The University of Iowa
Human Subjects Office

d. Review of Reportable Events

Manuals

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The following list are events that are reportable by investigators to the UI IRB:

  1. Any unanticipated problems involving risks to subjects or others which occur at the UI/VAHCS or that impacts subjects or conduct of the study.
  2. A serious adverse drug event (either expected or unexpected) occurring in a UI\VAHCS subject.
  3. A serious adverse device effect (either anticipated or unanticipated) occurring in a UI\VAHCS subject.
  4. An unanticipated serious adverse device effect occurring in a non-UI/VAHCS subject.
  5. Receipt of new information (including risk or benefit) that may impact the willingness of subjects to participate or continue participation in the research study.
  6. Any incidents of noncompliance with the federal regulations or the requirements or determinations of the IRB.

Investigators are required to report to the appropriate UI IRB if any of the above items #1-6 occur in a study where IRB-01, IRB-02, IRB-03 is the IRB of record.  For WIRB studies, items #1- 6 are reportable directly to WIRB.

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

  1. was unexpected (in terms of nature, severity or frequency) given
  2. the research procedures that are described in the protocol-related documents, such as the IRB- approved research protocol and informed consent document; and
  3. the characteristics of the subject population being studied AND
  4. 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
  5. 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)

Examples of unanticipated problems involving risks to subjects or others include, but are not limited to:

  1. a breach of confidentiality
  2. a subject complaint when the complaint indicates unexpected risks or cannot be resolved by the investigators,
  3. a research team member experiences harm in the conduct of the study,
  4. a new risk of the study drug, device, or study procedure is identified by an outside source (sponsor, federal regulatory agency, outside site, etc.)

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.

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.

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.

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.

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.

If a subject is enrolled by UI\VAHCS investigators, the investigator must report either serious adverse device effects or unanticipated adverse device effects.  FDA regulations require the sponsor to report the results of any evaluation of an unanticipated serious adverse device effect to all reviewing IRBs and participating investigators.  Any such reports are initially received by the investigator who is in turn responsible for reporting this information to the IRB-01 or IRB-03.  By definition, these effects must be associated with the use of the device.

Investigators must also report any receipt of new information (including risk or benefit) that may impact the willingness of subjects to participate or continue participation in the research study.  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.

Investigators must also self-report noncompliance.  Noncompliance is a failure to follow the federal regulations 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.

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.

Investigators must report any of the above issues using the Reportable Event Form (REF) in the HawkIRB system.  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.

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 one of the reporting requirements, 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 study, the report is referred to the convened IRB for review.

All reportable events are electronically filed with the appropriate research study.  These reports are also reviewed by the IRB at the time of continuing review.  Reports of all such problems for all projects reviewed by the Chair or convened IRB are provided by e-mail to all IRB-01, IRB-02, or IRB-03 members as appropriate on a monthly basis.

A primary reviewer is assigned to lead the discussion at the full board meeting.  All IRB members including the primary reviewer receive appropriate materials such as the Reportable Events Form (REF), communications with the Principal Investigator or other relevant individuals, approved IRB application, consent documents and other documentation from the project files as appropriate, prior to the full board meeting.  All IRB members are expected to review and be familiar with all materials.  The convened IRB makes a determination whether the event is an unanticipated problem involving risk to subjects or others.  If the determination made by the convened IRB differs from that made by the IRB Chair, the determination of the convened IRB supersedes that made by the IRB Chair.  When a quorum of IRB members is present, and after discussion, the IRB will vote on the recommended actions.

The IRB or IRB Chair may take any of the following actions or other actions as appropriate:

  1. Modification of the protocol,
  2. Modification of the consent document,
  3. Providing additional information to current subjects – this is done whenever the information relates to the subject’s willingness to continue participation,
  4. Providing additional information to past subjects,
  5. Requiring current subjects to re-consent to participation,
  6. More frequent continuing review or monitoring (this can include observation of the research or consent process),
  7. Requiring additional training of the investigator,
  8. Notification of investigators at other sites,
  9. Suspension or termination of the research
  10. Obtain additional information