Unanticipated Problems Involving Risks to
Subjects or Others & Adverse Events
Purpose
The purpose of this policy is to outline the procedure for reporting and reviewing unanticipated
problems involving risks to subjects or others and adverse events.
Defined Terms
Unanticipated Problem Involving Risks to Subjects or Others: Any incident, experience or
outcome that is: 1) unexpected (in terms of nature, severity, or frequency) given the research
procedures that are described in the protocol-related documents, such as the IRB-approved
research protocol and the informed consent document, and the characteristics of the subject
population being studied, 2) related or possibly* related to participation in the research, AND 3)
suggests that the research places subjects or others at a greater risk of harm (including physical,
psychological, economic, or social harm) than was previously known or recognized.
*Possibly related means that there is a reasonable possibility that the incident, experience, or
outcome may have been caused by the procedures involved in the research
Adverse Event: Any untoward or unfavorable physical or psychological occurrence in a human
subject, including any abnormal sign (for example, abnormal physical exam or laboratory
finding), symptom, or disease temporally associated with the subject’s participation in the
research, whether or not considered related to the subject’s participation in the research.
Serious Adverse Event: Any adverse event that: 1) results in death, 2) is life-threatening (places
the subject at immediate risk of death from the event as it occurred), 3) results in inpatient
hospitalization or prolongation of existing hospitalization, 4) results in a persistent or significant
disability/incapacity, 5) results in a congenital anomaly/birth defect, or 6) based upon appropriate
medical judgment may jeopardize the subject’s health and may require medical or surgical
intervention to prevent one of the other outcomes listed in this definition.
Unexpected Adverse Event: Any adverse event occurring in one or more subjects participating
in a research protocol, the nature, severity or frequency of which is not consistent with either: 1)
the known or foreseeable risk of adverse events associate with the procedures involved in the
research that are described in (a) the protocol-related documents, such as the IRB-approved
protocol, any applicable investigator brochure, and the current IRB-approved informed consent
document, and (b) other relevant sources of information, such as product labeling and package
inserts or 2) the expected natural progression of any underling disease, disorder, or condition of
the subject(s) experiencing the adverse event and the subject’s predisposing risk factor profile for
the adverse event.
Unexpected Adverse Device Effect: Any serious adverse effect on health or safety or any lifethreatening problem or death caused by, or associated with, a device, if that effect, problem, or
death was not previously identified in nature, severity, or degree of incidence in the
investigational plan or application (including a supplementary or application), or any other
unanticipated serious problem associated with a device that relates to the rights, safety, or
welfare of the subjects.
Policy
Federal regulations require that the IRB have written procedures to ensure prompt reporting of
any unanticipated problems involving risks to subjects or others to the IRB, appropriate
institutional officials, and the department or agency head.
The following events must be reported to the IRB within 5 working days of discovery:
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Death of a research subject if the death is related or possibly related to the research study
Adverse events that are unanticipated (in terms of nature, severity, or frequency, related
or possibly related, and suggest that there is an increased risk to subjects or others than
was previously known.
Any event or problem that is unanticipated (in terms of nature, severity, or frequency,
related or possibly related, and suggest that there is an increased risk to subjects or others
than was previously known.
Breach of confidentiality
Suspension or termination of the research study by the Sponsor or other agency
Incarceration of a research subject enrolled into the study
Study staff misconduct
Medication or laboratory error regardless of whether subjects experienced harm
New information (e.g. interim analysis, safety monitoring report, publication, or other
finding) that suggests that there are new or increased risks to subject or others
A complaint by a research subject or others that suggests that rights, welfare, or safety of
a subject has been adversely affected.
Any other problem that suggests that the research places subjects or others at an increased
risk for harm or adversely affects the rights, welfare or safety of subjects or other.
The IRB will make a determination if the unanticipated problem constitutes serious and/or
continuing noncompliance.
Procedures
Submission of Unanticipated Problem/Adverse Event:
1. The Principal Investigator is responsible for submitting the unanticipated
problem/adverse event using the Unanticipated Problem/Adverse Event form.
Unanticipated problems and adverse events that are unexpected and related should be
reported within 5 working days upon discovery.
2. The Principal Investigator must submit all unanticipated problems and adverse events to
the Sponsor and other applicable agencies as required.
Screening of Submissions:
1. The unanticipated problem/adverse event is received by the IRB Coordinator and
screened for completeness. If information is missing, the IRB Coordinator will request
the missing information from the Principal Investigator.
Determining Review Type (Expedited vs. Full Board):
1. The IRB Coordinator forwards the unanticipated problem/adverse event form to the IRB
Director for review. The IRB Director confirms the completeness and accuracy of the
form and then forwards to the IRB Chair or Vice-Chair for review.
2. The IRB Chair/Vice-Chair and IRB Director makes a determination whether the event
meets the definition of an unanticipated problem involving risks so subjects or others.
3. If the event does not meet the definition of an unanticipated problem involving risks to
subjects or others, the IRB Chair/Vice-Chair and IRB Director conducts the review using
expedited procedures.
4. If the event meets the definition of an unanticipated problem involving risks to subjects
or others, it will be referred to the full board for review.
5. If the IRB Chair/Vice-Chair and IRB Director are unable to determine if the event is an
unanticipated problem involving risks to subjects, it will be referred to the full board for
review.
6. If additional expertise is needed, the IRB Director will contact the appropriate IRB
member for consultation.
Expedited Review Procedure for Unanticipated Problem/Adverse Event:
1. If the event is determined to not meet the definition of an unanticipated problem
involving risks to subjects or others, the IRB Chair/Vice-Chair will review the event
using expedited procedures. The review will be documented by the use of the appropriate
reviewer checklist.
2. The IRB Chair/Vice-Chair will determine the appropriate corrective action plan.
3. The Principal Investigator will be notified of the determination and corrective action plan
via letter.
4. All reported events will be reported to the full board at the next convened meeting.
Full Board Review Procedure for Unanticipated Problem/Adverse Event:
1. If the event is determined to be unanticipated problem involving risks to subjects or
others by the Chair/Vice-Chair and Director, the event will be reviewed by the full board.
2. The IRB Chair/Vice-Chair and Director will assign the event to an IRB member(s) for
review. The review will be documented by the use of the appropriate reviewer checklist.
3. The assigned reviewer will present the event at the full board.
4. The full board will review the event, determine if the event meets the definition of an
unanticipated problem involving risks to others, and determine the appropriate corrective
action. Corrective actions may include:
• Education
• Modifications to the protocol
• Notification of current and/or past subjects
• More frequent IRB review
• Additional monitoring
• Prohibit use of study data
• Suspension
• Termination
5. If the event is determined to be an unanticipated problem involving risks to subjects and
others it will be reported as outlined in the “Reporting Policy.”
6. The IRB will also determine if the event meets the definition of serious and/or continuing
non-compliance.
7. If the event meets the definition of serious and/or continuing non-compliance it will be
processed as outlined in the “Noncompliance Policy” and “Reporting Policy.”
8. The Principal Investigator will be notified of the determination and correction action plan
via letter.
Title
Author
Effective
Date
Last
Review/Update Date
Revision #
Approved
Unanticipated Problems Involving Risks to Subjects or
Others & Adverse Events
Cynthia Monahan
10/01/2012
09/19/2012
Cynthia Monahan, IRB Director
Ara Tahmassian, PhD, Associate Vice President-Research
Compliance