When the HSRO approves human-subjects research, the approval is based upon the information about how the research will be conducted and the risks and anticipated benefits to subjects that are known at the time the research is reviewed.
Once the research is approved, however, unexpected problems may occur or new information may become available that indicates that the research places subjects or others at an increased risk of harm.
These unexpected problems and new information about risks are referred to as unanticipated problems. Some unanticipated problems, such as adverse events, cause actual harm to subjects. Others may not cause actual harm to subjects but suggest that the research places subjects or others at an increased risk of harm. All such unanticipated problems must be reported promptly to the HSRO so that we can consider whether:
The risks to subjects are still minimized and reasonable in relation to anticipated benefits, and
Any changes to the research, or other corrective actions, are warranted in order to protect the safety of the subjects.
Investigators are required to report to the HSRO any of the following circumstances promptly and within 7 days of the date the investigator first becomes aware of the problem. Time-frame should be commensurate with the severity of the event/problem and with subjects’ safety, rights, and welfare in mind.
Performing non-exempt human subject research without obtaining prospective IRB approval;
Initiating research activities prior to obtaining consent;
Adverse events that are unexpected, and related or possibly related to the research and that indicate there are new or increased risks to subjects;
Adverse events that are serious, unexpected, and related or possibly related to the research and that indicate there are new or increased risks to subjects that require some action (e.g., modification of the protocol, consent process, or informing subjects);
Unanticipated adverse device effects that are serious and caused by, or associated with, the device;
Failure on the part of the Investigator or any member of the study team to follow the terms of the HSRO approved study or to abide by applicable laws, regulations, or RIT policies;
Any event that requires prompt reporting according to the research protocol or investigational plan or the sponsor;
Breach of confidentiality or violation of HIPAA (e.g., lost or stolen laptop);
Interim analysis, safety monitoring report, publication in a peer-reviewed journal, or other finding that indicates that there are new or increased risks to subjects or others or that subjects are less likely to receive any direct benefits from the research;
Complaint by/on behalf of a research subject that indicates that the rights, welfare, or safety of the subject have been adversely affected
Noncompliance with applicable regulations or requirements or determinations of the IRB identified by the research team or others;
Suspension or termination of the research based on information that indicates that the research places subjects at an increased risk of harm than previously known or recognized;
Suspension or disqualification of an investigator;
Scientific misconduct; or
Any other problem that indicates that the research places subjects or others at an increased risk of harm or otherwise adversely affect the rights, welfare or safety of subjects or others.
Note that investigators may have additional reporting obligations as specified by the study sponsor or oversight agency. Investigators who serve as sponsor-investigators of an IDE also have additional reporting obligations to the FDA.
Steps to Reporting
Contact the Director of the HSRO via email to report the incident. The investigator must provide the following information in the report:
A detailed description of the problem/event;
Include the HSRO #, Principal Investigator name, date(s), setting/location of the incident, individuals affected, description of incident and actions taken by research staff
The basis for determining that the problem/event is unexpected in nature, severity, or frequency;
The basis for determining that the problem/event is related or possibly related to the research procedures;
The basis for determining that the research study, or the problem/event, places subjects at an increased risk of harm (i.e., a serious adverse event); and
Whether any changes to the research or other corrective actions are warranted
Following review by the Director of the HSRO, the Director of Compliance and Vice President of Research (VPR) will be notified if the unanticipated problem is considered to be an adverse event, and the VPR will notify other institutional officials as necessary and DHHS when the event occurs in non-exempt research in accordance with the regulations at 45CFR46.108(4). The Chair and members of the IRB may also be notified if their participation is deemed helpful in determining corrective action.
Corrective Action Following Unanticipated Problems and Adverse Events
To minimize risks and improve safety corrective actions may be implemented following an unanticipated problem or adverse event. These may include:
New inclusion/exclusion criteria
Additional monitoring points during the data collection and changes to safety monitoring procedures
Changes to the recruitment materials
Changes to consent process and materials
Additional training of research staff
Additions to the research team
Monitoring of the consent process and data collection by the HSRO