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Curriculum VitaeCurriculum Vitae

N a m a : Prof. Dr. dr. Rozaimah Zain-Hamid, MS, SpFK

Pekerjaan : * Guru Besar Tetap Departemen Farmakologi dan Terapeutik,

Fakultas Kedokteran, USU, Medan

* Staf Pengajar Program S2 Biomedik & Program Administrasi

Kebijakan Kesehatan; Program S3 Kedokteran,

Sekolah Pascasarjana, USU, Medan

* Wakil Ketua Komisi Nasional Etika Penelitian Kesehatan

(KNEPK), Indonesia

Riwayat Pendidikan:

* Dokter (dr), dari Fakultas Kedokteran, USU. Medan

* Magister Sains (MS), Ilmu Kedokteran Dasar (‘Basic Medical Sciences’), dari Fakultas Pascasarjana, Universitas Indonesia, Jakarta

* Doktor (Ph.D), Farmakologi Klinik (‘Clinical Pharmacology’), dari Instituteof Post-graduated Studies, Universiti Sains Malaysia, Malaysia

* Spesialis Farmakologi Klinik (Sp.FK), dari Dewan Penilai Kepakaran Persatuan Dokter Ahli Farmakologi Klinik Indonesia (PERDAFKI) Pusat,Jakarta.

“Evidence-Based Medicine”Therapy

Rozaimah Zain-Hamid

Community Research Program (‘KBK’)Faculty of Medicine

Universitas Sumatera Utara

‘‘ EE EE EE EEvidencevidence-- BB BB BB BBasedased MMMMMMMMedicine’edicine’

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‘‘ CC CC CC CCriticalritical AA AA AA AAppraisal’ppraisal’

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Zain-Hamid, R; CRP-’KBK’, Faculty of Medicine, Universitas Sumatera Utara.

“Evidence-Based Medicine”(Papers in Journal of Medicine / Health Sciences)

�� ‘Valid’ �� Methodology of study

‘VIA’

�� ‘Valid’ �� Methodology of study

�� ‘Important’ �� Result of study

�� ‘Applicability’ �� Discussion


Treatment / Therapeutic intervention

EBM : Valid, important and applicable

to particular patientsto particular patients

High rank of hierarchy of evidence(Systematic reviews /meta-analyses;

Randomized Controlled clinical trial / RCT)


Treatment / Therapeutic intervention

Answerable Clinical Question (ACQ)

P : Patient, Problem, Population I : InterventionC : ComparisonO : Outcome


Hypertensive patient – should I start ACE inhibitors?

� Patient : middle aged man withdiastolic 100 mm Hg

�� Intervention : ACE inhibitors�� Intervention : ACE inhibitors

�� Comparison : Diuretics

� Outcome : prevent heart disease;stroke; end-organ damage?


“EBM” for therapy

1. Reports of individual studies

2. Reports of systematic reviews (‘RCT’)

3. Reports of Clinical Decision Analyses

5. Reports of qualitative study

3. Reports of Clinical Decision Analyses (CDA)

4. Reports of economic analyses


Integrative literature

Review article :* unsystematic

Systematic review :* in gathering, evaluating, presenting evidence* in gathering, evaluating, presenting evidence* no formal statistical method

Meta-analysis :* systematic review + formal statistical analysis


Integrative literature

Review article

Systematic review

Meta-analysis


Reports of individual studies

High rank of hierarchy of evidenceHigh rank of hierarchy of evidence(Randomized Controlled clinical trial / RCT)


Key elements of RCT

Randomization

Control Blinding


Reports of individual studies

1. Are the results of individual studies valid?

2. Are the valid results of individual studies,important?important?

3. Are the valid, important results of individual studies;

applicable to our patient?


‘Validity’ of individual studies


1. Are the results of individual studies, valid?

Primary guides:Primary guides:

1. 1. 1. 1. Was the assignment of patients Was the assignment of patients to treatments randomized? to treatments randomized?

1. 2. 1. 2. Was followWas follow--up of patients sufficiently longup of patients sufficiently longand complete? and complete?

1. 3. 1. 3. Were patients analyzed in the groups Were patients analyzed in the groups to which they were randomized? to which they were randomized?


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1.1. Was the assignment of patients to treatments randomized?

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1. 2. Was follow-up of patients sufficiently long and complete?

Lost to follow up no more than 20%

JJournals like Evidence-Based Medicine and ACP Journal Club

won’t publish trials with > 80% follow-up.


1. 3. Were patients analyzed in the groups to which they were randomized?

““IIIIIIIIntentionntention toto treattreat analysis”analysis”

All patients are analyzed in the groups to which they were initially assignedto which they were initially assigned

A strategy for analyzing data in which all participants are included

in the group to which they were assigned, whether or not they completed

the intervention given to the group.


1. Are the results of the study valid?

Secondary guides:Secondary guides:

1e 5e 1e 5e 1e 5e 1e 5e 1e 5e 1e 5e 1e 5e 1e 5e Aside from the experimental intervention,

1e 4e 1e 4e 1e 4e 1e 4e 1e 4e 1e 4e 1e 4e 1e 4e Were patients, health workers, and study personnel "blind" to treatment?

1. 7. Was the randomization concealed1. 7. Was the randomization concealed? ?

1e 5e 1e 5e 1e 5e 1e 5e 1e 5e 1e 5e 1e 5e 1e 5e Aside from the experimental intervention, were the groups treated equally?

1. 6. 1. 6. Were the groups similar at the start of the trial?


1. 4. Patients, health workers, and study personnel "blind" to treatment?

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�� Double blind Double blind

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�� Triple blindTriple blind


Similar:

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EFFECT

CLINICAL TRIAL DESIGNS

TREATMENT GROUP

1.�� PARALLEL DESIGN TWO GROUPS :

SUBJECTS

EFFECT

EFFECT

TREATMENT GROUP

CONTROL GROUP


“Wash-out

2. �� CROSS-OVER DESIGN :

TREATMENTA

EFFECT

TREATMENTA

EFFECT

“Wash-outPeriod”SUBJECTS

TREATMENTB

EFFECT

TREATMENTB

EFFECT


‘Important’ of individual studies


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2. Elements of important of the treatment effect

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( 5 5 5 5 years’ eeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeee

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1.2. 1. Elements of magnitude of the treatment effect

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(‘ CC CControl EE EEvent RRRRate = CERCERCERCER’)

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(‘ EE EExperimental EE EEvent RRRRate = EEREEREEREER’)

�� RRR = {(CER – EER) / CER}


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2. 1. Elements of magnitude of the treatment effect

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� RRR = {(CER – EER) / CER}RRR = (5.7% – 4.3%) / 5.7% = 25%

��Statin therapy decreased the risk of stroke by 25% relative to those who receive placebo



The situation in which the experimentaltreatment increase the risk of a good event as the ‘Relative Benefit Increase (RBI)’ or the risk of bad event as ‘Relative Risk Increase(RRI)‘Relative Risk Increase(RRI)

��also can use the same formula ��(RRR):

��RRR = RBI = RRI = {(CER – EER) / CER}RRR = RBI = RRI =(5.7% – 4.3%) / 5.7% = 25%


� 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 an adverse event

� Absolute Risk reduction (ARR):is the difference in risk between the control group and the treatment group



The situation in which the experimentaltreatment increase the risk of a good event as the ‘Absolute Benefit Increase (ABI)’ or the risk of bad event as ‘Absolute Risk Increase(ARI)‘Absolute Risk Increase(ARI)

��also can use the same formula ��(ARR):

��ARR = ABI = ARI = (CER – EER) ARR = ABI = ARI =(5.7% – 4.3%) = 1.4%


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 new

treatment might have less than 1/2 risk of dying

compared to not treated


The greater the relative risk reduction the more effective the therapy

(>>> RRR�� efficacy of therapy)

2.1. Element of magnitude of the treatment effect

RRR = {(CER – EER) / CER}

CER : Control Event Rate (without treatment/placebo)

EER : Experimental Event Rate (with treatment)


� Number Needed to Treat (NNT) :

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� Number Needed to Harm (NNH) :

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�Number Needed to Treat (NNT) = 1 / ARR* NNT = 1 / 1.4% = 72


* 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


Therapy / treatment - case study

A randomized double blind control clinical trialon 3 month – 5 year old children with mild to moderate croup (laryngotracheobronchitis).

The experimental group : 2 mg (4 ml) nebulizedThe experimental group : 2 mg (4 ml) nebulized

budesonide.

The control group : 4 ml nebulized normal saline.

Event being prevented : hospital admission due to upper-airway obstruction.


27

1

26

R

The study protocol

Hospitalized

Non-Hospitalized

N = 54

27

7

20

R

Hospitalized

Non-Hospitalized

budesonide

normal salineZain-Hamid, R; CRP-’KBK’, Faculty of Medicine,

Universitas Sumatera Utara.

No Yes

Budesonide (E) 26 1 27

Upper-airway obstruction

Important


NaCl (C) 20 7 27

X2 df =1 p = 0.04


No Yes


NaCl (C) 20 7 27

Upper-airway obstructionImportant

CER = 7 / 27 = 0.26 ; EER = 1 / 27 = 0.04

RRR = (CER – EER) / CERRRR = (0.26 – 0.04) / 0.26 = 85%

ARR = (CER – EER) = (0.26 – 0.04) = 0.22

NNT = 1 / ARR = 1 / 0.22 = 5Zain-Hamid, R; CRP-’KBK’, Faculty of Medicine,

Universitas Sumatera Utara.

Budesonide vs normal saline; Upper-airway obstruction

CER EER ARR NNT

In the actual trial 26% 4% 22% 5

Important

In the actual trial 26% 4% 22% 5

In the hypothetical trivial case 0.00026 0.00004 0.00022 5000


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2. 2. Elements for deciding precision of the treatment effect

�� (<< CI �� precission of the treatment effect)�� (<< CI �� precission of the treatment effect)


‘Applicability’ of individual studies


3e 1e 3e 1e 3e 1e 3e 1e Is our patient so different from those Is our patient so different from those in the study that its results cannot apply?in the study that its results cannot apply?

3e 2e 3e 2e 3e 2e 3e 2e Is the treatment feasible in our setting?Is the treatment feasible in our setting?

3e 3e 3e 3e Are the valid, important results of this individual studies applicable to our patient?

3e 3e 3e 3e 3e 3e 3e 3e What are our patient’s potential benefits What are our patient’s potential benefits 3e 3e 3e 3e 3e 3e 3e 3e What are our patient’s potential benefits What are our patient’s potential benefits and harms from the therapy?and harms from the therapy?

3e 4e 3e 4e 3e 4e 3e 4e What are our patient’s values and expectations What are our patient’s values and expectations for both the outcome we are trying for both the outcome we are trying to prevent and the treatment to prevent and the treatment we are offering?we are offering?


ConclusionsConclusions

��Application of good therapy must be Application of good therapy must be supported by EBM supported by EBM

��Ability to appraise the results of many Ability to appraise the results of many kind of studies, reviews, analyses etc kind of studies, reviews, analyses etc


Arigatoo gozaimasu


Therapy Worksheet


THERAPY WORKSHEET

Are the results of this single preventive or therapeutic trial valid?

Citation:

Was the assignment of patients to treatments randomized?

Was the randomization list concealed?

Was follow-up of patients sufficiently long and complete?

Were all patients analyzed in the groups to which they were randomized?

THERAPY WORKSHEET

Are the results of this single preventive or therapeutic trial valid?

Citation:

Were patients, clinicians, and study personnel kept “blind”to treatment? to treatment?

Were the groups treated equally, apart from the experimental treatment?

Were the groups similar at the start of the trial apart from the experimental therapy?

THERAPY WORKSHEET

Are the valid results of this randomized trial important?

What is the magnitude of the treatment effect?of the treatment effect?

How precise is the estimate of the treatment effect?

SAMPLE CALCULATIONS

Occurrence of diabetic

neuropathy at 5 years

among insulin-dependent

diabetics in the DCCT trial

Relative risk

reduction

(RRR)

Absolute risk

reduction

(ARR)

Number

needed

to treat

(NNT)

Usual

insulin

Regimen

control

Intensive

insulin

regimen

experimental

CER − EER CER

CER − EER1/ARR

control

event rate

(CER)

9.6 %

experimental

event

rate

(EER)

2.8 %

9.6% − 2.8% 9.6% 9.6% − 2.8%

1/6.8%

=15 patients

71 % 6.8 %

95% CI a 4.4% to 9.2% 11 - 23

a 95% confidence interval (CI) on an NNT =1/(limits on the CI of its ARR)

YOUR CALCULATIONS

Relative risk

reduction

(RRR)

Absolute risk

reduction

(ARR)

Number

needed

to treat

(NNT)

CER − EER CER − EER

EER

CER − EER CER

CER − EER1/ARR

95% CI a

CER

THERAPY WORKSHEET

Can you apply this valid, important evidence about therapy in caring for your patient?

Do these results apply to our patient?

Is our patient so different from those in the study that from those in the study that its results cannot apply?

Is the treatment feasible in our setting?

What are our patient’s potential benefits and harms from the therapy?

Risk of the outcome in our patient, relative to patients in the trial.

Expressed as a decimal:______

NNT/ f =______/______=______

Method I : f

(NNT for patients like ours)

Our patient’s expected event rateif they received

the control treatment (PEER) =______

1/(PEER × RRR) = 1/________=______

(NNT for patients like ours)

Method II : 1/(PEER × RRR)

THERAPY WORKSHEET

Are our patient’s values and preferences satisfied by the regimen and its consequences?

Do we and our patient have a clear assessment of their values and preferences?of their values and preferences?

Are they met by this regimen and its consequences?

Additional notes:

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