Promptly Reportable Information

Promptly Reportable Information

Per federal regulations, institutions engaged in human subjects research are required to have written procedures in place for ensuring prompt reporting of (i) Unanticipated Problems Involving Risk to Subjects or Others, (ii) Serious or Continuing Non-compliance, and (iii) suspension or a termination of IRB approval to the IRB, appropriate institutional officials, and applicable federal agencies.

The OHRE Standard Operating Procedures (SOPs) serve to fulfill the requirements of these regulations and to protect the rights, safety, and welfare of research participants.

New Safety Information is reported through IRBIS.

Relevant Links

OHRP Guidance on Reviewing and Reporting Unanticipated Problems Involving Risks to Subjects or Others and Adverse Events (January 15, 2007)

FDA Guidance for Clinical Investigators, Sponsors, and IRBs. Adverse Event Reporting to IRBs — Improving Human Subject Protection (January 2009)

FDA Guidance for Industry and Investigators. Safety Reporting Requirements for INDs and BA/BE Studies (December 2012)

This page provides guidance to research teams completing Promptly Reportable Information (PRI) submissions in the University of North Carolina at Chapel Hill (UNC-CH) IRB Information System (IRBIS). Each section below explains what the Institutional Review Board (IRB) is looking for when reviewing your responses, based on the criteria outlined in OHRE SOP 1401. The goal is to help teams provide clear, accurate, and complete information to support effective and efficient IRB review.

IRBIS screenshot highlighting the button labeled "submit a promptly reportable information"

The PRI submission form can be found by signing into IRBIS, selecting the specific study, and then selecting the <<Submit a Promptly Reportable Information>> icon.

Brief description of PRI

This section is intended for the PI to give a title to the event so that it can be easily identified among all submissions in IRBIS related to the study. It is better to keep this title as brief as possible (e.g., 25 characters in length). In a subsequent section of the PRI submission, the PI will be able to provide a detailed description of the event (section B3).

A1) Did this event occur at a site for which a UNC-Chapel Hill IRB has direct oversight responsibility or involve a research participant at one of those sites?

UNC-Chapel Hill IRB has oversight if it is the reviewing IRB (IRB of record) for the site or participants involved. This includes:

  • Studies submitted to and approved by the UNC-CH IRB, even if the study protocol involves contacting participants remotely.
  • Sites with a UNC reliance agreement indicating UNC-CH is the IRB of record or the single IRB (sIRB), including international ones.

If another IRB has direct oversight responsibility for the study, and that IRB has determined that the event meets the definition of an Unanticipated Problem Involving Risks to Subjects or Others (UPIRSO), Serious or Continuing Noncompliance, or Suspension / Termination, the event must be reported to the UNC IRB per OHRE SOP 1401 with supporting documentation.

If ‘No’ is selected for question A1, indicating that the study relies on an external IRB, you will be prompted to respond to a question as to whether a determination has been made by a data safety monitoring board (DSMB) or other oversight committee, such as the reviewing IRB. Please indicate ‘Yes’ to this question and proceed with creating a PRI submission when the PI receives documentation of the review.

A2) Was the event unexpected in nature, severity, or frequency? (see SOP 1401)

An event is “unexpected” if it is not described as a potential research risk in the protocol, consent document, Investigator’s Brochure (IB), product labeling, package insert, or other study materials, or if it occurs with greater severity or frequency than expected. If the event was expected based on the information provided in the research protocol and related documents, it may not need to be submitted as PRI. However, investigators should still document the event and monitor any patterns or changes that might require further action.

To determine this:

  • Compare the event to what is described as potential adverse events in study documents.
  • Consider the expected natural progression of an underlying disease, disorder, or condition of the participant experiencing the event and the participant’s predisposing risk profile for the event when assessing whether an event is unexpected.
  • Use SOP 1401: Promptly Reportable Information and SOP 6001: Definitions to guide your answer.

Tip: Be specific when explaining why the event is considered unexpected. Focus on how the unfavorable occurrence in the participant was not known or recognized in any way, or at a specificity or severity not previously observed.

A3) Do you think the event was related or possibly related to this research?

Answer “Yes” if there is a reasonable possibility that the event was caused by any procedure or activity involved in the research. Events related to study procedures, screening, recruitment, consent, data collection, data transfers, or communication with participants are considered research related. Even if the event could have other causes, select “Yes” if it is reasonably possible that the research activities contributed to the issue.

Tip: Think beyond the intervention. If the issue arose during or because of research tasks (e.g., consent, surveys, coordination), it’s likely related. If the PI does not think the event was related to the research, provide an explanation. For example, the PI can assess if the event is a consequence of underlying diseases as opposed to the research or if the event is considered common in the study population.

A4) Does the event suggest that the research places subjects or others at a greater risk of harm than was previously known or recognized?

Answer “Yes” if the event introduces a new risk or increases the level of known risk in any category:

  • Physical such as discomfort, injury, pain, side effects, or impacts to a nursing child or a fetus (either through mother or father).
  • Psychological such as emotional distress, anxiety, distress, or fear.
  • Social such as loss of reputation or standing within the community, stigma, discrimination, loss of privacy, or harm to a larger group or community beyond the participants of the study.
  • Legal such as disclosure of illegal activity or negligence.
  • Economic such as unexpected costs, loss of employment or insurability, loss of professional standing or reputation, or loss of standing within the community.

Tip: If the event might make a participant reconsider participation, it likely reflects greater risk. The PI should also take into consideration any hypothetical risk. For example, if the wrong dose of a study drug is administered and the participant did not experience side effects, but there was the potential for side effects, this would be considered placing the participant at greater risk of harm even though no actual harm occurred.

A5) Does the event involve a potential (1) inappropriate sharing or disclosure of a participant’s personal identifiers and/or protected health information, (2) privacy incident, (3) security incident, or (4) breach of privacy or confidentiality?

Answer “Yes” if any identifiable participant information such as names, dates of birth, medical details, or study data was shared, accessed, or used improperly, even by mistake.

UNC-CH policy requires you to report to the IRB if the event involves any of the following:

  • Privacy incident: any loss of control, compromise, or unauthorized disclosure, acquisition, or access of Protected Health Information (PHI), which also applies in instances of inappropriate sharing or disclosure of personal identifiers and/or PHI.
  • Security incident: any attempt, successful or unsuccessful, to access, use, disclose, modify, or destroy ePHI or interfere with protective system controls.
  • Breach of privacy or confidentiality: any successful compromise of protective controls, or unauthorized acquisition, disclosure, access, or use of PHI not permitted by Health Insurance Portability and Accountability Act (HIPAA), especially if it triggers a legal obligation to notify affected individuals under state/federal law.

Tip: A security incident often involves someone outside of the study personnel attempting to access or use protected information or impact systems designed to protect that information. The characteristics of a security incident will likely involve an unauthorized person, an unauthorized purpose, includes both successful efforts and unsuccessful attempts, and intent is not required.

Tip: A breach is typically when someone outside of the study personnel is successful in accessing or using protected information.

Tip: If you are unsure whether an event meets reporting criteria, you may consult with the Office of Human Research Ethics (OHRE) compliance staff via email at [email protected] and/or the UNC-CH Institutional Privacy Office (IPO) before submitting.

Tip: The IPO is often notified of these events so that they can perform a separate assessment from the IRB to determine whether the privacy incident is reportable under applicable federal or state data privacy law. The IRB will review these types of events from a risk to human participants perspective.

A8) Is this submission regarding other Promptly Reportable Information as outlined in SOP 1401?

This question applies if the issue does not meet the criteria for UPIRSO, noncompliance, or a privacy / security breach, but is still required to be reported under SOP 1401 Section 4.3.

Answer “Yes” if the event involves:

  • An unresolved, research-related participant complaint or concern.
  • A protocol deviation made to eliminate immediate hazard to a participant without IRB approval.
  • An audit, inspection, or federal inquiry.
  • Institution, investigator, or sponsor-initiated hold or early closure as a result of safety concerns.
  • An Investigational New Drug (IND) safety report from the Sponsor that meets FDA reporting criteria under 21 CFR 312.32 (also see Safey Reporting Requirement for INDs and BA/BE Studies).
  • Incarceration of a participant who is actively participating in a research study that is not approved to involve prisoners.
  • An event or situation that triggered media attention or congressional interest.

If you answer “Yes,” additional questions will appear asking you to:

Confirm if the report is an IND safety report that meets FDA reporting criteria and provide confirmation that the Sponsor has submitted the report to the FDA.

  • Confirm if the report is an IND safety report that meets FDA reporting criteria and provide confirmation that the Sponsor has submitted the report to the FDA.
  • Describe what’s being reported
  • Indicate whether any modifications or study document updates are needed

Tip: This is a “catch-all” for other events that need IRB attention. If in doubt, refer to SOP 1401 Section 4.3 or contact OHRE compliance staff via email at [email protected] for clarification.

B1) Date of Event

Indicate the date the event occurred. This may be different than the date the investigator became aware of the event, such as in the cases of an audit report or internal review. If this is the case, then in section B3, Full Description of Event, please explain in further detail the timeline of events, including when the PI became aware of the event. Please be aware that a PRI submission should be created within 7 calendar days of the investigator becoming aware of the event as indicated in OHRE SOP 1402.

B3) Full Description of Event

Describe what happened, including relevant details about the participant(s) and study context. Your response should include:

  • What precipitated the event and the circumstances.
  • How many participants were involved or affected (if applicable). If there are references to participants, please use participant ID numbers or something similar and do not include names or any other specific personal identifiers / Protected Health Information.
  • Date each affected participant enrolled in the study .
  • Date of each participant’s last treatment or participation in the intervention.
  • Any relevant medical history that helps contextualize the event and/or explains the final outcome of the event (e.g., whether the participant recovered from the incident).

Tip: Keep the description factual and chronological. Review the content before submitting to verify the clarity of the description, keeping in mind that the reviewer is not a part of the study team and may not be as intimately familiar with the study beyond what is described in the IRB application (e.g., spell out any uncommon acronyms).

E1) Root Cause Analysis (RCA)

The root cause is the most basic cause of a problem that if eliminated, should prevent recurrence of the problem. The root cause can be identified by asking basic questions, such as, “What was the error? How did it occur? How widespread? Why did it occur?” A Root Cause Analysis (RCA) is a formal process for identifying and documenting the root cause and the downstream effects.

Your response should describe:

  • The methods used to complete the Root Cause Analysis (e.g., brainstorming, the 5 Whys, flowcharting, fishbone diagram).
  • What caused the event (the basic error, failure, or issue).
  • Why it occurred.
  • How widespread the issue was (isolated, recurring, systemic).
  • Who participated in the root cause analysis.

Tip: Do not just describe what happened and repeat previous sections, focus on why it happened.

Tip: Clearly state the RCA method used, even if informal (e.g., brainstorming, 5 Whys method).

Tip: For more information about completing a formal RCS, contact the Office of Clinical Trials.

E2) Corrective and Preventive Actions (CAPA)

Once the root cause has been identified, the next step is to develop a CAPA Plan to eliminate the root cause. A PRI always requires a CAPA Plan. Corrective actions are those taken to address a problem that has already occurred and mitigate risk to the impacted participant(s). Preventive actions are those taken to eliminate the root cause of a potential problem and ensure the event will not occur again in the future. 

Consistent with Quality Improvement (QI) methodology, it is expected that CAPA Plans are thoroughly documented, implemented, and that their effectiveness is evaluated over time, as appropriate.

Your CAPA Plan should describe:

  • The actions taken or planned to resolve the issue (both corrective and preventive).
  • The rationale for actions taken or proposed based on the root cause and participant status.
  • When each action was completed or is planned.
  • The person(s) responsible for each action.
  • The proposed plan for how the study team will communicate with participants (e.g., reconsent or notification).

Tip: Be sure to incorporate all steps in the final CAPA plan that received IRB approval, including any additional steps described in PI responses to stipulations.

Tip: Use a clear structure so that actions, dates, and responsibilities are easy to follow.

Tip: Be specific, avoid general statements like “staff were retrained” without explaining what was covered or improved.

Tip: If reconsent or participant notification is involved, explain who will be notified, how, when, and why.

E3) Plan for Effectiveness Check

The Principal Investigator (PI) is responsible for assigning personnel who will assess the effectiveness of the corrective and/or preventive actions described in the CAPA Plan. The adequacy of the actions taken is a key focus of the IRB, Health and Human Services (HHS) Office of Human Research Protections (OHRP), and Food and Drug Administration (FDA). A CAPA Plan is considered effective if, after implementation, the root cause has been eliminated, risk to participant(s) was mitigated, and the actions have ensured that the event will not happen again.

Your plan should include:

  • How effectiveness will be measured.
  • When the assessment will be conducted.
  • By whom the assessment will be conducted.
  • What action will be taken if the plan is found to be ineffective.

Tip: If the event happens again, the IRB will be looking at whether the plan for effectiveness check was actually implemented and what was the result of the review of the approved CAPA plan as way to determine the root cause of the Continuing Noncompliance.

Tip: Effectiveness should be assessed using clear criteria tied to the issue that occurred.

Tip: Be sure to state who is responsible for the evaluation and when it will take place.

Frequently Asked Questions about PRIs

What is a PRI (Promptly Reportable Information)?

The Health and Human Services (HHS) and Food and Drug Administration (FDA) regulations (45 CFR 46.108(a)(4), 21 CFR 56.108(b)) require that institutions establish and follow written procedures for:  

Ensuring prompt reporting to the Institutional Review Board (IRB), appropriate institutional officials, the department or agency head, the HHS Office for Human Research Protections (OHRP), and the FDA of:  

  1. Any unanticipated problems involving risks to subjects or others (UPIRSO) 
  2. Any Serious or Continuing Noncompliance 
  3. Any Suspension or Termination of IRB approval 

UNC uses the term PRI for information that may represent an UPIRSO, Serious Noncompliance, or Continuing Noncompliance and is promptly reportable to the IRB.  

UNC written procedures for prompt reporting (reporting of PRI) are described in SOP 1401, Promptly Reportable Information and SOP 1402, IRB Review of Promptly Reportable Information.

  • SOP 1401 provides definitions of UPIRSO, Serious Noncompliance, or Continuing Noncompliance and examples. 
  • SOP 1402 describes the IRB’s procedures for reviewing PRI. Back to top

What is the reporting timeframe for a PRI? 

PRI is promptly reportable to the OHRE within 7 calendar days of the investigator becoming aware of the information. Back to top 

What are the Investigator’s responsibilities when a potential PRI occurs?  

  1. Take necessary steps to ensure that the participant receives appropriate care for the adverse event (AE).
  2. Make immediate changes, when appropriate, to the protocol to eliminate immediate hazards to other participants.
  3. Analyze the event to determine if it meets the criteria for an UPRISO, and if so, report promptly to the IRB in IRBIS (within 7 calendar days). 
  4. Regardless of whether the investigator decides if the event meets the criteria for an UPIRSO, report the AE to a monitoring entity (i.e., Sponsor, coordinating center, independent medical monitor, or data safety and monitoring board) if required in the protocol or by institutional policy.
  5. If an external monitoring agency determines that an event is an UPRISO, then inform the IRB.
  6. Review all external AE to identify if they meet the UPRISO criteria. In the PRI, explain why the AE is an UPRISO and describe any protocol changes or other corrective actions. Back to top

What should I do if I am still gathering information about an incident for the PRI report?  

The 7-calendar-day PRI reporting requirement may be met by submitting a preliminary PRI report and following up with a complete report once the information is available. Back to top

When is an Adverse Event (AE) reportable as PRI for a study that UNC is the IRB of record?  

Only AEs that are determined to meet the criteria for an UPIRSO are promptly reportable as PRI. An UPIRSO is any incident, experience, or outcome that meets all the following criteria: 

i. is unexpected (in terms of nature, severity, or frequency) given: 

  1. the research procedures that are described in the protocol-related documents, such as the IRB-approved research protocol, investigator brochure and informed consent document; and
  2.  the characteristics of the participant population being studied;  

ii. is related or possibly related to a participant’s participation in the research; and  

iii. is serious or suggests that the research places participants or others at a greater risk of harm (including physical, psychological, economic, or social harm) than was previously known or recognized. 

The assessment of unexpectedness and relatedness should be done by the PI. The IRB will also ask for the Sponsor’s assessment of the event (if the investigator is not the Sponsor), but the PRI should be submitted based on the immediate assessment of the PI.   

AEs that are UPIRSOs are reportable to the IRB as PRI within 7 calendar days of the study team/PI learning of the event. Back to top

When is an AE considered unexpected?  

The HHS OHRP definition of an unexpected AE: “Any AE occurring in one or more participants participating in a research protocol, the nature, severity, or frequency of which is not consistent with either: 

  1. 4.6.1. the known or foreseeable risk of AE associated with the procedures involved in the research that are described in (a) the protocol related documents, such as the IRB-approved research protocol, any applicable investigator brochure (IB), and the current IRB-approved consent document, and (b) other relevant sources of information, such as product labeling and package inserts; or 
  2. 4.6.2. the expected natural progression of an underlying disease, disorder, or condition of the participant(s) experiencing the AE and the participant’s predisposing risk profile for the AE.” 

In other words, an AE or suspected AE for the investigational product (drug, biologic, device) being studied (not a similar product or product in the same family, but the product being studied) is “unexpected” if:

  1. The risk is not listed in any of the protocol-related documents (Investigator’s Brochure or IB, consent documentation, and/or protocol).
  2. The risk occurs at a specificity or a severity that has not been observed.
  3. An IB is not required or available when the risk is observed.
  4. The risk is not consistent with the risk information described in the protocol and other related documents (i.e., investigational plan, IRB application, or consent documents)

The determination of whether a particular AE is unexpected by virtue of an unexpected higher frequency of occurrences requires an analysis of appropriate data on all participants. The UNC IRB requires reporting of any clinically important increases in frequency of known serious adverse events. The decision to report is a matter of judgement based on factors such as the seriousness of the AE, the population being studied and the magnitude of the observed increase. Back to top

Do all AEs that meet the criteria for reporting in an investigational new drug (IND) Safety Report to the FDA also have to be reported to the IRB as PRI?  

Generally, an AE that requires an IND Safety Report Suspected Unexpected Serious Adverse Reaction (SUSAR) to the FDA is also reportable to the UNC IRB as PRI (UPIRSO). However, as there are differences in the FDA’s definition of an AE that requires IND Safety Reporting and UNC’s definition of a reportable AE there are exceptions. 

The FDA considers an AE unexpected if the AE is not listed in the Investigator’s Brochure (IB) or is not listed at the specificity or severity that has been observed; or if an IB is not required or available; or the AE is not consistent with the risk information described in the general investigational plan or elsewhere in the current application. UNC IRB considers an AE unexpected if the nature, severity, or frequency is not consistent with the known or foreseeable risk of the AE that are described in the approved research documents (protocol, IB, or consent document).  

As such, an AE that meets the criteria for reporting in an IND Safety Report because it is considered unexpected per the IB may not be reportable to the UNC IRB as a PRI if the AE has already been observed with the investigational product and is described in the consent documentation, provided the frequency and severity of the event has not changed. 

Investigators should review the PRI reporting requirements prior to reporting an AE to ensure that it is reportable per UNC PRI reporting requirements. Back to top

Is PRI reportable to the UNC IRB when UNC is ceding review to another IRB?  

The information is reportable to the IRB of record by their prompt reporting policies. If the IRB of record makes a determination of an UPIRSO, Serious Noncompliance, Continuing Noncompliance, Suspension or Termination, the information is reportable to the UNC IRB as PRI. The PRI report must include a copy of the determination letter issued by the IRB of record, a copy of the report submitted to the IRB of record that describes the event, and a copy of the IRB approved CAPA Plan. Back to top 

Are all protocol deviations/noncompliance reportable as PRI? 

Protocol deviations or noncompliance that do not suggest that the research placed participants or others at increased risk or adversely affects the rights or welfare of participants should be documented with a CAPA Plan in the research record. This documentation is subject to review by the OHRE or other agents of the UNC Human Research Protection Program (HRPP). Back to top

When and how should participants be provided with new findings identified in the course of the study? 

The UNC IRB requires that research participants receive additional information about changes or findings that may affect participants AND/OR their willingness to continue participation in the research.  

HHS regulations 45 CFR 46.116(c)(5) and FDA regulations 21 CFR 50.25(b)(5) both indicate that any significant new findings developed during the course of the research that may relate to the participant’s willingness to continue participation will be provided to the participant. 

The Secretary’s Advisory Committee on Human Research Protections (SACHRP) provides examples of instances where changes to the study may affect a participant’s willingness to continue and therefore should be disclosed. They include: 1) identification of new research-related risks, 2) increase in the frequency or magnitude of previously described risks, 3) unanticipated problem that exposes participants to new risks, such as a data breach, 4) decrease in expected benefits to participation, 5) a change to the research that results in increased burden/discomfort, 6) availability of new alternative therapies, and 7) the impact of participation on alternative therapies. 

The investigator should consider the following in developing a notification / reconsent plan: 

  • What is the change that requires communication? 
  • Who needs to be notified or reconsented? (e.g., participants actively undergoing research intervention, all participants, subset of participants) 
  • When must notification or reconsent occur to protect participant safety and rights (e.g., immediate, at next study visit, within a specified time, varies depending on the affected participants)?   
  • How should notification or reconsent be implemented? (e.g., phone, email, letter, email / letter with phone follow-up, in-person visit, updated consent document or consent addendum).  
  • Should participants be notified or reconsented? Generally, participants affected by the new information, who are active, are reconsented whereas participants, who have completed intervention, and study visits, are notified. Back to top

Median Turnaround Times for Rely On Study Reviews (Jan 2025-July 2025)

Rely On Review: 63 days IRB Review: 8 days PI Review: 55 days

Rely On Review: 63 days
IRB Court: 8 days
PI Court: 55 days

Updated 8/05/2025