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Automatic generation of MedDRA terms
groupings using an ontology
Gunnar DECLERCKa, Cédric BOUSQUETa,b and Marie-Christine JAULENTa
a
INSERM, UMRS 872 EQ20, Université Paris Descartes, France.
b Department of Public Health, CHU University of Saint Etienne, France.
MIE 2012, August 27th, Pisa
Context and Rationale
 MedDRA (Medical Dictionary for Drug Regulatory Activities) : standard terminology used to
code adverse drug reactions (ADRs) in safety reports for postmarketing drug surveillance.
 Used for Signal detection :
 Case reports coded with MedDRA stored in databases (i.e. FDA pharmacovigilance Database
for the US, WHO Vigibase for Europe)
 Data mining algorithms used to find statistical correlations between ADRs (several MedDRA
terms defining a unique medical condition) and drugs (a “signal”)
 Empirical studies to assess the causal relationship between the drug and ADR.
MedDRA hierarchical
structure
2
PROTECT WP3-SP6 “Novel techniques for grouping ADRs to improve signal
detection”
 Main goal: To develop and evaluate semantic driven methods for grouping MedDRA terms to
improve signal detection performances.
 Hypothesis: Signal detection is improved when algorithms use groupings of MedDRA terms
referring to the same ADR condition (rather than one single term).
 Need a way to assist human experts to build MedDRA groupings (currently made manually)
 Method: Building an ADR ontology (OntoADR) providing MedDRA terms with formal machineprocessable defintions to support automatic MedDRA terms grouping procedures (OWL queries
selecting terms on the basis of their semantic properties).
WP
Work Package title
1
Project management and administration
2
Framework for pharmacoepidemiological studies
3
Methods for signal detection
4
New tools for data collection from consumers
5
Benefit-risk integration and representation
6
Validation studies involving an Extended Audience
7
Training and communication
PROTECT. Pharmacoepidemiological Research on Outcomes
of Therapeutics by a European ConsorTium.
IMI (Innovative Medicines Initiative) project (2009- 2014).
3
OntoADR ontology
 MedDRA terminology enriched with Snomed-CT
concepts formal definitions
 34994 concepts (20856 MedDRA 13.0 terms / others
from Snomed-CT)
 26 Snomed-CT relations used to express medical
meaning of MedDRA concepts
HASFINDINGSITE
specifies the body site affected by a
condition
HASOCCURRENCE
refers to the specific period of life
during which a condition first occurs
…
4
Ontologizing MedDRA
 Hierarchical relations from SOC level to
PT (Preferred terms) level are converted
to subsomption (subclass_of) relations
SOC level
HLGT level
HLT level
 LLT (low level terms) are integrated as
annotation labels of PT concepts
PT level
5
Mapping process
 When it is possible, MedDRA concepts are
mapped with Snomed-CT concepts via UMLS
metathesaurus
 Semantic information describing Snomed-CT
concepts used to build the formal definition of
MedDRA concepts.
Formal definition of « Dilatation intrahepatic duct congenital »
Meddra PT concept after Snomed-CT mapping (mapped with
“Congenital dilatation of lobar intrahepatic bile duct”)
 When mapping impossible, formal definition
made manually (via collaboration between
knowledge engineers and medical experts)
6
OntoADR generation: general schema
Mapping process
SOC
HLPT
HLT
PT
Snomed-CT
MedDRA
Medical experts:
Validation of mappings
Manual enrichment of OntoADR
• 55.6 % of MedDRA 13.0 terms could be
defined using (i) a direct mapping with a
Snomed-CT concept (UMLS or other mappings
methods) or (ii) a handmade definition.
• Those terms cover 97.02 % of MedDRA
terms used in the FDA database (calculated for
the period 2004-2010: 11 millions reports).
= MEDDRA TERMS + FORMAL DEFINITIONS
ONTOADR.owl
7
Using OntoADR to perform automatic query-based MedDRA terms
groupings
 Thanks to OntoADR, OWL queries can be built to select the MedDRA PTs whose formal
definition fits some definitional criteria.
 Example : Query to catch MedDRA terms related to “Upper gastrointestinal bleeding”
hasAssociatedMorphology some ‘Hemorrhage’
AND hasFindingSite some ‘Upper gastrointestinal tract structure’
 Will select from MedDRA hierarchy all PTs matching those two properties:
Duodenal ulcer haemorrhage
Gastric haemorrhage
Mallory-Weiss syndrome
Peptic ulcer haemorrhage
etc.
8
Using OntoADR to perform automatic query-based MedDRA terms
groupings
 Through the subsomption mechanism, MedDRA terms referring to hemorrhages of parts of
the Upper gastrointestinal tract are also selected.
ex. Oesophageal ulcer haemorrhage, Gastric varices haemorrhage, etc.
9
Evaluation of the OntoADR-based grouping method
 Focus on 13 ADR safety topics identified by Trifirò et al (2009)
as first importance pharmacovigilance targets (EU-ADR project).
 For each safety topic:
i.
ii.
Groupings of MedDRA PTs have been realized with
OntoADR queries.
ST 1 Bullous eruptions
ST 2 Acute renal failure
ST 3 Anaphylactic shock
ST 4 Rhabdomyolysis
ST 5 Aplastic anaemia/pancytopenia
ST 6 Neutropenia
ST 7 Cardiac valve fibrosis
ST 8 Extrapyramidal disorders
ST 9 Confusional state
ST 10 Thrombocytopenia
ST 11 Upper gastrointestinal bleeding
ST 12 Peripheral neuropathy
ST 13 Maculo-papular erythematous eruptions
ADR topics identified by Trifirò et al (2009)
The content of those groupings has been evaluated by comparison with existing handmade
MedDRA groupings of PTs targeting same or close conditions:
A. Original MedDRA hierarchy groupings (HLTs or HLGTs)
B. SMQs (Standard Medical Queries): collections of MedDRA PTs developed manually by the MSS0
(Maintenance and Support Services Organization) to describe a common clinical condition
Trifirò G, Pariente A, Coloma PM, Kors JA, Polimeni G, Miremont-Salamé G, Catania MA, Salvo F, David A, Moore N, Caputi AP, Sturkenboom M,
Molokhia M, Hippisley-Cox J, Acedo CD, van der Lei J, Fourrier-Reglat A. Data mining on electronic health record databases for signal detection in
pharmacovigilance: which events to monitor? Pharmacoepidemiol Drug Saf. 2009; 18(12):1176-84.
10
Neutropenia Safety Topic
HLT Neutropenias
Type (for Label
SMQ)
Agranulocytosis
Autoimmune neutropenia
Cyclic neutropenia
Febrile neutropenia
Felty's syndrome
Granulocytopenia
Granulocytopenia neonatal
Idiopathic neutropenia
Infantile genetic agranulocytosis
Neutropenia
Neutropenia neonatal
Neutropenic colitis
Neutropenic infection
Neutropenic sepsis
Id Meddra
10001507
10055128
10053176
10016288
10016386
10018687
10018688
10051645
10052210
10029354
10029358
10062959
10059482
10049151
SMQ Leukopenia
Narrow
Narrow
Narrow
Narrow
Narrow
Narrow
Narrow
Narrow
Narrow
Narrow
Broad
Broad
Broad
Broad
Agranulocytosis
Band neutrophil count decreased
Band neutrophil percentage decreased
Cyclic neutropenia
Febrile neutropenia
Idiopathic neutropenia
Neutropenia
Neutropenic infection
Neutropenic sepsis
Neutrophil count decreased
Myelocyte percentage decreased
Neutropenia neonatal
Neutrophil count abnormal
Neutrophil percentage decreased
10001507
10057950
10059130
10053176
10016288
10051645
10029354
10059482
10049151
10029366
10052227
10029358
10061313
10052223
 Generally
defined as “an abnormally low
number of neutrophils” (*), which are the
most abundant type of white blood cells
(leukocytes) in mammals.
 Leukopenia Sometimes used as synonym of
Neutropenia
 But stricly speaking Leukopenia semantically
broader (refers to a deficit in the number of all
types of white blood cells)
 To enable comparison with query-based
neutropenia grouping, only neutropenia relevant
PTs were selected in the SMQ
(*) http://www.nlm.nih.gov/medlineplus/ency/article/007230.htm
Neutropenia: Building the OWL query
hasDefinitionalManifestation some Neutropenia
OR interprets some (hasComponent some 'Segmented neutrophil'
OR hasComponent some 'Myelocyte'
OR hasComponent some 'Stab form')
AND
(hasInterpretation some 'Below reference range'
OR hasInterpretation some 'Decreased'
OR hasInterpretation some 'Abnormal')
Semantic relations used by
Description
the query
interprets
Refers to the entity being evaluated or interpreted, when an evaluation, interpretation or “judgment”
is intrinsic to the meaning of a concept.
hasInterpretation
This attribute is grouped with the attribute “Interprets”, and designates the judgment aspect being
evaluated or interpreted for a concept (e.g., presence, absence, degree, normality, abnormality, etc.).
hasComponent
hasDefinitionalManifestation
Refers to what is being observed or measured by a procedure.
Links disorders to the manifestations (observations) that define them.
(*) http://en.wikipedia.org/wiki/Neutrophil_granulocyte
Neutropenia: Building the OWL query
hasDefinitionalManifestation some Neutropenia
Selecting disorders defined by an abnormally low
number of neutrophils
(ex. autoimmune neutropenia, cyclical neutropenia, etc.)
OR interprets some (hasComponent some 'Segmented neutrophil'
OR hasComponent some 'Myelocyte'
OR hasComponent some 'Stab form')
AND
(hasInterpretation some 'Below reference range'
OR hasInterpretation some 'Decreased'
OR hasInterpretation some 'Abnormal')
Semantic relations used by
Description
the query
interprets
Refers to the entity being evaluated or interpreted, when an evaluation, interpretation or “judgment”
is intrinsic to the meaning of a concept.
hasInterpretation
This attribute is grouped with the attribute “Interprets”, and designates the judgment aspect being
evaluated or interpreted for a concept (e.g., presence, absence, degree, normality, abnormality, etc.).
hasComponent
hasDefinitionalManifestation
Refers to what is being observed or measured by a procedure.
Links disorders to the manifestations (observations) that define them.
(*) http://en.wikipedia.org/wiki/Neutrophil_granulocyte
Neutropenia: Building the OWL query
hasDefinitionalManifestation some Neutropenia
OR interprets some (hasComponent some 'Segmented neutrophil'
OR hasComponent some 'Myelocyte'
OR hasComponent some 'Stab form')
AND
(hasInterpretation some 'Below reference range'
OR hasInterpretation some 'Decreased'
OR hasInterpretation some 'Abnormal')
Selecting analyses measuring quantity of
neutrophils cells or neutrophils precursor
cells
(ex. Myelocyte count, Myelocyte percentage)
Myelocyte = precursor cell in the development of the granulocyte series.
Neutrophils or neutrophil granulocytes “are generally referred to as either neutrophils
or polymorphonuclear neutrophils (or PMNs), and are subdivided into segmented
neutrophils (or segs) and banded neutrophils [also called band neutrophil or stab
cell]. They form part of the polymorphonuclear cell family (PMNs) together with
basophils and eosinophils.” (*)
Semantic relations used by
Description
the query
interprets
Refers to the entity being evaluated or interpreted, when an evaluation, interpretation or “judgment”
is intrinsic to the meaning of a concept.
hasInterpretation
This attribute is grouped with the attribute “Interprets”, and designates the judgment aspect being
evaluated or interpreted for a concept (e.g., presence, absence, degree, normality, abnormality, etc.).
hasComponent
hasDefinitionalManifestation
Refers to what is being observed or measured by a procedure.
Links disorders to the manifestations (observations) that define them.
(*) http://en.wikipedia.org/wiki/Neutrophil_granulocyte
Neutropenia: Building the OWL query
hasDefinitionalManifestation some Neutropenia
OR interprets some (hasComponent some 'Segmented neutrophil'
OR hasComponent some 'Myelocyte'
OR hasComponent some 'Stab form')
AND
(hasInterpretation some 'Below reference range'
OR hasInterpretation some 'Decreased'
OR hasInterpretation some 'Abnormal')
Selecting abnormal / low results of
those analyses
(ex. Neutrophil count abnormal, Myelocyte
percentage decreased, etc.)
Myelocyte is precursor cell in the development of the granulocyte series.
Neutrophils or neutrophil granulocytes “are generally referred to as either neutrophils
or polymorphonuclear neutrophils (or PMNs), and are subdivided into segmented
neutrophils (or segs) and banded neutrophils [also called band neutrophil or stab
cell]. They form part of the polymorphonuclear cell family (PMNs) together with
basophils and eosinophils.” (*)
Semantic relations used by
Description
the query
interprets
Refers to the entity being evaluated or interpreted, when an evaluation, interpretation or “judgment”
is intrinsic to the meaning of a concept.
hasInterpretation
This attribute is grouped with the attribute “Interprets”, and designates the judgment aspect being
evaluated or interpreted for a concept (e.g., presence, absence, degree, normality, abnormality, etc.).
hasComponent
hasDefinitionalManifestation
Refers to what is being observed or measured by a procedure.
Links disorders to the manifestations (observations) that define them.
(*) http://en.wikipedia.org/wiki/Neutrophil_granulocyte
Results: comparison with HLT
OntoADR OWL Query
HLT
SMQ
Type (for Label
SMQ)
Agranulocytosis
Autoimmune neutropenia
Cyclic neutropenia
Febrile neutropenia
Felty's syndrome
Granulocytopenia
Granulocytopenia neonatal
Idiopathic neutropenia
Infantile genetic agranulocytosis
Neutropenia
Neutropenia neonatal
Neutropenic colitis
Neutropenic infection
Neutropenic sepsis
Narrow
Narrow
Narrow
Narrow
Narrow
Narrow
Narrow
Narrow
Narrow
Narrow
Broad
Broad
Broad
Broad
Agranulocytosis
Band neutrophil count decreased
Band neutrophil percentage decreased
Cyclic neutropenia
Febrile neutropenia
Idiopathic neutropenia
Neutropenia
Neutropenic infection
Neutropenic sepsis
Neutrophil count decreased
Myelocyte percentage decreased
Neutropenia neonatal
Neutrophil count abnormal
Neutrophil percentage decreased
Id Meddra
Q
Label
Id Meddra
10001507
10055128
10053176
10016288
10016386
10018687
10018688
10051645
10052210
10029354
10029358
10062959
10059482
10049151
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
13
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
14
Agranulocytosis
Autoimmune neutropenia
Band neutrophil count decreased
Band neutrophil percentage decreased
Cyclic neutropenia
Febrile neutropenia
Felty's syndrome
Granulocytopenia
Granulocytopenia neonatal
Idiopathic neutropenia
Myelocyte count decreased
Myelocyte percentage decreased
Neutropenia
Neutropenia neonatal
Neutropenic colitis
Neutropenic infection
Neutropenic sepsis
Neutrophil count abnormal
Neutrophil count decreased
Neutrophil percentage abnormal
Neutrophil percentage decreased
Neutrophil percentage decreased
10001507
10055128
10057950
10059130
10053176
10016288
10016386
10018687
10018688
10051645
10050986
10052227
10029354
10029358
10062959
10059482
10049151
10061313
10029366
10058134
10052223
10052223
10001507
10057950
10059130
10053176
10016288
10051645
10029354
10059482
10049151
10029366
10052227
10029358
10061313
10052223
Recall
HLT Precision
F-measure
SMQ
100,0%
59,1%
74,3%
100,0%
63,6%
77,8%
Results: comparison with HLT
OntoADR OWL Query
HLT
SMQ
Type (for Label
SMQ)
Agranulocytosis
Autoimmune neutropenia
Cyclic neutropenia
Febrile neutropenia
Felty's syndrome
Granulocytopenia
Granulocytopenia neonatal
Idiopathic neutropenia
Infantile genetic agranulocytosis
Neutropenia
Neutropenia neonatal
Neutropenic colitis
Neutropenic infection
Neutropenic sepsis
Narrow
Narrow
Narrow
Narrow
Narrow
Narrow
Narrow
Narrow
Narrow
Narrow
Broad
Broad
Broad
Broad
Id Meddra
Q
10001507
10055128
10053176
10016288
10016386
10018687
10018688
10051645
10052210
10029354
10029358
10062959
10059482
10049151
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
13
Agranulocytosis
10001507
Y
Band neutrophil count decreased
10057950
Y
Band neutrophil percentage decreased
10059130
Y
Cyclic neutropenia
10053176
Y
Febrile neutropenia
10016288
Y
Idiopathic neutropenia
10051645
Y
Neutropenia
10029354
Y
Neutropenic infection
10059482
Y
Neutropenic sepsis
10049151
Y
Neutrophil count decreased
10029366
Y
Myelocyte percentage decreased
10052227
Y
Neutropenia neonatal
10029358
Y
Neutrophil count abnormal
10061313
Y
 All PTs present in the handmade
reference
Neutrophil percentage decreased
10052223
Y
groupings can be selected automatically
14
Perfect recall and correct precision
Label
Id Meddra
Agranulocytosis
Autoimmune neutropenia
Band neutrophil count decreased
Band neutrophil percentage decreased
Cyclic neutropenia
Febrile neutropenia
Felty's syndrome
Granulocytopenia
Granulocytopenia neonatal
Idiopathic neutropenia
Myelocyte count decreased
Myelocyte percentage decreased
Neutropenia
Neutropenia neonatal
Neutropenic colitis
Neutropenic infection
Neutropenic sepsis
Neutrophil count abnormal
Neutrophil count decreased
Neutrophil percentage abnormal
Neutrophil percentage decreased
Neutrophil percentage decreased
10001507
10055128
10057950
10059130
10053176
10016288
10016386
10018687
10018688
10051645
10050986
10052227
10029354
10029358
10062959
10059482
10049151
10061313
10029366
10058134
10052223
10052223
Recall
HLT Precision
F-measure
SMQ
100,0%
59,1%
74,3%
100,0%
63,6%
77,8%
Bullous eruptions Safety Topic
HLT Bullous conditions
OntoADR OWL Query
Label
Id Meddra
Q
Acquired epidermolysis bullosa
Application site vesicles
Benign familial pemphigus
Blister
Blood blister
Bullous impetigo
Cervical bulla
Coma blister
Dermatitis bullous
Dermatitis herpetiformis
Diabetic bullosis
Epidermolysis
Epidermolysis bullosa
Erythema multiforme
Herpes gestationis
Implant site vesicles
Incision site blister
Infusion site vesicles
Injection site vesicles
Linear IgA disease
Lip blister
Ocular pemphigoid
Oculomucocutaneous syndrome
Paraneoplastic pemphigus
Pemphigoid
Pemphigus
Penile blister
Porphyria non-acute
Pseudoporphyria
Staphylococcal scalded skin syndrome
Stevens-Johnson syndrome
Toxic epidermal necrolysis
Vaccination site vesicles
10056508
10048941
10004265
10005191
10005372
10006563
10050019
10069827
10012441
10012468
10062356
10053177
10014989
10015218
10019939
10063870
10067990
10065491
10022111
10024515
10049307
10067776
10030081
10057056
10034277
10034280
10052898
10036186
10037145
10041929
10042033
10044223
10069623
TOTAL
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
N
Y
N
N
Y
Y
Y
Y
N
Y
Y
Y
Y
Y
Y
Y
N
N
N
N
N
Y
23
Label
Acne pustular
Acquired epidermolysis bullosa
Acute generalised exanthematous pustulosis
Application site pustules
Application site vesicles
Blister
Blister infected
Blood blister
Bovine pustular stomatitis virus infection
Bullous impetigo
Cervical bulla
Coma blister
Dermatitis bullous
Dermatitis herpetiformis
Diabetic bullosis
Eczema herpeticum
Eosinophilic pustular folliculitis
Eosinophilic pustulosis
Epidermolysis bullosa
Heat rash
Herpes zoster oticus
Impetigo herpetiformis
Implant site pustules
Implant site vesicles
Incision site blister
Infusion site pustule
Infusion site vesicles
Injection site pustule
Injection site vesicles
Lip blister
Ocular pemphigoid
Oculomucocutaneous syndrome
Paraneoplastic pemphigus
Id
Meddra
10000513
10056508
10048799
10049044
10048941
10005191
10005192
10005372
10006048
10006563
10050019
10069827
10012441
10012468
10062356
10014197
10052834
10049172
10014989
10019343
10063491
10021534
10063866
10063870
10067990
10065487
10065491
10054994
10022111
10049307
10067776
10030081
10057056
Pemphigoid
Pemphigus
Penile blister
Pustular psoriasis
Rash follicular
Rash pustular
SAPHO syndrome
Subcorneal pustular dermatosis
Urticaria vesiculosa
Vaccination site pustule
Vaccination site vesicles
10034277
10034280
10052898
10037575
10037857
10037888
10051316
10042342
10046755
10066047
10069623
This is not always the case!
For other safety topics some PTs can’t
be caught with the query method
Recall
Precision
F-measure
71,9%
52,3%
60,5%
Overview of results
Recall, precision and F-measure rates of automatic OntoADR groupings. SELECT (third column) indicates that a manual selection of PTs has been made
in the MedDRA grouping taken as gold standard. (++) MedDRA reference groupings having a perfect semantic match with the safety topic. (+) MedDRA
reference groupings having an imperfect semantic match with the safety topic (broader or narrower topic).
19
Overview of results
Our query-based grouping method
allows catching most of the terms
present in the MedDRA reference
groupings.
Recall, precision and F-measure rates of automatic OntoADR groupings. SELECT (third column) indicates that a manual selection of PTs has been made
in the MedDRA grouping taken as gold standard. (++) MedDRA reference groupings having a perfect semantic match with the safety topic. (+) MedDRA
reference groupings having an imperfect semantic match with the safety topic (broader or narrower topic).
20
Overview of results
Better recall and precision rates
for HLT reference groupings
than for SMQ
Recall, precision and F-measure rates of automatic OntoADR groupings. SELECT (third column) indicates that a manual selection of PTs has been made
in the MedDRA grouping taken as gold standard. (++) MedDRA reference groupings having a perfect semantic match with the safety topic. (+) MedDRA
reference groupings having an imperfect semantic match with the safety topic (broader or narrower topic).
21
Overview of results
Very good recall and correct precision when
considering only Meddra groupings perfectly
matching the Safety topics
Recall, precision and F-measure rates of automatic OntoADR groupings. SELECT (third column) indicates that a manual selection of PTs has been made
in the MedDRA grouping taken as gold standard. (++) MedDRA reference groupings having a perfect semantic match with the safety topic. (+) MedDRA
reference groupings having an imperfect semantic match with the safety topic (broader or narrower topic).
22
Conclusion
 Results demonstrate that OntoADR and this OWL query-based grouping method can
efficiently support the realization of automatic MedDRA terms groupings.
 Promising result:
 MedDRA terms groupings for pharmacovigilance (mainly SMQs) so far achieved
manually
 An automation of the process could allow an important saving of time
 Next step:
(a) Some terms of the handmade reference MedDRA groupings not retrieved by our automatic
queries, and (b) new terms are caught.
Does this difference in content has an impact (and if so is it positive?) on the signals detected
by traditional statistical methods?
 Further study to address the question of the reliability of those query-based groupings for
signal detection (comparison with standard MedDRA groupings - first of all of SMQs - signal
detection performances).
Forthcoming: Souvignet, J., Declerck, G., Trombert, B., Rodrigues, J.M., Jaulent, M.C., Bousquet, C. Evaluation of
automated term groupings for detecting anaphylactic shock signals with drugs. AMIA 2012, American Medical
Informatics Association Annual Symposium, 3-7 novembre 2012, Chicago (US).
23
ANNEX. Snomed-CT relations used in OntoADR
24
ANNEX. Snomed-CT relations used in OntoADR
25
ANNEX. UMLS mapping difficulties
 Only about 50% of MedDRA terms are mapped with Snomed-CT concepts within UMLS. A
complete mapping of MedDRA seems very difficult to realize.
Especially most MedDRA terms have no direct equivalent in Snomed-CT: their meaning must
be decomposed to be mapped.
Ex.: MedDRA « Joint dislocation postoperative » |10049912| : No direct Snomed-CT equivalent
 Decompositon of MedDRA term to perform the mapping:
• Snomed-CT « Dislocation of joint » |108367008|
• Snomed-CT « Postoperative complication » |385486001|
 A single MedDRA term can be mapped to several Snomed-CT concepts within the same
UMLS concept.
 UMLS embed one-to-one mappings but also one-to-several mappings.
 Necessity to make manual selection to get a unique definition.
26
ANNEX. UMLS mapping difficulties
 UMLS synonymy links between MedDRA terms and Snomed-CT concepts are not always
correct.
 Sometimes one term is more specific than the other.
Ex. MedDRA ‘Pericardial neoplasm’ |10054945| is mapped with Snomed-CT
‘Neoplasm of uncertain behavior of pericardium’ |94997003| and ‘Neoplasm of
pericardium’ |126734005|
Ex. MedDRA ‘Spondylitis’ |10061371| is mapped with Snomed-CT ‘Undifferentiated
spondylitis’ |399096009|, ‘Inflammatory spondylopathy’ |202649003| and ‘Spondylitis’
|84172003|
 Sometimes terms are not at all synonyms:
Ex. MedDRA ‘Vascular disorders’ |10047065| refers to disorders of blood and
lymphatic systems.
Snomed-CT ‘Vascular disorder’ |27550009| only refers to disorders of blood vessels
(‘Disorder of lymphatic system’ is used to refer to lymphatic system troubles)
 With our mapping method, 39.8 % of MedDRA 13.0 terms (i.e. 8305 terms) were mapped via
a one-to-one mapping and 9.5 % (i.e. 1984) were mapped via a one-to-several mapping.
27