EudraVigilance

The foundational data unit of EudraVigilance. An ICSR is a structured report detailing a single suspected adverse reaction in a patient exposed to a medicinal product. It contains:

• Patient demographics (age, sex, medical history)
• Suspect and concomitant drugs (dosage, route, dates)
• Adverse event descriptions coded to MedDRA
• Reporter assessment of causality EudraVigilance processes millions of ICSRs, using the E2B (R3) XML standard for electronic transmission between MAHs and NCAs.

The Medical Dictionary for Regulatory Activities is the clinically validated international terminology used to code adverse event information in EudraVigilance. Its hierarchical structure includes:

• System Organ Class (SOC) — highest level grouping
• High-Level Group Terms (HLGT)
• High-Level Terms (HLT)
• Preferred Terms (PT) — the standard unit for coding
• Lowest Level Terms (LLT) — most granular synonyms Every ICSR submitted to EudraVigilance must have adverse reactions coded to MedDRA PTs, enabling consistent signal detection across languages and regions.

The core quantitative methodology powering EudraVigilance's signal detection module. It identifies drug-event combinations reported more frequently than expected against a background reference set. Key measures include:

• Proportional Reporting Ratio (PRR) — a frequentist measure comparing observed vs. expected reporting rates
• Reporting Odds Ratio (ROR) — the odds of an event being reported for a specific drug vs. all others
• Empirical Bayes Geometric Mean (EBGM) — a Bayesian approach using shrinkage to adjust for low-count combinations and reduce false-positive signals EudraVigilance Data Analysis System (EVDAS) applies these methods systematically across the entire database.

The World Health Organization's global ICSR database, maintained by the Uppsala Monitoring Centre (UMC). While EudraVigilance covers the European Economic Area, VigiBase aggregates reports from over 170 member countries, making it the world's largest pharmacovigilance repository. Key distinctions:

• Contains over 30 million ICSRs
• Uses WHODrug Global for medicinal product coding
• Provides VigiLyze for statistical signal detection
• Complements EudraVigilance data in global safety assessments Cross-database analysis between EudraVigilance and VigiBase strengthens signal validation for globally marketed products.

The rigorous process following initial detection in EudraVigilance to confirm whether a new causal association or a new aspect of a known association exists. Steps include:

• Triaging detected signals by clinical impact and public health significance
• Literature review for corroborating evidence
• Case-level review of individual ICSRs for causality assessment
• Dechallenge/rechallenge analysis — did the event resolve upon withdrawal and recur upon re-administration?
• Confounding by indication assessment — is the underlying disease, not the drug, the true cause? Only validated signals proceed to the EMA's Pharmacovigilance Risk Assessment Committee (PRAC) for regulatory action.

The FDA Adverse Event Reporting System is the U.S. counterpart to EudraVigilance. This publicly accessible database contains millions of spontaneous reports submitted by healthcare professionals, consumers, and manufacturers. Key parallels and differences:

• Both use E2B (R3) standards for electronic submission
• FAERS uses MedDRA for event coding but does not mandate the same level of structured narrative
• FAERS data is released quarterly as raw ASCII/XML files for public download
• EudraVigilance provides more controlled access through EVDAS with built-in analytics Cross-referencing FAERS and EudraVigilance signals is standard practice for global pharmacovigilance teams.