EBM Therapy
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Transcript of EBM Therapy
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Evidence-Based Medicine
Therapy
Dr. Rina Amelia, MARS
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Antiinflammatory effect of Drug A vs. Drug B
for dysmenorrhoea
Cured Not Cured
Drug A 87 (87%) 13 (13%)
Drug B 74 (74%) 26 (26%)
Example
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Reports of individual studies
I. Are the results of the study valid?
II. What were the results?
III. Are these valid, important results applicable to our patient?
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Evidence-Based Medicine
Critical Appraisal
Research Methodology
Health Services
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Evidence-Based Medicine(Papers in Journal of Medicine / Health Sciences)
Valid Methodology of study
Important Result of study
Applicability Discussion
VIA
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Treatment / Therapeutic intervention
EBM : Valid, important and applicable
to particular patients
High rank of hierarchy of evidence(Systematic reviews /meta-analyses;
Randomized Controlled clinical trial / RCT)
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Treatment / Therapeutic intervention
Answerable Clinical Question (ACQ)
P : Patient, Problem, Population
I : InterventionC : ComparisonO : Outcome
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Hypertensive patientshould I startACE inhibitors?
Patient : middle aged man withdiastolic 100 mm Hg
Intervention : ACE inhibitors
Comparison : Diuretics
Outcome : prevent heart disease;stroke; end-organ damage?
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EBMfortherapy
1. Reports of individual studies
2. Reports of systematic reviews (RCT)
5. Reports of qualitative study
3. Reports of Clinical Decision Analyses(CDA)
4. Reports of economic analyses
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Integrative literature
Review article :* unsystematic
Systematic review :
* in gathering, evaluating, presenting evidence
* no formal statistical method
Meta-analysis :* systematic review + formal statistical analysis
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Integrative literature
Review article
Systematic review
Meta-analysis
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1. Reports of individual studies
High rank of hierarchy of evidence(Randomized Controlled clinical trial / RCT)
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Key elements of RCT
Randomization
Control Blinding
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1. Reports of individual studies
1. Are the results of individual studies valid?
2. Are the valid results of individual studies,important?
3. Are the valid, important resultsof individual studies;
applicable to our patient?
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1. Are the results of individual studies,valid?
Primary guides:
1.Was the assignment of patients
to treatments randomized?
2. Was follow-up of patients sufficiently long
and complete?
3. Were patients analyzed in the groups
to which they were randomized?
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Preventing bias Equal chance
Balance of subjects characteristic
Toast / coin
Simple randomization (random table)Block randomizationStratified randomization
1. Was the assignment of patientsto treatments randomized?
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2. Was follow-up of patients sufficiently longand complete?
Lost to follow up no more than 20%
Journals like Evidence-Based Medicine and
ACP Journal Clubwont publish trials with > 80% follow-up.
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3. Were patients analyzed in the groupsto which they were randomized?
Intention to treat analysis
All patients are analyzed in the groups
to which they were initially assigned
A strategy for analyzing data
in which all participants are includedin the group to which they were assigned,whether or not they completed
the intervention given to the group.
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1. Are the results of the study valid?
Secondary guides:
4. Was the randomization concealed?
2. Aside from the experimental intervention,were the groups treated equally?
1. Were patients, health workers,and study personnel "blind" to treatment?
3. Were the groups similar at the start
of the trial?
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1. Patients, health workers, and study
personnel "blind" to treatment?
Prevent bias
Single blind
Double blindTriple blind
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Similar:FormColorTaste
Drug of administration
Blind intervention
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SUBJECTS
EFFECT
EFFECT
CLINICAL TRIAL DESIGNS
TREATMENT GROUP
CONTROL GROUP
1. PARALLEL DESIGNTWO GROUPS :
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Wash-out
PeriodSUBJECTS
2. CROSS-OVER DESIGN :
TREATMENT
A
TREATMENT
B
EFFECT
EFFECT
TREATMENT
B
TREATMENT
A
EFFECT
EFFECT
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1. 2. 1. What is magnitudeof the treatment effect?
1. 2. 2. How precise is the estimateof the treatment effect?
1. 2. Are the valid results of individual study,important?
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1. 2. Elements of important of the treatment effect
p value, RRR, RRI, ARR, ARI, NNT, NNH1. 2. 1. Magnitude of the treatment effect:
1. 2. 2. How precise is the treatment effect :Confidence Interval (CI)
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Study of statin to prevent stroke5 years follow-up)
Stroke occurred among 5.7 of patients randomized tocontrolgroupControl Event Rate = CER)
Stroke occurred among 4.3 of patients randomized toexperimental groupExperimental Event Rate = EER)
1.2. 1. Elements of magnitudeof the treatment effect
RRR = {(CEREER) / CER}
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CER (study for preventing stroke) = 5.7
1.2. 1. Elements of magnitudeof the treatment effect
RRR = {(CEREER) / CER}RRR = (5.7%4.3%) / 5.7% = 25%
Statin therapy decreased the risk of strokeby 25% relative to those who receive placebo
EER (study for preventing stroke) = 4.3
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1.2. 1. Elements of magnitudeof the treatment effect
The situation in which the experimental
treatment increase the risk of a good event
as the Relative Benefit Increase (RBI) or
the risk of bad event asRelative Risk Increase(RRI)also can use the same formula (RRR):
RRR = RBI = RRI = {(CEREER) / CER}
RRR = RBI = RRI =(5.7%4.3%) / 5.7% = 25%
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Relative Risk Reduction (RRR) :is the percent reduction in risk in treated group compared to the control group
The RRR is measure of how the treatment studied has reduced the frequency of anadverse event
1. 2. 1. Elements of magnitudeof the treatment effect
Absolute Risk reduction (ARR):is the difference in risk between the control group and the treatment group
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1.2. 1. Elements of magnitude
of the treatment effect
The situation in which the experimental
treatment increase the risk of a good event
as the Absolute Benefit Increase (ABI) or
the risk of bad event asAbsolute Risk Increase(ARI)also can use the same formula (ARR):
ARR = ABI = ARI = (CEREER)
ARR = ABI = ARI =(5.7%4.3%) = 1.4%
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Significance of Relative Risk Reduction
Negative RRR (- 38%):treatment may do harm:
patients given the new treatment
might be 38% more likely to die
than the control patients
RRR of 0%:no treatment effect or benefit
Positive RRR (50%):patients receiving the newtreatment might have less than 1/2 risk of dying
compared to not treated
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The greater the relative risk reduction
the more effective the therapy
(>>> RRRefficacy of therapy)
1.2.1. Element of magnitude
of the treatment effect
RRR = {(CEREER) / CER}
CER : Control Event Rate (without treatment/placebo)
EER : Experimental Event Rate (with treatment)
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Number Needed to Treat (NNT) :* Number of patients should be treatedto avoid 1 (one) bad outcome
* Number of patients should be treatedto have additional good outcome
1.2. 1. Elements of magnitude
of the treatment effect
Number Needed to Harm (NNH) :Number needed to harm 1 (one) patientfrom the therapy
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Number Needed to Treat (NNT) = 1 / ARR* NNT = 1 / 1.4% = 72
we need to treat 72 people with a statin(rather than placebo) for 5 years
to prevent one additional person
from suffering a stroke
1.2. 1. Elements of magnitudeof the treatment effect
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Therapy / treatment - case study
A randomized double blind control clinical trial
on 3 month5 year old children with mild to
moderate croup (laryngotracheobronchitis).
The experimental group : 2 mg (4 ml) nebulizedbudesonide.
The control group : 4 ml nebulized normal saline.
Event being prevented : hospital admission due
to upper-airway obstruction.
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27
N = 54
27
1
26
7
20
R
The study protocol
Hospitalized
Hospitalized
Non-Hospitalized
Non-Hospitalized
budesonide
normal saline
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No Yes
Budesonide (E) 26 1 27
NaCl (C) 20 7 27
Upper-airway obstruction
X2 df =1 p = 0.04
Important
Important
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No Yes
Budesonide (E) 26 1 27
NaCl (C) 20 7 27
Upper-airway obstruction
CER = 7 / 27 = 0.26 ;
Important
EER = 1 / 27 = 0.04
RRR = (CEREER) / CER
RRR = (0.260.04)/ 0.26 = 85%ARR = (CEREER) = (0.260.04)= 0.22
NNT = 1 / ARR = 1 / 0.22 = 5
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Budesonide vs normal saline;Upper-airway obstruction
CER EER ARR NNT
In the actual trial 26% 4% 22% 5
In the hypothetical
trivial case 0.00026 0.00004 0.00022 5000
Important
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Confidence interval
1. 2. 2. Elements for deciding precision
of the treatment effect
(
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1. 3. 1. Is our patient so different from thosein the study that its results cannot apply?
1. 3. 2. Is the treatment feasible in our setting?
1. 3.Are the valid, important results of thisindividual studies applicable to our patient?
1. 3. 3. What are our patients potential benefitsand harms from the therapy?
1. 3. 4. What are our patients values andexpectations for both the outcome
we are trying to prevent
and the treatment we are offering?
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2. Reports of systematic reviews
2. 1. Are the results of this systematic review,
valid?
2. 2. Is the valid evidence from thissystematic review, important ?
2. 3. Are the valid, important results
of this systematic review,applicable to ourpatient?
2 1 I th id f thi t ti i
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2. 1. Is the evidence from this systematic review,valid?
2. 1. 1. Is the systematic reviewof randomized trials?
2. 1. 2. Does it describe a comprehensive and
detailed search for relevant trials?
2. 1. 3. Were the individual studies assessed
for validity?
Primary guide
Secondary guide
2. 1. 4. Were individual patient data
(or aggregate data) used in analysis?
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2. 2. Is the evidence from this systematic review,important?
2. 2. 1. Are the results consistent across studies?
2. 2. 2. What is the magnitude of treatment effect?
2. 2. 3. How precise is the treatment effect?
2 3 A h lid i l f
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2. 3. Are the valid, important results ofthis systematic review, applicable to our patient?
2. 3. 1. Is our patient so different from thosein the study that is results cannot apply?
2. 3. 2. Is the treatment feasible in our setting?
2. 3. 3. What are our patients potential benefits
and harm from the therapy?
2. 3. 4. What are our patients values and
expectations for both the outcome
we are trying to prevent and
the adverse effects we may cause?
3 1 Are the results of this clinical decision
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3. 1. Are the results of this clinical decisionanalysis (CDA), valid?
3. 1. 1. Were all important therapeutic alternatives
(including no treatment) &
outcome included?
3. 1. 2. Are the probabilities of the outcomes
valid & credible?
3. 1. 3. Are the utilities of the outcomes valid &credible?
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3. 2. Are the valid results of this CDA, important?
3. 2. 1. Did one course of action lead
to clinically important gains?
3. 2. 2. Was the same course of action preferred
despite clinically sensible changes
in probabilities & utilities?
3 3 A th lid i t t lt f thi CDA
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3. 3. Are the valid, important results of this CDA,applicable to our patient?
3. 3. 1. Do the probabilities in this CDA
apply to your patient?
3. 3. 2. Can our patient state his/her utilities
in a stable, usable form?
4 1 Are the results of this economic analysis
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4. 1. Are the results of this economic analysis,valid?
4. 1. 1. Are well-defined courses of action
compared?
4. 1. 2. Does it provide a specified view from
which the costs & consequences
are being viewed?
4. 1. 3. Does it cite comprehensive evidenceon the efficacy of alternatives
4 1 Are the results of this economic analysis
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4. 1. Are the results of this economic analysisvalid?
4. 1. 4. Does it identify all the costs &
consequences we think it should &
select credible & accurate measures
of them?
4. 1. 5. Was the type of analysis appropriate
for the question posed?
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4. 2. Are the valid resultsof this economic analysis,important?
4. 2. 1. Are the resulting costs,
or costs per unit of health gained,
clinically significant ?
4. 2. 2. Did the results of this economic analysis
change with sensible changes to costs &
effectiveness?
4 3 A th lid i t t lt
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4. 3. Are the valid, important resultsof economic analysis applicableto our patient?
4. 3. 1. Do the costs in the economic analysis
apply in our setting?
4. 3. 2. Are the treatments likelyto be effective in our setting?
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Conclusions
Application of good therapy must besupported by EBM
Ability to appraise the results of many
kind of studies, reviews, analyes etc
Elements of magnitude of the treatment effect
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Example:To express results
in a study where 20 % of the treatment group
(Y)
25 of the control group (X)died
X-Y =
0.25 0.20 = 0.05
Y / X =0.20 / 0.25 = 0.80
1- (Y / X) x 100 =
(1- 0.80) x 100 = 20 %
Elements of magnitude of the treatment effect
Absolute Risk Reduction(ARR or risk difference)
Relative risk (Ratio)
Relative Risk Reduction(RRR)
Elements of magnitude of the treatment effect
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Interferon as secondary prevention
of multiple sclerosis (33 months of treatment)
NNT 10 month = 9 x (33 / 10) = 29.7NNT = (1 / ARR)
RRR = (CER-EER / CER)
ARR = (CER-EER)
(50% - 39%) / 50% = 22%
50% - 39% = 11 %
1 / 11% = 9
CER : 50 % & EER : 39 %
Elements of magnitude of the treatment effect