Events Requiring Prompt Reporting to the IRB including Unanticipated Problem Involving Risks to Subjects or Others
Reporting Requirements
Federal Regulation 21CFR §56.108(b)(1) and 45 CFR 46.103(b)(5) require the IRB to "follow written procedures for ensuring prompt reporting to the IRB…any unanticipated problems involving risk to human subjects or others."
Investigators are required to promptly report to the IRB:
(1) Unanticipated problems including adverse events that are unexpected and related.
An event is “unexpected” when its specificity and severity are not accurately reflected in 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);
An event is “related to the research procedures” if the event is deemed probably or definitely related.
(2) Unanticipated adverse device effect. Any serious adverse effect on health or safety or any life-threatening problem or death caused by, or associated with, a device, if that effect, problem, or death was not previously identified in nature, severity, or degree of incidence in the investigational plan or application (including a supplementary plan or application, or any other unanticipated serious problem associated with a device that relates to the rights, safety, or welfare of subjects.
(3) In addition to unanticipated problems, the IRB also requires prompt reporting of the following events:
Complaint of a participant when the complaint indicates unexpected risks or the complaint cannot be resolved by the research team.
Violation or deviation (meaning an accidental or unintentional change to the IRB approved protocol) only when:
one or more participants were placed at increased risk of harm or or the event has the potential to occur again,
or,
the event represents serious or continuing noncompliance.
Breach of confidentiality.
Incarceration of a participant when the research was not previously approved under Subpart C and the investigator believes it is in the best interest of the subject to remain on the study.
The IRB requires investigators to submit reports within 10 working days (with one exception) of events that meet the definition of an unanticipated problem involving risks to subjects or others. Exception: If the adverse event involved a death and indicates that participants or others are at increased risk of harm, investigators are required to submit a report to the IRB within 3 days.
Submit a narrative summary of adverse events at the time of continuing review. Submit routine, periodic reports (e.g. DMC reports that indicate no changes, sponsor annual progress reports) to the IRB at Continuing Review.
Unnecessary reporting of events or problems that do not potentially affect the rights, welfare or safety of subjects in the study may impair the IRB’s ability to review and respond in a timely manner to actual situations where subject rights, welfare or safety are threatened.
The IRB will not acknowledge safety reports or bulk AE submissions that do not meet the criteria outlined below. These submissions will be returned. Notify your sponsor of this policy.
The IRB encourages study teams to communicate this policy to sponsors and should use this document for verification as necessary.
The IRB will accept other reports when the investigator is unsure whether the event should be reported, and the IRB will review such reports to determine whether the event meets the threshold for an unanticipated event presenting risk to the participant.
Principal investigators will submit a written report of the above events. Initial reports may be accepted by other means such as e-mail, or phone with a follow up written report.
The IRB staff, when necessary in conjunction with the IRB chair, review reports and decide whether the event meets the definition of an unanticipated problem increasing risks to subjects or others.
Events that meet these criteria will be considered unanticipated problems involving risks to participants or others, will be reviewed by the convened IRB, and will be reported according to CO 602.
Primary reviewers will receive the sponsor protocol, investigator brochure, original IRB application form, consent document, copy of the report form, any supplemental information
All other IRB members will receive the original application form, consent document, copy of the report form, any supplemental information.
The IRB considers the following actions:
Accept report or with no additional requirements.
Approve investigator’s proposed changes.
Administrative hold on the study pending IRB receipt of further information from the PI in a time period not to exceed 90 days.
Modification of the protocol.
Modification of the information disclosed during the consent process.
Providing additional information to current participant the information may relate to the participant’s willingness to continue participation.
Making arrangements for clinical care outside the research or additional follow-up for participants.
Providing additional information to past participants.
Requiring current participants to re-consent to participation.
Alteration of the frequency of continuing review.
Observation of the research or the consent process.
Requiring additional training of the investigator.
Notification of investigators at other sites.
Obtaining additional information.
Termination or suspension of the research. If this action is taken, the IRB Director will notify the Institutional Official to initiate any reporting actions. If the IRB does not consider the event to represent an unanticipated problem involving risks to participants or others, no further action needs to be taken.
