Adverse Event Reporting

Adverse Event Definitions

An adverse event (AE) is any untoward medical occurrence in a clinical trial participant, whether or not it is related to the study drug. This broad definition captures all negative health events during the trial period. An adverse drug reaction (ADR) is a subset where a causal relationship with the drug is at least reasonably possible.

A serious adverse event (SAE) meets any of these criteria: death, life-threatening condition, hospitalization or prolongation of hospitalization, persistent or significant disability, congenital anomaly, or any event requiring medical intervention to prevent one of these outcomes.

Reporting Timelines

Investigator to Sponsor

Investigators must report all SAEs to the sponsor within 24 hours of awareness. Non-serious AEs are reported according to the protocol-defined schedule, typically at each study visit.

Sponsor to Regulatory Authority

The sponsor must report unexpected and related fatal or life-threatening SAEs to the FDA within 7 calendar days (with a follow-up within 8 additional days). All other unexpected and related SAEs must be reported within 15 calendar days. Annual safety reports (Development Safety Update Reports, DSURs) provide comprehensive safety summaries.

Sponsor to Investigators and IRBs

Sponsors must notify all participating investigators and their Institutional Review Boards of any safety information that could affect participant safety or willingness to continue participation.

Causality Assessment

Investigators assess the relationship between the adverse event and the study drug using categories:

• Unrelated: Clear alternative explanation; no temporal relationship
• Unlikely: Alternative explanation more likely; weak temporal relationship
• Possible: Temporal relationship exists; alternative explanation equally likely
• Probable: Strong temporal relationship; no obvious alternative
• Definite: Clear temporal relationship confirmed by rechallenge or specific testing

Severity Grading

The Common Terminology Criteria for Adverse Events (CTCAE) provides a standardized five-grade system: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening), Grade 5 (death). Severity and seriousness are independent -- a Grade 1 AE (mild rash) can be an SAE if it requires hospitalization.

MedDRA Coding

All adverse events are coded using the Medical Dictionary for Regulatory Activities (MedDRA), which provides standardized terminology across a five-level hierarchy from System Organ Class down to Lowest Level Term. This enables consistent safety data aggregation across trials and sponsors.

Key Takeaways

• All adverse events are captured, regardless of suspected relationship to the drug
• Serious adverse events must be reported to sponsors within 24 hours
• Fatal or life-threatening SAEs require regulatory notification within 7 days
• Causality assessment ranges from unrelated to definite
• Standardized coding (MedDRA) and grading (CTCAE) enable cross-trial comparison