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The following serves as an abbreviated guide of common events that may occur during the conduct of a human research study, which the Principal Investigator (PI) should report to the IRB. 

Unanticipated Problem Involving Risks to Subjects or Others (UPIRSO)

This is an event that: 

  • Is unexpected (in terms of nature, severity, or frequency) given (a) the research procedures that are described in the protocol-related documents, such as the IRB-approved research protocol and informed consent document; and (b) the characteristics of the subject population being studied; and
  • Is related or possibly related to participation in the research; and
  • Suggests that the research places subjects or others at a greater risk of harm (including physical, psychological, economic, or social harm) than was previously known or recognized.

Note: According to federal guidance, “UPIRSOs” typically warrant consideration of substantive changes to the protocol or informed consent process or corrective actions in order to protect the safety, welfare, or rights of subjects.

IRB Policy on Unanticipated Problem and Safety Reporting [D2.0000]

UPIRSO Prompt/Non-Prompt Reporting Guidance [D162.0000]

Unanticipated Adverse Device Effect (UADE)

This is an unanticipated, serious adverse effect on health or safety or any life-threatening problem or death caused by, or associated with, an investigational device.

Change in Protocol Status

Such as suspension, discontinuation, completion of a study, FDA Clinical Hold, etc.

Anything New that Wasn't Anticipated/Increases Risk

New information may be generated from a number of sources including the Food and Drug Administration (FDA), published literature, results on clinicaltrials.gov, or a sponsor that may require a change in the consent form.

Data and Safety Monitoring Communications

If the study has a Data Safety Monitoring Board (DSMB), the PI must solicit and provide the IRB with communication or documentation, including DSMB summary reports, meeting minutes, determinations, conclusions, etc.

Allegations or Oversight Agency Compliance Actions

Including actions by government oversight agencies (FDA Warning Letter, OHRP Determination Letter), lawsuits, or negative press coverage (TV, radio, publication) regarding Human Research Protections.

Protocol Violations

See Protocol Violation Information, Form, and SOP.

Any exception or deviation involving a single subject that is not approved by the IRB prior to its initiation. 

Failure to Follow Regulations or IRB Requirements

FDA Correspondence

Any ruling from the FDA (e.g., IND/IDE correspondence, clinical hold, FDA Form 483, or Warning Letter).

Investigator Medical License Restrictions or Suspension

Unresolved Subject Complaint

Audit, Inspection, or Federal Agency Inquiry, Negative Press, or Lawsuit

Subject Incarceration