Adverse Events and Unanticipated Problems

The following definitions are used by the IRB:

Related event is an event that in the opinion of the investigator is more likely than not to be caused by or affects the research procedures.

Unanticipated problem involving risks to subjects or others is an event that includes any incident, experience, or outcome that meets all of the following criteria:

  1. 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;
     
  2. related or possibly related to participation in the research; and
     
  3. 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.      

Adverse event is any untoward or unfavorable medical occurrence in a human subject, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the subject’s participation in the research, whether or not considered related to the subject’s participation in the research.

Unexpected adverse event is an adverse event occurring in one or more subjects participating in a research protocol, the nature, severity, or frequency of which is not consistent with either:

  1. the known or foreseeable risk of adverse events associated with the procedures involved in the research that are described in (a) the protocol-related documents, such as the IRB-approved research protocol, any applicable investigator brochure, and the current IRB-approved informed consent document, and (b) other relevant sources of information, such as product labeling and package inserts; or
     
  2. the expected natural progression of any underlying disease, disorder, or condition of the subject(s) experiencing the adverse event and the subject’s predisposing risk factor profile for the adverse event.  

Serious adverse event is any event that results in death; is life-threatening and places the subject at immediate risk of death from the event as it occurred; results in inpatient hospitalization or prolongation of existing hospitalization; results in a persistent or significant disability or incapacity; results in a congenital anomaly or birth defect; or based upon appropriate medical judgment, may jeopardize the subject’s health and may require medical or surgical intervention to prevent one of the other outcomes listed in this definition.

Expected adverse event is an adverse event that does not meet the criteria for an “unexpected event.”

Investigators are required to report to the Institutional Review Board (IRB) the following using the Full Unanticipated Problem and Adverse Event Report Form when discovered during the course of research and no later than 5 working days after their occurrence:

  1. Unexpected AND related adverse events (on-site or off-site)
  2. The death of a research subject on site
  3. Unanticipated problem that is a serious adverse event (on-site or off-site)
  4. Any complaint of a participant that indicates an unanticipated risk or which cannot be resolved by the research staff
  5. Any other event or other problems which in the opinion of the principal investigator was (1) previously unforeseen and (2) presents risks to research subjects or others
  6. Any event that requires prompt reporting according to the protocol or the sponsor

Events that do not meet the above reporting requirements, but which sponsors request Investigators to report to the IRB, should be logged on a Tracking Form for Unanticipated Problems and Adverse Events and submitted to the IRB as soon as possible.  Multiple events can be reported on a single form, with theIND or manufacturer’s safety report attached.  If the investigator answers “yes” to the following three questions on the form, a Full Unanticipated Problem and Adverse Event Report Form must be filled out and submitted for that event: 1. Did the event place subjects at greater risk of harm than was previously known or recognized?  2.  Was the event unexpected?  3.  Was the event related to study drug/device or procedure?

The Chair of the IRB or a designated member reviews all reports.  If the IRB Chair determines that the event did not represent an unanticipated problem involving risks to participants or others, the chair signs and dates the report and the report is approved.  If the IRB Chair or designated member determines that an event might represent an unanticipated problem involving risks to participants or others, and related to the investigation, the event is reviewed at the next convened IRB meeting.  The IRB votes to determine whether the event is an unanticipated and related problem involving risks to participants or others.   

If IRB determines that an event is an unanticipated and related problem involving risks to participants or others, it will consider the following actions:

  1. No action
  2. Modification of the research protocol  
  3. Modification of the information disclosed during the consent process  
  4. Additional information provided to past participants  
  5. Notification of current participants (required when such information may relate to participants’ willingness to continue to take part in the research)  
  6. Requirement that current participants re-consent to participation  
  7. Modification of the continuing review schedule  
  8. Monitoring of the research  
  9. Monitoring of the consent  
  10. Suspension or termination of the research  
  11. Referral to other organizational entities (e.g., legal counsel, risk management, or institutional official)