EBM Therapy

7/22/2019 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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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. 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


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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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


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


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



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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


(


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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 %


Absolute Risk Reduction(ARR or risk difference)

Relative risk (Ratio)

Relative Risk Reduction(RRR)



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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 %


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EBM Therapy