Basic Workbook: Preface
Introduction: The Importance of Clinical Trials
1: The Clinical Trial Process
2. Advancing Cancer Care through Clinical Trials
3. Participant Protection in Clinical Trials
4. Barriers to Clinical Trial Participation
5. Finding Clinical Trials
Answers to Exercises
Glossary
Basic Workbook: Preface
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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.
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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 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.
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.
 Back to Top
Introduction: The Importance of Clinical Trials
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.
 Think about the reasons that have the
most meaning for you or your community. Keep these reasons in mind as you go
through this workbook.
Cancer affects us all-whether we have it, care about someone who
does, or worry about getting it in the future.
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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 1 of every 4 deaths are caused by cancer About 1,284,900 new cancer cases are diagnosed
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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.
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.
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.
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.
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.
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.
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.
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].
Back to Top
1: The Clinical Trial Process
Clinical trials are research studies involving
people.They seek to answer specific scientific questions to
find better ways to prevent, detect, and treat diseases, and
to improve care for people with diseases. Clinical trials
differ by type of trial and phase of trial. Each clinical
trial follows a set of strict scientific guidelines called a
protocol.
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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
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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.
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:
Phases of Clinical Trials
Trials take place in four phases, each designed to answer
different research questions.
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filler
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Phase
1
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Phase
2
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Phase
3
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Phase
4
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Number of participants
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15-30 people
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Less than 100 people
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Generally, from 100 to thousands of people
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Several hundred to several thousand people
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Purpose
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To find a safe dosage
To decide how the agent should be given
To observe how the agent affects the human
body
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To determine if the agent or intervention has an
effect on a particular cancer
To see how the agent or intervention affects the
human body
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To compare the new agent or intervention (or new
use of a treatment) with the current standard
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To further evaluate the long-term safety and
effectiveness of a new treatment
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The trial phases are explained in the context of drug treatment
trials, but the same concepts apply to most types of clinical
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
phase 1 trial can begin. A phase 1 trial is the first step in testing
a new cancer agent in humans.
In these studies, researchers look for the best way to give people
the new agent (for example, by pill or by injection), how often it
should be given, and what the safest dose is. These studies also
include special laboratory tests such as blood tests and biopsies to
evaluate how the new agent is working in
the body.
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An agent is a substance
that produces, or that researchers believe
is capable of producing, an effect that fights
cancer.
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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 usually increased group by group in order to find the
highest dose that does not cause unacceptable harmful side
effects, called toxicity. This process determines a safe and
appropriate dose to use in a phase 2 trial. Although the primary
purpose of phase 1 trials is to find the safest dose of a new
agent, researchers also evaluate whether the new agent benefits
people.
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Toxicity refers to harmful side effects caused
by the agent or intervention being tested.
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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.
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.
Phase 3: Comparing a New Treatment to the Standard Treatment
Phase 3 trials focus on learning how a new treatment compares to
standard, or the most widely accepted, treatment. Researchers want to
learn whether the new treatment is better than, the same as, or worse
than the standard treatment.
In phase 3 trials, participants have an equal chance to be
assigned to one of two or more groups (also called "arms"). In a
study with two groups:
Placebos are almost never used in cancer treatment trials. In rare
cases in which no standard treatment exists for a cancer, some
studies compare a new treatment with a placebo.
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A placebo is designed to look like the medicine
being tested but doesn't contain any active ingredient.
Some people call a placebo a "sugar pill."
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The process of assigning participants to groups is called
randomization. Additional discussion of randomization is included
later in this section.
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Finding Out About Standard Cancer Care
The National Cancer Institute's Web site www.cancer.gov
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.
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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.
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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.
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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 Chemoprevention Trials Work
Chemoprevention trials also go through phases. In phase 3 agent
studies:
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
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.
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:
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 is
there.
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 and quality of
life of 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 and/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.
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Genetics Research
Genetics studies may be a part of any cancer clinical
trial and focus on understanding how someone's genetic
make-up 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.
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Phase 3 studies are randomized clinical trials. Some phase 2
trials may also be randomized.
Randomization is a method used to prevent bias in research. In
phase 3 studies (and some phase 2 studies), participants are assigned
to either the investigational group or the control group by chance,
via a computer program, or with a table of random numbers.
Randomization ensures that unknown factors do not influence the trial
results.
The control group is made up of people who will
get the 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.
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.
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)
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Bias can be human
choices, beliefs, or any other factors besides those
being studied which can affect a clinical trial's
results.
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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.
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
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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
Tumor response
Survival
Quality of life
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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.
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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:
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
reasons for the results are due to the agent or intervention
being studied and not other factors.
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These exercises are optional. They are provided as tools to review the information presented in each chapter.
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.
_____________________________________________________
_____________________________________________________
_____________________________________________________
Answers to Exercise 1.1
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. You may
want to print these questions for a reference.
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 participating
in this trial?
_____________________________________________________
_____________________________________________________
_____________________________________________________
Note that the protocol contains some blanks to indicate words
omitted for the purpose of this exercise.
Answers to Exercise 1.2
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.
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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.
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Back to Top
2. Advancing Cancer Care through Clinical Trials
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.
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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
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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, 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.
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Peer review is a process by which experts
critique a study's report before it is published to make
sure that the analysis and conclusions are sound.
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Once a new drug or technique is proven safe and effective in a
clinical trial, it may become the new standard of practice for
physicians.
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.
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The
Drug Development and Approval Process in the
1990s
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Preclinical Testing
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Clinical Trials
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Post-Clinical Trials
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Total Years for Drug Approval
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Step 1
Laboratory / Preclinical
Testing
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Step 2
File IND1 application with
FDA2
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Step 3
Phase 1
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Step 4
Phase 2
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Step 5
Phase 3
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Step 6
File NDA3 or BLA4 with
FDA
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Step 7
FDA Approval
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Purpose
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Assess safety and biological
activity in the laboratory and in animal
models
|
Obtain FDA approval to begin clinical testing in humans after promising
results in laboratory
|
Determine what dosage is safe,
how treatment should be given
|
Evaluate effectiveness, looks
for side effects
|
Determine whether the new
treatment (or new use of a treatment) is a better
alternative to current standard
|
Inform the FDA of Phase 3 data which supports drug safety and better
performance over standard treatment
|
Review
process/ approval
|
|
All anticancer drugs
(average number of years)
|
4.4 years
|
|
8.6 years
|
|
1.4 years
|
14.4 years
|
|
All drugs*
(average number of years)
|
3.8 years
|
|
10.4 years
|
|
1.5 years
|
15.7 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.
|
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 see www.fda.gov/cder/about/whatwedo/testtube.pdf.
|
How Can the Public Influence the Drug Development
Process?
As shown on the Drug Development and Approval Process chart, 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.
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.
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).
|
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.
|
|
How Clinical Trials Advance Cancer Care
|
|
Apply what you've learned about clinical trials to respond to
the following questions. You may wish to print these questions for
a reference.
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?
__________________________________________________________
__________________________________________________________
__________________________________________________________
Answers to Exercise 2
Back to Top
3. Participant Protection in Clinical Trials
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:
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
|
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
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
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:
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.
|
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 children and young people over age 7 unless:
The child is found to be incapable of assenting
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 avaialable 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?
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:
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.
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.
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 DMSB 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.
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?
|
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, Sub Part A
5 Title 21 CFR Part 50, 56.
|
Participant Protection
|
|
How would you respond to the following questions? You may wish to print
them for a reference.
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?
__________________________________________________________
__________________________________________________________
__________________________________________________________
Answers to Exercise 3
Back to Top
4. Barriers to Clinical Trial Participation
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
|
|
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? You may wish to print
this question for a reference.
__________________________________________________________
__________________________________________________________
__________________________________________________________
Compare your answer to the information in this
section.
* Excerpted from an American Society of Clinical Oncology news release, 1999.
|
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 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.
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.
|
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 of 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 www.harrisinteractive.com
Supported by the Coalition of National Cancer Cooperative Groups, the Cancer Research Foundation of America, the Cancer Leadership Council, and the Oncology Nursing Society.
|
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, including:
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.
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.
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.
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 are 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
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.*
*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.
Health Plan Coverage - Chemoprevention Trials
Although participants receive prevention 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 g | 
