Adverse Event Reporting

“Continuing Review” (CR) consists of annual submission by study team of a report on the study’s status and continued plans, for renewed review and approval by the IRB. See IRBMED FAQ heading “Ongoing Review.” If an approved study space shows an Expiration Date, the study requires CR.

Click here for printable PDF

This chart is for studies requiring annual Continuing Review that follow IRBMED standard AE reporting. It may be appropriate for some studies to consider a Study-Specific AE Reporting Plan. See the gray boxes below for information about External AE and UaP reporting.

SCR: Scheduled Continuing Review; Expected: Has been addressed in one or more of following: Protocol, Investigator Brochure, Package Insert or equivalent, published literature, IRB application, grant application, Data Safety Monitoring Board/Data Safety Committee reports, other documentation, informed consent document (ICD) or characteristics of the study population. Note, per OHRP guidance, event may be “expected” per the natural progression of any underlying disease, disorder, or condition of the subject(s) experiencing the adverse event; Unexpected: Has not been addressed in one or more of the above examples; Related: See below; Unrelated: See Below

• 21 CFR 312.32
• Adverse Event Reporting to IRBs
• OHRP-Which AEs are UaPs?
• OHRP—Guidance on Reviewing and Reporting UaPs and AEs
• Common Terminology Criteria for Adverse Events (CTCAE) – Oncology studies Grade System

The IRB recognizes that it can be difficult to determine the relationship of event or events to a specific drug/device/procedure when there are several contributing factors. Events should be rated according to the following parameters:

Per 2018 Revised Common Rule, some ongoing studies no longer  require annual Continuing Review (CR). The study workspace indicates “No Continuing Review Required for this application” when applicable. Studies not requiring CR should report only potential Unanticipated Problems (UaPs or UPIRSOs) that come to the attention of the study team. Routine AEs need not be reported. This also applies to studies that previously had an approved Study-specific AE reporting plan.

Unanticipated Problems meet all of the following criteria:

1. Unexpected (in terms of nature, severity, or frequency);
2. Related or possibly related to participation in the research; and
3. Suggests that the research places subjects or others at a greater risk of harm than was previously known or recognized.

See the Unanticipated Problems Involving Risks to Subjects or Others page and U-M HRPP Operations Manual Part 12.III.B.1.a for more details.

• The event is a known effect of the drug, device, or procedure (e.g., listed in the protocol documents including IB, consent, publications)
• The event follows an obvious sequence of time, from the drug’s administration, device’s implantation or activation, or procedure, for which the event is directly attributed to the administration, implantation, activation, or procedure.
• The event ceases with discontinuation of the drug, device, or procedure (and reoccurs on restarting).
• The event includes data that was only collected for the study.
• The event included disturbing or upsetting questions that the subject was asked for the purpose of the
  research.

• The event is lesser known or suspected effect of the drug, device, or procedure (listed in the protocol documents including IB, consent, publications, etc.)
• The event follows a reasonable sequence of time from the drug’s administration, device implantation, activation, or procedure, for which the event may be attributed to the administration, implantation, activation, or procedure.
• The event ceases or diminishes with discontinuation of the drug, removal/discontinued activation of the device, or procedure.

• The event is a lesser known or possible effect of the drug, device, or procedure.
• The event occurred within a sequence of time from the drug’s administration, device implantation and/or activation, or procedure, for which the event may be attributed to the administration, implantation, activation, or procedure.
• The event could be explained by the characteristics of the population under study.

• The event is NOT a previously known or suspected effect of the test drug, device, or procedure.
• The event does NOT follow a sequence of time# from drug administration, device implantation and/or activation, or procedure, for which the event could be attributed to the administration, implantation, activation, or procedure.
• The event can be readily explained by the characteristics of the population under study.

• The event is NOT known to be an effect of the test drug, device, or procedure.
• The event does NOT follow a sequence of time from drug administration, device implantation and/or activation, or procedure, for which the event could be attributed to the administration, implantation, activation, or procedure.
• The event can be readily and easily explained by the characteristics of the population under study.
• Subject never received study drug, study device, or underwent research study procedure.

Step-by-step instructions (below) for applying these guidelines appear below.

• Study-Specific Adverse Event (AE) Reporting
  • Encouraged for minimal- to moderate-risk studies that are not under FDA oversight; many sponsored studies include an AE reporting plan.
• External/Non-UM AE Reporting
• Humanitarian Use Device (HUD) under a Humanitarian Device Exemption (HDE)
• Other Reportable Information and Occurrences (ORIO)
  • Events that are not adverse events (no harm occurred) or reports to or from and oversight bodies

Open the approved study in eResearch. Click on AE/ORIO function tab in the left column (which looks like the screen shot shown to the here).

• Instructions for submitting an AE are available here.
• If the event necessitates an amendment to the protocol or informed consent document, you must submit an amendment after submitting the AE. If the AE obliges the investigator to inform previously enrolled subjects, include in the amendment the mechanism by which this will be done.
  • For example, sending a letter to all previously enrolled subjects, upload the letter in the amendment submission.