RANCANGAN PENELITIAN EKSPERIMENTAL

NOOR CAHAYA,M.SC,APT.
 QUANTITATIVE METHOD

Research Design

Observational Experimental
study study

Quasi
Descriptive Analytic RCT
Experimental

Case report, case

outcome exposure both
series,

Case Cohort Cross

control study sectional
study study
 Quantitative Method

Research Design

Analytical studies Descriptive

Observational Experimental Case Case

studies studies report series

Cros Case - Quasi

Cohort RCT
sectional ontrol experiment
TYPES OF EXPERIMENTS
There are four kinds of experiments:
▪ True experiments
▪ Quasi-experiments
▪ Natural experiments
▪ Naturalistic experiments
TRUE EXPERIMENTS

▪ Some true experiments are done in

the lab, others are done in the field.

▪ There are five steps to follow in

conducting true experiments:
TRUE EXPERIMENTS

1. Need at least two groups: an experimental

group and a control group. One groups gets the
intervention, the other group does not.

2. Random assignment of individuals to the groups.

(The degree to which random assignment
ensures equivalence of the groups is dependant
upon the size of the groups.)
TRUE EXPERIMENTS
3. The groups are measured on one or more
dependent variables. This is called the pretest.

4. The intervention (independent variable) is

introduced.

5. The dependent variables are measured again.

This is the post test.
HIERARKHI METODOLOGI PENELITIAN

Systematic
review/MA

RCT

Quasi Experimental

Cohort/Case Control

Cross
challenge
sectional/Case
the process
Series
 Kategori Evidence

Ia • evidence dari meta analisis pada RCT

Ib • evidence dari minimal 1 RCT

• evidence dgn kelompok kontrol, tanpa

IIA randomisasi

IIb • evidence dari suatu quasi experimental

• evidence dari non-experimental/descriptive

III study
• evidence dari laporan Expert
IV Committee/pendapat ahli
RCT (randomized controlled clinical trial)

Randomized Randomisasi

Inclusion

Controlled Prosedur

Outcome

Intervensi
Clinical Trial
vs. control group
 RCT

Investigator Clinical manouvre Participants

 RCT

Quantitative Comparative Control Experiment

Measuring outcome Comparing 2 or more All variables are

quantitatively intervention Closely controlled
TUJUAN UJI KLINIK

Uji
klinik

obat pasien
populasi

Efficacy Safety Quality

RCTs according to the aspects of the interventions they evaluate

Explanatory and pragmatic trials

Efficacy and effectiveness trials

Phase I, II, and III trials

 • inclusion criteria sangat ketat
• highly homogeneous study groups
Explanatory • Mis. Hanya pasien usia 40 – 50
trial tahun, tanpa penyakit penyerta

• Memasukkan subyek dengan

karakteristik yang heterogen
• Sesuai dengan pasien yang
pragmatic ditemui di ruang praktek
trials • Menggunakan kontrol aktif (mis
antihypertensive vs. b-blocker),
flexible regimens
 RCTs according to the aspects of the interventions they evaluate

Efficacy trials effectiveness trials

Ideal setting Real setting

Semua variabel yang berpengaruh

thd outcome dikendalikan

e.g.
Keparahan penyakit
Ketaatan minum obat,
Setelah/sebelum makan
 TAHAP-TAHAP UJI KLINIK

• sukarelawan sehat
• efek samping & toleransi
Fase I • hubungan 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
PHASES OF CLINICAL TRIALS

Phase I: Small sample [20-80]

Phase II: larger group [100-300]

Phase III: 1,000-3,000

Done after rx/tx has been

Phase IV:
marketed
 SUMMARY OF PHASES 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- 2 safety; mainly
100 yrs. effectiveness
Phase 100s – 1-4 yrs. Safety, dosage 25-30%
III several & effectiveness
1000
 DESIGN

(RCT-parallel design) (RCT cross-over design)

(RCT factorial design)

 RCT-PARALLEL DESIGN

Patient
treatment A O
U
T
C
O
eligible Random M
E

Treatment B
 RCT 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
 RCT-FACTORIAL DESIGN

Patient

O
tx A U
T
C
O
eligible Random Tx B M
E

tx A + tx B
 Prospective, randomized, open, blinded-endpoint evaluation
(PROBE)

Pengukuran endpoint bersifat obyektif

misal
kadar gula darah, kadar kholesterol Kadar CD20 Kadar asam urat
REVIEW OF STEPS FOR RCT DESIGN

1. Select sample from population

2. Measure baseline variables

3. Randomize

4. Apply interventions & placebo

5. Follow-up cohorts

6. Measure outcomes
TYPES OF DESIGNS
Is random assignment used?
No
Yes

Randomized or
Is there a control group or
True experiment multiple measures?
Yes No

Quasi-experiment Non-experiment
QUASI-EXPERIMENTAL DESIGN
▪ Similar to the experimental design, but lacks the key
ingredient, “random assignment”
▪ Easily and more frequently implemented
▪ Extensively used in the social sciences
▪ A useful method for measuring social variables
▪ Two classic quasi-experimental designs
▪ The Nonequivalent Groups Design
▪ The Regression-Discontinuity Design
Quasi Experimental Designs

▪ This type of design involves a treatment (manipulation )

and an outcome but lacks one of the other two properties
that characterize a true experiment: randomization or a
control group.
▪ Example: if you want to study the effects of smoking on a
variable, you cannot randomly assign people to smoking vs
nonsmoking group.
 QUASI-EXPERIMENTS
▪ Are experiments where the ability to
randomly assign individuals to the
experimental and control groups is limited or
nonexistent.

▪ Quasi-experiments are more commonly used

in evaluating management policy
 KOMPONEN UJI KLINIK

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
 Seleksi/pemilihan subyek

1. Hospital based / community based

2. Diagnosis ? Kriteria
3. Kondisi yang tidak memungkinkan
diikutsertakannya pasien
 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
 EXAMPLE OF ELIGIBILITY
RCT: azithromycin
CRITERIA vs clarithromycin for adult with mild to
moderate CAP
▪ Male and female outpatients
▪ Clinically diagnosed as CAP
▪ Chest-X-ray: pulmonary infiltrate or consolidation
▪ Showing at least three of the following symptom/sign:
▪ nonproductive cough,
▪ new onset of purulent sputum (productive cough), or
▪ change in the character of their sputum;
▪ sputum culture positive for gram-positive diplococci;
▪ body temperature of 38 7C or more at least twice within a 24 h
period; and/or
▪ elevated leukocyte count (10x10 9 /l).
 Seleksi/pemilihan subyek

Exclusion criteria

Kontraindikasi terapi
Kehamilan
Hipersensitivitas
Mencetuskan kondisi emergency
 Contoh exclusion criteria
• Penyakit terminal
• Pasien dengan keadaan berikut:
1. Mengganggu absorpsi antimikroba pada sistema
gastrointestinal
2. Penyakit hepar dengan kenaikan kadar serum
transaminase 3 kali lebih tinggi dari nilai ambang
atasnya SGOT: 0.02–0.90 mM/s/; SGPT: 0.15–0.95
mM/s/l].
3. Hypersensitiv terhadap azithromycin,
clarithromycin, atau jenis macrolide lainnya,
4. Dalam terapi dengan cyclosporine, theophylline,
astemizole, terfenadine, or antacids
 TREATMENT & CONTROL GROUP

Treatment Control

▪ Drug formulation ▪ standard drug (DOC)

▪ therapeutic class ▪ placebo
▪ dosage
▪ non fatal outcome/ disease
▪ drug administration,
frequency
▪ duration of treatment
 Treatment schedule

 Formulasi obat
 Cara pemberian
 Dosis
 Frekuensi pemberian
 Lamanya terapi
 Efek samping, modifikasi dosis
 Supervisi
 RANDOMISATION

 Objective measures
 Equal chance for treatment or control group
 Both groups are balanced
 To prevent bias

metode

Simple Random Random

randomisation permuted block permuted block
within strata
 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

Random permuted blocks

 2 treatment groups:
AB for 0-4; BA for 5-9
 3 treatment groups:
ABC= 1; ACB= 2; BAC= 3
BCA= 4; CAB= 5; CBA= 6
 2 treatment group with block of 4 patient
AABB= 1; ABAB= 2; ABBA= 3
BBAA= 4; BABA= 5; BAAB= 6
 RANDOMISASI

Random permuted blocks within strata

 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

Single blind Double blind Triple blind

Patient Patient Patient

doctor/examiner Doctor/examiner
Statistician
 BLINDING

Aims:
 To prevent bias
 To prevent prediction effect
 Objective measures
 Reducing risk of overwhelming
examination
MEASUREMENT

 Measurable
 Objective
 Accurate
 Consistent
 MEASURING RESPONSE

▪ Baseline ▪ Before treatment

assessment
▪ Main criteria
▪ main indication
▪ Additional criteria
▪ e.g. adverse event
▪ Monitoring
▪ patient compliance
 MEASURING RESPONSE
e.g: cytostatics

 Survival time: early treatment vs. dead

 tumor response: reduction of tumor size
 Duration of treatment vs. treatment response
 Patients improvement
 Toxicity
 KRITERIA UTAMA PENGUKURAN OUTCOME

 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
 PROTOKOL UJI KLINIK
Treatment procedure
Design

 background  Randomisation
 objective  sample size
 patients criteria  analysis
 procedure  informed consent
 measuring response  record form
 design  administration
The Quality Assurance Cycle

Patient/Client Prep
Sample Collection
Personnel competency
Reporting Test Evaluations
•Data and Lab
Management
•Safety
•Customer
Service Sample Receipt
and Accessioning

Record Keeping

Quality Control Sample Transport

Testing