Other Reportable Information or Occurrence (ORIO)

Report as Part of SCHEDULED CONTINUING REVIEW (SCR)

NOTE: These events or reports do not require a separate ORIO submission. They should be uploaded into field 4.1 of the Scheduled Continuing Review (SCR) application, and discussed within the SCR field 1.2.

(see Examples heading below)

(whenever possible, report planned protocol deviations ahead of the event)

• Major protocol deviations that may adversely impact safety of participants, or impact integrity/validity of the data (e.g. missed or out of window labs, procedures, or visits that would have been conducted for safety purposes)
• Minor protocol deviations as part of a pattern and/or suggesting a systemic problem in study conduct that potentially places subjects or others at a greater risk of harm than was previously known or recognized
• Informed consent process deviations for the purpose of accommodating a specific participant’s special communication needs

Minor protocol deviations that do not impact safety of participants or impact integrity/validity of the data. For example:

• schedule deviations (out of window), except when the visit or test would assess participant safety
• minor informed consent deviations (wrong version date, wrong expiration date, as long as the content is the same)

The aggregate deviation report should contain the same information as it the events were reported individually, such as:

• date of occurrence
• subject ID (do not include direct identifiers)
• adequate description of the event for IRBMED to determine the seriousness of the event
• whether the sponsor was notified of the event
• (if PI initiated study) effects to participant and/or data safety

• DSMB/DSMC reports with findings that yield implications for the conduct of the study (issues of safety, data validity or regulatory compliance)
• Routine monitoring reports with implications for the conduct of the study (issues of safety, data validity or regulatory compliance)

This includes reports from sponsor or CRO monitoring visits, and internal monitoring committees such as ORCR, MICHR, and QARC

• Reports of internal or external audits
• Reports on Drug or Device recalls or safety notices from the sponsor
• Study holds or suspensions that are not built into the study design
• Study completed or enrollment closed/completed notifications with safety or regulatory concerns
• Any other reports from sponsor, oversight entity or other sources with safety or regulatory concerns

• DSMB/DSMC (formally charged oversight entity) reports without any action items or safety issues
  (Note: Letters of explanation or clarification, and other requests for additional information from a DSMB/DSMC, are mostly interpreted by IRBMED to imply the study may “Continue without Modification” and can be reported at the time of Continuing Review.)
• FDA annual reports
  • For U-M held IND or IDE
  • For industry-sponsored IDE, per FDA guidance
• Temporary Hold notifications as indicated in the approved protocol and limited to activities not impacting subject safety, such as routine interim data analyses
• Study completed or enrollment closed/completed notifications without safety or regulatory concerns
• ORCR monitoring reports
• For U-M held IND or IDE: All monitoring reports (i.e. MICHR reports), per HRPP OM Part 8.VII.B

NOT REQUIRED TO SUBMIT: Routine monitoring reports (Interim monitoring reports, or other) without issues impacting safely, data validity, or regulatory compliance. These must be retained by the study team and available upon request.

This includes reports from sponsor or CRO monitoring visits, and internal monitoring committees such as  QARC. (Exception for UM held IND/IDE: see above.)

• For Federal audits (e.g., FDA, NIH, OHRP), contact the Office of Regulatory Affairs and IRBMED by phone immediately upon notification of audit.  Submit “Report(s) to or from oversight entity” ORIO to IRBMED once the audit has been conducted
• All other audits (e.g., by Sponsor or an external IRB), submit ORIO via eResearch notifying IRBMED when the audit will occur and the anticipated length.
• Internal Monitoring Committee (ORCR, MICHR) reports may need to be submitted as soon as they are received.

• Federally sponsored or FDA regulated studies irrespective of study activity during lapse in approval (see exceptions below**)
• Non-federally sponsored and non-FDA regulated studies with any study activity during lapse in approval

• Accidents/Incidents involving subjects/data/specimens/facilities
• Breach of confidentiality — see examples heading below for further discussion

NOTE: Additional reporting beyond IRB is also required per U-M SPG 601.25: if PHI is involved, contact the Compliance Office; if research data are involved, notify UMOR.

If any complaint cannot be readily resolved by the study team and requires numerous and/or detailed steps towards resolution, submit the plan to IRBMED for review and approval.

When in doubt

If you are not sure about your reporting obligation for a specific subject complaint, please reach out to the IRBMED office for assistance (734-763-4768; [email protected]).

• A participant is upset about a delay in payment or with making an appointment, but it is readily resolved by the study team and to the participant’s satisfaction

The SCR should include a summary or tabulation of complaints not previously reported to the IRBMED, along with their resolution.

The study closure (termination) report should include a summary of complaints not previously reported, and a summary of the number of participant complaints over the course of the study, a description of those complaints, and their resolution.

See Prisoners in Research guidance page

• Unintentional enrollment of a prisoner or
• Intent to continue participation of a previously enrolled subject who becomes incarcerated

• Safety reasons
• Participant Complaint
• Atypical/unusual reason

Withdrawal of a participant due to routine reasons such as:

• PI discretion
• Met the criteria outlined in the Protocol for Withdrawal
• Time restrictions
• Not wanting to complete study procedures

• Urgent information affecting the risk/benefit ratio of the study when notification of IRB cannot wait for an amendment to be submitted (i.e., memo regarding newly identified risk, but the revised protocol/IB are not ready to be published yet)
• Information affecting subjects willingness to participate in the research
• Newsletters that will be sent to enrolled subjects that need more timely review than annually

• Contact the IRB

• If there is any event or information that is not identified above or identified but needs immediate IRBMED attention, contact the IRBMED office for guidance.
• IRBMED must review – in advance – any communication provided to research subjects.

If you judge that a deviation or change from the approved research plan is necessary to eliminate apparent immediate hazards to the subject or others, you should implement the change. An amendment to the protocol and, if needed, to the informed consent document must then be submitted to IRBMED within 7 days (or as soon as possible if the revised protocol is coming from a sponsor). You must obtain IRBMED approval before implementing a deviation or change that does not serve to eliminate an immediate hazard. In some situations, it may be most appropriate for you to cease enrollment until the needed change is requested and approved. Contact the IRBMED office for further guidance.

Examples where a deliberate deviation IS permissible:

• An investigator realizes that a diagnostic blood test was not described in the protocol but is needed to regulate serum levels of the study drug.
  • Since this scenario involves a compromise to subject safety, the investigator may deviate from the protocol and then immediately report the deviation to the IRBMED.
• Newly published information indicates that one of the drugs used on a study has the same efficacy, with significantly fewer side effects, when administered at a lower dose than had been the previous standard of care (and the dose approved in the protocol).
  • If the higher dose poses significant hazards to subjects, the investigator may decrease it and then promptly report the change to IRBMED. The investigator should ensure that the decision is in keeping with all principles of good clinical and research practice.
  • If, on the other hand, the study will maintain a favorable risk/benefit ratio without a change in dosage, and the investigator decides not to change the protocol, s/he must submit an ORIO, notifying IRBMED of the new information, and a consent amendment, notifying subjects of the new information, and await IRBMED approval before proceeding.

Examples where a deliberate deviation IS NOT permissible:

• The protocol indicates that a nurse will conduct intake interviews and review the consent document with subjects. The nurse retires, so the study coordinator will carry out the procedure instead.

Since this scenario involves no compromise to subject safety, the investigator must submit an amendment and await IRBMED approval before proceeding.

• A sponsor believes that study data to date indicate that a potential participant could safely participate but doesn’t meet currently approved eligibility criteria.

Since this scenario involves no compromise to subject safety, the investigator must submit an amendment and await IRBMED approval before proceeding.

Event: A subject is enrolled in the study but does not meet the eligibility criteria stated in the protocol and/or informed consent document.

What the report will include: The team member in question is relatively new to the position and was not familiar with the approved protocol. Therefore, they did not complete the case report forms appropriately. To assure this will not happen in the future, the team member will be trained on the completion of the case report forms and will be closely observed in the future to assure that all study procedures are completed appropriately and fully.

Example: The clinic and lab are closed during the Holidays. All appointments will be moved to before or after the holiday for completion.

Examples:

• Two subjects who should have received a substance abuse survey and interview instead received a sexual abuse survey and interview.
• The pharmacy provided the wrong medication. It was administered to three healthy control participants on three different days without incident before the study nurse discovered the error.