Why this matters
MedDRA (Medical Dictionary for Regulatory Activities, an ICH standard) is the dictionary for coding adverse events (AEs), medical history, and other medical terms; medications use a separate drug dictionary such as WHODrug. Consistent, defensible coding is the backbone of safety and efficacy summaries. If you misunderstand what each MedDRA level means or how multi‑axiality works, you can mis‑group events, inflate or hide signals, and trigger rework right before submission. Get the hierarchy and the primary SOC rules right, and you’ll produce stable tables that clinical, safety, and regulators can trust.
Core concepts & definitions
Plain‑language map (most specific → least specific):
LLT — Lowest Level Term The exact phrase you code to (closest to the site’s verbatim). LLTs include synonyms, spelling variants, and lay phrases. Each LLT belongs to exactly one PT (every PT is also an LLT). Code only to current LLTs. Think: the specific wording that matches the verbatim best.
PT — Preferred Term A single medical concept representing many LLTs. Tabulations and analysis typically use PT and SOC. Think: the clinical concept for the LLT.
HLT — High Level Term A grouping of related PTs that share features (e.g., similar pathophysiology, location, or mechanism). Think: a neighborhood of closely related PTs.
HLGT — High Level Group Term A broader grouping made of multiple HLTs. Think: the whole district.
SOC — System Organ Class The top level. Broadest grouping by body system, etiology, or purpose (e.g., “Cardiac disorders,” “Investigations”). Think: the entire city map section.
Multi‑axiality (the essential rule):
- Many PTs belong to more than one SOC to reflect different ways to look at the same concept (e.g., by body system vs. etiology).
- For consistency in standard summary tables, one SOC is designated as the primary SOC for each PT. MedDRA assigns it (not the sponsor or the coder); the PT’s other SOCs are secondary SOCs.
- As a rule, congenital, neoplasm, and infection terms have their own SOC as primary (e.g., Infections and infestations). Terms in Investigations, Surgical and medical procedures, and Social circumstances are not multi‑axial.
- You can roll‑up to a different (non‑primary) SOC for a justified analysis (e.g., a renal‑focused review), but you must document that rule.
Versioning:
- MedDRA is released twice a year (March x.0, September x.1). New versions can add terms, move terms, or change relationships (including a PT’s primary SOC). Terms are never deleted: an outdated LLT is flagged non‑current and not used for new coding.
- When your study or pooling strategy changes dictionary version, you may need recoding and impact assessment. Always store the dictionary version with your data.
The process, step‑by‑step
Capture the verbatim (uncoached). Let sites describe the event in their own words. Avoid leading them toward a term.
Read the verbatim as reported; never edit it. The verbatim is site data: the coder never changes it. The coder may read through an obvious typo or an unambiguous abbreviation (e.g., “HTN” → hypertension) when choosing a term. If the meaning is unclear, data management (DM) queries the site rather than guessing; only the site corrects its entry.
Code to an LLT that best matches the verbatim’s meaning.
- Choose the LLT that matches the verbatim: as specific as the report, never more.
- Do not split a single clinical concept into multiple codes unless clearly separate events are described.
- Record which LLT you chose, not only the PT.
Store key fields for traceability. At minimum on each coded record:
- PT code and text (the analysis concept)
- LLT used (what you actually selected)
- MedDRA version (e.g., 27.0) Also store the LLT code. HLT/HLGT/SOC are optional in the coding tool, but submission datasets (CDISC SDTM) normally carry the full primary path with codes.
Roll up for analysis using the primary SOC. Standard “TEAEs by SOC and PT” tables (TEAE = treatment‑emergent adverse event) should use primary SOC to avoid double‑counting across SOCs. Within the table, a participant with several events is counted once per PT and once per SOC.
Quality control (QC).
- Use coder conventions (see below) and periodic dual‑coding/QC sampling.
- Trend common problem verbatims and update conventions.
Govern changes and versions.
- If you upgrade MedDRA mid‑study or for integrated summaries, impact‑assess, recode consistently, and document. The impact assessment checks the terms the study has used: LLTs now non‑current, LLTs moved to another PT, and PTs whose primary SOC changed. Recode affected records under change control with an audit trail; recoding never alters the verbatim. One analysis uses a single MedDRA version.
- Freeze versions for key milestones (e.g., database lock) and annotate outputs with the version used.
Coder conventions to keep teams aligned
- Start from the ICH‑endorsed MedDRA Term Selection: Points to Consider guide.
- How to handle combined concepts (“nausea with vomiting” vs separate events).
- How to interpret abbreviations and site slang (without editing the verbatim).
- Rule‑of‑three words for searching (carry three salient words from the verbatim when searching); a search habit, not a MedDRA rule.
- When to query the site for clarification vs. coding as “unspecified.”
What good looks like
- Every coded record carries PT, LLT, and MedDRA version. Your tabulation layer also knows the primary SOC used.
- Coder conventions are published, versioned, and referenced in QC.
- Primary SOC is used for standard tables; any alternative roll‑up is explicitly justified in the Statistical Analysis Plan (SAP) or a programming specification.
- Version upgrades are handled through a formal impact assessment and controlled recoding (with a change log and before/after counts).
Worked examples
These examples are self‑contained. They illustrate the hierarchy, primary SOC usage, and documentation you should retain.
Example 1 — Cardiovascular AE from a verbatim
- Verbatim: “fast heartbeat episodes”
- Coding: Choose LLT that matches the clinical concept; this maps to PT Tachycardia.
- Roll‑up: PT Tachycardia → HLT Rate and rhythm disorders NEC (NEC = not elsewhere classified) → HLGT Cardiac arrhythmias → SOC Cardiac disorders (primary).
- Analysis: In “TEAEs by SOC and PT,” count under Cardiac disorders (primary).
- Traceability you keep: LLT chosen, PT code/text, MedDRA version (e.g., 27.0).
Example 2 — Lab abnormality vs. clinical diagnosis
Scenario A (lab finding): Verbatim “ALT increased.”
- Coding: LLT maps to PT Alanine aminotransferase increased.
- Roll‑up: This PT is treated as a lab finding and appears under SOC Investigations for standard tables. Investigations terms are not multi‑axial, so it has no link to Hepatobiliary disorders.
- Analysis: Count under Investigations in TEAE by SOC/PT.
Scenario B (clinical condition): Verbatim “toxic hepatitis.”
- Coding: LLT maps to PT Hepatitis toxic.
- Roll‑up: Appears under SOC Hepatobiliary disorders for standard tables.
- Takeaway: Similar real‑world signal, different PTs and SOCs depending on whether the site reported a test result vs a diagnosis. A hepatic review therefore needs a prespecified grouping across SOCs, such as a Standardised MedDRA Query (SMQ).
Example 3 — Infection illustrating multi‑axiality
- Verbatim: “urinary tract infection.”
- Coding: LLT → PT Urinary tract infection.
- Roll‑up: For standard tables, PT counts under SOC Infections and infestations (its primary SOC).
- Note on multi‑axiality: The PT is also linked to SOC Renal and urinary disorders as a secondary SOC; infection terms have Infections and infestations as primary. You still tabulate by the primary SOC unless your analysis plan specifies otherwise (e.g., a renal‑focused review that groups UTIs with renal disorders, documented and consistently applied).
Pitfalls & misconceptions
“HLGT is more specific than HLT.” Incorrect. Specificity decreases as you go LLT → PT → HLT → HLGT → SOC.
“MedDRA is single‑axial.” Incorrect. Many PTs have multiple SOC links. Use the primary SOC for standard summaries to avoid double‑counting.
“Any roll‑up is fine if it looks right.” Risky. Unless justified and documented, use primary SOC. Alternative roll‑ups must be prespecified.
“Dictionary version doesn’t matter if PT stayed the same.” Risky. Relationships and primary SOC assignments can change across versions. Always store and display the version used.
“Procedures are AEs.” Incorrect. Procedures (e.g., “appendectomy”) are coded in the SOC Surgical and medical procedures. The adverse event is the condition (e.g., “appendicitis”), not the treatment performed.
Practice in the wild (checklist)
- Each coded record contains PT code/text, LLT used, and MedDRA version.
- Standard TEAE tables use primary SOC; any deviation is documented in SAP/specs.
- Coder conventions exist, are versioned, and are applied in QC sampling.
- Ambiguous verbatims trigger queries, not guesses.
- For pooling (integrated summaries of safety and efficacy, ISS/ISE), a target MedDRA version is chosen and recoding is planned and logged.
- Outputs (tables/listings/figures) state the MedDRA version.
Key points to remember
- Hierarchy (most specific → least): LLT → PT → HLT → HLGT → SOC.
- Multi‑axiality: A PT can belong to multiple SOCs; one primary SOC is designated to keep summaries consistent.
- Primary SOC in tables: Standard “TEAEs by SOC and PT” must use the primary SOC to avoid double‑counting; alternative roll‑ups are allowed only when prespecified and documented (e.g., in the SAP/programming specs).
- Traceability on every record: Retain the LLT selected, PT code/text, and MedDRA version (plus the LLT code; HLT/HLGT/SOC are optional in the coding tool but normally carried in submission datasets) and carry this lineage into outputs. The site’s verbatim is never edited by the coder or DM.
- Lab finding vs diagnosis: Test‑result PTs (e.g., Alanine aminotransferase increased) usually roll to Investigations; clinical diagnoses (e.g., Hepatitis toxic) roll to disease SOCs such as Hepatobiliary disorders.
- Version governance: When MedDRA changes, perform an impact assessment, recode consistently, log changes, and annotate outputs with the version; freeze the version at key milestones (e.g., lock).
- Common trap to avoid: HLGT is broader than HLT—specificity decreases LLT → PT → HLT → HLGT → SOC.