Before you agree to participate in a trial, you should make sure
you understand "informed consent" and why you need to
What to Expect
What Will I Find in the Informed Consent
Other Useful Tips
Questions to Ask
A Definition of Informed Consent
You may already have experience with signing consent forms for
other kinds of medical procedures, such as surgery, or for cancer
treatments such as radiation or chemotherapy. However, informed
consent for a clinical trial involves much more than just reading
and signing a piece of paper. Rather, it involves two essential
parts: a document and a process.
The informed consent document provides a summary of the clinical
trial (including its purpose, the treatment procedures and schedule,
potential risks and benefits, alternatives to participation, etc.)
and explains your rights as a participant. It is designed to begin
the informed consent process, which consists of conversations between
you and the research team. If you then decide to enter the trial,
you give your official consent by signing the document. You can
keep a copy and use it as an information resource throughout the
course of the trial.
The informed consent process provides you with ongoing explanations
that will help you make educated decisions about whether to begin
or continue participating in a trial. Researchers and health professionals
know that a written document alone may not ensure that you fully
understand what participation means. Therefore, before you make
your decision, the research team will discuss with you the trial's
purpose, procedures, risks and potential benefits, and your rights
as a participant. If you decide to participate, the team will continue
to update you on any new information that may affect your situation.
Before, during, and even after the trial, you will have the opportunity
to ask questions and raise concerns. Thus, informed consent is an
ongoing, interactive process, rather than a one-time information
Myth and Reality
Before you start exploring this section of the site, you may find
it helpful to confront some of the most common misperceptions about
informed consent and clinical trials. Even if these do not represent
your thinking about informed consent, they can serve as a helpful
reminder of what the process is really about before you go through
Myth: Informed consent is
designed primarily to protect the legal interests of the research
Reality: The purpose of the process is to protect you and other
participants by providing access to information that can help you
make an informed choice. It also is designed to make you aware of
your rights as a participant.
Myth: The most important part
of this process is signing the informed consent document.
Reality: Actually, the heart of this process is your ongoing interaction
and discussions with the research team and other medical personnel-before,
during, and after the trial. The document is designed to get this
Myth: My doctor knows best;
he or she can tell me whether or not I should consent to participate.
Reality: Your doctor is likely to be a valuable source of advice
and information, but only you can make this decision. No one-not
even medical experts-can predict whether a treatment, screening,
prevention, or supportive care method under evaluation in a trial
will prove successful. The informed consent process is designed
to help you weigh all of the information and make the right choice
for you or your child.
Myth: Once I sign the consent
form, I have to enroll and stay enrolled in the trial.
Reality: That's not true. Even after you sign the form, you are
free to change your mind and decide not to participate. You also
have the right to leave a clinical trial at any time for any reason,
without forfeiting access to other treatment.
Myth: Medical personnel are
busy, so I can't really expect them to keep me informed as the trial
progresses or listen to my questions.
Reality: The research team has a duty to keep you informed, make
sure that you understand the information they provide, and answer
your questions. If you ever feel that you are not getting what you
need, do not hesitate to speak up. You will be given the name and
phone number of a key contact person who can answer your questions
throughout the course of the trial. Keep in mind that people like
you are making this research possible through their willingness
Back to Top
Informed Consent and the Larger System of Protections
Informed consent for clinical trials is just one part of a larger
system in place to safeguard people who want to help researchers
evaluate new practices that may improve treatment, supportive care,
screening, and prevention, while perhaps benefiting from these new
methods. This system ensures that clinical trials are conducted
ethically, without undue risk to participants. What follows are
links to some of the resources that contribute to this system of
Back to Top
Simplification of informed consent documents
The informed consent process can be effective only if patients understand
the study information presented by the medical team. After both
participants and investigators voiced concerns that informed consent
documents for clinical trials were becoming too long, complicated,
and difficult to understand, the National Cancer Institute issued
new recommendations and other guidance for the documents' developments.
The recommendations had three goals in mind:
- to make the forms more useful and understandable
to people who want to participate in clinical trials;
- to aid investigators in developing better informed consent
- to assist Institutional Review Boards (IRBs) in reviewing the
documents and ensuring their quality.
Office of Human Research Protections (OHRP)
This OHRP, which is part of the U.S. Department of Health and Human
Services (DHHS), is responsible for:
- guiding the medical community on ethical issues
in biomedical or behavioral research, and
- implementing DHHS's Regulations for the Protection
of Human Subjects (Title 45, Part 46 of the Code of Federal Regulations,
Protection of Human Subjects; also referred to as 45 CFR 46).
These federal regulations set standards for the informed consent
process; the formation and function of Institutional Review Boards
(see below); the involvement of prisoners, children, and other vulnerable
groups in research; and many other protective measures.
The regulations apply to any federally funded research that involves
people. Participating institutions must provide OHRP with a written assurance that they
will comply with the regulations. In addition, many research institutions
conducting independent (i.e., not federally funded) trials have
volunteered to adhere to these regulations.
Human Subject Protection Program, FDA
The U.S. Food and Drug Administration (FDA), through its Office
of Health Affairs, has developed its own set of regulations on the
protection of human subjects (Title 21, Parts 50 and 56 of the Code
of Federal Regulations; also referred to as 21 CFR 50, 56).
The regulations apply to any clinical trial that involves an investigational
drug, biological product, or other device that is regulated by the
FDA under the Food, Drug, and Cosmetics Act -- regardless of whether
or not the trial receives Federal funding. If a trial is supported
by the Department of Health and Human Services and involves an FDA-regulated
drug or device, then it is subject to both organizations' regulations.
The American Hospital Association's "Patient's
Bill of Rights"
In 1992, the American Hospital Association (AHA) revised the patient's
bill of rights that it first adopted in 1973. This bill lists a
patient's rights to considerate and respectful care, privacy, confidentiality,
information about options, and access to medical records, among
others. The AHA expects hospitals to use the bill to ensure quality
care and encourages them to adapt it to meet the needs of the communities
Institutional Review Boards
Institutions have an Institutional Review Board (IRB) made up of
medical specialists, nurses, social workers, medical ethicists,
and patient advocates. The IRB reviews all clinical trial protocols
and approves only those that address medically important questions
in a scientifically and ethically responsible manner. It also reviews
all informed consent documents to make sure that they provide clear
and complete information for those who may wish to take part.
You might be interested in taking a look at the Institutional Review
Board Guidebook issued by the NIH's Office of Human Research Protections.
Back to Top
Before a clinical trial gets under way, it also may be reviewed
by experts chosen by the sponsoring organization (such as the National
Cancer Institute, the Food and Drug Administration, or pharmaceutical
company) for scientific merit, patient safety, and ethical considerations.
For more information about peer review at the National Institutes
of Health (NIH), see the Office of Extramural Research:
Peer Review Policy and Issues or the NIH Center for Scientific Review.
Many hospitals and clinical centers employ patient representatives,
who work to make sure that those who receive care (including clinical
trial participants) are informed of and understand their rights
Groups such as Public Responsibility in Medicine and Research (PRIM&R)
and its memberships affiliate, the Applied Research Ethics National
Association (ARENA), help to educate medical personnel and the public
about the ethical, legal, and policy issues involved in clinical
Back to Top
The History of Informed Consent and the
System of Protections
Over the past half-century, the international and U.S. medical communities
have taken numerous steps to protect people who take part in clinical
research. The following timeline provides an overview of some of
the key events that have contributed to the development of the current
1947 - The Nuremberg Code
Developed in response to the Nuremberg Trials of Nazi doctors who
performed unethical experimentation during World War II, the Code
was the first major international document to provide guidelines
on research ethics. It made voluntary consent a requirement in clinical
research studies, emphasizing that consent can be voluntary only
- participants are able to consent;
- they are free from coercion (i.e., outside pressure);
- they comprehend the risks and benefits involved.
The Code also states that researchers should minimize risk and
harm, make sure that risks do not significantly outweigh potential
benefits, use appropriate study designs, and guarantee participants'
freedom to withdraw at any time. The Nuremberg Code was adopted
by the United Nations General Assembly in 1948.
1964 - Declaration of Helsinki
At the 18th World Medical Assembly in Helsinki, Finland, the World
Medical Association adopted 12 principles to guide physicians on
ethical considerations related to biomedical research. It emphasizes
the distinction between medical care that directly benefits the
patient and research that may or may not provide direct benefit.
These guidelines were revised at subsequent meetings in 1975 (Tokyo,
Japan), 1983 (Venice, Italy), and 1989 (Hong Kong).
1974 - The National Research Act
The U.S. Congress signed this act into law, creating the National
Commission for the Protection of Human Subjects of Biomedical and
Behavioral Research. The Commission was charged with:
- identifying the basic ethical principles that
should govern medical research involving people, and then
- recommending steps to improve the Regulations
for the Protection of Human Subjects.
1979 - The Belmont Report
After four years of work, the National Commission for the Protection
of Human Subjects of Biomedical and Behavioral Research issued "The
Belmont Report: Ethical Principles and Guidelines for the Protection
of Human Subjects of Research." The report sets forth three
principles underlying the ethical conduct of research:
- respect for persons: recognizing the autonomy
and dignity of individuals, and the need to protect those with
diminished autonomy (i.e., impaired decision-making skills), such
as children, the aged, and the disabled;
- beneficence: an obligation to protect persons
from harm by maximizing benefits and minimizing risks;
- justice: fair distribution of the benefits and
burdens of research.
The Belmont Report explains how these apply to research practices;
for example, it identifies informed consent as a process that is
essential to the principle of respect. In response to the report,
both the U.S. Department of Health and Human Services and the U.S.
Food and Drug Administration revised their regulations on research
studies that involve people.
1991 - Federal Policy for the Protection
of Human Subjects
This policy was adopted to ensure a uniform system of protections
in all federal agencies and departments that conduct research.
What to Expect
What Should I Expect During the Informed Consent Process?
According to The Belmont Report, the informed consent process relies
on three principles:
- adequate information is provided (generally,
what a "reasonable person" would want to know to make
- participants comprehend the information; and
consent is given voluntarily.
While this process varies among different research institutions
and clinical centers, you generally should expect the following:
- An initial meeting during which a member (or
members) of the research team provides you with the informed consent
document and explains its content to you. This discussion may
also include your specialist and primary care doctor, as well
as a nurse, social worker, patient representative, and/or staff
psychologist. You may wish to bring along a family member or friend
for support, and to help you keep track of the information presented.
This information should be given logically and at a comfortable
pace, with plenty of time allowed for you to consider it and ask
questions. You may be given a video, audiotape, or even an interactive
computer program to help you better understand the information
in the consent document.
If your child (under age 18) is the one who will participate in
the clinical trial, you will go through this process on his or her
behalf. More and more frequently, children over the age of 6 are
being asked to give their "assent" to participation as
well. If this is the case, you will be asked to give permission
for your child to take part in the assent process. During this process,
a child or teenager is provided with a form that explains, in concrete
and age-appropriate terms, the purpose of the research, what they
will be asked to do, and what procedures they will undergo. Usually,
a nurse or other heath professional also explains the information
and gives the child a chance to ask questions. Then they are asked
to indicate their assent either by signing the form or making a
mark in a specific place. This example, from a trial at the University
of California, San Francisco, gives you an idea of what an assent
form might look like.
- Time to digest the information. It can be very
difficult to absorb this information in one sitting, especially
at a time of emotional distress. You should be given a copy of
the document so that that you can take it home, review it as many
times as you need, and discuss it with family, friends, social
workers, clergy, a patient representative, or other trusted advisors.
- Assessment of your understanding. The research
team should take some steps to ensure that you comprehend the
information, either by having you fill out a questionnaire, asking
you questions orally, or having you explain certain aspects of
the trial in your own words. You also should alert team members
to anything you do not understand. If you find that the document
is written in words that are too difficult for you, don't hesitate
to let them know that.
Opportunities to ask questions. Both during the initial meeting
and in follow-up discussion(s), you should be given the chance
to ask questions and raise concerns. Keep asking questions until
you have all the information you need to make your decision.
- Continuing updates on new information. As the
trial proceeds, the research team may discover new information
that could affect your health, welfare, or willingness to remain
in the study. They will share this with you and may ask you to
sign a new informed consent document. Of course, you are free
to leave the study if this information leads you to have doubts
about continuing to participate.
What Will I Find in the Informed Consent
In 1998 the National Cancer Institute Working Group on Informed
Consent issued recommendations designed to help research institutions
and clinical centers write comprehensive, user-friendly informed
consent documents. The group also developed a template and sample
forms that provide models for covering all of the information that
federal regulations require for informed consent documents.
You may wish to print out the template or a sample form and use
it as a model of what to look for in the document that you receive.
While informed consent documents do vary from place to place, they
should communicate all of the information described below in language
that you can understand, with some help from the research team (if
needed). Even if your trial is not federally funded and therefore
not governed by these regulations, you should know that any scientifically
valid trial will provide an informed consent document that supplies
such information. The information covered should include:
[Why is this clinical trial being
In this section, researchers explain why they are conducting the
trial. Their reasons will depend on the type of disease and the
trial type (i.e., whether they are investigating new prevention,
screening, supportive care, or treatment methods). Researchers conduct
treatment trials either because they have not found an effective
treatment for a certain type of disease, or they are not sure which
treatment method works best.
In these trials, Phase I tests the safety and effectiveness of
a new treatment, or aims to find out what dosage of a new drug can
be given safely. Phase II treatment trials evaluate the effects
(good and bad) that a treatment may have on people with a certain
type of disease. Phase III treatment trials compare the effectiveness
of a new treatment or treatment combination with that of standard
treatment. Researchers use prevention, screening, and supportive
care trials to evaluate new strategies for preventing disease, detecting
it more accurately and effectively, and alleviating treatment side
DESCRIPTION OF PROCEDURES
[What is involved in the trial?]
This section describes the procedures that you will undergo, how
frequently you will have them, and where they will take place (at
home, in the hospital or clinical center, or in an outpatient setting).
For treatment trials, this section should include:
procedures that are part of regular disease care and may be done
even if you do not join the trial;
standard procedures being done because you are in the trial; and
procedures that are being tested or evaluated by the trial.
If this is a "randomized" trial, then you will be assigned
at random (by computer) into one of two or more study groups. People
in the different groups will receive different treatments or treatment
combinations, so that researchers can evaluate which is most effective.
If this is the case, the document should make clear what procedures
each group will undergo. It should also indicate what your chances
are of being placed in any one group.
[How long will I be in the trial?]
This section indicates how long the trial will last and whether
it involves followup, and if so, for how long. It also includes
information about any circumstances under which the researcher might
remove you from the trial (for example, if your condition worsens
or new information indicates you shouldn't continue). The document
should make clear that you have the right to stop participating
at any time, and it should describe any possible medical consequences
of sudden withdrawal.
[What are the risks of the trial?]
This section includes the foreseeable physical and nonphysical risks
of participating in the trial. A nonphysical risk might be time
away from work, while physical risks might include side effects
such as nausea, vomiting, pain, or susceptibility to infection,
among others. The document should indicate the likelihood of these
risks occurring, how serious they may be, and whether they are more
likely to be short-term (last only during the trial or shortly afterward)
or long-term (last weeks, months, or even years after the trial
is over). The document should make clear which risks are related
to the investigational aspects of the trial. It also should include
specific information about reproductive risks (Could participating
make you infertile? Should you not get pregnant or father a child
while on the trial? Can you nurse a child during the trial?).
[Are there benefits to taking part?]
The document describes any benefits to you or to others which may
reasonably be expected. A trial may or may not involve direct medical
benefits to you, but it might lead to new knowledge that can help
others in the future.
ALTERNATIVES TO PARTICIPATION
[What are my options if I don't participate?]
For treatment trials, this section describes what care options you
have besides participating in the trial, such as other commonly-used
therapies or no treatment at all.
This statement tells you the extent to which your information will
be kept confidential. It should inform you about any groups or organizations
that may have access to your records for quality assurance and data
analysis (such as the National Cancer Institute, the Food and Drug
Administration, or other trial sponsor).
COSTS/ ADDITIONAL EXPENSES
[What are the costs?]
This section indicates whether participating in the trial will result
in added costs to you or your insurance company (see Clinical Trials
and Insurance Coverage for more information on this topic). It also
covers other cost issues, such as who will pay for emergency medical
treatment in case of injury or illness, whether you will have to
pay for drugs that become commercially available during the trial
(if this is a drug trial), and whether or not you will receive payment
[What are my rights as a participant?]
The document should specify that:
- your participation is voluntary;
- you can choose not to take part or leave at any
time without penalty or loss of benefits; and
- any new information that might affect your participation
will be shared with you.
[Whom do I call if I have questions
You should have a contact name and phone number (usually of a member
of the research team) for getting answers to questions about the
study or a research-related injury. You also should be given a phone
number for the Institutional Review Board or a patient representative,
in case you have questions about your rights as a research participant.
[Where can I get more information?]
This section lists additional resources that may prove useful as
you make your decision, such as informational booklets, community organizations, and Web resources.
Your signature represents your legal consent to participate in the
If any of these sections appears to be incomplete or missing from
the informed consent document, don't hesitate to ask for the information.
Other Useful Tips
- Keep a copy of the informed consent document
as a helpful resource for the duration of the trial. Ask for a
copy if one isn't offered to you. You may also request a copy
of the protocol (full study plan).
- According to Federal regulations, no informed
consent document may include any language that asks or appears
to ask you to waive your legal rights, or that releases or appears
to release the investigator, the sponsor, or the institution from
liability for negligence.
- If you cannot understand the forms you are signing,
don't be afraid to let someone know that you are having trouble.
If you have difficulties reading the document at first, try not
to get upset. Many people feel anxious about reading and signing
documents and communicating with physicians. Just take your time
and ask for help when you need it.
Questions to Ask
A Checklist of Questions to Ask the Research
The following questions deal with many of the areas that should
be covered in the informed consent document (see previous section).
To double-check that you have all the information you need, consider
printing out this checklist and bringing it to a meeting with the
research team. You also may wish to fill it out as you read the
informed consent document, both to ensure your own understanding
of the trial and to create a ready reference written in your own
words. Many of these questions are specific to treatment trials,
but the checklist still should prove useful if you are considering
a prevention, screening, or supportive care trial.
- What is the purpose of the study?
- Why do researchers think the approach may be effective?
- Who will sponsor the study?
- Who has reviewed and approved the study?
- How are study results and safety of participants being checked?
- How long will the study last?
- What will my responsibilities be if I participate?
- Whom can I speak with about questions I have during and after
the trial to find out the study results?
- What steps will be taken to protect my privacy and the confidentiality
of my medical records?
Possible Risks and Benefits
- What are my possible short-term benefits?
- What are my possible long-term benefits?
- What are my short-term risks, such as side effects?
- What are my possible long-term risks?
- What other options are there?
- How do the possible risks and benefits of this trial compare
with other options?
Participation and Care
- What kinds of therapies, procedures, and/or tests will I have
during the trial?
- Will they hurt, and if so, how long?
- How do the tests in this study compare with those I would have
outside of the trial?
- Will I be able to take my regular medications while in the clinical
- Where will I have my medical care?
- Will I have to be hospitalized? If so, how often and for how
- Who will be in charge of my care?
- What type of follow-up care is part of the study?
- How could being in the study affect my daily life?
- Can I talk to other people in the study?
- Will I have to pay for any part of the trial such as tests or
the study drug?
- If so, what will the charges likely be?
- What is my health insurance likely to cover?
- Who can help answer any questions from my insurance company
or health plan?
- Will there be many travel or child care costs that I need to
consider while I am in the trial?
Resources for Understanding Informed
You may find that the informed consent process and conversations
with your medical team are sufficient in helping you arrive at a
decision. Or you may wish to gather more outside information before
making up your mind. Other good sources of information include:
- local hospitals
- Institutional Review Boards
- patient advocacy and support groups
- health plans
- library and Internet research.
You can also search the National Library of Medicine's PubMed database
for additional articles on informed consent and clinical trials.
Keep in mind that everyone's information needs are different. You
should do whatever makes you feel most comfortable as you make this
Back to Top
Used with permission of the National Cancer Institute