UNANTICIPATED PROBLEMS
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.
It 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.
- 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;
- 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.
- 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.
- 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.
- a serious adverse event; or