Reporting Unanticipated Problems and Adverse Events Involving Risk to Service Recipients/Participants or Other Entities

Per OHRP, unanticipated problems incorporate any experience, incident, or outcome that meets all three of the following criteria:

1. The problem is unexpected. It was not expected given the research procedures described in the informed consent document and/or the IRB- approved research protocol. Neither was the problem expected given the characteristics of the participant population under study. The unexpectedness may relate to how the problem occurred, how often the problem occurred, or to the extent at which the problem occurred.
2. The problem is related or possibly related to a participant’s participation in the research. “Possibly related” indicates there is a reasonable likelihood that the experience, incident, or outcome may have been caused by the procedures involved in the research. If it is determined that an event is solely caused by an underlying condition, disease, or disorder of the participant OR other circumstances not related to either the condition, disease, or disorder of the participant or the research, then the event would be considered unrelated to participation in the research.
3. The research places the service recipients/participants or others at a greater risk of harm than was previously recognized or known. “Harm” can include economic, psychological, physical, or social harm. Moreover, this harm needs to be serious such as causing the participant to move to a higher level of care or the participant dies. If a death occurs, it must be related to the research.

Unanticipated problems are reportable to OHRP, whether or not they are adverse events.  Adverse events are neither defined nor used in 45 CFR Part 46, but broadly encompass both physical and psychological harm. The harm must be serious and related to the research.  Most adverse events are not unanticipated problems. Such events are not reportable to OHRP under 45 CRF Part 46, but may be reported to the IRB.  Adverse events that are additionally unanticipated problems must be reported to the IRB, who will, in turn, report to OHRP. (It is the responsibility of the PI to report these events to the sponsor.  Often action, such as suspension of research, takes place when these types of events occur.)

Unanticipated problems that are not adverse events but might, in the opinion of the PI, involve risk to the service recipients/participants, affect others in the research study, or significantly impact the integrity of the research data such as accidental destruction of study records, breaches of confidentiality, or unaccounted-for study drug often warrant consideration of substantive changes in the informed consent process/document, research protocol, or other corrective actions in an effort to protect the rights, safety, or welfare of participants or others.

All adverse events or unanticipated problems must be documented by the PI/researcher.

Responsibilities When Unanticipated Problems/Adverse Events Occur.

• Unanticipated problems must be reported to the IRB even after service recipients/participants have completed the study or after withdrawal from the study including after study closure.
• The PI should submit an adverse event/unanticipated problem form for each individual participant to the IRB. Adverse events/unanticipated problems should be incorporated into continuing review proposals.
• Any adverse event/unanticipated problem must be reported to the IRB. The IRB Administrator, in conjunction with the IRB Chairperson, will determine whether the event/problem needs full IRB review.
• Serious adverse events such as death of a participant, whether or not the incident is determined to be related to the research, must be addressed at a full IRB meeting.
• Communication with the PI regarding adverse events/unanticipated problems will be conducted in writing.