1. Purpose
This SOP outlines the additional protections required by federal regulations for
planned emergency research when the requirements of informed consent are waived
2. Overview
The IRB may approve an exception to the requirements for informed consent for research
on life-threatening conditions for which available treatments are unproven or unsatisfactory
and where it is not possible to obtain informed consent from research participants
or their legally authorized representatives
3. General Information
3.1. Persons with life-threatening conditions who cannot provide informed consent
or refuse research participation are considered a vulnerable population. The lack
of participant autonomy and inability of prospective participants to provide informed
consent requires additional protections to be provided in the review, approval,
and conduct of this research.
3.2. Previous and continuing IRB reviews are required for planned emergency research.
The IRB must approve both the research and the exception to the requirements for
informed consent (i.e., waiver) by finding and documenting that the regulatory
criteria described below are met.
3.3. To approve a waiver of informed consent for research conducted in emergencies,
a licensed physician who is a member (or consultant) of the IRB and who is not
otherwise participating in the research must agree with the IRB’s determination
that the criteria for consent waiver are met. Documentation of the physician’s
concurrence is also required for approval; therefore, IRB meeting minutes should
record the physician’s vote when the planned emergency research is reviewed.
3.4. The requirements for planned emergency research subject to FDA regulations differ
slightly from the requirements for research subject to DHHS regulations, as described
below. For information on activities defined by FDA and DHHS regulations as “research
involving human subjects,” see SOP 011: Human Subject Research Determination. All
planned emergency research at WVU must meet the requirements described below in
“Exceptions to the Requirements for Informed Consent.
3.5. Planned emergency research conducted in life-threatening situations must be
differentiated from the “emergency use” of an investigational drug or biologic
or unapproved medical device. The emergency use provision in FDA regulations allows
for a single use of an investigational drug or biologic or unapproved medical device
for a human subject in a life-threatening situation for which no standard acceptable
treatment is available and when there is insufficient time to obtain IRB approval.
For more information about the requirements for emergency uses, see SOP 053: Emergency
Use of Investigational Drugs, Biologics, or Devices.
4. Exceptions to the Requirements for Informed Consent
4.1. The IRB may approve emergency research without requiring that informed consent
is obtained from participants or their legally authorized representatives only
if the IRB finds and documents that each of the following requirements has been
me:
- The participants are in a life-threatening situation
- Intervention is required before consent from legally authorized representatives
is feasible
- Available treatments are unproven or unsatisfactory
- The relative risks and benefits of the proposed intervention are unknown or
thought to be equivalent (or better) compared to standard therapy
- The collection of valid scientific evidence (including evidence from randomized,
placebo-controlled studies) is necessary to determine the safety and efficacy
of the intervention
- Obtaining informed consent is not feasible because of all of the following:
-
The participants will not be able to give their informed consent as a result of their
medical condition(s)
- The intervention under investigation must be administered before obtaining
consent from the participants’ legally authorized representatives is feasible
- There is no reasonable way to prospectively identify the individuals likely
to become eligible for participation in the research
- Participation in the research presents the prospect of direct benefit to the
subjects because of all of the following:
- Participants are facing a life-threatening situation that necessitates intervention
- Appropriate animal and other preclinical research has been conducted, and the
information derived from the research (and related evidence) supports the
potential for the intervention to provide a direct benefit to the participants
- Risks associated with the research are reasonable to known information about
the medical condition of the potential class of participants, the risks and
benefits of standard therapy, and the known information about the risks and
benefits of the proposed intervention or activity
- The research could not be practicably carried out without the IRB approval of
a waiver of informed consent
- Recruitment of participants providing informed consent could bias the science,
the science is less rigorous as a result of restricting the research to subjects
who can provide consent, or the research would be unreasonably delayed by
restricting it to consenting subjects
- The protocol defines the length of the potential therapeutic window based on
scientific evidence, and the researcher has committed to attempting to contact
a legally authorized representative for each participant within that window
of time and, if feasible, to asking the legally authorized representative for
consent rather than proceeding without consent
- Researchers will summarize efforts made to contact legally authorized representatives
and provide this information to the IRB at the time of continuing review
- The IRB has reviewed and approved an informed consent process and consent document
meeting all the requirements described in regulations and policies outlined
in SOP 012: Informed Consent Requirements and SOP 016: Documentation of Informed
Consent Process.
- The approved informed consent procedures and consent document are to be used
with participants or their legally authorized representatives when feasible
- The IRB has approved procedures and information to be used when providing an
opportunity for a family member to object to the participant’s participation
(as described below)
- Additional protections of the rights and welfare of participants will be provided,
including at least:
- Consultation (including consultation carried out by the IRB, where appropriate)
with representatives of the communities in which the research will be conducted
and from which the participants will be drawn
- Examples: holding a public meeting in the community from which participants
will be recruited to discuss the research, conducting a telephone poll,
establishing a separate panel of community members, including community
consultants to the IRB, and adding unaffiliated members to the IRB who
are representative of the community
- The IRB will consider community input when reviewing the research
- Before initiation of the research, public disclosure of plans for the research
and its risks and expected benefits to the communities in which the research
will be conducted and from which the participants will be recruited
- 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
- Establishment of an independent data monitoring committee to provide oversight
of the research
- If obtaining informed consent is not feasible (and a legally authorized representative
is not reasonably available), the researcher has committed to attempting
to contact within the therapeutic window the participant’s family member
who is not a legally authorized representative, if feasible, and asking whether
they object to the subject’s participation in the research
- Only one family member must be consulted and agree (or object) to the subject’s
participation in the research
- If more than one family member is present and family members disagree, the
family members must work out the disagreement to enroll the potential participant
- Researchers will summarize efforts made to contact family members and provide
this information to the IRB at the time of continuing review
Note: If a participant is enrolled in the study with waived consent and the participant
dies before a legally authorized representative, or family member can be contacted,
information about the study (as described below) is to be provided to the participant’s
legally authorized representative or family member, if feasible.
4.2. The IRB will approve procedures to inform the participant, the participant’s
legally authorized representative (if the participant remains incapacitated), or
a family member (if the legally authorized representative is not reasonably available)
of the following at the earliest feasible opportunity:
- That the participant was included in the research
- Details of the research and other information contained in the informed consent
document
- The subject’s participation may be discontinued at any time without penalty or
loss of benefits to which the participant is otherwise entitled
Note: If it is a legally authorized representative or family member that is told
about the research and the participant’s condition improves, the participant
is also to be informed as soon as feasible.
5. Research Subject to FDA Regulations
For planned emergency research subject to FDA regulations, other specific requirements
also apply, as described below.
5.1. The IRB will confirm and document that a separate IND or IDE is obtained for
the use of the investigational drug, biologic, or device to be studied in the research
that identifies the protocol as one that may include participants who are unable
to consent.
Note: A separate IND or IDE is required even if an IND for the same drug or an
IDE for the same devices as the one to be studied already exists.
5.2. If the IRB cannot approve the research either because the criteria described
above are not met, or because of relevant ethical concerns, documentation of the
IRB’s findings will be provided in writing to the researcher and sponsor within
14 calendar days.
- The sponsor must promptly disclose this information to FDA and to researchers
who have been asked to participate in the research or a “substantially equivalent
clinical investigation” and to other IRBs that have been or are asked to review
this or a substantially equivalent investigation by that sponsor
6. Research Subject to DHHS Regulations
6.1. The IRB may approve research subject to DHHS regulations involving an “emergency
research consent waiver” under either of the following two conditions:
- The IRB finds and documents all of the following:
- The research is subject to FDA regulations
- The research will be performed under a separate IND or IDE (see “Research Subject
to FDA Regulations” above)
- The FDA requirements for exception from informed consent for emergency research
have been met (see “Exception to the Requirements for Informed Consent” above)
- The IRB finds, documents, and reports to OHRP all of the following:
- The research is not subject to FDA regulations
- The DHHS requirements for waiver of informed consent for emergency research
have been met (see “Exception to the Requirements for Informed Consent” above).
Because of the regulatory limitations relating to research involving prisoners, fetuses,
pregnant women, and human in vitro fertilization, a waiver of informed consent cannot
be approved for emergency research involving these populations. Note: these limitations
do not apply to research subject only to FDA regulations
7. References
WVU Policies:
SOP 011: Human Subject Research Determination
SOP 012: Informed Consent Requirements
SOP 016: Documentation of Informed Consent Process
SOP 053: Emergency Use of Investigational Drugs, Biologics, or Devices
Federal Regulations:
21 CFR 50.24
21 CFR 50.25
21 CFR 50.27
45 CFR 46.116
45 CFR 46.117
AAHRPP:
Element II.4.C
