On This Page
- Reportable New Information (RNI) Overview
- Submission Instructions
- Types of Events to Consider
- Adverse Biomedical Events
- Noncompliance Event
- Unanticipated Problems that Involve Risk to Research Participants or Others (UPIRSO)
- Third-Party Safety Report that Requires Reporting to the IRB
- Third-Party Safety Report that Does NOT Require Reporting to the IRB
- Additional Reporting Requirements for Other Events
Relevant IRB Policies/Procedures
This page includes information about the requirements for reporting new information to the IRB, including unanticipated problems, noncompliance, and third-party safety events (when applicable).
Reportable New Information (RNI) Overview
The principal investigator (PI) must ensure that serious or continuing noncompliance, or problems, events, and information involving risks to research participants or others are reported to the Institutional Review Board no later than 10 calendar days after becoming aware of them.
It is the responsibility of the PI to determine and assess events to see whether they meet the reporting criteria as described in the policies linked above. If the team is unclear, consult with IRO@fredhutch.org, or if there is any question, the event should simply be reported for the IRB to assess.
Submission Instructions
All events meeting IRB reporting criteria must be submitted in Hutch IRB as a Reportable New Information submission. You must submit a separate RNI for each study or site involved in the event, altering the submission from the perspective of the institution involved. A Reportable New Information Supplement is required for each submission.
If the facts in the RNI necessitate changes to study documentation on file with the IRB, you will also need to submit a separate Modification in Hutch IRB to provide those changes/updates to the IRB, for example changes to the Protocol.
In-depth instructions for how to create and submit an RNI in Hutch IRB can be found here: Online Video
Types of Events to Consider
The below sections further describe the types of events that may meet reporting requirements.
Adverse Biomedical Events
When, in the opinion of the PI, any adverse event meets all three of the following criteria, whether they occur on- or off-site (including Third-Party Safety Reports), they must be submitted to the IRB within 10 calendar days.
- Unexpected: An adverse event is unexpected when its nature (specificity), severity or frequency are not consistent with (a) the known or foreseeable risk of adverse events associated with the research procedures described in the protocol-related documents, such as the IRB-approved research protocol, informed consent document and other relevant sources of information such as product labeling and package inserts; and are also not consistent with (b) the characteristics of the subject population being studied, including the expected natural progression of any underlying disease, disorder or condition, or any predisposing risk-factor profile for the adverse event.
- Related or possibly related to the research: An adverse event is related or possibly related to research procedures if, in the opinion of the PI, it was more likely than not caused by the research procedures. Adverse events that are solely caused by an underlying disease, disorder or condition or by other circumstances unrelated to the research or any underlying disease, disorder or condition are not "related or possibly related." If there is any question whether an adverse event is related or possibly related to the research, report the adverse event.
- Serious: An adverse event is serious when it results in any of the following outcomes: death, risk of death, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity/or change in psychosocial status, a congenital anomaly or the requirement of an intervention to prevent permanent impairment or damage.
ONLY report adverse events that appear to meet all three reporting requirements (unexpected, related or possibly related to the research, and serious).
Noncompliance Event
| Definition | |
|---|---|
| Noncompliance | An intentional or unintentional action or activity relating to human subjects research by a person subject to the human research protection program of Fred Hutch (HRPP) that violates or otherwise fails to adhere to one or more of (i) the requirements or determinations of the IRB, (ii) the HRPP, or (iii) laws or regulations governing the conduct of human subjects research, including applicable FDA, DHHS, and DoD regulations. “Noncompliance” does not include protocol deviations that are beyond the immediate control of the Principal Investigator and his or her study staff (e.g. delays caused by weather, the acts or omissions of third parties such as outside labs, or scheduling changes not caused by the Principal Investigator or his or her staff). However, this type of protocol deviation may constitute an unanticipated problem involving risks to research subjects or others that still must be reported to the IRB. |
| Serious Noncompliance | Noncompliance that materially increases the risks to or otherwise seriously jeopardizes the rights and welfare of human research participants or materially impairs the integrity of the study data. |
| Continuing Noncompliance | A pattern of repeated noncompliance that continues after initial discovery, including inadequate efforts to take corrective actions within a reasonable timeframe. Examples include a pattern of behavior that evidences a lack of attention to or knowledge of the HRPP, or the protection of research participants, or that is likely to continue without intervention. Continuing noncompliance generally does not apply if the PI discovers non-compliance and undertakes an audit or other investigation that uncovers additional incidents of the same type—because these are considered to be part of the same “discovery”. Instead, continuing noncompliance generally applies when noncompliance has been discovered and addressed with a corrective and preventive action (CAPA) plan, but then that CAPA is ineffective such that additional incidents of the same kind occur later. |
| Minor Noncompliance | Noncompliance that does not meet the definition of serious or continung noncompliance.. |
PI Responsibility for Noncompliance
PIs and their study staff members are required to report each event that may meet the above definition of serious or continuing noncompliance within 10 calendar days of learning of the event.
Additionally, the IRB directs that the following noncompliance events must also be reported to the IRB within 10 calendar days, whether or not the PI feels it meets the reporting criteria:
- Failure to obtain IRB approval of human subjects research when required under the federal Human Research Protections Program or applicable laws and regulations;
- Enrolling a research participant who does not fit the inclusion and/or exclusion criteria in the protocol;
- Failing to obtain or document informed consent; and
- Administering radiation, drugs, biologics, or cell products, or using devices required by the protocol, at a dose or schedule that has not been approved by the IRB except when necessary to eliminate apparent immediate hazards to the research participant (see IRB Policy 2.5 Modification to Ongoing Activities).
Examples of continuing noncompliance which should be reported promptly to the IRB:
- A pattern of behavior that continues after initial discovery, including inadequate efforts to take corrective action within a reasonable timeframe. Examples include a lack of attention to or knowledge of the Human Research Protection Program or the protection of research participants or that is likely to continue without intervention.
The IRB will determine if the event constitutes serious and/or continuing noncompliance.
NOTE: Noncompliance does not include protocol deviations that are beyond the control of the principal investigator and his or her study staff (e.g., pandemics, delays caused by weather, or by the acts or omissions of third parties such as outside labs). However, this type of protocol deviation may constitute an unanticipated problem involving risks to research subjects or others, reportable under IRB Policy 2.6, Unanticipated Problems Involving Risks to Subjects or Others.
Unanticipated Problems that Involve Risk to Research Participants or Others (UPIRSO)
Definition of an Unanticipated Problem Involving Risks to Research Participants or Others
Any incident, experience, or outcome that meets ALL of 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;
- 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 research participants or others at a greater risk of harm (including physical, psychological, economic, or social harm) than was previously known or recognized.
PIs must assess all Third-Party Safety Reports received on a study to determine if a non-local event also may meet the above definition for the study and therefore requires reporting locally.
The following are a few examples of events that may meet the UPIRSO criteria:
- A series of related adverse events that individually may not be unexpected, but that indicate a trend placing research participants or others at a greater risk of harm than was previously known or recognized.
- An interim analysis or safety monitoring report that may potentially affect a study's risk/benefit ratio, or that is considered to place research participants at higher risk.
- A paper published from another study that shows that the risks or potential benefits of the research may be different than initially presented to the IRB.
- A breach of confidentiality.
- A study participant complaint, when the complaint indicates unexpected risks, or if a participant’s complaint cannot be resolved by the research team.
- Changes made to the research without prior IRB approval to eliminate apparent hazard to participants (see IRB Policy 2.5 Modification to Ongoing Activities).
PI Responsibility
Unanticipated problems, events, or new information that indicates research participants or others are at greater risk of harm must be submitted to the IRB within 10 calendar days.
Third-Party Safety Report that Requires Reporting to the IRB
The PI is responsible for assessing whether the adverse event(s) described in a Third-Party Safety Report needs to be reported to the IRB. If the event meets the UPIRSO criteria above, it must be submitted to the IRB within 10 calendar days.
Third-Party Safety Report that Does NOT Require Reporting to the IRB
If a Third-Party Safety Report does not appear to meet the UPIRSO definition, the event should not be reported to the IRB.
However, if the sponsor of a study or protocol requires documentation of IRB review of these types of reports, the PI may submit a Reportable New Information (RNI) submission in Hutch IRB, selecting “Sponsor/Protocol Requirement” as the category of new information. IRO staff will acknowledge the RNI. The PI, Primary Contact, and PI Proxies will receive an email notification acknowledging the submission. A formal acknowledgement letter will not be issued for reports that are required by the Sponsor to be submitted to the IRB but that do not meet the IRB reporting criteria.
If the research study is permanently closed to local accrual and there are no local participants receiving interventions or in long-term follow-up, then third-party safety reports do not need to be evaluated by the PI or submitted to the IRB.
Additional Reporting Requirements for Other Events
The occurrence of one or more of the following events in connection with any study in which Fred Hutch is enrolling research subjects or is a participating site must be reported to the IRB as soon as possible but no later than 10 calendar days after the investigator or study staff learn of the event. The following events should be reported with a Modification (see Modifications for further guidance and forms):
- Suspension or enrollment hold of the research trial
- Significant changes in the associated risks of the trial