INFORMED
CONSENT OF RESEARCH SUBJECTS
Informed
consent is a vital part of the research process, and
as such entails more than obtaining a signature on a
form. Investigators must educate potential subjects
to ensure that they can reach a truly informed decision
about whether or not to participate in the research.
Their informed consent must be given freely, without
coercion, and must be based on a clear understanding
of what participation involves.
The process of educating subjects about the study begins
during initial contact and continues for the duration
of their participation. Thus, information conveyed through
advertisements, recruitment letters, pre-screening phone
calls, study description sheets as well as written informed
consent documents and discussions must be understandable
to the subjects and should contribute to their understanding
of the research. Technical and medical terminology should
be avoided or explained in “lay” language, and materials
should be written at an 8th grade reading level or lower.
Non-English speaking subjects must have information
presented in a language they understand (refer to Obtaining
and Documenting Informed Consent of Subjects Who Do
Not Speak English for guidance). The Partners Human
Research Committee (PHRC) must approve written and oral
information (including recruitment materials) provided
to subjects before and during the informed consent process.
The consent discussion should begin sufficiently in
advance of the initiation of study-related procedures
to allow potential subjects time to reflect on the potential
benefits and risks and possible discomforts of participation.
The following method is preferred by the PHRC, though
clearly it may need to be tailored to the circumstances
of individual studies and may not be appropriate or
feasible in all situations. First, potential subjects
are given general information about the research (e.g.,
through advertisements, information sheets, letters
or discussion with their treating physicians), and if
they are interested in learning more about the study,
they contact study staff. The investigator then meets
with the potential subject to review and to discuss
the details of the research study using the informed
consent document as a guide. This discussion should
include all of the required elements of informed consent,
e.g., the purpose of the research, the procedures to
be followed, the risks and discomforts as well as potential
benefits associated with participation, and alternative
procedures or treatments, if any, to the study procedures
or treatments.
Preferably, potential subjects are then given a copy
of the informed consent document to take home so they
can carefully read the document and discuss the research
with their family, friends and/or physician and develop
questions to ask at their next meeting with the research
staff. Please note that subjects must always be given
the opportunity to ask questions and have them answered
by the investigator and, whenever possible, to consult
with friends/family and/or their physicians. Once they
have read the consent document and their questions are
answered, if they agree to participate in the research,
they sign and date the informed consent document. (Note
also that under the new federal Privacy Rule, subjects
must be asked as well for written authorization for
the use and disclosure of their identifiable information
for research. For an explanation and forms, see HIPAA
and the Privacy Rule.)
Special consideration must be given to the timing of
the consent process when the subject population includes
patients who will be same-day admissions for surgical
procedures or who present for diagnostic or other tests,
such as cardiac catheterizations or radiological examinations.
Clearly, the time frame for the consent process will
be more limited in these situations. Generally, the
investigator should allow potential subjects at least
12 hours to consider participation. Whenever possible,
the patient’s physician should be asked to provide potential
subjects with information about the study well in advance,
for example, when the surgery, test, or examination
is scheduled.
With few exceptions, the informed consent of subjects,
whether patients or healthy volunteers, must be obtained
and documented in writing before the start of any study-related
procedures, including screening tests and exams done
solely to determine their eligibility for the study
(refer to Pre-screening
of Research Subjects During Recruitment for guidance).
Informed consent is to be obtained directly from each
subject, with the exception of children (see below)
and adults who have impaired decision-making capacity.
For guidance, refer to the Obtaining Surrogate Consent
to Research for Individuals with Impaired
Decision-Making Capacity memo (Partners Intranet
link). Once the informed consent document has been signed,
subjects are considered enrolled in the study.
Individuals who can Obtain Informed Consent
For most studies involving more than minimal risk and
all studies involving investigational drugs/devices,
a licensed physician investigator listed on the protocol
must obtain informed consent. Study nurses or other
study staff may assist in the consent process, but physicians
should be actively involved in the consent discussions
and should not delegate this vital investigator function.
It is the investigator’s responsibility to ensure that
proper informed consent is obtained from every subject
according to the procedures approved by the PHRC.
For minimal risk studies and very carefully selected
studies involving more than minimal risk (but not investigational
drugs/devices), it may be appropriate for study nurses
or other study staff to obtain consent, with “back up”
provided by licensed physician investigators. The PHRC
will allow a licensed nurse or non-licensed physician
investigator to obtain informed consent if that nurse
or non-licensed physician would be permitted, in a clinical
setting, to perform the procedures for which consent
is required. If the investigator proposes that other
than licensed physician investigators obtain informed
consent, the rationale and justification for this approach
and the qualifications and training of the relevant
study staff must be submitted to the PHRC for review
and approval.
If subjects are to be enrolled from among the investigator’s
own patients, consent procedures must be put in place
to ensure that subjects do not feel obligated to participate
because the investigator is their treating physician.
There is always concern about the possibility of patients
feeling obligated to participate because it is their
physician who is doing the asking. While the PHRC does
not have an absolute prohibition about physicians obtaining
consent from their own patients, researchers are asked
to think about this issue and address it. There are
many possible ways to do this. One can contact the patient
in writing initially, and allow him/her to make the
first contact if interested. One can ask a physician
colleague to present the study to a patient to try to
make it more impartial. One can have a nurse or colleague
re-contact the patient after the investigator has had
the consent discussion and offer them an opportunity
to ask additional questions, raise concerns, or opt
out, with someone who is not their physician.
Obtaining Parental/Legal Guardian Consent for
Children
Federal regulations require that consent to participate
in research on behalf of a child be provided by a parent
or an individual authorized under applicable state or
local law to provide consent on the child’s behalf to
general medical care. Under Massachusetts law, a parent
is generally authorized to consent to general medical
care on behalf of their child. However, in some circumstances
(such as when both parents are deceased), it may be
necessary to identify another individual with this authority
(for example, a court-appointed guardian). Before an
investigator allows an individual other than a parent
to consent on behalf of a child, the investigator should
document the basis for the individual’s authority to
consent on behalf of the child to general medical care
and place any relevant documentation in the research
file. In situations when it is unclear under state law
who has the authority to provide consent to general
medical care on behalf of a child, and thus who can
consent to the child’s participation in research, the
PHRC will consult with the Office of General Counsel
as needed.
Under the federal regulations, where consent to the
research is to be provided by a child’s parent and the
research involves no greater than minimal risk or greater
than minimal risk, but with the prospect of direct benefit
to the subjects, the PHRC may decide that consent of
one parent is sufficient. However, when the research
involves greater than minimal risk and no prospect of
direct benefit to the subjects, permission must be obtained
from both parents, unless one parent is deceased, unknown,
incompetent, or not reasonably available, or when one
parent has legal responsibility for the care and custody
of the child.
In addition to permission of the parent(s) or guardian,
assent to participate in the study must be obtained
from each child age 7 years or older who, in the opinion
of the investigator, is able to provide assent based
on their age, maturity or psychological state. When
the PHRC determines 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 children involved in the research and the intervention
or procedure is only available in the context of the
research, the assent of the children is not a necessary
condition for proceeding with the research. Even when
the children are capable of assenting, the PHRC may
waive the assent requirement as described elsewhere
in this document [Alteration or Waiver of Elements of
Informed Consent].
When obtained, assent must be documented in writing
using the PHRC-approved consent/assent form. When assent
is not obtained, the investigator must document his/her
rationale in the research records.
Minors Who Can Give Legally Effective Informed Consent
Under Massachusetts State law and MGH/BWH clinical policies,
some minors (less than 18 years of age) can provide
legally effective consent for their own medical care,
in certain circumstances, without parental consent or
knowledge and therefore may not meet the DHHS and FDA
definition of “children” and the requirements of Subpart
D may not apply. “Emancipated” minors, i.e., those who
are married, widowed or divorced, or have a child or
are pregnant (or believe themselves to be), are in the
armed forces, or living apart from their parents and
managing their own affairs, can provide informed consent
for their own medical care. Minors in Massachusetts
may also give consent to research procedures that involve:
-
psychiatric treatment, if the minor is 16 or over;
-
treatment
of drug dependency, if the minor is 12 or over; and
-
treatment
of certain diseases dangerous to public health (VD
and others).
Because these minors nonetheless may represent a vulnerable
population, the IRB will review all consent issues involving
these minors on a case-by-case basis to ensure that
any required additional protections are met. For example,
although these minors may be allowed to consent to the
research, the IRB may decide that permission of a parent
or other individual is appropriate either instead of
or in addition to the minor’s consent.
If the PHRC approves the obtaining of informed consent
from specified minors, informed consent follows generally
the same procedures that are being followed for adults.
The investigator must also document the specific circumstances
that justify designating a particular subject less than
18 years of age as capable of providing consent to the
treatments and procedures involved in the particular
research.
Use of a Subject Advocate
In certain situations, the PHRC will require the use
of a subject advocate in the consent process. The subject
advocate is an individual who has no vested interest
in the research and who agrees to act as an impartial
third party in the consent process. When a subject advocate
is appointed, the subject advocate is expected to act
in the best interests of the subject by sharing in discussions
with the investigator and with those responsible for
giving consent. Individuals who might fulfill this role
include the subject's primary care physician or other
health care professional not involved in the research.
The subject advocate is responsible for ensuring that
the subject understands the research procedures and
the risks and potential benefits of participation and
that his/her consent is free and voluntary. When a subject
advocate is used, the subject advocate must sign and
date the consent form.
Situations in which the use of a subject advocate may
be required include:
-
When the risks to subjects are significant and the
subject is the patient of the investigator and,
as such, may feel obligated to participate; or
-
when
consent is to be obtained in the emergency room
or in an emergency situation when the time frame
to obtain consent prior to start of study-related
procedures is limited; or
-
when
surrogate consent is to be obtained for research
involving more than minimal risk with the potential
for direct benefit to the subject.
Documentation of Informed Consent
In almost all cases, investigators must document the informed
consent process by use of a written consent document (research
consent form) signed and dated by the subject or his/her
legally authorized representative (or surrogate) and the
investigator (or study staff if approved by the PHRC)
who obtained the subject’s consent. When the research
will begin on the same day that informed consent is obtained,
the PHRC recommends recording time of consent in addition
to date of consent to document that informed consent was
obtained prior to any study-related procedures. In certain
situations, the PHRC may approve a waiver or alteration
in the consent process (see below).
The research consent form must include the basic elements
of informed consent outlined in Appendix
A. The entire text of all research consent forms must
be approved by the PHRC as part of the review process.
The effective date of the PHRC-approved consent form and
expiration date of PHRC approval (one year or less) are
noted in the footer added to the research consent form
by the Human Research Office staff. Subjects must be given
and sign the most recently approved version of the research
consent form. Out-dated and/or expired research consent
forms must not be used in the consenting process and to
document informed consent.
Usually, three copies of the signed and dated research
consent form are needed. The original signed and dated
research consent form should be retained in the research
records. A copy of the signed and dated research consent
form must be given to the subject and a copy placed in
the subject’s medical record, if relevant to his/her ongoing
medical care. If the study involves sensitive research,
(e.g., alcohol or drug use, some genetic studies) a copy
of the research consent form ordinarily should not be
placed in the subject’s medical record. (If the sensitive
study involves a drug or otherwise might implicate care
decisions, the investigator should discuss with the IRB
how best to make this information available to a caregiver
with a need to know.)
To further document and facilitate clarification of any
future questions regarding the consenting process, the
investigator should consider including the following information
in a clinic chart/progress note/other source document:
that XX study was explained, questions were answered (if
any), subject agreed to participate and signed the consent
form, and a copy of the signed consent form was given
to subject. This note should be signed and dated by the
person obtaining consent.
Waiver of Written Informed Consent
The PHRC may waive the requirement to document informed
consent with a signed written informed consent document
for some OR all subjects if it finds either:
(1) that the research is not subject to FDA regulations
and 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 s/he wants documentation
linking him/her with the research, and his/her wishes
will govern;
If the PHRC approves waiver of signed consent based on
consideration (1), the full consenting
process for these subjects including being given a written
informed consent document embodying all the elements of
informed consent remains the same except that the subject
will have the option to not sign the consent document
or have information linking them to the study placed in
their medical file.
OR
(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.
If the PHRC approves waiver of the requirement to obtain
a signed written consent form based upon consideration
(2), investigators must fully inform prospective subjects
about the study, answer their questions and obtain their
verbal informed consent. In lieu of a written consent
form, the PHRC may require the investigator to provide
subjects with a written statement regarding the research.
(To obtain oral authorization for use/disclosure of identifiable
information under the Privacy Rule, see Obtaining
Oral Authorization For Use and Disclosure of Identifiable
Information.)
When the PHRC approves waiver of the requirement to obtain
a signed written consent form based upon consideration
(2), the investigator should consider including the following
information in a clinic chart/progress note/other source
document: who was approached, for what study, who explained
the study, brief summary of what was explained, subject
(or surrogate) expressed an understanding of the research
study and willingness to participate, questions (if any)
were answered to the subject’s satisfaction, subject agreed
to participate, and written information about the study
was given to the subject, if appropriate. This note should
be signed and dated by the person obtaining consent.
Alteration or Waiver of Elements of Informed Consent
The PHRC can approve a consent process that does not include,
or that alters, some or all of the elements of informed
consent or even waive the requirement to obtain informed
consent provided the PHRC finds that the research is not
subject to FDA regulations and documents that all of the
following requirements are met:
-
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
- whenever
appropriate, the subjects will be provided with additional
pertinent information after participation.
Requests
for alterations in or a waiver of informed consent requirements
should be made in writing and justified by addressing
each of the 4 points above. (For waiver or alteration
of authorization under the Privacy Rule, see Waiver and
Alteration of Informed Consent and Authorization for Research.)
Obtaining New Consent and/or Notifying Subjects
of Major Changes to any Component of the Informed Consent
Document
Subjects should be asked for new consent -- i.e., through
the investigator’s explanation and request to sign a revised,
PHRC-approved consent form -- when they are actively engaged
in the research and there have been major changes to any
component of the consent form, e.g., drug dose(s), device,
study procedures, risks and discomforts, benefits, and
alternatives. This is paramount if knowledge of the new
information might affect subjects’ willingness to continue
participation. Subjects should also be notified of a change
of the principal investigator or contact information;
however, in most cases this type of change can be adequately
communicated in a letter. Please note that a change in
co-investigators and/or study staff is not considered
a major change requiring new consent or notification.
It is important to note that as part of the review of
amendments to the protocol and/or informed consent document,
the PHRC will determine whether the change(s) require
obtaining new consent from subjects enrolled in the study.
Examples of when a subject should be asked for new consent
in writing:
-
the Procedures section of the consent form has been
revised to include a new procedure that the subject
will be asked to undergo, e.g., genetic testing, cardiac
catheterization, biopsy, colonoscopy, mammogram, ultrasound,
etc. An investigator may not perform a procedure on
a subject without new consent if the procedure was not
mentioned in the original consent process and form.
Subjects
should be given the following information in a timely
manner so that they can make a fully informed decision
about whether they wish to continue their participation.
The greater the import of the new information, the more
quickly subjects should be made aware of it.
-
the Risks and Discomforts section of the consent form
has been revised to include a newly identified serious
adverse event
- the
Risks and Discomforts section of the consent form has
been revised to include a change in the severity or
frequency of a serious expected event
- the
Alternatives section has been revised to include newly
identified alternative therapies or diagnostic tests
- the
Procedures and Alternatives section have been revised
to include a change in FDA approval status of the drug
or device being studied
Examples
of when the PHRC may approve a letter being sent to notify
the subject of the change include:
- the
principal investigator has been changed
- the
study contacts have been changed and/or the contact
telephone numbers have been changed
- the
subject has completed the study interventions and is
in the follow-up phase of the study or in some cases
has completed the study, and the information is such
that learning it would not materially affect the subject’s
decision to continue participation in follow-up
APPENDIX
A – BASIC ELEMENTS OF INFORMED CONSENT
45 CFR 46.116(a)(b) and 21 CFR 50.25(a)(b)
The following information about the study must be provided
to research subjects when obtaining informed consent:
-
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, that might be advantageous
to the subject;
- A
statement describing the extent, if any, to which confidentiality
of records identifying the subject will be maintained,
and when applicable, that notes the possibility that
the Food and Drug Administration may inspect the records;
- 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;
- 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; and
- 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.
When
appropriate, the following information must be provided
to each subject:
-
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;
-
Anticipated circumstances under which the subject’s
participation may be terminated by the nvestigator without
regard to the subject’s consent;
- Any
additional costs to the subject that may result from
participation in the research;
- The
consequences of a subject’s decision to withdraw from
the research and procedures for orderly termination
of participation by the subject;
- 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; and
- The
approximate number of subjects involved in the study.
NOTE:
Any informed consent, whether written or oral,
must not include exculpatory language such that the subject
is made to waive, or appear to waive, any of his or her
legal rights or to release the institutions or its agents,
the investigators, from liability or negligence.
Examples of exculpatory language:
-
By agreeing to this use, you will give up all claim
to personal benefit from commercial or other use of
these substances.
- I
voluntarily and freely donate any and all blood, urine,
and tissue samples to the U.S. Government and hereby
relinquish all right, title, and interest to said items.
- By
consent to participate in this research, I give up any
property rights I may have in bodily fluids or tissue
samples obtained in the course of the research.
- I
waive any possibility of compensation for injuries that
I may receive as a result of participation in this research.
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