Reportable New Information (RNI)

Regardless of whether the event meets the IRB reporting criteria, other notifications may be required.  Please reach out to the applicable entities below to notify them of the incident, develop a Corrective and Preventive Action (CAPA) Plan, and incorporate any changes they request:

• Data Incident: If the incident involves the unintended disclosure of private/personal information, please reach out to FSM Director of Clinical Research Operations (a-cosentino-boehm@northwestern.edu). Please reference the Guidance on Evaluating Reports of Data Incidents on the Guidance Page for the appropriate steps and notifications.
• NM Investigational Drug Services: If the incident involves or affects the NM Investigational Drug Services, please reach out to Investigational Drug Service (NM) nminvestigationaldrugservice@nm.org

On all communications, please include the IRB Compliance Unit irbcompliance@northwestern.edu. 

Please submit an RNI in eIRB+.  The Principal Investigator must notify the IRB of unanticipated problems or other events that meet the reporting criteria in a timely manner.  Please see the Reporting Requirements and Timeframes section below.

Please refrain from including participant identifiers (name, date of birth, etc.) within the RNI application.  The IRB will review the RNI and make any needed recommendations to protect the rights and welfare of human participants.

Perform and document a Root Cause Analysis to determine the reason(s) that the issue arose.  There may be multiple reasons or causes that contribute to a problem.  The root cause is the initiating, most basic cause of a problem that may or may not lead to a chain of causes or other problems.  Eliminating the root cause should prevent a recurrence.

Utilize the guidance on the Corrective and Preventative Action Plan page to document the corrective and preventative actions you are taking and have planned to prevent future recurrence (if applicable). Please note that the IRB would not expect to see a CAPA for UPIRSOs or SAEs.

Reference the Study Support Resources page for templates and tools to help maintain compliant research (such as the Protocol Deviation Log and Note to File Template).

Please contact IRBCompliance@northwestern.edu with questions.  You may submit an RNI to report the event if the PI is not able to make a determination. In the RNI application, include a narrative of the PI's assessment of the event, and why the PI was unable to make a determination.

Please review the following reporting requirements and timeframes for the following events:

Death of an NU/NU Affiliate^* Participant that is:

• Unanticipated
• Related or Possibly Related
• Reporting Timeframe: Within 24 hours of knowledge or notification

Reportable New Information

• Reporting Timeframe: Within 5 business days of knowledge or notification

  Further information and specific examples can be found below.

  *NU participants include participants enrolled at NU’s affiliate sites (Shirley Ryan Ability Lab and Northwestern Memorial Healthcare) or sites for which NU has agreed to serve as the IRB of Record through a reliance agreement

If your event meets reporting criteria or you are otherwise submitting the event as an RNI in eIRB+, you must select the categories that represent the information being submitted. Carefully read each category description and select all those that apply in the RNI application. If you are unsure which categories to select, email the IRB Office at irbcompliance@northwestern.edu for assistance.

• Risk: Information that indicates a new or increased risk, or a safety issue. This includes a chance that something bad could happen.  For example:
  • New information (e.g., an interim analysis, safety monitoring report, publication in the literature, sponsor report, or investigator finding) that indicates an increase in the frequency or magnitude of a previously known risk or uncovers a new risk.
  • Withdrawal, restriction, or modification of a marketed approval of a drug, device, or biologic used in a research protocol.
  • Protocol violation that harmed participants or others or that indicates participants or others might be at increased risk of harm.
  • Complaint of a participant that indicates participants or others might be at increased risk of harm or at risk of a new harm.
  • Any changes significantly affecting the conduct of the research.

• Harm: Any harm experienced by an NU participant or other individual(s) that, in the opinion of the investigator, is unexpected and related or possibly related to the research procedures. Harms can include psychological, economic, legal, and other non-physical harms.
  • A participant at the Northwestern site has experienced a severe and unexpected reaction to the study drug. The PI thinks this is possibly related to the study drug.
  • An investigator finds out that the study involves a currently approved drug that may cause renal failure according to newly published literature. An interim analysis or safety monitoring report that indicates that frequency or magnitude of harms or benefits may be different than those initially presented to the IRB.
  • Change in FDA labeling or withdrawal from marketing of a drug, device, or biologic used in a research protocol.
  • An investigator realizes participants have accidentally been given study drug at a higher dose than was approved by the IRB. While no side effects were reported, the increase in dosage placed the participants at potential risk of harm.
  • Four weeks into the study of a new asthma drug, a participant informs the research staff that she is pregnant although the pregnancy test done at screening was negative. Pregnancy is an exclusion factor in the study.

• (Reportable) Non-compliance: Serious and/or continuing non-compliance with the federal regulations governing human research or with the requirements or determinations of the IRB that causes harm, increases the risk of harm, adversely affects the rights or welfare of participants or undermines the scientific integrity of the data, or is an allegation of such non-compliance. Incidents of non-compliance on the part of research participants which do not involve risk need not be reported to the IRB (i.e., failure to turn in medication diary). Examples of Reportable Non-compliance include, but are not limited to, the following:
  • Human participant research conducted without IRB approval.
  • Research personnel do not obtain written consent or assent for a study when the IRB has determined that consent or assent is required for a study that involves the collection of discarded tissue. While no harm occurred, failure to obtain consent/assent is a violation of the research participant’s rights.
  • Enrollment of participants before IRB approval has occurred and/or after IRB approval has lapsed.
  • Continued treatment of participants after IRB approval has lapsed without first obtaining permission from the IRB.
  • PI enrolls a participant that does not meet all of the inclusion/exclusion criteria. The criteria that were not met puts the participant at risk of harm.
  • Enrollment of children, prisoners, pregnant women and fetuses, without prior IRB approval.
  • Use of an unapproved consent form.
  • Use of unauthorized study personnel to conduct study procedures, obtain informed consent, or have access to identifiable participant information.
  • A required lab test is not done whose omission, in the opinion of the PI, poses risk of harm to participants.
  • Assessment for any inclusion/exclusion criterion was not done prior to beginning of study procedures. The criteria that were not evaluated prior to study procedures puts the participant at risk of harm.
  • A procedure, treatment, or visit specified in the protocol is conducted outside of the required time frame and has clinical consequence; the PI has determined that it poses risk of harm to participant or others; and/or the PI determined it has impacted the scientific integrity of the study.

• Audit: Audit, inspection, or inquiry by a federal agency and any resulting reports (e.g., FDA Form 483). The information investigators should provide to the IRB after an FDA inspection is outlined on the FDA Site Inspections Page.

• Reports: Only certain written reports of study monitors must be reported. Prompt reporting (within 5 business days) is required for monitoring reports for which the industry sponsor determines the findings could affect the safety of participants or influence the conduct of the study.

• Researcher Error: Failure to follow the protocol due to the action or inaction of the investigator or research staff.

• Confidentiality: Breach of confidentiality, data breach, or data incident. See Guidance on Evaluating Reports of Data Incidents (HRP-1908) to follow the steps outlined in the guidance. Include a summary of correspondence and any follow-up actions requested. For example:
  • Sharing identifiable information with a study sponsor or non-IRB authorized personnel
  • Sending communications to incorrect individuals (i.e., sending addressed recruitment letters to the wrong patient)
  • Misplacement/lost fully executed consent forms containing participant name

• Unreviewed Change: To eliminate immediate hazard to participants. For example:
  • A participant at a non-Northwestern site has experienced a severe and unexpected reaction to the study drug. The sponsor thinks this may be related to the study drug and instructs sites to promptly lower the drug dosage to eliminate an immediate hazard to participants. In this case, the PI should immediately implement the dosage change prior to IRB approval and then submit an RNI to notify the IRB.

• Incarceration: Incarceration of a participant in a study not approved by the IRB to involve prisoners.

• Complaint: Complaint of a participant that cannot be resolved by the research team.

• Suspension/Termination: Premature suspension or termination of the research by the sponsor, investigator, institution, or external IRB.

• Unanticipated Adverse Device Effect: Any serious adverse effect on health or safety or any life-threatening problem or death caused by, or associated with, a device, if that effect, problem, or death was not previously identified in nature, severity, or degree of incidence in the investigational plan or application (including a supplementary plan or application), or any other unanticipated serious problem associated with a device that relates to the rights, safety, or welfare of participants.

• Investigational Pharmacy Error: An error involving the investigational pharmacy that puts participants’ rights and/or welfare at risk or undermines the scientific integrity of the data. If selecting this option, please notify the Investigational Drug Services Pharmacy at  nminvestigationaldrugservice@nm.org to get additional information for your RNI (e.g., Corrective and Preventive Action Plan). 

• Short Form: If using a translated short form from the IRB website and the English language consent document as the written summary, the short form consent process may take place prior to IRB review. An RNI should be submitted to the IRB within 10 business days, to report the use of the short form consent process. The RNI should contain the documents and confirmations as described on the Short Forms webpage.
• Death of a Research Participant: Northwestern University investigators are required to report deaths of NU participants to the IRB office if the death was not anticipated and related or possibly related to participation in the study. NU participants include participants enrolled at NU’s affiliate sites (Shirley Ryan Ability Lab and Northwestern Memorial Healthcare) or sites for which NU has agreed to serve as the IRB of Record through a reliance agreement.
  
  • The investigator should contact the IRB Office as soon as possible via phone or email.
  • Depending on the circumstances, the IRB may need to take immediate action to minimize further harm to participants such as halting the enrollment of additional participants or suspending approval of the research.
  • Formal notification to the IRB of the event is still required and accomplished through a Reportable New Information submission under the applicable study in eIRB+.
  • Note: Effective June 7, 2021, the IRB Office separated the previously combined RNI categories of harm/death into two separate categories. The RNI application allows the user to categorize the reportable incident as a harm and/or death or a research participant. Additionally, the criteria for a harm or a death of a research participant, which were previously defined as probably related, were changed to possibly related.

The IRB makes a determination on the RNI submission after the PI has made the initial assessment to report the event. Only events that may meet the definition of serious non-compliance, continuing non-compliance, Unanticipated Problem Involving Risks to Subjects or Others (UPIRSO), or combinations of these require reporting to the IRB. The IRB Office provides the Incident Assessment Tool (HRP-1207) to guide investigators through the reporting criteria.

The following are definitions of IRB determinations. See the above section on RNI Categories and Examples for the available categories for you to select in your RNI form.  

• Non-compliance: Failure to follow the federal regulations governing human research, requirements, and/or determinations of the IRB. Non-compliance may result from actions or omissions by study personnel and can range from relatively minor or technical deviations to serious deviations that threaten participants’ rights or welfare.
  • Examples of non-compliance which may not be reportable to the IRB may include, but are not limited to the following: Inadvertent use of an IRB approved but non-stamped informed consent form (ICF); an out of window study visit that did not cause any harm or increase the risk of harm or adversely affect the participants rights and welfare or negatively affect the integrity of the study data; or other administrative errors. Please note all occurrences of non-compliance should be documented within the study records, within the protocol deviation log or a note to file, or by using the Incident Assessment Tool, as applicable. 
• Serious Non-compliance: Non-compliance with the federal regulations governing human research or with the requirements or determinations of the IRB that causes harm, increases the risk of harm, adversely affects the rights or welfare of participants and/or undermines the scientific integrity of the data. Examples of serious non-compliance include but are not limited to the following:  use of an incorrect version of an ICF that omitted a potential risk of participation; safety laboratory assessments not being conducted prior to administering the next cycle of drug; conducting study procedures prior to obtaining informed consent; numerous instances of not adhering to the protocol, such that the participants data is no longer usable. The IRB Panel may consider mitigating factors, such as corrective action, that play a role in the determination of whether the event increased risk, decreased potential benefits, or negatively affected the integrity of the study data but if despite these factors, the panel may determine the event’s occurrence meets the definition of serious noncompliance, and then the event will be categorized as such.
• Continuing Non-compliance: A pattern of non-compliance through failure to adhere to the regulations or institutional requirements that protect the rights and welfare of participants and others and suggests a likelihood that non-compliance will continue without intervention, or involves frequent instances of minor non-compliance. Continuing non-compliance may also include failure to respond to a request from the IRB to resolve an episode of non-compliance or a pattern of minor non-compliance. Examples of continuing non-compliance may include but are not limited to the following: non-safety related laboratory assessments were not completed on day 15 for cycles 1-12; the quality of life assessments were not administered for participants #6-15; despite a corrective action plan the study team continues not to distribute the drug diary.*Note that multiple instances of non-compliance that are deemed not serious individually may constitute serious and/or continuing non-compliance when considered collectively. 
• Unanticipated Problem Involving Risks to Subjects or Others (UPIRSO):  Any information, including any incident, experience, or outcome that meets ALL of the following conditions:
  1. is unexpected (in terms of nature, severity, or frequency) given the procedures described in the research protocol documents (e.g., the IRB-approved research protocol and informed consent document) and the characteristics of the human participant population being studied;
  2. is 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 human participants or others at a greater risk of harm (including physical, psychological, economic, or social harm) than was previously known or recognized, even if no harm has actually occurred.
• Suspension of IRB Approval: An action of the IRB, IRB Executive Director, Institutional Official/Organizational Official, or designee of the Institutional Official/Organizational Official to temporarily or permanently withdraw IRB approval of some or all research procedures short of a Termination of IRB Approval. Suspended studies remain open and are subject to continuing review.
• Termination of IRB Approval: An action of the IRB, IRB Executive Director, Institutional Official/Organizational Official, or designee of the Institutional Official/Organizational Official to permanently withdraw IRB approval of all research procedures. Terminated studies are permanently closed and no longer require continuing review.
• Additional information needed before determination:  When additional information is needed before the board can make a determination.  The PI should consult the RNI letter and/or eIRB+ and follow the directives of the IRB to complete any required action/provide the requested information and submit the RNI back to the IRB for a final determination.
• None of the above: When an event does not fit the criteria for UPIRSO, Non-compliance (including Serious or Continuing), Suspension/termination of IRB approval, Allegation of non-compliance with no basis in fact, the IRB acknowledges the event as none of the above.

Before You Submit

Review the Incident Assessment Tool (HRP-1027) to determine if the event is reportable to the IRB. You may use the tool to document the event in your research record and/or to help you prepare your RNI submission in eIRB+.

• Note: Documentation for all events should be kept in the study files regardless of whether they meet the criteria to report to the IRB within an RNI. Please see the Study Support Resources and Templates webpage to find the Protocol Deviation Log and Note To File templates.

If the PI determines that the event meets the IRB reporting criteria, provide all of the details as outlined in the RNI application, including details of the event you are submitting to the IRB, the actions taken to resolve the incident. If the event is a deviation, non-compliance, or error, also describe the root cause and how you will prevent this type of incident from happening again. If applicable to the event, the description must address the following:

• What happened, when, and where
• What factors and who contributed (role, not name) to why it happened? Conduct a Root Cause Analysis to identify the primary source of the event.
• What steps did the Principal Investigator (PI) take to address the issue before submitting the RNI to the IRB?
• What is the plan going forward for preventing this from happening again? Provide a Corrective and Preventive Action (CAPA) Plan that is specific, timely, and measurable. You must maintain documentation that demonstrates that you implemented the CAPA plan. Contact IRBCompliance@northwestern.edu for additional guidance.
• If the event required Additional Notifications (for example, Data Incident or NMHC investigational drug services pharmacy) include the correspondence and outcome of the correspondence in your description of the event, if available
• Include NU/NU affiliate participant ID numbers in your description if applicable

See our Corrective and Preventative Action (CAPA) Plans webpage for guidance on writing a specific, timely, and measurable CAPA plan and for performing a robust root cause analysis.

Steps To Complete The Submission

• Log-in to eIRB+ using your NU NetID and password.
• Determine if the new information applies to a specific study or several studies.
  1. If the new information is related to a particular study:
     1. Click My Studies and filter by PI or Study Number.
     2. Choose the applicable study from the resulting list.
     3. Click Report New Information.   (Located in the left column of the page under My Current Activities.)
  2. If the new information is not related to a particular study:
     1. Click Report New Information. (Located in the upper left corner of your Inbox.)
  3. If the new information is related to several studies under the same PI:
     1. Click Report New Information (Located in the upper left corner of your Inbox.)
     2. In the Related Studies section of the submission, add each study related to the new information.
  4. If the new information is related to several studies under different PIs: Determine if the new information is applicable to a specific study or several studies.
     1. Follow the above as appropriate to open a separate RNI submission for each PI.
• A blank submission will open. You must complete all questions.
• Provide a short descriptive title for the submission. The title will be the “name” of the RNI submission and reflected within in the eIRB+ system.
  1. If the event is for a study where the Northwestern University IRB ceded IRB review to an external IRB, include “xIRB” at the beginning of the short title.
• Indicate the date you first became aware of the information. If reporting on behalf of the PI, indicate the date the PI first became aware of the information.
  1. If you are reporting the event outside of the IRB required timeframes, disclose this in the RNI summary and provide a preventive action plan to prevent late reporting in the future.
• Select the appropriate category(ies) the information represents.
• Indicate where the event occurred:
  1. If the incident occurred at NU or an NU affiliate study site, also identify the IRB of record.
  2. If the incident occurred at a site external to NU or an NU affiliate study site, also indicate whether the external site is relying on or unaffiliated with NU IRB.
• Describe the new information. Provide sufficient detail to describe the event using the prompts as a guide.
• Respond in the form to the following questions and justify these responses in the description above:
  1. Does this information indicate a new or increased risk, or a safety issue?
  2. Does the study need revision?
  3. Does the consent document need revision? If revisions are required, describe them in the space provided and submit a study modification for review.
• Add each study related to the new information (if not already listed).
• Attach any files containing supporting information related to the event, the root cause analysis, or the corrective and preventive action plan.
  1. If the event is for a study where the Northwestern University IRB ceded IRB review to an external IRB, also upload the xIRB determination letter. If not available at the time of submission, proceed with submission and upload it once available.
• Click Continue when you have completed the application. Please Note: This activity does not submit the form to the IRB Office.
• The PI or PI Proxy must click Submit for the submission to reach the IRB.

• An overview of the basic process for Reportable New Information submissions in the eIRB+ system is outlined here: Following Your eIRB+ Submission. 
• A Reportable New Information is submitted in eIRB+
• The IRB review process begins: 

Pre-Review

The Reportable New Information Submission will undergo a pre-review by IRB staff to ensure that the submission is complete and in keeping with the IRB’s requirements.  This includes (if applicable):

• The applicable RNI categories have been selected that represent the event.
• The event description is robust. The PI has provided a timeline with dates specified.
• The PI describes their root cause analysis.
• The PI describes their corrective and preventative action (CAPA) plan.
• The PI may provide supporting documentation to support the event’s narrative, root cause analysis, and/or CAPA plan.

The investigator may be asked to provide additional information.  Once the submission is determined to be complete, it will be routed for IRB review.

IRB Review

Expedited Review

The submission is sent to an IRB member for review. The submission will receive one of the following determinations:

• Non-compliance that is neither serious nor continuing,
• None of the above.

Full Board Review

The submission will be assigned to a Board meeting for review. The submission will be presented at a convened IRB meeting by a primary reviewer. The submission will receive at least one of the following determinations by the IRB:

• Unanticipated problem involving risks to subjects or others (UPIRSO)*,
• Suspension or termination of IRB approval*,
• Serious non-compliance*,
• Continuing non-compliance*,
• Non-compliance that is neither serious nor continuing,
• Additional information needed before determination,
• None of the above

*Reportable determinations - see Institutional Reporting Obligations below

If the IRB determines the reported event constituted a UPIRSO, or serious and/or continuing non-compliance and the study is funded by HHS or subject to FDA regulations, these agencies will be notified by the IRB of this finding.

An acknowledgment letter that may or may not request additional actions will be issued through eIRB+. If additional action is specified, a modification or an additional New Information Report must be submitted.

Determination

If the RNI undergoes Expedited or Full Board review, an RNI determination letter will be issued through eIRB+. If additional action is required by the IRB, this will be noted within the RNI determination letter. The PI must review the determination letter and take the required actions as outlined in the letter. This might include: revising the CAPA plan, submitting a modification or an additional Reportable New Information (RNI), etc.  

 Northwestern University is obligated to report to institutional officials and all applicable federal oversight agencies information that represents Serious Non-Compliance, Continuing Non-Compliance, Unanticipated Problems Involving Risks to Subjects or Others (UPIRSO), Suspension of IRB Approval, Termination of IRB Approval, or any combination of the above. Refer to the IRB Office SOP for submitting external and institutional reports at External Reporting Process (HRP-094).

If the IRB makes a reportable determination in reviewing an RNI, the Principal Investigator (PI) of the associated study must review their study’s funding sources in the eIRB+ application for accuracy and email irbcompliance@northwestern.edu within 5 business days from the date of the RNI letter to confirm the accuracy of the funding sources or provide an accurate list of funding sources. The IRB Office uses the study’s funding sources to help determine the parties to whom to report. Outdated or inaccurate funding information may cause unnecessary reporting, which poses an institutional risk. If the funding sources are inaccurate, the PI must submit a modification request in the eIRB+ system to correct the funding sources and include the modification request number (e.g., MOD0002) in their email to irbcompliance@northwestern.edu.