8.3 IRB Review of Unanticipated Problems Involving Risk to the Subject or Others

1.0 Purpose

The purpose of this policy and procedure is to describe: 1) the procedure to ensure prompt reporting to the IRB any event or outcome that may be an unanticipated problem involving risk to the subject or others (UP), and 2) the IRB’s process for determining when an event or outcome is, in fact, a UP reportable to OHRP and FDA (as applicable).


2.0 Policy

  • 2.1. It is the policy of the Organization to comply with: a) HHS regulations at 45 CFR 46.103(b)(5)(i); b) any additional requirements of Common Rule agencies (as applicable); and c) FDA regulations at 21 CFR 56.108(b)(1), 21 CFR 312.32(a), and 21 CFR 812.3(s) (as applicable).
  • 2.2. It is the policy of the Organization that any AE, UADE, noncompliance incident, unexpected incident, unexpected outcome, or complaint, regardless of the level of associated or potential risk, which appears to meet the criteria for classification as a UP will be submitted to the full IRB for review.
  • 2.3. It is the policy of the Organization that the full IRB is responsible for determining whether the event, incident, outcome, or complaint meets the criteria for classification as a UP.

3.0 Definitions

  • 3.1. Unanticipated Problems Involving Risk to Subjects or Others (UP):
    • 3.1.1. Any event (incident, experience, or outcome) which meets all of the criteria specified below:

      • 3.1.1.1. The event is unexpected in terms of specificity, severity, or frequency, considering the nature of the research, the characteristics of the subject population, and the information contained in the protocol, protocol-related documents, and the ICF. In addition, the event is not consistent with the expected natural progression of any underlying disease, disorder, or condition of the subject.
      • 3.1.1.2. The event is related, or possibly related to subjects’ participation in the research or procedures involved in the research. This means there is a reasonable possibility that the event may have been caused by procedures involved in the research or resulted from participation in the research by the subject.
      • 3.1.1.3. The subject or others suffered harm, or were placed at greater risk of harm (including physical, psychological, economic, social, or legal) than was previously known or recognized when the IRB approved the research either initially, at continuing review, or at the time of approval of a Request for Change.
    • 3.1.2. Though not a required criterion for definition of an event as a UP, an event which meets the three criteria specified above will generally warrant substantive changes in the research protocol or informed consent process/document or other corrective actions in order to protect the safety, welfare, or rights of subjects or others

      Note: A UP may only involve exposure of a subject or others to an unexpected risk or the risk may culminate in a subject or another individual actually experiencing a harm.

      Note: A UP may arise from an AE, UADE, noncompliance incident, unexpected incident, unexpected outcome, or a complaint. Classification as a UP, however, requires the criteria specified under Section 3.1.1 to be met.

      Note: UPs may occur in research other than clinical trials, for example social and behavioral research (for example, a stolen laptop or thumb drive containing identifiable information), and may involve risks other than physical harm (for example, loss of confidentiality).


4.0 Procedures for Reporting Events that are Potential UPs to the IRB

  • 4.1. Reports of AEs/UADEs are submitted in accordance with HRPP policy 8.1 (IRB Review of Adverse Events and Adverse Device Effects).
  • 4.2. Reports of complaints are submitted in accordance with HRPP policy 8.2 (IRB Review of Study Related Complaints).
  • 4.3. Reports of noncompliance are submitted in accordance with HRPP policy 8.4 (Review of Noncompliance Involving the PI and Study Personnel).
  • 4.4. IND safety reports, DSMB reports, or other outcome information on risk are submitted in accordance with HRPP policy 3.2 (Data and Safety Monitoring).
  • 4.5. Reports of other unanticipated events related to the research that either expose subjects or others to potential risk or result in harm, but do not fall under the reporting requirements above (Sections 4.1-4.4 above) must be promptly reported to the IRB via letter or email.
    • 4.5.1. The report must include appropriate identifying information for the research protocol, such as the title, investigator’s name, and the IRB project number; a detailed description of the adverse event, incident, experience, or outcome; an explanation of the basis for determining that the adverse event, incident, experience, or outcome represents an unanticipated problem; and a description of any changes to the protocol or other corrective actions that have been taken or are proposed in response to the unanticipated problem

5.0 IRB Review of Potential UPs

  • 5.1. The IRB will review reports under Section 4.1 - 4.5 above in accordance with the criteria specified in HRPP policies 2.2 (Full IRB Review), 8.1 (IRB Review of Adverse Events and Adverse Device Effects), 8.2 (IRB Review of Study Related Complaints), and 8.4 (Review of Noncompliance Involving the PI and Study Personnel), and will make determinations as described in those policies
  • 5.2. The IRB will determine whether or not the event is a UP in accordance with Section 3.1 of this policy.
  • 5.3. The IRB will ensure all necessary steps will be taken in order to protect the rights and welfare of human subjects and maintain compliance with applicable federal regulations and HRPP policies.
  • 5.4. In addition to the required actions specified in HRPP policy 2.2 (Full IRB Review), the IRB may consider the following possible actions:
    • 5.4.1. Modification of the protocol.
    • 5.4.2. Modification of the information disclosed during the consent process.
    • 5.4.3. Notification of current participants when such information might relate to participants’ willingness to continue to take part in the research.
    • 5.4.4. Providing additional information to past participants.
    • 5.4.5. Requiring current participants to re-consent to participation.
    • 5.4.6. Modification of the continuing review schedule.
    • 5.4.7. Monitoring of the research.
    • 5.4.8. Monitoring of the consent process.
    • 5.4.9. Referral to other organizational entities.

6.0 Reporting UPs to Institutional 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 NOVEMBER 27, 2018

 INITIAL APRIL 4, 2016