Subject: Reporting Unanticipated Problems Involving Risk to Subjects or Others (UPIRTSO)

Procedure:

1. Investigator Responsibilities.
   1. The Investigator shall assess whether a problem/event may be a UPIRTSO
   2. The Investigator shall report UPIRTSOs as follows.
      1. Occurring at Mayo Clinic or a site for which the Mayo Clinic IRB serves as the IRB of Record:
         1. Submit to the IRB by completing the UPIRTSO form as soon as possible, but no later than 5 working days after the Investigator first learns of the problem/event.
         2. Include any relevant documents such as medical record notations or reports with the name and medical record number of the individual removed.
         3. Assess whether protocol modifications are required as a result of the UPIRTSO. If a modification is required, complete the link that takes you to the modification form. If not, the Investigator must provide an explanation on the UPIRTSO form explaining what corrective actions have already been taken.
      2. Occurring at a non-Mayo Clinic site:
         1. Submit to the IRB at the time of your scheduled continuing review in a narrative format.
         2. If other monitoring bodies (e.g. IRB at the site where the UPIRTSO occurred, the sponsor, or the Data Safety Monitoring Board) require changes to the protocol as a result of the non-Mayo Clinic problem/event, a modification must be submitted.
   3. The Investigator shall report Non-UPIRTSOs as follows:
      1. At the time of continuing review, submit a brief narrative summary describing the nature, type, and frequency of events that have occurred since the last progress report.
      2. Continually monitor severity and frequency of Non-UPIRTSO events throughout the course of the study and consider whether any changes caused such events to be considered UPIRTSOs. If so, such UPIRTSOs shall be reported to the IRB as stated in this procedure.
      3. Non-UPIRTSOs shall not be immediately reported to the IRB simply because immediate reporting is requested by the sponsor.
   4. Investigators are reminded they must also comply with requirements for reporting to other reviewing entities (e.g. sponsors, funding agencies, DSMBs).

      **Please note: Unnecessary reporting of problems/events that do not potentially affect the rights, welfare or safety of subjects in the study or others may impair the IRB's ability to review and respond in a timely manner to actual situations where subjects or others' rights, welfare or safety are threatened.

2. IRB Specialist Responsibilities
   1. Upon receipt of a UPIRTSO, the Specialist shall review the report within one working day.
      1. Problems/Events that meet the definition of UPIRTSO are referred to a Chair or Vice Chair for determining whether an Administrative Hold is necessary as set forth in IRB Policy II.B, ^[1] and assigned to next available Full Committee.
      2. Problems/Events that do not clearly meet the definition of UPIRTSO shall be referred to a Chair or Vice Chair to make the determination for appropriate triage and whether an Administrative Hold is necessary as set forth in IRB Policy II.B. ¹
      3. Problems/Events that are determined to be Non-UPIRTSOs will be returned to Investigator with instructions to submit in accordance with Section I.C of this procedure.
   2. For those problems/events determined to be UPIRTSOs, the Specialist shall ensure all IRB Committee Members have access to the following documents for review at the next available meeting:
      1. The UPIRTSO form;
      2. The DSMB or safety report, if applicable;
      3. Supplemental material submitted with the report;
      4. A modification request, if applicable;
      5. The current IRB approved application and consent document;
      6. The study protocol;
      7. The Investigator's Brochure, if applicable; and
      8. Any other pertinent materials.
   3. The Specialist will generate a minute item describing the Full Committee's decision regarding the UPIRTSO. The minute item will be reviewed and approved by the Full Committee and sent to the Investigator.
   4. The Specialist will complete all appropriate IRB database entries.
3. IRB Committee Responsibilities
   1. The Chair or Vice Chair will receive UPIRTSO reports from the Specialist in accordance with Section II.A.1, 2 of this procedure.
   2. Problems/Events that are determined by the Chair or Vice Chair to be Non-UPIRTSOs will be returned to Investigator with instructions to submit in accordance with Section II.A.3 of this procedure.
   3. If the Chair or Vice Chair determines the problem/event is a UPIRTSO or cannot make a determination, the report will be forwarded to the Full IRB Committee to make these decisions.
   4. A primary reviewer will be assigned. All IRB Committee Members will receive a copy of the UPIRTSO form and supporting documents provided by the Investigator to assist in determining whether the problem/event meets the applicable criteria.
   5. If the IRB determines that more information is needed, it may postpone a decision while awaiting the requested information. In such cases, the IRB will consider the appropriateness of an "Administrative Hold" on the research until a final determination is made.
   6. Problems/events that are determined by the IRB to be Non-UPIRTSOs will be documented as set forth in IRB Policy III.G. ^[2]
   7. If the IRB determines that the problem/event meets all three criteria, (serious, unanticipated, and related), the problem/event will be considered a UPIRTSO and the following actions may take place:
      1. The IRB may:
         1. Approve the report with no changes;
         2. Approve the report with changes to the protocol requested in the modification;
         3. Request a meeting with the Investigator;
         4. Request further information from the Investigator, Data Safety Monitoring Board (DSMB) or other monitoring bodies;
         5. Increase the frequency of continuing progress report review;
         6. Impose additional monitoring;
         7. Ask the Investigator to place the study on "Administrative Hold" pending receipt of further information;
         8. Suspend the study for cause as set forth in IRB Policy II.B ¹ with:
            1. Suspension of recruitment;
            2. Suspension of screening and enrollment;
            3. Suspension of intervention and interaction; or
            4. Suspension of follow-up.
         9. Terminate the study for cause as set forth in IRB Policy II.B. ¹
      2. The problem/event will be reported as set forth in IRB Policy II.C. ^[3]
      3. The IRB will consider whether the problem represents serious or continuing non-compliance as set forth in IRB Policy II.C.³
      4. In the case of changes in the protocol taken without prior IRB review to eliminate apparent immediate hazard to a research subject, the IRB will consider whether the changes were consistent with the protection of the rights and welfare of subjects.
   8. If the IRB Committee determines that the problem/event does not meet one or more of the three criteria, the problem/event will be considered not to represent a UPIRTSO. The Investigator will be informed of the Full Committee's decision as set forth in in Section III of IRB Policy III.G. ^[4]

^[1] IRB Policy II.B

^[2] IRB Policy III.G

^[3] IRB Policy II.C

^[4] Section III of IRB Policy III.G