Reporting
Unanticipated Problems to the IRB
Federal
regulations [45CFR46.103(b)(5) and 21CFR56.108(b)(1)] require the
IRB to ensure that investigators promptly report “any unanticipated
problems involving risk to subjects or others” (UPIRTSO).
The IRB defines UPIRTSO as any problem or event which in the
opinion of the local investigator was unanticipated, serious AND
at least possibly related to the research procedures.
These
should be reported to the IRB within 10 working days using the reporting
form found
here.
What to Report
The following
events meet the IRB’s definition of UPIRTSO and should be
reported within the 10 day time frame:
- Any serious
event (including on-site and off-site adverse events, injuries,
side effects, deaths or other problems) which in the opinion of
the local investigator was unanticipated, involved risk to subjects
or others, and was possibly related to the research procedures.
- Any serious
accidental or unintentional change to the IRB-approved protocol
that involves risk or has the potential to recur.
- Any deviation
from the protocol taken without prior IRB review to eliminate
apparent immediate hazard to a research subject.
- Any publication
in the literature, safety monitoring report (including Data and
Safety Monitoring Reports), interim result or other finding that
indicates an unexpected change to the risk/benefit ratio of the
research.
- Any breach
in confidentiality that may involve risk to the subject or others.
- Any complaint
of a subject that indicates an unanticipated risk or that cannot
be resolved by the research staff.
- Any other
serious and possibly related event which in the opinion of the
investigator constitutes an unanticipated risk.
Note that
issues such as whether the event was on-site or off-site or whether
the event involved a death are no longer of primary relevance
in determining what should be reported. If the event meets all
3 criteria in the IRB’s definition of UPIRTSO, it should
be reported using the reporting form within the 10-day time frame.
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Definitions
Unanticipated
(unexpected) problems/events are those that are not already
described as potential risks in the consent form, not listed
in the Investigator’s Brochure or not part of an
underlying disease. Anticipated (expected) problems/events
do NOT meet the IRB’s definition of UPIRTSO.
Serious
problems/events are those which in the opinion of the local investigator
involve risk to subjects or others. Examples may include death,
hospitalization, disability as well as breach of confidentiality.
Non-serious problems/events do NOT meet the IRB’s definition
of UPIRTSO.
Problems/events
that are unanticipated and serious should be reported to the IRB
within 10 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.
• Follow-up
reports on previous events should be reported as UPIRTSOs if the
initial event itself met the IRB’s definition of UPIRTSO AND
in the local investigator’s judgment, this follow-up report
adds value to the initial report.
• Reports of off-site events on studies that are now closed
at this site should be reported as UPIRTSOs if the event meets the
IRB’s definition of UPIRTSO AND in the local investigator’s
judgment, this event may affect risk to subjects who have completed
the study.
• For reports involving blinded study drug, the assessment
of relatedness will often be “at least possibly related”
as relatedness cannot always be ruled out. If there are numerous
reports on the same blinded drug and these reports all meet the
3 criteria for UPIRTSO, they may be reported on one UPIRTSO form
with an accompanying table/spreadsheet. A narrative regarding whether
risk is altered or subjects should be notified may be provided for
each group of similar events.
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Additional Guidance
Reviwing and Reporting Unanticipated Problems Involving Risks to Subjects or Others and Adverse Events dated January 15, 2007 can be found at the Office for Human Research Protections (OHRP) Website.
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IRB Review of UPIRTSOs
Once received
in the IRB office, completed UPIRTSO reporting forms will be pre-reviewed
by IRB staff to determine the level of IRB review required.
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Non-UPIRTSO
Problems or Events
All problems/events
that do NOT meet the IRB’s definition of UPIRTSO should be
reported to the IRB in summary form (using a table or spreadsheet)
at the time of annual continuing review. Accompanying documentation
(sponsor report forms, etc.) should NOT be included with this summary.
If received, such accompanying documentation will be returned to
the investigator.
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UPIRTSO Form
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Form
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