MedDRA is the internationally harmonized medical terminology for regulatory activities in the field of human medicinal products. It serves to uniformly code reported medical information and subsequently analyze it at different levels. In clinical trials, it is particularly relevant for adverse events, medical history, indications and safety analyses.
Structure and coding
The MedDRA hierarchy comprises five levels, from very specific to very general: Lowest Level Term, Preferred Term, High Level Term, High Level Group Term and System Organ Class. A Lowest Level Term, LLT for short, represents the reported phrasing as precisely as possible and is assigned to exactly one Preferred Term, PT for short. PTs each designate a single medical concept. HLTs and HLGTs bundle related PTs; the highest level, the System Organ Class or SOC, groups concepts by etiology, manifestation site or purpose.
Coding does not translate a free, reported statement into a diagnosis that is not stated there. According to the MedDRA guidance, the current LLT must be selected that most accurately reflects the verbatim reported information; subsequently, the overarching hierarchy must be checked for plausibility. Non-current LLTs are retained for historical purposes but should not be used for new coding. If a suitable term is missing, submitting a change request to the Maintenance and Support Services Organization, MSSO, is the correct approach rather than an internal redefinition within the organization.
Versioning, re-coding and license
MedDRA is continuously maintained. Organizations therefore require a documented strategy for version changes: the version used must be stated in outputs and analyses, and the impact of new or modified terms on already coded data must be evaluated. Which data is re-coded during an update depends on the development program, the data pool and the predefined procedure. Re-coding can, for example, be limited to non-current terms or be broader in scope to utilize more precise new terms.
For comparisons and queries, the data pool, search strategy and MedDRA version must match. If a query using terms from a newer version is applied to data from an older version, hits may be missing. MedDRA is a licensed terminology; access, use and distribution are subject to the license terms of the MSSO or the regionally responsible organization. The licensing requirement concerns the terminology itself and must be distinguished from a technically sound coding strategy.
Distinction from WHODrug and Standardised MedDRA Query
MedDRA codes medical and regulatory concepts such as symptoms, diagnoses, findings or events. WHODrug, on the other hand, is a drug terminology for coding medicinal products and their active ingredients; both terminologies can be used in the same safety dataset but fulfill different tasks. MedDRA is therefore not the correct terminology to standardize trade names or active ingredient information.
A Standardised MedDRA Query, or SMQ, is not an additional hierarchical level and not an alternative terminology. It is a predefined grouping of MedDRA terms maintained by the MSSO for a specific medical condition. If the content or logic of an SMQ is changed by users, the result is no longer an SMQ, but a modified MedDRA query based on an SMQ. This labeling is important so that search results can be properly classified and reproduced.
Relevance for clinical trials
Consistent MedDRA coding makes safety data from sites, countries and trials comparable and enables analyses at both the PT and grouping level. Crucial are qualified coders, binding coding conventions, the medical review of unclear information and a documented handling of versions. The coding must neither weaken the reported content nor alter it through additional assumptions; it is therefore a professional data processing task, not a purely technical assignment.
Full-service CROs such as Mediconomics support through coding plans, the establishment of coding workflows in data management, medical quality control, version changes and re-coding assessments. They also coordinate the traceable transfer of coded data to pharmacovigilance and biostatistics, verify the consistency of MedDRA version, database and analysis documentation and support the preparation of safety listings and clinical study reports.
Frequently Asked Questions (FAQ)
What is the difference between LLT and PT?
An LLT is the detailed coding level that reflects the reported phrasing as closely as possible. A PT represents a single medical concept and bundles its own LLT as well as synonyms or linguistic variants.
Must everything be re-coded with every new MedDRA version?
No. The organization must apply its documented versioning strategy and evaluate the impact. Re-coding can be targeted or more comprehensive; the decision should be justified for the program and data pool.
May an SMQ be adapted for a specific research question?
An adapted search logic can be technically reasonable. However, it may then no longer be referred to as an SMQ, but must be documented as a modified MedDRA query based on an SMQ.
Regulatory references
- MedDRA, Hierarchy — describes the five-level terminology hierarchy from LLT to SOC.
- MedDRA Term Selection: Points to Consider — governs principles for selecting current and as specific as possible LLTs.
- MedDRA Data Retrieval and Presentation: Points to Consider — covers version management, queries and the documentation of the used version.
- ICH E2D, Post-Approval Safety Data Management — establishes the standardized transmission of safety-relevant information in the regulatory context.