Reporting Research Related Events

A RNI Smart Form is the communication method used to submit specific protocol-related events that require expedited reporting in PROTECT. This must occur within the time frames as specified in Policy 801.

Any questions about an event form can be sent via email to OHSRPCompliance@od.nih.gov. You will be provided a response within 24 hours, Monday-Friday except for federal holidays.

The following research-related events need to be reported within seven calendar days of an investigator becoming aware of the event:

• Major deviations from the IRB-approved protocol. Major Deviations are deviations from the IRB-approved protocol that have, or may have the potential to, negatively impact, the rights, welfare, or safety of the participant, or to substantially negatively impact the scientific integrity or validity of the study.
• Potential Unanticipated Problem Involving Risks to Subjects or Others (UP) is any incident, experience, or outcome that meets all the following criteria:
  • 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
  • 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
  • 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.
• Non-compliance unrelated to protocol deviations: Any actual or suspected non-compliance by any investigator or entity associated with the protocol. 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 IRB, whether the failure is intentional or not.
• 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.
• Use of the short form consent process to enroll a non-English speaking subject.
• Audit, inspection, or inquiry by a federal agency.
• Receipt of an inspection report (e.g., FDA Form 483) issued regarding an NIH research protocol and/or investigator.
• Potential PII breach.
• Incarceration of a subject who is participating in a study not approved by the IRB to involve prisoners.
• Complaint of a subject that cannot be resolved by the research team.

The following research-related event needs to be reported within 24 hours of an investigator becoming aware of the event:

• Death of a subject that is at least possibly due to the research.

• Noncompliance including major and minor protocol deviations and noncompliance that is not related to a protocol deviation. Minor Deviations are deviations that do not have the potential to negatively impact the rights, safety, or welfare of participants or others, or the scientific integrity or validity of the study.
• Anticipated Adverse Events and Serious Adverse Events ONLY need to be reported at CR if they have occurred at a greater frequency or severity than expected.
• Summary of all UPs.
• Unresolved subject complaints.
• Information about new risks.
• Regulatory actions that could affect safety and risk assessments.

When NIH is not the Reviewing IRB, the NIH Site PI/Lead Investigator must report research related events to the Reviewing IRB in accordance with that IRB’s instructions. Additionally, when the Reviewing IRB is an external IRB, and the reportable event occurred at an NIH site, or directly impacts the NIH site, the NIH PI must also report to the IRB using the RNI Smart Form in PROTECT within 7 calendar days of the NIH PI becoming aware of the event.

When the Reviewing IRB is an external IRB, and the event occurred at a non-NIH site, the NIH PI/Lead Investigator is required to ensure that the reporting requirements of the Reviewing IRB are followed. The investigator does not also report these events to the IRB, except as follows:

• 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 using the RNI Smart Form in PROTECT 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 documentation from the Reviewing IRB.
• 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.

The consent form provides contact information if subjects have a study related problem or question, or if they have questions about their rights as a research subject. This includes the PI, and any other study investigator specifically listed on the form. Additionally, subjects seen at the Clinical Center (CC) can contact the NIH CC Patient Representative. For investigators conducting human subjects research at other locations, it is necessary to identify specific individuals or offices external to the research team within the Institute/Center (IC) whom subjects can contact about complaints, such as the IC’s Clinical Director’s Office.

If you receive a study related complaint from a subject, you should:

• Communicate respectfully with the subject who expresses the complaint (i.e., the “complainant”), and address their concerns to the extent possible within your ability, scope, and authority, as soon as feasible.
• Report the complaint to the study PI or IC leadership for response or referral of the matter, as appropriate.
• Document the complaint in the medical and/or research record.
• Report the event to the IRB using the RNI form if the event relates to a possible unanticipated problem, or possible noncompliance.
• Contact the NIH Communication Director if you believe that the subject's complaint may result in a public relations concern.

FDA Guidance: FDA Guidance for Clinical Investigators, Sponsors, and IRBs: Adverse Event Reporting to IRBs —Improving Human Subject Protection

OHRP: OHRP Guidance on Reviewing and Reporting Unanticipated Problems Involving Risks to Subjects or Others (2007)