Protecting Human Subjects Guide
4. The Process of
Consent
Since the central requirement for human subjects research is
that people participate voluntarily, the informed consent process is
one of the most important parts of planning a research proposal. The
process must assure that the potential subject understands the study
and its risks and benefits and can certify his or her willingness to
participate.
4.1 A process - not a form
Since subjects retain the right to withdraw from a study, consent
is an ongoing process. It starts well before any forms are signed
and continues until the subject's participation is complete.
The informed consent process is different from the consent form.
It involves meeting with a potential subject, finding out whether he
or she is capable of giving consent, and discussing the purpose,
risks, and benefits of participation. The consent form formalizes
the agreement to participate and should be designed to document the
process. Obtaining informed consent is not just giving a prospective
subject a consent form and getting it signed.
If consent is to be informed, the subjects must genuinely
understand the study. Hence, researchers should strive to convey
information to subjects, not merely disclose it to them. Subjects
should be able to demonstrate their understanding of the study
procedures, risks, and benefits in which they are agreeing to
participate.
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4.2 When to discuss participation
To achieve understanding, potential subjects should not be
presented information all at once or only at the last minute. People
need time to think about whether or not they want to participate.
They may wish to discuss the decision with family, close friends, or
religious advisors. They should not feel rushed or coerced. They
need time, especially if the information is disturbing or
particularly complex, to digest the information and come to terms
with it.
Information must be comprehensible. Even highly educated people
need to have technical information presented in simple terms. How
information is best expressed will vary with the population of
course. In studies involving nurses as subjects, for example,
researchers can explain a project using some medical terminology,
but lay persons need to have information presented as simply and
straightforwardly as possible. Some of the suggestions offered here
for writing readable consent forms are also useful for presenting
information in discussions.
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4.3 What must be said about the
research
Consent for research involving clinical procedures should be
discussed during prior visits to the clinic, not on the day of the
procedure. Whenever possible, subjects should be approached when
they are rested, lucid, and able to use eyeglasses or hearing
devices if they need them.
Federal regulations for human research identify some information
as "essential" for understanding any research project [45 CFR
46.116(a)&(b)]. At a minimum, investigators should:
- explain the purposes of the research;
- report the expected duration of the subject's
participation;
- describe the procedures to be followed;
- identify any procedures or products that are
experimental;
- explain why the subject is eligible to participate;
- describe any foreseeable risks or discomforts that the subject
will bear;
- describe any benefits to the subject or to others that can
reasonably be expected;
- disclose appropriate alternative procedures or courses of
treatment, if any, that might be advantageous to the
subject;
- explain the confidentiality of any records that identify the
subject;
- explain, for research that involves physical contact or
physical activity, whether compensation or medical treatment will
be available if the subject is injured and where to get further
information about this;
- identify people who can answer questions about the research,
including the principal investigator and a neutral third party who
can explain the rights of research subjects and who should be
contacted if the subject suffers injury related to the
research.The "out-of-study" contact language for patients in the
Fairview-University Hospitals and Clinics is as follows:
"If
you have any questions or concerns regarding the study and would
like to talk to someone other than the researcher(s), contact the
Fairview Research Helpline at telephone number 612-672-7692 or
toll free at 866-508-6961. You may also contact this office in
writing or in person at Fairview University Medical Center -
Riverside Campus, #815 Professional Building, 2450 Riverside
Avenue, Minneapolis, MN 55454."
- explain that participation is voluntary, that refusal to
participate will involve no penalty or decrease in benefits to
which the subject is otherwise entitled, and that the subject may
discontinue participation at any time without penalty or loss of
benefits.
In addition to this essential information, circumstances may
require researchers to:
- Explain that a treatment or procedure might involve currently
unforeseeable risks (including risks to an embryo or fetus, if a
participant is or becomes pregnant).
- Explain conditions under which the investigator can remove
people from the study without their concurrence.
- Explain any additional costs that participating in the study
might involve.
- Discuss the consequences of and the procedures for withdrawing
from the study.
- Declare that research findings that could affect participants'
willingness to remain in the study will be disclosed to
them.
- State the approximate number of people involved in the
study.
- Identify pilot or feasibility studies. Some subjects are
willing to participate in a study that has a track record but are
not willing to participate in a pilot phase. Participants need to
be told if they are among the first people to receive the
treatment or intervention.
- Inform women of child-bearing age whenever a pregnancy test is
part of the research protocol. They must also be told whether such
tests will be repeated during the course of a research project and
whether they must use contraceptives to participate in a clinical
trial. Men, too, need to be told if contraception is recommended
for them.
- Make clear whether the procedures or drugs used in a study are
standard, standard but used in a non-standard manner, or
experimental.
- If the study involves experimental drugs or devices, inform
the subject that the research and medical records may be reviewed
by the Food and Drug Administration (FDA) and by the company
sponsoring the research.
- Avoid stating that drugs or devices have been approved for
human use by the FDA if any part of the study is outside the
licensed and approved indications of those items. Patients
interpret such a claim to mean that the FDA has licensed and
approved this use of the item, not that the FDA has merely granted
permission to investigate the use of the item.
- Distinguish between consent to a study and consent to a
treatment. In "treatment studies" (in which a patient who is
undergoing a treatment is given a choice between undergoing it as
part of a study or undergoing it in a standard health care
context), the study and the treatment involve different benefits,
risks, and alternatives.
- If consent to the research and consent to the treatment can
be confused, they should be presented in separate consent forms.
- In discussing risks, the subject should be informed that
there might not be any benefit to being treated "on study"
instead of "off study."
- In discussing risks, the subject should be informed whether
the risks of being treated "on study" are different from the
risks of being treated "off study."
- In discussing alternatives, the subject should be told
whether the study treatment (drug or device) is or is not
available outside of the study context.
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4.4 What must be said about the
conduct of the research
Confidentiality
The researcher should describe the level of confidentiality of
the research data and the measures that will be taken to ensure that
confidentiality is maintained.
The phrase "only aggregate data will be presented" is appropriate
only when it is true. Strictly understood, it means that the
researcher will not describe a patient individually, even if the
patient has a unique event. What is more common, however, and what
the subject should be told, is that the subject's identity will not
be disclosed.
Conflict of interest
The University
Regents' Policy on Disclosure of Conflict of Interest requires
that researchers inform their subjects of any conflicts of interest
they have in the research. For example, researchers should disclose
any stake they have in companies that might be affected by the
research.
Finder's fees
Companies sometimes offer researchers incentives for recruiting
subjects or conducting research on an investigational drug or device
manufactured by the company. The incentive may be either a monetary
fee or a donation of equipment or materials. Researchers should
report these incentives to the IRB, which may require that this
information be disclosed to prospective subjects.
Payments to research subjects
If researchers plan to compensate subjects for participating in a
study, the consent form must describe the terms of payment and the
conditions under which subjects would receive partial payment or no
payment (for example, if they withdraw from the study before their
participation is completed). See section 3.14
Payments to subjects
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4.5 Assessing the subject's
understanding
The responsibility of ensuring that someone who might participate
genuinely understands the research and the risks and benefits
involved falls upon the researcher, not upon the prospective
subject. Hence it is critical to the consent process that the
researcher not only field questions but also ask questions. Asking
questions can further the discussion, elicit questions from the
prospective subject, prompt the prospective subject to think more
carefully about the project, and help the researcher decide whether
the person has adequately understood the project. These questions
must be prepared in advance.
Useful questions will be open-ended and non-directive. Rather
than asking for yes or no answers, they ask for explanation because
these questions often can be answered in a variety of ways, and do
not already contain the correct answer. Open-ended questions are
often introduced with "what," "where," "how often," "when," and
"please describe." Examples of open-ended questions are:
- "Just so that I'm sure you understand what is expected of you
here, would you please explain to me what you think we're going to
ask you to do?"
- "Describe in your own words the purpose of the study."
- "What more would you like to know?"
- "What is the possible benefit to you of taking the new
experimental drug? What are the possible risks?"
In contrast, examples of closed-ended and far less useful
questions are:
- "Do you understand?"
- "Do you have any questions?"
- "Do you see that there are some risks to taking this drug?"
Instead of furthering the discussion, closed-ended questions tend
to bring it to a stop and so should be avoided.
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4.6 Documenting the subject's consent
with a consent form
Once a subject understands a study and has expressed a
willingness to participate, researchers must document the subject's
consent with a consent form. Although a dated signature certifies
the subject's willingness to participate, it is not equivalent to
assuring that the subject has understood the research. Including a
date with the signature avoids confusion about whether the subject
began to participate before giving informed consent.
A researcher may need to prepare several consent forms, depending
on who the subjects are likely to be. For example, a single project
may require a consent form for the guardian or parent of a child, a
consent form for the competent adult subject, and a simplified
assent form for the 8- to 18-year-old or for the adult who is not
competent to give consent alone. [See following sections for
discussion of assent forms.] Foreign-language versions of consent
forms will be needed if people who do not speak English are to be
enrolled. [See section 4.11 for discussion of translated consent
forms. This section also discusses unexpected enrollment of
non-English-speaking subjects.]
The person who prepares the documents
should:
- Print all documents in type no smaller than 12 points to make
sure they are readable. If the subjects will have difficulty with
12 point font, a larger font is necessary.
- Place the title of the study on the first page, exactly as it
appears in the IRB files unless there is a compelling reason to
shorten or change the title. "Informed Consent" is not an
acceptable title because it obscures the fact that informed
consent is a process, not the document itself, and implies a
completeness that the form may not have.
- Number each page after the title page so that pages appear in
a logical order and missing pages are readily noted (example:
"page 2 of 4").
- Print the IRB code number assigned to the study on the consent
form.
- Include a consent form version date. This date should be
updated each time a new version of the consent form is approved by
the IRB.
Format and specific requirements
The consent form should:
- Identify the researchers by name along with their
University and Departmental Affiliation on the first page of the
consent form.
The form should not say that the
study is "sponsored" or "endorsed" by the University.
If
the project is conducted by faculty or staff, the first page of
the consent form should be printed on departmental letterhead. For
student projects, the words "University of Minnesota" should
appear in the header on the first page, and advisers' names and
phone numbers should be given with the student's name and contact
information.
- Invite participation
Consent
forms should "invite" participation. They should not say that a
patient's physician or friend recommends participation, nor should
they "offer the opportunity" to participate. It may be appropriate
to point out that withdrawing from a study could have adverse
consequences to subject treatment.
- Summarize Cautiously
Information
described earlier in the consent form should be summarized only in
order to clarify. Summaries that suggest a warning or limitation
of liability or opportunity for redress are not acceptable.
Examples that are unacceptable are:
- "You understand that..."
- "The possible risks associated with this study have been
presented."
- "The method and purpose of administration of this study have
been explained to you."
- "You have been made aware of certain risks and
consequences."
Readability and technical language
In writing consent forms, researchers should:
- Use declarative sentences suited for an eighth-grade reading
level.
- Write in the second person ("you") rather than the first
person ("I"), and avoid shifting from one to other.
- Avoid strike-out formats (such as "You/Your spouse/Your
child"), since they depersonalize the form and often make it
difficult to read.
- Keep the description of the study as brief as possible, even
if the study is complex. The details can be placed in an appendix.
- List only the major risks associated with an experimental drug
or procedure. Some effective consent forms simply state, "The risk
of being on this study is that the treatment may not turn out to
be as successful as we hope, and may even be less effective than
our previous standard treatment. In addition to this risk of being
on the study, the drugs used in the treatment have their own risks
and side effects. The most important ones are: ..." Again, the
details go in an appendix.
- Use paragraph headings and illustrations. Use flow charts or
calendar-like tables to explain studies that involve multiple
visits, that ask subjects to go from one place to another, or that
involve different protocols depending on research benchmarks.
- Describe quantities in lay terms (teaspoons, for example).
Communicate size with an illustration or a reference to a common
household object of the same size.
- Ask a neighbor, friend, or someone else who is unfamiliar with
the field to read the final draft of a consent form. Software
packages that evaluate a text's "readability" may be helpful.
- Replace technical language with lay terms. Some commonly used
technical terms and possible replacements follow:
Term |
Definition |
acute |
new, recent, sudden |
adverse effect |
side effect |
assay |
lab test |
benign |
not malignant, usually without serious
consequences |
bolus |
an amount given all at once |
carcinogenic |
capable of causing cancer |
catheter |
a tube for withdrawing or introducing fluids |
chronic |
continuing for a long time |
clinical trial |
an experiment with patients |
controlled trial |
a study in which the experimental procedures are
compared to a standard (accepted) treatment or
procedure |
culture |
test for infection, or organisms that could cause
infection |
double blind |
study in which neither investigators nor subjects know
which drug the subject is receiving |
dysplasia |
abnormal cells |
edema |
increased fluid |
efficacy |
effectiveness |
extravasate |
to leak outside of a blood vessel |
hematoma |
a bruise, a black and blue mark |
heparin lock |
needle placed in the arm with blood thinner to keep the
blood from clotting |
monitor |
check on, keep track of, watch carefully |
morbidity |
undesired result or complication |
mortality |
death or death rate |
necrosis |
death of tissue |
oncology |
the study of tumors or cancer |
percutaneous |
through the skin |
placebo |
a substance of no medical value, an inactive
substance |
PRN |
as needed |
protocol |
plan of study |
random |
by chance, like the flip of a coin |
relapse |
the return of a disease |
retrospective |
looking back over past
experience |
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4.7 When to submit the form to the
IRB
Researchers must submit consent forms when they first apply for
IRB review and approval, and when they apply for continuing review.
Since the standards for consent forms change over time, in part due
to changes in regulatory mandates and community styles and
expectations, the IRB reviews the form at renewal to ensure that it
is up to date.
In addition, the IRB may ask researchers to modify consent forms
at other times, when circumstances warrant. Any revisions made to a
previously approved consent form must be submitted to the IRB for
approval before use.
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4.8 When the consent requirement can be
waived
On rare occasions, the federal regulations for human subjects
research allow a waiver of the requirement for informed consent. For
example, a waiver is possible if a study investigates certain
aspects of public benefit or service programs (see 45
CFR 46.116[c]). Also, either a waiver or a consent process that
omits or modifies the essential elements of informed consent is
possible if the IRB finds that:
- the research involves no greater than minimal risk to the
subjects;
- the waiver or alteration will not adversely affect the rights
and welfare of the subjects;
- the research would be impracticable without the waiver or
alteration; and
- the subjects will be informed of the study when it is over (if
at all possible).
Only the IRB can waive or modify the consent process. Researchers
are not authorized to make this decision.
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4.9 The Certificate of Confidentiality -
an additional protection
A "Certificate
of Confidentiality" protects subjects' anonymity by protecting
research records from subpoena. The assistant secretary for health
in the Department of Health and Human Services issues the
certificate under two conditions: the research is on a sensitive
topic, and the protection is necessary to achieve the research
objectives. The certificates are granted sparingly. The study's
funding source is not relevant to the decision.
The certificate goes beyond the consent form in ensuring
confidentiality and anonymity. Without the certificate, researchers
can be required by a court-ordered subpoena to disclose research
results (usually as part of a criminal investigation of the
subjects).
Research can be considered "sensitive" if it involves the
collection of:
- information about sexual attitudes, preferences, practices;
- information about the use of alcohol, drugs, or other
addictive products;
- information about illegal conduct;
- information that could damage an individual's financial
standing, employability, or reputation within the community;
- information in a subject's medical record that could lead to
social stigmatization or discrimination; or
- information about a subject's psychological well-being or
mental health.
This list is not exhaustive. Researchers contemplating research
on a topic that might qualify as sensitive should contact the IRB
office for help in applying for a certificate. The IRB sometimes
requires investigators to apply for a certificate.
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4.10 Children and adolescents
Written parental permission is required for studies involving
children under the age of 18. If the research involves greater than
minimal risk, signatures from both parents are required unless the
second signature is not reasonably available. A single signature is
sufficient if only one parent has legal responsibility for the care
and custody of the child or if one parent is deceased, unknown, or
incompetent. Parental permission is documented in a form similar to
an adult subject consent form, tailored to invite "your child" to
participate rather than "you".
On rare occasions, the IRB can grant a "waiver of parental
consent," but only if the research will yield great benefit to the
population being studied and if obtaining parental consent would
pose a considerable risk to the potential subjects.
Once parental permission has been obtained, the agreement of the
child is required. Parental permission overrules a child's decision
not to participate in therapeutic settings.
The child's agreement is documented with an "assent form," a
child-friendly document that outlines the essential information
about the research. All children 8 years through 17 years old should
be given an opportunity to assent, since most children 8 years old
have the cognitive and emotional maturity to understand a research
project and to decide whether they want to participate in it.
Some children under the age of 8 may also be capable of granting
and withholding assent, and the IRB asks researchers to be sensitive
to the needs of these children on an individual basis. Researchers
should try to draft a form that is age-appropriate and
study-specific, taking into account the typical child's experience
and level of understanding, and composing a document that treats the
child respectfully and conveys the essential information about the
study. The form should:
- tell why the study is being conducted;
- describe what will happen and for how long or how often;
- say it's up to the child to participate and that it's okay to
say no or withdraw;
- explain if it will hurt and for how long and how often;
- say what the child's other choices are;
- describe any good things that might happen;
- say whether there is any compensation for participating; and
- ask for questions.
The document should be limited to one page if possible.
Illustrations might be helpful, and larger type makes a form easier
for young children to read. Studies involving older children or
adolescents should include more information and may use more complex
language.
In instances where critical therapeutic research is involved,
parental permission overrules a child's decision to participate. In
such cases, a child's dissent would not be honored; therefore an
"information sheet" rather than an assent form should be used. The
information sheet should include the same info found in an assent
form except:
- it should not indicate that the decision to participate is up
to the child nor that it is okay to say no.
- it should not include signatures.
Subpart
D of 45 CFR 46.401-409, "Additional Protections for Children
Involved as Subjects in Research," outlines the conditions of
participation for minor subjects.
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4.11 Consent and language barriers
When planning research which will include non-English speaking
subjects, researchers should prepare both English-language and
translated consent forms for proposals involving
non-English-speaking subjects. An explanation of the translations
and the expertise of the translator should be provided for IRB
review. The IRB may consult with language experts or require a
"back-translation" into English.
As an alternative to translated consent
forms, an oral presentation of informed consent
information in conjunction with a short form written consent
document (stating that the elements of consent have been presented
orally) and a written summary of what is presented orally can be
approved by the IRB. A witness to the oral presentation is required,
and the subject must be given copies of the short form document and
the summary.
When this procedure is used with subjects who do not speak
English:
- the oral presentation and the short form written document (see
sample attached) should be in a language understandable to the
subject;
- the IRB-approved English language informed consent document
may serve as the summary; and
- the witness should be fluent in both English and the language
of the subject.
At the time of consent, the following signatures should be
obtained:
- the short form document should be signed by the subject (or
the subject's legally authorized representative);
- the summary (i.e., the English language informed consent
document) should be signed by the person obtaining consent as
authorized under the protocol; and
- the short form document and the summary should be signed by
the witness. When the person obtaining consent is assisted by a
translator, the translator may serve as the witness.
The IRB must receive all foreign language versions of the short
form document as a condition of approval (see 46.117(b)(2)).
Expedited review of these versions is acceptable if the protocol,
the full English language informed consent document, and the English
version of the short form document have already been approved by the
convened IRB.
Download
short forms in different language (languages available: Arabic,
Cambodian, Croatian, French, Hmong, Lao, Oromo, Russian, Somali,
Spanish, Vietnamese)
Sometimes a subject understands English but does not read or
write English. An impartial witness should document that the subject
understands the study and the consent process and consented to
participate.
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4.12 Cross Cultural Consent Issues
The requirements for documenting informed consent vary among
cultures. The IRB does not exempt projects conducted in foreign
countries or with other cultural groups here from the consent
requirement, but it can waive the requirement for written
documentation of consent. In some settings, the process of signing
the form is very intimidating and is thought to be riskier than the
research itself.
Researchers planning to conduct cross cultural research should
justify their proposed method of documenting consent. The
justification should include a description of customs if they
constrain the typical informed consent process.
Subjects in foreign sites should be given local contacts for any
questions they may have about the research or about their
rights.
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4.13 Research in acute care settings
Although the subject's consent must be obtained whenever
possible, research on drugs or devices that are employed during
emergencies is sometimes an exception.
Food and Drug Administration (FDA) regulations for human subjects
research allow for an emergency exception to informed consent if the
situation is life-threatening and if there is no alternative
approved therapy with an equal or greater likelihood of saving the
patient's life (21
CFR 50.23 [a]). The intent is to allow physicians, exercising
their judgment about patients' conditions, to use innovative
treatments on incompetent patients. (See 3.22
Emergency waivers)
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Next Section: 5.
Sponsored Projects: Special Requirements
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