Provided by the National Institute of Mental Health
Foreword
Through the ages, disorders of the mind have been among the most devastating and
feared illnesses of humanity. Today, thanks to ambitious and productive research
on mental illnesses and to the willingness of many persons to participate in
research, highly effective treatments for mental illnesses exist. As a result of
these treatments, many thousands of persons who have brain diseases such as
depression, manic-depressive illness, schizophrenia, and anxiety disorders lead
fulfilling and productive lives.
Just as the pace of progress to date would not have been possible without the
participation in research of patients with mental illness and other volunteers,
neither will the advances of tomorrow be realized without their continued
participation. It is important to note that just as research on treatments has
evolved and become more effective, so too has our society's attentiveness to the
well-being of research volunteers grown. Procedures now in place to protect
volunteers are more effective than ever before.
The National Institute of Mental Health (NIMH) recognizes the Nation's debt of
gratitude to research participants, and is striving to maintain the trust that
human subjects place in the excellence of the research enterprise. Thus, we
prepared this booklet to highlight some of the questions a person may have in
thinking about joining a research study. We hope that by anticipating some
questions and helping persons better understand why they might consider
participating in mental illness research, all Americans will benefit in the
years ahead.
Steven E. Hyman, M.D.
Director
Introduction
In research on mental illness, as in other areas of medical science, volunteers
are all-important. Thanks in large part to their help, clinical researchers are
learning more and more about the causes of mental disorders and are finding new
and better treatments.
If you wonder whether to take part in a mental illness-related research study,
this booklet may help. (It also may be useful as you help a family member or
friend with this decision.) Anything you decide will, of course, be personal and
will depend upon your interests, needs, and expectations about research. In
coming to your decision, you need to understand your rights as a research
volunteer. Because your rights and well-being as a subject in research come
first, this booklet will review the safeguards designed to protect you.
You also should know how scientists study mental illness. Research volunteers
are not merely "subjects" of research, but actively take part in the search for
knowledge. When you do participate, you deserve to understand a few of the most
important requirements for good clinical research.
We encourage you to review the information in this booklet and discuss it with
others whom you trust. The topics are in a question-and-answer format. As you
read, make notes of any additional questions you have for the director of the
research project you are considering. We hope this will help you to get the
facts, raise your concerns knowledgeably, and decide then about taking part in a
research study.
Why Do Patients Participate in Research on Mental Disorders?
Although remarkable progress has been made in defining and treating mental
illnesses, some treatments are not effective for all persons or may have
significant side effects. Thus, most people who agree to take part in studies of
mental illness hope the research will produce knowledge about the disease
itself?for example, the role of genetics in illness?or about treatments that
will benefit them directly.
Research may allow you to try a new treatment before it is widely available.
Even if the aim of a study is not to test the effectiveness of a new treatment,
the research may offer a degree of care that you might not get otherwise. Such
care may allow the investigators to monitor your symptoms very closely to be
sure of your diagnosis.
Medical, psychological, and behavioral research are our best hope for better
understanding of and treatments for mental illnesses. Although most who take
part in research hope to benefit themselves, they may also simply wish to help
others, which is a reward in itself.
What Is Mental Health Clinical Research?
Scientists study and try different ways to diagnose, treat, and prevent human
disease more effectively. The needed research may take place in a basic science
laboratory, a clinic, or in the community.
In mental health clinical research, the term "clinical" means that the research
involves persons in actual patient care settings. These may be inpatient
settings (for patients whose illness requires hospitalization) and outpatient
settings (for those who live in the community).
Some clinical research may examine how well a new treatment works?perhaps a drug
or other type of therapy. In other instances, a clinical study might explore
factors that affect mental disorders. These factors might include the role of
genes and their interactions with life experiences in ways that might alter the
chemistry of the brain and lead to illness.
In making your decision to participate in a research study, you should discuss
the purpose of the research with the study director. Ask where the research will
take place and how long it will last. What does the research involve? What are
the potential benefits of participation? What are the risks? Does the research
involve treatment of your illness? You will probably have many other questions
for the researcher. Again, it may be helpful to write them down.
In the search for new knowledge, both you and the researcher will be trying out
new things. If you do not know about the many safeguards that exist to protect
research subjects, you may overestimate the risks of research. On the other
hand, if you expect to receive only the most advanced new treatments, you may
become disappointed.
How Will Treatment in a Clinical Research Study Differ from Treatment Your Own
Doctor Provides?
Clinical research often involves providing treatment. Yet, treatment research is
different from the care that you would get from your own doctor. Usually, when
you go to a doctor, you want help with a particular problem. You count on your
doctor to do what is best for you. You know that anything your doctor suggests
is meant to make you well.
A treatment research project, however, is different. The investigator wants to
learn about your illness, and not just treat you. Of course, a researcher will
try very hard to see that you benefit from the treatment research and that any
risk will be small. Yet one goal remains the most important: learning how well a
new treatment works for someone with your illness.
In research, the design of a study may call for standardized procedures. For
instance, when a researcher studies a medicine, or drug, the research plan may
require that only the drug under study be available to you. It may mean that you
will receive it only in a fixed dose; that is, the researcher cannot tailor the
amount of a medication to your immediate needs. Or, standardized procedures may
mean that you will receive a medication only in one specific way?for example, by
a shot or as a pill.
In such a study, or drug trial, the treatment you will receive likely will be
based on your random assignment to a particular medication or, sometimes, to an
inactive pill (a placebo). You should be told what is known about the relative
benefits and risks of each treatment used in the research study. You should also
be told what is known about alternative treatments that might be given outside a
research project. In contrast, treatment outside of a research study seldom uses
random choice of treatment and never uses a placebo; your doctor will always
prescribe a treatment that he or she believes would be good for you. However,
situations remain where no one may know what treatment is best, and that is one
instance where the importance of research is clear.
It should help to know that even investigational treatments are well-tested for
safety before their use in a clinical study. Also, remember that you always can
decide to withdraw from a study. You, or someone close to you, should know whom
to contact if you want to do so at any time.
How Are Clinical Studies of Mental Disorders Designed?
Clinical researchers call the standard scientific approach for trying out
treatments a double-blind, randomized, controlled clinical trial. Understanding
this term, and knowing how and why this approach is used, should help you to
decide whether to become a research volunteer.
An important part of scientific research is comparison. Clinical research often
will compare an investigational treatment to one that is used frequently and
thus has familiar, or predictable, effects. To make the comparison useful, the
investigator must try both methods on similar groups of subjects.
Researchers call the treatment with the predictable or known effect the control.
The control may be a standard, commonly used treatment, or it may be a placebo.
A placebo is something that does not directly affect the illness or symptoms
under study in any specific way. (You may have heard a placebo described as a
"sugar pill.") Some studies use both a standard treatment and a placebo as
controls.
The control helps an investigator find out if any changes seen in patients in
the experimental group are, in fact, due to the new treatment.
The term randomized means how a researcher assigns each patient to a particular
treatment under study. Researchers assign patients by chance either to a group
taking the new treatment (called the treatment group) or to a group taking a
standard treatment or a placebo (called the control group). This method, called
randomization, helps avoid bias: having the study's results affected by human
choices or other factors not related to the treatments being tested. In some
studies, researchers do not tell the patient whether he or she is in the
treatment or control group (called a single-blind study). This approach is
another way to avoid bias, because when people know what drug they are taking,
it might change the way they react. For instance, patients who knew they were
taking the new treatment might expect it to work better and report hopeful signs
because they want to believe they are getting well. This could bias the study by
making the results look better than they really were.
Random assignment helps to make sure that those in the group who receive an
investigational treatment are similar to those in the group who receive the
control treatment. By making certain that all who take part are similar, random
assignment helps a researcher to make better conclusions.
The term double-blind in research design means that neither you nor the
researcher will know if you are assigned to the experimental or to the control
group. The aim is to avoid letting either the investigator's hopes or
expectations about a particular treatment or your hopes and expectations
influence the manner in which he or she views improvements and side effects.
Your random assignment to a particular treatment group usually will occur after
the researcher decides that you can be in the study, and after you agree to join
the research by signing an informed consent form. Informed consent, which is key
to the successful conduct of all clinical research, is discussed later in this
pamphlet.
What Is a "Placebo Control" in a Medication Trial?
Studies of new drugs often compare the effects of an investigational drug with
the effects of a placebo. If you are considering whether to take part in a drug
trial, the director of the study must tell you if the study will use a placebo
control. The informed consent form that you will sign if you agree to join the
study must also explain any plans to use a placebo control.
The reason for using a placebo control is that the benefits from taking
medications are not always due to the drug itself. These benefits are called
"placebo effects." An example is when an investigator's enthusiasm about a new
medication sometimes influences the patient's response.
A researcher must be able to separate placebo effects from the actual effects of
the drug being studied. When equal numbers of patients receive either a placebo
or another standard drug that will help treat their symptoms, the researcher can
better judge the actual effects of the drug being tested.
In a "double-blind, placebo-controlled" research design, the doctors and nurses
working directly with patients in the study will not know which group patients
are in. Only members of the research team not involved in providing day-to-day
clinical care will know which patients are receiving an active treatment or a
placebo. This information is shared only when there is a medical necessity to do
so to protect the patient and at the end of the study.
Some scientists have questioned the use of placebo controls in clinical
research. They argue that if any drug is effective in treating a given
condition, then only that drug, and not a placebo, should be given as the
control. Other researchers, however, believe that without a placebo control, it
is harder to know whether an investigational medication is better than existing
drugs. The choice depends on what is being studied, the medicine, and the
illness.
If, during a study, an investigational drug seems to work very well, the
researcher may stop using the placebo. In some instances, as discussed in a
later section, participants may have a chance to use the investigational drug
after a study is completed.
It is important that the director of a medication trial explain thoroughly any
planned use of a placebo. Ask how the researcher plans to keep track of your
symptoms. Also, ask if there is a possibility that your symptoms could become
severe during the research project. If your symptoms worsen, at what point will
the researcher decide to remove you from the study and provide standard
treatment? In talking about these possibilities with the researcher, you must
remember that participating in a study does not guarantee that you will receive
a promising new medication. Indeed, you must consent to that fact. Also, you
should remember that even if you receive an investigational drug, it may not be
helpful for you. Remember you can always withdraw from a study.
What Is the Investigator's Responsibility if a Patient Has a Clinical Crisis?
You read earlier about the differences between clinical research and the care
you receive from your personal doctor. In most research, an investigator will
try to follow the research design: Following a research plan that has met all of
the conditions described in the next section of this pamphlet?conditions meant
to ensure that any proposed clinical research has scientific merit and is fully
attentive to participants' well-being?takes precedence over "tailoring"
treatments to a patient's unique needs. However, a patient who becomes much
worse during a study will be withdrawn from the project and given immediate
personal care, even though the worsening may not be related to the treatment
being given.
You and, if it is appropriate, your legally authorized representative should
discuss with the investigator the possibility that your illness could worsen
during the research study. Then you can decide how to handle any emergencies
that might arise during the study.
Among the issues you may wish to discuss is how the researcher will judge the
nature and severity of your symptoms. Another issue could be that, under certain
conditions such as a medication washout or a pharmacologic challenge, you might
decide to reject all treatment. If you are seriously ill, you might not
recognize how dangerous that decision could be. Thus, you should agree in
advance on how to handle this situation.
What Protections Exist for Research Subjects?
Many "checkpoints" ensure that research meets strict scientific guidelines and
follows rules that protect the subject. Several groups who are not part of the
research team examine both the scientific plan and procedures to protect the
interests of participants before an investigator may begin the research.
Each proposed study, including its provisions for the protection of human
subjects and its consent form, must be approved by an Institutional Review Board
(IRB). Every organization that conducts research, for example a university or
hospital, must have an IRB. The membership of these boards includes scientists,
persons who are not scientific experts, and at least one "public" member who is
not associated with the organization.
An important IRB responsibility is to review the informed consent materials that
an investigator develops for those who take part in the study. This information
allows the IRB and?more critically?you to judge the value, risks, and potential
benefits of a research project. If an IRB has concerns about any part of the
research proposal, the committee will tell the director of the study. The
researcher must attend to these concerns before submitting the research proposal
to a funding agency.
A funding agency, such as the National Institute of Mental Health (NIMH),
provides the next review of human subject provisions for clinical research
proposals. The funding agency also judges the scientific importance of a
research proposal, and how the researcher will learn from it. Both the IRB and
the funding agency conduct regular reviews to be sure that the researchers are
meeting all the rules for the protection of human subjects.
You can be certain that a range of persons, both scientists and others, have
reviewed any IRB-approved research that you may be asked to join. Nonetheless,
having a general understanding yourself of how scientists conduct clinical
research will help you feel more confident when talking about the project with
the research director.
Does Research Involve Special Risk?
Well before a clinical study begins, the researcher has attempted to reduce any
risk of physical discomfort or harm to you and others who take part. The effort
likely began with preclinical, or basic, laboratory research that probably
included animal studies, for example, to test the safety of a new drug. Yet, for
research to be absolutely "risk-free," every possible outcome would have to be
known?and if it were, then the research would not be necessary.
In fact, various different causes or forms of discomfort could result from a
particular research study. A patient/subject may have to take off from work, or
pay for some of the treatment. These requirements could be inconvenient or
expensive. As you will see in the next section describing informed consent, you
will be told about any foreseeable risks or discomforts that may occur in the
research before you agree to participate.
Naturally, the chance that there might be pain or harm worries most people who
are thinking about joining a clinical research project. Some discomforts may be
like what you are used to in routine health care, such as a needle prick when
blood is drawn for testing purposes. However, sometimes a research design may
call for more uncomfortable procedures, procedures with known risks, or
procedures for which the risk may not be fully known. These could include, for
example, being deprived of sleep, receiving injections, having a spinal tap,
receiving a small dose of a radioactive substance needed for a brain scan, or
treatment with an investigational drug.
Remember, nothing is without risks, including illness itself, and risks in
clinical research are minimized as best as possible. Also remember that the
research plan is reviewed by an IRB to insure the protection of people who
participate in the research study, and any known risks should be described in
the consent form.
What Is Informed Consent?
Federal regulations have been created to protect the well-being and rights of
volunteers in biomedical research. These regulations (Title 45 Code of Federal
Regulations Part 46 or 45 CFR 46) say no investigator may involve anyone as a
subject in research without getting that person's informed consent, either
directly or from the person's legal representative.
A researcher must ask you to sign a written informed consent form in which you
agree to take part in a certain study. The form contains a description of the
study, possible risks, and benefits of the research. The director of the
research must prepare the form and an IRB must approve it. The researcher must
then go over this form with you and get your permission to enter you into the
study.
Having a mental disorder does not necessarily mean that a person cannot
understand and see the value and risks of taking part in research. Most people,
therefore, who enter research studies on mental disorders can provide informed
consent. Additional guidelines and safeguards exist for patients who are not
able to give their permission with full understanding. In those cases consent is
obtained both from the participant and the legally authorized representative.
Informed consent is not a one-time event, but a continuing process. Throughout a
study, the research team must continue to provide information about
participating in the study. They must respond to any questions you have about
the research and inform you if any new risks are identified. You may, at any
time, reappraise your decision to take part in the project and withdraw your
consent. It is advisable to discuss any concerns with the director of the study.
Every informed consent form developed by an investigator and submitted to an IRB
for approval must include eight basic parts. These parts are:
A statement that the study involves research and that tells what its goals are,
how long the research will last, and what methods will be used.
A description of any reasonably foreseeable risks or discomforts you could
experience as a result of the research.
A description of any benefits that the research may be reasonably expected to
yield to you or to others.
A description of alternative courses of treatment, or therapies, if any, which
might help you.
A statement describing how the researcher will protect the confidentiality, or
privacy, of your medical records.
For research in which risk is somewhat more likely than you would expect in
routine health care, an explanation and description of the availability of
compensation or medical treatments if injury occurs.
The name and phone number of the person to contact about the research and your
rights, and whom to contact in case the research causes an injury.
A statement that your taking part in the research is voluntary, and that if you
change your mind, or quit later on, you will not be penalized in any way, or
lose any benefits you have coming to you.
The informed consent process must include the following items when they apply to
you:
A statement that the particular treatment or method used may not work as planned
and may be risky for you.
The reasons why the investigator might have to drop you from the study without
asking you first.
A list of any extra charges you may have to pay to take part in the research.
A description of what would happen if you decide to drop out of the study, and
what the researcher will do to make sure you keep receiving appropriate
treatment if you do drop out.
A statement that you will be told of any important results of the research which
may help you to decide whether to continue taking part in the study.
Approximately how many subjects are in the study.
Clinical researchers try to write informed consent forms that are brief and
understandable by people without scientific or medical training. Even so, some
informed consent forms appear long and complicated. Thus, it is important that
you are given the opportunity to read the form thoroughly, perhaps discuss it
with a family member or a trusted friend, and raise any questions you have with
the investigator. We hope you will feel comfortable talking to the investigator
or other members of the research team and asking questions until you are
satisfied that you understand the informed consent form.
Some investigators prepare additional material to help research subjects
understand the contents of an informed consent form. These might include, for
example, a videotape that describes the illness under study, the research
project, and the methods it will use. There may be a short quiz you can take to
help identify issues you wish to discuss further with the researcher. You may be
able to complete such a quiz at home at your convenience. If these ideas sound
useful, ask the director of the research if these or similar items are
available. You can ask for a copy of the protocol to take home to discuss with
family members, your physicians and others.
Involvement of Family Members and Others
You may wish to involve family members in some parts of a research study. For
example, you might consult with a family member about taking part in the study,
or you may wish to look over this booklet with a family member or close friend
and discuss being a research subject with that person. If you are a parent or
otherwise legally authorized representative of someone who might be a research
subject, you may wish to involve other concerned family members in any decision
you make.
Many family members welcome the chance to make sure, along with the research
team, that no one will take advantage of you during the study. This role is
clear if a family member is a patient's formal legally authorized
representative; but even lacking such legal status, families usually do all they
can to protect a family member who is ill.
Remember that Federal regulations protect your right to privacy in the handling
of your records throughout (and following) a study. You must give clear
permission if you wish the researcher to share personal information about you
with family members. Still, you should be aware that, with your consent, your
family members or other friends may have several opportunities to provide
information during the study.
Will You Have Access to Those Drugs That Work After a Trial Is Complete?
Understandably, if an investigational drug helps you, you may wish to continue
to take it after the trial has been completed. In some instances, a medication
that is being investigated for use in treating your illness may have been
approved by the Food and Drug Administration (FDA) for other uses. If you find
that you benefit from such a medication, your own doctor can prescribe it for
you.
Often, the company developing a new drug may try to see that you can continue to
get it, even before the FDA has approved it for sale. You may be able to do this
under what is termed a compassionate plea basis. This means that because the new
drug has been so helpful, the manufacturer can give it to a physician, who may
then prescribe it for you.
While companies often make such a new drug available, there may also be good
reasons why a company cannot. Perhaps only a very small amount of a drug was
prepared for the research project, and no more is available for use afterwards.
Then again, a manufacturer may want to further test the drug under certain
conditions, or to examine the results of a research study more fully before
releasing it for compassionate plea use. A company would be especially careful
if a new medication required that the doctor who prescribed it have some special
knowledge or skill to monitor its safe use.
You and any family members interested in your well-being should discuss with the
director of the research your questions about compassionate plea use. Each case
is different, so the agreement has to be between the drug manufacturer and your
own doctor.
Obtaining Care After a Research Project Has Ended
If you decide to take part in a research study?and, especially one that takes
place in a hospital?you may find that you will have to stop, or interrupt, the
care you now are getting for a mental disorder. Doing that, even temporarily,
may result in your losing access to a program of personal care that had been
expensive and hard to come by. The director of research on your study often will
help you to get back into a program of care when the study is finished. The
investigator's institution may assist in arranging for follow-up care.
Learning About the Results of Research
In most informed consent forms, the researcher promises to share what is learned
from the study with you. These results will sum up the responses of everyone who
took part in the study. In addition, the researcher will discuss with you any
results that relate to your diagnosis or that may be useful in deciding on the
best treatment for your disorder.
Be sure to ask the director of research when you can expect to hear about the
results. Ask how you will get this information. Will the researcher write an
article describing the study, or will those who took part be invited to a
meeting with the study director when all the results are in? If you have
questions about the results when you receive them, ask the researcher who can
help you to understand what they mean.
A frustrating thing about research is that it often takes years before the
results of a study are available. This is because of the time it takes to
conduct the study, including getting enough people in the study to make the
results meaningful. Be patient, but remember to ask for the results if you have
not received them when you expected them.
Checklist of Questions
So you have been asked to take part in a research study! This can be a very
satisfying experience, allowing you to help yourself now and to help others in
the future. After all, without research, treatment cannot improve, and without
those who take part, there would be no research! You are the one who makes
research possible.
But how do you know if you want to take part? What questions should you ask? The
researcher should answer these basic questions clearly for you. Others
undoubtedly will arise during the discussion.
Q: Why do you want me in your study?
Q: What is the research about? How will this research help in treating or
understanding my disorder?
Q: What do I need to do and how much time will this take?
Q: How might this study help me, my relatives, or other people with my disorder?
Q: What possible risks are there to me or my relatives if I take part?
Q: How will this be different from the care I am getting now, and do I have
other options or choices?
Q: Could my illness become worse during the study? What will happen if it does?
Q: What will happen to me at the end of the study?
Q: What should I do if I want to drop out of the study?
Q: May I get back to you after I discuss this with my family/friend/case
manager/doctor?
Remember to ask again if you do not understand the explanation to any question
you have. And, if you forget the answers to these questions during the study,
just ask them again.
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