Reportable New Information FAQs

What is Reportable New Information?

Reportable New Information (RNI) is a catch-all category that includes any event (i.e., an accident, experience, new information or outcome) that occurs during the course of a study that may:

Place human subjects or others at a greater risk of harm,
Adversely affect the safety, rights or welfare of human subjects,
Compromise the quality or integrity of the research data,
Significantly adversely affect the Human Research Protection Program (HRPP), or
Represent a pattern of on-going non-compliance.

Reportable New Information must be promptly reported to the IRB. Unlike a protocol submission, an RNI submission is not restricted to the Principal Investigator.
A single RNI submission can be submitted for multiple protocols. For example, if the FDA issued a new black box warning for a medication that is being used in multiple protocols, one RNI could be submitted and the report can be linked to all the Investigator’s affected protocols.

What type of events are required to be reported to the IRB as Reportable New Information (RNI)

Events that may meet the below definitions of an Unanticipated Problem Involving Risk to Human Subjects or Others, Serious Non-Compliance, and/or Continuing Non-Compliance must be promptly reported to the University IRB.

Unanticipated Problems (UAP) Involving Risk to Human Subjects or Others defined as any accident, experience, new information or outcome that meets all of the following criteria:
- Unexpected in terms of nature, severity, or frequency; AND
- Related, or possibly related, to a subject’s participation in the research; AND
- Places human subjects or others at a greater risk of harm (including physical, psychological, economic, or social harm) than was previously known or recognized.
Serious Non-compliance: Non-compliance that significantly adversely affects the safety, rights or welfare of human research subjects or others, significantly compromises the quality or integrity of the research data (i.e., negatively impacts the ability to draw conclusions from the study data), or significantly negatively affects the integrity of HRPP.
Continuing Non-compliance: Non-compliance that has been previously reported or a pattern of ongoing Non-compliance that significantly adversely affects the safety, rights or welfare of human research subjects or others, significantly compromises the quality or integrity of the research data (i.e., negatively impacts the ability to draw conclusions from the study data), or significantly negatively affects the integrity of the HRPP.

What is an Adverse Event (AE)

An unfavorable medical occurrence, which may include abnormal signs (for example, abnormal physical exam or laboratory finding), symptoms, or disease, temporally associated with, but not necessarily considered related to, the subject’s participation in the research study.

What is the difference between and Internal and External Adverse Event?

Internal Adverse Events: Any adverse event, unanticipated problem, experience, incident or outcome occurring under the jurisdiction of the University of Pittsburgh (UPitt) IRB-HRPP will be considered internal. If an event occurs in a subject enrolled in a single-IRB (sIRB) protocol where UPitt IRB is the IRB of record, then the event is considered Internal even if the site is not part of UPitt or UPMC. For example, if an event occurs at a Chicago site in a sIRB protocol with UPitt IRB is the IRB of record, then the event will be considered internal.
External Adverse Events: Any adverse event, unanticipated problem, experience, incident or outcome occurring outside the jurisdiction of the UPitt IRB-HRPP will be considered external. For example, an event happens at a site that is not part of UPitt or UPMC in a multicenter protocol where each site has its own IRB review.

What is a Serious Adverse Event or Suspected Adverse Reaction?

The FDA defines an adverse event or suspected adverse reaction as “serious” if, in the view of either the investigator or sponsor, it results in any of the following outcomes:

Death,
A life-threatening adverse event,
Inpatient hospitalization or prolongation of existing hospitalization,
A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or
A congenital anomaly/ birth defect.
For Devices, required intervention to prevent permanent impairment or damage

Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. Examples of such medical events include allergic bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias or convulsions that do not result in inpatient hospitalization, or the development of drug dependency or drug abuse.

What is an Adverse Event Log?

An Adverse Event log is a record of all adverse medical events that occur, including both significant and non-significant Adverse Events.

Adverse event logs must be maintained by an Investigator conducting FDA regulated research or if required by the study sponsor or oversight agency. It is recommended for all clinical trials. Note that Investigators may have additional reporting obligations as specified by the study sponsor or oversight agency.

Failure to maintain an Adverse Event log as required may represent Serious and/or Continuing Non-compliance.

Adverse event logs are not required to be submitted at continuing review but must be available upon request.

Unanticipated Problem Involving Risk to Human Subjects or Others

While an UAP is often an Adverse Event, it includes other negative events in addition to Adverse Events. An UAP may involve breach of confidentiality, published literature that may impact the conduct of the study, unresolved subject complaint, etc.
An adverse event may be an UAP if it meets ALL of the definitions below for an Internal or External Adverse event, depending on where the event occurred:

Internal Adverse Events that are 1) unexpected, 2) related or possibly related to the research intervention, and 3) serious or otherwise suggests that the research places the subject or others at a greater risk of harm (including physical, psychological, economic or social harm) than was previously known or recognized.
External Adverse Events that are 1) unexpected, 2) related to the research intervention, and 3) serious or otherwise suggests that the research places subjects or others at greater risk of harm (including physical, psychological, economic or social harm) than was previously known or recognized.

Please refer to Chapter 17 of the HRP Policies and Procedures for the special reporting requirements for Adverse Events Involving Gene Transfer Interventions.

Most Adverse Events will not meet the definition of an Unanticipated Problem Involving Risk to Subjects or Others. Expected Adverse Events or Adverse Events which are determined by the Investigator to be unrelated to the research intervention do not need to be submitted to the IRB as Reportable New Information but should be documented in an adverse event log.

The following Venn diagram summarizes the general relationship between Adverse Events and Unanticipated Problems:

OHRP venn diagram showing AEs that are UAPs and UAPS that are not AEs need reporting

What are examples of events that may meet the definition of an Unanticipated Problem (UAP) Involving Risk to Human Subjects or Others?

Examples of UAPs Involving Risk to Human Subjects or Others include (but are not limited to):

An internal Adverse Event that was determined to be 1) unexpected, and 2) related or possibly related to the research intervention, and 3) serious or otherwise suggests that the research places the subject or others at a greater risk of harm (including physical, psychological, economic, or social harm) than was previously known or recognized.
An external Adverse Event that was determined to be 1) unexpected, and 2) related to the research intervention, and 3) serious or otherwise suggests that the research places subjects or others at greater risk of harm (including physical, psychological, economic, or social harm) than was previously recognized.
A publication in the literature, safety monitoring report, interim result, or other finding that indicates an unexpected increase in the risk to benefit ratio of the research.
A complaint of a subject that indicates an unanticipated risk or which cannot be resolved by the research staff.
An untoward event that significantly affects the safety, rights, welfare, privacy, confidentiality or other rights of research subjects or members of their family (e.g., lost, or stolen research data or breach of confidentiality).
An untoward event that presents a risk to Investigators and research staff involved in the conduct of the research.
Premature suspension or termination of the research for safety reasons by the Sponsor, Investigator, or Institution.

What is the definition of Non-compliance?

Non-compliance is defined as failure on the part of the Investigator or any member of the study team to follow the terms of University of Pittsburgh IRB-approved study protocol or to abide by applicable laws or regulations, or University of Pittsburgh HRP policies. This includes protocol deviations.

What is a Non-compliance/deviation log?

A Non-compliance/deviation log is a record of all protocol deviations and instances of Non-compliance that occur during the course of a study.

It is a mandatory requirement for non-compliance/deviation logs to be maintained for:

Greater than minimal risk studies;
Studies that meet the federal definition of a clinical trial; or
Studies for which reporting is required by the funding agency.

Non-compliance logs are not required to be submitted at continuing review but must be available upon request. Failure to maintain a log as required by the IRB may represent Serious Non-compliance and/or Continuing Non-compliance. Non-compliance/deviation logs are recommended but non-mandatory for all other studies.

When does Non-compliance need to be reported to the IRB?

Non-compliance (including protocol deviations) needs to be reported to the IRB if it:

Significantly adversely affects the safety, rights, or welfare of human subjects or others OR
Significantly compromises the quality or integrity of the research data (i.e., negatively impacts the ability to draw conclusions from the study data) OR
Significantly negatively affects the integrity of the Human Research Protection Program OR
Represents Continuing Non-compliance (i.e., Non-compliance that has been previously reported or a pattern of ongoing Non-compliance).

What are examples of Non-compliance that may meet the IRB’s reporting requirement?

Examples of Reportable Non-compliance include (but are not limited to):

Performing non-exempt human subject research without obtaining prospective University IRB approval.
Failing to notify the IRB of an event that meets the IRB reporting requirements (i.e., death, SAE, UAP Involving Risk to Human Subjects or Others, Serious and/or Continuing Non-compliance).
Implementing protocol modifications without obtaining prospective IRB approval.
Initiating research activities prior to obtaining informed consent.
Deviating from the informed consent process as described in the IRB-approved study application.
Consent being obtained by a member of the research team that is not a licensed Investigator if the study involves a drug, device, or surgical procedure.
Research activities being performed by individuals who are not sufficiently trained or credentialed to perform the task.
Obtaining informed consent using an outdated consent form when the new consent form contains new information that may cause the subject to change their mind about participating.
Conducting research during a lapse in IRB approval.
Not adhering to inclusion/exclusion criteria.
Enrolling more subjects than were approved in a greater than minimal risk study.
Performing research at an unapproved site.
Failing to maintain a Non-compliance/deviation log if the study is greater than minimal risk, meets the federal definition of a clinical trial or is a requirement by the funding agency.
Failing to maintain a log of Adverse Events if the Investigator serves as a Sponsor-Investigator of an IND or IDE.
Failing to submit Reportable New Information to the IRB in accordance with the reporting timeframes (i.e., late submissions).
Repeated informed consent deficiencies (i.e., missing signatures/dates, missing pages of the consent document, not maintaining the original signed document, etc.).
Failing to comply with federal, state, or local regulations governing human subject protections or University HRP policies (this includes activities of the IRB and/or University HRP staff).

Non-compliance that does not meet the IRB reporting requirements should be entered in a Non-compliance/deviation log.

What steps should be taken to determine if Non-compliance (i.e., a protocol deviation) must be reported to the IRB or can be entered in a log?

The Investigator, in conjunction with medical monitor, data and safety monitoring board, and/or other applicable study monitoring groups, [GLA1] [MOU2] must evaluate the Non-compliance to determine if it meets the IRB’s reporting requirement for Non-Compliance as listed above. Making this determination can be challenging. Assessing the event in the context of subject safety often provides the best direction. First ask, “What are the specific risks and/or research activities that this subject consented to, and were these risks elevated in any way by the Non-compliance/protocol deviation”. Then ask, “Did this Non-compliance (or series of non-compliant activities) create a situation where the quality or integrity of the research data may be affected”. Next ask, “Did this Non-compliance significantly compromise the integrity of the University’s Human Research Protection Program (e.g. violate local, state or federal regulations)”. Finally consider, “Has the Non-compliance been previously reported or represent a pattern or ongoing Non-compliance”. If all of these questions can be answered negatively, it is likely that the Non-compliance does not need to be promptly to the IRB and can be entered in a non-compliance/deviation log.

An Investigator should err on the side of reporting to the IRB or consult the IRB if there is uncertainty whether an event meets the reporting requirements.

What are the reporting requirements if there is Non-compliance on the part of a research participant?

Non-compliance on the part of a research subject may not need to be submitted to the IRB as Reportable New Information if it does not meet the IRB reporting requirements. Examples of subject Non-compliance that may not need to be reported include (but are not limited to):

Study visits/procedures falling outside the protocol specified timeframes at the subject’s request (e.g., due to inclement weather or time and burden).
Research procedures not being completed at the subject’s request.
Unreturned study medication or unreturned diary.

Subject Non-compliance that does not meet the IRB reporting requirements should be entered in a Non-compliance/deviation log. Subject Non-compliance that meets the definition of an Unanticipated Problem Involving Risk to Subjects or Others or Reportable Non-compliance should be reported to the IRB within 10 working days of the Investigator becoming aware of the event.

Should the IRB be notified if there is a planned protocol deviation?

An exception request should be approved by the IRB before implementing a prospective, one-time, intentional action or process that departs from the IRB-approved study application (e.g., a planned protocol deviation).

Prospective – The study team must obtain prior IRB approval if planning to perform a study procedure outside of the parameters of the IRB-approved study application, unless the deviation is needed to avoid an apparent, immediate hazard to the research subject. An exception request cannot be submitted to the IRB after it has already taken place.
One-time – Each exception request is intended for a single occurrence and generally for one specific subject. The IRB may require a change to the study application if the same exception request is submitted multiple times.

For example, an eligibility criterion is for the subject to have an MRI within 30 days prior to enrollment. An Investigator may submit an exception request to enroll a subject that had an MRI 35 days prior to enrollment but otherwise meets all other eligibility criteria. If the exception request was submitted after the subject had already been enrolled, the exception request would not be approved, and would then need to be submitted as Reportable New Information as it now constitutes Non-compliance.

Within what timeframe does Reportable New Information (RNI) need to be submitted to the IRB?

Unanticipated Problems Involving Risk to Human Subjects or Others and instances of Reportable Non-compliance are required to be submitted to the IRB within 10 working days of the Investigator becoming aware of the information.
Internal Adverse Events that are 1) unexpected, 2) fatal or life-threatening, and 3) related or possibly Related to the Research Intervention must be reported to the IRB within 24 hours of learning of the event.
Non-fatal or life-threatening internal Adverse Events that meet the definition of an Unanticipated Problem Involving Risks to Human Subjects or Others need to be reported to the IRB within 10 working days of the Investigator learning of the event.
External Adverse Events that are 1) unexpected, 2) serious AND suggest that the research places subjects or others at greater risk than was previously recognized, and 3) Related to the Research Intervention will be reported to the IRB within 30 working days of their receipt by the University/UPMC Investigator. (Note: Only sponsor-generated safety reports that meet the Adverse Event reporting of the IRB should be submitted to the IRB)
Non-compliance that needs the IRB reporting requirement must be reported to the IRB within 10 working days of the Investigator becoming aware of the information
Please refer to Chapter 17 of the HRP Policies and Procedures for the special reporting requirements for Adverse Events Involving Gene Transfer Interventions.

How do reporting responsibilities of the PI change if the University of Pittsburgh is not the IRB of record?

Responsibilities for reporting are case-by-case and are dictated through either the IRB reliance agreement or additional study specific research plans executed for the project. For more information, please see the Pitt Cede IRB Review guidance.

How is Reportable New Information submitted to the IRB?

Please refer to the IRB Researchers’ Quick Reference Guide available in PittPRO Help Center that provides detailed submission instructions (Create and submit Reportable New Information).

What does the IRB do with the Reportable New Information once it has been submitted?

The Reportable New Information will be referred to a fully convened IRB Committee if there is the possibility that the new information represents an Unanticipated Problem Involving Risk to Human Subjects or Others, Serious Non-compliance and/or Continuing Non-compliance. A detailed description of IRB Committee procedures is available in Chapter 17, Responsibilities of the IRB, of the HRP Policies and Procedures.

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updated 8/16/2024