The Basics of Clinical

Trials

Dorothy M K Keefe MD FRACP

Chairman
Cancer Research Advisory Committee
Cancer Council South Australia
What is a Clinical trial?

A test of a new intervention or

treatment on people
Why are Clinical Trials
conducted in Cancer?
To allow medical professionals and patients
to gain information about the benefits, side
effects and possible uses of new drugs as
well as new ways to use existing drugs

To translate results of basic scientific

research into better ways to prevent,
diagnose, or treat cancer
Why do we need them?

We need to know that any treatments we

recommend are both safe and effective in humans
Cell culture and animal work can only take us so
far!
Especially in Oncology, people are always looking
for the miracle cure-and it is easy to get dragged
into the idea
Scientific, medical, evidence-based paradigm
Types of Clinical Trials

Treatment trials
Prevention trials
Early-detection trials/screening trials
Diagnostic trials
Quality-of-life studies/supportive care
studies
Genetic trials
Types of clinical trial

It can be a phase I, II or III trial

It can be randomized or not
It can be blinded or not
It can involve a placebo or not
And it can be a pilot study or not
Phase I

15-30 people
Determines
what dose is safe
How the treatment should given
How the treatment affects the body
safety
Phase II

Less than 100 people

Determines
Whether the treatment does what
it is supposed to
How the treatment affects the body
If the drug or intervention has an
effect on the cancer
Does not compare with other
treatments
Phase III

From 100 to thousands of people

Equal chance to be assigned to one of two
or more groups
Determines
How the new treatment compares with
the current standard
Or how it compares with placebo
Phase IV

From hundreds to thousands of people

Usually takes place after drug is approved
to provide additional information on the
drugs risks, benefits and optimal use
Randomised Clinical
Trials
Equal chance to be assigned to one of two
or more groups
One gets the most widely accepted
treatment (standard treatment)
The other gets the new treatment being
tested, which researchers hope and
have reason to believe will be better
than standard treatment
All groups are as alike as possible
Provides the best way to prove the
effectiveness of a new agent or
intervention
 Randomisation 7
9

1 2 3
3 4 10

5 6 7 8 Control Group

9 10 5
8

6
2 4

Investigational group
Open versus Blinded Clinical
Trials

Open Label clinical trials

The doctor and patient know which drug or
vaccine is being administered

Blinded clinical trial

Single Blind: the patient doesnt know which
treatment he/she is getting

Double Blind: neither doctor nor patient knows

Placebo control

The new treatment is tested against an

inactive (or dummy) treatment that
looks the same
Pilot Study

A small study that helps develop a

bigger study
A first foray into a particular area
Used to iron out possible difficulties,
and help with design of the bigger,
more pivotal study.
Treatment Trials
Involve people who have cancer
Test new treatments, new combinations of
drugs or new approaches to surgery or
radiotherapy
Determine the most effective treatment
for people who have cancer
Test safety and effectiveness of new
agents or interventions in people with
cancer
Prevention Trials
Evaluate the effectiveness of
ways to reduce the risk of cancer
or prevent the recurrence of
cancer
Enroll healthy people at high risk
for developing cancer
Assess new means of detecting
cancer earlier in healthy people
Early
detection/screening/diagnosis
Early-detection trials/screening trials
Test the best way to detect early cancer,
Pap smears, Mammograms
Blood tests, X-rays
Detect disease at an earlier stage, resulting in
improved outcomes

Diagnostic trials
Develop better tools for classifying types and
phases of cancer and managing patient care
Usually include people who have signs or
symptoms
 Quality-of-life/supportive care
studies
Aim to improve comfort and quality of life for
patients and their families

Genetic trials
Determine how ones genetic makeup can
influence detection, diagnosis, prognosis, and
treatment
Broaden understanding of causes of cancer
Develop targeted treatments based on the
genetics of a tumor
What happens in a
clinical trial?
Clinical research team check the health of the
participant at the beginning of the trial, give
specific instructions for participating in the
trial, monitor the participant carefully during
the trial, and stay in touch after the trial is
completed.
Tests
Doctors visits
Frequent follow up
Who can participate in
clinical trials?
All clinical trials have guidelines about who
can participate. Exclusion / inclusion
criteria help produce reliable results
Criteria based on factors such as
Age / Gender
Type and stage of disease
Previous treatment
Medical conditions
Do Many People Participate
in Cancer Clinical Trials?

Less than 5% of Adults with

cancer participate in clinical
trials
Barriers to Participation in
Clinical Trials
Physicians and other health professionals
may:
Be unaware of appropriate trials
Be unwilling to lose control of patients care
Believe that standard therapy is best
Believe that clinical trials are more work
Have concerns about the patients care or how
the person will react to suggestion of clinical
trial participation
Barriers to Participation in
Clinical Trials

Patients may:
Be unaware of clinical trials
Lack access to trials
Fear, distrust, or be suspicious of research
Have practical or personal obstacles
Be unwilling to go against their physicians
wishes
Benefits of Participation
in Clinical Trials
At a minimum, the best standard treatment
Early access to new treatments. If the new treatment
or intervention is proven to work, patients may be
among the first to benefit
Participation in advancing medical knowledge. Patients
have a chance to help others and improve cancer care
Active role in own health care
The medical team conducting the trial will carefully
and regularly monitor the patients progress
Risks of Participation in
Clinical Trials

New treatments or interventions under

study are not always better than, or even as
good as, standard care
Even if a new treatment has benefits, it may
not work for every patient
Unpleasant, serious or even life threatening
side effects
May require more time and attention than a
non-protocol treatment
How Are Patients Rights
Protected?

Ethical and legal codes that govern medical

practice also apply to clinical trials
Informed consent
Review boards
Scientific review
Institutional review boards (IRBs)
Data safety and monitoring boards
Informed Consent
Informed consent is a document designed to inform the
patient of the purpose and design of a clinical study,
possible side effects and benefits and if there are any
other options. It should also include information on
Voluntary participation
Duration of trial
Insurance and compensation
Name and phone number of contact person
Procedures
Individual rights and confidentiality
Review boards
Scientific review
Panel of experts
Institutional review boards (IRBs)
Qualified people to evaluate new and ongoing trials
All institutions that conduct clinical trials must, by law, have a IRB that
approves the protocol
Data and safety monitoring boards:
Ensure that risks are minimized
Ensure data integrity
Stop a trial if safety concerns arise or objectives have
been met
Are they Ethical?
Yes, in general they are.
We (the scientific community) strive to make them
so.
There are unscrupulous people (and companies) in
any area
Guidelines make it easier for us to check up on
ourselves!

Dr James will discuss

Are they safe?

Yes (usually)
There are stringent guidelines in place
Safety and toxicity are closely
monitored
Trials have built-in stopping rules
Subjects are indemnified
How can we tell they are
done properly?

The Declaration of Helsinki

GCP guidelines
Transparency and good communication
Use of Institutional Ethics committees
So what do I personally do
if I have an idea for a trial?

Consider the question I want to answer

Write a draft protocol
Decide if it is a phase I, II, III or pilot
study
Write the Ethics Committee application
Submit that
Work out where funding will come from
RAH Cancer Centre
Clinical Trials

A wide variety of clinical trials are performed.

These include phase I/II and III studies of new
drugs, and ongoing program in supportive care
and psychosocial research
 The Protocol

A study plan on which all clinical trials are base

(recipe or blueprint)
Provides background about the trial
Describes trials design and organisation
Ensures that trial procedures are consistently
carried out
Each study enrolls people who are alike in key
ways
The Sponsor
Sponsor can be
Pharmaceutical company
Co-operative group (NHMRC, TROG, NSABP)
Another Investigator
Foundation

Responsibilities of the sponsor

update available data
liaise with the appropriate regulatory bodies
communication between trial centre and sponsor
monitoring trial at the site
ensuring all data collected
The Investigator

Profile
Adequate qualifications to conduct research in a given area
Necessary resources
Sound knowledge of the investigational drug and protocol
Sound knowledge of GCP

Responsibilities
training of staff
ethics submission
facilities and equipment
resources for data collection
informed consent
reporting of serious adverse events
The Clinical Trials Nurse

Patient education
Emotional support
Management of side effects
Source documentation
Vital signs
Adverse events - CTC
Protocol deviations
ECOG Performance status
The Clinical Trial
Coordinator or Data
Manager
Responsible for the collection, handling,
manipulation, tracking and quality of the data.

Ensure
clinicians adhere to the protocol,
trial patients receive the therapy dictated by the protocol,
provide support to the patients

All in accordance with Good Clinical Practice (GCP)

What should you
consider before joining a
clinical trial
What is the purpose of the study?
Why do researchers believe the new treatment being
tested may be effective?
What kinds of tests and treatments are involved?
How do the possible risks, side effects, and benefits in
the study compare with my current treatment?
How long will the trial last?
Who will pay for the treatment?
How will I know that the treatment is working?
Can I leave the study after it has begun?
How do you find out
about Clinical Trials?
Oncologist
NCI Web site www.cancer.gov
NHMRC Web site www.ctc.usyd.edu.au
National Breast Cancer Centre www.nbcc.org.au
RAH Cancer Centre
www.rah.sa.gov.au/cancer/medical1.php