Unanticipated Problems Involving Risks to
Participants and Others
UMCIRB Rule No.
Effective Date
Revisions Date
Revision No.
Approval: VC RGS; IRB
Chairs
17
10/01/08
1.1
1.0
Purpose: This rule establishes guidelines for submitting and reviewing unanticipated events involving
risks to participants or others. This rule will address submissions to the University & Medical Center
Institutional Review Board (UMCIRB), appropriate institutional officials, sponsor, coordinating center,
appropriate regulatory agencies, and research participants.
2.0
Research Protocols Affected:
2.1
Human research reviewed and approved by the UMCIRB (both single site and multi-center).
2.2
Human research in which an ECU or ECU affiliate’s faculty, staff, or student serves on the
research team.
3.0
SOP: This rule is to ensure unanticipated problems involving risks to participants or others, including
serious, related, and unexpected adverse events, are appropriately reported to the UMCIRBs,
appropriate institutions officials, applicable agencies or sponsors, and when appropriate, to research
participants, in a timely fashion.
4.0
Definitions:
4.1
Unanticipated Problems Involving Risks to Participants or Others: any event or outcome that
was previously unforeseen and indicates that participants or others are at an increased risk of
harm. OHRP considers unanticipated problems in general to include any incident, experience,
or outcome that meets all of the following criteria:
4.1.1 unexpected;
4.1.2 related or possibly related to participation in research; and
4.1.3 increased risk of harm.
4.2
Unexpected event: not previously identified in nature, severity, or degree of incidence in the
investigational plan, protocol, or Internal Processing form (including any supplementary plan or
application); any adverse experience, the specificity or severity of which is not consistent with
the current investigator brochure; or, if an investigator brochure is not required or available, the
specificity or severity of which is not consistent with the risk information described in the
general investigational plan or elsewhere in the current processing form, as amended (based on
21 CFR 312.32(a))
4.2.1 Any breaches in confidentiality that would place the participant or others at risk.
4.2.2 Any change in FDA labeling or withdrawal from marketing of a drug, device, or
biologic used in a research protocol.
4.2.3 Any change to the protocol that was taken without prior IRB approval to eliminate
apparent immediate hazard to a research participant.
4.2.4 Incarceration of a participant when enrolled on a study not approved under Subpart C
provisions.
4.3.
Related or possibly related to participation in research: there is at least a reasonable possibility
that the incident, experience, or outcome may have been caused by the procedures involved in
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4.4
4.5
the research. UMCIRB extends this definition to a minimum of 30 days post-administration of
the test article or intervention
Increased risk of harm: suggests that the research places participants or others at a greater
risk of harm (including physical, psychological, economic, or social harm) than was previously
known or recognized.
Serious event: Any research-related event (occurring at any dose or level of intervention) that
results in any of the following outcomes:
4.5.1 Death: Must be reported within two business days of the PI becoming aware of the
event
4.5.2 Life-threatening event: Must be reported within business two days of the PI
becoming aware of the event
4.5.2.1 Life-threatening: Any event that places the participant, in the view of the
Principal Investigator, at immediate risk of death from the reaction as it
occurred, i.e., it does not include a reaction that, had it occurred in a more
severe form, might have caused death (based on 21 CFR 312.32(a)).
4.5.3 Inpatient hospitalization or prolongation of existing hospitalization: the participant must
be hospitalized as a result of the event or, if the participant is already hospitalized, that
hospitalization is prolonged. Must be reported within two business days of the PI
becoming aware of the event
4.5.4 A persistent or significant disability/incapacity: Must be reported within two
business days of the PI becoming aware of the event
4.5.4.1 Disability: A substantial disruption of a person’s ability to conduct normal life
functions
4.5.5 Congenital anomaly or birth defect:. Must be reported within two business days of the
PI becoming aware of the event
4.5.6 Any event, based upon the judgment of the principal investigator, which jeopardizes the
well-being of the human research participant or others and may require medical or
surgical intervention to prevent one of the outcomes listed above. Must be reported
within two business days of the PI becoming aware of the event
4.5.7 Unexpected change to the risks or potential benefits: Any publication in the literature,
safety monitoring report, interim result, or other finding that indicates an unexpected
change to the risks or potential benefits of the research. Must be reported within five
business days of the PI becoming aware of the event. Examples include, but are not
limited to:
4.5.7.1 An interim analysis or safety monitoring report indicating that harms or
benefits may differ than those initially reviewed and approved by the IRB;
4.5.7.2 Published work from another (related in some manner) study which purports
findings which differ from the proposed risks or benefits initially reviewed and
approved by the IRB for the study at hand).
4.5.7.3 Any complaint of a participant that indicates an unanticipated risk or one which
cannot be resolved by the research staff.
4.5.7.4 Any unanticipated adverse device effect.
4.5.7.5 Any change in the informed consent/assent document as a result of new
information or newly identified risks or benefits.
4.5.7.6 Any other information that might represent unanticipated problems involving
risks to participants or others.
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4.6
Administrative Hold: A directive of the FDA, the sponsor, or the facility at which the research is
being conducted, a DSMB, or a convened IRB, IRB chair, or a facility's Institutional Official, to
temporarily stop some or all research activities pending a specified action. Administrative
holds are usually based on identification of information that may place participants or others
at risk unless additional safeguards are put in place. Must be reported within five business
days of the PI becoming aware of the event
5.0
Responsibilities:
5.1
Institutional Review Board will review all unanticipated problems involving risks to participants
and others including related, serious adverse events to determine whether:
5.1.1 the study poses potentially greater risks than benefits to participants
5.1.2 the research procedures should be modified to minimize the risk of the event occurring
again
5.1.3 The consent document should be modified to inform potential participants of the risk of
the event.
5.1.4 All current and previously enrolled participants should be informed of the event through
re-consenting.
5.1.5 The study should be suspended until such time that the risks can be minimized.
5.1.6 The study should be terminated, i.e., risks to participants outweigh any potential for
benefit that can be gained from participation in the study.
5.1.7 Review of any administrative hold placed on a study by a sponsor, a Data Safety and
Monitoring Board, a facility at which the research is conducted, or by another IRB and
take appropriate actions to protect the welfare and safety of participants.
5.1.8 Request additional information as necessary when the event, at the time of reporting,
was not resolved, or when additional information is required to make a determination
5.2
UMCIRB Administrative Director or designee will ensure compliance with this policy.
5.3
The IRB Chairperson or designee will review all materials when submitted to determine if
immediate action is required
5.3.1 The IRB Chairperson has the authority, immediately upon notification of an
unanticipated event to suspend enrollment or research procedures to protect
participants’ safety and welfare.
5.3.2 Suspension of enrollment or research procedures will be conveyed immediately to the
Principal Investigator, both verbally and in writing.
5.3.3 The IRB Chairperson’s or designee’s actions will be reported at the next convened
meeting of the designated IRB.
6.0
Procedures:
6.1
Administrative Director or designee will:
6.1.1 Assist in review of submitted reports, at the request of UMCIRB Chair or IRB staff.
6.2
If a submitted report implies the potential for immediate harm to participants and others:
6.2.1 IRB staff will notify the Administrative Director who immediately notifies the
appropriate IRB Chairperson or designee
6.2.2 Collectively the Chair, Director and staff member will make a decision on what
action, if any, is required to best protect participants. These actions can include, but
are not limited to:
6.2.2.1 suspending the study,
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6.3
6.4
6.2.2.2 suspending enrollment,
6.2.2.3 no further intervention can occur (unless in the best interest of the
participant),
6.2.2.4 the study should be put under a different PI, nursing staff, or coordinator
6.2.3 The PI is immediately notified of the decision both verbally and in writing of any action
that is required
The UMCIRB will:
6.3.1 review only unanticipated events involving risks to participants or others which are
related to the administration of the test article, are unexpected in nature including
severity or frequency, and have the potential for increased risk of harm to the
participants or others
6.3.2 review the actions taken by the Chairperson or designee regarding suspension of
research activities (see Section 6.2.2) and determine whether such actions should be
continued, additional actions are required or the imposed actions should be lifted.
6.3.3 deliberate on any actions required to protect participants’ safety and welfare
6.3.4 suspend any or all research procedures until such time that the risks to participants can
be minimized.
6.3.5 terminate the research based on the determination by the IRB that the risks outweigh
any potential for benefit from participation, now or in the future.
6.3.6 provide UMCIRB determinations, in writing, to the Principal Investigators. Actions can
include, but are not limited to:
6.3.6.1. Accept the report as submitted, with no further action required
6.3.6.2
Request additional information/clarification.
6.3.6.3
Require the consent document and/or protocol to be revised to reflect
information relative to the event.
6.3.5.4
Suspend all or some of the procedures or terminate approval when there
appears to be a major risk to participants until such time that the Principal
Investigator can demonstrate that revised procedures have been put in
place to protect the welfare and safety of participants.
6.3.7 Internal events that are not related or not possibly related or are serious but do not
place participants or others at risk of harm will not be accepted unless the PI can
demonstrate that these events are routinely occurring and may have possible negative
implications for participants or others.
Distribution List: List of agencies or institutional entities which, if providing financial support or
have oversight responsibilities, would be notified in the determination of unanticipated
problems involving risks to participants or others
6.2.1 Agency for International Development (22 CFR 225)
6.2.2 Central Intelligence Agency (Executive order)
6.2.3 Consumer Products Safety Commission (16 CFR 1028)
6.2.4 Department of Agriculture (7 CFR 1c)
6.2.5 Department of Commerce (15 CFR 27)
6.2.6 Department of Defense (32 CFR 219)
6.2.7 Department of Education (34 CFR 97)
6.2.8 Department of Energy (10 CFR 745)
6.2.9 Department of Health and Human Services (45 CFR 46)
6.2.9 Department of Homeland Security (Public law 108-458 Sec. 8306)
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6.2.10
6.2.11
6.2.12
6.2.13
6.2.14
6.2.15
6.2.16
6.2.17
6.2.18
6.2.19
6.2.20
6.2.21
6.2.22
6.2.23
6.2.24
6.2.26
6.2.27
6.2.28
Department of Justice (28 CFR 46)
Department of Transportation (49 CFR 11)
Department of Veterans’ Affairs (38 CFR 16), Office of Research Oversight
Environmental Protection Agency (40 CFR 26)
Housing and Urban Development (24 CFR 60)
National Aeronautics and Space Administration (14 CFR 1230)
National Institutes of Health and Human Services (45 CFR 46)
National Science Foundation (45 CFR 690)
Office of Science and Technology Policy (Adoption of policy)
Social Security Administration (Public law 7.5.26)
Food and Drug Administration (21 CFR 56)
Office for Human Research Protections
External sponsors
Institutional Official
Division, Department, or Unit Chairperson and Dean
Administrators at Affiliate site(s)
Director, Office of Research Compliance Administration
Any Compliance Officers, Risk Management, or State Agencies that may have a need to
be informed
6.2.29 Biomedical and/or Social & Behavioral IRB members and ex-officios
7.0 Revision History:
Date
Revision #
10/01/09
1.1
Change
New format; Clarification on authority,
procedures, what is reportable
Reference Section(s)
All Sections
References
21 CFR 312.32(a)
OHRP Guidance, January 15, 2007
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