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NIH Investigator Manual for Human Subjects Research

Chapter 9 - Reporting Research Related Events or New Information to the IRB

Overview

Key points

  • When NIH is the Reviewing IRB, investigators are required to ensure that all reportable events are communicated to the OHSRP office of Compliance and Training via the electronic IRB system within the time frames as specified in Policy 801 – Reporting Research Events. (The information below provides a summary of these events and timeframes.)

  • When NIH is not the Reviewing IRB, NIH investigators are responsible for complying with the Reviewing IRB's event reporting policy and must understand which events also need to be reported in the NIH electronic IRB system.

  • If the study is FDA regulated, NIH investigators are responsible for event reporting as required by the sponsor or FDA.
Which research related events need to be reported to the IRB (Compliance and Training) in an expedited timeframe when NIH is the Reviewing IRB?

Reportable events, from an NIH IRB perspective, are those that occur during the course of human subjects research that require notification to the NIH IRB. For the purposes of NIH HRPP policy, reportable events include non-compliance, unanticipated problems involving risks to subjects or others (also referred to as UPs), major deviations, deaths related or possibly related to research activities, new information that might affect the willingness of subjects to enroll or continue participation in the study, and suspension or termination of research activities.

  • Deaths that are at least possibly related to research need to be reported in the electronic IRB system within 24 hours of an investigator becoming aware.

  • The following research-related events need to be reported within 7 calendar days:
    • Major Deviation: A deviation must be reported within 7 calendar days of an investigator becoming aware of an actual or suspected deviation. Major deviations from the IRB-approved protocol are those that have, or may have the potential to, negatively impact, the rights, welfare, or safety of the subject, or to substantially negatively impact the scientific integrity or validity of the study.

    • Unanticipated Problem (UP): If the event meets the definition of a UP below, it must be reported within 7 calendar days of an investigator becoming aware of the actual or suspected UP. An Unanticipated Problem Involving Risks to Subjects or Others (UP) is any incident, experience, or outcome that meets all the following criteria:
      1. Unexpected (in terms of nature, severity, or frequency) given (a) the research procedures that are described in the protocol-related documents, such as the IRB-approved research protocol and informed consent document; and (b) the characteristics of the subject population being studied; and
      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 subjects or others (which may include research staff, family members or other individuals not directly participating in the research) at a greater risk of harm (including physical, psychological, economic, or social harm) related to the research than was previously known or expected.

    • New information that might affect the willingness of a subject to enroll or remain in the study should be reported within 7 calendar days of an investigator first becoming aware.

    • Non-compliance: Any actual or suspected non-compliance by any investigator or entity associated with the protocol must be reported by the NIH PI/designee within 7 calendar days of any investigator or individual associated with the protocol first becoming aware. Non-compliance means failure of an investigator to follow the applicable laws, regulations, or institutional policies governing the protection of human subjects in research, or the requirements or determinations of the Institutional Review Board (IRB), whether the failure is intentional or not. Please refer to Policy 802, Non-compliance in Human Subjects Research for additional information.
      • External IRB determinations of serious and/or continuing non-compliance about an NIH investigator: If the NIH is relying on an external IRB and the Reviewing IRB makes a determination of serious and/or continuing non-compliance regarding an NIH investigator, the NIH PI/designee must report this in the NIH electronic IRB system within 7 calendar days of any member of the NIH research team being notified of the determination by the Reviewing IRB. The NIH PI must provide the OHSRP office of Compliance and Training with documentation from the Reviewing IRB.

    • Any suspension or termination of research activities, including holds on new enrollment placed upon the research by the study sponsor, NIH or IC leadership, or any regulatory agency must be reported within 7 calendar days of an investigator becoming aware.
      • Suspension or termination of research activities at NIH by an external IRB: If the NIH is relying on an external IRB and the Reviewing IRB suspends or terminates NIH research activities, this must be reported within 7 calendar days of any NIH member of the research team being notified.

  • Investigators must provide to the OHSRP office of Compliance and Training a copy of any and all FDA Form 483 issued regarding an NIH research protocol within 7 calendar days of receipt of the Form 483. This should be submitted as an attachment to the report submitted in the electronic IRB system.

  • The guidance document, Reporting Research Events and Non-compliance, is available on the OHSRP website in the sections for Policy 801.
When NIH is the Reviewing IRB, which research related events should be reported to the IRB at the time of the continuing review submission?
  • Investigators must provide the following information about research related events to the IRB at the time of continuing review:
    • Noncompliance including major and minor protocol deviations
    • Anticipated Adverse Events and Serious Adverse Events that have taken place at a  greater frequency or severity than expected 
    • All UPs
    • Unresolved subject complaints
    • Information about new risks
If NIH is not the Reviewing IRB, what do NIH investigators need to report to the Reviewing IRB and what needs to still be reported in the NIH electronic IRB system?
  • In this case, NIH investigators must comply with the Reviewing IRB's event reporting requirements.

  • If the reportable event occurred at an NIH site, or directly impacts the NIH site, the NIH PI must also report to the OHSRP office of Compliance and Training in the NIH electronic IRB system within 7 calendar days of the NIH PI becoming aware of the event.
Which research related events need to be reported to the FDA?
What happens once I have submitted a reportable new information (RNI) form in the electronic IRB system within the required expedited time frame?
  • If OHSRP Compliance and Training analysts have additional questions about the RNI report, these will be provided as a request for clarification prior to further review.

  • After review by OHSRP leadership, the event may be referred for further review by the NIH IRB or the NIH Research Compliance Review Committee (RCRC).

  • Review by the NIH IRB: If the reported event is thought by OHSRP leadership to be a possible UP or new information that may affect a subject's willingness to enroll or continue study participation, it is referred for review by the IRB (full board review). If there will be a modification to update the protocol and/or consent as a result of the event, this modification is often reviewed at the same full board meeting as the relevant event report.

  • Review by the NIH Research Compliance Review Committee (RCRC): If the reported event is thought by OHSRP leadership to constitute possible serious and/or continuing noncompliance, it is referred for review by the RCRC. See additional information about the RCRC in the next question.

  • For events that are not referred to the NIH IRB or NIH RCRC, an acknowledgement letter is sent to the PI and study contacts indicating that the report form has been reviewed and includes any additional actions that must be taken by the study team.
What is the RCRC?
  • The NIH Research Compliance Review Committee (RCRC) is a duly established NIH IRB that adheres to the membership and committee requirements described in NIH Policy 201, IRB Membership and Composition. The RCRC primarily reviews allegations of non-compliance that have been deemed by the office of Compliance and Training and OHSRP leadership to be both credible and potentially serious and/or continuing. As a duly convened committee, the RCRC may exercise the full authority of an IRB including suspension or termination of IRB approval of research.
Are there any specific considerations I should think about when completing an event report/reportable new information form in the electronic IRB system?
  • Provide complete and comprehensive answers to the required questions on the RNI form used to submit information about the event or to follow-up questions posed by the Compliance Analysts after their review of your submission.

  • If the event form being submitted reports that consent was not obtained prior to the start of research, list all of the research procedures that occurred without the subject's consent.

  • Compliance and Training as well as OHSRP leadership who initially review the RNI event forms submitted in the electronic IRB system, as well as the IRB or RCRC members who review the event(s) referred to their board pay particular attention to what corrective action has been taken or will be taken to mitigate the problem and prevent it from recurring. In most cases, these entities will require a robust explanation of what investigators will do in this regard. If an inadequate plan for corrective steps to be taken is submitted, it is likely to be sent back to the team with request for a more thorough plan.

  • Electronically attach any relevant supporting documents when you submit the RNI form in the electronic IRB system. For example, if the event was reviewed by the DSMB, attach the DSMB's follow-up report of its review.
Where can I find additional information about reporting research related events to the IRB?


Chapter 10 - Modifications