CLINICAL TRIAL

•Pelatihan GCP
•RS Dr. Kariadi, Semarang; 28 -29 Sept. 2015
7/19/2019
1
 INTRODUCTION
What are Clinical Trials and Why Investigate Them?
• 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.
• 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. 7/19/2019
2
 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.

7/19/2019
3
 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
7/19/2019
4
 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.
7/19/2019
5
 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?
7/19/2019
6
 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?

7/19/2019
7
PHASES CLINICAL TRIALS

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

7/19/2019
8
 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
7/19/2019
9
 PHASE 1 TRIALS
• Once laboratory studies show that a new
approach has promise, a phase 1 trial can
begin. A phase 1 trial is the first step in
testing a new drugs in humans.
• The goal of the Phase I trial is not to see how
well a new treatment works but rather just to
discover how much of the drug can be given
safely, and to understand its side effects and
chemistry in the body.
• These trials most closely fit the stereotype of
a truly experimental treatment. 7/19/2019
10
 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. 7/19/2019
11
 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.
7/19/2019
12
 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). 7/19/2019
13
 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.
7/19/2019
14
 PHASE 3 TRIALS
Primary Objectives
• Phase 3 trials compare two treatments for a
particular kind of diseases. Typically an experimental
treatment is compared to a standard treatment. The
usual objective is to see if the new treatment
produces better survival than the old one
• In some cases the objective is to show that a
treatment with lesser side-effects is at least as good
as the standard treatment.
• 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.
7/19/2019
15
 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.
7/19/2019
16
 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.

7/19/2019
17
 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.
– The control group is made up of people who will get the
standard treatment for their disease.
– The investigational group is made up of people who will get
the new drug being tested.
• Anyone who is considering participation in a randomized
clinical trial needs to understand that she or he has 7/19/2019
an
equal chance to be assigned to one of the groups. 18
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.
• 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.
7/19/2019
20
 GUIDING PRINCIPLES
• Ethics
• Scientific validity and integrity
• Medical relevance
• Regulatory and medicolegal
issues
• Cost
7/19/2019
21
 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”
7/19/2019
22
 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. 7/19/2019
23
 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) 7/19/2019
24
 Endpoints in Clinical Trial
• An endpoint is what researchers will measure to evaluate
the results of a new treatment being tested in a clinical
trial. Research teams establish the endpoints of a trial
before it begins.
• It is important to note that endpoints differ, depending on
the type and phase of the clinical trial. Examples of
endpoints are:
– 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? 7/19/2019
25
THANK YOU

7/19/2019
26