenario 4
4

Suatu
Suatu uji
uji klinis
klinis acak
acak terandomisasi,
terandomisasi, dari
dari 100
100
subyek
subyek yang
yang diberi
diberi obat
obat standar
standar sembuh
sembuh 60%,
60%,
sedangkan
sedangkan yang
yang diberi
diberi obat
obat baru
baru sembuh
sembuh 75%.
75%.

1.Berapa
1.Berapa nilai
nilai NNT
NNT yang
yang didapat
didapat ??
2.
2. Apa
Apa arti
arti nilai
nilai NNT
NNT tersebut
tersebut ??
David Sackett