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Asking Answerable

Question
Anang Endaryanto
Division of Allergy Immunology, Child Health Department
School of Medicine University of Airlangga Dr Soetomo Hospital

Learning
Objective

Setelah mengikuti perkuliahan ini


mahasiswa diharapkan mampu
memformulasikan pertanyaan
klinis & menyusun pertanyaan
klinis tersebut dalam answerable

LO-1: Mampu Menyusun Pertanyaan


Klinis
(PICO untuk Track-down)
Patient /
Problem /
Population

Intervention

Comparison Outcome

In a child with
frequent febrile
seizures

would
anticonvulsant
therapy

compared to no
treatment

result in seizure
reduction?

LO-2. Mampu melakukan pencarian


pustaka dengan struktur umum
PICO untuk Track-down

(Population OR synonym1 OR synonym2) AND


(Intervention OR synonym1 OR synonym2) AND
(Comparator OR synonym1 OR synonym2) AND
(Outcome OR synonym1 OR synonym2)

Search: (Healthy Child OR Child OR Children)


AND (Probiotics OR Lactobacillus OR
Bifidobacterium) AND (Placebo) AND (Influenza
OR Cold OR Common Cold OR Influenza-like)

LO-3 : Mampu Menyebutkan


PICO dari Jurnal untuk Critical
Appraisal
Population/Problem dari penelitian yang dilaporkan di jurnal
tersebut
adalah...............................................................................................
..........................................................................................................
......
Intervension/Indicator/Index dari penelitian yang dilaporkan di
jurnal tersebut
adalah...............................................................................................
..........................................................................................................
......
Control dari penelitian yang dilaporkan di jurnal tersebut
adalah...............................................................................................
..........................................................................................................
......
Outcome dari penelitian yang dilaporkan di jurnal tersebut
adalah...............................................................................................
..........................................................................................................
......

LO-4: Mampu menyebutkan Disain,


Fokus dari Jurnal & Worksheet yang
digunakan untuk telaah kritis dari
Jurnal yang diperoleh.
Disain dari penelitian yang dilaporkan di jurnal tersebut
adalah:
A). Cross sectional.
B). Case control.
C). Cohort.
D). Eksperimental.
E). Kuasi Eksperimental.

Fokus dari penelitian tersebut adalah:


A). Manifestasi klinik.
B). Causation.
C). Prognosis.
D). Diagnosis.
E). Terapi.

Worksheet yang paling tepat untuk digunakan untuk


telaah kritis laporan penelitian dalam jurnal tersebut
adalah worksheet:
A). Manifestasi klinik.
B). Systematic Review/Metaanalysis.
C). Prognosis.
D). Diagnosis.
E). Terapi.

LO-5: Mampu melakukan telaah kritis


(VIA)
(Critical Appraisal)
Apakah penelitian yang dilaporkan
dalam jurnal tersebut VALID?
Apakah IMPORTANCY dalam penelitian
tersebut tergambar dalam jurnal
tersebut?
Apakah hasil penelitian yang dilaporkan
dalam jurnal tersebut bersifat
APPLICABLE untuk pasien kita?

Contoh kasus:
Pertanyaan orang tua pasien kepada dokter: Apa
yang seharusnya saya lakukan untuk mencegah
anak saya terserang sakit flu?.

Langkah pertama
(menyusun pertanyaan klinis)
Sebelum melangkah ke kegiatan penelusuran pustaka uji
klinis, yang harus dilakukan adalah menentukan masalah
apa yang sebenarnya dihadapi oleh pasien yang
memerlukan solusi.
Bila pertanyaan orangtua: Apa yang seharusnya saya
lakukan untuk mencegah anak saya terserang sakit
flu?, maka pertanyaan tersebut sulit dicarikan jawabannya
dari pencarian pustaka dalam uji klinis.
Agar pertanyaan klinis dapat dijawab, maka pertanyaan klinis
tersebut harus memiliki ciri-ciri pertanyaan yang baik, yaitu:
Pertanyaan klinis harus relevan dengan masalah yang
dihadapi.
Pertanyaan klinis disusun dalam frasa yang dapat
diterapkan untuk penelusuran pustaka
Pertanyaan klinis harus fokus pada masalah dan
terartikulasi dengan baik.

Perbaikan pertanyaan klinis


Harus diperjelas:
Karakteristik Subyek

Subyeknya siapa?
Bayi, anak, remaja, atau orang dewasa.
Bagaimana kondisi Subyek?
Sehat, menderita penyakit tertentu, atau sehat
dengan risiko tertentu.

Intervensi

Intervensi apa yang ingin dilakukan?.


Obat-obatan, vaksinasi, nutrisi, atau edukasi.

Manfaat

Manfaat apa yang kita harapkan? (mencegah,


meredakan atau menyembuhkan gejala).
Bila manfaat yang dipikirkan adalah mencegah,
bagaimana cara mengukurnya? (kriteria klinis atau
laboratoris)

Menyusun pertanyaan
Bila klinisi tertarik untuk menelaah pencegahan sakit flu
dengan probiotik, maka kalimat pertanyaan
Apa yang seharusnya saya lakukan untuk
mencegah anak saya terserang sakit flu?
harus diperbaiki menjadi pertanyaan yang yang bisa
dijawab, contoh: Pada anak sehat apakah X
dapat mencegah sakit flu.
Sehingga dari pertanyaan tersebut kita dapat membuat
susunan pertanyaan sebagai berikut:

P (population/problem)
: anak sehat
I (intervention)
: probiotik
C (comparator/control)
: tanpa probiotik
O (outcome) : sakit flu

Langkah kedua
(mencari bukti terbaik)
Setelah jelas susunan pertanyaan yang mencerminkan masalah pasien
dengan karakteristik tertentu (P) dengan rencana penyelesaian masalah
dengan menggunakan intervensi tertentu (I) dengan indikator
keberhasilan tertentu (O), maka kita bisa melakukan pencarian pustaka
dengan struktur umum untuk pertanyaan klinis:

(Population OR synonym1 OR synonym2) AND


(Intervention OR synonym1 OR synonym2) AND
(Comparator OR synonym1 OR synonym2) AND
(Outcome OR synonym1 OR synonym2)

Search

#1:
#2:
#3:
#4:

Probiotics OR Lactobacillus OR Bifidobacterium


Healthy Child OR Child OR Children
Placebo
Influenza OR Cold OR Common Cold OR Inflienza-like

Search: (Probiotics OR Lactobacillus OR Bifidobacterium) AND (Healthy


Child OR Child OR Children) AND (Placebo) AND (Influenza OR Cold OR
Common Cold OR Inflienza-like)

Langkah kedua
(mencari bukti terbaik)
Searching:
(Probiotics OR Lactobacillus OR
Bifidobacterium) AND (Healthy
Child OR Child OR Children) AND
(Placebo) AND (Influenza OR Cold
OR Common Cold OR Inflienza-like)

Asking Answerable
Question

Frequency of Questions

Brassey et al. BMJ 2001;322:529-530.

Question:
For women with abdominal pain, is
ultrasonography as accurate (ie
with equal or better sensitivity and
specificity) as MRI for diagnosing
appendicitis?

How
diag accura
in va nostic t te a
grou rious pa est is
compps and intient
othe arison w
test r availa ith
test s. Measu ble
inclu accuracy res of
LH, Pde its Sn
PV, N , Sp,
P V.

Menyusun pertanyaan
penelitian?
An answerable questions
Formulate research questions
Breaks down the question into 4 key
elements

Good clinical question:


PICO
The Patient or Problem
The Intervention / Indicator /Index test
Comparative intervention (if relevant)
The Outcome

Be brief and
specific.....

Patient, Population,
(clinical) Problem
Patient or patient group (gender, race,
age)
Disease or condition
Stage of the illness
Care setting

Penting
untuk
generalisas
i hasil
penelitian

Intervention, Indicator,
Index Test
INTERVENTION
Type of treatment (drug, procedure, therapy)
Intervention level (dosage, frequency)
Stage of intervention (preventative, early,
advanced)
Delivery (who delivers the intervention? where?)
INDICATOR
Exposure
Factors that affect a health outcome
INDEX TEST : a Diagnostic test

Comparison
Alternative interventions (standard
treatment, placebo, another
intervention), indicators or diagnostic
test
There may not always be a
comparison

Outcome
The outcome or effects you (and/or
patients)
Improvement of symptoms, healing
Side effects
Improved quality of life
Cost effectiveness and benefits for the
provider

Menyusun pertanyaan
klinis?
Patient /
Problem /
Population

Pada
penderita
dengan
sindrom
syok
dengue
pada
resusitasi
inisial

Intervention

Comparison

Outcome

apakah
pemberian
cairan
koloid

dibandingka akan
n kristaloid memberika
isotonis
n respons
terapi yang
lebih baik

Treatment
Patient /
Problem /
Population

In a child
with
frequent
febrile
seizures

Intervention

Comparison

would
compared
anticonvuls to no
ant therapy treatment

Outcome

result in
seizure
reduction?

Diagnosis
Patient /
Problem /
Population

In an
otherwise
healthy 7year-old
boy with
sore throat

Intervention

Comparison

Outcome

how does
the clinical
exam

compare to
throat
culture

in
diagnosing
Group-A
Streptococc
al infection?

Prognosis
Patient /
Problem /
Population

In children
with Down
syndrome,

Intervention

is IQ an
important
prognostic
factor

Comparison

Outcome

in
predicting
Alzheimers
later in life?

Etiology / Harm
Patient /
Problem /
Population

controlling
for
confoundin
g factors,
do
otherwise
healthy
children

Intervention

Comparison

Outcome

exposed in
utero to
cocaine,

compared
have
to children increased
not exposed incidence of
learning
disabilities
at age six
years?

Relevance: POEs and DOEs


Focused

DOE = Disease oriented


evidence

On

disease

Ologies (path-, etiol-, pathophys-)


ie Med school

POE = Patient oriented evidence


Morbidity, mortality or quality of life
Something a patient would care
about without explanation
Highest quality evidence

Focused

On

patient need

Comparing DOEs and


POEMs
Example

DOE

POEM

Antiarrhythmic Drug A PVC


On ECG
Therapy

Drug A >
mortality

Antihypertens. Drug X BP
Therapy

Drug X
mortality

Comment
DOE & POEM
contradicts

POEM agrees
With DOE

PSA screening ? whether PSA


Prostate detects prostate screening DOE exists, but
POEM unknown
screening
Ca. early
mortality

POEMs
Patient Oriented Evidence that
Matters
Matters because if it is true,
it requires you to change your
practice
(Also a review of an article written
and published in a specified format =
secondary literature)

PICO in
Researc
h
PICO.
Where?

Title

P, I, (C), O

Background Sejauh ini pengaruh I untuk terjadin


O pada P (dibanding C) belum jela
(Clinical question)
Background
(Objective)
Method

Result

Conclusion

Mengetahui efek I dalam hal O


pada P
P=
I= C=.
O=.
O=

Pada P, I berpengaruh pada


terjadinya O

Pemilihan disain penelitian

Cohort studies

Least risk
Most biased

Cross-sectional studies
(Clinical observation (Case
report,case-series)

Descriptive

Case-control studies

Observational

Randomised controlled trial

Analytical

Least biased

Experiment
al

Hierarchy of study designs BIAS vs


Most risk
RISK

Tackling confounding
Validitas penelitian

RANDOMISATION

STRATIFICATION/MULTIVARIATE ANALYSIS

Balance known, important prognostic factors


between treatment groups

MATCHING

Allocate subjects among study groups randomly (by


change)

The comparison subject can be matched individually


to single subjects or groups (case-control)

RESTRICTION

admit only those who fall into specified catagories of


each variable of interest (inclusion/exclusion criteria)

Tackling confounding
Validitas penelitian
V (O)utcome V (I)ntervention, indicator, index

Y1...Yn =

X1 .

X2. X3. X4. X5. X6. X7...Xn

V etc.
V place

V host
V agent

V time

V environment

Confounder

Menetapkan disain
penelitian
Longitudinal

Cross-sectional

exp

a
ent
erim

Research
Focus

obse
rvas
iona
l

(+)
trol
n
o
C

Con
tr

Research
Approach

Controlled?
Randomized?

ol ()

Research
Goal

Researcher
Involvement

Clinical Manifestation / Diagnosis / Causation/Prognosis / Therapy / Review

Menetapkan disain penelitian

Menetapkan disain penelitian

Mendisain
penelitian

MATCHING/STRATIFICATION

MATCHING

RANDOMISAT

Pertanyaan penelitian &


Formulasi statistik
V (O)utcome V (I)ntervention, indicator, index

Y1...Yn =

X1 .

X2. X3. X4. X5. X6. X7...Xn

V etc.
V place

V host
V agent

V time

V environment

Confounder

Pertanyaan penelitian &


Formulasi statistik

Pertanyaan penelitian &


Formulasi statistik
Relationship

Influence

Difference

Hypothesis
of
Relationship

Hypothesi
s of
Influence

Hypothesis
of
Difference

Regression
Linier
Logistic

t-test, Z-test,
Anova,
42
Manova, Mann

Pearson Corr
Rank Spearman
Multiple Corr

Pertanyaan penelitian,
Fokus penelitian & Disain
penelitian
Risk Factors

Frequency

Cohort Study

Prognosis

Survey Inception Cohort Study

Radiography
Treatments

Treatment Effec

Randomised Trial

Cause(s)
Past

Symptoms
Signs, Tests

Cross Sectional Study

current

future

How to Find
Current
Best Evidence

Dr. Anang Endaryanto, dr., Sp.A(K)


Division of Allergy Immunology, Child Health Department
School of Medicine University of Airlangga Dr Soetomo Hospital

Steps in EBM
1. Formulate an answerable question
2. Track down the best evidence
3. Critically appraise the evidence for:
Validity
Impact (size of the benefit)
Applicability
4. Integrate with clinical expertise and patient
values
5. Evaluate our effectiveness and efficiency
keep a record; improve the process
45

PICO
Literature
Searching
46

PICO of Track down


Search
#1: Healthy Child OR Child OR Children
#2: Probiotics OR Lactobacillus OR Bifidobacterium
#3: Placebo
#4: Influenza OR Cold OR Common Cold OR Inflienzalike
Search: (Healthy Child OR Child OR Children) AND
(Probiotic* OR Lactobacillus OR Bifidobacterium) AND
(Placebo) AND (Influenza OR Cold OR Common Cold OR
Influenza-like)
47

PICO of Track down

(infant* OR newborn* OR neonat* OR pediatric* OR


paediatric*)
AND
(hydrolysed*)
AND
(feed* OR food OR formula* OR protein OR milk*)
AND
(asthma OR atopic dermatitis OR eczema OR allergic rhinitis
OR cows milk intolerance OR soy protein intolerance OR
cows milk allergy OR soy protein allergy OR food allergy
OR food intolerance OR urticaria OR anaphylaxis)
48

PICO
Critically appraise
49

PICO of Critically appraise


Recruit. Was a defined
P

Source

Population
Subjects

Indicator

C Comparator

O Outcomes

yes

no

representative sample of
patients assembled at a
common (usually early)
point in the course of their
disease?
Adjustment How were
patients treated? Did
adjustment for important
prognostic factors take
place?
Maintenance Was the
comparable status of the
study groups maintained
through equal management
and adequate followup? ?
Measure outcomes with :

blinded subjects & assessors &


or

Fokus
Peneliti
an
&
Metode
Telaah
Validita
s

PICO of
Critically
appraise
PICO.
Where?

Title

P, I, (C), O

Background Sejauh ini pengaruh I untuk terjadin


O pada P (dibanding C) belum jela
(Clinical question)
Background
(Objective)
Method

Result

Conclusion

Mengetahui efek I dalam hal O


pada P
P=
I= C=.
O=.
O=

Pada P, I berpengaruh pada


terjadinya O

West CE, Hammarstrom ML, Hernel O.


Probiotics during weaning reduce the incidence of eczema.
Pediatr Allergy Immunol. 2009 Aug;20(5):430-7
A reduced microbial load early in life has been suggested to be linked to the
increasing prevalence of allergic diseases in the industrialized world. Some
studies have indicated that probiotics may be effective in the prevention of
eczema. In vitro studies indicate that probiotics have immunomodulatory effects.
In the present study, we evaluated the effects of feeding Lactobacillus F19 during
weaning on the incidence of eczema and Th1/Th2 balance.
In a double-blind, placebo-controlled randomized intervention trial, infants were
fed cereals with (n = 89) or without Lactobacillus F19 (n = 90) from 4 to 13
months of age. We assessed the cumulative incidence of eczema at 13 months of
age. The ratio of interferon-gamma (IFN-gamma) to interleukin 4 (IL4) mRNA
expression levels in polyclonally stimulated peripheral blood T cells was used as a
proxy for immune balance. Total and specific IgE serum levels were also assessed.
The cumulative incidence of eczema at 13 months was 11% (4-17%, 95% CI) and
22% (13-31%, 95% CI) in the probiotic and placebo groups, respectively (p <
0.05). The number needed to treat was 9 (6.5-11.5, 95% CI). At 13 months of age,
the IFN-gamma/IL4 mRNA ratio was higher in the probiotic compared with the
placebo group (p < 0.05). In contrast, there were no differences between groups
in serum concentrations of IgE.
In summary, feeding Lactobacillus F19 during weaning could be an effective tool
in the prevention of early manifestation of allergy, e.g., eczema. The higher
Th1/Th2 ratio in the probiotic compared with the placebo group suggests
enhancing effects of Lactobacillus F19 on the T cell-mediated immune response.

West CE, Hammarstrom ML, Hernel O.


Probiotics during weaning reduce the incidence of eczema.
Pediatr Allergy Immunol. 2009 Aug;20(5):430-7
Design:
Double-blind, placebo-controlled randomized intervention trial
Population
Infant (Fed cereals)
Intervention
Lactobacillus F19 (n = 89) from 4 to 13 months of age.
Control
Placebo (or without Lactobacillus F19) (n = 90)
Outcome & Result
The ratio of interferon-gamma (IFN-gamma) to interleukin 4 (IL4) mRNA
expression levels in polyclonally stimulated peripheral blood T cells was
used as a proxy for immune balance.
The cumulative incidence of eczema at 13 months was 11% (4-17%, 95%
CI) and 22% (13-31%, 95% CI) in the probiotic and placebo groups,
respectively (p < 0.05).
The number needed to treat was 9 (6.5-11.5, 95% CI).
At 13 months of age, the IFN-gamma/IL4 mRNA ratio was higher in the
probiotic compared with the placebo group (p < 0.05).
There were no differences between groups in serum concentrations of IgE.
Conclusions
Feeding Lactobacillus F19 during weaning could be an effective tool in the
prevention of early manifestation of allergy, e.g., eczema.
The higher Th1/Th2 ratio in the probiotic compared with the placebo group
suggests enhancing effects of Lactobacillus F19 on the T cell-mediated
immune response.

Soal Ujian
Akhir EBM

Soal tipe pilihan


berganda

Petunjuk: pilihlah 1 jawaban yang


paling benar:
Disain dari penelitian yang dilaporkan di jurnal tersebut
adalah:

A). Cross sectional.


B). Case control.
C). Cohort.
D). Eksperimental.
E). Kuasi Eksperimental.

Fokus dari penelitian tersebut adalah:


A). Manifestasi klinik.
B). Causation.
C). Prognosis.
D). Diagnosis.
E). Terapi.

Worksheet yang paling tepat untuk digunakan untuk


telaah kritis laporan penelitian dalam jurnal tersebut
adalah worksheet:
A). Manifestasi klinik.
B). Systematic Review/Metaanalysis.
C). Prognosis.
D). Diagnosis.
E). Terapi.

Soal tipe jawaban


singkat:

Petunjuk: Jawablah dengan 1 kalimat


saja
Population/Problem dari penelitian yang dilaporkan di jurnal
tersebut
adalah...............................................................................................
..........................................................................................................
......
Intervension/Indicator/Index dari penelitian yang dilaporkan di
jurnal tersebut
adalah...............................................................................................
..........................................................................................................
......
Control dari penelitian yang dilaporkan di jurnal tersebut
adalah...............................................................................................
..........................................................................................................
......
Outcome dari penelitian yang dilaporkan di jurnal tersebut
adalah...............................................................................................
..........................................................................................................
......

Soal Esei uraian


terbatas.

Petunjuk: Jawablah dengan salah satu dari 3 pilihan


(Ya, Tidak, atau Tidak jelas), yang diikuti
dengan alasan jawaban maksimal 1 paragraf
dengan isi maksimal 5 kalimat/paragraf)

Apakah penelitian yang dilaporkan


dalam jurnal tersebut VALID?
Apakah IMPORTANCY dalam penelitian
tersebut tergambar dalam jurnal
tersebut?
Apakah hasil penelitian yang dilaporkan
dalam jurnal tersebut bersifat
APPLICABLE untuk pasien kita?