Guidance

Other Reportable Information or Occurrence (ORIO)

IRBMED
Feb 26, 2021 4:30 pm

Investigators sometimes receive information that has a direct impact on a research study. This information is reportable to the IRBMED. Frequently this information falls within the Adverse Event Reporting context, or it is reported to IRBMED in conjunction with a protocol, investigatorship, or informed consent amendment. When those contexts don't apply, information should be reported as an ORIO in accordance with the guidelines below.

For information about other types of required reporting, see the Adverse Events (AEs), Other Reportable Information and Occurrences (ORIOs), and Other Required Reporting page.

Special Considerations

  • When notified of a (for cause or not-for-cause) Audit by a Federal Regulatory Agency (i.e., FDA, NIH, OHRP etc.), immediately call the Office of Regulatory Affairs (734-647-1576) and IRBMED (734-763‑4768) to inform each unit of the date of inspection.  Then submit an ORIO: Notification of Audit/Inspection/Inquiry to provide all documentation/details.
  • If an ORIO indicates notification of research subjects is necessary, IRBMED must review and approve materials prior to utilization.
  • If items are received from the sponsor regarding updates to the study, these items should be submitted via an amendment.  Such as protocol clarification memos, etc.  
  • Ceded studies should report to IRBMED only the information required by their IRB-of-record.
  • Multi-site studies where IRBMED is the IRB of record should follow the Multi-Site Research reporting plan available in the IRBMED Multi-site Research Documents folders
  • For each event assess whether it is a potential Unanticipated Problem Involving Risks to Subjects or Others (UaP or UPIRSO). This is captured in the eResearch ORIO submission. Potential UaPs meet all of the following criteria:
    • Unexpected (in terms of nature, severity, or frequency);
    • Related or possibly related to participation in the research; and
    • Suggests that the research places subjects or others at a greater risk of harm than was previously known or recognized

Click on the headings below to expand.

  • Reporting timetable for approved studies subject to annual Continuing Review (CR)

    “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.

    The following chart is for studies requiring annual Continuing Review that follow IRBMED standard ORIO reporting.

    TYPE OF EVENT  OR INFORMATION REPORTING MECHANISM AND TIMEFRAME for INFORMATION AND OCCURRENCES (NON-AE)    
    Report as an ORIO within 7 CALENDAR DAYS of becoming aware of the event or information

    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.

    Protocol Deviations

    (see Examples heading below)

    • 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

    Upload an aggregate report into SCR submission

    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
    Report(s) to or from oversight entity

     

    • 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

    Upload these reports individually into SCR submission or separately as required by the Sponsor's protocol or contract.

    • DSMB/DSMC (formally charged oversight entity) reports without any action items or safety issues 
    • FDA annual reports
    • 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

    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 ORCR, MICHR, and QARC

    Notification of Audit/Inspection/Inquiry
    • 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.
    N/A
    Report of lapse in IRB approval
    • Federally sponsored or FDA regulated studies irrespective of study activity during lapse in approval
    • Non-federally sponsored and non-FDA regulated studies with any study activity during lapse in approval
    • Non-federally sponsored and non-FDA regulated studies with a lapse in IRB approval and with no study activities – post-correspondence or indicate in the SCR application question 1.2 (free-text field on study progress) that no study activity occurred during the lapse in approval.
    Accident/Incident
    • 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.

    N/A

    Complaint

    Complaints related to participant safety, study conduct, supporting documents content or unresolved participant payment—

    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; irbmed@umich.edu).

    Complaints not related to subject safety, study conduct, or supporting document content, e.g.:

    • 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 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.

    Subject Incarceration

    See Prisoners in Research guidance page

    For studies, not previously approved by IRBMED to enroll prisoners and there is:

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

    N/A

    Subject Withdrawal

    It is preferred that withdrawals are not routinely reported individually.  Only withdrawals for the following reasons should be reported individually:

    • Safety reasons
    • Participant Complaint
    • Atypical/unusual reason

    Report Withdrawals section 02-3 of the SCR application

    Withdrawal of a participant due to routine reasons such as:

    • PI discretion
    • Met protocol stopping rules
    • Death
    • Time restrictions
    • Not wanting to complete study procedures
    Pertinent publication/public announcement
    • 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

    N/A

    Not Regulated activities including QA/QI projects
    • Contact the IRB

    N/A

    Other Miscellaneous Information
    • 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.

     

  • Studies not requiring Continuing Review (CR)

    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.

    Certain routine items (such as interim monitoring reports or DSMB reports that indicate no safety issues) need not be reported. via ORIO.This also applies to studies that previously had an approved study-specific 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.

    Similarly, studies that have been Terminated, studies with Exempt determination, and projects with Not Regulated determination should report only potential Unanticipated Problems (UaPs or UPIRSOs).

  • Further Discussion and Examples

    Breach of Confidentiality or Privacy

    If confidential information about a subject is revealed in inappropriate settings, or to persons without a need to know, or by data exposure (computer security breach, documents left unsecured, lost laptop), report this event or pattern and how it was/will be corrected or addressed.

    NOTE: Immediately after identifying a breach, contact the Michigan Medicine Corporate Compliance Office (734-615-4759, or anonymously at 866-482-1252).  See U-M SPG 601.25 for additional reporting requirements.

    If you must commit a breach of confidentiality in order to comply with legal or ethical obligations, and if your informed consent document does not already note such a possibility, inform the IRBMED.

    Example: Investigator suspects potential child abuse during the course of a study. The contact with UM Child Protection Team should be reported to the IRBMED if this possibility was not noted in the informed consent document.

    A breach of confidentiality or privacy may need to be reported as potential Unanticipated Problems (UaPs or UPIRSOs) if the breach places the subjects at a greater risk of psychological and social harm from than was previously known or recognized.

    Protocol Deviation/Violation/Exception

    Protocol deviations (also called “exceptions” or “violations”) include both purposeful and accidental variances from the procedures outlined for a study in its IRBMED approved protocol, or the IRBMED application(s), or by State or Federal regulations.

    Changes to eliminate apparent immediate hazards to the subject

    Regulations require IRBMED approval of all proposed changes in research activity PRIOR to implementation, including those that are sponsor-approved. When changes are necessary to eliminate apparent immediate hazards to the participant, implement the change and report by a formal AE/ORIO submission within 7 days after the action is taken. See guidance Reporting Time-Sensitive Modifications, heading IV.

    Amendments may not be implemented prior to obtaining the approval, including those changes perceived to reduce risk (other than those taken to eliminate apparent immediate hazards).

    The IRBMED requests the following information regarding protocol deviations/violations:

    • Description of the deviation
    • The root cause of an accidental deviation; or justification for a deliberate deviation
    • Notice of whether a corresponding protocol amendment will be submitted to the IRBMED
    • Justification for inclusion of the subject's data in the study despite the deviation, if the investigator plans to use the data
    • Report the event or pattern and how it was/will be corrected or addressed and how it will be avoided in the future

    Report Major deviations within 7 days; minor deviations at time of SCR

    For each protocol deviation, the study team should evaluate whether the event is major (report within seven calendar days) or minor (report at the time of SCR, unless a pattern of minor deviations suggests a systemic problem).

    A few general situations follow; assessments of particular situations may be different.

     
    Situation Major or Minor
    Deviation from study visit schedules Often minor
    Missed visits that include safety assessments (scans, vitals, labs, etc.) or procedures impacting participant safety; or missed assessments during visits Likely Major
    Informed consent errors that do not miss significant information relevant to the subject’s decision to participate (outdated version is used, but the content is the same as the current version) Often minor
    Informed consent errors that miss significant information relevant to the subject’s decision to participate Likely Major

    Table of sub-categories and examples

    REMINDER: Assess whether each event is major (report by ORIO within seven calendar days) or minor (report at the time of SCR, unless a pattern of minor deviations suggests a systemic problem).

    Also assess whether each event may need to be reported as potential Unanticipated Problem (UaP or UPIRSO).

    Type of ORIO Brief Description, Examples and Additional Information
    Deliberate Procedural Deviations

    As an investigator, you may decide, for one subject (or more if they are seen on the same day as the discovery of the protocol error), to follow a procedure different from that set forth in your protocol. Reasons may include subject safety or a change in circumstances of the study. The sponsor may be involved in the decision to deviate.

    NOTE that the “Urgent Amendment” process (active up to 3/2020) involving a telephone call has been obsoleted; refer to the current 12/2020 Time-senstive Modifications guidance.

    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 t 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.

    Accidental Procedural Deviations

    For one or more subjects, a member of the research team inadvertently follows a procedure different from that set forth in the approved protocol. Report the event or pattern, how it was/will be corrected or addressed, and how it will be avoided in the future.

    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.

    Appointment / Visit Deviations

    Report appointment deviations such as missed exams, tests, appointments or treatments, only when the subject is not withdrawn from the study (report withdrawn subjects in the Scheduled Continuation Review submission).

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

    Dosage / Intervention Errors or Deviations

    If a subject receives an incorrect dosage, medication, or intervention, due to misidentification or improper labeling, report the occurrence to the IRBMED. If the occurrence was not an adverse event (physical, social, or emotional harm or risk of harm), submit the occurrence as an ORIO. If it was an adverse event, submit it as an AE. Report the event or pattern, how it was/will be corrected or addressed, and how it will be avoided in the future.

    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.