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HUMAN RESEARCH PROTECTION MANUAL

1. Introduction
2. IRB Structure and Function
3. IRB: General Policies and Procedures
4. COI: General Policies and Procedures
5. Recruitment and Participation
6. Initial IRB Application Procedure
7. Continuing IRB Review
8. Modifications and Amendments
9. Unanticipated Problems
10. Protocol Deviations and Non-Compliance
11. Suspensions and Deactivations
12. Vulnerable Populations
13. Non-Traditional Research
14. Research with Investigational Devices
15. Traditional Research

CHAPTER 9

 

9.0 Principal Investigator Reporting Requirements

The IRB requires PIs promptly report (within 5 days) a summary of each unanticipated problem involving risks to subjects and others to the IRB using the amendment submission process in the electronic protocol system.

Unanticipated problems are defined as events that meet all the following three criteria:

  1. Unexpected (in terms of nature, severity, or frequency) given:
    1. the research procedures that are described in the protocol-related documents, such as the IRB- approved research protocol and informed consent document; and
    2. the characteristics of the subject population being studied.
  2. Related or possibly related to participation in the research (possibly related means there is a reasonable possibility that the incident, experience, or outcome may have been caused by the procedures involved in the research); and
  3. Suggests that the research places participants or others at a greater risk of harm (including physical, psychological, economic, or social harm) than was previously known or recognized.

Examples of events that require reporting to the IRB include but are not limited to the following:

  • Adverse or other events that meet the 3 criteria above.
  • External events that are determined to be unanticipated problems (e.g., by another IRB for a multicenter study).
  • New information about a research study (e.g., a publication in the literature, interim findings, safety information released by the sponsor or regulatory agency, or safety monitoring report) that indicates a possible increase in the risks of the research.
  • Changes in approved research initiated without IRB review and approval to eliminate apparent immediate hazards to the subject.
  • Incarceration of a participant.
  • A sponsor-imposed suspension of a protocol due to possible increased risk.
  • A complaint from a subject when the complaint indicates potential increased risk or when the complaint cannot be resolved by the PI.
  • A protocol deviation that places one or more subjects at increased risk or has the potential to occur again.

9.1.1 Initial Review

The IRB staff will make an initial assessment to determine whether the report is likely to represent an unanticipated problem, and, if so, assign the report for review by the IRB Chair or designated IRB member. If the IRB Chair or designated IRB member concludes that the report meets the criteria for an unanticipated problem, the report will be referred for review at a full board meeting of the IRB where the final determination will be made.

If the reported problem clearly does not meet the unanticipated problem criteria, the report will be acknowledged. All reports will be reviewed to determine if non-compliance has occurred.

9.1.2 Full Board Review

The report, the protocol, and informed consent will be provided to the IRB members for review prior to the full board meeting. The IRB will consider whether the event meets all three criteria for an unanticipated problem involving risks to subjects or others.

Upon discussion, the IRB will determine whether the event does in fact represent an unanticipated problem involving risks to subjects or others. However, if after reviewing the information, the IRB determines that the event was not an unanticipated problem, the issue will be returned to IRB staff to be handled administratively.

Deliberations and determinations of the IRB will be fully documented in the minutes.

9.2 Possible IRB Actions

Any unanticipated problem or an event that is determined by the IRB to be unanticipated and indicates that subjects or others are at increased risk may require substantive changes in the research protocol and/or consent document/process or other corrective actions to protect the safety, welfare, or rights of subjects or others. Some corrective actions may include:

  • Changes to the protocol initiated by the PI prior to obtaining IRB approval to eliminate apparent immediate hazards to subjects may need to be made a permanent part of the protocol.
  • Modification of inclusion/exclusion criteria to mitigate the newly identified risks.
  • Implementation of additional procedures for monitoring subjects, the consent process, and/or the research.
  • Halt to enrollment of new subjects.
  • Suspension of research procedures on currently enrolled subjects.
  • Modification of the protocol.
  • Modification of the continuing review schedule.
  • Modification of informed consent documents to include a description of newly recognized risks or any other information that should be disclosed during the consent process.
  • Notification of current subjects when such information may relate to subjects’ willingness to continue.
  • Provision of additional information about newly recognized risks to previously enrolled subjects.
  • Re-consenting current participants.
  • Monitoring research or consent process.
  • Termination of the protocol with consideration for health and well-being of currently enrolled subjects and referral to other organizational entities.

9.3 University Reporting Requirements

Any event that meets the criteria for an unanticipated problem involving risks to subjects as determined by the convened IRB and is federally funded must be reported to the appropriate Federal agencies (OHRP, FDA) and sponsoring entities within 30 days of finalizing a determination. For federally funded and non-federally funded research, unanticipated problems may be reported to the PI’s department and/or other university leadership, as appropriate.

9.4 Notification to Principal Investigators

The PI will be notified by letter upon completion of the review.

If the problem/event does not meet the criteria of unanticipated and indicates that subjects or others are not at increased risk, the letter will acknowledge the report.

If the problem/event meets the criteria of being unanticipated and indicates that subjects or others are at increased risk, the letter will inform the PI that the IRB determined the problem/event to be an unanticipated problem involving risks to subjects or others, that the problem/event will be reported to the appropriate Federal agency, and provide a list of required actions and/or changes to the protocol or consent form.