8.
Special Classes of Research Subjects
There are a number of
research populations described in the federal regulations as "vulnerable" or
that require additional consideration or protection. "Vulnerable" or special
classes of subjects specifically described in the regulations include children,
prisoners, pregnant women, fetuses, and mentally disabled persons, handicapped
persons, or economically or educationally disadvantaged persons
[45 CFR 46.111]. Additionally, the regulations include specific
provisions for research involving fetuses, pregnant women, and neonates
[45 CFR 46 Subpart B]; prisoners
[45 CFR 46 Subpart C]; and children
[45 CFR 46 Subpart D]. Exemption from IRB review does not
apply to some research involving vulnerable populations or special classes of
subjects.
The following section is a brief discussion regarding some "vulnerable" subject
populations.
Fetuses
Research involving the
human fetus poses challenges for investigators and IRBs reviewing such projects
as the fetus has an inextricable relationship to the mother. A fetus cannot
provide informed consent to participate as a research subject. The National
Commission for the Protection of Human Subjects in Biomedical and Behavioral
Research studied the subject of fetal research. The Commission, in its
findings, did not define the "personhood" of the fetus, however, it did
recognize the genetic heritage and vulnerability of the fetus and affirmed that
it should be treated respectfully and with dignity, regardless of its life
prospects. The Commission also affirmed the legitimacy and importance of fetal
research for improving the health of fetuses both in the present and future.
The DHHS refined regulations pertaining to pregnant women and fetuses in 2001
[45 CFR 46 Subpart B].
The federal regulations
provide the following definitions:
1.
Pregnancy: “encompasses
the period of time from implantation until delivery. A woman shall be assumed to
be pregnant if she exhibits any of the pertinent presumptive signs of pregnancy,
such as missed menses, until the results of a pregnancy test are negative or
until delivery.”
2.
Fetus: “the
product of conception from implantation until delivery.” Delivery means
“complete separation of the fetus from the woman by expulsion or extraction or
any other means.”
3.
Dead Fetus:
“a fetus that exhibits neither heartbeat, spontaneous
respiratory activity, spontaneous movement of voluntary muscles, nor pulsation
of the umbilical cord.”
4.
Delivery: “complete
separation of the fetus from the woman by expulsion or extraction or any other
means.”
5.
Viable: “as it pertains to the neonate, means being able, after delivery, to
survive (given the benefit of available medical therapy) to the point of
independently maintaining heartbeat and respiration. The Secretary may from time
to time, taking into account medical advances, publish in the Federal Register
guidelines to assist in determining whether a neonate is viable for purposes of
this subpart. If a neonate is viable then it may be included in research only to
the extent permitted and in accordance with the requirements of the general
federal regulations or the subpart on children as research subjects.”
Research Involving
Pregnant Women or Fetuses and the Requirements for Informed Consent
The IRBs may only approve
research involving pregnant women or fetuses when all of the following
criteria are met in addition to any other applicable institutional, Federal,
State and local requirements:
Science/Risk-Benefit: 45 CFR 46.204
(a) Where scientifically appropriate, preclinical studies,
including studies on pregnant animals, and clinical studies, including studies
on nonpregnant women, have been conducted and provide data for assessing
potential risks to pregnant women and fetuses;
(b) The
risk to the fetus is caused solely by interventions or procedures that hold out
the prospect of direct benefit for the woman or the fetus; or, if there is no
such prospect of benefit, the risk to the fetus is not greater than minimal and
the purpose of the research is the development of important biomedical knowledge
which cannot be obtained by any other means;
(c) Any
risk is the least possible for achieving the objectives of the research.
Informed Consent: 45 CFR 46.204
(d) If the
research holds out the prospect of direct benefit to the pregnant woman, the
prospect of a direct benefit both to the pregnant woman and the fetus, or no
prospect of benefit for the woman nor the fetus when risk to the fetus is not
greater than minimal and the purpose of the research is the development of
important biomedical knowledge that cannot be obtained by any other means, her
consent is obtained in accord with the informed consent provisions of subpart A
of this part;
(e) If the
research holds out the prospect of direct benefit solely to the fetus then the
consent of the pregnant woman and the father is obtained in accord with the
informed consent provisions of subpart A of this part, except that the father's
consent need not be obtained if he is unable to consent because of
unavailability, incompetence, or temporary incapacity or the pregnancy resulted
from rape or incest.
(f) Each
individual providing consent under paragraph (d) or (e) of this section is fully
informed regarding the reasonably foreseeable impact of the research on the
fetus or neonate;
(g) For
children (as defined by the regulations) who are pregnant, assent and permission
are obtained in accord with the provisions outlined in Subpart D of the federal
regulations;
(h) No
inducements, monetary or otherwise, will be offered to terminate a pregnancy;
(i)
Individuals engaged in the research will have no part in any decisions as to the
timing, method, or procedures used to terminate a pregnancy; and
(j) Individuals engaged
in the research will have no part in determining the viability of a neonate.
Research not Otherwise Approvable that Presents an
Opportunity to Understand, Prevent, or Alleviate a Serious Problem Affecting the
Health or Welfare of Pregnant Women, Fetuses, or Neonates
[45 CFR 46.207]
If the research is HHS funded and does not meet any of the
above criteria, the following regulations apply:
(a)
The IRB finds that the research presents a reasonable opportunity to
further the understanding, prevention, or alleviation of a serious problem
affecting the health or welfare of pregnant women, fetuses or neonates; and
(b)
The Secretary, after consultation with a panel of experts in pertinent
disciplines (for example: science, medicine, ethics, law) and following
opportunity for public review and comment, including a public meeting announced
in the Federal Register, has determined either:
(1)
That the research in fact satisfies the conditions of 45 CFR 46.204, as
applicable; or
(2)
The following:
(i)
The research presents a reasonable opportunity to further the
understanding, prevention, or alleviation of a serious problem affecting the
health or welfare of pregnant women, fetuses or neonates;
(ii)
The research will be conducted in accord with sound ethical principles;
and
(iii)
Informed consent will be obtained in accord with the informed consent
provisions of 45 CFR 46.116 and 117 and other applicable sections in Subpart B.
Research with Human
Embryonic Stem Cells (hESC)
Research involving the derivation and use of human embryonic germ cells from
fetal tissue may be conducted with federal support if the cell lines meet the
criteria announced by President George W. Bush’s on August 9, 2001 (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005l
). Research involving the derivation of new human embryonic stem cells (hESC)
or the use of hESC lines that are not listed on the NIH Embryonic Stem Cell
Registry may not be conducted with federal support and may be subject to UCLA
restrictions.
Federal Regulation
and State Law
Use of archived hESCs or hESC lines that have not been implanted in a woman and
that do not have direct or indirect identifiers linked to the donors of the
original cells does not meet the DHHS regulatory definition of human subjects
and are not covered by the DHHS regulations. Nevertheless, California law does
regulate research with such material [Health and Safety Code 125118-9]. The
California law includes all hESC research conducted with hESCs or cell lines,
including cells obtained from in vitro fertilization clinics.
hESC:
Residual cells from IVF Clinics
|
Covered by
Federal Regulation
|
Covered by
State Law
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Informed
Consent of the Donor
|
No identifiers linked to the donor
|
No
|
Yes
|
May be waived under 45 CFR 46.116(d)
|
Direct or indirect identifiers linked to the donors
|
Yes
|
Yes
|
May be required or waived under 45 CFR 46.116(d)
|
Compliance with
State and Local Laws
California law requires prospective IRB review of all hESC
research. The law indicates:
o
An IRB shall, in its review of human embryonic stem cell research
projects, consider and apply the guidelines developed by the applicable State
department in compliance with California law. The IRB may require modifications
to the plan or design of a proposed hESC project as a condition of approving the
research project.
o
The State is required by law to develop guidelines and name a hESC
Advisory Committee.
o
IRB review of hESC research must be reported annually to the
State.
o
State law requiring IRB review of hESC research includes research
with hESC lines.
Research Involving,
After Delivery, the Placenta, the Dead Fetus, or Fetal Material
The use of after delivery;
the placenta; the dead fetus; macerated fetal material; or cells, tissue, or
organs excised from a dead fetus shall be conducted only in accord with any
applicable Federal, State, or local laws and regulations regarding such
activities.
If
information associated with material described in the previous paragraph is
recorded for research purposes in a manner that living individuals can be
identified, directly or through identifiers linked to those individuals, those
individuals are research subjects and all pertinent subparts of 45 CFR 46
Subpart B are applicable
[45 CFR 46.206].
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October 29, 2004
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