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NEBRASKA’S HEALTH SCIENCE CENTER
OFFICE OF REGULATORY AFFAIRS (ORA)
Institutional Review Board (IRB)
ADDENDUM E
Research Involving Decisionally-Impaired Persons
SECTION I
DATE:
IRB #:
TITLE OF PROTOCOL:
PRINCIPAL INVESTIGATOR
SECTION II
Instructions: HHS and non-HHS funded research involving decisionally impaired individuals
must comply with 1) HHS regulations at 45 CFR 46.111(b), and 2) FDA regulations at 21 CFR
56.111(b), as applicable. The regulations require additional appropriate protections because these
individuals are considered to be a vulnerable subject population. This addendum application is
designed to assist the investigator in developing the documentation necessary to verify compliance
with this requirement. All questions should therefore, be completely addressed by consulting this
section of the regulations and IRB policies which can be accessed at the IRB website
(http://www/unmc.edu/irb.)
This addendum should be submitted with the IRB application. Information should be provided by
site for all studies involving more than one site for which the UNMC IRB or PedsIRB is the only IRB
of record. The Addendum must provide sufficient information to facilitate an effective review by all
members of the IRB including non-specialists. Applications that do not allow for an effective review
may be returned to the investigator, without IRB review, for revision and resubmission.
1. What is the justification for enrolling decisionally impaired persons as subjects in this
research?
Note: Individuals who are decisionally impaired are considered vulnerable. When the research
objectives can be accomplished using less vulnerable subjects, this should be done.
2. What is the likely degree of impairment of the subjects which affects their decisionmaking ability?
Note: Subjects may have varying degrees of cognitive impairment due to underlying
pathological, psychological or other conditions. This section should clearly provide an estimate
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of the likely degree of impairment which would affect the subject’s ability to make a legally
effective informed decision whether to participate in research.
3. If the subjects have not been declared legally incompetent by the courts, how will
capacity to consent to participate in research be assessed, who will perform the
assessment and how will the results be documented?
Note: Different clinical specialties have specific standards for assessing capacity in very diverse
patient groups. The standards of the clinical specialty area where the research will be
conducted should generally be used for the assessment. The method of assessment of capacity
to consent should be based upon the likely degree of cognitive or decisional impairment in the
prospective subject population. In some cases, it would be appropriate to use more
comprehensive assessment tools such as a neuropsychological evaluation and even utilize an
independent assessor. In other cases where there is not a need for a lengthy assessment, the
investigator may choose to use the Assessment of Capacity to Consent to Participate in
Research Form available on the IRB website at www.unmc.edu/irb. The questions on this form
are based upon Arch Gen Psychiatry, 2005; 62:726-733.
4. How will subject capacity to consent be reassessed throughout the study? If it is
extremely unlikely that subjects will regain capacity to consent, this should be stated.
Note: Some decisionally impaired subjects who are enrolled in research (using a legally
authorized representative LAR consent) may regain some cognitive function and may even
become competent. Therefore, subject capacity should be re-assessed throughout the study. If
a subject regains capacity, they must either provide written consent to continue to participate or
withdraw from the study. However, if the improvement in cognitive function may be transient,
consent from the subject’s LAR must be maintained.
5. Process of obtaining consent from a legally authorized representative (LAR)
A. Who will provide consent?
Note: Individuals authorized to provide consent for a decisionally impaired subject include:
1) legal guardian with health care decision-making authority, 2) a Power of Attorney for
Health Care (POA-HC), 3) an Institutionally Authorized Surrogate (IAS) [pursuant to
Nebraska Medical Center Policy (MS14)] in the following order: subject’s spouse; adult
child of the subject or, if the subject has more than one adult child, all of the adult children
who are reasonably available for consultation; and a parent of the subject or parents if both
are reasonably available; any relative of the incapacitated person with whom he or she has
resided for more than six months; an adult sibling; an adult person in the next degree of
kindred in the order named by the succession laws of the state of Nebraska; or significant
others who have a current sustained relationship with the patient and can present the
patient’s preferences.
B.
When will the LAR be approached relative to the subject’s actual participation in the
study?
Note: The LAR for the prospective subject should be approached sufficiently far in
advance to enable them to have time to make an informed decision to permit the subject to
participate in the study.
C. Who will approach the LAR about the prospective subject’s participation in the
study?
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Note: This section should describe the involvement and responsibility of study personnel
who will be involved in the process of consent.
D. How much time will be allotted to the process of consent?
Note: The amount of time allotted to the process of consent is dependent upon the nature
and complexity of the study.
E. What is the location where informed consent will be obtained?
Note: The environment where informed consent will be obtained should be a private and
quiet location, conducive to discussion and thoughtful consideration by the proxy
F. Will a delayed consent procedure be used?
Yes
No. Provide justification.
Note: A delayed consent procedure is one where the LAR for the prospective subject is
presented with the consent form after discussion with the investigator and is encouraged to
discuss participation in the study with family, friends, counselors, or other confidants before
they sign. Delayed consent is strongly encouraged except where the research is simple
and of low risk, or where the prospective subject’s medical condition precludes such a
delay
G. How will it be determined that the LAR understood the information presented?
Note: All investigators have a legal and an ethical obligation to ensure that the LAR has
sufficient knowledge and comprehension of all the elements of informed consent to enable
them to make an informed and enlightened decision whether or not to permit the
decisionally-impaired subject to participate in research. The fact that an individual is
prepared to sign the informed consent form and has no unanswered questions does not
necessarily represent sufficient evidence of an adequate level of comprehension. Some
investigators, therefore, choose to determine the level of a person’s comprehension by
questioning the individual concerning their understanding of all the elements of informed
consent. This section should clearly document that the investigator has an adequate plan
in place to assure existence of an acceptable level of comprehension of all the elements of
consent
H. Will there be a formal process of on-going re-consent (over and above re-consent
associated with changes in protocol)?
No
Yes. Describe.
Note: Federal regulations, UNMC IRB policies, and sound ethical practice require that the
LAR for a decisionally-impaired subject have the opportunity to withdraw the subject from
the research at any time. In certain cases, it may be appropriate to seek active re-consent
from the LAR. Preferences and interests may change over time, even in the absence of
material changes in the research protocol. Therefore, investigators should consider
obtaining re-consent, or at least reaffirmation of the LAR’s willingness to permit the subject
to continue participation, on a routine basis. In most cases, such re-consent need only be
verbal agreement on the part of the LAR after questioning by the investigator or research
team member. In rare cases, more formal re-consent (for example, quarterly or at the time
of each research intervention) may be appropriate.
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6. Process of obtaining assent from the decisionally-impaired adult
A. Will the investigator ask the prospective subject to assent to participate in the
research?
Yes
No. Provide justification for a waiver of assent.
Note: “Assent” means the subject’s affirmative agreement to participate in research.
Mere failure to object should not be construed as assent. Sound ethical practice
requires that assent be obtained when, in the judgment of the investigator, the
prospective subject has sufficient cognitive ability to provide assent. If a subject
assents and then changes their mind during the course of the study, that subject
should normally be withdrawn from the study if their dissent is active and persistent.
B. How will it be determined that the prospective subject understood the
information presented?
Note: All investigators have an ethical obligation to ensure that the prospective subject
has sufficient knowledge and comprehension of the elements of assent to enable them
to make an informed decision to participate in the research. The fact that the
prospective subject is prepared to sign the assent form and has no unanswered
questions does not necessarily represent sufficient evidence of an adequate level of
comprehension. Some investigators, therefore, choose to determine the level of
comprehension by simply questioning the subject’s understanding of the elements of
assent. This section should clearly document that the investigator has an adequate
plan in place to assure existence of an acceptable level of comprehension of the
elements of assent.
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