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8.4 Review of Noncompliance Involving the PI or Study Personnel

1.0 Purpose

The purpose of this policy and procedure is to describe the: 1) definitions and classifications of noncompliance involving the PI and other study personnel; 2) procedures for reporting allegations of noncompliance, 3) procedures for reporting documented incidents of noncompliance; 4) the process for review; 5) possible actions in response to noncompliance;reviewing and 6)reporting proceduresincidents for reportingof noncompliance toby OHRP,the FDA,PI andand/or Organizationalstudy officials.personnel.

2.0 Policy

  • 2.1.

    It is the policy of the Organization thatthat:

    any
    • 2.1. allegations or reportsReports of noncompliance with Federal Regulations related to the protection of human subjects of research,Regulations, HRPP policies, or the requirements or determinations of the IRB, or the provisions of the IRB approved research study must be promptly reported to the IRB and the IO.ORA.
    • 2.2. It is the policy of the Organization that theThe PI is ultimately responsible for the proper conduct of research and for assuring that both incidents and allegations of noncompliance areis promptly reported in accordance with this policypolicy, and for implementing any required corrective action plan.
    • 2.3. It is the policy of the Organization that allegations or incidentsIncidents of noncompliance will be promptly addressed by the ORA/IRB and appropriate action taken in order to ensure protection of the rights and welfare of research subjects.
    • 2.4. It is the policy of the Organization that findingsFindings of serious or continuing noncompliance and suspensions or terminations of IRB approval as a result of noncompliance will be promptly reported to OHRP, FDA and sponsors or funding agency heads in accordance with the requirements of 45 CFR 46.108(a)(4)(i), and 21 CFR 56.108(b)(2), and the Organization’s FederalWide assurance, as specified in HRPP policy 8.7 (Reporting Incidents to Institutional Officials and Federal Agencies).

    3.0 Definitions

    • 3.1. Noncompliance is defined as any failure to follow federal regulations (including but not limited to 45 CFR 46, including any applicable subparts, or 21 CFR 50, 56), HRPP policies, the lackrequirements or determinations of compliancethe byIRB PI and other study personnel withor the applicable requirements specified in Section 2.1 above.

      Findingsprovisions of noncompliancethe areIRB classifiedapproved asresearch non-serious,study. serious,Noncompliance may be serious and/or continuing, or combinationsneither ofserious these.nor Itcontinuing. should be noted that noncomplianceNoncompliance may also be classified as an unanticipated problem involving risk to the subject or others (UP) as defined in HRPP policy # 8.3 (IRB Review of Unanticipated Problems Involving Risk to the Subject or Others).

      • 3.1.1. Serious noncompliance is defined as an incident that represents a violation of applicable federal regulations, HRPP policies, or the determinations of the IRB which include one or more of the following consequences: (a) significantly increases the risk to subject(s);subjects, or otherwise compromises the rights and welfare of research subjects; or (b) appreciably decreases the potential direct benefit to thesubjects; subject(s);or (c) compromises the scientific integrity of the research;research.
        • 3.1.1.1. In accordance with OHRP guidance, non-exempt human subject research conducted without IRB review and approval or d)without otherwiseappropriate compromisesinformed theconsent, rightsor andsignificant welfaremodifications to IRB-approved research without IRB approval is considered serious non-compliance.
        • 3.1.1.2. The IRB may decide that certain classes or types of thenon-compliance research(for subjects.example, protocol violations involving drug dosing errors) represent serious noncompliance.
      • 3.1.2. Non-seriousContinuing noncompliance is defined as an incident that does not satisfy the definition of serious noncompliance in Section 3.2 of this policy.
      • 3.1.3. Continuing noncompliance is defined as(1) repeated incidents of the same or substantially similar noncompliance after the investigator or staff has been notified that the action represents non-compliance or despite appropriate retraining and/or a specific corrective action asplan; directedor by(2) repeated incidents of the IRB,same or substantially similar noncompliance of such a nature that anthe investigator should have reasonably been expected to know that such an action was noncompliance..

    • 3.2. Allegation of noncompliance is defined as an unproved assertion of noncompliance.

    • 3.3. Incident of noncompliance is defined as a proven noncompliance.

    4.0 Reporting an AllegationNoncompliance ofto Noncompliancethe ORA

    • 4.1. AllegationsReports of possible noncompliance by the PI or study team must be made to the ORA within ten (10) business days of the study team becoming aware of the event, or five (5) business days when the possible noncompliance was associated with harm to subjects or others. Reports of noncompliance may be receivedmade by the Principal Investigator, other investigators, study staff, IRB members, IRB staff, the Research Subject Advocate, or any other Organizationalperson officials.
      • should be made as soon as feasible.
      • 4.2.1.1. AllegationsPersons ofreporting possible noncompliance may alsodo beso receivedanonymously throughand may use any mechanism they wish to report to the IRBORA. website,This utilizingincludes use of the “Report a Problem or Complaint” tab,tab on the IRB website, or through other electronic reporting systems sponsored by the Organization.
      • 4.3. Lists of deviations from protocol are often provided after a review of CRFs and other materials by a sponsor, CRO or Audit committee. If these deviations are submitted to the ORA they will be reviewed administratively. Violations which represent non-serious noncompliance as defined here do not need to be formally reported to the IRB.

    5.0 ORA Procedures for Reviewing Allegations of NoncomplianceResponsibilities

    • 5.1. AllegationsUpon receipt of a report of possible noncompliance receivedthe byfollowing thewill occur:
      • 5.1.1. The ORA will be reviewed byconduct the appropriateinitial IRB Administrator.investigation. Additional information will be obtained from the reporter, the study documents, the investigatorORA or researchHRPP staff,records, and/or from other sources as appropriate.
      • 5.1.2. BasedIf on thisthe initial review,investigation discloses that no noncompliance occurred, the IRB Analyst responsible will notify the reporter, and no further action need be taken.
      • 5.1.3. If the initial investigation confirms that noncompliance occurred, the IRB Analyst responsible, in consultation with the Executive Chair or designee as necessary, IRB Administratordesignee, will determine:
        • 5.2.1.3.1. Whether the allegation of noncompliance has a basis in fact.
          • 5.2.1.1. If the IRB Administrator, in consultation with the Executive Chair or designee determines that the episode of noncompliance may represent serious or continuing noncompliance, it will be referred for review by the full IRB at a convened meeting (HRPP policy 2.2: Full IRB Review).noncompliance
          • 5.1.3.2.1.2. If the IRB Administrator, in consultation with the Executive Chair or designee determines that the episode of noncompliance does not represent serious or continuing noncompliance, it will be reported to the full IRB as a notification item (HRPP policy 2.2: Full IRB Review).
        • 5.2.2. Whether the allegation of noncompliance merits further investigation by an IRB Compliance Subcommittee. This determination is made based on the seriousness of the allegation, and the available information regarding the allegation’s basis in fact. If this determination is made, the IO and UNMC Chief Compliance Officer will be informed, and the full IRB will be notified at the next convened meeting that an investigation is ongoing.
        • 5.2.3. Whether additional actions need to be taken immediately to protect the rights and welfare of human subjects, in accordance with HRPP policy 8.6 (Study Hold, Suspension, and Termination).
        • 5.2.1.3.3. Whether additional investigation is necessary, by the ORA, or by other parties including but not limited to the Institutional Compliance Officer (UNMC, UNO CHMC or BMC as appropriate), General Counsel, other IRB Analysts, other IRB members and internal consultants.
      • 5.1.4. If the allegationreport of noncompliance comes from someone other than the investigator then the IRB Administrator or Executive ChairORA will notify the PI (and other involved individuals) thatof therethe has been an allegation,investigation, and the investigator will be provided an opportunity to provide any relevant information and/or records that should be considered.
      • 5.2.1.5. During the investigation, the investigator (or other relevant party) will have a reasonable opportunity to provide additional information.
      • 5.1.6. The PIIRB, Institutional Official (and other involved individuals) will be afforded due process,IO) and Whistleblower protection will be provided in accordance with UNMC Policy 8003.

    6.0 Procedures for IRB Compliance Subcommittee Investigations

    • 6.1. If the allegation of noncompliance merits further investigation by an IRB Compliance Subcommittee, the subcommittee will be assembled by the IRB Administrator. The subcommittee will consist of the IRB Executive Chair/designee, the Institutional Compliance Officer (UNMC,will UNObe CHMCinformed orof BMCany ongoing investigations as appropriate), IRB Administrator(s), other IRB memberssoon as necessary,is andappropriate internalto consultantsdo asso.
      • necessary.
    • 6.1.1.5.2. AAfter written recordcompletion of the on-goinginvestigation investigationby the ORA and review by the Executive Chair or designee, the following will occur:
      • 5.2.1. A report determined to be possibly serious or continuing noncompliance, will be maintained.
        • referred
      • 6.1.2. As necessary,to the subcommitteeconvened willIRB, obtain additional information from the reporter, the study documents, the investigator or research staff, or from other sources as appropriate.
      • 6.1.3. During the investigation, or at the conclusion of the investigation, the subcommittee will determine whether additional actions need to be taken immediately to protect the rights and welfare of human subjects, in accordancealong with HRPP policy 8.6 (Study Hold, Suspension, and Termination).
      • 6.1.4. Upon conclusion of an investigation of noncompliance the IRB Administrator will prepare a written report of the results of the investigation.
        • 6.1.4.1.5.2.2. If the Subcommittee finds that the allegation is substantiated, theA report determined to be neither serious, nor continuing will be providedsent to the full IRB at a convened meeting (HRPP policy 2.2: Full IRB Review), and further action taken by the IRB as per section 7.2 below.
          • 6.1.4.1.1. The report will be provided to the IO, the Institutional Compliance Officer, and the investigator.
          • 6.1.4.1.2. The investigator will be instructed to complete a Noncompliance Report via RSS, including a corrective action plan.
        • 6.1.4.2. If the Subcommittee finds that the allegation is not substantiated, the report will be provided to the full IRB as a notification itemitem.
    • 5.3. Lists of protocol violations noted by a sponsor, CRO or Audit committee after a review of CRFs and other materials may be submitted to the ORA at the time of discovery, and will be reviewed by the ORA in consultation with the Executive Chair or designee. Incidents determined to be possibly serious or continuing noncompliance, will be referred to the convened IRB for action, and incidents determined to be neither serious nor continuing will be sent to the convened IRB as a notification item, as described above.

    7.6.0 IRB Procedures for Reviewing Episodes of Noncompliance*Responsibilities

    • 7.6.1. Noncompliance which may represent serious or continuing noncompliance will be referred for review by the convened IRB. The fullconvened IRB will determine:
      • 7.6.1.1. Whether the episodeincident represents serious and/or continuing noncompliance.
      • 7.6.1.2. Whether the non-complianceincident is an unanticipated problem involving risk.
      • 7.6.1.3. Whether the corrective action plan is adequate.
      • 7.6.1.4. Whether the research continues to satisfy the approval criteria at 45 CFR 46.111 or 21 CFR 56.111.
      • 7.6.1.5. Whether subject accrual should be allowed to continue.
      • 7.6.1.6. Whether currently enrolled subjects should be notified of information related to the noncompliance.incident.
      • 7.6.1.7. Whether previously enrolled subjects who have completed participation in the study should be notified of information related to the noncompliance.incident.
    • 7.6.2. After making the determinations above, the IRB may acttake inaction accordanceincluding, withbut itsnot authority as per §.108 and §.109, and HRPP policieslimited to:
      • 7.6.2.1. RequireRequiring modification of protocol or consent forms, require notification and/or re-consent of enrolled subjects, institute monitoring of the research and/or the consent process, require more frequent continuing review.
      • 7.6.2.2. AuditAuditing the research, or any of the investigator’s other active or completed studies.
      • 7.6.2.3. RequireRequiring additional investigator or study staff education and training.
      • 7.6.2.4. SuspendSuspending or terminateterminating the research.
      • 7.6.2.5. Notify other components of the Organization, including senior Organizational Officials, Nebraska Medicine or CHMC Risk Management or QA/QI, General Counsel, or Research Integrity Officer (RIO).
      • 7.2.6. MakeMaking recommendations to the IO regarding restrictions on, or termination of, other protocols submitted by the investigator.
        • investigator,
      • 7.2.7. Make recommendations to the IOor regarding other sanctions against the investigator or staff,staff including withdrawal or modification of pending or published manuscripts and/or destruction of research data or biological materials.
    • 6.3. After completion of the review by the convened IRB the investigator (or other relevant party) will be informed of the results of the review, and of any determinations and requirements by the IRB.

    8.7.0 Reporting Noncompliance to Organizational Officials, OHRP, FDA and Department or Agency Heads

    All required reports will be submitted in accordance with HRPP policy 8.7 (Reporting Incidents to Institutional Officials and Federal Agencies).

    DOCUMENT HISTORY:

     Written: 1/20/2016 (Approved: 1/20/2016) - original author not recorded

     Revised: 1/19/2018 - revision not documented

     Revised: 1/18/2023 - Simplified purpose statement; corrected regulatory citations in section 2.4; added caveat that reporting will occur in accordance with the Organization’s FWA; clarified definition of noncompliance; clarified criteria for serious noncompliance in section 3.1.1; specified additional conditions which might be considered serious noncompliance (sections 3.1.1.1 and 3.1.1.2); clarified definition of continuing noncompliance; simplified description of reporting to ORA (section 4.0); revised to separate and delineate responsibilities of ORA and of IRB; minimized specific details of processes associated with ORA and/or IRB review (moved to SOP); stylistic changes for clarity.{Approved Rusty McCulloh (Institutional Official), Bruce Gordon (Assistant Vice Chancellor for Regulatory Affairs, Executive Chair)}

     Revised: 3/8/2023 – Deleted reference to “minor” non-compliance and substituted “neither serious nor continuing”; minor revisions in wording of definition of non-compliance, serious non-compliance, and continuing non-compliance; changes “alleged non-compliance” to “possible non-compliance”; simplified section on reporting non-compliance to ORA; deleted list of types of people who may report non-compliance and of possible ways to report non-compliance; simplified section on ORA responsibilities; clarified method of reporting non-compliance discovered at time of CRO or other audit; stylistic changes{Approved Rusty McCulloh (Institutional Official), Bruce Gordon (Assistant Vice Chancellor for Regulatory Affairs, Executive Chair)}

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