14
Informed Consent
14.1 Informed Consent Process
No investigator may involve a human being as a subject in research without obtaining the
legally effective informed consent of the subject or the subject’s legally authorized
representative unless a waiver of consent has been approved by the COMIRB. In general,
the COMIRB considers individuals who are unable to consent for their own clinical care to be
unable to consent for research participation. Tools or instruments such as the Mini Mental
Exam can also be used to determine capability to consent.
Investigators must obtain consent prior to entering a subject into a study and/or conducting
any procedures required by the protocol, unless consent is waived by the COMIRB.
Consent must always be sought under circumstances that:
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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.
The COMIRB will consider where the consent process will take place and the individual who
will be obtaining consent (e.g. the investigator, collaborator, or qualified designee) in its
determination regarding the appropriateness of the consent process. When the potential
participant’s understanding of the research may be impaired due to the timing, location, or
individuals participating in the proposed consent process, the COMIRB will require an
alternative process.
The information that is given to the subject or the representative must be in language
understandable to the subject or the representative.
No informed consent, whether oral or written, may include exculpatory language which the
subject or the representative is made to waive or appear to waive any of the subject’s legal
rights.
No informed consent, whether oral or written, may include exculpatory language through
which releases or appears to release the investigator, the sponsor, the institution, or its
agents from liability for negligence.
A person knowledgeable about the consenting process and the research (i.e., a member of
the project’s research team) to be conducted must obtain the informed consent.
If someone other than the investigator conducts the interview and obtains consent, the
investigator needs to formally delegate this responsibility and the person so delegated must
have received appropriate training to perform this activity.
14.2 Basic Elements of Informed Consent
Informed consent must be sought from each potential subject or the subject’s legally
authorized representative, in accordance with, and to the extent required by 45 CFR 46.116
and 21 CFR 50.25.
14.2.1 Basic Elements
 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; a description of any reasonably foreseeable risks or discomforts to the
subject;
 A description of any benefits to the subject or to others which may reasonably be
expected from the research;
 A disclosure of appropriate alternative procedures or courses of treatment, if any,
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that might be advantageous to the subject (for biomedical research);
A statement describing the extent, if any, to which confidentiality of records
identifying the subject must be maintained;
 For applicable FDA-regulated studies information about ClinicalTrials.gov.
Applicable studies include:

Phase 2 – 4 Interventional studies;
Studies involving drugs, biologics, or medical devices regulated by FDA;
Studies that have at least one site in the US or is conducted under an IND or
IDE; and
Studies initiated or ongoing as of September 27, 2007 or later
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For biomedical research involving more than minimal risk, an explanation as to the
availability of medical treatment in the case of research-related injury, including who
will pay for the treatment and whether other financial compensation is available;
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;
A statement that participation is voluntary, refusal to participate will involve no
penalty or loss of benefits to which the subject is otherwise entitled, and the subject
may discontinue participation at any time without penalty or loss of benefits to which
the subject is otherwise entitled;
For FDA-regulated studies, the possibility that the Food and Drug Administration
may inspect the records needs to be included in the statement regarding subject
confidentiality.
An explanation of whom to contact to voice concerns or complaints about the
research.
Contact information for the COMIRB to obtain answers to questions about the
research; to voice concerns or complaints about the research; to obtain answers to
questions about their rights as a research participant; in the event the research staff
could not be reached; and in the event the subject wishes to talk to someone other
than the research staff.
14.2.2 Additional Elements
 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 (For example: Include when the research involves
investigational test articles or other procedures in which the risks to subjects is not
well known.);
 Anticipated circumstances under which the subject’s participation may be terminated
by the investigator without regard to the subject’s consent (For example: Include
when there are anticipated circumstances under which the investigator may
terminate participation of a subject.);
 Any additional costs to the subject that may result from participation in the research
(For example: Include when it is anticipated that subjects may have additional
costs.);
 The consequences of a subject’s decision to withdraw from the research and
procedures for orderly termination of participation by the subject (For example:
Include when withdrawal from the research is associated with adverse
consequences);
 A statement that significant new findings developed during the course of the
research which may relate to the subject’s willingness to continue participation must
be provided to the subject (For example: Include when the research is long term and
interim information is likely to be developed during the conduct of the research.);
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The approximate number of subjects involved in the study (For example: Include
when the research involves more than minimal risk).
14.2.3 Additional Elements Required by the VA
When appropriate, VA requires one or more of the following elements of information be
provided to the subject:
 Commercial Product: If applicable, that the investigator believes that the human
biologic specimens obtained could be part of, or lead to the development of,
commercially valuable products.
 Future Use of Specimens: if the specimens are to be retained after the end of the study
for future research, where the specimens will be retained, who will have access to
them, and how long they will be retained.
 Future Use of Data: If any of the data will be retained after the study for future research,
where the data will be stored, and who will have access to the data.
 Re-Contact: if the subject will be re-contacted for future research whether within the VA
or outside the VA.
 Payment for Participating in the Study: If appropriate, a statement regarding any
payment the subject is to receive for participating in the study and how the payment is
to be made.
 Disclosure of Results: If the subject will receive a report of the aggregate results or any
results specific to the subject.
14.3 Documentation of Informed Consent
Informed consent must be appropriately documented, in accordance with, and to the extent
required by 45 CFR 46.117 or 21 CFR 50.27.
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Informed consent is documented by the use of a written consent form approved by
the COMIRB and signed and dated by the subject or the subject’s legally authorized
representative at the time of consent.
A copy of the signed and dated consent form must be given to the person signing
the form.
The consent form may be either of the following:
a. A written consent document that embodies the elements of informed consent may
be read to the subject or the subject’s legally authorized representative, bu t the
subject or representative must be given adequate opportunity to read it before it is
signed;
If use of facsimile is approved by the IRB, the subject may submit the signed and dated
informed consent form to the investigator or designee by facsimile.
b.
Or
A short form written consent document detailing the elements of informed
consent is presented / translated orally to the subject or the subject’s legally
authorized representative. When this method is used:
1)
There must be a witness to the oral presentation; and
2)
The COMIRB must approve a written summary (usually the full consent
form) of what is to be signed by the subject or representative; and
3)
The witness must sign both the short form and a copy of the summary;
and
4)
The person actually obtaining consent must sign a copy of the summary;
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and
A copy of the summary must be given to the subject or representative, in
addition to a copy of the short form.
Note: The HIPAA B form in English (unless the Spanish translation is being used)
must also be translated by the interpreter as part of the summary and the HIPAA B
form must be signed and dated by the subject or representative.
5)
14.3.1 Documentation of the Consent Process
The informed consent form must be signed and dated by:
The subject or the subject’s legally authorized representative;
The person obtaining the informed consent, and
A witness, if required by COMIRB (e.g., the COMIRB may require a
witness if the study involves an invasive intervention or an investigational
drug or device). A witness is always required when a short form consent
is employed to enroll non-English speaking or non-reading subjects.
4)
The PI should sign and date the consent document as part of his or her
oversight of the study especially for FDA regulated research. This
signature and date may be later than the other required signatures
detailed above but should be within 30 days of the subject signature,
unless a shorter time frame is specifically directed by COMIRB or
COMIRB may determine that a PI signature line is not required for the
particular study.
Note: the witness is required to witness only the subject’s or subjects’ LAR ‘s signature not
the informed consent process unless the sponsor or COMIRB requires the witness to
witness the informed consent process.
1)
2)
3)
The witness cannot be the potential subject or the person who obtained informed consent
from the subject, but may be another member of the study team, a translator, or may be a
family member.
Withdrawal:
When a participant withdraws from a study, the data collected on the participant to the point
of withdrawal remains part of the study database and may not be removed. A researcher
may ask a participant who is withdrawing whether the participant wishes to provide
continued follow-up and further data collection subsequent to their withdrawal from the
interventional portion of the study. It must be clear to subjects what was considered studyrelated intervention and what is continued follow-up. The researcher must obtain the
participant’s sent for this limited participation in the must if it was not clearly delineated in the
original consent and COMIRB must prospectively approve the consent form. If a participant
withdraws and does not want to continue follow-up the researcher cannot access records for
purposes related to the study. However, the research may review study data prior to the
participant’s withdrawal and may consult public records such as those establishing survival
status.
14.4 Waiver of Informed Consent
The COMIRB may approve a consent procedure which does not include, or which alters, some
or all of the elements of informed consent set forth above, or waive the requirement for informed
consent provided the COMIRB finds and documents that:
1.
2.
3.
The research involves no more than minimal risk to the subjects;
The waiver or alteration will not adversely affect the rights and welfare of the
subjects;
The research could not practicably be carried out without the waiver or alteration;
and
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4.
Whenever appropriate, the subjects must be provided with additional pertinent
information after participation;
Or
1. The research or demonstration project is to be conducted by or subject to the
approval of state or local government officials and is designed to study, evaluate, or
otherwise examine:
 public benefit or service programs;
 procedures for obtaining benefits or services under those programs;
 possible changes in or alternatives to those programs or procedures; or
 possible changes in methods or levels of payment for benefits or services
under those programs; (Exempt Category 5) and
2. The research could not practicably be carried out without the waiver or alteration.
Note: Informed Consent cannot be waived for research involving FDA-regulated
products. Exceptions from the FDA requirements for informed consent may be
waived for emergency situations (21 CFR 50.23) or for emergency research (21 CFR
50.24).
For VA regulated research only: The investigator must maintain a master list of all
subjects from whom informed consent has been obtained whether or not COMIRB
granted a waiver of documentation of informed consent. If COMIRB waives the
requirement to maintain such a master list, COMIRB must provide written
documentation in the COMIRB minutes or COMIRB protocol file justifying the waiver.
14.5 Waiver of Documentation of Informed Consent
(Waiver of Signed Consent)
The COMIRB may waive the requirement for the investigator to obtain a signed consent form
for some or all subjects if it determines that the research meets the criteria described below.
In cases in which the documentation requirement is waived, the COMIRB requires the
investigator to provide in the application materials a written summary of the information to be
communicated to the subject, and the COMIRB will consider whether to require the
investigator to provide subjects with a written statement regarding the research.
14.5.1 For Studies that are NOT Regulated by the FDA
The COMIRB may waive the requirement for the investigator to obtain a signed consent
form for some or all subjects if it finds either that the:
1. Only record linking the subject and the research would be the consent document and
the principle risk would be potential harm resulting from a breach of confidentiality.
Note: Subjects must be asked whether they want documentation linking them with
the research, and their wishes must govern.
(Example: domestic violence research where the primary risk is discovery by the abuser that
the subject is talking to researchers.)
OR
2.
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. Procedures such as non-sensitive surveys, questionnaires and interviews
generally do not require written consent when conducted by non-researchers.
For VA regulated research only: The investigator must maintain a master list of all
subjects from whom informed consent has been obtained whether or not COMIRB
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granted a waiver of documentation of informed consent. If COMIRB waives the
requirement to maintain such a master list, COMIRB must provide written
documentation in the COMIRB minutes or COMIRB protocol file justifying the waiver.
COMIRB can waive the requirement for the investigator to maintain a master list
for a given study if both of the following conditions are met:
a)
There is a waiver of documentation of consent; and
b)
The COMIRB determines that including the subjects on such a master list poses a
potential risk to the subjects from a breach of confidentiality.
14.5.2 For Studies that ARE Regulated by the FDA
For studies that involve items regulated under the FDA Regulations, the COMIRB, at its
discretion, may waive the requirement for the PI to obtain a signed consent document if:
 The Research presents no more than Minimal Risk of harm to the Human
Subjects and involves no procedures for which written consent is normally
required outside the Research context; or
 The requirements for an exception from informed consent for Emergency
Research are met.
14.6 Review and Approval of the Informed Consent Form
The COMIRB is responsible for the review and approval of the informed consent form
prepared by the investigator. The wording on the informed consent form must contain all
of the required elements and meet all other requirements as described in this section. If
the wording of the informed consent has been initially prepared by an external entity
(e.g., a pharmaceutical company or a cooperative study group, including National Cancer
Institute (NCI) groups) other than by a University Principal Investigator, the COMIRB
needs to ensure that the wording of the consent meets all the requirements of, or has
been reviewed by, the appropriate University committees and subcommittees such as the
Institutional Biosafety Committee.
COMIRB approval of the wording of the consent must be documented through the use of
a certification stamp on the front page that indicates the date of the most recent COMIRB
approval of the document and the expiration date. If the consent form is amended during
the protocol approval period, the form must have the approval date of the amendment
rather than the date of the approved protocol.
For research conducted at the Eastern Colorado Health Care System, the VA Form 101086, Research Consent Form, must be used. COMIRB approval of the wording of the
consent must be documented through the use of a certification stamp on each page that
indicates the date of the most recent COMIRB approval of the document and the
expiration date. The consent form must also be approved by the R&D committee
indicated with the R&D committee stamp. If the consent form is amended during the
protocol approval period, the form must bear the approval date of the amendment rather
than the date of the approved protocol. The amended consent form must also be
approved by the R&D committee indicated with the R&D committee stamp.
14.7 Consent Monitoring
In reviewing the adequacy of informed consent procedures for proposed research, the
COMIRB may on occasion determine that special monitoring of the consent process by
an impartial observer (consent monitor) is required in order to reduce the possibility of
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coercion and undue influence, ensure that the approved consent process is being
followed, or ensure that subjects are truly giving informed consent.
Such monitoring may be particularly warranted where the research presents significant
risks to subjects, or if subjects are likely to have difficulty understanding the information
to be provided. Monitoring may also be appropriate as a corrective action where the
panel has identified problems associated with a particular investigator or a research
project.
If the panel determines that consent monitoring is required, the IRB panel will outline the
request. The panel Chair and the COMIRB Director will identify the appropriate individual
to monitor the consent process, and work with the individual(s) concerned to implement
the plan. The consent monitoring may be conducted by Regulatory Compliance Office,
panel members or another party, either affiliated or not with the institution. The PI will be
notified of the panel’s determination and the reasons for the determination. Arrangements
will be made with the PI for the monitoring of the consent process for a specified number
of subjects. Following the monitoring, a report of the findings will be submitted to the
COMIRB, which will determine the appropriate action to be taken.
14.8 Assent Process
14.8.1 Assent Process for Children
Because “assent” means a child’s affirmative agreement to participate in research, (45
CFR 46.402(b), the child must actively show his or her willingness to participate in the
research, rather than just complying with directions to participate and not resisting in any
way. When judging whether children are capable of assent, the COMIRB is charged with
taking into account the ages, maturity, and psychological state of the children involved.
The COMIRB has the discretion to judge children’s capacity to assent for all of the
children to be involved in a proposed research activity, or on an individual basis.
The COMIRB takes into account the nature of the proposed research activity and the
ages, maturity, and psychological state of the children involved when reviewing the
proposed assent procedure and the form and content of the information conveyed to the
prospective subjects. For research activities involving adolescents (generally ages 13 -17
years) whose capacity to understand resembles that of adults, the assent procedure
should likewise include information similar to what would be provided for informed
consent by adults or for parental permission. For children whose age and maturity level
limits their ability to fully comprehend the nature of the research activity but who are still
capable of being consulted about participation in research, it may be appropriate to focus
on conveying an accurate picture of what the actual experience of participation in
research is likely to be (for example, what the experience will be, how long it will take,
whether it might involve any pain or discomfort). The assent procedure should reflect a
reasonable effort to enable the child to understand, to the degree they are capable, what
their participation in research would involve.
The COMIRB presumes that children ages 7 and older should be given an opportunity to
provide assent. Written assent using a written document is usually sought.
At times there may be inconsistency between parent permission and child assent.
Usually a “no” from the child overrides a “yes” from a parent, but a child typically cannot
decide to be in research over the objections of a parent. Obviously, there are individual
exceptions to these guidelines (such as when the use of an experimental treatment for a
life threatening disease is being considered). The general idea, however, is that children
should not be forced to be research subjects, even when their parents consent to it.
If the COMIRB determines that the capability of some or all of the children is so limited
that they cannot reasonably be consulted or that the intervention or procedure involved in
the research holds out a prospect of direct benefit that is important to the health or well7
being of the children and is available only in the context of the research, the assent of the
children is not a necessary condition for proceeding with the research.
Even when the COMIRB determines that the subjects are capable of assenting, the
COMIRB may still waive the assent requirement.
14.8.2 Assent Process for Decisionally Challenged Adults
Assent is also required by COMIRB, when it is feasible, for adults who have been
determined to be unable to consent.
The assent procedure should reflect a reasonable effort to enable the person to
understand, to the degree they are capable, what their participation in research will be. It
is prohibited for potential subjects to be forced or coerced to participate in a research
study. The assent template should be adapted as needed.
If the COMIRB determines that the capability of some or all of the decisionally challenged
adults is so limited that they cannot reasonably be consulted or that the intervention or
procedure involved in the research holds out a prospect of direct benefit that is important
to the health or well-being of the individual and is available only in the context of the
research, the panel may determine that assent of the individual may not be a necessary
condition for proceeding with the research.
14.8.3 The Assent Form
Researchers should try to draft a form that is age appropriate and study specific, taking
into account the typical child’s / decisionally challenged adult experience and level of
understanding, and composing a document that treats the child respectfully and conveys
the essential information about the study. COMIRB provides an assent template as a tool
for the Principal Investigator. The assent form should:
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Tell why the research is being conducted;
Describe what will happen and for how long or how often;
Say it’s up to the child/decisionally challenged adult to participate and that it’s
okay to say no;
Explain if it will hurt and if so for how long and how often;
Say what the child’s / decisionally challenged adult’s other choices are;
Describe any good things that might happen;
Say whether there is any compensation for participating; and
Ask for questions.
For younger children, 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. COMIRB may also determine that it is
appropriate for the adolescent to sign the consent document.
The regulations at 45 CFR 46.408(a) identify three types of circumstances where the
IRB may determine that waiver of children’s assent is appropriate:
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If the capability of some or all of the children is so limited that they cannot
reasonably be consulted;
If the intervention or procedure involved in the research holds out the
prospect of direct benefit to the health or well-being of the children and is available
only in the context of the research.
If the research meets the same conditions as those for waiver or
alteration of informed consent in research involving adults, as specified in the
regulations at either 45 CFR 46.116(c) or 45 CFR 46.116(d).
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14.8.4 Parental Override of a child’s decision:
For studies that do not provide any prospect of direct benefit for the child, COMIRB will
not approve parental override. For studies with potential benefit to the child, COMIRB
will assess the child’s psychological state. There comes a time in a child’s illness when
their autonomy and right to justice has to be respected.
14.8.5 Surrogate Consent
This policy is designed to protect human subjects from exploitation and harm and, at the
same time, make it possible to conduct essential research on problems that are unique to
persons who are incompetent, or who have impaired decision-making capacity.
Unless waived by the COMIRB, informed consent must be obtained directly from the
individual subject. Under appropriate conditions, investigators also may obtain informed
consent from a legally authorized representative of a subject (surrogate consent).
Definition: Legally authorized representative means an individual or judicial or other body
authorized under applicable law to consent on behalf of a prospective subject to the
subject’s participation in the procedure(s) involved in the research [45 CFR 46.102(c)].
The General Counsel of the University has determined that, in Colorado, the following
meet the definition legally authorized representative and, thus, can give surrogate
consent:
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A court appointed guardian of the person.
A health care agent appointed by the person in a Durable Power of
Attorney for Health Care (DPAHC) that specifies that the individual also has
the power to make decisions of entry into research.
Proxy consent under certain conditions [see section 18.5]
Investigators should consult with the General Counsel of the University when conducting
research outside of Colorado to determine what the requirements for a legally authorized
representative in the jurisdiction in which the research is taking place.
Such consent may be requested and accepted only when the prospective research
participant is incompetent or has an impaired decision-making capacity, as determined
and documented in the person’s medical record in a signed and dated progress note.
The determination must be made in accordance with the following requirements:
1. The practitioner [in consultation with the Chief of Service, or COS – at the VA
MEDICAL CENTER (VAMC)] may determine after appropriate medical
evaluation that the prospective research subject lacks decision-making
capacity and is unlikely to regain it within a reasonable period of time.
2. Consultation with a psychiatrist or licensed psychologist must be obtained
when the determination that the prospective research subject lacks decisionmaking capacity is based on a diagnosis of mental illness. (See Vulnerable
Population, Decisionally Challenged below.)The IRB will require investigators
to conduct a competency assessment whenever there is a possibility of
either impaired mental status or decision-making capacity in prospective
subjects.
At the VA MEDICAL CENTER (VAMC), surrogate consent may be obtained
from next-of-kin in the following order of priority, unless otherwise specified
by applicable state law: spouse, adult child (18 years or older), parent, adult
sibling (18 years of age or older), grandparent, or adult grandchild (18 years
of age or older).
If feasible, the investigator must explain the proposed research to the
prospective research subject even when the surrogate gives consent. Under
no circumstances may a subject be forced or coerced to participate in a
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research study.
14.9 Consent and Language Barriers
Sometimes a subject understands English but does not read or write. If illiterate or legally
blind subjects are enrolled in research an impartial witness is required. The witness should
observe the consent process, sign the informed consent document, and attest that the
subject appears capable of making an informed decision and was given the opportunity to
ask questions.
Researchers should prepare both English language and translated consent forms for
proposals that include non-English-speaking subjects. After the English version is
approved, a translated consent form should be obtained by the PI and submitted to
COMIRB. The credentials of the translator must be provided.
Non-English speaking subjects may not be enrolled with a short form process of consent
documentation unless reviewed and approved in advance by the COMIRB. For studies
reviewed by COMIRB, if a non-English-speaking subject is enrolled unexpectedly,
researchers may rely on an oral translation of the English language consent form or the
COMIRB template short consent form, but should take extra care in the informed consent
process to ensure that the subject has understood the project. A statement in the
research records (and on the English language consent form) should indicate that the
translation took place, identify the translator, and document the translator’s belief that the
subject understands the study and the consent process. If the subject is a patient, a note
about the translation should be made in the patient’s research records as well.
Researchers should try to provide a written translation of the vital emergency contact
information.
A study is permitted to utilize the short form up to three times in the same language. If a 4 th
subject is to be enrolled then a translation of the entire consent form should be provided to
COMIRB for approval.
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