Investigators are required to report to the appropriate UI IRB if any of the below items occur in a study where IRB-01, IRB-02, IRB-03 is the IRB of record. (For studies approved by an external IRB, events are reportable directly to that IRB of record.) When IRB-03 is the IRB of record, all VHA reporting actions are in accordance with the requirements of the VHA Handbook 1058.01. Research Compliance Reporting Requirements found here.  The HSO has developed a Reportable Event Decision Tree to help guide researchers through the process.

Reportable events may fall into one or more categories listed below.  All reportable events must be reported to the appropriate UI IRB using the Reportable Event Form (REF) in the HawkIRB system (for IRB-01, IRB-02, or IRB-03).  This form includes a description of the event, the date of occurrence, whether it is a local or outside report, how the event affected the rights, safety or welfare of the subject or others, current status of subjects, and any planned changes or modifications to the project as a result of the event.

Reports from the investigator to the IRB must be submitted via HawkIRB within ten working days of the event or within 10 working days of the PI becoming aware of the event. For IRB-03 studies, reporting must occur within five working days.

An unanticipated problem involving risks to subjects or others is any event or problem that:

  • was unexpected (in terms of nature, severity or frequency) given (a) the research procedures that are described in the protocol-related documents, such as the IRBapproved research protocol and informed consent document; and (b) the characteristics of the subject population being studied AND 
  • suggests that the research places subjects or others (those not directly involved in the research such as research staff or family members) at a greater risk of harm (including physical, psychological, economic, or social harm) than was previously known or recognized AND
  • is related or possibly related to participation in the research (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).

When a research study includes investigational drugs or devices, some unanticipated problems may also meet the definition of an unexpected adverse drug experience (serious or otherwise), or an unanticipated adverse device effect.

If a subject is enrolled by UI\VAHCS investigators, the investigator must report to the UI IRB either serious adverse drug events or unexpected adverse drug events. By definition, these events must be associated with the use of the drug.

 

A serious adverse drug event is any adverse drug experience (associated with the use of the drug) occurring at any dose that results in any of the following outcomes:

  • Death
  • Life-threatening adverse drug experience
  • Inpatient hospitalization or prolongation of existing hospitalization
  • A persistent or significant disability/incapacity
  • A congenital anomaly/birth defect
  • Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered a serious adverse drug event when, based upon appropriate medical judgment, they may jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the outcomes listed above (21 CFR 312.32).
  • An unexpected adverse drug event is any adverse drug experience (associated with the use of the drug), the frequency, specificity, or severity of which is not consistent with the current investigator brochure; or, if an investigator brochure is not required or available, the specificity or severity of which is not consistent with the risk information provided to the subjects and the IRB (21 CFR 312.32).

The University of Iowa complies with the federal regulations at 21 CFR 312.32(c) which state:

The sponsor shall notify FDA and all participating investigators in a written IND safety report of:

  • Any adverse experience associated with the use of the drug that is both serious and unexpected; OR
  • Any finding from tests in laboratory animals that suggests a significant risk for human subjects including reports of mutagenicity, teratogenicity, or carcinogenicity. 

NOTE: 21 CFR 312.32(c)(ii) states “In each written IND safety report, the sponsor shall identify all safety reports previously filed with the IND concerning a similar adverse experience and shall analyze the significance of the adverse experience in light of the previous, similar reports.”

Events meeting the criteria in this regulation should be reported as unanticipated problems involving risks to subjects or others and must include associated documentation and summary information from the sponsor. By their nature, such reports would require amendment of the IRB-approved study and associated documents to address the new information. More information about IND\Outside Safety Reports can be found here.

If a subject is enrolled by UI\VAHCS investigators, the investigator must report either serious adverse device effects or unanticipated adverse device effects. By definition, these effects must be associated with the use of the device.

An unanticipated adverse device effect is 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 the frequency, specificity, or severity of which has not previously been identified in the investigational plan or application, or any other unanticipated serious problem associated with a device that relates to the rights, safety, or welfare of subjects (21 CFR 812.3).

During the course of a study, researchers may become aware of new information that would impact a subject’s decision to participate or continue participating in the research study. For example, interim analyses of data may identify a trend which impacts the safety of subjects, or may identify early efficacy (benefit) of one of the interventions under study. In addition, results from other research studies or changes in standards of practice or care may affect conduct of a study and would need to be communicated to research subjects.

Noncompliance is a failure to follow the federal regulations (45 CFR 46; 21 CFR 50) with respect to protection of human subjects in research or failure to follow the determinations of the IRB with respect to conduct of the research as approved by the IRB.

More information can be found in the UI Investigator’s Guide/IRB Standard Operating Procedures (Section II, Part 19.B)