Reporting Unanticipated Problems to the IRB (UPIRTSO)

A. Purpose

This policy describes research investigator responsibilities for reporting unanticipated problems involving risk to subjects or others for IRB-approved research.

B. Revision history

Originally issued: May 2005 as IRB Reporting of Adverse Events Related to Research Protocols; Revised: June 2007 based on the University of Minnesota IRB’s Reporting Unanticipated Problems to the IRB policy

C. Persons affected

All Northwestern Health Sciences University faculty, staff, and student investigators engaged in research activities.

D. Additional guidance

Guide for Reviewing and Reporting Unanticipated Problems Involving Risks to Subjects or Others and Adverse Events dated January 15, 2007.

E. Policy

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. The obligation to review UPIRTSOs is shared among the individual investigators, the project Data Safety Monitoring Board (DSMB), and the IRB.

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, if in the local investigator’s judgment, the 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, if in the local investigator’s judgment, this event may affect risk to subjects who have completed the study.
  • For reports involving blinded study drugs, 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.

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.

Reporting of adverse events for multi-center studies

If an UPIRTSO occurs at another institution in a multi-center study, it must be reported to that institution's IRB according to their IRB regulations by that site’s principal investigator. That site’s principal investigator must notify the NWHSU principal investigator. It is the responsibility of the NWHSU principal investigator to complete the UPIRTSO report and forward the subsequent conclusions of the other institution’s IRB to the NWHSU IRB as soon as possible but no later than 60 days after the occurrence of the event.

Establishment and function of a Data Safety Monitoring Board (DSMB)

Studies that involve a therapeutic or diagnostic intervention with a drug, biologic, device, or procedure must include a plan for monitoring data safety. In most instances, this requirement should be met by having a DSMB, unless the investigator can justify in the rationale for not having one. Whether the study has a formal DSMB or not, a list of the individuals responsible for data safety monitoring, the frequency of data safety evaluations, the safety endpoints to be measured, the definitions used for grading the severity of UPIRTSO, and the procedures for handling them should be provided in the application for IRB approval of human subjects research.

For research projects that have a DSMB, it is the responsibility of the principal investigator to provide the IRB with any communication from the DSMB about the DSMB's recommendations regarding the UPIRTSO within 10 working days of the receipt of the communication. All communications with outside agencies, such as the sponsor must also be forwarded to the IRB within 10 working days of receipt.

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.

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.

UPIRTSO form

UPIRTSO form (Word)

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