LINKS TO
HARMONIZED
RULE ON WAIVER OF CONSENT FOR EMERGENCY RESEARCH
Harmonized rule on waiver of consent for emergency research, October 2, 1996. This rule was published simultaneously by FDA and DHHS to provide comparable regulations for carrying out planned emergency research with a waiver of informed consent. The two versions are presented side by side, with paragraphs matched where they are substantially the same.
Note: The contents of the rules are given in the columns on the right. The notes on the left have been added solely for the purpose of indexing the sections.
|
|
||
|
|
FDA Regulation: 21 CFR 50.24 |
DHHS Regulation: Waiver under 45 CFR 46.101(i) |
|
[Code of Federal Regulations] [CITE: 21CFR50.24] [Page 282-284] TITLE 21--FOOD AND DRUGS PART 50--PROTECTION OF HUMAN SUBJECTS Subpart B--Informed Consent of Human Subjects
Sec. 50.24 Exception from informed consent requirements for emergency research. |
[Federal Register: October 2, 1996 (Volume 61, Number 192)] [DOCID:fr02oc96-22] DEPARTMENT OF HEALTH AND HUMAN SERVICES 45 CFR Part 46
Waiver of Informed Consent Requirements in Certain Emergency Research |
|
|
Limited waiver allowed. Not applicable for research
covered by Subparts B and C. Waiver allowed if these conditions are met: |
|
--------------------------------------------------- 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 activities1 , each of which have met the following strictly limited conditions detailed under either (a) or (b) below: ________________________________________ 1Because 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.
|
|
The responsible IRB has approved the activity, the waiver
and has found that: |
|
(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: |
|
Research is subject to FDA regulations with appropriate
IND or IDE, and |
|
(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 |
|
The FDA requirements under 21 CFR 50.24 have been met, or |
|
(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 |
|
The research is not subject to FDA rules, the following conditions have been met and
reported to OPRR: |
|
(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: |
|
The IRB may approve the waiver with the concurrence of an
independent licensed physician if these conditions have been met: |
(a) The IRB responsible for the review, approval, and continuing review of the clinical investigation described in this section may approve that investigation without requiring that informed consent of all research subjects be obtained if the IRB (with the concurrence of a licensed physician who is a member of or consultant to the IRB and who is not otherwise participating in the clinical investigation) finds and documents each of the following: |
|
|
Subjects are in life-threatening situation, no proven
treatment is available, collection of
research data is needed to determine
safety and effectiveness of interventions. Placebo controlled trials allowed. |
(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. |
(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. |
|
Consent is not feasible because: |
(2) Obtaining informed consent is not feasible because: |
(2) Obtaining informed consent is not feasible because:
|
|
DHHS(b)(2)(i) &
21CFR50.24(a)(2)(i) Subjects’ medical condition precludes it |
(i) The subjects will not be able to give their informed consent as a result of their medical condition; |
(i) The subjects will not be able to give their informed consent as a result of their medical condition; |
|
DHHS(b)(2)(ii) &
21CFR50.24(a)(2)(ii) Treatment window does not allow time to get proxy consent |
(ii) The intervention under investigation must be administered before consent from the subjects' legally authorized representatives is feasible; and |
(ii) The intervention involved in the research must be administered before consent from the subjects' legally authorized representatives is feasible; and |
|
DHHS(b)(2)(iii) &
21CFR50.24(a)(2)(iii) Subjects cannot be identified prospectively |
(iii) There is no reasonable way to identify prospectively the individuals likely to become eligible for participation in the clinical investigation. |
(iii) There is no reasonable way to identify prospectively the individuals likely to become eligible for participation in the research. |
|
Subjects might benefit from research because: |
(3) Participation in the research holds out the prospect of direct benefit to the subjects because: |
(3) Participation in the research holds out the prospect of direct benefit to the subjects because: |
|
DHHS(b)(3)(i) &
21CFR50.24(a)(3)(i) They have a life-threatening condition requiring
intervention |
(i) Subjects are facing a life-threatening situation that necessitates intervention; |
(i) Subjects are facing a life-threatening situation that necessitates intervention; |
|
DHHS(b)(3)(ii) &
21CFR50.24(a)(3)(ii) Animal and preclinical studies indicate a potential for
direct benefit |
(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 |
(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 |
|
DHHS(b)(3)(iii) &
21CFR50.24(a)(3)(iii) Risks of research are reasonable in relation to known
risks of condition and alternatives |
(iii) Risks associated with the investigation 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. |
(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. |
|
Research cannot practicably be carried out without the
waiver |
(4) The clinical investigation could not practicably be carried out without the waiver. |
(4) The research could not practicably be carried out without the waiver. |
|
Investigator will attempt to contact a legally authorized
representative within the treatment window and will document those attempts |
(5) The proposed investigational plan 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 legally authorized representatives and make this information available to the IRB at the time of continuing review. |
(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. |
|
An informed consent procedure has been approved for use
when consent or proxy consent is feasible. Information and procedure for
family member to object have been approved. |
(6) The IRB has reviewed and approved informed consent procedures and an informed consent document consistent with Sec. 50.25. 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 clinical investigation consistent with paragraph (a)(7)(v) of this section. |
(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. |
|
These additional protections will be provided: |
(7) Additional protections of the rights and welfare of the subjects will be provided, including, at least: |
(7) Additional protections of the rights and welfare of the subjects will be provided, including, at least: |
|
DHHS(b)(7)(i) & 21CFR50.24(a)(7)(i) Consultation with community of potential subjects |
(i) Consultation (including, where appropriate, consultation carried out by the IRB) with representatives of the communities in which the clinical investigation will be conducted and from which the subjects will be drawn; |
(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; |
|
DHHS(b)(7)(ii) &
21CFR50.24(a)(7)(ii) Prior public disclosure of research plans |
(ii) Public disclosure to the communities in which the clinical investigation will be conducted and from which the subjects will be drawn, prior to initiation of the clinical investigation, of plans for the investigation and its risks and expected benefits; |
(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; |
|
DHHS(b)(7)(iii) &
21CFR50.24(a)(7)(iii) Public disclosure of research results |
(iii) Public disclosure of sufficient information following completion of the clinical investigation to apprise the community and researchers of the study, including the demographic characteristics of the research population, and its results; |
(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; |
|
DHHS(b)(7)(iv) &
21CFR50.24(a)(7)(iv) Establishment of independent data monitoring board |
(iv) Establishment of an independent data monitoring committee to exercise oversight of the clinical investigation; and |
(iv) Establishment of an independent data monitoring committee to exercise oversight of the research; and |
|
DHHS(b)(7)(v) &
21CFR50.24(a)(7)(v) If a legally authorized representative is not available,
investigator will attempt to contact a family member within the treatment
window and ask if he/she objects to subject’s participation. Investigator
will document those attempts. |
(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 clinical investigation. The investigator will summarize efforts made to contact family members and make this information available to the IRB at the time of continuing review. |
(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. |
|
Subject, legally authorized representative, family member
will be informed of subject’s participation at earliest feasible opportunity and
will be given opportunity to withdraw |
(b) 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 clinical investigation, the details of the investigation 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 clinical investigation and the subject's condition improves, the subject is also to be informed as soon as feasible. If a subject is entered into a clinical investigation with waived consent and the subject dies before a legally authorized representative or family member can be contacted, information about the clinical investigation is to be provided to the subject's legally authorized representative or family member, if feasible. |
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. |
|
Definition of family member |
|
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. |
|
Records of IRB determinations and documentation IRB
disapproval to be retained for 3 years |
(c) The IRB determinations required by paragraph (a) of this section and the documentation required by paragraph (e) of this section are to be retained by the IRB for at least 3 years after completion of the clinical investigation, and the records shall be accessible for inspection and copying by FDA in accordance with Sec. 56.115(b) of this chapter. |
|
|
Separate IND or IDE required for protocols which will use
this exception |
(d) Protocols involving an exception to the informed consent requirement under this section must be performed under a separate investigational new drug application (IND) or investigational device exemption (IDE) that clearly identifies such protocols as protocols that may include subjects who are unable to consent. The submission of those protocols in a separate IND/IDE is required even if an IND for the same drug product or an IDE for the same device already exists. Applications for investigations under this section may not be submitted as amendments under Secs. 312.30 or 812.35 of this chapter. |
|
|
If an IRB disapproves an application to carry out research
under this rule, it must document its reasons and forward them to the
investigator and sponsor. Sponsor must notify FDA, other investigators and
other IRBs |
(e) If an IRB determines that it cannot approve a clinical investigation because the investigation does not meet the criteria in the exception provided under paragraph (a) of this section or because of other relevant ethical concerns, the IRB must document its findings and provide these findings promptly in writing to the clinical investigator and to the sponsor of the clinical investigation. The sponsor of the clinical investigation must promptly disclose this information to FDA and to the sponsor's clinical investigators who are participating or are asked to participate in this or a substantially equivalent clinical investigation of the sponsor, and to other IRB's that have been, or are, asked to review this or a substantially equivalent investigation by that sponsor. [61 FR 51528, Oct. 2, 1996] |
|