Medical Dictionary for Regulatory Activities (MedDRA)

1. Medical Dictionary for
Regulatory Activities
(MedDRA)
Prof. Lokendra Sharma
Department of Pharmacology,
SMS Medical College
Jaipur

2. INTRODUCTION
MedDRA is a hierarchical terminology
with 5 levels and is multiaxial: terms may
exist in more than 1 vertical axis
Providing specificity of terms for data
entry and flexibility in data retrieval.
It is a structured vocabulary of medical
and other terms relevant to the
development and use of medicines

4. Terms in MedDRA were derived from
several sources including the WHO’s
Adverse Drug Reaction Terminology
(WHO-ART),
Coding symbols for a Thresaurus of ARTs
(COSTART), International Classification of
Diseases (ICD) 9 and ICD9-CM (Clinical
Manifestations).

5. Owner–International Federation of
Pharmaceutical Manufacturers
Associations (IFPMA)
 Maintained, further developed and
distributed by – Maintenance Support
Services Organization (MSSO)
Use by pharmaceutical
industry/regulatory bodies

6. INTRODUCTION
• Work began in 1990, MEDDRA (1993) and
MedDRA (1999)
• MedDRA is based upon the Medical Dictionary
for Drug Regulatory Affairs (MEDDRA)
• Which was created by UK Medicines Control
agency (MCA) and was modified by a working
party of representatives from pharmaceutical
companies and European regulatory
authorities.

7. • Released every 6 months – CD / Internet
download
• Subscription
–Free for regulatory authorities
–Paid from MSSO
–Charge – based on revenue
• $3825 for $1 million revenue
• $92 292 for more than $5 billion revenue

8. INTRODUCTION
• Guidance for use:
–MSSO – Introductory guide
–The Council for International Organizations
of Medical Sciences (CIOMS) - SMQs
– Joint industry-regulators working group
(ICH endorsed)
• MedDRA Term Selection – ‘points to consider’
• MedDRA Data Retrieval, Analysis and
Presentation

9. MedDRA USER GUIDE
• The MedDRA user guide explains the
development of the terminology and
defines hierarchical levels and the
rationale and conventions for their use.
• A noteworthy convention applies to
investigations:
–these are represented only in the
investigations’ SOC; there are no secondary
linkages

10. • However, terms describing clinical
conditions, e.g. hypoglycaemia and
hyperkalaemia are not found in the
investigations’ SOC:
–they are present only in other SOCs such as
the ‘disorders of metabolism and
nutrition’ SOC.

11. CONTENTS
• > 60 000 terms (medical conditions, syndromes, diagnoses,
clinical signs, symptoms, laboratory and clinical investigations
and social circumstances)
• Terms in MedDra were included from several sources:
– Version 2.0 includes all PTs and ‘included terms’ from the
• latest version of the WHO ADR Terminology (WHO-ART) and its Japanese
adaptation (J-ART, 1996),
• 5th
edition of the Coding Symbols for a Thesaurus of Adverse Reaction
Terms (COSTART) Preferred Terms and Glossary Terms,
• Hoeschst Adverse Reaction Terminology (release 2.2) terms,
• International Classification of Diseases (ICD) 9 3- and 4-digit code terms
and ICD 9-CM (4th
revision) 3-, 4- and 5-digit code terms
• Terms from the Japanese adaptation of ICD9, MEDIS
– These terms are included in LLTs in MedDRA and some are also as PTs

12. CONTENTS
• Terms from other dictionaries and ICD:
– Original terms & numerical codes or symbols from these
sources are retained and stored in attribute fields linked to
the MedDRA terms in order to facilitate the migration of
legacy data at the time of transfer to using MedDRA.
• Does not include:
– Drug or device names
– Definitions of terms
– Demographic terms (gender, age or race)
– Numerical expressions ………..some exceptions
• Limited to human experience

13. USES
• In Regulatory process of drug development
• In Post-authorization/Post-marketing Research and
Studies
• In Clinical studies
– For describing Adverse Drug Events – IB & DCSI
– For Electronic reporting – ICH -E2B(M), ICH-M4
– For Recording social & medical history
• Marketed medicines
– CCSI, PI and SPC
– PSURs
• Regulatory authority request – expedited reporting
(ICH-E2A)
– EU, Japan , US, Australia & Canada

14. STRUCTURE

15. STRUCTURE
• The basic units in MedDRA are the Preferred Terms
(PTs) each of which is a distinct descriptor for a
condition covered by the scope of MedDRA:
– It is the term preferred for use in the regulatory
environment, formatted according to MedDRA
conventions
– PTs are unambiguous, specific and self descriptive:
eponymous terms are only used if recognized
internationally.
– Each PT is duplicated as a ‘Lowest Level Term’ (LLT) and
may be linked to 1 or more other LLTs, which are
synonyms, lexical variants or alternative spellings.

16. STRUCTURE
– Each PT is represented only once under a particular ‘system
organ class’ (SOC), to which it is concerned vertically via a
single ‘High Level Term’ (HLT) which in turn is fixed in location
and represented only once in that SOC under 1 ‘High Level
Group Term’ (HLGT)
• This arrangement represents the ‘Primary System
Organ Class’ (Primary SOC) location for the PT.
• However, the parallel vertical SOC axes are not
mutually exclusive: a PT may also be linked to
secondary locations in 1 or more other SOC, in which it
is again placed under a specified HLT and HLGT,
retaining its associated LLTs.
• The 26 MedDRA SOCs are shown in table

17. Table: Internationally agreed order of
SOCs in MedDRA
1. Infections and infestations
2. Neoplasms benign and malignant
(including cysts and polyps
3. Blood and lymphatic system
disorders
4. Immune system disorders
5. Endocrine disorders
6. Metabolism and nutrition disorders
7. Psychiatric disorders
8. Nervous system disorders
9. Eye disorders
10. Ear and labyrinth disorders
11. Cardiac disorders
12. Vascular disorders
13. Respiratory, thoracic & mediastinal
disorders
14. Gastrointestinal disorders
15. Hepato-biliary disorders
16. Skin and subcutaneous tissue
disorders
17. Musculoskeletal, connective
tissue and bone disorders
18. Renal and urinary disorders
19. Pregnancy, puerperium and
perinatal disorders
20. Reproductive system and breast
disorders
21. Congenital and familial/genetic
disorders
22. General disorders and
administration site conditions
23. Investigations
24. Injury and poisoning
25. Surgical and medical
procedures
26. Social circumstances

18. STRUCTURE
• Lowest level Terms (LLTs)
– Synonyms, lexical variants, and other similar
representations of medical terms
– Intended for data entry and coding
– Provides a high degree of probability of words used by an
individual
– ‘Non current’ LLTs – should not be used
– Similar ‘LLTs’ – linked to a ‘PT’
• Preferred Terms (PTs)
– Duplicated as a ‘LLT’
– Favored for use in case of retrieval and data presentation
– May be represented in more than one SOC – Primary &
Secondary
• ‘PTs’ to ‘HLTs’ to ‘HLGTs’ to ‘SOCs’

19. STRUCTURE

20. RULES AND CONVENTIONS
• Linguistic/lexical
– Abbreviations (e.g., Alanine aminotransferase (ALT) or
SGPT & Aspartate aminotransferase (AST/SGOT)
– Word order (e.g., Penumonia Streptococcal)
– Spelling: PTs – British and LLTs – American
• Location of terms under SOC – primary/secondary
– Pathological process takes precedence over anatomical
location
– Heart disease congenital : Primary -Congenital, familial and
genetic disorders / Secondary-Cardiac disorders SOC
– Pharyngitis streptococcal – Primary-Infections and
infestations / Secondary-Respiratory, thoracic and
mediastinal disorders

21. RULES AND CONVENTIONS
• Reports of investigational finding and apparent
medical condition
– LLT Hyponatraemia – SOC Metabolism and nutrition
disorders
– LLT Serum sodium decreased – SOC Investigations
– PT in Investigation SOC does not have secondary SOC
• Multiaxiality

24. DATA ENTRY
• Involves use of ‘browser’ or ‘autoencoder’ and/or a
computerized search programme.
– It is intended that data entry should use LLTs
– When a MedDRA LLT is selected for data entry, there is automatic
assignment of PTs, HLT, HLGT and location in primary SOC together with
secondary SOC linkages.
– If a suitable LLT does not exist, the MSSO may allocate a new term.
– However, strict guidance has been provided to prevent uncontrolled
proliferation
– Permits to search MedDRA for an LLT to match the verbatim / ‘as
reported’ term
– Additional facilities – ‘and/or’, ‘begins with’, ‘containing’, MedDRA tree
view
– Autoencoders – scan narrative texts
• Guidance – ‘MedDRA Term Selection’ by MSSO

25. DATA ENTRY – GENERAL
PRINCIPLES
• Clarify ambiguous, confusing or unintelligible data
• Promote quality by training
• Select the LLT that most accurately reflects the
reporter’s words
• Use current LLTs only
• Use medical judgment if no exact match for a verbatim
• Not appropriate to address deficiencies in MedDRA by
developing organization-specific solutions
• If there is no adequate representation in MedDRA,
submit a change request to MSSO

26. DATA ENTRY – GENERAL PRINCIPLES
• If no MedDRA term, request a new term, and use one
or more existing terms
• Do not subtract or add information
• Code regardless of causality assessment
• Do not invent diagnoses or mechanisms
• Document selection strategies and Quality Assurance
procedures
• Human intervention is essential to ensure appropriate
end result
• Do not make ad hoc structural changes to MedDRA
• Term selection should be reviewed by a qualified
individual (medical background / trained in using
MedDRA)

27. SEARCH AND DATA RETRIEVAL
• When?
– Review of safety data
– Signal evaluation
– Response to regulatory requests
– Information requests
• Strategy is based on requirement
• PT is the point of focus
• Multiaxial structure helps the search
• Large size presents challenges
– Representation of PTs under SOCs in reports might run in
pages
– Necessary to look at several SOCs – including Investigations
SOC

28. SEARCH AND DATA RETRIEVAL
• Needs care to not to miss relevant terms
• Special Search Categories
• CIOMS SMQs may ease the process (Draft
Nov. 2005)
• Guidelines on data retrieval &
presentation (Ver. 1.5 Apr 01, 08)

31. ANALYSIS AND PRESENTATION
• Issues
– Large number of terms
– Choosing most appropriate levels
– Groupings for the required purpose
– Multiaxiality
– Higher ratio of terms (2:1 Vs. WHO-ART) and
– Version changes
• Subject of guidelines on MedDRA data retrieval &
presentation
– Approaches to presenting data
– Advantages and disadvantages

32. ANALYSIS AND PRESENTATION GUIDELINES
• Distribution of ADRs/AEs across SOCs
• In a way that allows ready recognition of
patterns AEs
• Display of PTs under SOCs alone may not be
sufficient and can be misleading
• Should display overview according to primary
SOC, HLGT, HLT and PT
– In standard tables
– Identifies clusters
– Forms basis for in depth analysis

33. ANALYSIS AND PRESENTATION GUIDELINES
• Line listing by primary SOC and PT
– Preferable to display data by HLGTs and HLTs as well as show
SOC and PTs (for complex data)
• Graphical representation may facilitate understanding
by the viewer
• May be appropriate to expand to secondary SOCs
• For terms involving more than one SOC - use SMQs
• For information to health professionals - Translate
MedDRA terms into more familiar medical terms

34. ANALYSIS AND PRESENTATION GUIDELINES
• Proposed guidance on use of MedDRA in SPC
– Section 4.8 (Undesirable effects) with a table of ADRs
according to MedDRA SOC
– Usually PTs, sometimes LLTs
– ADRs ranked under headings of frequency
– List under most relevant SOC
– Annex devoted to the use of MedDRA
– Natural word order (‘Interstitial pneumonia’ not
‘Pneumonia interstitial’)
– Most widely recognized term for a particular condition

35. CONCLUSION
• MedDRA is a large, hierarchical, multiaxial
medical terminology
• Provides distinct advantages over some
other coding systems
• Use is increasing in Pvig environment
• Guidance on use are becoming available
• SMQs will overcome the complexities