Unanticipated problems involving risk to subjects or others & Serious/Continuing Noncompliance
Federal regulations require the organization to ensure prompt reporting of any unanticipated problems involving risk to subjects or others (UPIRTSO) and noncompliance to the IRB, regulatory agencies, and institutional officials. The IRB makes the determination of whether the problem meets the definition of a UPIRTSO or noncompliance. Investigators are responsible for complying with reporting requirements for unanticipated problems, adverse events, and noncompliance.
IRB Review of Reportable Events
Reportable events are any events or incidents that may be determined by the IRB as a UPIRTSO or serious and/or continuing noncompliance. An event is deemed reportable to the IRB when it is (1) possibly or definitively related to the research, and (2) expected in terms of nature, severity, or frequency, and (3) suggests that subjects or others (i.e., study staff, future subjects, partners/family, community members, etc.) are at greater risk of harm than was previously known or recognized. Additionally, any noncompliance with any regulations, requirements, or IRB-approval determinations that present the potential for increased risk to subjects is reportable.
Reportable events require prompt reporting, which is defined at within 10 working days (5 days for VA) of the research team becoming aware of the event or incident. The PI or study staff should report events using the Reportable Event xForm (previously Form 109) in IRBManager. The form will be prioritized for review by the IRB Chair, and if determined to possibly be a UPIRTSO or serious and/or continuing noncompliance, will be scheduled for IRB review at the next monthly convened committee meeting. More information about the review process is available in the IRB Policy 18: Unanticipated Problems.
A. Unanticipated Problem Involving Risks to Subjects or Others (UPIRTSO): Any event or information possibly related to the research that was unforeseen and indicates that the research procedures, approved by the IRB and carried out as expected, caused harm (including physical, psychological, economic, or social harm) to participants or others, or indicates that participants or others are at increased risk of harm than was previously known or recognized.
B. Adverse Event: Any unfavorable or unintended sign, symptom, or disease temporally associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure.
C. Serious Adverse Event: Any adverse event that results in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect, or other medical events, based upon appropriate medical judgment, that may jeopardize the patient or subject and may require medical, surgical, behavioral, or other intervention to prevent one of the outcomes listed in this definition.
D. Unanticipated or unexpected event: Any problem, event, information occurring that is new or where the nature, severity, or frequency is not consistent with either (1) the procedures involved in the research that are described the approved protocol, investigator brochure, or consent document and 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.
E. Possibly related: In the opinion of the PI, the incident, experience, or outcome may be reasonably associated with the procedures involved in the research.
F. Serious Problem: Any event, problem, or information, including research information security, that may reasonably be regarded as presenting a genuine risk of substantive harm to the safety, rights, or welfare of human research subjects, research personnel, or others, including their rights to privacy and confidentiality of identifiable private information; or substantively compromising the HRPP or research information security program.
G. Prompt Reporting: Events must be reported to the IRB within 10 business days using the appropriate report xform; for VA, reporting must occur within 5 business days.
Events the require prompt reporting
The following events must be promptly reported using the Reportable Events xForm in IRBManager:
- An unexpected harmful or unfavorable occurrence to participants or others that possibly relates to the research protocol (injuries, side effects, psychological events, dosing errors)
- A serious adverse event or problem that are unexpected and probably related to the research procedures, interventions, or treatment
- An unforeseen development that potentially increases the likelihood of harm to subjects or others
- Any new information that indicates a change to the risks, safety, or benefits of the research
- Any deviation from the protocol taken without IRB approval to eliminate apparent immediate hazard to a research participant
- Any subject complaints that indicates an unanticipated problem or cannot be resolved by the research staff
- Any problem reflecting a deficiency that substantially compromises the effectiveness of the institution’s human research protection or human research oversight programs
- Any accidental change to the study procedures or approved materials that results in a serious problem or indicates the potential for increased harm to subjects
Examples of Reportable Events
The following are examples of events that require prompt reporting:
- A local subject death possibly related to the research
- Incarceration of a subject for research not previously approved to enroll prisoners
- Sponsor imposed suspension of research for any reason
- A publication from another study that shows the risks, or potential benefits, of your study may be different than what was initially considered by the IRB
- A data and safety monitoring report that indicates the frequency or magnitude of harm or benefits may be different than what was initially considered by the IRB
- A black box warning (or VA PBM Safety Alert) for any drug or device used in your research study
- A problem involving data storage, privacy, or confidentiality
- Eliminating apparent immediate hazards to subjects or others, and reporting the incident to the IRB
- Ensuring that study staff follow the IRB-approved protocol and are aware of the reportable event requirements
- Documenting the details of all events/incidents in the study records including relevant outcome information
- Determining if the events meets the definition of a reportable event
- Ensuring prompt reporting of all reportable events using the appropriate xform in IRBManager
- Submitting a Modification Request, as appropriate, to prevent future occurrences/incidents
What if I am unsure if an event meets Reportable Event criteria?The IRB encourages the study team and PI to communicate with the IRB directly about whether an event is reportable. You can call the IRB office at 423-439-6054 to discuss any events and reporting requirements. If you do not have enough information to complete the Reportable Events form, the IRB will accept the submission with the information that is available, and you can submit a Follow-up Report once all information is available.
What should I do if I determine an event is not reportable?The PI is responsible for documenting the details of all study events/incidents, including subject complaints, protocol deviations, adverse event, and relevant new information, in the study records. Research records should be maintained and easily accessible upon inspection request by the IRB, regulatory agencies, or other officials responsible for research compliance. All adverse events and protocol deviations should be reported in summary form at Continuing Review or Administrative Check-in. If sponsors require reporting of events that do not meet reportable criteria, you may submit to the IRB using either the Adverse Events Reporting Log xform or the Protocol Deviations Reporting Log xform.
How does the IRB review Reportable Events?IRB staff will review the initial report for completeness and may request additional information to facilitate the review. The submission will be prioritized for IRB Chair review, and if the Chair determines that the event is neither a UPIRTSO or serious and/or continuing noncompliance, the IRB will issue an acknowledgment letter. If the IRB Chair determines that the event is reportable, it will be assigned to the next convened IRB meeting for review. The full board will review the submission to determine if the event is a UPIRTSO or serious and/or continuing noncompliance and if any preventive or corrective actions are necessary. The PI will receive written notification of the IRB determinations and actions.
What types of actions will the IRB take?If the IRB Chair or convened IRB determine that subjects are at risk, the study may be temporarily suspended or permanently terminated. The IRB may request more information about the event and outcomes prior to making a final determination. The IRB may make the following decisions: require a Modification Request xform, additional study follow-up of participants, modify the DSMP, subject notification, more frequent continuing review, re-consent of all active study subjects, notification of other relevant parties.