An Unanticipated Problem (UP) is any incident, experience, or outcome that meets all of the following criteria:

  • unexpected in terms of nature, severity, or frequency;
  • related or possibly related to participation in the research; AND
  • suggests that the research places subjects or others at a greater risk of harm than was previously known or recognized.

Not all events or instances of non-compliance meet the criteria for UP requiring prompt reporting.  The diagram below provides a schematic of how to conceptualize Unanticipated Problems.

UP Conceptualization-3It is the responsibility of the PI, based on his/her scientific and medical expertise and judgment, to assess if an event or non-compliance/deviation qualifies as a UP requiring prompt reporting.

The following considerations offer some guidelines:

  • An event may be considered “unexpected” if
    • it is not listed in the current protocol, investigator’s brochure, consent form, or other relevant sources of information such as product labeling and package inserts;
    • it is not characteristic of the subject population being studied;
    • it is not consistent with the expected natural progression of any underlying disease, disorder, or condition of the subject, and the subject’s predisposing risk factor profile; or
    • the severity and/or frequency of the event is beyond the range previously known.
  • An event may be caused by one or more of the following: (1) procedures involved in the research; (2) an underlying disease, disorder, or condition of the subject; or (3) other circumstances unrelated to the research or any underlying disease, disorder, or condition of the subject.
    • If an event is caused at least partially by (1), then the event should be considered “related or possibly related” to participation in the research.
    • Events caused solely by (2) or (3) would be considered “unrelated” to participation in the research and are not reportable.
  • An event places the subjects at a “greater risk of harm than previously known or recognized” if the event is
    • a serious adverse event; or
    • an adverse event occurring at a higher frequency or severity than initially identified, or
    • an incident that compromises the subject’s safety, privacy, or confidentiality.