The Problem Before MedDRA
Before the implementation of a global standard, pharmacovigilance professionals relied on non-standardized, free-text reports of adverse events from sources like healthcare professionals and clinical trial participants. This 'natural language' data often contained inconsistencies, synonyms, and abbreviations, making it incredibly difficult to aggregate and analyze safety data across different regions or drug products. This lack of uniformity hampered effective signal detection and global regulatory communication, potentially delaying a timely response to emerging safety issues.
What is MedDRA in PV?
MedDRA (Medical Dictionary for Regulatory Activities) is a comprehensive, clinically validated, and standardized medical terminology developed by the International Council for Harmonisation (ICH). In pharmacovigilance (PV), MedDRA provides a universal language for describing and classifying adverse events (AEs), adverse drug reactions (ADRs), patient medical history, and other safety-related medical information. By mapping raw, reported terms to a single, internationally agreed-upon code, MedDRA ensures consistency, comparability, and clarity in the data, which is fundamental for effective drug safety monitoring.
The Multi-Level MedDRA Hierarchy
MedDRA’s power lies in its five-level hierarchical structure, which allows for precise coding at the most detailed level while enabling broader analysis and retrieval at higher levels.
- Lowest Level Term (LLT): The most granular level, containing reported verbatim terms, including synonyms, abbreviations, and different lexical variations. There are over 80,000 LLTs. For example, a reported term might be 'feeling queasy'.
- Preferred Term (PT): A distinct medical concept or single descriptor representing a group of LLTs with the same meaning. All LLTs under a PT represent the same concept. For example, 'feeling queasy', 'sick to stomach', and 'nausea' might all map to the single PT 'Nausea'.
- High-Level Term (HLT): A group of clinically or anatomically related PTs. For instance, the PTs 'Nausea', 'Vomiting', and 'Diarrhoea' might be grouped under the HLT 'Gastrointestinal signs and symptoms'.
- High-Level Group Term (HLGT): A higher-level grouping of HLTs. The HLT 'Gastrointestinal signs and symptoms' could fall under the HLGT 'Gastrointestinal disorders, signs and symptoms'.
- System Organ Class (SOC): The highest, broadest level of the hierarchy, grouping terms by organ system, etiology, or purpose. Examples include 'Gastrointestinal disorders' or 'Nervous system disorders'.
The Importance of MedDRA's Multi-Axiality
To accurately reflect the complexity of a medical event, MedDRA incorporates multi-axiality. This means that a single Preferred Term (PT) can be represented in more than one System Organ Class (SOC). For example, a PT like 'Acute pancreatitis' could be linked to both the 'Gastrointestinal disorders' SOC and the 'Hepatobiliary disorders' SOC, as the clinical event can affect both systems. This feature allows for thorough analysis from multiple clinical perspectives, which is crucial for comprehensive safety signal detection.
MedDRA in the Pharmacovigilance Workflow
MedDRA is integrated throughout the entire pharmacovigilance process, providing a structured approach to safety data management.
- Case Intake and Processing: Raw adverse event reports from various sources are received and validated.
- Medical Coding: Trained personnel use MedDRA guidelines and browsers to code the verbatim terms in the report to the most accurate and specific LLT.
- Database Integration: The coded data is stored in safety databases, such as Argus or ArisG, enabling standardized retrieval and analysis.
- Signal Detection: Standardised MedDRA Queries (SMQs), predefined sets of terms related to specific medical conditions, are used to efficiently search and analyze large datasets for potential safety signals.
- Regulatory Reporting: The coded data is used to generate regulatory submissions, such as Individual Case Safety Reports (ICSRs) and Periodic Safety Update Reports (PSURs), ensuring a consistent format for health authorities like the FDA and EMA.
MedDRA vs. Older Terminologies: A Comparison
Before MedDRA, several terminologies existed, such as the WHO Adverse Reaction Terminology (WHO-ART), which MedDRA largely replaced as the global standard around 2008. A comparison highlights MedDRA's enhanced capabilities:
| Feature | MedDRA | WHO-ART (Legacy) |
|---|---|---|
| Development | Developed by ICH through international collaboration | Developed by Uppsala Monitoring Centre (UMC) |
| Current Status | Current global regulatory standard | Legacy tool, no longer actively maintained |
| Size | More than 80,000 terms across five levels | ~6,000 terms across four levels |
| Structure | Five-level hierarchy with multi-axiality | Four-level hierarchy |
| Specificity | Rich and highly specific terminology | Less specific and comprehensive |
| Updates | Regular, semi-annual updates | No longer actively updated |
| Key Feature | Standardised MedDRA Queries (SMQs) for signal detection | No equivalent feature for standardized queries |
Conclusion
In pharmacovigilance, MedDRA is far more than just a dictionary; it is the essential framework that transforms raw, unstructured adverse event reports into standardized, analyzable data. By providing a common, highly specific, and globally accepted language, MedDRA enables regulatory authorities, pharmaceutical companies, and healthcare professionals to effectively communicate, analyze, and monitor drug safety information. Its hierarchical structure, combined with features like multi-axiality and SMQs, empowers robust signal detection and regulatory compliance, ultimately contributing to the enhanced safety of medical products for patients worldwide. The regular updates and structured maintenance by the MSSO ensure MedDRA remains a relevant and critical tool in an ever-evolving medical landscape. For anyone working with adverse event reporting, a deep understanding of MedDRA is a prerequisite for ensuring data quality and compliance. For more information, visit the official MedDRA website.
