8.4 Review of Noncompliance Involving the PI and 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; and 6) procedures for reporting noncompliance to OHRP, FDA, and Organizational officials.


2.0 Policy

  • 2.1. It is the policy of the Organization that any allegations or reports of noncompliance with Federal Regulations related to the protection of human subjects of research, HRPP policies, or the requirements or determinations of the IRB, must be promptly reported to the IRB and the IO.
  • 2.2. It is the policy of the Organization that the PI is ultimately responsible for the proper conduct of research and for assuring that both incidents and allegations of noncompliance are promptly reported in accordance with this policy and for implementing any required corrective action plan.
  • 2.3. It is the policy of the Organization that allegations or incidents 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 findings 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) as specified in HRPP policy 8.7 (Reporting Incidents to Institutional Officials and Federal Agencies).

3.0 Definitions

  • 3.1. Noncompliance is defined as the lack of compliance by PI and other study personnel with the applicable requirements specified in Section 2.1 above.

    Findings of noncompliance are classified as non-serious, serious, continuing, or combinations of these. It should be noted that noncompliance 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); b) appreciably decreases the potential direct benefit to the subject(s); c) compromises the scientific integrity of the research; or d) otherwise compromises the rights and welfare of the research subjects.
    • 3.1.2. Non-serious 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 repeated incidents of the same or substantially similar noncompliance despite appropriate retraining and/or specific corrective action as directed by the IRB, or of such a nature that an 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 Allegation of Noncompliance

  • 4.1. Allegations of noncompliance may be received by the Principal Investigator, other investigators, study staff, IRB members, IRB staff, the Research Subject Advocate, or any other Organizational officials.
  • 4.2. Allegations of noncompliance may also be received through the IRB website, utilizing the “Report a Problem or Complaint” tab, 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 Noncompliance

  • 5.1. Allegations of noncompliance received by the ORA will be reviewed by the appropriate IRB Administrator. Additional information will be obtained from the reporter, the study documents, the investigator or research staff, or from other sources as appropriate.
  • 5.2. Based on this initial review, in consultation with the Executive Chair or designee as necessary, IRB Administrator will determine:
    • 5.2.1. 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).
      • 5.2.1.2. 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).
    • 5.2.4. If the allegation of noncompliance comes from someone other than the investigator then the IRB Administrator or Executive Chair will notify the PI (and other involved individuals) that there has been an allegation, and the investigator will be provided an opportunity to provide any relevant information and/or records that should be considered.
    • 5.2.5. The PI (and other involved individuals) will be afforded due process, 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, UNO CHMC or BMC as appropriate), IRB Administrator(s), other IRB members as necessary, and internal consultants as necessary.
    • 6.1.1. A written record of the on-going investigation will be maintained.
    • 6.1.2. As necessary, the subcommittee will 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 accordance 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. If the Subcommittee finds that the allegation is substantiated, the report will be provided 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 item

7.0 IRB Procedures for Reviewing Episodes of Noncompliance*

  • 7.1. The full IRB will determine:
    • 7.1.1. Whether the episode represents serious and/or continuing noncompliance.
    • 7.1.2. Whether the non-compliance is an unanticipated problem involving risk.
    • 7.1.3. Whether the corrective action plan is adequate.
    • 7.1.4. Whether the research continues to satisfy the approval criteria at 45 CFR 46.111 or 21 CFR 56.111.
    • 7.1.5. Whether subject accrual should be allowed to continue.
    • 7.1.6. Whether currently enrolled subjects should be notified of information related to the noncompliance.
    • 7.1.7. Whether previously enrolled subjects who have completed participation in the study should be notified of information related to the noncompliance.
  • 7.2. After making the determinations above, the IRB may act in accordance with its authority as per §.108 and §.109, and HRPP policies to:
    • 7.2.1. Require 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.
    • 7.2.2. Audit the research, or any of the investigator’s active or completed studies.
    • 7.2.3. Require additional investigator or study staff education and training.
    • 7.2.4. Suspend or terminate the research.
    • 7.2.5. 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. Make recommendations to the IO regarding restrictions on, or termination of, other protocols submitted by the investigator.
    • 7.2.7. Make recommendations to the IO regarding other sanctions against the investigator or staff, withdrawal or modification of pending or published manuscripts and/or destruction of research data or biological materials.

8.0 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).


ADMINISTRATIVE APPROVAL: BRUCE G. GORDON, MD IRB EXECUTIVE CHAIR & ASSISTANT VICE CHANCELLOR FOR REGULATORY AFFAIRS CHRISTOPHER KRATOCHVIL, MD INSTITUTIONAL OFFICIAL

POLICY AMENDED:

 REVISED JANUARY 19, 2018

 INITIAL JANUARY 20, 2016