1. By
MedDRA
Basics
Somnath Mondal
Technical Associate (PVPI)
Dept. of Clinical & Experimental
Pharmacology
School of tropical Medicine,
Kolkata
Dated 20th Nov continuance from 7th Nov,2013

2. Agenda
1. Introduction to MedDRA
2. ABC of Coding
3. Brief History of MedDRA
Development
4. Scope of MedDRA
5. MedDRA Term
vs.
MedDRA Code
6. Basic of Structural Elements of the
Terminology

3. What is MedDRA?
Med =
Medical
D =
Dictionary
R = Regulatory
A = Activities

4. MedDRA Definition
MedDRA
is
a
clinically-validated
international medical terminology
used by regulatory authorities and the
regulated biopharmaceutical industry.
The terminology is used through the
entire regulatory process, from
pre-marketing to post-marketing,
and for data entry, retrieval,
evaluation, and presentation.

5. Requirements for MedDRA development
• International applicability
• Supported and used by both industry and regulators
• Broader coverage of health data
• Increased specificity
• Structure to support analysis and presentation
• Centrally and externally maintained
• Compatible with IT systems and tools

6. Rationale For MedDRA
Global Standardization and Universal Harmonization
Across Regulatory Agencies
Across Multinational Pharmaceutical Companies
Necessary through out Product Life Cycle
Necessary for Electronic Data Transfer
Avoid Translation Distortions and Errors Across Countries
Save Time:
No need to cross reference through life time of
product.
No need to Translate
Provide a classification for a wide range of clinical
information, able to support for multiple medical product
areas

7. Who participates in the MedDRA ?
Representatives of Authorities and Pharmaceutical Companies from :
Europe
Japan
United States
European Union
All reports (electronic) – January 2003
 EudraCT
SUSARs
 Starting 2003
all severe single case safety reports
going back to 1995 must be electronically submitted
before the start of 2004.
 Internal adverse event database
Japanese Ministry of Health, Labour and Welfare
 Required use of MedDRA for electronic
filing start 1 October 2003
 Proposed Rule for Safety Reporting
Requirements (2003): FDA proposes to use
MedDRA for post marketing safety reports
MedDRA to be used in Periodic Infection &
Safety Reports from April 2004
Observers:
WHO, European Free Trade Association (EFTA), Nordic Countries (Denmark,
Finland, Iceland, Norway and Sweden, Greenland), Canada, Australia

8. Sample of Current Regulators
MedDRA

9. ABC of Coding

10. Why Do Medical and Drug Terms Need to Be
Classified?
Investigators report the same medical and treatment terms (called
verbatim terms) in many different ways on the CRF/ ADR Reporting
Form.
In order to compare the frequency of adverse events in drug
treatment versus non treatment groups the terms need to be classified
into standardized terminology.

11. Why?
• To facilitate the aggregation of verbatim
reports into medically meaningful groupings
so that they can be reviewed, analysed and
communicated to the regulatory authorities.
• To ensure the accurate, unbiased &
consistent classification of CRF verbatim
terms as reported by the investigators

12. What is Coding?
Etymology: L, caudex, book
The process of organizing information into
categories, which are assigned codes for the
purposes of sorting, storing, and retrieving the data.
The process of transforming qualitative data into
numerical data that can be entered into a computer
file.
Medical coding is essentially the process of assigning
formal, standardized medical codes to patient
medical records.

13. Why is Medical Coding?
Medical coding is the transformation of narrative
descriptions of diseases, injuries, and healthcare procedures
into numeric or alphanumeric designations (that is, code
numbers).
The code numbers are detailed in order to
Accurately describe the diagnoses (that is, what is wrong with the patient).
and
The procedures performed to test or correct these diagnoses.
Because medicine is not always an exact science,
codes were developed to identify all reasons for
seeking healthcare.

14. Why do Medical Coding?
If we search for "medical coding" on web , we will be driven to websites which deals
with the ICD (9,10 etc.), CPT (Current Procedural Terminology) or HCPCS
( Healthcare Common Procedure Coding System) medical coding particularly deals
with mapping various medical diagnosis and procedures to codes.
Common uses of medical codes in healthcare include:
Identifying symptoms that must be evaluated and to alert other
healthcare professionals to life-threatening allergies.
The services performed for reimbursement
ReportingICD or CPT coding is out of scope here in this
presentation.
Helping with administrative functions such as staffing, scheduling, and
adding or decreasing healthcare services
Comparing facilities and planning for new services in underserved areas
These mostly deals with medical insurance data and medical billing which is different from
the coding in all phases of drug development.

15. Coding decisions during all phases of drug development
directly impact
submissions for New Drug Applications (NDAs),
safety surveillance
and
product labelling.
The success of a submission to the concerned regulatory
authority (e.g. USFDA, EMEA or DCGI?) can be significantly
impacted by the analysis of adverse events, medical history
and concomitant medications. The analysis relies on the
interpretation of what has been transcribed from the subject
CRF (Case Report Form) or ADR reporting form.
Ultimately, medical coding data permits access to health records according
The coding of patient data is critical in the grouping, analysis, and
to diagnoses and procedures for use in clinical care, research, education
reporting of data.
and for regulatory activities.

16. Brief History of MedDRA
Development

17. Pre-MedDRA Era
The essentiality and importance for an internationally accepted medical
terminology, classification system was recognized at the First
International Statistical Conference in Brussels in 1853 to evaluate
medical data statistically to optimize and regulate public
health issues globally.
The standardization effort bore fruit in 1969 with the FDA’s
use of the COSTART (Coding Symbols for a Thesaurus of
Adverse Reaction Terms) dictionary.
For the next quarter century, adverse event coding was
dominated
by
WHOART
(WHO
Adverse
Reaction
Terminology, required by EU) and COSTART (required by
FDA).

18. 1989 -UK MCA ( Medicines Control Agency (UK))identifies need for a single
medical terminology to support new computer databases
•1991–ADROIT ( Adverse Drug Reactions Online Information Tracking )
medical terminology created by UK MCA
•January 1993 -identification of need for a medical terminology to support
European Community drug regulatory system
2Q 1993 -Working party set-up of European regulators and pharmaceutical
industry representatives to evaluate wider applicability of MCA
terminology
•November 1993 to October 1994 -Working party reviews and amends
MCA terminology, now called MedDRA
December 1993 -European Committee for Proprietary Medicinal Products
approves MedDRA Project.
•October 1994 -ICH recommends that MedDRA (version 1.0) should form
basis of a new medical terminology

19. November 1994 –ICH Steering Committee released a draft (alpha) version
(version 1.1) of terminology for review and evaluation .
•March 1995 –ICH working group evaluated the alpha test results and evaluated
suggested changes
February 1996 -MedDRA Version 1.5 released for review in US and Japan
•July 1997 –ICH approval of international terminology
November 1998 –IFPMA (Trustee of ICH Steering Committee, holder of
intellectual property) selected BDM International Inc. (a subsidiary of TRW Inc.)
as the Maintenance and Support Services Organization (MSSO)
•March 1999 –MedDRA version 2.1 released

20. Version
HLGT
HLT
PT
LLT
1.5
307
670
8,659
35,346
2.0 (1Q99)
334
1663
11,344
46,427
2.2 (3Q99)
3.0 (1QOO)
NA
334
1653
3.1 (2Q 00)
4.0 (June 01)
333
1652
332
7.1 (November,2004)
8.0 (March,05)
8.1 (August,2005)
54,107
1683
16,102
56,981
NA
6.0 (March03)
7.0 (March, 04)
15,149
NA
5.1 (September,02)
6.1 (September,03)
47,892
NA
4.1 (November 01)
5.0 (March, 02
12117
1632
332
332
332
16,293
60,518
NA
1681
1683
16,449
61,204
16,559
61,704
16,751
62,348
16,976
62,950

21. 9.0 (March, 2006)
17,320
63,817
1682
17505
64,620
332
1682
17719
17,867
65,147
332
1,688
18,075
66,135
18,209
66,587
18483
67159
18641
67503
18,786
68,258
18,919
68,661
1,710
19,086
69,019
1710
1,713
19294
19,550
69524
70,177
1713
19737
70634
20057
71236
332
9.1 (January, 2007)
10.0 ( April, 2007)
10.1(September 1, 2007 )
11.0 (March, 2008)
11.1 (1 September , 2008)
12.0 (March, 2009)
12.1 (September 2009)
13.0 (March 2010 )
13.1 (September 2010)
14.0 (March 2011)
333
1699
335
1709
335
14.1 (1 September 2011
15.0 ( March, 2012)
15.1 ( September, 2012)
16 ( March, 2013)
65,605
335

22. Conditions before MedDRA

23.  Use of different types of terminologies
Most organizations processing regulatory data used one of the international
adverse drug reaction terminologies in combination with
morbidity terminology.
Europe
United States
European Union
WHO-ART
ICD-9
Japan
J-ART
J-MEDIS
COSTART(C)
ICD-9-CM
Individualized Modified Terminologies to Suit Individual need.
Major Technical Lacunae:
 Lacked specificity of terms at the data entry level,
 Provided limited data retrieval options
(e.g., too few levels in the hierarchy, or capacity to retrieve data via one axis only),
and
 Ineffective handling of syndromes.
Solution:
Organizations with sufficient resources developed their
terminologies to address some or all of these deficiencies.
own
“in-house”

24. The use of multiple terminologies raised several problems:
 Use of different terminologies for various
cycle:
Phases of regulatory
Complicates data retrieval and analysis, making it difficult to cross-reference data.
For example, for Pre-registration clinical trials safety data had frequently been
classified by using ICD terminology and for post-marketing surveillance using JART, WHO-ART, or COSTART.
 Protracted International Communication:
Using different terminologies in separate geographic regions impaired international
communication and necessitated the conversion of data from one terminology to
another. This data conversion had the potential to cause time delays and loss or
distortion of data.
 The use of multiple terminologies also affected communication between
companies and clinical research organizations.
It became increasingly difficult to manage the information required for product
registration applications and to meet the time scale requirements for data
exchange between regulatory authorities and the medical product industries.

25. Scope of MedDRA

26. The MedDRA Terminology applies to all phases of drug
development (including biologicals but excluding animal toxicology).
It also applies to the health effects and malfunction of devices
(e.g., Catheter related infection and device leakage).
The categories of “medical” terms are as follows:
 symptoms
Although social circumstances are not usually regarded as medical terms,
they fall within signs
the “medical” scope if they are relevant to the evaluation

of regulatory data diseases
(e.g., in the assessment of clinical outcome of treatment in the light
 diagnoses
of exposure to 
risk factors).
therapeutic indications
 names and qualitative results of investigations,
Examples are:
including pharmacokinetics
the preferred term Foreign travel, the preferred term Occupational
 surgical and the high level terms
exposure to toxic agent and medical procedures Tobacco use and
Bereavement.  medical/social/family history

27. The above defined terminology, was developed for
regulators and the regulated medical product
industry.
data entry, retrieval,
evaluation and presentation, and in both pre- and postmarketing phases of the regulatory process as follows:
Hence, these groups can utilize the terminology for
clinical studies
reports of spontaneous adverse reactions and events
 regulatory submissions
regulated product information

28. Inclusion of terms from established terminologies
The MedDRA Terminology includes references to other terminologies
J-ART (1996)
Preferred Terms, Included Terms
COSTART (Fifth Edition
Preferred Terms, Glossary Terms
WHO-ART© (3rd Quarter, 1998)
Preferred Terms, Included Terms
ICD-9
ICD-9-CM (4th revision)
Not Specified
HARTS (Release 2.2)
The terminology was not developed as a metathesaurus and the
hierarchies of these other terminologies are not subsets of it.
Thus, data entry terms from other terminologies do not necessarily have the same
PT (Preferred Term) in the MedDRA terminology as they did in their “parent”
terminology. The hierarchies used for data retrieval and presentation are unique to
the MedDRA.

29. Exclusion Criteria
The exclusion criteria used in the development of the terminology do not
necessarily limit the terminology’s expansion scope.
1. Since this is a medical terminology, the following terms used
in regulatory affairs are out of scope:
 Drug/product terminology
 Equipment/device/diagnostic product terminology
 Study design
 Demographics (including patient sex, age, race and religion)
2. As its focus is on health effects in individual patients, the
following are excluded:

Failure of devices
(except for a small number of clinically relevant terms)
Qualifiers that refer to populations rather than individual
patients, e.g., rare, frequent


30. Exclusion Criteria
3. Inclusion of terms is restricted to those within the scope of the
terminology as defined above. Thus, when terms from a particular field
(e.g., clinical pharmacology) are represented, only terms relevant to
regulatory affairs should be included.
4. Numerical values associated with parameters are not
included.
5. As a rule, descriptors of severity are not included in the
terminology.
Terms such as severe and mild are used only when
pertinent to the specificity of the term
(e.g., severe versus mild retardation).

31. OUT
IN
Diseases
Diagnoses
Signs
Drug product terms failure terms
Device
Symptoms
Therapeutic indications
Investigation Equipment, device,
names &
Numericalqualitative results
values for diagnostic product
terms
results
Medical & surgical procedures
Medical, social, family history
Medication Error
Terms study
Severity descriptorsfrom: design
Clinical trial
COSTARTterms
Population-level terms
Patient demographicqualifiers
WHO-ART©
HARTS
J-ART

32. MedDRA Term
vs.
MedDRA Code
MedDRA Term: a word(s)
Urticaria
MedDRA Code:
numbers representing each term
Urticaria
10046735

33. MedDRA Code
Unique numerical number assigned to each term in the
dictionary :
8 digits
•Starts with
alphabetically
10000001,
initially
started
•As terms added, codes assigned sequentially
•These are just identification numbers; they don’t
reflect the relational organization of the data files
(unlike WHO-ART)

34. Development Philosophy
• Based upon ANSI Z911 standard (American
National Standards Institute standard for
the development of a thesaurus)
• Provided structure for development and
future maintenance activities
• Chosen to ensure the product would support
the use of information technology
• Internationally recognized standard
34

35. Basic of Structural Elements
of the Terminology

36. Structural Elements of the Terminology
Relationships between terms in the terminology fall into the
following three categories:
1. Equivalence
The equivalence relationship groups synonymous
terms, or equivalent terms, under Preferred Terms.
2. Hierarchical
The hierarchy provides degrees or levels of
superordination and subordination. The superordinate
term is a broad grouping term applicable to each
subordinate descriptor linked to it.
3.Associative
Associative groupings of terms are linked horizontally in the
terminology.

37. Hierarchy
Hierarchies are an important mechanism for flexible
data retrieval and for the clear presentation of
data.
The five level hierarchy in this terminology provides
options for retrieving data by specific or broad
groupings, according to the level of specificity
required.
The Lowest Level Term (LLT) level provides maximum
specificity.

38. Hierarchy
System Organ Class (SOC)
Link
High Level Group Term (HLGT)
Vertical
High Level Term (HLT)
Preferred Term (PT)
Lowest Level Term (LLT)
SSC or SMQ
Detail discussion will be on
later phases of discussion

39. Example:
SOC
Blood and lymphatic system disorders
HLGT
White Blood Cell Disorder
HLT
Neutropenias
PT
Neutropenia
LLT
Neutropenia
aggravated
LLT
Neutropenia
SSC
Bone Marrow Depression
and Secondary
immunocompromised State

40. Example:
SOC
Cardiac Disorders
HLGT
Cardiac Arrhythmias
HLT
Rate and Rhythm of Disorders NEC
PT
Arrhythmia
LLT
Arrhythmia NOS
LLT
Arrhythmia
LLT (Non-current)
Other Specified Cardiac
Dysrhythmias
LLT
Dysrhythmias

41. System Organ Class (SOC)
Highest level of the hierarchy that
broadest concepts
for data retrieval.
provides the
SOCs identified or grouped by
Anatomical or physiological system or manifestation
site
(Gastrointestinal disorder)
Etiology (Infection of Infestation)
Purpose (Surgical and Medical procedure)

42. Anatomical or physiological system or manifestation site
or
Anatomy (Body System)
1.Blood and lymphatic system
disorders
9. Musculoskeletal and connective
tissue disorders
10. Nervous system disorders
2.Cardiac disorders
11. Psychiatric disorders
3.Ear and labyrinth disorders
12. Renal and urinary disorders
4.Endocrine disorders
5.Eye disorders
6.Gastrointestinal disorders
7.Hepatobiliary disorders
8.Immune system disorders
13. Reproductive system and breast
disorders
14. Respiratory, thoracic and mediastinal
disorders
15. Skin and subcutaneous tissue
disorders
16. Vascular disorders

43. Other (Cause/Association)
System Organ Class (SOC)
1.Congenital, familial and genetic
disorders
2.General disorders and
administration site conditions
3.Infections and infestations
4.Injury, poisoning and procedural
6. Metabolism and nutrition disorders
7. Neoplasms benign, malignant and
unspecified (including cysts and
polyps)
8. Pregnancy, puerperium and perinatal
conditions
complications
5.Investigations
9. Social circumstances
10. Surgical and medical procedures

44. Etiology-based SOCs
Supporting SOCs
1.Congenital, familial and genetic
1.Investigations
disorders
2.Social circumstances
2.Neoplasms benign, malignant and
3.Surgical and medical procedures
unspecified (including cysts and polyps)
3.Infections and infestations

45. High Level Group Term
（ HLGT ）
Subordinate
only
to
System
Organ
Classes
and
superordinate descriptor for one or more HLTs related to
anatomy, pathology, physiology, etiology or function.
SOC
Gastrointestinal disorders
HLGT
Dental and gingival
conditions
HLGT
Gastrointestinal
infections
HLGT
Gastrointestinal
vascular conditions

46. High Level Term (HLT)
Subordinate to HLGTs and super
descriptors for the PTs linked to it.
ordinate
Categories linked to PTs by anatomy, pathology,
physiology, etiology or function.
Used
solely
presentation
for
data retrieval
( not a coding level).
and

47. High Level Term
SOC
Gastrointestinal disorders
HLGT
Gastrointestinal infections
HLT
Intestinal infections
HLT
Gastrointestinal infections,
site unspecified
HLT
Peritoneal infections

48. HLGT
Vascular Hypertensive Disorder
HLT
Accelerated and malignant
Hypertension
HLT
Pregnancy Associated with
hypertension
HLT
Hypertension complication
HLT
Portal hypertension
HLT
Pulmonary hypertension

49. Preferred Term
Each Preferred Term represents a single
medical concept:
• Clinical
pathologic
/etiologic
data
represented at PT level.
• Unambiguous, self- descriptive.
• No limit to the amount of LLTs that can be
associated with a single PT ( A PT must have at least
one LLT linked to it).
• When a new PT is added an identical LLT is created
automatically for data entry purposes.

50. • A PT must be linked to at least one SOC.
Each path to a SOC from a PT should have exactly one
HLT and HLGT (one route)
PT → HLT → HLGT → SOC
• PTs can be represented in multiple
SOCs (multiaxality)
• PTs may be groups with other PTs from the
same SOC or different SOCs in SSC for
cross hierarchy searches.

51. Example of PT
PT
Headache
LLT (Non-current)
LLT
Head Pain
LLT
Head Pressure
LLT
Head aggravated
Head dull
LLT
Head fullness
LLT
Headache
LLT
Head throbbing

52. Example of PT
PT
Dysponea
LLT (Non-current)
LLT
Air Hunger
LLT
Breath
Shortness
Breathlessness
LLT
Breathing Difficult
LLT
Dysponea
LLT
Difficult breathing

53. Lowest Level Term (LLT)
The most Specific level of terminology.
Facilitate the data transfer from other
terminologies.
Facilitate the data entry by subjective
choice.
Use for Auto coding.

54. Lowest Level Term (LLT)
Important Features:
Each LLT is linked to only one
preferred descriptor in the terminology.
PT;
this is its
Has one of the following relationships to the
Preferred Term (PT)
 Synonyms
 Lexical variants
 Quasi-synonym
 Sub-element
 Identical LLT

55. Synonyms
Different terms for the for the same descriptor
same concept inherent in the PT
For Example:
PT
Arthritis
LLT
Joint Inflammation

56. Lexical variants
Different word forms for the same expression
These include
full names vs. abbreviations
For Example:
PT
Acquired immunodeficiency
syndrome
LLT
AIDS
OR
direct vs. inverted word order
PT
Biopsy tongue
LLT
Tongue biopsy

57. Quasi-synonym
Terms that are not precisely the same meaning as
another term, but are treated as synonymous in a
given terminology.
PT
Otitis externa
LLT
Bilateral otitis externa
Based on site and laterality
descriptions
both
the
terms are considered as
Synonymous or equivalent
clinically
for
medical
product
regulatory
purposes.

58. Sub-element
Sub-elements (of the parent PT) are represented by LLTs
with more detailed information such as anatomic specificity.
PT
Contusion
LLT
Bruising of face
LLT
Bruising of leg

59. Identical LLT
One LLT is identical to its PT for data entry purposes
PT
Arrhythmia
LLT
Arrhythmia NOS
LLT
Arrhythmia
LLT (Non-current)
Other Specified Cardiac
Dysrhythmias
LLT
Dysrhythmias
PT
Dementia Alzheimer’s type
LLT
Dementia Alzheimer’s type
In these instance, the LLT and parent
PT have the same MedDRA code but
appear at both levels.

60. Basic Rules in MedDRA
PT: British Spelling
LLT: British and American Spelling
Medical Term: Dorland’s Medical
Dictionary (29th Ed)
Non-Medical Term: Merrian-Webster
English Dictionary (29th Ed)

61. Thank you

62. But First, Some Definitions
• Controlled vocabulary: a bunch of words, no relationships
– But there is advantage if all users use the same terms to
describe things
• Taxonomy: is a controlled vocabulary with hierarchy
• Thesaurus: is interchangeable with controlled vocabulary,
also sometimes referred to as an ontology
• Ontology: all of the above; think neural network with a
bunch of relationships
• MetaData: data about data (I really hate this definition, but
it’s accurate)
•
MetaThesaurus – a collection of all of these things
– EXAMPLE: UMLS

63. UMLS – Unified Medical Language
System
• More than 5 million terms or named entities
• Divided into concepts, and each term has
unique identifier
• Not a vocabulary, but a mapping BETWEEN
vocabularies
• Vocabularies included in the UMLS:
–
–
–
–
MeSH Headings in 8 languages (MeSH = Medical Subject Headings)
ICPC-93 in 14 languages (ICPC = International Classification of Primary Care)
WHO Adverse Drug Reaction Terminology in 5 languages
SNOMED-2, SNOMED-3, and UK Clinical Terms (former Read Codes) (SNOMED
= Systemized Nomenclature of Medicine)
– ICD-10 in English and German (ICD = International Classification of Diseases)