The University of Iowa
Human Subjects Office

ii. Serious adverse drug event (either expected or unexpected) occuring in a UI subject

Manuals

Printer-friendly versionPrinter-friendly version

If a subject is enrolled by U/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:

  1. Death
  2. Life-threatening adverse drug experience
  3. Inpatient hospitalization or prolongation of existing hospitalization
  4. A persistent or significant disability/incapacity
  5. A congenital anomaly/birth defect
  6. 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).
  7. 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) .

Investigators must report any serious adverse drug event using the Reportable Event Form (REF).  This form includes a description of the event, the date of occurrence, the type of risk, whether the event was unexpected, the outcome, and an assessment of degree of relatedness to the research.  The form also includes the proposed actions to be taken by the investigator with regard to modifying approved study materials (including change in consent documents or other notification procedures) and notifying current subjects.  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.

Reports of serious and expected adverse drug events occurring in a UI/VAHCS subject are reviewed by an IRB Chair to verify that the event would be considered “expected” based on the information previously reviewed and approved by the IRB.  If the Chair verifies that this information is correct, the Chair signs the report through the HawkIRB system.
 

All reports of serious and unexpected adverse drug events occurring in a UI/VAHCS subject are reviewed by the IRB Chair and/or the IRB in the following manner:

The IRB chair compares the content of the REF with the previously approved project materials such as applications, informed consent document(s), protocols, investigator brochures, or other supporting documents to determine whether this event meets the definition of an unanticipated problem involving risk to subjects or others.

If the chair agrees the event meets the definition of an unanticipated problem involving risks to subjects or others, the chair determines whether the event represents minimal risk of harm or more than minimal risk of harm to subjects enrolled under the UI study.

If the event represents minimal risk of harm, the chair reviews and signs the report through the HawkIRB system.

If the event represents more than minimal risk of harm to subjects enrolled under the UI\VAHCS study, the report is referred to the convened IRB for review.  The full board determines whether subjects must be notified of the new information, and if so, the method of notification and whether any study materials (e.g. consents, protocol) must be updated to reflect the new information.

All reports of serious adverse drug events occurring in a UI\VAHCS subject are electronically filed with the appropriate research study.  These reports are also reviewed by the IRB at the time of continuing review.  In addition, reports of all serious adverse drug events for all projects reviewed by the Chair or full board IRB are provided by e-mail to all IRB-01 or IRB-03 members on a monthly basis.

In addition to the above requirements, investigators conducting human gene therapy research must submit a written report of serious adverse experiences that are unexpected and associated with the use of the gene transfer product to the NIH Office of Biotechnology Activities (NIH/OBA), the U of I Institutional Biosafety Committee, the IRB, and the FDA or study sponsor within specified timeframes as found in Appendix M-I-C-4 in the NIH Guidelines for Research Involving Recombinant DNA Molecules (NIH Guidelines). Gene therapy investigators must submit annual reports to OBA as set forth in Appendix M-I-C-3 of the NIH Guidelines.