2. CONTENTS:
2
INFORMED CONSENT : DEFINITION
ADMINISTERING OF INFORMED
CONSENT
VALID ELEMENTS
GENERAL REQUIREMENTS
INFORMATION TO BE GIVEN TO STUDY
SUBJECTS
OBLIGATIONS OF INVESTIGATOR
WAIVER OF REQUIREMENT
DOCUMENTATION
IMPLEMENTATION
4. INFORMED CONSENT
Informed consent is based on the
principle that competent individuals
are entitled to choose freely whether
to participate in research. Informed
consent protects the individual’s
freedom of choice and respects the
individual’s autonomy.
Freely given informed consent should
be obtained from every subject prior
to research participation in
accordance with national culture(s)
and requirements. When a subject is
not capable of giving informed
consent, the permission of a legally
authorized representative should be
obtained in accordance with
applicable law. (as per Principle 7
GCP)
4
5. Who may administer informed consent?
The person who conducts the consent
interview should be knowledgeable
about the study and able to answer
questions. Some sponsors and some
IECs/IRBs require the clinical
investigator to personally conduct the
consent interview. If someone other
than the clinical investigator conducts
the interview and obtains consent, the
clinical investigator should ensure that
this responsibility is formally
delegated to that individual, and that
the person so delegated is qualified
and receives appropriate training to
perform this activity.
5
6. Obtaining informed consent is a process that is begun when initial
contact is made with a prospective subject, and continues
throughout the course of the study.
For an individual to give valid informed consent, three components
must be present:
DISCLOSURE: Implies that the consent form be written in lay
language suited for the comprehension skills of subject
population, as well as assessing the level of understanding
during the meeting.
CAPACITY: Capacity pertains to the ability of the subject to both
understand the information provided and form a reasonable
judgment based on the potential consequences of his/her
decision.
VOLUNTARINESS: Refers to the subject’s right to freely exercise
his/her decision making without being subjected to external
pressure such as coercion, manipulation, or undue influence
6
VALID ELEMENTS:
7. The IRB should ensure that technical and scientific terms are
adequately explained or that common terms are substituted.
Use of the wording, "I understand..." in informed consent
documents may be inappropriate as many prospective subjects
will not "understand" the scientific and medical significance of all
the statements.
Consent documents should not contain unproven claims of
effectiveness or certainty of benefit, either explicit or implicit, that
may unduly influence potential subjects.
Each individual must be given as much time as is needed to
reach a decision, including time for consultation with family
members or others.
7
GENERAL REQUIREMENTS:
8. In general, all individuals, including healthy volunteers, who participate as
research subjects should be viewed as intrinsically vulnerable because:
1) during the course of the study they are (or may be) exposed to an
investigational product about which the safety and efficacy is unknown or
incompletely understood; and
2) there may be other factors – social, cultural, economic, psychological,
medical – that may adversely affect the subjects’ ability to make rational,
objective choices that protect their own interests, but which may not be
readily apparent to the researcher.
Vulnerable persons are those who are relatively (or absolutely) incapable
of protecting their own interests. More formally, they may have insufficient
power, intelligence, education, resources, strength or other needed
attributes to protect their own interests.
Examples of vulnerable persons include, but are not limited to: children,
individuals with diminished mental capacity, prisoners, institutionalized
persons (including orphans), patients in emergency situations, the
economically disadvantaged, individuals who cannot give consent.
8
VULNERABLE PERSONS
9. Certain essential elements of informed consent should be included
in the informed consent discussion, the written informed consent
form, and any other information to be provided to subjects who
participate in the study.
“The manner and context in which information is conveyed is as
important as the information itself. For example, presenting
information in a disorganized and rapid fashion, allowing too little
time for consideration or curtailing opportunities for questioning, all
may adversely affect a subject’s ability to make an informed
choice.”
Informing the individual subject must not be simply a
ritual recitation of the contents of a written document.
9
“Information” to be given to study subjects
10. “Information” to be given to study
subjects
• Title of the protocol; and identity of the sponsor and clinical
investigator and institutional affiliation of the investigator;
• Source of research funding (e.g., public, private, or both);
• That the subject’s participation in the trial is voluntary and that
the subject may refuse to participate or withdraw from the trial, at
any time, without penalty or loss of benefi ts to which the subject
is otherwise entitled;
• The purpose of the trial; and the trial treatment(s) and the
probability for random assignment to each treatment;
• The subject’s responsibilities;
10
All information must be communicated in a comprehensive and
understandable manner to the trial subject. This includes, but is not limited
to:
11. “Information” to be given to study
subjects
11
• The trial procedures to be followed, including all invasive
procedures; and those aspects of the trial that are experimental;
• The reasonably foreseeable risks or inconveniences to the subject
and, when applicable, to an embryo, fetus or nursing infant;
• The reasonably expected benefits. When there is no intended
clinical benefit to the subject, the subject should be made aware of
this;
• The alternative procedure(s) or course(s) of treatment that may
be available to the subject, and their important potential benefits
and risks;
• The compensation and/or treatment available to the subject in the
event of trial-related injury;
• The anticipated prorated money or other forms of payment (e.g.,
material goods), if any, to the subject for participating in the trial;
12. “Information” to be given to study
subjects
12
• The anticipated expenses, if any, to the subject for participating in the
trial. This may include expenses to the subject for routine medical care
for conditions that are not within the scope of the research;
• That the monitor(s), the auditor(s), the IEC/IRB, and the regulatory
authority will be granted direct access to the subject’s original medical
records for verification of clinical trial procedures and/or data, without
violating the confidentiality of the subject, to the extent permitted by
the applicable laws and regulations and that, by signing a written
informed consent form, the subject or the subject’s legally authorized
representative is authorizing such access;
• That records identifying the subject will be kept confidential and, to
the extent permitted by the applicable laws and/or regulations, will not
be made publicly available. If the results of the trial are published, the
subject’s identity will remain confidential;
13. • The potential risks should confidentiality measures be
compromised (e.g., stigma, loss of reputation; potential loss of
insurability);
• That the subject or the subject’s legally authorized representative
will be informed in a timely manner if information becomes
available that may be relevant to the subject’s willingness to
continue participation in the trial;
• The person(s) to contact for further information regarding the trial
and the rights of trial subjects, and whom to contact in the event of
trial-related injury;
• The foreseeable circumstances and/or reasons under which the
subject’s participation in the trial may be terminated;
• The expected duration of the subject’s participation in the trial;
• The approximate number of subjects involved in the trial.
13
“Information” to be given to study
subjects
14. The investigator must convey the information, whether orally or
in writing, in language that suits the individual’s level of
understanding.
The investigator must then ensure that the prospective subject
has adequately understood the information.
The investigator should give each one full opportunity to ask
questions and should answer them honestly, promptly and
completely.
In some instances the investigator may administer an oral or a
written test or otherwise determine whether the information has
been adequately understood.
14
Obligations of Investigator
15. Waiver of the consent requirement may be applied in
certain circumstances:
No foreseeable harm is expected to result from the study or when
permitted by law, federal regulations, or if an ethical review committee
has approved the non-disclosure of certain information.
Waivers of consent may be obtained in a military setting. Waiver of
advanced informed consent may be granted by the Secretary of Defense
if a research project would:
1. Directly benefit subjects.
2. Advance the development of a medical product necessary to the
military.
3. Be carried out under all laws and regulations (i.e., Emergency
Research Consent Waiver) including those pertinent to the FDA.
If a patient is incapacitated due to injury or illness, it is still important that
patients benefit from emergency experimentation.
15
WAIVER OF REQUIREMENT
16. The subject may imply consent by voluntary actions, express consent
orally, or sign a consent form.
As a general rule, the subject should sign a consent form, or, in the case
of incompetence, a legal guardian or other duly authorized
representative should do so.
When consent has been obtained orally, investigators are responsible
for providing documentation or proof of consent.
When material changes occur in the conditions or the procedures of a
study, and also periodically in long-term studies, the investigator should
once again seek informed consent from the subjects.
16
INFORMED CONSENT DOCUMENTATION
17. Except as provided in 56.109(c), informed consent shall be
documented by the use of a written consent form approved by
the IRB and signed and dated by the subject or the subject's
legally authorized representative at the time of consent. A copy
shall be given to the person signing the form.
Except as provided in 56.109(c), the consent form may be either
of the following:
• A written consent document that embodies the elements of
informed consent required by 50.25.
• A short form written consent document stating that the
elements of informed consent required by 50.25 have been
presented orally to the subject or the subject's legally authorized
representative. When this method is used, there shall be a
witness to the oral presentation. The witness must sign both the
short form and a copy of the summary, and the person actually
obtaining the consent must sign a copy of the summary.
17
INFORMED CONSENT DOCUMENTATION:
18. The responsibility for implementing and overseeing the
informed consent process is shared by sponsors, clinical
investigators, IECs/ IRBs, and regulatory authorities.
IECs/IRBs are responsible for:
Reviewing the informed consent document to ensure that it is
accurate, complete, and written in language that will be
understood by the potential study subjects and translated into
other languages, as appropriate;
Requesting modifications to the informed consent document, as
appropriate; and
At their discretion, observing the consent process and the
research.
18
Implementation
19. Staff responsible for obtaining informed consent receive
appropriate training, both in research ethics and in the
requirements of the specific study protocol.
The IEC/IRB reviews and approves the informed consent form
and other written information to be used in the study prior to its
use.
Informed consent is obtained from each subject or the subject’s
representative prior to involving the subject in any study related
activities, including diagnostic or other tests that are
administered solely for determining the subject’s eligibility to
participate in the research.
19
Investigators are responsible for ensuring:
20. Monitoring the research at study sites to ensure that sites are obtaining
informed consent from all study subjects prior to subjects’ inclusion in
the research study.
In accordance with national and local laws and regulations, regulators
may inspect the various parties who conduct or oversee research to
ensure that they are complying with applicable laws and regulations
and enforcing non-compliance.
Regulators may inspect IECs/IRBs to ensure that informed consent
documents and procedures are appropriately reviewed; they may
inspect clinical investigators to determine whether informed consent was
obtained prior to subjects’ inclusion in the study; they may inspect
sponsors to ascertain whether studies are being appropriately
monitored.
20
Sponsors and Regulators are responsible
for:
