INFORMED CONSENT: PROCESS,
DOCUMENTATION, ALTERATION
AND WAIVERS
Suzanne Sparrow
Objectives
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Significance & History
Regulations (DHHS/FDA)
Elements of Consent
Waiving/altering consent
Waiving documentation of consent
Process of consent
Consent for Non-English speaking participants/
English speaking participants with low literacy
Document Management/Tips
Why is consent important?
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Nazi War Crimes (1940’s)
 Freezing
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Tuskegee (1932-1972)
 Withheld
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information/treatment
Belmont Report (1979)
 Respect
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experiments, sea water experiments
for Persons, Beneficence and Justice
Havasupai Indian Tribe/Arizona State University
(1990-1992)
 Use
of samples not specified in informed consent.
What regulations must be adhered to
regarding informed consent?
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Studies subject to DHHS requirements (45 CFR 46.116)
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Obtain the legally effective informed consent of the subject or the subject's
legally authorized representative prior to involvement in research.
Provide the prospective subject or the representative sufficient opportunity to
consider whether or not to participate and minimize the possibility of coercion
or undue influence.
Information shall be in language understandable to the subject or the
representative. No informed consent, whether oral or written, may include any
exculpatory language.
contain the information required by each of the eight basic elements of 45
CFR 46.116(a), and each of the six elements of 45 CFR 46.116(b) that is
appropriate to the study.
What regulations must be adhered to
regarding informed consent (cont.)?
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Studies subject to FDA requirements (21 CFR 50.20)
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identical requirements as DHHS except the
confidentiality statement for FDA trials must include a
statement that the FDA may inspect research records
 Provisions for altering or waiving consent within DHHS
regulations but not FDA
 Provisions for waiving documentation of consent found in
both DHHS and FDA regulations with only slight differences
 FDA requires a specific statement if a clinical trial--21 CFR
50.25(c)
8 Essential Elements of Consent
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(1) A statement that the study involves research, an explanation of the purposes of the research and
the expected duration of the subject's participation, a description of the procedures to be followed,
and identification of any procedures which are experimental.
(2) A description of any reasonably foreseeable risks or discomforts to the subject.
(3) A description of any benefits to the subject or to others which may reasonably be expected from
the research.
(4) A disclosure of appropriate alternative procedures or courses of treatment, if any, that might be
advantageous to the subject.
(5) A statement describing the extent, if any, to which confidentiality of records identifying the subject
will be maintained [and that notes the possibility that the FDA may inspect the records].
(6) For research involving more than minimal risk, an explanation as to whether any compensation and
an explanation as to whether any medical treatments are available if injury occurs and, if so, what
they consist of, or where further information may be obtained.
(7) An explanation of whom to contact for answers to pertinent questions about the research and
research subjects' rights, and whom to contact in the event of a research-related injury to the subject.
(8) A statement that participation is voluntary, that refusal to participate will involve no penalty or loss
of benefits to which the subject is otherwise entitled, and that the subject may discontinue participation
at any time without penalty or loss of benefits to which the subject is otherwise entitled.
6 Additional Elements of Consent
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(1) A statement that the particular treatment or procedure may involve risks to the
subject (or to the embryo or fetus, if the subject is or may become pregnant) which
are currently unforeseeable.
(2) Anticipated circumstances under which the subject's participation may be
terminated by the investigator without regard to the subject's consent.
(3) Any additional costs to the subject that may result from participation in the
research.
(4) The consequences of a subject's decision to withdraw from the research and
procedures for orderly termination of participation by the subject.
(5) A statement that significant new findings developed during the course of the
research which may relate to the subject's willingness to continue participation will
be provided to the subject.
(6) The approximate number of subjects involved in the study.
Consent Element for Clinical Trials
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When seeking informed consent for applicable clinical trials, the
following statement shall be provided to each clinical trial subject
in informed consent documents and processes. This will notify the
clinical trial subject that clinical trial information has been or will
be submitted for inclusion in the clinical trial registry databank.
The statement is: "A description of this clinical trial will be
available on http://www.ClinicalTrials.gov, as required by U.S.
Law. This Web site will not include information that can identify
you. At most, the Web site will include a summary of the results.
You can search this Web site at any time."
Waiving/Altering Consent (only for nonFDA regulated research)
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An IRB may approve a consent procedure which does not
include, or which alters, some or all of the elements of
informed consent, or waive the requirements to obtain
informed consent provided the IRB finds and documents that:
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(1) The research involves no more than minimal risk to the subjects;
(2) The waiver or alteration will not adversely affect the rights and
welfare of the subjects;
(3) The research could not practicably be carried out without the
waiver or alteration; and
(4) Whenever appropriate, the subjects will be provided with
additional pertinent information after participation.
Waiving Documentation of Consent
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An IRB may waive the requirement for the investigator to obtain a signed
consent form for some or all subjects if it finds either:
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(1) That the only record linking the subject and the research would be the consent
document and the principal risk would be potential harm resulting from a breach of
confidentiality. Each subject will be asked whether the subject wants documentation
linking the subject with the research, and the subject's wishes will govern (not found in
FDA regulations); or
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(2) That the research presents no more than minimal risk of harm to subjects and
involves no procedures for which written consent is normally required outside of the
research context.
In cases in which the documentation requirement is waived, the IRB may
require the investigator to provide subjects with a written statement
regarding the research.
Consent Process
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Informed consent is more than just a signature on a form, it is a process of information exchange—not
a means to an end.
 Institutional Review Boards (IRBs), clinical investigators, and research sponsors all share
responsibility for ensuring that the informed consent process is adequate.
The investigator is responsible for ensuring that informed consent is obtained from each research
subject before that subject participates in the research study. While the investigator is not required to
personally conduct the consent interview, the investigator remains ultimately responsible, even when
delegating this task.
In addition to signing the consent, the subject/representative should enter the date of signature on
the consent document, to verify that consent was actually obtained before the subject began
participation in the study. If consent is obtained the same day that the subject's involvement in the
study begins, the subject's research record should document that consent was obtained prior to
participation in the research (time). A copy of the consent document must be provided to the subject
and the original signed consent document should be retained in the study records.
The IRB should be aware of who will conduct the consent interview. Those conducting consent
procedures should be adequately trained.
The consent process begins when a potential research participant is initially contacted. Although an
investigator may not recruit subjects to participate in a research study before the IRB reviews and
approves the study, an investigator may determine if an adequate number of potentially eligible
subjects is available.
Non-English Speaking Participants
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When the study subject population includes non-English speaking people or the
clinical investigator or the IRB anticipates that the consent interviews will be
conducted in a language other than English, the IRB requires a translated consent
document to be submitted. As required by both the FDA and DHHS regulations, a
copy of the consent document must be given to each subject. In the case of nonEnglish speaking subjects, this would be the translated document. While a
translator may be helpful in facilitating conversation with a non-English speaking
subject, this should not be substituted for a written translation.
If a non-English speaking subject is unexpectedly encountered, investigators will
not have a written translation of the consent document and must rely on oral
translation. If investigators enroll subjects without an IRB approved written
translation, a "short form" written consent document, in a language the subject
understands, should be used to document that the elements of informed consent
were presented orally. The required signatures on a short form are stated in 21
CFR 50.27(b)(2) and 45CFR46.117(b)(2).
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Investigators should carefully consider the ethical/legal ramifications of enrolling subjects when a
language barrier exists. If the subject does not clearly understand the information presented, the
subject's consent will not truly be informed and may not be legally effective.
ECU UMCIRB allows the short form to be used only once per study before expecting a fully
translated consent to be submitted.
English Speaking Subjects with Low Literacy
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A person who speaks and understands English, but does not read and write,
can be enrolled in a study by "making their mark" on the consent document,
when consistent with applicable state law.
A person who can understand and comprehend spoken English, but is
physically unable to talk or write, can be entered into a study if they are
competent and able to indicate approval or disapproval by other means. If
(1) the person retains the ability to understand the concepts of the study
and evaluate the risk and benefit of being in the study when it is explained
verbally (still competent) and (2) is able to indicate approval or
disapproval to study entry, they may be entered into the study. The consent
form should document the method used for communication with the
prospective subject and the specific means by which they communicated
agreement to participate in the study. An impartial third party should
witness the entire consent process and sign the consent document.
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Video tape recording of the consent interview is recommended.
http://www.fda.gov/RegulatoryInformation/Guidances/ucm126431.htm
Minor Assent
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Assent means a child's affirmative agreement to participate in a clinical investigation. Mere
failure to object should not, absent affirmative agreement, be construed as assent.
In determining if children are capable of giving meaningful assent, the IRB will take into
account the ages, maturity, and psychological state of the children, either individually or as
a group, as it deems appropriate.
The PI, in consultation with the UMCIRB, will decide if the protocol requires an assent
document for the child in addition to a permission form for the parents or guardian. The
decision will be based primarily on the expected level of comprehension of the proposed
research participants.
At ECU, unless otherwise determined by the IRB, documented assent is required for children
12 to 17 years of age. Children 7 to 11 years of age should be given the opportunity to
give verbal assent, with the script to be used in these situations submitted for IRB review
and approval. This verbal assent should be documented in the research record or on the
parental permission form. For children under the age of 7 years, the research should be
explained to the extent of the child’s understanding but no documentation is required.
Parent/Guardian Signatures for
Minor Assent
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Investigators must consider the number of parental signatures
required according to 45 CFR 46 Subpart D and 21 CFR 50
Subpart D as follows:
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Research that does not involve more than minimal risk. Requires one parent’s signature.
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Research involving more than minimal risk but presents the prospect of direct benefit to the
individual participants. Requires one parent’s signature.
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Research involving more than minimal risk and no prospect of direct benefit to individual
participants, but likely to yield generalizable knowledge about the participant's disorder
or condition. Requires both parents’ signatures, unless one parent is deceased, unknown,
incompetent, or not reasonably available, or when only one parent has legal responsibility
for the care and custody of the child.
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Research not otherwise approvable which presents an opportunity to understand, prevent,
or alleviate a serious problem affecting the health or welfare of children. Requires both
parents’ signatures, unless one parent is deceased, unknown, incompetent, or not
reasonably available, or when only one parent has legal responsibility for the care and
custody of the child.
Document Management
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Ensure correct consent document is being utilized by
those performing consent (check date stamps).
Include new version number or date when making
an Amendment to the consent.
Track and document re-consent when necessary.
Verify necessary signatures, initials and date.
Tips
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Read the consent through in its entirety before
submitting for approval.
Lay language.
Run spell check and investigate grammar issues
(Microsoft Word can do this for you).
Charts and tables.
Send consents to potential participants ahead of
time.
Document consent conversation.
Consent: Example
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http://www.carilionclinic.org/Carilion/Informed+Co
nsent
Questions/Comments?