IRB: Reporting Events Including Unanticipated Problems
Involving Risks to Subjects or Others (UPIRTSO)
Policy number:
411
References:
45 CFR 46.103(b)(5)(i), 45 CFR 46.116(b)(5)
21 CFR 50.25(b)(5), 21 CFR 56.108(b)(1), 21 CFR 812.150(a)(1)
OHRP Guidance on Reviewing and Reporting Unanticipated Problems
Involving Risks to Subjects or Others and Adverse Events, OHRP
Guidance on Reporting Incidents to OHRP
Guidance for IRBs, Clinical Investigators, and Sponsors: IRB Continuing
Review After Clinical Investigation Approval; Guidance for Clinical
Investigators, Sponsors, and IRBs: Adverse Event Reporting to IRBs –
Improving Human Subject Protection
FDA Info Sheet: Continuing Review After Study Approval
AAHRPP II.2.F
AAHRPP II.3.A
Date: 06/19/2014
Policy Owner:
Executive Director, HRPP
Cross reference:
409 Reporting
410 Suspension and Termination
Definitions:
UPIRTSO: The acronym used for the regulatory phrase “unanticipated problems involving risk to subjects or others”
which is a reportable event under federal regulations.
Anticipated (expected) problems/events are those that are already described as potential risks in the consent form, listed
in the Investigator’s Brochure or are part of an underlying disease. These do NOT meet the IRB’s definition of UPIRTSO
and should be reported in summary form only at the time of IRB continuing review.
Problems/events that are unanticipated and involve new or increased risk to subjects should be reported to the IRB within
5 working days only if in the opinion of the local investigator they are possibly, probably or definitely related to the
research procedures. Those serious, unanticipated problems/events that the local investigator deems unlikely or not
related do NOT meet the IRB’s definition of UPIRTSO and should be reported in summary form only at the time of IRB
continuing review.
1.0 Reason for Policy
This policy describes the types of unanticipated problems that researchers must report to the IRB and the
process the IRB will follow to review and address unanticipated problems involving risks to subjects or
others.
2.0 Scope of Policy
This policy applies to the IRB and HRPP staff and affects the University of Minnesota research
community and its healthcare components.
Page 1 of 4
3.0 Policy Statement
Researcher Reporting
Researchers must promptly report to the IRB unanticipated problems that may involve risks to subjects
or others. Reports must be submitted to the IRB within five (5)working days of knowledge of the event.
The following must be reported:

















New or increased risk (For example, publications indicating a new risk, new risk in an
investigator brochure, FDA black box warning, new risk identified in a data safety monitoring
report, information or change that adversely affects subject safety, or information or change that
adversely affects the conduct of the research)
Adverse events or IND safety reports that require a change to the protocol or consent
Protocol deviation due to the action or inaction of the investigator or research staff
Protocol deviation that harmed a subject or placed subject at risk of harm
Protocol deviation made without prior IRB approval to eliminate an immediate hazard to a
subject
Audit, inspection, or inquiry by a federal agency
Written reports of federal agencies (e.g., FDA Form 483)
Written reports of study monitors
Allegation of Noncompliance or Finding of Noncompliance
Unauthorized disclosure of confidential information
Unresolved subject complaint
Suspension or premature termination by the sponsor, investigator, or institution
Incarceration of a subject enrolled in a research study not approved to involve prisoners
State medical board or hospital medical staff actions
Unanticipated adverse device effect
Unexpected death of a locally enrolled subject
Any other unanticipated information that is related to the research and indicates that participants
or others might be at increased risk of harm
All problems/events that do not meet the IRB’s 5-day reporting requirement should be reported to the
IRB in summary form, using a table or spreadsheet, at the time of continuing review.
IND safety letters that do not meet the IRB’s 5-day reporting requirement, should not be included with
the continuing review summary and will be returned to the investigator if received.
UPIRTSO Report:
 The Principal Investigator makes a written report which:
o Outlines the details of the event, including any safety or interim reports
o Describes the nature and severity of the problem
o Provides an assessment using professional judgment of the likely impact of the event on
the study subjects or others
o Assesses the likelihood of the event recurring.
Page 2 of 4
The report should include any relevant interim reports or information, including but not limited to:
interim safety reports, interim data analyses, or data safety monitoring board reports.
IRB Review and Action:
 The IRB reviews the reports to evaluate the unanticipated problem and determine whether the
report fits the criteria of UPIRTSO and whether the likelihood or magnitude of risks to
participants or other has increased since the research was last approved by the IRB. IRB review
of the unanticipated problem will include an assessment of the adequacy of plans and provisions
for monitoring the safety of participants. The IRB reviewer will receive the report and
accompanying documents, the original application, current consent forms, review sheet, and
other relevant documents as appropriate
 The IRB will make determinations concerning:
o whether the Unanticipated Problem meets the criteria as a UPIRTSO and if so, must
therefore, be reported to appropriate officials
o whether the study should continue, or be suspended
o recommendation to the Institutional Official that the event be reported (see IRB Policy 409
Reporting Requirements )

If the study is continued:
o whether information concerning the event should be shared with current or previous enrolled
subjects as it may relate to their willingness to continue
o the adequacies of the protection plan
o whether changes are required in the plan or protocol to assure continued safety
o whether changes are required in the consent forms to be provided to new subjects
o whether a formal re-consent of enrolled persons is in order as it may relate to their
willingness to continue
o whether the time frame for continuing review reports should be modified
o Whether additional information is required from the researcher or through a monitoring or
audit mechanism.

All actions are recorded in the IRB files
Notification to Researcher and Limited Appeal:
The outcome of the IRB’s UPIRTSO review is reported to the investigator in writing. If the IRB
suspends or terminates a study based on harm to subjects, the researcher may have an opportunity to
submit an appeal under the terms of IRB Policy 410A Appeals of Suspension and Termination.
4.0 Required approvals for this document
Title
Executive Director, HRPP
Page 3 of 4
5.0 Revision History
Revision
06/19/14
03/29/10
11/11/09
10/14/09
06/22/09
09/26/06
Reason for change
Update AAHRPP references
Update per AAHRPP revisions
Revision and editing
Update AAHRPP revisions
Revision
Reformat
Date of release
09/02/14
03/29/10
11/11/09
10/14/09
09/11/09
05/18/09
To obtain a copy of a historical policy, e-mail at irb@umn.edu or call 612-626-5654
Page 4 of 4