The Principal Investigator is responsible for ensuring that the following are promptly reported to the IRB:
(a) Changes to an approved protocol. Approval of the IRB is necessary prior to implementation of the change unless it was necessary to eliminate apparent immediate hazards to the subject. In this case the change should be reported as soon as possible. Changes in study personnel must also be reported.
(b) All research related injuries and unanticipated problems which involve risks to subjects or others. This information should also be reported to the senior clinical authority in the facility. The IRB should submit all such reports to RFMH.
(c) Newly available information which the IRB should have in order to fulfill its responsibility for ongoing review and monitoring. For example, if new information becomes available about the side effects associated with a study medication this should be sent to the IRB.
(d) Any unanticipated problems involving risks to subjects or others or any serious or continuing noncompliance with the requirements or determinations of the IRB.
The IRB is responsible for informing RFMH of the above information provided by the investigator or any other person and any subsequent action that has been taken by the IRB and/or the facility. The IRB must also report to RFMH:
(a) Any serious or continuing non-compliance by investigators with the requirements and determinations of the IRB.
(b) Any suspension or termination of IRB approval for a study.
(c) All changes in IRB membership.
RFMH is required to report to the federal Office for Human Research Protections:
(a) Research related injuries to subjects and unanticipated problems related to the research involving risks to subjects or others. This information must also be reported to the FDA if investigational drugs or devices are involved.
(b) Serious or continuing noncompliance by investigators with the requirements and determinations of the IRB. This information must also be reported to the FDA if investigational drugs or devices are involved.
(c) Suspension or termination of IRB approval.
(d) Changes in IRB membership.
Reporting Unanticipated Problems and Adverse Events
Investigator Reporting Responsibilities:
Reporting of Internal Adverse Events:
For an internal adverse event, the investigator typically becomes aware of the event directly from the subject, another collaborating local investigator, or the subject’s healthcare provider. Upon becoming aware of an internal adverse event, the investigator should assess whether the adverse event represents an unanticipated problem following the criteria described in Section 3.9. If the investigator determines that the adverse event represents an unanticipated problem, the investigator must report it promptly to the IRB (45 CFR 46.103(b)(5)).
Regardless of whether the internal adverse event is determined to be an unanticipated problem, the investigator also must ensure that the adverse event is reported to a monitoring entity (e.g., the research sponsor, a coordinating or statistical center, an independent medical monitor, or a DSMB/DMC) if required under the monitoring provisions described in the IRB-approved protocol or by institutional policy.
If the investigator determines that an adverse event is not an unanticipated problem, but the monitoring entity subsequently determines that the adverse event does in fact represent an unanticipated problem (for example, due to an unexpectedly higher frequency of the event), the monitoring entity should report this determination to the investigator, and such reports must be promptly submitted by the investigator to the IRB (45 CFR 46.103(b)(5)).
Reporting of External Adverse Events:
When an investigator receives a report of an external adverse event, the investigator should review the report and assess
whether it identifies the adverse event as being:
related or possibly related to participation in the research; and
serious or otherwise one that suggests that the research places subjects or others at a greater risk of physical or psychological harm than was previously known or recognized.
Only external adverse events that are identified in the report as meeting all three criteria must be reported promptly by the investigator to the IRB as unanticipated problems under HHS regulations at 45 CFR 46.103(b)(5).
Multi-Site Adverse Events Reports:
Adverse events occurring in subjects enrolled in a multicenter study should be submitted for review and analysis to a monitoring entity (e.g., the research sponsor, a coordinating or statistical center, or a DSMB/DMC) in accordance with a monitoring plan described in the IRB-approved protocol.
When a particular adverse event or series of adverse events is determined to meet the criteria for an unanticipated problem a report of the adverse event(s)should be submitted to the IRB at each institution under the HHS regulations at 45 CFR part 46. Any distributed reports should include: (1) a clear explanation of why the adverse event or series of adverse events has been determined to be an unanticipated problem; and (2) a description of any proposed protocol changes or other corrective actions to be taken by the investigators in response to the unanticipated problem.
Adverse Event Reports from Sponsors:
The principal investigator is responsible for submitting to the IRB adverse event reports from sponsors that describe events at other research sites. It is recommended that the principal investigator provide a cover memo or form that explains the event in plain English and provides information to the IRB about whether the event has any relevance to the study being conducted at his/her site (e.g., an adverse event may be specific to the use of the drug in young children and your study may be limited to adults, or the adverse event may not be related to the person's study participation).
Adverse event reports from sponsors should be forwarded to RFMH whenever they result in a change to the protocol or consent form, or raise a clinically significant concern that is, or could be, relevant to the subject population involved in the study of the drug at the facility.
Reporting Other Unanticipated Problems:
Upon becoming aware of any other incident, experience, or outcome (not related to an adverse event) that may represent an unanticipated problem, the investigator should assess whether the incident, experience, or outcome represents an unanticipated problem by applying the criteria described in section 3.9. If the investigator determines that the incident, experience, or outcome represents an unanticipated problem, the investigator must report it promptly to the IRB (45 CFR 46.103(b)(5)).
Content of adverse event reports:
Investigators should include the following information when reporting an adverse event, or any other incident, experience, or outcome as an unanticipated problem to the IRB:
appropriate identifying information for the research protocol, such as the title, investigator’s name, and the IRB project number;
a detailed description of the adverse event, incident, experience, or outcome;
an explanation of the basis for determining that the adverse event, incident, experience, or outcome represents an unanticipated problem; and
a description of any changes to the protocol or other corrective actions that have been taken or are proposed in response to the unanticipated problem.