[Federal Register Volume 61, Number 192 (Wednesday, October 2, 1996)]
[Rules and Regulations]
[Pages 51531-51533]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-24968]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
45 CFR Part 46
Waiver of Informed Consent Requirements in Certain Emergency
Research
AGENCY: National Institutes of Health, HHS.
ACTION: Waiver.
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SUMMARY: The Department of Health and Human Services (HHS) is
announcing the waiver of the applicability of the title 45 CFR part 46
(protection of human subjects) requirement for obtaining and
documenting informed consent, for a strictly limited class of research
involving activities which may be carried out in human subjects who are
in need of emergency therapy and for whom, because of the subjects'
medical condition and the unavailability of legally authorized
representatives of the subjects, no legally effective informed consent
can be obtained. However, because of special regulatory limitations
relating to research involving prisoners (subpart C of 45 CFR part 46)
and research involving fetuses, pregnant women, and human in vitro
fertilization (subpart B of 45 CFR part 46), this waiver is
inapplicable to these categories of research.
EFFECTIVE DATE: November 1, 1996.
FOR FURTHER INFORMATION CONTACT:
F. William Dommel, Jr., J.D. Senior Policy Advisor, Office for
Protection from Research Risks, 6100 Executive Boulevard, Suite 3B01J,
National Institutes of Health, MSC 7507, Rockville, MD 20892-7507.
Telephone (301) 496-7005, ext. 203 (not a toll-free number).
SUPPLEMENTARY INFORMATION:
Waiver
Pursuant to Section 46.101(i) of title 45 of the Code of Federal
Regulations, the Secretary of Health and Human Services (HHS) has
waived the general requirements for informed consent at 45 CFR 46.116
(a) and (b), and at 46.408, to be referred to as the ``Emergency
Research Consent Waiver,'' for a class of research consisting of
activities \1\, each of which have met the following strictly limited
conditions detailed under either (a) or (b) below:
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\1\ Because of special regulatory limitations relating to
research involving prisoners (subpart C of 45 CFR part 46), and
research involving fetuses, pregnant women, and human in vitro
fertilization (subpart B of 45 CFR part 46), this waiver is
inapplicable to these categories of research.
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[[Page 51532]]
(a) The Institutional Review Board (IRB) responsible for the
review, approval, and continuing review of the research activity has
approved both the activity and a waiver of informed consent and found
and documented:
(1) that the research activity is subject to regulations codified
by the Food and Drug Administration (FDA) at Title 21 CFR part 50 and
will be carried out under an FDA investigational new drug application
(IND) or an FDA investigational device exemption (IDE), the application
for which has clearly identified the protocols that would include
subjects who are unable to consent, and
(2) that the requirements for exception from informed consent for
emergency research detailed in title 21 CFR section 50.24 have been met
relative to those protocols, or
(b) The IRB responsible for the review, approval, and continuing
review of the research has approved both the research and a waiver of
informed consent and has found and documented that the research is not
subject to regulations codified by the FDA at title 21 CFR part 50 and
found and documented and reported to the Office for Protection from
Research Risks, Department of Health and Human Services, that the
following conditions have been met relative to the research:
(1) The human subjects are in a life-threatening situation,
available treatments are unproven or unsatisfactory, and the collection
of valid scientific evidence, which may include evidence obtained
through randomized placebo-controlled investigations, is necessary to
determine the safety and effectiveness of particular interventions.
(2) Obtaining informed consent is not feasible because:
(i) The subjects will not be able to give their informed consent as
a result of their medical condition;
(ii) The intervention involved in the research must be administered
before consent from the subjects' legally authorized representatives is
feasible; and
(iii) There is no reasonable way to identify prospectively the
individuals likely to become eligible for participation in the
research.
(3) Participation in the research holds out the prospect of direct
benefit to the subjects because:
(i) Subjects are facing a life-threatening situation that
necessitates intervention;
(ii) Appropriate animal and other preclinical studies have been
conducted, and the information derived from those studies and related
evidence support the potential for the intervention to provide a direct
benefit to the individual subjects; and
(iii) The risks associated with the research are reasonable in
relation to what is known about the medical condition of the potential
class of subjects, the risks and benefits of standard therapy, if any,
and what is known about the risks and benefits of the proposed
intervention or activity.
(4) The research could not practicably be carried out without the
waiver.
(5) The proposed research protocol defines the length of the
potential therapeutic window based on scientific evidence, and the
investigator has committed to attempting to contact a legally
authorized representative for each subject within that window of time
and, if feasible, to asking the legally authorized representative
contacted for consent within that window rather than proceeding without
consent. The investigator will summarize efforts made to contact
representatives and make this information available to the IRB at the
time of continuing review.
(6) The IRB has reviewed and approved informed consent procedures
and an informed consent document in accord with Sections 46.116 and
46.117 of title 45 of the Code of Federal Regulations. These procedures
and the informed consent document are to be used with subjects or their
legally authorized representatives in situations where use of such
procedures and documents is feasible. The IRB has reviewed and approved
procedures and information to be used when providing an opportunity for
a family member to object to a subject's participation in the research
consistent with paragraph (b)(7)(v) of this waiver.
(7) Additional protections of the rights and welfare of the
subjects will be provided, including, at least:
(i) Consultation (including, where appropriate, consultation
carried out by the IRB) with representatives of the communities in
which the research will be conducted and from which the subjects will
be drawn;
(ii) Public disclosure to the communities in which the research
will be conducted and from which the subjects will be drawn, prior to
initiation of the research, of plans for the research and its risks and
expected benefits;
(iii) Public disclosure of sufficient information following
completion of the research to apprise the community and researchers of
the study, including the demographic characteristics of the research
population, and its results;
(iv) Establishment of an independent data monitoring committee to
exercise oversight of the research; and
(v) If obtaining informed consent is not feasible and a legally
authorized representative is not reasonably available, the investigator
has committed, if feasible, to attempting to contact within the
therapeutic window the subject's family member who is not a legally
authorized representative, and asking whether he or she objects to the
subject's participation in the research. The investigator will
summarize efforts made to contact family members and make this
information available to the IRB at the time of continuing review.
In addition, the IRB is responsible for ensuring that procedures
are in place to inform, at the earliest feasible opportunity, each
subject, or if the subject remains incapacitated, a legally authorized
representative of the subject, or if such a representative is not
reasonably available, a family member, of the subject's inclusion in
the research, the details of the research and other information
contained in the informed consent document. The IRB shall also ensure
that there is a procedure to inform the subject, or if the subject
remains incapacitated, a legally authorized representative of the
subject, or if such a representative is not reasonably available, a
family member, that he or she may discontinue the subject's
participation at any time without penalty or loss of benefits to which
the subject is otherwise entitled. If a legally authorized
representative or family member is told about the research and the
subject's condition improves, the subject is also to be informed as
soon as feasible. If a subject is entered into research with waived
consent and the subject dies before a legally authorized representative
or family member can be contacted, information about the research is to
be provided to the subject's legally authorized representative or
family member, if feasible.
For the purposes of this waiver ``family member'' means any one of
the following legally competent persons: spouses; parents; children
(including adopted children); brothers, sisters, and spouses of
brothers and sisters; and any individual related by blood or affinity
whose close association with the subject is the equivalent of a family
relationship.
Background
It had come to the attention of HHS that there are proposals to
conduct certain research, including National Institutes of Health (NIH)
funded research, which could not go forward in
[[Page 51533]]
the context of the current HHS regulations for the protection of human
subjects (45 CFR part 46), unless certain informed consent requirements
of those regulations were waived in accord with the waiver provisions
provided at 45 CFR 46.101(i). HHS carefully reviewed the need for the
exercise of the Section 46.101(i) waiver authority in these
circumstances, and the requirements for informed consent were waived by
the Secretary in the instance of only one specific multi-site study of
head injuries which is currently underway (60 FR 38353).
The Secretary is now waiving the informed consent requirements for
the class of research activities and no longer restricting the waiver
to a single research project. This waiver provides clear instruction as
to when research in emergency circumstances may proceed without
obtaining an individual subject's informed consent. Elsewhere in this
edition of the Federal Register, the FDA is publishing a final rule
which amends FDA regulations to authorize a nearly identical waiver of
informed consent in research which is regulated by FDA. The joint
publication of these actions permit harmonization of the HHS and FDA
regulations regarding research in emergency circumstances. The HHS
waiver, just as the FDA regulatory change, provides a narrow exception
to the requirement for obtaining and documenting informed consent from
each human subject or his or her legally authorized representative
prior to initiation of research if the waiver of informed consent is
approved by an IRB. The waiver authorization applies to a limited class
of research activities involving human subjects who are in need of
emergency medical intervention but who cannot give informed consent
because of their life-threatening medical condition, and who do not
have available a legally authorized person to represent them. The
Secretary, HHS is authorizing this waiver in response to growing
concerns that current regulations, absent this waiver, are making high
quality research in emergency circumstances difficult or impossible to
carry out at a time when the need for such research is increasingly
recognized.
HHS notes testimonies to this effect delivered to (i) the
Subcommittee on Regulation, Business Opportunities, and Technology,
Committee on Small Business, U.S. House of Representatives (Washington
DC, May 23, 1994); (ii) the Coalition Conference of Acute Resuscitation
Researchers (Washington DC, October 25, 1994); (iii) the meeting of
Applied Research Ethics National Association (Boston MA, October 30,
1994); (iv) the meeting of Public Responsibility in Medicine & Research
(Boston MA, November 1, 1994); and (v) the Food and Drug
Administration/National Institutes of Health Public Forum on Informed
Consent in Clinical Research Conducted in Emergency Circumstances
(Rockville MD, January 9-10, 1995).
Periodic Review
A periodic review of the implementation by IRBs of this Section
101(i) waiver will be conducted by the Office for Protection from
Research Risks, National Institutes of Health, to determine the
adequacy of the waiver in meeting its intended need or if adjustments
to the waiver might be necessary and appropriate.
Dated: July 17, 1996.
Donna E. Shalala,
Secretary.
[FR Doc. 96-24968 Filed 9-26-96; 8:59 am]
BILLING CODE 4150-04-M
