Unanticipated Problems and Reportable New Information

1. Purpose

This SOP describes how [SITE NAME] identifies, assesses and reports to the IRB unanticipated problems involving risks to participants or others, and other information the IRB requires investigators to report promptly (commonly called reportable new information).

2. Scope

This SOP applies to all trials overseen by an IRB at [SITE NAME], whether a central IRB ([CENTRAL IRB NAME]) or another IRB of record. It covers events, findings and information from any source: site observations, monitoring, sponsor communications, audits, inspections, complaints and privacy incidents.

Out of scope: investigator-to-sponsor SAE reporting (SOP-501), routine IRB submissions such as amendments and continuing review (SOP-203), and detailed procedures for deviations (SOP-308), privacy incidents (SOP-400), audits and inspections (SOP-701, SOP-702), and misconduct (SOP-704). Those SOPs point here for the IRB report.

The IRB's own written policy defines what to report and when. Follow the IRB's policy, and the protocol or sponsor requirement, where it is stricter than or more specific than this SOP. Where this SOP and the IRB policy differ, the IRB policy governs IRB reporting.

3. Responsibilities

4. Definitions

5. Procedure

5.1 Know the IRB's policy

• the IRB's reportable categories
• the reporting window and whether it counts calendar or business days
• the submission route (IRB portal form name)
• any events the IRB states it does not want reported

5.2 Regulatory basis

• UADE: to sponsor and IRB as soon as possible, no later than 10 working days after first learning of it ((a)(1))
• emergency deviation from the investigational plan to protect the life or physical well-being of a participant: to sponsor and IRB as soon as possible, no later than 5 working days after the emergency ((a)(4))
• use of a device without informed consent: to sponsor and IRB within 5 working days after the use ((a)(5))
• withdrawal of IRB approval: to the sponsor within 5 working days ((a)(2))

• IND safety reports received from the sponsor describe UPs, and the investigator must submit them to the IRB (21 CFR 312.66). Where the sponsor submits them to the IRB on the investigator's behalf and the investigator has confirmation that it did, FDA does not expect a duplicate; the arrangement is documented (SOP-501 5.10.4).
• In IND-exempt BA/BE studies, any SAE is a UP that must be reported to the IRB.
• Events that do not meet IND safety reporting criteria may still be UPs that must be reported. They may occur at the participant, site or study level, for example serious and unexpected AEs before IP administration, during a washout period or attributable to a screening procedure, medication errors (such as a wrong dose or contaminated study medication), breaches of privacy or confidentiality, and untimely destruction of study records.
• The IRB's written procedures may require other events in addition.

5.3 Categories of reportable new information

• information indicating a new or increased risk, or a UP, including AEs that are unexpected and related or possibly related and that suggest greater risk
• IND safety reports, unless the sponsor submits them on the investigator's behalf (5.2.4), and other sponsor safety information (SUSAR line listings, DSMB reports) that requires a change to the protocol or consent form, or that the IRB policy otherwise requires
• UADEs
• protocol deviations that harmed a participant or placed a participant at increased risk of harm, including monitoring findings that materially affect participant safety
• changes made without prior IRB approval to eliminate an apparent immediate hazard to a participant
• allegations or findings of noncompliance that may be serious or continuing, and any other noncompliance the IRB's policy lists
• audits, inspections or inquiries by a federal agency, and written reports from those agencies (for example, FDA Form 483)
• breaches of confidentiality or loss of participant data
• participant complaints that indicate unexpected risk or that the site cannot resolve
• incarceration of a participant in a study not approved for prisoner involvement
• premature suspension or termination of the study by the sponsor, investigator or site
• state medical board or licensing actions against an investigator
• any other information the sponsor or protocol requires to be reported promptly to the IRB

5.4 Identifying potentially reportable information

5.5 Assessment and PI determination

• Is it unexpected, given the IRB-approved protocol, consent form, IB and the characteristics of the population?
• Is it related or possibly related to participation in the research (IP or study procedures)?
• Does it suggest that participants or others are at greater risk of harm than previously known?

5.6 Immediate protective actions

5.7 Sponsor coordination

5.8 Submission to the IRB

• a factual description of the event or information and the date of awareness
• the PI's assessment and the basis for it
• actions taken or planned (including any change to protocol, consent or procedures, and whether participants need to be told)
• whether the sponsor has been informed

5.9 After submission

6. Related Forms and SOPs

• F-502-01 Reportable New Information Assessment
• F-308-01 Protocol Deviation Log
• F-400-01 Privacy Incident Report
• F-703-01 CAPA Record
• SOP-203 IRB Submissions, Approval and Continuing Oversight
• SOP-204 Essential Documents and the Investigator Site File
• SOP-301 Informed Consent Process and Documentation
• SOP-308 Protocol Deviations and Noncompliance
• SOP-400 Participant Privacy and HIPAA in Research
• SOP-500 Adverse Event Identification, Assessment and Recording
• SOP-501 Serious Adverse Event and Expedited Safety Reporting
• SOP-600 Sponsor Monitoring Visits
• SOP-701 Sponsor and IRB Audits
• SOP-702 FDA Inspections and Remote Regulatory Assessments
• SOP-703 Corrective and Preventive Action (CAPA)
• SOP-704 Research Misconduct and Fraud Reporting
• SOP-903 Network Oversight of Member Sites (Metrics, Central QA, Escalation) (Model N only)
• SOP-905 Network Data, Systems, Privacy and Records Across Sites (Model N only)
• Appendix B Central and Site Responsibility Matrix (Model N only)

7. References