Introduction to Evidence Based

Medicine
dr. Rahma Yuantari, MSc, Sp.PK
Departemen Patologi Klinik
FK UII
 What is
“evidence-based
medicine?”
 Two fundamental questions…

• What is the purpose of medicine?

• How do I decide what to do?
What is the purpose of medicine?
• Patient care
• Public health
• Research

 Improving the quality of

patients’ lives…
 What is evidence-based medicine?
Evidence based medicine is the conscientious,
explicit, and judicious use of current best
evidence in making decisions about the care of
individual patients.

EBM  penggunaan bukti terbaik

saat ini dengan hati-hati, jelas, dan
bijak, untuk pengambilan
keputusan pelayanan pada individu
pasien.
Sackett, et al. BMJ 1996;312:71-72
 How do I decide what to do?
How do I make decisions?
• Dogma: “Natural is best”
• Tradition: “We’ve always done it that way”
• Convention: “Everyone does it this way”
• Evidence-Based: “Evidence supports this way”
• Why do EBM
– Provide high quality care to patients
– Utilize high quality evidence in patient care
– Overcome limitations of current practice
 HOW DO WE ACTUALLY PRACTICE EBM?

• Step 1: converting the need for information

(about prevention, diagnosis, prognosis,
therapy, causation, etc.) into an answerable
question.
 HOW DO WE ACTUALLY PRACTICE EBM?

• Step 2: tracking down the best evidence with

which to answer that question.
 HOW DO WE ACTUALLY PRACTICE EBM?

• Step 3: critically appraising that evidence for

its
validity (closeness to the truth)
impact/ importancy (size of the effect)
applicability (usefulness in our clinical
practice).
 HOW DO WE ACTUALLY PRACTICE EBM?

• Step 4: integrating the critical appraisal with

our clinical expertise and with our patient’s
unique biology, values, and circumstances.
• "Without clinical expertise, practice risks
becoming tyrannized by external evidence, for
even excellent external evidence may be
inapplicable to or inappropriate for an
individual patient. Without current best
external evidence, practice risks becoming
rapidly out of date, to the detriment of
patients."
 HOW DO WE ACTUALLY PRACTICE EBM?

• Step 5: evaluating our effectiveness and

efficiency in executing steps 1–4 and seeking
ways to improve them both for next time.
 The Question
• Background
– Anatomy and Physiology
– Pathophysiology
– Pharmacology and Toxicology
– Differential diagnosis
– Diagnostic testing
– Treatment
– Textbooks, reviews, lectures, experts
 Developing clinical questions

“To get the right answer,

you must first ask the right question.”
 Developing The Clinical Question
 Step 1: Formulate the clinical issue into a
searchable, answerable question.
 Step 2: Distinguish what type of question you
may have.

Background

Foreground

Experience with Condition

 Background questions
 Background questions ask for general
information about a condition or thing.
 A question root (who, what, when, etc) combined
with a verb.

What is the indication of giving birth

induction ?

Background questions are typically answered by textbooks.

 Foreground questions
 Foreground questions ask for specific
knowledge about a specific patient with a
specific condition.

Is MgSO4 effective to prevent seizure in

eclamsia patient?

Foreground questions are typically answered by

databases that access the research literature
 Developing the question
 Foreground questions usually have four
components.:
P = Patient population

I = Intervention

C = Comparison

O = Outcome
 PICO: Components of an answerable, searchable question

Patient population/disease The patient population or disease of interest

- age
- gender
- ethnicity
- with certain disorder (e.g., hepatitis)
Intervention The intervention or range of interventions of interest
- Exposure to disease
- Prognostic factor A
- Risk behavior (e.g., smoking)
Comparison What you want to compare the intervention against
- No disease
- Placebo or no intervention/therapy
- Prognostic factor B
- Absence of risk factor (e.g., non-smoking)
Outcome Outcome of interest
- Risk of disease
- Accuracy of diagnosis
- Rate of occurrence of adverse outcome (e.g., death)

Melnyk, B. M., & Fineout-Overholt, E. (2005). Evidence-based practice in nursing & healthcare : A guide to best practice. Philadelphia,
PA: Lippincott Williams & Wilkins.
In patient with does or affect
[Patient/ [Intervention] [Comparison, [Outcome]
Problem] if any]

In patients with chronic pain, does the use of progressive

muscle relaxation lead to a lessening of pain?

In patients with eclampsia, do MgSO4 (magnesium

sulphate) therapy effective?

Is caffein cause spontaneus abortion in pregnant

woman?
Types of Questions
 Harm or Etiology: Are there harmful effects of a particular
intervention, or how these harmful effects can be avoided.

 Diagnosis: How to select a diagnostic test or how to

interpret the results of a particular test.

 Therapy: Which treatment is the most effective, or what is

an effective treatment for a particular condition.

 Prognosis: What is the patient's likely course of disease, or

screen for or reduce risk of outcome.

 Prevention: How can the patient's risk factors be adjusted to

help reduce the risk of disease?

 Cost: Looks at cost effectiveness, cost/benefit analysis.

 Best Type of Study for Your Question
Type of Question Suggested Best Type of Study

Etiology / Harm RCT > cohort > case control > case series

Diagnosis Prospective, blind comparison to gold standard

Therapy RCT > cohort > case control > case series

Prognosis Cohort study > case control > case series

Prevention RCT > cohort study > case control > case series

Cost Economic analysis

 Medical Literature
Primary – original research Secondary – reviews of original
research
 Experimental (an intervention is  Meta-analysis
made or variables are  Systematic reviews
manipulated)  Practice guidelines
 Randomized Control Trials
 Reviews
 Controlled trials
 Decision analysis
 Observational (no intervention or
variables are manipulated)  Consensus reports
 Cohort studies  Editorial, commentary
 Case-control studies
 Case reports
Filtered resources Unfiltered Resources

• Systematic Reviews / Meta- Original /primary research

Analyses
• PubMed
• The Cochrane Database of
Systematic Reviews • Ovid Medline
• Ovid MEDLINE • bmj
• PubMed
• Critically-Appraised Topics
• National Guideline
Clearinghouse
• Critically-Appraised
Individual Articles
• The ACP Journal Club
Finding the Evidence
Quality of evidence
 Levels of Evidence
+

Bias >>
Finding the Evidence
Finding the Evidence
Finding the Evidence
Finding the Evidence
Finding the Evidence
“Not all evidences are
created equal”
 Critical Appraisal
• Is the evidence valid?
• Is evidence important?
• Does the evidence apply to our patient?
Harm Study
A. Are the results of this harm study valid?
Were there clearly defined groups of patients, similar in all
important ways other than exposure to the treatment or
other cause?
Were treatments/exposures and clinical outcomes
measured in the same ways in both groups (was the
assessment of outcomes either objective or blinded to
exposure)?
Was the follow-up of study patients complete and long
enough?
Do the results satisfy some “diagnostic tests for causation”?
Is it clear that the exposure preceded the onset of the
outcome?
Is there a dose-response gradient?
Is there positive evidence from a “dechallenge-rechallenge”
study?
Is the association consistent from study to study?
Does the association make biological sense?
Harm study ..
Harm study ..
C. Should these valid, potentially important results change the
treatment of your patient?
Is your patient so different from those in the study that
its results don’t apply?
What are your patient’s risks of the adverse event?
To calculate the NNH (number of patients you need to
treat to harm one of them) for any odds ratio (OR) and
your patient’s expected event rate for this adverse
event if they were not exposed to this treatment
(PEER):
PEER(OR  1)  1
NNH 
PEER(OR  1)  (1  PEER)

What are your patient’s preferences, concerns and

expectations from this treatment?
What alternative treatments are available?
 Diagnostic study
A. Are the results of this diagnostic study valid?
Was there an independent, blind comparison with
a reference (“gold”) standard of diagnosis?
Was the diagnostic test evaluated in an appropriate
spectrum of patients (like those in whom it would
be used in practice)?
Was the reference standard applied regardless of
the diagnostic test result?
Was the test (or cluster of tests) validated in a
second, independent group of patients?
Diagnostic Study…
Are the valid results of this diagnostic study important?

Table 2x2
Target disorder
Totals
Present (+) Absent (-)
Positive a b a+b
Diagnostic
test result Negative c d c+d
a+c b+d a+b+c+d
Totals
Sensitivity = a/(a+c)
Specificity = d/(b+d)
Likelihood ratio for a positive test result = LR+ = sens/(1-spec)
Likelihood ratio for a negative test result = LR - = (1-sens)/spec
Positive Predictive Value = a/(a+b)
Negative Predictive Value = d/(c+d)
Pre-test probability (prevalence) = (a+c)/(a+b+c+d)
Pre-test odds = prevalence/(1-prevalence)
Post-test odds = pre-test odds  LR
Post-test probability = post-test odds/(post-test odds +1)
 Likelihood ratio
• >10 atau < 0,1, menghasilkan perubahan yg besar
dari pre dan post test probability. Dan sering
conclusive
• 5-10 dan 0,1-0,2, perubahan sedang
• 2-5 daan 0,2-0,5 perubahan kecil (kadang-kadang
penting)
• 1-2 dan 0,5-1, mengubah probability kecil sekali (dan
jarang penting)
 Diagnostic study..
C. Can you apply this valid, important evidence about a diagnostic
test in caring for your patient?

Is the diagnostic test available, affordable, accurate, and

precise in your setting?
Can you generate a clinically sensible estimate of your
patient’s pre-test probability (from personal experience,
prevalence statistics, practice databases, or primary
studies)?
 Are the study patients similar to your own?
 Is it unlikely that the disease possibilities or probabilities
have changed since the evidence was gathered?
Will the resulting post-test probabilities affect your
management and help your patient?
 Could it move you across a test-treatment threshold?
 Would your patient be a willing partner in carrying it out?
Would the consequences of the test help your patient?
 Therapeutic study
A. Are the results of this single preventive or therapeutic trial valid?

Was the assignment of patients to treatments

randomised?
Was the randomisation list concealed?
Was follow-up of patients sufficiently long and
complete?
Were all patients analysed in the groups to which
they were randomised?
Were patients and clinicians kept “blind” to
treatment?
Were the groups treated equally, apart from the
experimental treatment?
Were the groups similar at the start of the trial?
Therapeutic study..
B. Are the valid results of this trial Important?
• What is the magnitude of the treatment effect?
• How precise is this estimate of the treatment effect?
– 95% CI
– Directly related to number of patients in a study
Therapeutic study..

What is the magnitude of the treatment effect?

– CER = control event rate
– EER = experimental event rate
– RRR = relative risk reduction
= |CER – EER|/CER
– ARR = absolute risk reduction
= |CER – EER|
– NNT = Number needed to treat
= 1 / ARR
Therapeutic study..
C. Are the valid, important results applicable to our
patient?
• How similar is our patient to the patients studied?
• Is the treatment feasible?
• What are our patient’s potential benfits and harms
from the therapy?
• What are our patient’s values and expectations for both
the outcome we are trying to prevent and the
treatment we are offering?
Prognostic Study
A. Are the results of this prognosis study valid?
Was a defined, representative sample of patients
assembled at a common (usually early) point in the
course of their disease?
Was patient follow-up sufficiently long and
complete?
Were objective outcome criteria applied in a “blind”
fashion?
If subgroups with different prognoses are identified,
was there adjustment for important prognostic
factors?
Was there validation in an independent group (“test
set”) of patients?
Prognostic Study..
B. Are the valid results of this prognosis study important?

How likely are the outcomes over time?

How precise are the prognostic estimates?
C. Can you apply this valid, important evidence about prognosis in caring for
your patient?
Were the study patients similar to your own?

Will this evidence make a clinically important impact on your

conclusions about what to offer or tell your patient?
 Applying the study
The questions you should ask before :
• Is the treatment or test feasible in my setting?
• What else do I need to apply this evidence?
• What alternatives are available?
• Is my patient so diff erent to those in the study that the
results cannot apply at all?  age, comorbidity, compliance
• Will the potential benefits of treatment outweigh the
potential harms of treatment for my patient?
• What does my patient think about it?
Adapted from: Sackett D.L., Rosenberg M.C., Gray J.A., Haynes R.B., Richardson W.S. (1996).
Evidence based medicine: what it is and what it isn't. BMJ, 312, 71-72.
 Evaluation practice of EBM
• How am I doing?
• Diary of a reflective practitioner
 Reflective question :
• 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?
• Are you sharing your efforts with others?