Unanticipated and Adverse Events

An adverse event is any untoward or unfavorable occurrence in a human subject, temporally associated with the subject’s participation in the research. Adverse events involving risks to subjects or others must be reported to the IRB via the Unanticipated/Adverse Events Report within 3 days upon the Primary Investigator’s knowledge of the event.

Adverse events encompass both physical and psychological harms.

Attribution: Adverse event attribution will fall into one of the following categories:

• related or possibly related to participation in the research (in this guidance document, possibly related means there is a reasonable possibility that the incident, experience, or outcome may have been caused by the procedures involved in the research);
• unrelated events are those that could in no way be attributed to study participation. These events are not reportable.

Severity: Adverse event severity will fall into one of the following categories:

• Mild: Event results in transient discomfort; does not influence performance or functioning; does not require intervention or treatment; does not limit or interfere with daily activities; expected to resolve quickly with no physical, psychological, social, or economic consequences.
• Moderate: Of sufficient severity to make the patient uncomfortable; may include worsening of conditions present at the onset of the study; treatment of symptom(s) may be needed; expected to resolve but short term physical, psychological, social, or economic consequences are possible.
• Severe: Event results in significant symptoms that prevents normal daily activities; may require hospitalization or invasive intervention. Long term physical, psychological, social, or economic consequences are possible.

Link to the Unanticipated problem report and definitions form

Devices may have an UADE to participants or others. The investigational device exemption (IDE) regulations define an UADE as “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”.

UADEs must be reported by the primary investigator to the sponsor and the IRB (via the Unanticipated Event Report), as described below:

• For device studies, investigators are required to submit a report of a UADE to the sponsor and the reviewing IRB as soon as possible, but in no event later than 3 business days after the investigator first learns of the event.
• Sponsors must immediately conduct an evaluation of a UADE and must report the results of the evaluation to FDA, all reviewing IRBs, and participating investigators within 10 working days after the sponsor first receives notice of the effect.

The IRB will review the Unanticipated Events Report in a timely manner and confirm whether the submission constitutes an unanticipated problem involving risk to participants or others.

The IRB will consider a range of possible corrective actions such as:

• Suspend or terminate the research
• Notify current participants when such information might be related to their willingness to continue to take part in the research (e.g., reconsenting participants)
• Require modifications to the protocol and/or consent documents
• Provide additional information to past participants (e.g., long-term risks have been identified that could affect them)
• Increase the frequency of continuing review
• Impose additional monitoring requirements
• Require additional training of the researcher and research team
• Notify other Texas State committees or departments

The IRB will report any unanticipated problems to the Primary Investigator, appropriate Texas State officials, the funding agency or study sponsor, if applicable, the Office for Human Research Protections (OHRP), the Food and Drug Administration (FDA) and other applicable regulatory authorities.

The IRB has the authority to suspend or terminate approval of research that has been associated with unexpected serious harm to participants. When an IRB Committee takes such action, it is required to provide a statement of reason for the action and to promptly report this action to the Primary Investigator, appropriate Texas State officials, the funding agency or study sponsor, if applicable, the Office for Human Research Protections (OHRP), the Food and Drug Administration (FDA) and other applicable regulatory authorities.

A data security breach (e.g., a stolen laptop or misplaced thumb drive) almost always constitutes an unanticipated event. If this occurs an Unanticipated/Adverse Event Report must be submitted by the Primary Investigator. In addition, it is strongly advised that the Primary Investigator contact Research Integrity and Compliance at (512) 245-2314 to report that a potential security breach has occurred.

When a research team fails to comply with the requirements of an applicable law, regulation, or institutional policy pertaining to the protection of human subjects, and/or with the requirements or determinations of an IRB, this may be considered noncompliance. All reports of alleged non-compliance or inappropriate involvement of humans in research are investigated.

At times, noncompliance may not meet the definition of an unanticipated problem – reportable via the Unanticipated/Adverse Event Report. In instances where noncompliance may be involved, the New Information Report must be submitted within 5 business days of the occurrence or within 5 business days from the date in which the Primary Investigator learned of the occurrence. The New Information Report must be submitted to Research Integrity and Compliance for review. The IRB Chair will review the report to assess at what level the noncompliance involves. If the event entails more serious noncompliance (e.g., serious or continuing noncompliance), the matter will be forwarded to the IRB for consideration.

Possible examples of noncompliance may include:

1. A rescheduled study visit
2. Failure to collect an ancillary self-report questionnaire
3. Subject’s refusal to complete scheduled research activities
4. Failure to use the IRB stamped Consent Form when consenting a subject
5. Over-enrollment of subjects
6. Deviations of protocol procedures
7. Failure to obtain prospective IRB approval for an additional research related activity not currently listed on the IRB approved protocol
8. Failure to obtain signed informed consent from subjects as required from the IRB
9. Use of translated consent documents without first submitting to the IRB for review and approval

Please note: It is the responsibility of the Primary Investigator to ensure that all research staff involved in the conduct of the research follows the IRB-approved research protocol. When modifications are necessary, an IRB Modification Requestshould be submitted to the IRB for review and approval prior to implementation of the changes (unless necessary to avoid an immediate hazard to the subject).