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Experimental Design
RCT (Randomized Controlled Clinical
Trial)
Iwan Dwiprahasto
CE&BU FK UGM/RSUP Dr. Sardjito
Quantitative Method
Research Design
Observational Experimental
study study
Quasi
Descriptive Analytic RCT Experiment
al
Case report,
outcome exposure both
case series,
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Quantitative Method
Research Design
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Systematic
review/MA
RCT
Quasi Experimental
Cohort/Case Control
Cross
challenge
sectional/Case
the process
Series
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Kategori Evidence
We typically have a
to determine cause particular cause in mind,
and effect and want to know if it has
relationships an effect on an outcome,
and if so, to what degree.
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PRINCIPLE OF RANDOMIZATION
Subject
Treatment A Treatment B
- Similar chance
- No right to choose
R= randomization
- Neutral
- To prevent Iwan
biasDwiprahasto-CE&BU
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exposure
posure outcome
ACE--inhibitor
ACE Lowering
SBP
Treatment factor Other factors
Dose Compliance
Frequency Diet
Other drugs Life style Iwan Dwiprahasto-CE&BU
Definitions
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Randomized Randomisasi
Inclusion
Controlled Prosedur
Outcome
Intervensi
Clinical Trial
vs. control group
RCT
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RCT
Uji
klinik
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e.g.
Keparahan penyakit
Ketaatan minum obat,
Setelah/sebelum makan Iwan Dwiprahasto-CE&BU
sukarelawan sehat
efek samping & toleransi
Fase I hubungan dosis-
dosis-efek
farmakokinetika
uncontrolled
Fase II subyek terbatas
kemungkinan efek tx
controlled trial
Fase III efek terapi definitif
pms
Fase IV efek samping yg jarang
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Summary of Phases I-
I-III
% Drugs
# Subs. Length Purpose Successfully
Tested
Phase I 20 100 Several Mainly Safety 70%
months
Phase II Up to Several Short term 33%
several months--
months safety; mainly
100 2 yrs. effectiveness
Phase 100s 1-4 yrs. Safety, dosage 25-
25-30%
III several & effectiveness
1000
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DESIGN
RCT--parallel design
RCT
Patient
treatment A O
U
T
C
eligible Random O
M
E
Treatment B
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RCT cross-
cross-over design
Patient
washed
out
eligible
O O
Treatment A U Treatment B U
T T
Random C C
O O
M M
Treatment B E Treatment A E
Iwan Dwiprahasto-CE&BU
RCT--factorial design
RCT
Patient
O
tx A U
T
eligible Random Tx B C
O
M
tx A + tx B E
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misal
kadar gula kadar Kadar asam
Kadar CD20
darah, kholesterol urat
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3. Randomize
5. Follow-up cohorts
6. Measure outcomes
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Measurement
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3. Randomize RANDOMISATION
Objective measures
Equal chance for treatment or control
group
Both groups are balanced
To prevent bias
metode
RANDOMISATION
Simple randomisation
2 treatment groups:
(0-4= A; 5-9=B)
3 treatment groups:
(1-3= A; 4-6= B; 7-9 = C)
4 treatment groups
(1-2= A; 3-4= B; 5-6= C; 7-9=D)
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RANDOM LISTS
RANDOMISASI
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Allocation Scheme
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Treatment Control
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5. Follow-up cohorts
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Intention-to-Treat
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BLINDING
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BLINDING
Aims:
To prevent bias
To prevent prediction effect
Objective measures
Reducing risk of overwhelming
examination
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Outcome Measures
Free of measurement or
ascertainment errors
Clinically relevant
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MEASURING RESPONSE
e.g: cytostatics
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Severity of Illness
1. Difficult to measure
2. Disease specific vs. general
3. Use validated instruments
4. Applicability to study population
5. Acknowledge limitations
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1. Seleksi/pemilihan subyek
2. Rancangan
3. Perlakuan & pembanding
4. Randomisasi
5. Besar sampel
6. Blinding
7. Penilaian respons
8. Analisis data
9. Protokol uji klinik
10. Etika uji klinik
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Seleksi/pemilihan subyek
Seleksi/pemilihan subyek
Inclusion criteria
Jenis kelamin, umur, kriteria khusus
Kriteria penyakit
riwayat penyakit
diagnosis
cara menegakkan diagnosis
alat untuk menegakkan diagnosis
siapa yang melakukan pemeriksaan
Informed consent
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Seleksi/pemilihan subyek
Exclusion criteria
Kontraindikasi terapi
Kehamilan
Hipersensitivitas
Mencetuskan kondisi emergency
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Treatment Control
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Treatment schedule
Formulasi obat
Cara pemberian
Dosis
Frekuensi pemberian
Lamanya terapi
Efek samping
samping,, modifikasi dosis
Supervisi
RANDOMISATION
Objective measures
Equal chance for treatment or control group
Both groups are balanced
To prevent bias
metode
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RANDOMISATION
Simple randomisation
2 treatment groups:
(0-4= A; 5-9=B)
3 treatment groups:
(1-3= A; 4-6= B; 7-9 = C)
4 treatment groups
(1-2= A; 3-4= B; 5-6= C; 7-9=D)
RANDOMISASI
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RANDOMISASI
Stratified
Several criterias
Example:
Age < 50 year + 1-3 nodules
Age > 50 year + 1-3 nodules
Age < 50 year + > 4 nodules
Age > 50 year + > 4 nodules
BLINDING
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BLINDING
Aims:
To prevent bias
Objective measures
MEASUREMENT
Measurable
Objective
Accurate
Consistent
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MEASURING RESPONSE
MEASURING RESPONSE
e.g: cytostatics
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Easy to diagnose
Objective measures
Reducing risk of incorrect measurement
Could be independently observed
Clinically relevance
Determined and agreed upon before
research conduct
ANALYSIS
Qualitative
yes/no
cured/not cured
alive/dead
Quantitative
mean, SD, X- square, t-test
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background Randomisation
objective sample size
patients criteria analysis
procedure informed consent
measuring response record form
design administration
Patient/Client Prep
Sample Collection
Personnel competency
Reportin Test Evaluations
g Data and Lab
Management
Safety
Customer
Service Sample Receipt
and Accessioning
Record
Keeping
Quality Control Sample Transport
Testing
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