[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