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When does the UPIRTSO Policy go into effect (date)?

Monday, March 19, 2007


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What does an Investigator need to report?

Investigators are required to promptly report "any unanticipated problems involving risk to subjects or others" (UPIRTSO) as defined by Federal regulations [45 CFR 46.103(b)(5) and 21 CFR 56.108(b)(1)]. Once reported, Mayo Clinic's IRB will determine what constitutes an unanticipated problem involving risk to subjects or others (UPIRTSO) and will report to appropriate institutional officials, OHRP, and other relevant Federal agencies as set forth in IRB Policy III.C.


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What is the definition of an Unanticipated Problem Involving Risk to Subjects or Others (UPIRTSO)?

Mayo Clinic's IRB defines a UPIRTSO as any problem or event that was 1) serious; 2) unanticipated; AND 3) at least possibly related to research procedures.


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How are the criteria – serious, unanticipated, related – defined?

Serious: Serious problem/events can be well defined and include death; life threatening adverse experience; hospitalization: inpatient, new, or prolonged; disability/incapacity: persistent or significant; birth defect/anomaly; and/or per protocol OR may be problems/events that in the opinion of the local Investigator may have adversely affected the rights, safety, or welfare of the subjects or others, or substantially compromised the research data.

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. A problem/event is "unanticipated" when it was unforeseeable at the time of its occurrence. A problem/event is "unanticipated" when it occurs at an increased frequency or at an increased severity than expected.

Related: A problem/event is "related" if it is possibly, probably or definitely related to the research study.


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Who makes the assessment of whether an unanticipated problem/event constitutes a UPIRTSO?

The IRB relies on the Mayo Clinic Investigator to provide an assessment of whether UPIRTSO criteria are met for a given problem/event. As the person most familiar with and ultimately responsible for the conduct of the study, the Investigator is the person to provide his/her assessment of whether a problem/event meets UPIRTSO criteria. The Investigator's assessment of the problem/event should include a determination related to any changes to the approved study that should be made as a result of the UPIRTSO report.


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What do I do with a problem/event that has not previously been reported to the IRB but occurred prior to March 19, 2007?

Apply the current (March 19, 2007) UPIRTSO Reporting Policy.


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How do I reconcile on the continuing review/progress report between those problems/events that have already been reported to the IRB with those problems/events that are now considered non-UPIRTSOs?

Submit all non-UPIRTSOs including all adverse events, SAEs and deviations reported under the previous IRB SAE Reporting Policy since the last progress report approval.


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How are UPIRTSOs submitted to the IRB?

UPIRTSOs are submitted in IRBe via the Reportable Events button.


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How soon must a UPIRTSO be submitted to the IRB?

The Investigator should promptly assess unanticipated problems/events that occur on the research study. Once the Investigator has determined that a problem/event constitutes a UPIRTSO, it should be reported within 5 working days using the Reportable Events button found in IRBe. A UPIRTSO must be reported within this time frame, even if the problem/event is not yet resolved.


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What if the Investigator determines the problem/event does not meet the criteria for UPIRTSO?

When the 3 criteria are not met, the problem/event is called a non-UPIRTSO. All problems/events that do not meet Mayo Clinic IRB's definition of UPIRTSO should be reported to the IRB in summary format at the time of continuing review. Accompanying documentation (sponsor report form, etc) should not be included with this summary and if received will be returned to the Investigator.


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What are the Investigator's responsibilities related to study management of problems/events that will not meet Mayo's IRB definition of UPIRTSO?

  • Investigators are reminded that while a problem/event may not initially meet the definition of a UPIRTSO, it can transform (based on nature, severity and frequency) to a UPIRTSO. Therefore, while problems/events may not meet Mayo's IRB definition of UPIRTSO, continuous monitoring systems are needed to identify in 'real time' any changes in nature, severity and/or frequency of problems/events.
  • Investigators are reminded that Standard Operating Procedures (SOPs) are essential as they set forth:
    1. the documentation/tracking system used by the Investigator for problems/events; and
    2. frequency of study team meetings and/or communication procedures between the Investigator and study team for any changes in nature, severity and/or frequency of problems/events.
  • Investigators are reminded that while a problem/event may not meet Mayo's IRB definition of UPIRTSO, they must still comply with requirements for reporting to other reviewing entities (e.g. sponsor, funding agency, DSMB).

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What is expected at the time of IRB Continuing Review for problems/events that will not meet Mayo's IRB definition of UPIRTSO?

Investigators will provide a narrative summary of these problems/events (non-Mayo Clinic UPIRTSOs and Mayo Clinic non-UPIRTSOs) at the time of IRB Continuing Review.

Guidance for preparing the narrative summary:

  • The presentation of problems/events may be enhanced using a chart or diagram.
  • The narrative summary prepared by the Investigator at the time of Continuing Review should state whether the non-Mayo Clinic UPIRTSO and Mayo Clinic non-UPIRTSO event profile observed in Mayo Clinic subjects or others:
    • Is different (frequency and/or level of severity) from what is anticipated (research protocol, consent form, investigator brochure); and
    • Compares and contrasts what has happened here at Mayo Clinic to what has occurred at other sites, if applicable

Additional Questions? Please call the IRB Service Center at (77) 6-4000.