AE Worksheet
How to determine whether problems that occur during research are “unanticipated problems”
(UPIRSOs)
Is this incident, experience, or outcome an adverse event?
Definition - An adverse event is any untoward or unfavorable medical 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. (Encompasses
both physical and psychological harms.)
No
If no, go to the Non-AE Worksheet for determining whether a Non-Adverse Event is an unanticipated problem.
Yes
If yes, use the three criteria below to determine whether the adverse event is an unanticipated problem
(UPRISO).
Criterion 1: Is this adverse event UNEXPECTED?
Definition - An unexpected adverse event is any adverse event, the nature, severity, or frequency of which
is not consistent with either:
(1) the known or foreseeable risk of adverse events associated with the procedures involved in
the research that are described in (a) the protocol related documents, such as the
IRB-approved research 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 underlying disease, disorder, or condition of the
subject(s) experiencing the adverse event and the subject’s predisposing risk factor
profile for the adverse event?
To determine whether an adverse event is unexpected, answer the following 3 questions.
Yes
No
Questions
Q1. Is the nature of the AE a known or foreseeable
risk?
Yes
No
(e.g., liver failure due to diffuse hepatic necrosis
occurring in a subject without any underlying liver
(go to Q2)
This is an
disease would be an unexpected adverse event (by
Unexpected
virtue of its unexpected nature) if the protocolAE
related documents and other relevant sources of
(skip Q2&3 and
information did not identify liver disease as a
continue to
potential adverse event)
Criterion 2)
Q2. Is the severity of the AE greater than
anticipated?
Yes
No
(e.g., liver failure due to diffuse hepatic necrosis
occurring in a subject without any underlying liver
This is an
(go to Q3)
disease would be an unexpected adverse event (by
Unexpected
virtue of its unexpected greater severity) if the
AE
protocol-related documents and other relevant
(skip Q3 and
sources of information only referred to elevated
continue to
hepatic enzymes or hepatitis as potential adverse
Criterion 2)
events related to the procedures involved in the
research)
Q3. Is the frequency of the AE greater than
anticipated?
Yes
No
[Note: It may be difficult to determine whether an
individual AE is unexpected by virtue of an
This is an
This is not
unexpected higher frequency; this determination
Unexpected
an
Unknown
at this time
This is not an
can only be done through an analysis of appropriate
data on all or most subjects. This question can be
answered as unknown at the present time, as
appropriate]
(e.g., liver failure due to diffuse hepatic necrosis in a
group of subjects without any underlying liver
disease if the occurrence is in a higher percentage
of subjects than referenced in the protocol-related
documents and other relevant sources of
information)
AE
(continue to
Criterion 2)
Unexpected
AE
Unexpected
AE
at this time
Prompt Report
Not Needed
Prompt Report
Not Needed
Criterion 2: Is this unexpected adverse event RELATED OR PROBABLY RELATED to participation in
research?
Definition – There is at least a reasonable possibility that the unexpected adverse event may have been
caused by the procedures involved in the research.
To determine whether an unexpected adverse event is related or probably related, choose which statement is
accurate (you should only select one).
The unexpected adverse event is at least partially caused by the
procedures involved in the research.
The unexpected adverse event is caused solely by either:
 an underlying disease, disorder, or condition of the
subject;
or
 other circumstances unrelated to either the research or
any underlying disease, disorder, or condition of the
subject.
The unexpected AE is related,
(continue to Criterion 3)
The unexpected AE is not related
Prompt Report Not Needed
Criterion 3: Does this unexpected adverse event, that is related or probably related to participation in research
suggests that the research places subjects or others at a greater risk of harm than was previously known or
recognized?
This is a three step process
Step 1 - Is this unexpected adverse event, that is related or probably related to participation in research,
SERIOUS?
Yes
No
Is this an AE that:
results in death
is life-threatening (places the subject at immediate risk of
death from the event as it occurred)
results in inpatient hospitalization or prolongation of existing
hospitalization
results in a persistent or significant disability/incapacity
results in a congenital anomaly/birth defect
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
previous five statements.
If you answered yes to If you answered no to
ANY, then the AE is
ALL, the AE is not
serious,
serious,
(skip Step 2 and
(continue to
continue to
Step 2)
Step 3 check 3.a.)
Step 2 – Is this not serious, unexpected adverse event that is at least probably related suggest that the research
places subjects or others at a greater risk of physical or psychological harm than was previously known or
recognized?
YES
NO
If yes, go to Step 3, check 3.b.
If no, this AE is not an “unanticipated problem”
Prompt Report Not Needed
Step 3 – Unanticipated Problems
3a. You should promptly report this serious, unexpected adverse event that is at least probably related to
the research as an unanticipated problem because such events always suggest that the research places
subjects or others at a greater risk of physical or psychological harm than was previously known or recognized.
3b. You should promptly report this not serious, unexpected adverse event that is at least probably related
to the research as an unanticipated problem because it was determined that the event suggests that the
research places subjects or others at a greater risk of physical or psychological harm than was previously
known or recognized.