Cancer Clinical Trials
The Basic Workbook
National Institutes of Health
National Cancer Institute
The National Cancer Institute Clinical Trials
Education Series
Cancer Clinical Trials Books
Cancer Clinical Trials: The Basic Workbook
The self-modulated workbook, with its accompanying activities,
will help readers understand why cancer clinical trials are
important, how they work, how participant safety is protected, as
well as some of the reasons so few adults participate in these trials.
It is designed for individuals who want to develop a basic
understanding of clinical trials.
Cancer Clinical Trials: The In-Depth Program
The textbook expands on the subjects outlined in The Basic
Workbook. It features additional information on clinical trials
design, resources for physician participation, and referral of
individuals to studies. It is designed for health care professionals
and others who seek a more in-depth understanding of
clinical trials.
Cancer Clinical Trials: A Resource Guide for Outreach, Education,
and Advocacy
The interactive workbook provides direction and guidance for
individuals and organizations interested in developing clinical
trial outreach and education activities. This guide can also be used
along with either/both of the texts listed above.
Trainer's Guide for Cancer Education
A manual for planning and conducting educational sessions on
cancer-related topics, including clinical trials.
Cancer Clinical Trials Resources
The following resources will help support cancer clinical trials
education and outreach efforts.
Publications
Low literacy brochures on cancer clinical trials for potential participants:
· If You Have Cancer...What You Should Know About Clinical Trials*
· If You Have Cancer and Have Medicare... You Should Know About
Clinical Trials
Clinical trial participant booklets:
· Taking Part in Clinical Trials: What Cancer Patients Need to Know*
· Taking Part in Clinical Trials: Cancer Prevention StudiesWhat
Participants Need to Know*
*Also available in Spanish
Videos
· A clinical trial awareness video and speaker's guide, "Cancer
Trials...Because Lives Depend on It"
· A video and discussion guide on deciding to take part in a
clinical trial, "Cancer Clinical Trials: An Introduction for
Patients and Their Families"
Slide Program
Three slide programs are available in PowerPoint on CD-ROM and
on the www.cancer.gov Web site:
Cancer Clinical Trials: The Basics
Provides background on why cancer clinical trials are important,
how they work, and how participants' safety is protected.
Cancer Clinical Trials: The Way We Make Progress Against Cancer
A brief community awareness presentation.
Cancer Clinical Trials: In-Depth Information
Expands on the subjects outlined above, featuring additional
information on clinical trial design with resources for physician
participation and referral of individuals to studies.
Ordering Information
To order these publications, contact the Cancer Information Service
at 1-800-4-CANCER or log onto www.cancer.gov/publications. Most
materials are available as PDF files on the Web site.
The Cancer Information Service
NCI's Cancer Information Service (CIS), with regional offices throughout the
United States, may work with organizations and professionals to plan,
implement, and evaluate culturally appropriate clinical trials education
programs using the Clinical Trials Education Series. Contact the CIS at
1-800-4-CANCER.
Table
of
Contents
Table of Contents
Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Introduction: The Importance of Clinical Trials . . . . . . . . . . . . . . . 3
1. The Clinical Trial Process. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
What Are Clinical Trials? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
Cancer Clinical Trials--Types and Phases . . . . . . . . . . . . . . . 8
Cancer Treatment Trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Cancer Prevention Trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
Other Types of Cancer Clinical Trials . . . . . . . . . . . . . . . . . . 17
How Participants Are Assigned in Randomized Trials . . . 19
The Clinical Trial Protocol . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
2. Advancing Cancer Care Through Clinical Trials . . . . . . . . . . . 31
Evaluating Clinical Trial Results . . . . . . . . . . . . . . . . . . . . . . 32
Approving New Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
Advances in Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
Exercise . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
3. Participant Protection in Clinical Trials . . . . . . . . . . . . . . . . . . . 43
History of Participant Protection . . . . . . . . . . . . . . . . . . . . . . 44
The Informed Consent Process . . . . . . . . . . . . . . . . . . . . . . . . 45
Review Committees . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
Government Regulations and Agencies . . . . . . . . . . . . . . . . 52
Exercise . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
4. Barriers to Clinical Trial Participation. . . . . . . . . . . . . . . . . . . . . 57
Barriers for Health Care Professionals . . . . . . . . . . . . . . . . . 58
Barriers for the General Population . . . . . . . . . . . . . . . . . . . . 59
Barriers for Racially or Ethnically Diverse Populations . . . 61
Cost Barriers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
Exercise . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67
5. Finding Clinical Trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
Organizations That Sponsor Clinical Trials . . . . . . . . . . . . . 72
Finding Information on Cancer and Clinical Trials. . . . . . . 76
Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80
Glossary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
Preface
Preface
Scientific discoveries are providing more and more insights into
the causes of cancer. Many of these successes are limited to the
laboratory and have yet to be translated into improved care for
people with cancer.
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 cancer. But very few adults with cancer--only 3 percent--
participate in clinical trials. We need to test the best cancer
prevention, detection, and treatment ideas in the shortest time
possible, and this can only happen if more people participate in
clinical trials.
We know that most people understand very little about clinical
trials. National Cancer Institute (NCI) research has shown that the
general public is either unaware of clinical trials as a treatment/
prevention option or misinformed about the clinical trial process.
The reasons for this lack of understanding are complex, and there
is no simple solution. We do know, however, that there are many
barriers that discourage both physicians and potential participants
from taking part in clinical trials.
By reading this workbook, you are already helping to overcome
some of these barriers. Whether you are a cancer survivor, someone
who works with people with cancer, or someone who is touched
by cancer in another way--this workbook can help answer your
questions about clinical trials. It will help you understand why
cancer clinical trials are important, how they work, how the
participants' safety is protected, and some of the reasons why
more adults don't participate in trials.
With this information, you can help people in your community
make informed decisions about their cancer treatment and
prevention options, including the option of participating in a
clinical trial.
1
How to Use This Workbook
This workbook is designed to complement the other materials in
the NCI Clinical Trials Education Series. Each section of this
workbook features information about different aspects of clinical
trials, usually followed by an exercise or questions. Because each
section builds on the one that precedes it, it is strongly
recommended that you complete each exercise to enhance your
understanding of the concepts before moving on to the next
section. Some of the exercises expand on concepts introduced in
the text. If you are working within an organization, you may wish
to read the material on your own and review the exercises with
other members of your organization.
2
of
Introduction:
Clinical
Trials
The
Importance
Introduction:
The Importance of Clinical Trials
Why Cancer Clinical Trials Are Important
Before reviewing how cancer clinical trials work, think about why
they are important. Depending on your community, the people you
work with, or the organizations you belong to, the reasons clinical
trials are important to you and why more people need to
participate may be different than the ones listed here.
q Put a checkmark next to the reasons that have the most
meaning for you or write in your own reasons in the space that
follows. Keep these reasons in mind as you go through
this workbook.
Cancer Affects All of Us
q Cancer affects us all--whether we have it, care about someone
who does, or worry about getting it in the future. Consider the
impact of cancer in the United States1 each year:
About 555,550 people die of cancer--more than 1,500 people
a day
Cancer is the second leading cause of death, exceeded only
by heart disease
One out of every four deaths are caused by cancer
About 1,284,900 new cancer cases are diagnosed
q Research has shown that there are many differences between
who develops cancer, who dies from cancer, and who is
screened and treated for cancer among men and women,
and among people of different races, ethnicities, and
socioeconomic backgrounds.
1
American Cancer Society. (2002). Cancer facts and figures. Atlanta, GA.
3
Clinical Trials Lead to Advances in Cancer Care
q Clinical trials are a critical part of the research process. Clinical
trials translate basic scientific research results into better ways
to prevent, diagnose, or treat cancer. Clinical trials are the final
step in a long research process.
q Clinical trials contribute to knowledge of and progress against
cancer. Many of today's most effective cancer treatments are
based on previous study results. Because of progress made
through clinical trials, many people treated for cancer are now
living longer.
q The more people who participate in clinical trials, the faster
critical research questions can be answered that will lead to
better treatment and prevention options for all cancers. We
will never know the true effectiveness of a cancer treatment
or a way to prevent cancer unless more people are involved
in clinical trials.
q In the past, clinical trials were sometimes seen as the last resort
for patients who had no other treatment choices. This is not
true; there are many clinical trials for individuals whose cancer
has not spread.
Few People With Cancer Take Part in Clinical Trials
q Enormous improvements in treating childhood cancer have
come about as the direct result of clinical trials; more than 60
percent of U.S. children with cancer participate in clinical trials.
In 2000, more than 70 percent of children with cancer were
alive 5 years after diagnosis, compared to only 55 percent
in the mid-1970s.
q In contrast, only 3 percent of U.S. adults with cancer participate
in clinical trials--far fewer than the number needed to answer
the most pressing cancer questions quickly.
q According to a survey2 in 2000, most people with cancer were
either unaware or unsure that participation in clinical trials was
an option for their treatment, and most of them said they would
have been willing to enroll had they known it was possible.
2
Harris Interactive. (2001). Health Care News, 1(3). [Poll]. Available from
http://harrisinteractive.com/about/healthnews/HI_HealthCareNews2001Vol_iss3.pdf
4
Notes
5
1.
The
Clinical
Trial
Process
1
The Clinical Trial Process
Overview
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.
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
· Dispel common myths about clinical trials
The Clinical Trial Process
7
What Are Clinical Trials?
Clinical trials are research studies involving people. They are the
final step in a long process that begins with preliminary laboratory
research and animal testing. Clinical trials try to answer specific
scientific questions to find better ways to prevent, detect, or treat
diseases or to improve care for people with diseases.
In cancer research, a clinical trial is designed to show how a certain
anticancer approach--for instance, a promising drug, a new
surgical procedure, a new diagnostic test, or a possible way to
prevent cancer--affects the people who receive it.
Cancer Clinical Trials--Types and Phases
Types of Clinical Trials
There are several different types of cancer clinical trials. This
workbook will focus primarily on cancer treatment and prevention
trials. Each type of trial is designed to answer different research
questions:
· 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?
· Early-detection/screening trials
What are new ways of finding cancer in people before they
have any symptoms?
8
CANCER CLINICAL TRIALS: THE BASIC WORKBOOK
· 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?
Phases of Clinical Trials
Trials take place in four phases, each designed to answer different
research questions.
Phase 1
Phase 2
Phase 3
Phase 4
Number of
15-30 people
Less than 100
Generally,
Several
participants
people
from 100 to
hundred to
thousands of
several
people
thousand
people
Purpose
· To find a
· To determine
· To compare
· To further
safe dosage
if the agent or
the new
evaluate the
intervention
agent or
long-term
· To decide
has an effect
intervention
safety and
how the
on a
(or new use
effectiveness
agent
particular
of a
of a new
should be
cancer
treatment)
treatment
given
with the
· To see how
· To observe
current
the agent or
how the
standard
intervention
agent
affects the
affects the
human body
human body
The trial phases are explained in the context of drug treatment trials, but the same
concepts apply to most types of clinical trials.
The Clinical Trial Process
9
Cancer Treatment Trials
Most cancer clinical trials are treatment studies. These clinical trials
involve people who have cancer. Treatment studies are designed to
answer specific questions about and evaluate the effectiveness of a
new treatment or a new way of using an old treatment. These trials
test many types of treatments, such as new drugs, vaccines, new
approaches to surgery or radiation therapy, or new combinations
of treatments.
Phase 1: Looking at Safety
Once laboratory studies show that a new approach has promise, a
An agent is a
phase 1 trial can begin. A phase 1 trial is the first step in testing a
substance that
new cancer agent in humans.
produces, or
In these studies, researchers look for the best way to give people
that researchers
the new agent (for example, by pill or by injection), how often it
believe is capable
should be given, and what the safest dose is. These studies also
of producing,
include special laboratory tests such as blood tests and biopsies to
an effect that
evaluate how the new agent is working in the body.
fights cancer.
In phase 1 cancer trials, small groups of people with cancer are
treated with a certain dose of a new agent that has already been
extensively studied in the laboratory. During the trial, the dose is
10
CANCER CLINICAL TRIALS: THE BASIC WORKBOOK
usually increased group by group in order to find the highest
Toxicity refers
dose that does not cause unacceptable harmful side effects, called
to harmful side
toxicity. This process determines a safe and appropriate dose to use
effects caused
in a phase 2 trial. Although the primary purpose of phase 1 trials is
by the agent
to find the safest dose of a new agent, researchers also evaluate
or intervention
whether the new agent benefits people.
being tested.
Who Participates in Phase 1 Treatment Trials?
People with cancer who are eligible for phase 1 studies have no
known effective treatment options, or they have already tried other
treatment options. Many participate in these trials because they
want to help others and contribute to cancer research. Phase 1
cancer trials usually have 15 to 30 participants.
What Are the Benefits and Risks for Phase 1 Treatment Trial Participants?
Benefits
If the new agent under study has an effect on the cancer,
participants may be among the first to benefit.
Risks
Because most phase 1 trials are testing agents for the first time in
humans, unpredictable side effects can occur.
Phase 2: How Well the New Treatment Works
Phase 2 trials continue to test the safety of the new agent, and
begin to evaluate how well it works against a specific type of
cancer. In these trials, the new agent is given to groups of people
with one type of cancer or related cancers, using the dosage found
to be safe in phase 1 trials.
Who Participates in Phase 2 Trials?
In general, people with cancer who take part in phase 2 trials have
been treated with chemotherapy, surgery, or radiation, but the
treatment has not been effective. Participation in these trials is
often restricted based on the previous treatment received. Phase 2
cancer trials usually have less than 100 participants.
The Clinical Trial Process
11
What Are the Benefits and Risks for Phase 2 Treatment Trial Participants?
Benefits
If the new agent under study has an effect on the cancer,
participants may be among the first to benefit.
Risks
· It is important to remember that when a phase 2 trial begins,
it is not yet known if the agent tested works against the specific
cancer being studied.
· Unpredictable side effects can also occur in these trials.
A placebo is
Phase 3: Comparing a New Treatment to the
designed to look
Standard Treatment
like the medicine
Phase 3 trials focus on learning how a new treatment compares to
being tested but
standard, or the most widely accepted, treatment. Researchers
doesn't contain
want to learn whether the new treatment is better than, the same
any active
as, or worse than the standard treatment.
ingredient. Some
In phase 3 trials, participants have an equal chance to be assigned
people call a
to one of two or more groups (also called "arms"). In a study with
placebo a
two groups:
"sugar pill."
· One group gets the standard treatment (control group)
· The other group gets the new treatment being tested
Placebos are
(investigational group)
almost never
used in cancer
Placebos are almost never used in cancer treatment trials.
treatment trials.
In rare cases in
The process of assigning participants to groups is called
which no standard randomization. Additional discussion of randomization is included
treatment exists
later in this section.
for a cancer, some
studies compare
Finding Out About Standard Cancer Care
a new treatment
The National Cancer Institute's Web site www.cancer.gov
with a placebo.
contains the latest information about standard cancer
treatment, screening, prevention, genetics, supportive care,
and complementary and alternative medicine, as well as a
registry of cancer clinical trials. Most cancer information
summaries appear in two versions: a technical version for the
health professional and a nontechnical version for the public.
Many of the summaries are also available in Spanish.
12
CANCER CLINICAL TRIALS: THE BASIC WORKBOOK
Who Participates in Phase 3 Trials?
Participants in phase 3 studies range from people newly diagnosed
with cancer to people with extensive disease. Phase 3 studies are
designed to answer research questions across the disease
continuum. Phase 3 trials usually have hundreds to thousands of
participants, in order to find out if there are true differences in the
effectiveness of the treatment being tested.
What Are the Benefits and Risks for Phase 3 Treatment Trial Participants?
Benefits
· Regardless of the group a participant is assigned to, he or she
will receive, at a minimum, the best standard treatment.
· If a participant is taking the new treatment and it is proven to
work better than the standard treatment, he or she may be
among the first to benefit.
Risks
· New treatments under study do not always turn out to be better
than, or even as good as, standard treatment.
· New treatments under study may have side effects that are
worse than those of standard treatment.
· Despite phase 1 and 2 testing, unexpected side effects may occur.
· Like standard treatments, new treatments may not work for
every participant.
· A participant might receive standard treatment, which might be
found to be less effective than the new approach.
Phase 4: Continuing Evaluation
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.
The Clinical Trial Process
13
Biological Therapies: Finding Out How the Immune
System Works Against Cancer
Biological therapy (sometimes called immunotherapy, biotherapy,
or biological response modifier therapy) uses the body's immune
system, either directly or indirectly, to fight cancer or to lessen the
side effects that some cancer treatments might cause.
The immune system is a complex network of cells and organs that
work together to defend the body against attacks by "foreign"
or "non-self" invaders. This network is one of the body's main
defenses against disease. It works against disease, including
cancer, in a variety of ways.
Biological therapies are designed to repair, stimulate, or enhance
the immune system's responses. Many clinical trials are now
testing the use of biological therapies, such as monoclonal
antibodies and vaccines, to fight cancer.
Monoclonal Antibodies (MOABs)
Monoclonal antibodies are a form of biological therapy that is now
being studied in the laboratory and in clinical trials. MOABs may
help the body's own immune system fight cancer by locating
cancer cells and either killing them or delivering cancer-killing
substances to them without harming normal cells.
Cancer Vaccines
Cancer vaccines are another form of biological therapy now being
studied in the laboratory and in clinical trials.
Researchers are developing vaccines that may help a person's
immune system recognize cancer cells. These vaccines may help
the body reject tumors and prevent cancer from recurring. In
contrast to vaccines against infectious diseases, cancer vaccines are
designed to be injected after the disease is diagnosed, rather than
before it develops. Cancer vaccines given when the cancer is small
may be able to eradicate the cancer.
Many vaccines are not used alone, but in combination with other
treatments such as surgery, chemotherapy, or additional
interactions that help stimulate the immune response in general.
14
CANCER CLINICAL TRIALS: THE BASIC WORKBOOK
Cancer Prevention Trials
Unlike treatment trials, cancer prevention trials are studies
involving healthy people who are at high risk for developing
cancer. These studies try to answer specific questions about cancer
risk and evaluate the effectiveness of ways to reduce cancer risk.
They look at approaches to preventing cancer from developing in
people who have not previously had cancer.
There are two kinds of prevention trials:
· Action studies ("doing something") focus on finding out
whether actions people take--such as exercising more or
quitting smoking--can prevent cancer.
· Agent studies ("taking something") focus on finding out
whether taking certain medicines, vitamins, minerals, or food
supplements (or a combination of them) may lower the risk of a
certain type of cancer. Agent studies are also called
chemoprevention studies.
Researchers who conduct these studies want to know:
· How safe it is for a person to take this agent or do this activity
· Whether the new approach prevents cancer
The Clinical Trial Process
15
How Chemoprevention Trials Work
Chemoprevention trials also go through phases. In phase 3 agent
studies:
· One group takes the promising new agent (called the
study agent)
· The other group takes either a standard agent (already being
used for cancer prevention) or a placebo
Placebos are used in prevention trials when there is not yet a
known approach or standard agent for cancer prevention in the
population being studied. It is important to remember that
participants in prevention trials do not have cancer.
Who Participates in Prevention Trials?
Prevention trials include people who may be at risk for developing
cancer. Many chemoprevention trials require that participants be at
high risk for developing cancer.
What Are the Benefits and Risks for Prevention
Trial Participants?
Benefits
· If the drug or intervention being studied is found to be effective,
the participants may be among the first to benefit.
Risks
· New cancer prevention drugs or interventions may have
unknown side effects or risks.
· The side effects of the drug or intervention may be worse
and the effectiveness less than those of standard preventive
measures.
· Even if a new drug or intervention is effective, it may not work
for every participant.
16
CANCER CLINICAL TRIALS: THE BASIC WORKBOOK
Other Types of Cancer Clinical Trials
Early Detection/Screening Trials
The goal of early detection/screening trials is to discover methods
for finding cancer as early as possible. For many types of cancer,
detecting and treating the disease at an early stage can result in an
improved outcome--a better chance to shrink the tumor, minimize
its effects, or cause it to go away completely.
Ways to find cancer include:
· Imaging tests--tests that make pictures of areas inside the body.
Imaging can be used to see if a person has any suspicious areas
or abnormalities that might be cancerous
· Laboratory tests or physical exams--tests that check blood,
urine, and other body fluids and tissues
· Genetic tests--tests that look for inherited genetic markers
linked to some types of cancer
The Clinical Trial Process
17
Diagnostic Trials
These trials focus on how new tests or procedures can better
identify whether people have cancer. Diagnostic tests or procedures
are done to find out whether cancer is present and, if so, where it is
located in the body, if it has spread, and how much cancer there is.
Some diagnostic trials compare two or more techniques to
diagnose cancer, find out how accurate they are, and see whether
they can provide any new and valuable information about
someone's cancer. Genetic tests are being evaluated as diagnostic
tools to further classify cancers, which may help direct therapies or
improve treatments for people with specific genetic changes.
Quality-of-Life/Supportive Care Trials
These trials evaluate improvements in the comfort of and quality of
life for people who have cancer. They find ways to help people
who are having nutrition problems, infection, nausea and vomiting,
sleep disorders, depression, or other effects from cancer or its
treatment. Some supportive care trials focus on families and
caregivers to help them cope with both their own needs and those
of the person with cancer.
18
CANCER CLINICAL TRIALS: THE BASIC WORKBOOK
Genetics Research
Genetics studies may be a part of any cancer clinical trial and
focus on understanding how someone's genetic makeup can
assist in the early detection, diagnosis, or treatment of cancer.
Genetic research is also being used to help develop future
cancer treatments.
Population and family-based genetic research studies differ
from the traditional cancer clinical trials. In these studies,
researchers look at tissue or blood samples, either from
families or large numbers of people, to find genetic changes
that are associated with cancer. These people may or may not
have cancer. The goal of these studies is to help understand
what causes cancer.
Genetics research is an important part of cancer research
because it contributes to the knowledge of the causes of
cancer and can lead to developing new clinical trials that
focus on cancer prevention, detection, and treatment.
How Participants Are Assigned in
Randomized Trials
Phase 3 studies are randomized clinical trials. Some phase 2 trials
may also be randomized.
Bias can be human
Randomization is a method used to prevent bias in research. In
choices, beliefs, or
phase 3 studies (and some phase 2 studies), participants are
any other factors
assigned to either the investigational group or the control group by
besides those being
chance, via a computer program, or with a table of random
studied which can
numbers. Randomization ensures that unknown factors do not
affect a clinical
influence the trial results.
trial's results.
· The control group is made up of people who will get the most
widely accepted treatment (standard treatment) for their cancer.
· The investigational group is made up of people who will get the
new agent or intervention being tested.
The Clinical Trial Process
19
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. The doctor does not choose the
group for the participant.
Control Group
5
8
9
7
5
4
1
3
2
3
Randomization
2
1
6
6
7
8
9
10
4
10
Investigational Group
Randomization is a method used to prevent bias in research. A computer or a table
of random numbers generates treatment assignments, and participants have an
equal chance to be assigned to one of two or more groups (e.g., the control group
or the investigational group).
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 and the
subgroups are as similar as possible. Comparing similar groups of
people taking different treatments for the same type of cancer is a
way to ensure that the study results are caused by the treatments
rather than by chance or other factors.
20
CANCER CLINICAL TRIALS: THE BASIC WORKBOOK
The 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.
The protocol explains what the trial will do, how the study will be
carried out, and why each part of the study is necessary. It
includes information on:
· The reason for doing the study
· How many people will be in the study
· Who is eligible to participate in the study (requirements might
involve type of cancer, general health, age)
· Any agents participants will take, the dosage, and how often
· What medical tests participants will have and how often
· What information will be gathered about the participants
· The endpoints of the study
Endpoints
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 agent?
· Tumor response--how does the cancer 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?
The Clinical Trial Process
21
Every doctor or research center that takes part in the trial uses the
same protocol. This ensures that participants are treated identically
no matter where they are receiving treatment so the information
from all the participating sites can be combined and compared.
Although some people may choose to read the entire protocol
before they choose to participate, the law requires that, at a
minimum, participants learn about the study protocol through a
process called informed consent. This information helps
individuals decide whether to participate.
Guidelines on Who Can Join a Trial
Depending on the research questions, each clinical trial
protocol clearly states the type of person who can or cannot
participate in the trial. The reason for these guidelines
includes ensuring:
· Participant safety--some people have other health
problems that could be made worse by the treatments in a
study. All potential participants interested in a trial receive
medical tests to be sure that no one with special risks
joins the study.
· Accurate and meaningful study results--some clinical
trials will not take participants who already have had
another kind of treatment for the cancer. Otherwise,
doctors could not be sure whether the participant's results
were due to the treatment being studied; the earlier
treatment might have made a difference.
Other common qualifications for entering a trial include:
· Having a certain type or stage of cancer
· Having been previously treated with a certain kind of
therapy
· Being in a certain age group
These criteria help ensure that trial participants are as similar
as possible so doctors are confident that the results are due to
the agent or intervention being studied and not other factors.
22
CANCER CLINICAL TRIALS: THE BASIC WORKBOOK
Exercises
The exercises in this workbook are optional. They are provided
as tools to review the information presented in each chapter.
Exercise 1.1
Dispelling Myths About How Clinical Trials Work
Apply what you've learned about clinical trials to respond to the
following myths.
A. Cancer treatment clinical trials are the treatment of last resort.
_____________________________________________________________
_____________________________________________________________
_____________________________________________________________
_____________________________________________________________
B. Only people who have cancer are eligible to participate in a
cancer clinical trial.
_____________________________________________________________
_____________________________________________________________
_____________________________________________________________
_____________________________________________________________
C. Many people who join cancer treatment clinical trials get a sugar
pill (placebo) instead of being treated.
_____________________________________________________________
_____________________________________________________________
_____________________________________________________________
_____________________________________________________________
D. By restricting who can go on trials, investigators keep people
from getting a new treatment that could save their lives.
_____________________________________________________________
_____________________________________________________________
_____________________________________________________________
_____________________________________________________________
The Clinical Trial Process
23
Answers to Exercise 1.1
A. Cancer treatment clinical trials are the treatment of last resort.
Clinical trials are not only for those with the most advanced
disease. Phase 3 treatment trials, for example, can include people
who have all stages of disease, from the most advanced to
people newly diagnosed who have very limited disease.
B. Only people who have cancer are eligible to participate in a
cancer clinical trial.
Three types of cancer trials are open to people without cancer:
· Prevention trials study ways to prevent cancer in people.
· Early detection/screening trials look at ways to detect cancer
as early as possible.
· Diagnostic trials focus on ways to test for or better
identify cancer.
C. Many people who join cancer treatment clinical trials get a
sugar pill (placebo) instead of being treated.
Placebos are rarely used in cancer treatment trials. No one is
ever given a placebo when an effective treatment is available.
However, in rare cases, a placebo may be used when testing a
new drug if there is no known effective treatment.
D. By restricting who can go on trials, investigators keep people
from getting a new treatment that could save their lives.
There are important reasons that clinical trials have
eligibility criteria:
· To protect the participant's safety. Some people have other
health problems that could be made worse by the treatments
in a study.
· To ensure study results are accurate and meaningful. The trial
participants need to be as similar as possible so that doctors
can be sure of the reasons for the results. For example, if a
24
CANCER CLINICAL TRIALS: THE BASIC WORKBOOK
participant already had another kind of treatment, the
patient's response may reflect the earlier treatment rather
than the one being studied.
Remember, no one knows whether the treatment being tested
in a clinical trial will turn out to be better than the approaches
currently being used.
The Clinical Trial Process
25
Exercise 1.2
Looking at a Clinical Trial Protocol
Apply what you've learned about clinical trials to an actual clinical
trial protocol.
The following is an example of an abbreviated "patient version"
protocol taken from PDQ® (physician data query), a clinical trial
database sponsored by the National Cancer Institute. A "health
professional" version is also available for every trial.
Please note that this trial protocol is used for illustrative purposes only;
it may no longer be open to participants at the time you are reading
this guide.
Although some clinical trial participants may choose to read the
entire protocol before they choose to participate, the law requires
that participants learn about the study protocol through a process
called informed consent. This information helps them decide
whether to participate.
Directions
Read the following protocol and answer these questions:
A. What type of trial is this?
B.
What phase trial is this?
C.
Is it randomized?
D.
If someone meets the eligibility requirements, what kind of
person might be interested in participating?
E.
What might be of concern for someone considering
participation in this trial?
Note that the protocol contains some blanks to indicate words omitted for
the purpose of this exercise.
26
CANCER CLINICAL TRIALS: THE BASIC WORKBOOK
Protocol ID: NSABP-B-31
Phase _______, ________Study of Doxorubicin and
Cyclophosphamide Followed by Paclitaxel With or Without
Trastuzumab (Herceptin) in Women With Node Positive
Breast Cancer That Overexpresses HER2 (Summary Last
Modified 09/2000)
Patient Abstract
Rationale: Drugs used in chemotherapy use different ways
to stop tumor cells from dividing so they stop growing
or die. Monoclonal antibodies such as trastuzumab can
locate tumor cells and either kill them or deliver
tumor-killing substances to them without harming normal
cells.
It is not yet known whether combination chemotherapy
plus trastuzumab is more effective than combination
chemotherapy alone for treating breast cancer.
Purpose: _________ phase _______ trial to compare the
effectiveness of combination chemotherapy with or
without trastuzumab in treating women who have stage I,
stage II, or stage IIIA breast cancer that has spread to
lymph nodes in the armpit.
Eligibility:
·
No more than 9 weeks since diagnosis
·
Previous surgery to remove the tumor and lymph nodes
in the armpit
·
No previous biological therapy, chemotherapy, hormone
therapy, or radiation therapy for breast cancer
Treatment: Patients will be randomly assigned to one of
two groups. Patients in group one will receive infusions
of doxorubicin and cyclophosphamide every 3 weeks for
four courses. About 3 weeks after the last course, these
patients will receive an infusion of paclitaxel every 3
weeks for four courses.
Patients in group two will receive chemotherapy as in
group one. They will also receive an infusion of
trastuzumab on day 1 of the first course of paclitaxel.
They will continue to receive an infusion of trastuzumab
once a week for 51 weeks. Some patients will receive
tamoxifen by mouth once a day for 5 years. Some patients
may receive radiation therapy daily for 5-6 weeks. All
patients will receive follow-up evaluations every 6
months for 5 years and once a year thereafter.
The Clinical Trial Process
27
Key Protocol Terms
chemotherapy: Treatment with anticancer drugs.
monoclonal antibodies: Laboratory-produced substances that
can locate and bind to cancer cells wherever they are in
the body.
doxorubicin: An anticancer drug that belongs to the family of
drugs called antitumor antibiotics. It is an anthracycline.
cyclophosphamide: An anticancer drug that belongs to the
family of drugs called alkylating agents.
infusion: A method of putting fluids, including drugs, into the
bloodstream. Also called intravenous infusion.
tamoxifen: An anticancer drug that belongs to the family of
drugs called antiestrogens. Tamoxifen blocks the effects of the
hormone estrogen in the body. It is used to prevent or delay
the return of breast cancer or to control its spread.
28
CANCER CLINICAL TRIALS: THE BASIC WORKBOOK
Answers to Exercise 1.2
A. What type of trial is this?
Treatment trial
B. What phase trial is this?
It is a phase 3 trial because the description says it is not yet
known whether combination chemotherapy plus trastuzumab is
more effective than combination chemotherapy alone for treating
breast cancer. The combination chemotherapy is considered
standard treatment.
C. Is it randomized?
Yes. It says patients will be randomly assigned to one of
two groups.
D. If someone meets the eligibility requirements, what kind of
person might be interested in participating?
Someone who:
· Is willing to attend many chemotherapy treatment sessions
· Understands that she has an equal chance of being assigned to
either group
· Is willing to be followed for several years
· Is interested in contributing to scientific knowledge
E. What might be of concern for someone considering
participating in this trial?
· People will not be able to select the group they would like to
participate in
· Participants must agree to be followed for several years
· People will want to know how the protocol determines who
will need to:
Take tamoxifen daily
Have daily radiation treatments
The Clinical Trial Process
29
2.
Advancing
Clinical
Trials
Cancer
Care
Through
2
Advancing Cancer Care Through
Clinical Trials
Overview
Once a new drug or intervention is proven safe and effective in a
clinical trial, it may become the new standard of practice.
Everything we can tell people with cancer today about their
treatment options is based on the results of clinical trials. Members
of the interested public can help speed up the research process.
Learning Objectives
By reading this section and completing the exercises, you
will be able to:
· Explain the process of evaluation of clinical trial results
· Describe the steps by which the U.S. Food and Drug
Administration (FDA) approves a new drug
· Name some examples of clinical trials that have led to
advances in cancer prevention, detection, and treatment
· Explain how members of the public can help speed up the
research process
Advancing Cancer Care Through Clinical Trials
31
Evaluating Clinical Trial Results
After a clinical trial is completed, researchers look carefully at the
collected data before making decisions about further testing and
what their findings mean.
After a phase 1 trial is completed, researchers decide whether:
· There are enough data to support further study with a
phase 2 trial
· Further research will be discontinued because the agent
was not safe
After a phase 2 trial is completed, researchers decide whether:
· There are enough data to support further study with a
phase 3 trial
· Further research will be discontinued because the agent was not
safe or effective
After a phase 3 trial is completed, the researchers must look at the
data and decide whether the results have medical importance.
When the analysis is complete, the researchers will inform the
medical community and the public of the trial results.
In most cases, a trial's results are first reported in peer-reviewed
Peer review is a
scientific journals. But if a trial's results have significant medical
process by which
importance, a public announcement may be made while the formal
experts critique a
report is being submitted to ensure that people can quickly benefit
study's report
from the new advance. Particularly important results are likely to
before it is
be featured by the media and widely discussed at scientific
published to make
meetings and by advocacy groups.
sure that the
analysis and
Once a new drug or technique is proven safe and effective in a
conclusions are
clinical trial, it may become the new standard of practice
sound.
for physicians.
32
CANCER CLINICAL TRIALS: THE BASIC WORKBOOK
Approving New Drugs
By law, the Food and Drug Administration (FDA), an agency of the
U.S. Department of Health and Human Services (HHS), must
review all test results for new agents to ensure that products are
safe and effective for specific uses.
Once a new agent proves promising in the laboratory, the drug
company or research sponsor, such as NCI, must apply for FDA
approval through an Investigational New Drug (IND) application.
Once FDA gives approval to the sponsor, clinical trials may begin.
Once a trial sponsor feels there are adequate data from the results
of the trial to support a certain use for a drug, the sponsor submits
a New Drug Application (NDA) or a Biologics License Application
(BLA) to FDA.
Advancing Cancer Care Through Clinical Trials
33
The Drug Development and Approval Process
Total
Preclinical Testing
Clinical Trials
Post-Clinical Trials
Years for
Drug
Approval
Step 1
Step 2
Step 3
Step 4
Step 5
Step 6
Step 7
Laboratory/
File IND1
Phase 1
Phase 2
Phase 3
File NDA3 or
FDA Approval
Preclinical
application
BLA4 with
Testing
with FDA2
FDA
Assess
Obtain FDA
Determine
Evaluate
Determine
Inform the
Review
safety and
approval to
what dosage effective-
whether the
FDA of Phase
process/
biological
begin clinical is safe, how
ness, looks
new treatment
3 data which
approval
activity
testing in
treatment
for side
(or new use of
supports drug
Purpose
should be
effects
in the
humans after
a treatment) is
safety and
given
a better
laboratory
promising
better
alternative to
and in
results in
performance
current
animal
laboratory
over standard
standard
models
treatment
All
anticancer
drugs
4.4 years
8.6 years
1.4 years
14.4 years
(average
number
of years)
All drugs*
(average
3.8 years
10.4 years
1.5 years
15.7 years
number
of years)
1IND = Investigational New Drug
2FDA = Food and Drug Administration
3NDA = New Drug Application
4BLA= Biologics License Application
* Classified as "new chemical entities," which exclude diagnostic agents, vaccines, and other biological compounds.
Sources: DiMasi, J.A. (2001). New drug development in the United States 1963-1999. Clinical Pharmacology and Therapeutics May; 69(5);
Tufts Center for the Study of Drugs Development, Tufts University; adapted from Pharmaceutical Research and Manufacturers of America.
34
CANCER CLINICAL TRIALS: THE BASIC WORKBOOK
How FDA Makes Decisions
FDA uses independent advisory committees of professionals and
consumers from outside the agency for expert advice and guidance
in making decisions about drug approval. By law these committees
include both a patient representative and a consumer
representative.
As FDA looks at all the data submitted and the results of its own
review, it addresses two key questions:
1. Do the results of well-controlled studies provide substantial
evidence of effectiveness?
2. Do the results show the product is safe under the proposed
conditions for use? (In this context, "safe" means that potential
benefits have been determined to outweigh any risks.)
For an overview of the drug approval process from start
to finish, see FDA's book From Test Tube to Patient: New Drug
Development in the United States. This book tells the story of
new drug development in the United States and highlights
the consumer protection role of FDA. Call 1-888-INFO-FDA
or log on to http://www.fda.gov.
How Can the Public Influence the Drug
Development Process?
As shown on the chart on page 34, it takes 15 years, on average, for
an experimental drug to travel from the laboratory to U.S.
consumers. Often the longest part of the process is finding people
to participate in each trial phase. With increased public awareness
about clinical trials, more people may be willing to participate, and
more professionals may refer people into appropriate trials. This
awareness ultimately reduces the time it takes for researchers to
enroll participants in trials and complete them--and speeds the
movement of new drugs or treatments into standard care.
Advancing Cancer Care Through Clinical Trials
35
Advances in Care
Most of the ways we treat cancer today are based on the results
of earlier clinical trials. Recent clinical trials have resulted in
the following treatment benefits for people with chronic
myelogenous leukemia, cervical cancer, breast cancer, and
melanoma, for example.
Chronic Myelogenous Leukemia--A New
Treatment Option
In 2001, FDA approved Gleevec, offering a new treatment option
for many people with chronic myelogenous leukemia (CML). Until
then, bone marrow transplantation in the initial chronic phase of
the disease was the only known effective therapy for CML.
However, this is not an option for many people and the procedure
can cause serious side effects or death. Another option, treatment
with the drug interferon alfa, may produce remission (a decrease in
or disappearance of signs and symptoms of cancer) for many
people. But, if the drug is ineffective or people stop responding to
the drug, their prognosis is generally poor.
In three short-duration, early-phase clinical trials with Gleevec,
researchers found higher remission rates among people with CML
than they would have expected, and the people had few side
effects. Gleevec was designed to target an abnormal version of a
normal cellular protein present in nearly all people with CML. The
abnormal protein is much more active than the normal version and
is probably the cause of the disease. By blocking the abnormal
protein, called BCR-ABL, Gleevec kills the leukemia cells.
Gleevec represents a new class of cancer drugs, which target the
abnormal proteins that are fundamental to the cancer itself.
36
CANCER CLINICAL TRIALS: THE BASIC WORKBOOK
Cervical Cancer--Improved Survival Rates
For many years, the standard therapy for invasive cervical cancer
was surgery or radiation alone. The results of five large clinical
trials showed that women with invasive cervical cancer have
improved rates of survival when they receive a cisplatin-containing
chemotherapy regimen plus radiation therapy.
Breast Cancer
Less Extensive Surgery, Same Survival Rate
For many years, the standard therapy for all breast cancers was a
modified radical mastectomy with radiation or chemotherapy.
Clinical trials showed that for women with early-stage disease,
long-term survival after lumpectomy with axillary lymph node
dissection plus radiation therapy is similar to survival after
modified radical mastectomy.
Reduced Risk for Women at High Risk
For many years, there was no clear option for women seeking to
reduce their risk of breast cancer. A large study was designed to see
if the drug tamoxifen could reduce the risk of developing breast
cancer in women who were already at high risk for developing the
disease. The study found that those women who took the drug for
up to 5 years (an average of 4 years) had 49 percent fewer
diagnoses of invasive breast cancer than those who took a placebo.
Melanoma--Improved Survival Rates
According to the findings of a large, randomized clinical trial,
compared to low-dose interferon or no therapy, high-dose
interferon alfa-2b (Intron-A) significantly prolongs disease-free
survival for people at high risk for melanoma recurrence
(reappearance).
Advancing Cancer Care Through Clinical Trials
37
Finding Clinical Trial Results
To find trial results, look up the official name of the study
and search medical publication databases, such as PDQ
(www.cancer.gov) or PubMed from the National Library of
Medicine (www.nlm.nih.gov). If you have trouble locating
the study or searching for it, the research librarian at a
university or medical library may be able to help. It often
takes over a year for a scientific paper to be written,
submitted, reviewed, edited, and published. If an initial
search turns up nothing, try again after some time
has passed.
38
CANCER CLINICAL TRIALS: THE BASIC WORKBOOK
Exercise 2
How Clinical Trials Advance Cancer Care
Apply what you've learned about clinical trials to respond to the
following questions.
A. What happens to clinical trial results?
____________________________________________________________
____________________________________________________________
____________________________________________________________
B. Clinical trials answer research questions. How does this help
people?
____________________________________________________________
____________________________________________________________
____________________________________________________________
C. Sometimes researchers decide not to continue studying an agent
or to seek FDA approval. How do scientists decide when to
move from one clinical trial phase to the next?
____________________________________________________________
____________________________________________________________
____________________________________________________________
D. How can public awareness about clinical trials influence the
research process?
____________________________________________________________
____________________________________________________________
____________________________________________________________
Advancing Cancer Care Through Clinical Trials
39
Answers to Exercise 2
A. What happens to clinical trial results?
After a clinical trial is completed, researchers look carefully at
the collected data before making decisions about further testing
and what their findings mean.
After a phase 1 trial is completed, researchers decide whether:
· There are enough data to support further study with a
phase 2 trial
· Further research will be discontinued because the agent
was not safe
After a phase 2 trial is completed, researchers decide whether:
· There are enough data to support further study with a
phase 3 trial
· Further research will be discontinued because the agent was
not safe or effective
After a phase 3 trial is completed, the researchers must look
at the data and decide whether the results have medical
importance. When the analysis is complete, the researchers
will inform the medical community and the public of the
trial results.
In most cases, a trial's results are first reported in peer-reviewed
scientific journals. But if a trial's results have significant medical
importance for people with cancer, a public announcement may
be made while the formal report is being submitted to ensure
that people can quickly benefit from the new advance.
Particularly important results are likely to be featured by the
media and widely discussed at scientific meetings and by
advocacy groups.
Once an intervention is proven safe and effective in a clinical
trial, it may become the new standard of practice for physicians.
40
CANCER CLINICAL TRIALS: THE BASIC WORKBOOK
B. Clinical trials answer research questions. How does this
help people?
Clinical trials are initiated because we don't yet know whether
one treatment is better than another. Most of today's treatments
for cancer are based on the results of earlier clinical trials.
Clinical trials have also resulted in many new treatments and
prevention options for cancer care.
C. Sometimes researchers decide not to continue studying an
agent or to seek FDA approval. How do scientists decide when
to move from one clinical trial phase to the next?
Clear "yes" or "no" answers are rare in science. It is particularly
difficult to decide what is worth pursuing and what is not when
the data are unclear. Researchers make decisions based on
scientific evidence, which is why research moves in such slow
and careful steps. Even if some participants in a clinical trial
have a positive response to the new treatment, researchers must
look at the experience of all participants when deciding whether
to continue trials. For example, more people treated with the
standard therapy may have better results than those treated with
the experimental treatment.
D. How can public awareness about clinical trials influence the
research process?
With increased public awareness about clinical trials, more
people may be willing to participate. With a greater pool of
participants, researchers can complete the trial more quickly and
speed the development of new treatments.
E. How do clincial trials differ from unsound or alternative
treatments?
Clinical trials sponsored by NCI and other reputable agencies
evaluate new treatments for safety and possible benefit via IRB-
approved protocols.
Advancing Cancer Care Through Clinical Trials
41
Complementary and alternative medicine, as defined by the
National Center for Complementary and Alternative Medicine
(NCCAM), is a group of diverse medical and health care
systems, practices, and products that are not presently
considered to be part of conventional medicine. The list of
complementary and alternative medicine practices changes
continually, as those therapies that are proven to be safe and
effective become adopted into conventional health care and new
approaches to health care emerge.
· Neither new treatments tested in clinical trials nor untested
alternative treatments are known to be effective when they
are initially given.
· Alternative treatements that have not been carefully studied
may be harmful.
· Many CAM practices are now being evaluated within
protocols for their effectiveness and safety. For more
information, visit http://nccam.nih.gov.
· Other terms for CAM include unconventional,
non-conventional, unproven, and irregular medicine
or health care.
42
CANCER CLINICAL TRIALS: THE BASIC WORKBOOK
3.
Participant
Clinical
Trials
Protection
in
3
Participant Protection in
Clinical Trials
Overview
Many people think that participant rights are not protected in clinical
trials because of past abuses of research participants. Today, Federal
regulations help ensure that clinical trials are run in an ethical manner.
Participant rights and safety are protected through:
· Informed consent, a process through which potential participants learn
the purpose, the risks, and the benefits of a clinical trial before deciding
whether to participate. This process continues throughout the study.
· Two review panels, which approve a clinical trial protocol before it
begins:
A scientific review panel
The institutional review board (IRB) that oversees clinical research at
the local participating institution
· Monitoring, which continues during the trial, by:
IRBs, which monitor participant safety
Data and safety monitoring boards (DSMBs) for phase 3 trials, which
perform periodic reviews of the conduct of the clinical trials and
participant safety
Required reports to Federal agencies, which oversee the conduct of
the trial
Learning Objectives
By reading this section and completing the exercise, you will be able to:
· Review key historical events regarding participant protection
· Describe how participants are protected through the informed
consent process
· Explain how review boards and panels protect participants
· Demonstrate familiarity with Government regulations and agencies
43
Participant Protection in Clinical Trials
History of Participant Protection
Although we now have strong safeguards for protecting those
who participate in research, these protections have resulted from
notorious abuses of human rights in the past. The first formal
statement of protection for individuals in research emerged from
the Nuremberg trials in Germany, where Nazi scientists and
physicians who had conducted experiments on World War II
concentration camp victims were convicted. The Nuremberg Code
outlined broad concepts for the protection of human subjects and
forms the basis of today's international code of ethics for the
conduct of research.
In the United States, several controversial research studies
highlighted the critical need for protection for those participating
in clinical trials. None of these studies sought to inform the
participants about the research or gain their consent.
From 1932 to 1972, the infamous Tuskegee syphilis study followed
low-income African American men with syphilis but did not treat
them. During the study, the men were offered free medical care
and were told that they would be treated for "bad blood."
In the 1960s, two other research studies received major public
attention. The first was a series of experiments with mentally
retarded children; another involved debilitated elderly
participants.
In response to these tragedies, regulations and policies were
developed to ensure that people are told about the benefits, risks,
and purpose of research for which they volunteer.
In 1976, the National Commission for the Protection of Human
Subjects of Biomedical and Behavioral Research developed three
basic principles governing research involving human subjects that
were published in the Belmont Report. These principles, which
today form the basis for human subject protection regulations in
the United States are:
· Respect for persons--recognition of personal dignity and
autonomy of individuals, and special protection of persons with
diminished autonomy
44
CANCER CLINICAL TRIALS: THE BASIC WORKBOOK
· Beneficence--obligation to protect persons from harm by
maximizing unanticipated benefits and minimizing possible
risk of harm
· Justice--fairness in the distribution of research benefits
and burdens
The Informed Consent Process
Informed consent is a critical part of ensuring participant safety in
research. Informed consent is an ongoing process during which
potential participants learn important information about a clinical
trial. This information helps them decide whether to participate.
The research team, which is made up of doctors and nurses, first
explains the trial to potential participants in understandable
language. The team explains the trial's:
· Purpose
· Procedures
· Risks and benefits
· Participant rights, including the rights to:
Make an independent decision about participating
Leave the study at any time without jeopardizing
future treatment
Participant Protection in Clinical Trials
45
Before agreeing to take part in a trial, people have the right to:
· Learn about all their treatment options
· Learn all that is involved in the trial--including all details about
treatment, tests, and possible risks and benefits
· Discuss the trial with the principal investigator and other
members of the research team
· Both hear and read the information in language they can
understand
Informed Consent Form
After discussing all aspects of the study with a potential participant,
the team gives the person an informed consent form to read. The
form includes written details about the information that was
discussed and also describes the confidentiality of the participant's
records. If a person agrees to take part in the study, he or she signs
the form.
Although informed consent documents can vary in their length
and complexity, they should all contain information on:*
· The clinical trial's nature, purpose, and duration; the procedures
to be followed; and which procedures are experimental
· Reasonable, foreseeable risks and discomforts
· Benefits to the participants and to others
· Alternative procedures or treatments
· Confidentiality of records
· Procedures if the trial involves more than minimal risk
(e.g., compensation, availability of medical treatment)
· Contact for questions
· Voluntary participation--that there will be no loss of benefits
on withdrawal and that participants may stop participating
at any time
All Government-funded trials must contain this information
by law.
* These informed consent requirements are listed in Title 45 CFR Part 46,
Sub part A.
46
CANCER CLINICAL TRIALS: THE BASIC WORKBOOK
Informed Consent Forms: Making Them Easy
to Understand
The informed consent process can be effective only if
potential participants understand the information given to
them. In recent years, both participants and investigators
have voiced concerns that informed consent documents for
clinical trials were becoming too long, complicated, and
difficult to understand.
NCI has issued recommendations designed to help research
institutions and clinical centers write user-friendly informed
consent documents. Sample templates can be found online
in both English and Spanish in the clinical trials section of
www.cancer.gov.
An Ongoing Process
The informed consent process does not end once the form is
signed. If new benefits, risks, or side effects are discovered during
a trial, the researchers must inform study participants. In addition,
participants are encouraged to ask questions at any time about
what is happening during the trial. This information helps
participants make educated decisions about whether to continue
participating in a clinical trial.
Pediatric Assent to Participate in Trials
Children and adolescents are not deemed capable of giving true
informed consent, so they are asked for their assent to (or dissent
from) participation in a clinical trial. The trial must be explained in
age-appropriate language or using visual aids. Parents or
guardians are asked to give informed permission for their child to
participate in a trial. Assent must be obtained from all children and
young people over age 7 unless:
· The child is found to be incapable of assenting
Participant Protection in Clinical Trials
47
· The clinical trial offers a treatment or procedure that "holds out
a prospect of direct benefit that is important to the health or
well-being of the child and is available only in the context of
research" (in other words, if the trial offers a treatment that is
thought to be better than those currently available or if it offers
the only alternative to those available).
Even in these cases, permission from the parent or guardian is
required. For more information, see the clinical trials section of
www.cancer.gov.
Weighing Decisions About Participating
People thinking about taking part in a trial should ask researchers
the following questions to help with their decision-making:
· Why is this trial taking place?
· Why do the doctors who designed the trial believe that the
treatment being studied may be better than the one being used
now? Why may it not be any better?
· How long will I be in the trial?
· What kinds of tests and treatments are involved?
· What are the possible side effects or risks of the new treatment?
· What are the possible benefits?
· How could the trial affect my daily life?
· Will I have to travel long distances?
· Will I have to pay for any of the treatments or tests?
· Does the trial include long-term followup care?
· What are my other treatment choices, including standard
treatments?
· How does the treatment I would receive in this trial compare
with the other treatment choices in terms of possible outcomes,
possible side effects, time involved, costs to me, and quality
of my life?
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CANCER CLINICAL TRIALS: THE BASIC WORKBOOK
Review Committees
Most clinical trials are subject to different types of review
that are designed to protect all participants. Clinical trials that
are sponsored by NCI--whether funded by a grant, run by a
cooperative group, or run through a cancer center--are reviewed
through different types of panels, including experts who review
the scientific and technical merit of the proposed research. Many
other clinical trial sponsors, such as pharmaceutical companies,
also seek expert advice on the scientific and technical merit of
their trial protocols. In addition, all federally-funded clinical trials
must be reviewed by groups called institutional review boards
(IRBs).
Institutional Review Boards (IRBs)
IRBs are made up of people who are qualified to evaluate new and
ongoing clinical trials on the basis of scientific, legal, and ethical
merit. The board members determine whether the risks involved
in a trial are reasonable with respect to the potential benefits. IRBs
also monitor the ongoing progress of trials from beginning to end.
Federal regulations require that each IRB be made up of at least
five people; one member must be from outside the institution
conducting the trial. IRBs are usually made up of a mix of medical
specialists and lay members of the community, and many include
members from diverse occupations and backgrounds. In most
cases, IRBs are located where the trial is to take place. Many
institutions that carry out clinical trials have their own IRBs.
Federal law requires IRB approval for clinical trials that are:
· Federally funded
· Evaluating a new drug, agent, or medical device subject to
FDA regulation
A number of institutions require that all clinical trials, regardless
of funding, be approved and reviewed by local IRBs. Potential
participants considering a clinical trial should ask if it has been
approved by an IRB.
49
Participant Protection in Clinical Trials
During the Trial: IRB Monitoring
If the IRB grants approval for a trial, it also must decide how
frequently the trial should be reviewed once it is underway.
Frequency is usually determined according to the degree of risk
the trial involves.
At least once a year, the IRB must review a progress report
provided by the clinical researcher in charge of the trial. The
report features information about how many people are enrolled
and how many have withdrawn, a description of participants'
experiences, including benefits and adverse effects, and the
progress to date.
Based on this information, the IRB decides whether the trial
should continue as described in the original research plan, and,
if not, what changes need to be made. An IRB can decide to stop
a clinical trial at any time if the researcher is not following
requirements or if the trial appears to be causing unexpected
harm to participants.
CANCER CLINICAL TRIALS: THE BASIC WORKBOOK
50
Data and Safety Monitoring Boards (DSMBs)
For phase 3 trials, DSMBs are appointed to help ensure
participants' safety. A DSMB may also be appropriate and
necessary for certain phase 1 and 2 clinical trials.
The DSMB is an independent committee made up of statisticians,
physicians, and other expert scientists.
The data and safety monitoring board must:
· Ensure that any risks associated with participation are
minimized to the extent practical and possible
· Avoid exposing participants to excessive risk
· Ensure the integrity of data
· Stop a trial if safety concerns arise or as soon as its objectives
have been met
DSMBs also monitor all trial results. If early results show clear
advantages of a new drug, the sponsor of the study may choose to
end the trial early and establish a protocol allowing wider use of
the drug before final approval for marketing. If a drug is shown to
have a strongly negative effect, the trial is stopped immediately.
In 1995, a trial of the drug tamoxifen (tamoxifen citrate) showed
that the drug dramatically reduced the short-term risk of breast
cancer. The DSMB and the researchers assessed the data and
halted the trial so that the results could be made widely available
and all women in the trial could have the opportunity to take the
drug. Researchers submitted a new application to FDA, which
expedited its review status. The new application was the basis for
FDA approval of tamoxifen for reducing breast cancer risk.
51
Participant Protection in Clinical Trials
Government Regulations and Agencies
All federally sponsored trials are subject to two sets of similar
regulations enforced by HHS's Office for Human Research
Protections (OHRP) and the FDA to ensure the protection of
people who participate. If a trial is supported by the
Government and it involves an FDA-regulated drug or device,
then it is subject to both sets of regulations.
People thinking about taking part in a clinical trial should
ask researchers the following questions to be sure a trial is
reputable:
· Who has reviewed and approved it?
· What are the credentials of its researchers and personnel?
· What information or results is it based on?
· How are the study data and participant safety
being monitored?
· What happens with the results of the trial?
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CANCER CLINICAL TRIALS: THE BASIC WORKBOOK
OHRP Regulations
OHRP protects those participating in research and provides
leadership for all Federal agencies that carry out research
involving people.
The OHRP enforces important regulations for participant
protection in clinical trials called the Common Rule.4 These
regulations set standards regarding the:
· Informed consent process
· Formation and function of IRBs
· Involvement of prisoners, children, and other vulnerable
groups in research
FDA Regulations
FDA enforces another set of regulations on participant protection
in clinical trials.5 They concern any clinical trial that involves an
FDA-regulated drug or device, regardless of whether the trial
receives Federal funding. FDA periodically inspects IRB records
and operations to certify the adequacy of approvals, participant
safeguards, and conduct of business.
Strengthening Government Oversight
Although breaches in participant protection seldom occur,
recent discoveries of inadequate participant protection have
taken place. Beginning in 2000, HHS began to take additional
steps to:
· Strengthen regulations concerning participant safety
· Strengthen Government oversight of medical research
· Reinforce clinical researchers' responsibilities to follow
Federal research guidelines
4 Title 45 CFR Part 46, Subpart A
5 Title 21 CFR Part 50, 56
53
Participant Protection in Clinical Trials
Exercise 3
Participant Protection
How would you respond to the following questions?
A. Aren't people who join clinical trials just "guinea pigs" for
research without protections?
____________________________________________________________
____________________________________________________________
____________________________________________________________
B. Can a person be put on a clinical trial without his or her
knowledge?
____________________________________________________________
____________________________________________________________
____________________________________________________________
C. If someone is in a phase 3 trial and it is found that there
is a clear advantage for the participants in the other group,
what happens?
____________________________________________________________
____________________________________________________________
____________________________________________________________
D. What happens if someone wants to stop participating in a trial?
____________________________________________________________
____________________________________________________________
____________________________________________________________
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CANCER CLINICAL TRIALS: THE BASIC WORKBOOK
Answers to Exercise 3
A. Aren't people who join clinical trials just "guinea pigs"
for research?
Many safeguards are in place for people who join cancer trials.
All clinical trial participants go through the informed consent
process. Informed consent is an ongoing process in which
people learn important information about a clinical trial. This
information helps them decide whether to participate.
The trial is also monitored by an institutional review board
(IRB) and, if the study is a phase 3 clinical trial, by a data and
safety monitoring board (DSMB).
In response to breaches in protection that have been recently
identified and reported in the media, in 2000, the U.S.
Department of Health and Human Services took additional
steps to strengthen Government oversight of medical research
and to reinforce clinical researchers' responsibility to follow
guidelines.
B. Can a person be put in a clinical trial without his or
her knowledge?
No. The researchers running the trial are required by law to
present and explain the study as part of the informed consent
process. This process includes:
· Signing an informed consent document (so that people know
they are entering a study)
· Discussing with the research team what the trial entails
· Understanding the potential risks and benefits of
participating
Although reputable researchers do not fool people or sign them
up against their will, sometimes people have difficulty
understanding the information they need to know about a trial
before agreeing to join. For many people, it is important to ask a
friend or family member to come with them to be sure that all
important questions are raised. Taking notes or using a tape
recorder can also help.
55
Participant Protection in Clinical Trials
C. If someone is in a phase 3 trial and it is found that there
is a clear advantage for the participants in the other group,
what happens?
The DSMB would report the information to the study sponsor.
If early results show that there is a clear advantage for one of
the groups, the sponsor may choose to end the trial early and
establish a protocol allowing wider use of the drug before final
approval for marketing.
D. What happens if someone wants to stop participating
in a trial?
Under the informed consent process, a person has the right
to discontinue their participation in a trial at any time. A
participant's decision to leave a clinical trial does not jeopardize
future treatment, and the participant will have the chance to
discuss other treatments, or care with a doctor from the trial.
The person may be referred back to his or her primary doctor
for standard care.
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CANCER CLINICAL TRIALS: THE BASIC WORKBOOK
4.
Barriers
Participation
to
Clinical
Trial
4
Barriers to Clinical Trial
Participation
Overview
Many people with cancer do not participate in clinical trials.
Common barriers to participating include lack of awareness; lack
of access; fear, distrust, or suspicion of research; and financial and
personal concerns.
Learning Objectives
By reading this section and completing the exercise, you will
be able to:
· Identify some barriers people face when considering
participation in clinical trials
· Describe some of the costs associated with clinical trials
Barriers to Clinical Trial Participation
57
Participation in Clinical Trials
"Only 3 percent of adult cancer patients in the United States
participate in clinical trials--far fewer than the number needed
to answer the most pressing cancer questions quickly."*
Reflecting on the quote above, why do you think more people
don't participate in clinical trials?
Compare your answer to the information in this section.
* Excerpted from an American Society of Clinical Oncology news release, 1999.
Barriers for Health Care Professionals
· Lack of awareness of appropriate clinical trials. Physicians are
not always aware of available clinical trials. Some may not be
aware of the local resources, or some may assume that none
would be appropriate for their patients.
· Unwillingness to "lose control" of a person's care. Most
doctors feel that the relationship they have with their patients is
very important. They want what is best for the patient, and if
the person must be referred elsewhere to participate in a trial,
doctors fear they may lose control of the person's care.
· Belief that standard therapy is best. Many health care
providers may not adequately understand how clinical trials are
conducted or their importance. Some believe that the treatment
in clinical trials is not as good as the standard treatment. They
also might be uncomfortable admitting that there is uncertainty
about which treatment is best in a phase 3 clinical trial.
· Belief that referring to and/or participating in a clinical trial
adds an administrative burden. The length and details of most
research protocols may deter providers from participating in
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CANCER CLINICAL TRIALS: THE BASIC WORKBOOK
clinical trials. The possibility of incurring additional costs and
expenses that might be inadequately reimbursed is a deterrent
for many.
· Concerns about the person's care or how the person will react
to the suggestion of clinical trial participation.
Barriers for the General Population
· Lack of awareness of clinical trials. Research has consistently
shown that most people with cancer are not aware of the option
to participate in clinical trials.
· Lack of access to trials. The reality or the perception that there
are no trials nearby deters many potential participants. In
addition, seeking care at a distant trial site presents time and
travel barriers.
· Fear, distrust, or suspicions of research. For many people, the
loss of control (not choosing their treatment) that comes with
entering a randomized trial is too great. Many also fear being
treated like "guinea pigs" or being "experimented upon," as
well as not receiving treatment for their cancer. People may
have a general lack of trust in the medical profession based on
past negative experiences or the knowledge of historical abuses
of research participants.
· Practical or personal obstacles. Costs of being away from work
and family may be deterrents for some people. Others may not
wish to leave the care of their own physician. People from certain
racial or ethnic groups or who are medically underserved may
feel that care within a trial will not be sensitive to their needs.
Others may feel that recruitment strategies are not sensitive to
their needs. Still others may believe that standard care is better
than the treatment available in a trial.
· Insurance or cost problems. Another deterrent is the fear of
being denied insurance coverage for participation in a clinical
trial. If a person is uninsured, the cost of trial participation is
an issue.
· Unwillingness to go against personal physician's wishes.
Barriers to Clinical Trial Participation
59
A Survey on Clinical Trial Barriers
A survey of almost 6,000 people with cancer conducted in
2000 took a look at why so few adults participate in cancer
clinical trials. Some of the highlights included:
· About 85 percent of people with cancer were either
unaware or unsure that participation in clinical trials was
an option, though about 75 percent of these people said
they would have been willing to enroll had they known it
was possible.
· Of those who were aware of the clinical trial option, most
declined to participate because they believed common
myths about clinical trials. They either thought that:
The medical treatment they would receive in a clinical
trial would be less effective than standard care
They might get a placebo
They would be treated like a "guinea pig"
Their insurance company would not cover costs
· People who received treatment through a clinical trial
found it to be a very positive experience:
Ninety-seven percent said they were treated with
dignity and respect and that the quality of care they
received was "excellent" or "good"
Eighty-six percent said their treatment was covered
by insurance
Source: Harris Interactive. (2001). Health Care News, 1(3). [Poll]. Available from
http://harrisinteractive.com/about/healthnews/HI_HealthCareNews2001Vol_iss3.pdf
Supported by the Coalition of National Cancer Cooperative Groups, the Cancer
Research Foundation of America, the Cancer Leadership Council, and the
Oncology Nursing Society.
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CANCER CLINICAL TRIALS: THE BASIC WORKBOOK
Barriers for Racially or Ethnically
Diverse Populations
Additional barriers exist for people who are from certain
ethnic/racial backgrounds or who are medically underserved.
The following list is not meant to be a comprehensive overview
of all barriers associated with clinical trials, and what is outlined
should not be generalized to all diverse populations.
More information about these groups, as well as ideas for
addressing these barriers, can be found in Cancer Clinical Trials:
A Resource Guide for Outreach, Education, and Advocacy.
Diverse U.S. Populations: Definitions
Diverse populations include minority ethnic and racial groups
designated by the U.S. Government, such as:
· American Indian or Alaska Native
· Asian American
· Black or African American
· Hispanic or Latin American
· Native Hawaiian or other Pacific Islander
Ethnically diverse populations are growing rapidly; in the 2000
Census, about 25 percent of the U.S. population reported their
race as something other than White.
NCI's working definition of diverse populations also includes
medically underserved populations. Medically underserved
populations are those that lack easy or any access to, or don't
make use of, high-quality cancer prevention, screening and
early detection, treatment, or rehabilitation services. These
may include people of any racial or ethnic group who live in
rural areas or who have low income or literacy levels. Medically
underserved groups are generally characterized as experiencing
higher cancer mortality rates and insufficient participation rates
in cancer control programs.
Barriers to Clinical Trial Participation
61
Specific Barriers
· Long-standing fear, apprehension, and skepticism exist among
some minority populations about medical research because of
abuses that have happened in the past (e.g., the legacy of the
Tuskegee syphilis study). Among these populations, there is
often widespread fear and distrust of the medical care system as
a result of discrimination, indifference, and disrespect. Many feel
that they do not want to give up rights or lose power to be
"experimented on." Others may be skeptical about the quality of
care that would be provided in a clinical trial. Some may find
that trial recruitment strategies are not sensitive to their needs.
· Doctors may not mention clinical trials as an option for cancer
care. As noted above, many physicians do not refer people to
clinical trials. However, some physicians may avoid suggesting a
clinical trial to people who belong to racial or ethnic minorities
out of concern that they would seem insensitive. Moreover,
some physicians may inadvertently discriminate against older
people or those from certain ethnic or cultural backgrounds.
· People from various cultural or ethnic backgrounds may hold
values and beliefs that may be different than those of Western
medicine. Many people have a cultural belief that Western
medicine cannot address their health concerns. Different ethnic
and cultural views of health and disease (e.g., fatalism, family
decisions about treatment, use of "traditional healers," prayer,
herbal medicines, or use of complementary/alternative health
practices) may make clinical trials a less attractive treatment
option. For prevention trials, many may feel that the risk of a
potential disease and its consequences may be less important
than meeting daily needs.
· Language or literacy barriers may make it difficult for some
people to understand and consider participating in clinical
trials. The complexity of forms, including informed consent
documents, may also be a barrier to those considering
participation in a clinical trial. Translation can also be
difficult if the person translating information has not had
specialized training.
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CANCER CLINICAL TRIALS: THE BASIC WORKBOOK
· Additional access problems confront many people. Depending
on where they live or their access to transportation, people may
have difficulty getting back and forth from a clinical trial site.
Those with low incomes may find it difficult to take time off
work or find appropriate childcare. Other barriers, such as a lack
of health insurance or a source of health care, clearly present
difficulties in accessing trials.
For solutions to barriers for racially and ethnically diverse
populations, see NCI's Cancer Clinical Trials: A Resource Guide for
Outreach, Education, and Advocacy.
Cost Barriers
The costs associated with clinical trials can be a barrier for many
professionals and the public. Physicians are often concerned about
reimbursement related to the expenses of either caring for people
enrolled in trials or offering trials within their practice. Potential
trial participants often fear that their insurance company will not
cover their participation in a clinical trial. Those who are uninsured
will need to know how their participation in a trial will be covered.
There are two types of costs associated with clinical trials--
participant care costs and research costs.
Participant Care Costs
Participant care costs include:
· Usual care costs, such as doctor visits, hospital stays, clinical
laboratory tests, and x-rays, occur whether someone is
participating in a trial or receiving standard treatment.
· Extra care costs are those associated with clinical trial
participation, such as additional tests that may be required.
These costs may or may not be covered by a participant's
health plan.
Research Costs
Research costs include costs associated with conducting the trial,
such as:
· Data collection and management
· Research physician and nurse time
Barriers to Clinical Trial Participation
63
· Analysis of results
· Clinical laboratory tests and x-rays
· Cost of the agent being tested
Most of the time, research costs are covered by the sponsoring
organization or by a pharmaceutical company.
Health Plan Coverage--Treatment Trials
Health insurance companies and managed care providers do not
always cover all participant care costs in a study. What they cover
varies by plan and by trial. In general, the most important factor in
whether a treatment is covered is a health plan's judgment as to
whether the therapy is "established" or "investigational."
Health plans often claim that paying for clinical trials will be too
costly. However, several studies in 1999 and 2000 found that
participant care costs for clinical trials are not much higher than
costs for people who are not enrolled in trials.*
Health Plan Coverage--Chemoprevention Trials
Although participants receive preventive agents free of charge,
coverage for required medical tests is often at issue. For example,
pre-entry tests are paid for by the trial at some (but not all)
institutions. However, the individual may need a retest if the
pre-entry test shows any suspicious findings, and the retest costs
may not be covered. If a person belongs to a managed care
organization, coverage for the retest will be denied if the primary
care gatekeeper has not authorized it, regardless of other
considerations. In addition, some trials require certain preventive
screening tests annually, such as mammograms, but not all
insurers cover preventive screening tests for all participants.
*Bennett, C. L., et al. (2000). Evaluating the financial impact of clinical trials in oncology:
Results from a pilot study from the Association of American Cancer Institutes/
Northwestern University Clinical Trials Costs and Charges Project. Journal of Clinical
Oncology, 18, 2805-2810. Fireman, B., et al. (2000). Cost of care for patients in cancer
clinical trials. Journal of the National Cancer Insitute, 92, 136-142. Wagner, J. L., et al. (1999).
Incremental costs of enrolling cancer patients in clinical trials: A population-based study.
Journal of the National Cancer Institute, 91, 847-853.
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CANCER CLINICAL TRIALS: THE BASIC WORKBOOK
In considering options, interested persons should ask trial
personnel what the experience to date has been in the trial they
are considering. They should ask specifically about the type of
insurance involved. People may even be able to get examples of
how their employer or managed care plan has responded.
Potential participants should call NCI's Cancer Information
Service at 1-800-4-CANCER or visit the clinical trials section of
www.cancer.gov, which features tips and information about
organizations to help with clinical trials coverage.
People considering a trial should work with a doctor or social
worker to get specific information from the facility running
the trial. They should ask questions such as:
· What parts of treatment, if any, does the trial provide free
of charge?
· What parts of treatment must be paid for by me or by my
health plan?
· What is the situation for people who have no health
insurance?
· Will my total charges be higher as a clinical trial participant
than if I opt for standard care?
· How successful are you in getting insurers to cover the
patient care costs in the study I am considering?
· Are there other resources or organizations you can
recommend to help me meet the fees or to provide services
such as free transportation?
Legislation and Policies
Despite interest at the Federal level, as of 2001, no legislation has
been passed to require private third-party payers to uniformly
cover all clinical trial costs. However, there have been several
important developments at the Federal level regarding clinical trial
coverage:
· Medicare reimburses for all routine participant care costs for its
beneficiaries participating in clinical trials.
Barriers to Clinical Trial Participation
65
· Beneficiaries of TRICARE, the Department of Defense's health
program, are covered for NCI-sponsored phase 2 and phase 3
prevention and treatment clinical trials.
· Department of Veterans Affairs (VA) allows eligible veterans to
participate in a broad range of NCI clinical trials across the
country. The agreement covers all phases and types of NCI-
sponsored trials.
Many states have also passed legislation or developed policies that
require health plans to cover clinical trial costs. For an updated
legislation listing, see the clinical trials section of www.cancer.gov.
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CANCER CLINICAL TRIALS: THE BASIC WORKBOOK
Exercise 4
Barriers to Participation
A. Do doctors discuss clinical trials as options for their patients?
____________________________________________________________
____________________________________________________________
____________________________________________________________
B. If a doctor cannot or will not refer a person to a clinical trial, can
the person or family make the call directly?
____________________________________________________________
____________________________________________________________
____________________________________________________________
C. Is it more expensive to participate in a clinical trial compared to
standard treatment? Are clinical trials covered by insurance?
____________________________________________________________
____________________________________________________________
____________________________________________________________
D. Are chemoprevention trials covered by insurance? If so, will
participants compromise their coverage by entering trials for
those at "high risk" for cancer?
____________________________________________________________
____________________________________________________________
____________________________________________________________
Barriers to Clinical Trial Participation
67
Answers to Exercise 4
A. Do doctors discuss clinical trials as options for their patients?
Some health professionals may not discuss clinical trials with their
patients for the following reasons:
· They are not aware of clinical trials
· They are unwillingly to lose control of a person's care
· They believe that standard therapy is best
· They cannot find a trial which is compatible with the person's
clinical situation
No matter what the situation, people with cancer have the right to
consider all possible treatment options before deciding which
treatment option is right for them.
B. If a doctor cannot or will not refer a person to a clinical trial,
can the person or family make the call themselves?
Decisions about eligibility for a trial can be complicated and
require very specific medical information on a person's
condition. Therefore,
· It is preferable to have the contact made by a health care
professional familiar with the case
· Participants calling researchers directly may not have all the
information needed to make eligibility decisions
· If a physician is unwilling to make contact with clinical trial
investigators, the best alternative may be to request a referral to
another physician
C. Is it more expensive to participate in a clinical trial compared
to standard treatment? Are clinical trials covered by insurance?
There are two kinds of costs associated with clinical trials:
· Patient care costs
May be covered by a person's health plan
Include usual care cost items like doctor visits, hospital stays,
clinical laboratory tests, and x-rays, which occur whether
someone is participating in a trial or receiving standard
treatment.
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CANCER CLINICAL TRIALS: THE BASIC WORKBOOK
· Research costs
Usually covered by the trial's sponsor
Include extra care costs associated with clinical trial
participation such as additional tests
· Some health plans cover the costs associated with clinical trial
participation; other companies will not reimburse for
"experimental therapies"
· Decisions are usually made on a case-by-case basis
· Some clinical trial sponsors work with health plans to get
reimbursement
· People interested in clinical trial participation should ask the
trial team what their experience with reimbursement for this
trial has been
· Clinical trial participants may also contact NCI's Cancer
Information Service at 1-800-4-CANCER or visit the clinical trials
section of www.cancer.gov for information on organizations that
may help with clinical trial coverage
D. Are chemoprevention trials covered by insurance? If so, will
participants compromise their coverage by entering trials for
those at "high risk" for cancer?
There is no comprehensive data on insurance problems
related to entering a chemoprevention trial, but some issues
have been reported:
· Participants receive prevention agents free of charge
· Coverage for medical tests can be an issue
· Some institutions will pay for the initial tests, but not all
· If a re-test is needed it may not be covered, especially if it has
not been authorized by a primary care gatekeeper
· Prevention trials may require more frequent screening exams
(such as a mammogram or colonoscopy), and insurers may not
want to cover a test given more frequently than their guidelines
require (for example every six months versus every year)
· Many insurance companies have policies on "pre-existing
conditions," so entering a trial for those at "high risk" could
make it harder or more expensive to get health and life
insurance in the future
Barriers to Clinical Trial Participation
69
· Some states have laws about pre-existing conditions and
Federal law forbids companies to deny health care to people
with pre-existing conditions. It remains unclear how insurers
will handle "high risk" conditions.
· Participants may contact NCI's Cancer Information Service at
1-800-4-CANCER or visit the clinical trials section of
www.cancer.gov for information on organizations that help
with clinical trials coverage and insurance questions.
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CANCER CLINICAL TRIALS: THE BASIC WORKBOOK
5.
Finding
Clinical
Trials
5
Finding Clinical Trials
Overview
Cooperative groups, cancer centers, hospitals, and local physician
offices conduct clinical trials. NCI, pharmaceutical companies, and
other groups may fund them. They take place in diverse locations
all over the country.
When locating clinical trials, it is important to remember that no
single resource, including those from NCI, lists every cancer
clinical trial.
Learning Objectives
By reading this section and completing the exercises, you will
be able to:
· Identify who sponsors cancer clinical trials
· Describe the role of NCI in how clinical trials are conducted
at sites throughout the United States
· Describe the process by which people can be referred to
clinical trials
· Explain ways to locate clinical trials
Finding Clinical Trials
71
Organizations That Sponsor Clinical Trials
NCI, pharmaceutical companies, medical institutions, and other
organizations sponsor clinical trials. NCI often partners with
pharmaceutical companies to develop new agents.
Regardless of sponsor, clinical trials take place at universities, large
medical centers, small hospitals, and doctors' offices. Individual
physicians at cancer centers and other medical institutions can also
sponsor clinical trials themselves.
NCI-Sponsored Clinical Trials
NCI sponsors many clinical trials around the country that are
conducted through four different programs:
1. Clinical Trials Cooperative Group Program
2. Community Clinical Oncology Program (CCOP)
and the Minority-Based Community Clinical Oncology
Program (MBCCOP)
3. Cancer Centers Program
4. Clinical Grants Program
All NCI-sponsored trials must meet all FDA and Office for Human
Research Protections (OHRP) regulations for participant protection
in clinical trials.
Clinical Trials Cooperative Group Program
Clinical trials are often conducted through NCI cooperative
clinical trial groups, which are networks of institutions that jointly
carry out large clinical trials following the same protocols.
Members of these groups include:
· University hospitals
· Cancer centers
· Community physicians and community hospitals
Cooperative groups develop and conduct new clinical trials that
follow national priorities for cancer research. They conduct phase
3 trials as well as phase 2 trials.
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CANCER CLINICAL TRIALS: THE BASIC WORKBOOK
Some of the groups are categorized by type of cancer, others by
type of treatment, and at least one by age of participants. Other
groups are regional or focus on several cancer types.
There are 12 groups in the Clinical Trials Cooperative Group Program:
1. American College of Surgeons Oncology Group (ACOSOG)
2. Cancer and Acute Leukemia Group B (CALGB)
3. Children's Cancer Study Group (CCSG)
4. Eastern Cooperative Oncology Group (ECOG)
5. Gynecologic Oncology Group (GOG)
6. Intergroup Rhabdomyosarcoma Study Group (IRSG)
7. National Surgical Adjuvant Breast and Bowel Project (NSABP)
8. National Wilms Tumor Study Group (NWTSG)
9. North Central Cancer Treatment Group (NCCTG)
10. Pediatric Oncology Group (POG)
11. Radiation Therapy Oncology Group (RTOG)
12. Southwest Oncology Group (SWOG)
For more information about the Cooperative Group program, see
http://ctep.info.nih.gov.
Community Clinical Oncology Programs (CCOPs) and Minority-Based
CCOPs (MBCCOPs)
These programs allow community physicians to work with
scientists conducting NCI-supported clinical trials. Participation in
the CCOP benefits lay people and health professionals in the
community as well as scientists in research centers.
The MBCCOP provides members of ethnic and racial minorities
with access to state-of-the-art cancer treatment, prevention, and
control technology.
Cancer Centers Program
NCI cancer centers conduct clinical trials under an NCI-approved
protocol review and surveillance mechanism.
The Cancer Centers Program consists of more than 50
NCI-designated cancer centers involved in many different cancer
research efforts. Cancer centers also participate in at least one
cooperative group.
Finding Clinical Trials
73
Clinical Grants Program
Many clinical trial protocols are carried out under the direct
support of an NCI peer-reviewed grant.
Industry-Sponsored Trials
Pharmaceutical and biotech companies conduct their own trials,
both locally and nationally. They may have as partners
universities, hospitals, NCI, or local doctors. These trials are
subject to the companies' own review panels and to an IRB, which
may be local or national in scope.
Referrals to Clinical Trials
Once someone is diagnosed with cancer, the health care provider
may suggest several possible treatment options, one of which may
be a clinical trial. Similarly, health care providers may offer people
at high risk for cancer several options for prevention, including a
clinical trial. If a person finds that his or her physician does not
participate in clinical trials, the person can request a referral to a
physician who does.
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CANCER CLINICAL TRIALS: THE BASIC WORKBOOK
Decisions concerning eligibility for clinical trials are often
complicated, requiring very specific medical information about the
person's condition and previous treatment. For that reason, it is
always preferable to have a health care professional familiar with
the person's case make the initial contact with the clinical trials
team. People making calls directly may have insufficient medical
information, which may make decisions about eligibility difficult
and frustrating--for both the person making the call and for the
researcher taking the call.
Once contact with a clinical trial team is made, the clinical trial
staff assists potential participants and their health care providers
with information about potential clinical trials at the institution.
Depending on the institution, a referral coordinator, protocol
assistant, or nurse may accept telephone, mail, and e-mail inquiries
from physicians, potential participants, and others about a clinical
trial. Preliminary eligibility can be evaluated by phone, and
appointments with the clinical trial team can be scheduled.
Both patients and health care providers can find specific trials
through PDQ®, NCI's comprehensive cancer trial database. For
more information on PDQ, see the following page.
Finding Clinical Trials
75
Finding Information on Cancer and
Clinical Trials
NCI Resources
NCI's Web site, www.cancer.gov, provides access to a wealth of
information on clinical cancer care. The site contains information
from PDQ®, including the latest information about cancer
treatment, screening, prevention, genetics, supportive care, and
complementary and alternative medicine, as well as a registry of
cancer clinical trials. Clinical oncology specialists review current
literature from more than 70 medical journals, evaluate its
relevance, and synthesize it into clear summaries, which are then
reviewed monthly and updated as needed based on new
information. Most cancer information summaries appear in two
versions: 1) a technical version for the health professional, and 2)
a nontechnical version for patients, their families, and the public.
Many of the summaries are also available in Spanish.
The NCI Web site also includes approximately 100 fact sheets on
various cancer-related topics, information on ordering NCI
publications, and educational features and news summaries
concerning the latest results from cancer clinical trials.
NCI's clinical trials registry (PDQ) contains more than 1,800
ongoing clinical trials, including information about studies around
the world. All clinical trials undergo review prior to inclusion.
Although no single resource lists every cancer clinical trial being
conducted in the United States and abroad, PDQ is the most
comprehensive cancer clinical trials registry; it contains
information about trials sponsored by NCI, the pharmaceutical
industry, and some international groups. Users can narrow their
search by multiple parameters, such as stage of disease, phase of
trial, treatment modality, and geographic location. PDQ also
contains an archival file of more than 11,000 clinical trials that are
no longer accepting patients, including contact information for the
principal investigators of trials that may not yet be published in
the biomedical literature.
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CANCER CLINICAL TRIALS: THE BASIC WORKBOOK
Accessing NCI's Clinical Trials and Cancer Information
by Phone
NCI's Cancer Information Service--NCI's Cancer Information
Service is a national information and education network for
patients, the public, and health professionals. From regional offices
covering the entire United States, Puerto Rico, and the U.S. Virgin
Islands, trained staff provide the latest cancer information through
a toll-free telephone service. Staff can respond to calls in either
English or Spanish. With regional offices throughout the United
States, CIS staff members may work with organizations and
professionals to plan, implement, and evaluate culturally
appropriate clinical trials education programs using the Clinical
Trials Education Series.
Access: The toll-free number is 1-800-4-CANCER (1-800-422-
6237). For deaf and hard of hearing callers with TTY equipment,
the number is 1-800-332-8615. Hours of operation are Monday
through Friday, 9:00 a.m. to 4:30 p.m., local time. Callers also
have the option of listening to recorded information about
cancer 24 hours a day, 7 days a week.
NIH Web Site
It is important to note that there is no single resource that lists
every cancer clinical trial being conducted in the United States
and abroad. However, in 2000 the National Institutes of Health
launched a new Web site, www.clinicaltrials.gov, that aims to be a
complete listing of all U.S. Government- and industry-sponsored
clinical trials, including cancer trials.
The site contains approximately 7,200 clinical trials, most of them
Government-sponsored. However, additional trials from the
pharmaceutical industry are being added.
Finding Clinical Trials
77
Other Web Sites
The Internet includes a variety of clinical trial databases and
matching services. The owners of these sites can be:
· Not-for-profit organizations, where the content providers may
be volunteers and the site may be supported by an academic
institution or foundation
· Companies that are heavily funded by investors who
pharmaceutical companies pay every time a patient signs up for
a clinical trial
· Something in between (e.g., a for-profit organization that gives
some of its profits back to the cancer community)
Anyone interested in using any of these online services to find a
clinical trial should ask a number of questions and evaluate the
information before submitting personal information or calling an
investigator from the service:
· Who owns/runs the site?
· Where does the financial backing come from?
· How does the service get paid? By matching people to trials?
By clinical trial submission to the database? Other?
· Does anyone make money on this site? If so, then who?
· What is the source of clinical trial information?
· Does the site include all clinical trials? All Government-
supported trials? All pharmaceutical trials?
Most people would like to have all of their treatment/prevention
choices presented in an unbiased way before they make important
health-related decisions. People may wish to look at the
information from many of these sites and consider the source
of the information before deciding what actions to take.
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CANCER CLINICAL TRIALS: THE BASIC WORKBOOK
Guide To Finding Clinical Trial Resources
What is it?
How do I access it?
What will it provide?
National
Database produced by NCI
Go to www.cancer.gov
Summaries about clinical
Cancer
trials conducted by NCI-
Go to the clinical trials area
Institute's PDQ
Registry of approximately
sponsored researchers, the
1,800 active cancer clinical
and follow the search
pharmaceutical industry,
trials
directions
and some international
OR
groups
Call 1-800-4-CANCER
National
Database produced by NIH
Go to www.clinicaltrials.gov
Summaries about clinical
Library of
trials for a wide range of
Registry now lists 4,000
Can browse by disease or
conditions--most of the
Medicine
primarily NIH-supported
sponsor or insert key words
trials listed are sponsored
clinical studies on many
by NIH
conditions, and more will
be added
All trials on PDQ are listed in
this database
Food and Drug
A list of sources prepared by
Go to www.fda.gov/oashi/
Web addresses and
Administration's FDA's Office of Special
cancer/trials.html#table
telephone numbers
Cancer Clinical
Health Issues
Can browse by disease for
Trials Directory
different sources
Information listed on the
Guides user to other Web
Web sites in this directory
locations for institutions that
varies widely
conduct or list cancer
clinical trials
Local Cancer
Locally produced Web sites
Different sites can be found
Information that varies
Center Web
that include listings for trials
through:
from center to center
· www.cancer.gov
Sites
sponsored by NCI and some
pharmaceutical companies
· Local institutions
· Call 1-800-4-CANCER for a
center near you
Good supplementary
resources for locating clinical
Information on trials taking place
trials; a cancer center may
at NCI's Clinical Center in
begin participating in an NCI-
Bethesda, Maryland is available
sponsored trial before the
at http://ccr.nci.nih.gov then
center's information is listed in
select "clinical trials"
CancerNet/PDQ
Some centers may also have
telephone information centers
Example of
Pharmaceutical Research and
PhRMA
Descriptions, sites,
Pharmaceutical Manufacturers of America
Go to http://www.phrma.org
telephone numbers,
Resources/
(PhRMA) publishes a list of
Click on "New Medicines in
and investigator names
new cancer drugs in
Development" and search
by State
Internet Clinical development
by disease. The drugs are
Trial Matching
listed by cancer type or
Sites
CenterWatch's
call 202-835-3400.
Clinical Trials Listing Service
and EmergingMed.com's
CenterWatch
clinical trials matching service
Go to www.centerwatch.com
list many industry- and
Click on "Trial Listings" and then
Government-sponsored trials
"CenterWatch Trial Listings by
Medical Areas" or call
617-856-5900.
EmergingMed.com
Go to http://www.emergingmed.com
Finding Clinical Trials
79
Exercises
Exercise 5.1
Involvement in Clinical Trials
If a doctor seems too busy to refer a person to a clinical trial, can
the person make the calls directly?
____________________________________________________________
____________________________________________________________
____________________________________________________________
____________________________________________________________
CANCER CLINICAL TRIALS: THE BASIC WORKBOOK
80
Answer to Exercise 5.1
Decisions concerning eligibility for clinical trials
may be complicated, often requiring very specific medical
information on the person's condition.
· It is usually preferable to have the contact made by a doctor
familiar with the case.
· Potential participants making direct calls may
have insufficient information, which may make
decisions about eligibility difficult.
· Depending on the institution, a member of the research team
may accept telephone, mail, and e-mail inquiries from
physicians, potential participants, and others
about the clinical trial. In this case, preliminary eligibility can
be evaluated by phone, and appointments with the
clinical trial team can be scheduled.
Finding Clinical Trials
81
Exercise 5.2
Using PDQ to Locate Clinical Trials in Your Community
Choose two cancer diagnoses from the list below. Using
www.cancer.gov, locate at least three clinical trials going on in
your city or state.
When you have found at least three open trials, print out the
patient versions and answer the question below. You can use NCI's
PDQ or ask for printouts by calling 1-800-4-CANCER.
A. Someone diagnosed with stage II ovarian cancer who is looking
for treatment options in your city and state
B. Someone diagnosed with stage IV colon cancer who needs
options for supportive care
C. Someone diagnosed with stage III small cell lung cancer who
needs options for treatment
D. Someone who is found to be at high risk for breast cancer who
needs options for prevention
Question
What did you learn about clinical trials in your community
or State?
___________________________________________________________
___________________________________________________________
___________________________________________________________
___________________________________________________________
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CANCER CLINICAL TRIALS: THE BASIC WORKBOOK
Glossary
Glossary
adverse effect: See side effects.
agent: In a cancer clinical trial, an agent is a substance that
produces, or is capable of producing, an effect that fights cancer.
anthracycline: A member of a family of anticancer drugs that are
also antibiotics.
bias: Human choices, beliefs, or any other factors besides those
being studied that affect a clinical trial's results. Clinical trials use
many methods to avoid bias because biased results may not be
accurate.
biological therapy: Treatment to stimulate or restore the ability of
the immune system to fight infection and disease. Also used to
lessen side effects that may be caused by some cancer treatments.
Also known as immunotherapy, biotherapy, or biological response
modifier (BRM) therapy.
cancer: A term for diseases in which abnormal cells divide without
control. Cancer cells can invade nearby tissues and can spread
through the bloodstream and lymphatic system to other parts of
the body.
cancer vaccine: A form of biological therapy which may help a
person's immune system to recognize cancer cells. These vaccines
may help the body reject tumors and prevent cancer from
recurring.
chemoprevention: The use of drugs, vitamins, or other agents to
try to reduce the risk of or delay the development or recurrence of
cancer.
chemotherapy: Treatment with anticancer drugs.
clinical trial: Aresearch study that tests how well new medical
treatments or other interventions work in people. Each study is
designed to test new methods of screening, prevention, diagnosis,
or treatment of a disease.
Glossary
83
Community Clinical Oncology Program (CCOP): Aprogram that
links community physicians with NCI clinical research programs,
enabling more people with cancer to participate in clinical trials in
their own communities.
control group: In a randomized clinical trial, the group that
receives standard treatment.
cooperative groups: Networks of institutions that jointly carry out
large clinical trials following the same protocols.
data and safety monitoring board (DSMB): An independent
committee whose membership includes, at minimum, a statistician
and a clinical expert in the area being studied. Responsibilities of
the DSMB are to: ensure that risks associated with participation
are minimized to the extent possible, ensure the integrity of the
data, and stop a trial either if safety concerns arise or as soon as its
objectives have been met.
diagnostic trial: Aresearch study that evaluates methods of
detecting disease.
eligibility criteria: Participant eligibility criteria for clinical trials
can range from general (age, sex, type of cancer) to specific (prior
treatment, tumor characteristics, blood cell counts, organ function).
Eligibility criteria may also vary with trial phase. In phase 1 and 2
trials, the criteria often focus on making sure that people who might
be harmed because of abnormal organ function or other factors
are not put at risk. Phase 2 and 3 trials often add criteria regarding
disease type and stage, and number of prior treatments.
endpoint: What researchers 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. Examples of
endpoints include toxicity, tumor response, survival time, and
quality of life.
Food and Drug Administration (FDA): An agency of the U.S.
Department of Health and Human Services whose mission it is to
promote and protect the public health: 1) by ensuring that medical
products are proven safe and effective before they can be used by
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CANCER CLINICAL TRIALS: THE BASIC WORKBOOK
patients and 2) by monitoring products for continued safety after
they are in use.
gene: The functional and physical unit of heredity passed from
parent to offspring. Genes are pieces of DNA, and most genes
contain the information for making a specific protein.
gene therapy: Treatment that alters a gene. In studies of gene
therapy for cancer, researchers are trying to improve the body's
natural ability to fight the disease or to make the cancer cells more
sensitive to other kinds of therapy.
genetic: Inherited; having to do with information that is passed
from parents to offspring through genes in sperm and egg cells.
genetic testing: Analyzing DNA to look for a genetic alteration that
may indicate an increased risk for developing a specific disease or
disorder.
genetics research: Research that focuses on how someone's genetic
makeup can assist in the early detection, diagnosis, or treatment of
cancer. Genetics research may be a part of screening or treatment
trials.
investigational group: In a clinical trial, the group that receives the
new agent being tested. See also control group.
imaging: Tests that produce pictures of areas inside the body.
immune system: The complex group of organs and cells that
defends the body against infection or disease.
immunotherapy: See biological therapy.
informed consent: The process of providing all relevant
information about the trial's purpose, risks, benefits, alternatives,
and procedures to a potential participant, who then, consistent
with his or her own interests and circumstances, makes an
informed decision about whether to participate.
institutional review board (IRB): A board designed to oversee the
research process in order to protect participant safety. Made up
of researchers, ethicists, and lay people from the community, the
Glossary
84
board must review the trial protocols and the informed consent
forms participants sign.
investigational new drug (IND): Adrug that the Food and Drug
Administration (FDA) allows to be used in clinical trials, but that
the FDA has not yet approved for commercial marketing.
monoclonal antibodies: A form of biological therapy that may
help the body's own immune system fight cancer by locating
cancer cells and either killing them or delivering cancer-killing
substances to them without harming normal cells.
oncology: The branch of medicine that deals with tumors,
including study of their development, diagnosis, treatment, and
prevention.
National Cancer Institute (NCI): Part of the National Institutes of
Health of the United States Department of Health and Human
Services, is the Federal Government's principal agency for cancer
research. NCI conducts, coordinates, and funds cancer research,
training, health information dissemination, and other programs
with respect to the cause, diagnosis, prevention, and treatment of
cancer. Access the NCI Web site at www.cancer.gov.
New Drug Application (NDA): The application filed with FDA
by the trial sponsor once a trial has generated adequate data to
support a certain indication for a drug (usually by finding that the
drug is safe and superior to standard treatment in a definitive
phase 3 trial).
Office for Human Research Protections (OHRP): This office
safeguards participants in federally funded research and provides
unity and leadership for many federal departments and agencies
that carry out research involving human participants.
phase 1 trial: Small groups of people with cancer are treated with
a certain dose of a new agent that has already been extensively
studied in the laboratory. During the trial, the dose is usually
increased group by group in order to find the highest dose that
does not cause harmful side effects. This process determines a
safe and appropriate dose to use in a phase 2 trial.
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CANCER CLINICAL TRIALS: THE BASIC WORKBOOK
phase 2 trial: Phase 2 trials continue to test the safety of the new
agent and begin to evaluate how well it works against a specific
type of cancer. In these trials, the new agent is given to groups of
people with one type of cancer or related cancers, using the dosage
found to be safe in phase 1 trials.
phase 3 trial: Phase 3 studies are designed to answer research
questions across the disease continuum. Phase 3 trials usually have
hundreds to thousands of participants, in order to find out if there
are true differences in the effectiveness of the treatment being tested.
phase 4 trial: Phase 4 trials are used to 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.
Physician Data Query (PDQ): PDQ is an online database developed
and maintained by the National Cancer Institute. Designed to
make the most current, credible, and accurate cancer information
available to health professionals and the public, PDQ contains
peer-reviewed summaries on cancer treatment, screening, prevention,
genetics, and supportive care; a registry of cancer clinical trials from
around the world; and directories of physicians, professionals who
provide genetics services, and organizations that provide cancer care.
placebo: Atreatment, often a drug, designed to look like the
medicine being tested but that doesn't contain any active
ingredient. Some people call a placebo a "sugar pill." Placebos
are almost never used in cancer treatment trials.
preclinical testing: Aprocess in which scientists test promising new
anticancer agents in the laboratory and in animal models. This is
done to find out whether agents have an anticancer effect and are
safely tolerated in animals. Once a drug proves promising in the
lab, the sponsor applies for FDA approval to test it in clinical trials
involving people.
prevention trials: Trials involving healthy people who are at high
risk for developing cancer. These trials try to answer specific
questions about and evaluate the effectiveness of ways to reduce
the risk of cancer.
Glossary
87
principal investigator (PI): The person, usually a doctor, who is in
charge of a clinical trial. The PI prepares a protocol for the trial.
protocol: A written plan that acts as a "recipe" for conducting a
clinical trial. The protocol explains what a trial will do, how it will
be carried out, and why each part of the trial is necessary.
quality of life: The overall enjoyment of life. Many clinical trials
measure aspects of an individual's sense of well-being and ability
to perform various tasks to assess the effects of cancer and its
treatment on the quality of life.
radiation therapy: The use of high-energy radiation from x-rays,
gamma rays, neutrons, and other sources to kill cancer cells and
shrink tumors. Radiation may come from a machine outside the
body (external-beam radiation therapy) or it may come from
radioactive material placed in the body in the area near cancer
cells (internal radiation therapy, implant radiation, or
brachytherapy). Systemic radiation therapy uses a radioactive
substance, such as a radiolabeled monoclonal antibody, that
circulates throughout the body. Also called radiotherapy.
randomization: A method used to prevent bias in research. A
computer generates treatment assignments, and participants have
an equal chance to be assigned to one of two or more groups (e.g.,
the control group or the investigational group).
randomized clinical trial: A study in which the participants are
assigned by chance to separate groups that compare different
treatments; neither the researchers nor the participants can choose
which group. Using chance to assign people to groups means that
the groups will be similar and that the treatments they receive can
be compared objectively. At the time of the trial, it is not known
which treatment is best. It is the patient's choice to be in a
randomized trial.
remission: A decrease in or disappearance of signs and symptoms
of cancer. In partial remission, some, but not all, signs and
symptoms of cancer have disappeared. In complete remission, all
signs and symptoms of cancer have disappeared, although there
still may be cancer in the body.
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CANCER CLINICAL TRIALS: THE BASIC WORKBOOK
screening: Checking for disease when there are no symptoms.
screening trials: Clinical trials that focus on what tests can help
find cancer in people before they have any cancer symptoms. The
goal of early detection/screening trials is to discover new methods
for finding cancer as early as possible. For many types of cancer,
the ability to find and treat the disease at an early stage provides a
better chance for survival.
side effects: Problems that occur when treatment affects healthy
cells. Common side effects of cancer treatment are fatigue, nausea,
vomiting, decreased blood cell counts, hair loss, and mouth sores.
stage: The extent of a cancer, especially whether the disease has
spread from the original site to other parts of the body.
standard treatment: A currently accepted and widely used
treatment for a certain type of cancer, based on the results of past
research.
toxicity: Harmful side effects from an agent being tested.
treatment trials: Clinical trials conducted to examine new
treatment approaches for people who have cancer and to
determine the most effective treatments.
tumor: An abnormal mass of tissue that results from excessive cell
division. Tumors perform no useful body function. They may be
benign (not cancerous) or malignant (cancerous).
vaccine: A substance or group of substances meant to cause the
immune system to respond to a tumor or to microorganisms, such
as bacteria or viruses.
Glossary
89
Notes
The printing of this publication was supported by an educational gift from the Susan G.
Komen Breast Cancer Foundation.
This booklet was written and published by the National Cancer Institute (NCI), 9000
Rockville Pike, Bethesda, Maryland 20892.
NCI is the U.S. Government's main agency for cancer research and information about
cancer. To inquire about copyright and use of NCI materials contact: Clearance Officer,
National Cancer Institute.
Public Health Service
National Institutes of Health
NIH Publication No. 02-5050
Printed October 2001
Reprinted September 2002
P919