RANCANGAN PENELITIAN

SRI VITAYANI
Fakultas Kedokteran - UMI

08/12/2011
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 CLINICAL TRIAL
. (Uji Klinik)

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INTRODUCTION

RESEARCH DESIGN
OBSERVATIONAL
CROSS SECTIONAL
CASE CONTROL
COHORT

EXPERIMENTAL
CLINICAL TRIAL
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 INTRODUCTION
Apa yang dimaksud Clinical Trials / Uji
Klinik dan kenapa memeriksa mereka ?
Scientific discoveries are providing more and
more insights into the causes of diseases. Many
of these successes are limited to the laboratory
and have yet to be translated into improved
care for people with diseases.
A clinical trial is a test of a new treatment in
patients. Medicine is extremely conservative in
nature, and it takes many years for a treatment
to become generally available even after it has
shown promising results in patients.
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 INTRODUCTION

Clinical trials are a critical part of the

research process. Clinical trials help to move
basic scientific research from the laboratory
into treatments for people. By evaluating the
results of these trials, we can find better
treatments and ways to prevent, detect, and
treat diseases.

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 INTRODUCTION
Clinical trials are research studies involving
people. They seek to answer specific
scientific questions to find better ways to
prevent, detect, and treat diseases, and to
improve care for people with diseases.
Clinical trials differ by type of trial and
phase of trial. Each clinical trial follows a
set of strict scientific guidelines called a
protocol.
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 Why Do Clinical Trial?
To answer clinical problems
To gain new knowledge about a new
or established treatment
To support claim
For gaining government regulatory
approval
For marketing drug, device or technique
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 LEARNING OBJECTIVES
By reading this section and completing the
exercises, you will be able to:
Define clinical trials
Name the different types and phases of
clinical trials
Describe how participants are assigned to
groups in "randomized" clinical trials
Review the purpose of a clinical trial protocol
and its importance.
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 TYPES CLINICAL TRIALS
Treatment trials
What new treatment approaches can help
people who have cancer?
What is the most effective treatment for
people who have cancer?
Prevention trials
What approaches can prevent a specific type
of cancer from developing in people who have
not previously had cancer?
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 TYPES OF CLINICAL TRIALS

Early-detection/screening trials
What are new ways of finding cancer in people before
they have any symptoms?
Diagnostic trials
How can new tests or procedures identify cancer more
accurately and at an earlier stage?
Quality-of-life/supportive care trials
What kind of new approaches can improve the comfort
and quality of life of people who have cancer?

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PHASES CLINICAL TRIALS

Phase 1 Trials
Phase 2 Trials
Phase 3 Trials
Phase 4 Trials

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 PHASES CLINICAL TRIALS
Phase 1 Phase 2 Phase 3 Phase 4

Number of 15-30 <100 >100 thousands Several thousands

participants

Purpose To find a safe To determine if To compare a To further

dosage the drug has an new drug with evaluate long-
effect on current standard term safety and
To design how particular treatment effectiveness of
the drug should diseases new drugs
be given

To observe how To observe how

the drug affects the drug affects
the human body the human body
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 PHASE 1 TRIALS
Sekali hasil penelitian laboratorium memberi
suatu pendekatan baru yang menjanjikan, a
phase 1 trial dapat dimulai. Fase ini adalah
langkah awal dalam menguji coba obat baru
pada manusia.
Tujuannya bukan melihat bagaimana baiknya
obat baru ini bekerja tetapi lebih kepada
berapa banyak obat dapat diberikan dengan
aman dan mengerti efek samping dan
biokimia dalam tubuh.
These trials most closely fit the stereotype of
a truly experimental treatment. 08/12/2011
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 PHASE 1 TRIALS
Primary Objectives
A Phase 1 trial is a dose finding study where
the primary objective is to determine the
Maximum Tolerated Dose (MTD) of the
treatment and to define the toxicities of the
treatment.
The classic Phase 1 trial is only intended to
determine the dose and characterize the side
effects, not to show whether the treatment is
effective, but, of course, if it turns out the
treatment actually is effective, patients can
still benefit. 08/12/2011
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 PHASE 1 TRIALS
Standard Design
The standard Phase 1 design is a Dose Escalation trial
in which successive small groups of patients (Called
"cohorts") are given successively higher doses of the
treatment until some of the patients in a cohort
experience unacceptable side effects
If unacceptable side effects are not seen in the first
cohort, the next cohort gets a higher dose. This
continues until a dose is reached which is too toxic
for a set fraction of patients, say one in three. Then
the previous dose level is considered to be the
Maximum Tolerated Dose (MTD).
Many Phase 1 studies are single institution studies.
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 PHASE 2 TRIALS
Primary Objectives
Phase 2 trials test the ability of the treatment to
produce measurable effects in a small to medium
sized group of patients (typically <100), all with the
same kind of disease. A Phase 2 trial is the first test
directed at any measure of efficacy.
The specific statistic measured is the response rate.
Patients who achieve at least a 50% reduction in the
total size of their measurable tumors are considered
to have responded. If some tumor remains, it is
considered to be a partial response (PR), but if no
detectable tumor remains it is called a complete
response (CR). 08/12/2011
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 PHASE 2 TRIALS
Standard Design
One Stage Design: In the simplest Phase 2 trial, a pre-
determined number patients with the same type of
diseases are given the treatment at the dose determined in
the prior Phase 2 trial, and the response rate is measured.
Two Stage Design: Many Phase 2 trials conducted in two
stages. The idea is to avoid giving patients a treatment as
soon as it can be known that the treatment is ineffective.
In the two stage design, after a pre-determined number of
patients have been treated, the trial is paused, and the
response rate is evaluated. If the response rate is less than
a prespecified minimum goal, it's concluded that the
treatment is not worth pursuing and the trial is ended.
Many, but not all, Phase 2 studies are multi-center studies.
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 PHASE 3 TRIALS
Primary Objectives
Phase 3 trials membandingkan 2 jenis pengobatan
untuk alasan utama suatu penyakit. Umumnya
membandingkan dengan pengonbatan standard dan
melihat apakah obat baru memberikan hasil lebih
baik dari yang lama.
Menilai apakah efek samping lebih sedikit dengan
hasil yang sama daik dengan obat standard.
Finally, Phase 3 trials are used to compare treatments
in common use where there is significant uncertainty
or controversy over which is better.
Almost all modern Phase 3 trials also compare
"Quality of Life" (QOL) with the different treatments.
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 PHASE 3 TRIALS
Standard Design
The standard Phase 3 trial randomizes the patients
between the treatments being tested in the trial.
The purpose of randomization is to eliminate any
potential systematic difference between patients in
the arms of the trial. If patients or their doctors
choose their treatment, there might be some
difference in the patients who entered one arm
compared to those who selected the other.
Randomly assigning patients to treatment would be
unethical if it were known in advance that one of the
treatments was inferior to the other, simply because
intentionally treating patients with less than the best
is unethical.
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 PHASE 4 TRIALS
Phase 4 trials are used to further evaluate
the long-term safety and effectiveness of a
treatment.
Less common than phase 1, 2, and 3 trials,
phase 4 trials take place after the new
treatment has been approved for standard
use (post-approval studies).
Further exploration of intervention new
indications or new uses of drug.

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 RANDOMIZATION
How Participants Are Assigned in Randomized
Trials
Phase 3 studies are randomized clinical
trials. Some phase 2 trials may also be
randomized.
Randomization is used to prevent bias in
research. Participants are assigned to either
the investigational group or the control group
by chance, via a computer program, or with a
table of random numbers. Randomization
ensures that unknown factors do not
influence the trial results.
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 RANDOMIZATION
- The control group kelompok yang
diberikan pengobatan standard penyakit
pada penelitian.
The investigational group kelompok
yang diberikan obat baru yang sedang
diuji klinik.
Anyone who is considering participation in
a randomized clinical trial needs to
understand that she or he has an equal
chance to be assigned to one of the
groups.
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RANDOMIZATION
Why Is Randomization Important?

If participants or doctors choose

a particular group based on what
they think is best, then one of
the groups would likely be very
different than the other, making
comparison between the groups
difficult.
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Why Is Randomization Important?

Randomization eliminates this bias

because participants have an equal
chance of being assigned to either group
are as similar as possible.
Comparing similar groups of people taking
different treatments for the same type of
disease is a way to ensure that the study
results are caused by the treatments
rather than by chance or other factors.
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 GUIDING PRINCIPLES
Ethics
Scientific validity and integrity
Medical relevance
Regulatory and medicolegal
issues
Cost
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 WHAT IS STEP ONE?
Start it with hypothesis
Must be in the form of statement

Then turn it into a specific

question
The questions must be
answerable
This forms the basis of the study
objectives
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 CLINICAL TRIAL PROTOCOL
Clinical trials follow strict scientific
guidelines.
These guidelines clearly state the study's
design and who will be able to participate
in the study. Every trial has a person in
charge, usually a doctor, who is called the
principal investigator.
The principal investigator prepares a plan
for the study, called a protocol, which acts
like a "recipe" for conducting a clinical
trial. 08/12/2011
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 CLINICAL TRIAL PROTOCOL
Introduction and rationale
Study objectives: general and specific
Study design
Inclusion and exclusion criteria
Specific study protocols
Randomization
Intervention
Endpoints
Data analysis and statistics
Ethical considerations (Helsinki Declaration)
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 Endpoints in Clinical Trial
An endpoint apakah peneliti
akan memeriksa untuk evaluate
hasil dari obat baru tersebut.
Hal ini ditetapkan sebelum uji
klinik ini dimulai.
Penting dicatat bahwa endpoints
berbeda, tergantung pada tipe
dan fase dari clinical trial / uji
klinik. 08/12/2011
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 Endpoints in Clinical Trial
Contoh dari endpoints adalah :
Toxicity
what are the harmful effects of the drug?
Clinical response
how does the disease respond to the
treatment?
Survival
how long does the person live?
Quality of life
how does the treatment affect a person's
overall enjoyment of life and sense of well
being? 08/12/2011
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