Coding with MedDRA
MedDRA® trademark is owned by IFPMA on behalf of ICH
MedDRA was developed under the auspices of the
International Conference on Harmonisation of
Technical Requirements for Registration of
Pharmaceuticals for Human Use (ICH). The activities
of the MedDRA Maintenance and Support Services
Organization (MSSO) are overseen by an ICH MedDRA
Management Board, which is composed of the six ICH
parties (EU, EFPIA, MHLW, JPMA, FDA, PhRMA), the
M di i
Medicines
and
d Healthcare
H lth
products
d t Regulatory
R
l t
Agency
A
(MHRA) of the UK, Health Canada, and the WHO (as
Observer).
MSSO-DI-6017-16.0.1
2
Disclaimer and Copyright Notice
This presentation is protected by copyright and may be used, reproduced,
incorporated into other works, adapted, modified, translated or distributed
under a public license provided that ICH
ICH'ss copyright in the presentation is
acknowledged at all times. In case of any adaption, modification or
translation of the presentation, reasonable steps must be taken to clearly
label, demarcate or otherwise identify that changes were made to or
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modification or translation of the original presentation is endorsed or
sponsored by the ICH must be avoided.
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event shall the ICH or the authors of the original presentation be liable for
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presentation.
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copyright holder.
3
MSSO-DI-6017-16.0.1
Course Overview
•
•
•
•
•
•
•
MedDRA background
MedDRA’s structure, scope, and characteristics
MedDRA maintenance
Coding conventions
Synonym lists
QA of coding
MedDRA Term Selection: Points to Consider
document
• Hands-on coding exercises
MSSO-DI-6017-16.0.1
4
MedDRA Background
What is MedDRA?
Med = Medical
D = Dictionary for
R = Regulatory
A = Activities
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Objectives for MedDRA
Development
Result of an ICH initiative (M1)
To provide:
• An international multi-lingual terminology
• Standardized communication between
industry and regulators
• Support of electronic submissions
• Application through all phases of the
development cycle
7
MSSO-DI-6017-16.0.1
Objectives for MedDRA
Development (cont)
T provide
To
id ((cont):
)
• Classification for a wide range of clinical
information
• Support for multiple medical product
areas
• A terminology that saves time,
resources, and money
MSSO-DI-6017-16.0.1
8
MedDRA and the MSSO
• International support and development of
terminology
• Foster use of MedDRA through
communications and educational offerings
• “Custodians”, not owners, of the terminology
• JMO (partner organization for Japanese
Japaneselanguage MedDRA)
• Governed by a Management Board (industry,
regulators, multi-national, other interested
parties)
9
MSSO-DI-6017-16.0.1
MedDRA Definition
MedDRA is a clinically
clinically-validated
validated
international medical terminology used by
regulatory authorities and the regulated
biopharmaceutical industry. The
terminology is used through the entire
regulatory
g
y process,
p
, from pre-marketing
p
g to
post-marketing, and for data entry,
retrieval, evaluation, and presentation.
MSSO-DI-6017-16.0.1
10
Regulatory Status
• US FDA
–U
Used
d in
i severall d
databases
t b
iincluding
l di FAERS (drugs
(d
and
d
biologics), VAERS (vaccines), and CAERS (foods, dietary
supplements, cosmetics)
• FAERS and VAERS accept LLTs and PTs
• CAERS accepts PTs
– Recommended terminology for adverse event reporting
i severall Proposed
in
P
d Rules
R l
• Japanese Ministry of Health, Labour and Welfare
– Mandatory use in electronic reporting
• LLTs and PTs accepted
11
MSSO-DI-6017-16.0.1
Regulatory Status (cont)
• European Union
– EudraVigilance database
• Clinical trial SUSARs (Suspected Unexpected Serious Adverse
Reactions)
• Post-authorization Individual Case Safety Reports (ICSRs)
• Use MedDRA LLTs (current version or the one previous to it)
– New PV legislation covers suspected adverse reactions from:
• Use inside and outside terms of marketing authorization
• Overdose, misuse, abuse, and medication errors
• Occupational exposures
– Good pharmacovigilance practices (GVP) specifically mention
MedDRA
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12
Regulatory Status (cont)
• European Union (cont)
– Used in interface between EudraVigilance and EU Risk
Management Plan
– Used throughout Summary of Product Characteristics
(labeling)
• ICH M4E Guideline on Common Technical Document
– Recommended in adverse event summary tables
• Canada
– Recommended/preferred terminology for adverse
reaction reporting and Product Monograph (labeling)
13
MSSO-DI-6017-16.0.1
MedDRA Overview
Scope of MedDRA
OUT
IN
Not a drug
di i
dictionary
Patient demographic
terms
Clinical trial study
design terms
Frequency
qualifiers
lifi
Medical conditions
Indications
Investigations (tests, results)
Medical and surgical procedures
Medical, social, family history
Medication errors
Product quality issues
D i
Device-related
l t d issues
i
Pharmacogenetic terms
Toxicologic issues
Standardized queries
Numerical values for
results
Severity descriptors
Not an equipment, device,
diagnostic product dictionary
15
MSSO-DI-6017-16.0.1
MedDRA Structure
System Organ Class (SOC) (26)
High Level Group Term (HLGT) (334)
High Level Term (HLT) (1,717)
Preferred Term (PT) (20,057)
Lowest Level Term (LLT) (71,326)
MedDRA Version 16.0
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16
MedDRA Term Level Definitions
• SOC - Highest
Hi h t level
l
l off the
th terminology,
t
i l
and
d
representing an anatomical or physiological system,
etiology, or purpose
• HLGT - Subordinate to SOC, superordinate grouping
for one or more HLTs
• HLT - Subordinate to HLGT, superordinate grouping
for one or more PTs
• PT - Represents a single medical concept
• LLT - Lowest level of the terminology, related to a
single PT as a synonym, lexical variant, or quasisynonym (Note: All PTs have an identical LLT)
17
MSSO-DI-6017-16.0.1
System Organ Classes
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Blood and lymphatic system disorders
Cardiac
C
di disorders
di d
Congenital, familial and genetic disorders
Ear and labyrinth disorders
Endocrine disorders
Eye disorders
Gastrointestinal disorders
General disorders and administration site
conditions
Hepatobiliary
bl
disorders
d
d
Immune system disorders
Infections and infestations
Injury, poisoning and procedural
complications
Investigations
Metabolism and nutrition disorders
MSSO-DI-6017-16.0.1
•
•
•
•
•
•
•
•
•
•
•
•
Musculoskeletal and connective tissue
disorders
Neoplasms benign, malignant and unspecified
(incl cysts and polyps)
Nervous system disorders
Pregnancy, puerperium and perinatal
conditions
Psychiatric disorders
Renal and urinary disorders
Reproductive system and breast disorders
Respiratory, thoracic and mediastinal disorders
Skin and subcutaneous tissue disorders
Social circumstances
Surgical and medical procedures
Vascular disorders
18
High Level Group Term
Subordinate onlyy to SOCs and superordinate
p
grouping for one or more HLTs
SOC
Cardiac disorders
HLGT
Coronary artery
disorders
HLGT
Cardiac
arrhythmias
HLGT
Cardiac valve
disorders
19
MSSO-DI-6017-16.0.1
High Level Term
Subordinate to HLGTs and superordinate grouping
for the PTs linked to it
SOC
Cardiac disorders
HLGT
C di arrhythmias
Cardiac
h th i
HLT
Cardiac conduction
disorders
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HLT
Rate and rhythm
disorders NEC
HLT
Supraventricular
arrhythmias
20
Examples of PTs
SOC = Cardiac disorders
HLGT = Cardiac arrhythmias
HLT = Rate and rhythm disorders NEC
PT
Arrhythmia
PT
Bradycardia
PT
Tachyarrhythmia
21
MSSO-DI-6017-16.0.1
Examples of LLTs
SOC = Cardiac disorders
HLGT = Cardiac arrhythmias
HLT = Rate and rhythm disorders NEC
PT = Arrhythmia
LLT
Arrhythmia
NOS
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LLT
Arrhythmia
LLT
Dysrhythmias
LLT (Non-current)
Other specified cardiac
dysrhythmias
22
Non-Current Terms
• Non-current terms are flagged
gg at the
LLT level within MedDRA
• Not recommended for continued use
• Retained within the terminology to
preserve historical data for retrieval and
analysis
• Terms that are vague,
vague ambiguous
ambiguous, out
outdated, truncated, or misspelled
• Terms derived from other terminologies
that do not fit MedDRA rules
23
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MedDRA Codes
• Each MedDRA term assigned an 8-digit
numeric code
• The code is non-expressive
• Codes can fulfill a data field in various
electronic submission types (e.g., E2B)
• Initially assigned alphabetically by term
starting with 10000001
– New terms are assigned sequentially
• Supplemental terms are assigned codes
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24
A Multi-Axial Terminology
• Multi-axial = the representation
p
of a
medical concept in multiple SOCs
– Allows grouping by different classifications
– Allows retrieval and presentation via different
data sets
• Purpose of Primary SOC
– Determines which SOC will represent a PT
during cumulative data outputs
– Is used to support consistent data
presentation for reporting to regulators
25
MSSO-DI-6017-16.0.1
A Multi-Axial Terminology (cont)
SOC = Respiratory, thoracic and
mediastinal disorders
HLGT = Respiratory tract
infections
HLT = Viral upper respiratory
tract infections
SOC = Infections and
infestations
HLGT = Viral infectious
disorders
HLT = Influenza viral
infections
PT = Influenza
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A Multi-Axial Terminology (cont)
PTs in the follo
following
ing SOCs only
onl appear
appea in
that particular SOC and not in others,
i.e., they are not multi-axial
• Investigations
• Surgical
g
and medical procedures
p
• Social circumstances
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27
Rules for Primary SOC Allocation
• PTs for diseases, signs and symptoms are assigned to
prime manifestation site SOC
• Congenital and hereditary anomalies terms have SOC
Congenital, familial and genetic disorders as Primary SOC
• Neoplasms terms have SOC Neoplasms benign,
malignant and unspecified (incl cysts and polyps) as
Primary SOC
– Exception:
p
Cysts
y
and p
polyps
yp have prime
p
manifestation site SOC
as Primary SOC
• Infections and infestations terms have SOC Infections
and infestations as Primary SOC
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Primary SOC Priority
If a PT links to more than one of the
exceptions, the following priority will be
used to determine primary SOC:
1st: Congenital, familial and genetic disorders
2nd: Neoplasms benign, malignant and
unspecified (incl cysts and polyps)
3rd: Infections and infestations
29
MSSO-DI-6017-16.0.1
SOC Congenital, familial
and genetic disorders - Example
PT
HLT
Congenital Viral infections
HIV
congenital
infection
SOC
Congenital,
familial and
genetic
disorders (P)
Neonatal and
Pregnancy,
Congenital
perinatal
puerperium
neonatal
infections
conditions
and perinatal
conditions
Retroviral
Viral infectious
Infections and
infections
disorders
infestations
Acquired
Immunodeficiency Immune
immunodeficiency syndromes
system
syndromes
disorders
MSSO-DI-6017-16.0.1
HLGT
Infections and
infestations
congenital
30
Conditions vs. Investigations
PT
HLT
HLGT
Pregnancy test
positive
Reproductive Endocrine
Investigations
hormone
investigations
analyses
(incl sex
hormones)
Pregnancy
Normal
pregnancy,
labour and
delivery
Pregnancy,
labour,
delivery and
postpartum
conditions
SOC
Pregnancy,
puerperium
and perinatal
conditions
Be careful to distinguish between a condition and an
investigation or a result of an investigation
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Standardised MedDRA Queries
(SMQs)
• Groupings of terms from more than one SOC
related to defined medical condition or area of
interest
• Examples:
– Lack of efficacy/effect; Rhabdomyolysis/myopathy;
Osteonecrosis
• 90 SMQ topics available in MedDRA v16.0
• More information on MSSO Web site
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MedDRA Maintenance
MedDRA Maintenance
• MedDRA is a user responsive
p
terminology
gy
• Subscribers may submit change requests to the
MSSO for consideration
– Core and basic subscribers: 100 change requests
(CRs) per month
– For simple changes (PT and LLT levels), notification
of supplemental change within 7-10 working days
– Weekly supplemental changes posted on MSSO Web
site
– Complex changes above PT level received all year
round. Posted for subscribers’ comments mid-year.
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MedDRA Maintenance (cont)
• Twice yearly official updates
– 1 September X.1 release (Simple changes only)
– 1 March X.0 release (Complex and simple
changes)
35
MSSO-DI-6017-15.0.3
WebCR
• Web-based tool for Change Requests (CR)
– URL: https://mssotools.com/webcr/
– Via the Change Request Information page
• Ability to submit CRs online
• Immediate confirmation
• Review unsubmitted CRs online
• Ability to query CR history back to v5.1
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Change Request Justification
Statements
• Justification
f
statement always
l
required
d
• Inadequate justification – “Term does not
exist in MedDRA”
• Adequate justification – statement of need
pp
with definitions and references (PDFs
(
• Support
preferred)
• Examples of need:
– Term needed to code an indication
– Concept is being reported in a clinical trial
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Proactive MedDRA Maintenance
• What is the proactive approach?
– Corrections/improvements made internally by the MSSO
– General changes suggested by users
• Submitting ideas
– Send to MSSO Help Desk. Justification is helpful.
– Example: Consider consolidation of HLTs with only one PT
• Evaluation of proposals
– MSSO is not obligated to respond
– Proactive approach does not replace usual CR process
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MedDRA Version Analysis Tool (MVAT)
•
•
•
•
Web based (https://mssotools.com/mvat)
Web-based
Free to all subscribers
Allows for comparison of any two versions
Features
– Version Report Generator (produces exportable report
comparing any two versions)
– Data Impact Report (identifies changes to a specific
set of MedDRA terms or codes uploaded to MVAT)
– Search Term Change (identifies changes to a single
MedDRA term or code)
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MSSO-DI-6017-16.0.1
MSSO’s MedDRA Browsers
• MedDRA Desktop Browser
– Download from MSSO Web site
– View/search MedDRA and SMQs
– Export functionality
• MedDRA Web-Based Browser
– https://www.meddrabrowser.org/dsnavigator/
– Requires specific user ID and password
– Access to all MedDRA versions in English and
available EU languages (and Chinese, if subscribed)
– View/search MedDRA and SMQs
– Export functionality
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MedDRA Browser Demonstration
and Instruction
Coding Exercises
Assessing the Reported Information
• Consider what is being reported. Is it a:
–
–
–
–
–
–
–
–
–
–
Clinical condition - Diagnosis,
g
, sign
g or symptom?
y p
Indication?
Test result?
Injury?
Procedure?
The type of report will
Medication error?
influence the way you
search for a suitable LLT.
Product quality issue?
It may indicate in which
Social circumstance?
SOC you expect to find
Device issue?
the closest match.
Procedural complication?
– Is it a combination of these?
43
MSSO-DI-6017-16.0.1
MedDRA Browsing Tips
•
•
•
•
•
•
•
•
First, try using actual words from reporter
U “top-down”
Use
“t d
” and
d “bottom-up”
“b tt
” approaches
h
Look at the “neighbors”
Check the hierarchy
Consider synonyms, e.g., “Liver” and “Hepatic”
Use word stems, e.g., “Pancrea”
Search different word orders
orders, “and”
and , “or”
or , etc.
etc
Use available resources for difficult verbatim terms (web
search, medical dictionaries, colleagues)
MSSO-DI-6017-16.0.1
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Exercise 1
The patient states she has been experiencing
headaches, dizziness and vertigo.
_______________ LLT  _______________ PT
_______________ LLT  _______________ PT
_______________ LLT  _______________ PT
45
MSSO-DI-6017-16.0.1
Exercise 2
Lab results indicate an increase in erythrocytes.
_______________ LLT  _______________ PT
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Exercise 3
Drug was contaminated with Staphylococcus.
_______________ LLT  _______________ PT
47
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Exercise 4
A three year old boy was admitted for loratadine toxicity
after accidentally ingesting the remaining tablets in the
bottle.
_______________ LLT  _______________ PT
_______________ LLT  _______________ PT
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Exercise 5
The patient’s insulin pump was noted to be broken.
_______________ LLT  _______________ PT
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MSSO-DI-6017-16.0.1
Coding with MedDRA
What Does MedDRA Offer?
•S
Size and
d specificity
f
(“
(“granularity”)
l
”)
• Hierarchy/grouping terms
• “Support” SOCs widen data
collection/analysis options
p
and medicallyy rigorous
g
• Up-to-date
• User-responsive
• STANDARDIZATION
51
MSSO-DI-6017-16.0.1
Why Do We Need Coding
Conventions?
• Differences in medical aptitude of coders
• Consistency concerns (many more
“choices” to manually code terms in
MedDRA compared to older
terminologies)
i l i )
• Even with an autoencoder, may still need
manual coding
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Can I Make Coding Conventions Specific
to My Company/Product?
• MedDRA may reduce the need to do this
because:
– Increased size/granularity results in more accurate
representation of data
– Secondary
Seconda SOC allocations allow
allo for
fo different
diffe ent
“views” of the data
• This type of approach should be done
cautiously
53
MSSO-DI-6017-16.0.1
Synonym Lists
• Can be derived from existing
g term lists or
directly from verbatims
• For recurring, but unusual, verbatims – onetime assignment to a MedDRA term
• Enforces consistency by limiting choices once
g
MedDRA term is assigned
• Increases likelihood of autoencoding “hit”
• Natural outgrowth of a legacy data
conversion
• Maintenance required
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Synonym List Examples
Verbatim
e bat
LLT
Throbbing above
temple
Aching all over head
Pulsing pain in head
Headache
Comment
Co
e t
LLT Myalgia of
lower extremities is
Muscular pain in legs
Myalgia of lower
extremities
a better choice
than LLT Muscular
pain since it
captures both the
event and body site
55
MSSO-DI-6017-16.0.1
Synonym List Maintenance
• For new MedDRA versions, run synonyms
against new MedDRA LLTs
– Identify new non-current LLTs that are on
synonym list; flag for recoding
– Identify possible new current direct matches
• Remaining challenge is to determine if “better
medical matches” have been added
(essentially, a manual process)
• Communicate results to users of synonym list
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56
QA Reports
• Allows reviewers to check for
consistency (both auto-encoded and
human-coded terms)
• Check for adherence to/deviation from
coding conventions
• Check
Ch k for
f emerging
i drifts/biases
d ift /bi
• Multiple data views (verbatims to coded
terms; coded term to verbatims; by
SOC, etc.)
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MedDRA Term Selection:
Points to Consider (MTS:PTC)
• An ICH-endorsed guide for MedDRA users
• Provides term selection advice for industry
and regulatory purposes
• Objective is to promote accurate and
consistent term selection to facilitate a
common understanding of shared data
• Recommended to be used as the basis for
individual organizations’ coding
conventions
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60
MedDRA Term Selection: PTC (cont)
• Developed by a working group of the ICH Steering
Committee
– Regulators and industry representatives
– EU, Japan, USA
– Canadian observer, MSSO, JMO
• Updated twice yearly with each MedDRA release
• Available on MSSO, JMO, and ICH Web sites
– English and Japanese
– Variety of file formats for ease of viewing and editing
– Summary of Changes document
61
MSSO-DI-6017-16.0.1
MTS:PTC Points of Note
• In some cases with more than one option
for selecting terms, a “preferred option” is
identified but this does not limit MedDRA
users to applying that option.
Organizations should be consistent in their
choice of option.
• Section 4.1 – Versioning (Appendix)
– 4.1.1 Versioning methodologies
– 4.1.2 Timing of version implementation
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62
General Term Selection Principles
•
•
•
•
•
•
•
•
•
•
Quality of Source Data
Quality Assurance
Do Not Alter MedDRA
Always Select a Lowest Level Term
Select Only Current Lowest Level Terms
When to Request a Term
g
in Term Selection
Use of Medical Judgment
Selecting More than One Term
Check the Hierarchy
Select Terms for All Reported Information, Do Not
Add Information
63
MSSO-DI-6017-16.0.1
Quality of Source Data
Quality Assurance
• Quality of original information impacts quality of
output
• Obtain clarification of data
• Can be optimized by careful design of data
collection forms and proper training of staff
g
coding
g guidelines
g
should be
• Organizations’
consistent with MTS:PTC
• Review of term selection by qualified individuals
• Human oversight of automated coding results
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64
Do Not Alter MedDRA
•M
MedDRA
dDRA is
i a standardized
t d di d terminology
t
i l
with a pre-defined term hierarchy
• Users must not make ad hoc structural
alterations, including changing the
primary SOC allocation
• If terms are incorrectly placed, submit a
change request to the MSSO
65
MSSO-DI-6017-16.0.1
Always Select a Lowest Level Term
Select Only Current LLTs
• Lowest Level Term that most accurately
reflects the reported verbatim information
should be selected
• Degree of specificity may be challenging
– Example: “Abscess on face”  select “Facial
abscess
b
,”” nott simply
i l “Abscess
Ab
”
• Select current LLTs only
– Non-current terms for legacy conversion/historical
purposes
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When to Request a Term
Use of Medical Judgment
• Avoid company-specific “work-arounds” for
MedDRA deficiencies. If concept not
adequately represented in MedDRA, submit
Change Request to MSSO.
• If no exact match in MedDRA, use medical
judgment to match to an existing term that
adequately represents the concept
67
MSSO-DI-6017-16.0.1
Selecting More than One Term
Check the Hierarchy
• Can select more than one LLT to represent
reported information. Document procedures.
– Selecting one term may lead to loss of specificity
– Selecting more than one term may lead to
redundant counts
• Check the hierarchy above a selected LLT
(PT, HLT, HLGT, SOC) to ensure placement
accurately reflects meaning of reported term
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Select Terms for All Reported
Information
• Select terms for every AR/AE reported,
regardless of causal association
• Select terms for device-related events,
product quality issues, medication errors,
medical and social history, investigations
and indications as appropriate
• If diagnosis reported with characteristic
signs and symptoms, preferred option is to
select term for diagnosis only
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MSSO-DI-6017-16.0.1
Do Not Add Information
• Do not make diagnosis if only
signs/symptoms reported
Reported
LLT Selected
Comment
Abdominal pain
Abdominal p
pain,
increased serum
amylase, and increased
serum lipase
Serum amylase
S
l
increased
It is inappropriate
pp p
to assign an LLT for
diagnosis of
“pancreatitis”
Lipase increased
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Pitfalls and Solutions
• In selecting an LLT for a result of an
investigation parent PT of the selected LLT should
investigation,
contain a qualifier/adjective
– E.g., “present/absent”, “increased/decreased”, etc.
• If parent PT of selected LLT does not contain a
qualifier/adjective, you may have inadvertently
selected an LLT for the test name,, not a result
– E.g., “Blood found in urine”, select LLT Blood in
urine (PT Blood urine present). Do not select LLT
Blood urine (PT Blood urine has no qualifier/
adjective and thus represents the test name only)
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Pitfalls and Solutions (cont)
• Inappropriate terms may be selected by
autocoder
t
d
• Review all autocoding carefully
– “Allergic to CAT scan” autocoded as
LLT Allergic to cats
– “Myocardial infarction in the fall of 2000”
a tocoded as LLT Myocardial
autocoded
M oca dial infarction
infa ction and
LLT Fall
MSSO-DI-6017-16.0.1
72
FDA-Defined Coding Errors
• Missed Concepts
– All medical concepts described after the product is
taken should be coded
– Example: “The patient took drug X and developed
alopecia, increased LFTs and pancreatitis”.
Manufacturer only codes alopecia and increased
LFTs (missed concept of pancreatitis)
– Example: “The patient took drug X and developed
interstitial nephritis which later deteriorated into
renal failure”. Manufacturer only codes interstitial
nephritis (missed renal failure concept)
Acknowledgement: Dr. Toni Piazza-Hepp, Office of Surveillance
and Epidemiology, CDER
73
MSSO-DI-6017-16.0.1
FDA-Defined Coding Errors (cont)
• “Soft
Soft Coding”
Coding
– Selecting a term which is both less specific and less
severe than another MedDRA term is “soft coding”
– Example: “Liver failure” coded as hepatotoxicity or
increased LFTs
– Example: “Aplastic anemia” coded as unspecified
anemia
– Example: “Rash subsequently diagnosed as Stevens
Johnson syndrome” coded as rash
Acknowledgement: Dr. Toni Piazza-Hepp, Office of Surveillance
and Epidemiology, CDER
MSSO-DI-6017-16.0.1
74
Term Selection Points
• Diagnoses and Provisional Diagnoses with or without Signs and
Symptoms
• Death
D th and
d Other
Oth Patient
P ti t Outcomes
O t
• Suicide and Self-Harm
• Conflicting/Ambiguous/Vague Information
• Combination Terms
• Age vs. Event Specificity
• Body Site vs. Event Specificity
• Location Specific vs. Microorganism Specific Information
• Modification of Pre-existing
Pre existing Conditions
• Exposures During Pregnancy and Breast Feeding
• Congenital Terms
• Neoplasms
• Medical and Surgical Procedures
• Investigations
MSSO-DI-6017-16.0.1
75
Term Selection Points (cont)
• Medication/Administration Errors, Accidental Exposures and
Occupational Exposures
• Misuse,
Misuse Abuse and Addiction
• Transmission of Infectious Agent via Product
• Overdose, Toxicity and Poisoning
• Device-related Terms
• Drug Interactions
• No Adverse Effect and “Normal” Terms
• Unexpected Therapeutic Effect
• Modification
M difi ti off Effect
Eff t
• Social Circumstances
• Medical and Social History
• Indication for Product Use
• Off Label Use
• Product Quality Issues
MSSO-DI-6017-16.0.1
76
Diagnoses and Provisional Diagnoses
SINGLE DIAGNOSIS
DEFINITIVE DIAGNOSIS
Single diagnosis without signs
and symptoms
PROVISIONAL DIAGNOSIS
Single provisional diagnosis
without signs and symptoms
•Diagnosis (only possible option) •Provisional diagnosis (only
possible option)
p “Myocardial
y
Example:
infarction”  select
“Myocardial infarction”
Example:
p “Possible myocardial
y
infarction”  select
“Myocardial infarction” (select
term as if definitive diagnosis)
Similar principles apply for multiple diagnoses
77
MSSO-DI-6017-16.0.1
Diagnoses and Provisional Diagnoses (cont)
SINGLE DIAGNOSIS
DEFINITIVE DIAGNOSIS
PROVISIONAL DIAGNOSIS
Single diagnosis with signs/
symptoms
Single provisional diagnosis with
signs/symptoms
•Preferred: Diagnosis only
•Preferred: Provisional
diagnosis and signs/symptoms
Example: “Anaphylactic
Example: “Possible myocardial
reaction with rash,
rash dyspnea,
dyspnea
hypotension, and laryngospasm”
 select “Anaphylactic
reaction”
infarction with chest pain,
pain
dyspnea, diaphoresis”  select
“Myocardial infarction” “Chest
pain”, “Dyspnea”, and
“Diaphoresis”
Similar principles apply for multiple diagnoses
MSSO-DI-6017-16.0.1
78
Diagnoses and Provisional Diagnoses (cont)
SINGLE DIAGNOSIS
DEFINITIVE DIAGNOSIS
PROVISIONAL DIAGNOSIS
Single diagnosis with signs/
symptoms
Single provisional diagnosis with
signs/symptoms
•Alternate: Diagnosis and
signs/symptoms
•Alternate: Signs/symptoms
only (as provisional diagnosis
may change
Example:
E
mp “Anaphylactic
p y
reaction E
Example:
mp “Possible my
myocardial
with rash, dyspnea, hypotension, infarction with chest pain,
and laryngospasm”  select
dyspnea, diaphoresis”  select
“Anaphylactic reaction”, “Rash”, “Chest pain”, “Dyspnea”, and
“Dyspnea”, Hypotension”, and
“Diaphoresis”
“Laryngospasm”
MSSO-DI-6017-16.0.1
Similar principles apply for multiple diagnoses
79
What Terms to Select?
•
Sepsis
p leading
g to shock from possible
p
spontaneous bacterial peritonitis or
bowel perforation
Sepsis?
Shock?
Septic shock?
Spontaneous bacterial peritonitis?
Bowel perforation?
MSSO-DI-6017-16.0.1
80
Diagnoses and Provisional Diagnoses (cont)
• Always include signs/symptoms not associated
with
i h diagnosis
di
i
Reported
LLT Selected
Myocardial infarction
Myocardial infarction, chest
Jaundice (note that jjaundice is
pain dyspnea,
pain,
dyspnea diaphoresis,
diaphoresis
not typically associated with
ECG changes and jaundice
myocardial infarction)
81
MSSO-DI-6017-16.0.1
Conflicting/Ambiguous Information
• First, try to obtain more specific information
Reported
Hyperkalemia with a
serum potassium of 1.6
mEq/L
GU pain
MSSO-DI-6017-16.0.1
LLT Selected
Serum potassium
abnormal
Pain
Comment
LLT Serum potassium
abnormal covers both of
the reported concepts
(note: serum potassium of
1.6 mEq/L is a low result,
not high)
GU could be either
“GU”
“genito-urinary” or “gastric
ulcer”. If additional
information is not available,
then select a term to
reflect the information
that is known, i.e., LLT Pain
82
Vague Information
• First, try to obtain more specific information
Reported
Turned green
Patient had a medical
problem of unclear type
LLT Selected
Comment
Unevaluable event
“Turned green” reported
alone is vague; this could
refer to a patient condition
or even to a product (e.g.,
pills)
Ill-defined disorder
Since it is known that there
is some form of a medical
disorder, LLT Ill-defined
disorder can be selected
83
MSSO-DI-6017-16.0.1
What Terms to Select?
•
•
Clinical complication
p
of IUD
IUD complication (PT Medical device
complication)?
Intra-uterine death (PT Foetal death)?
Unevaluable event?
Hypoglycemia (blood glucose = 200
mg/dL)
Blood glucose abnormal?
Blood glucose increased?
Hypoglycemia?
MSSO-DI-6017-16.0.1
84
Combination Terms
• One condition is more specific than the other
Reported
LLT Selected
Arrhythmia due to atrial
fibrillation
Atrial fibrillation
• A MedDRA combination term is available
Reported
LLT Selected
Retinopathy due to diabetes
Diabetic retinopathy
85
MSSO-DI-6017-16.0.1
Combination Terms (cont)
• If splitting provides more clinical information,
select mo
more
e than one te
term
m
• In all cases of combination terms, apply medical
judgment
MSSO-DI-6017-16.0.1
Reported
LLT Selected
Diarrhea and vomiting
Diarrhea
Vomiting
Wrist fracture due to fall
Wrist fracture
Fall
86
What Terms to Select?
•
Retinal disease from HIV with near total
blindness (R and L)
Retinal damage?
Retinal disorder?
HIV disease?
Blindness?
HIV retinopathy?
ti
th ?
Blindness both eyes?
87
MSSO-DI-6017-16.0.1
Investigations
• Medical condition vs. investigation result
MSSO-DI-6017-16.0.1
Reported
LLT Selected
Comment
Hypoglycemia
Hypoglycemia
LLT Hypoglycemia
links to SOC
Decreased glucose
Glucose decreased
Metabolism and
nnutrition
t iti n disorders
dis d s
LLT Glucose
decreased links to
SOC Investigations
88
Investigations (cont)
• Unambiguous investigation result
Reported
LLT Selected
Comment
Glucose 40 mg/dL
Glucose low
Glucose is clearly
below the reference
range
• Ambiguous investigation result
Reported
His glucose was 40
LLT Selected
Comment
Glucose abnormal
No units have been
reported. Select LLT
Glucose abnormal if
clarification cannot
be obtained.
89
MSSO-DI-6017-16.0.1
Investigations (cont)
• Investigation results consistent with diagnosis
Reported
LLT Selected
Comment
Elevated potassium, K
7.0 mmol/L, and
hyperkalemia
Hyperkalemia
It is not necessary to
select LLT Potassium
increased
• Grouped investigation result terms
Reported
LLT Selected
Increased alkaline
phosphatase,
increased SGPT,
increased SGOT and
elevated LDH
Alkaline phosphatase
increased
SGPT increased
SGOT increased
LDH increased
MSSO-DI-6017-16.0.1
Comment
Select four individual
terms. A single term
such as LLT Liver
function tests
abnormal should not
be selected.
90
What Terms to Select?
•
Testing showed increased serum
creatinine and
d BUN, with
h increased
d
BUN/creatinine ratio
Increased serum creatinine?
BUN increased?
Blood urea nitrogen/creatinine ratio increased?
Renal function tests NOS abnormal?
•
CSF was positive for Candida spp.
Candidal meningitis?
Candida test positive?
91
MSSO-DI-6017-16.0.1
Medication Errors
See Appendix B of MedDRA Introductory Guide for
p Descriptions
p
Concept
“Top-down” navigation in HLGT Medication errors
is best approach for term selection
• Medication error with clinical consequences
Reported
LLT Selected
Patient was administered wrong
drug and experienced hypotension
Wrong drug administered
Hypotension
Because of similar sounding drug
names, the patient took the wrong
drug and experienced a rash
Drug name confusion
Wrong drug administered
Rash
MSSO-DI-6017-16.0.1
92
Medication Errors (cont)
Important to record occurrence or potential
occurrence of medication error
• Medication error without clinical consequences
Reported
LLT Selected
Medication was given
intravenously instead of
intramuscularly without
sequelae
Intramuscular
formulation
administered by other
route
N adverse
No
d
s effect
ff t
Pharmacist notices that
the names of two drugs
are similar and is
concerned that this may
result in a medication
error
Circumstance or
information capable of
leading to medication
error
Comment
If specifically reported
that there is no adverse
effect, acceptable to
select LLT No adverse
effect
ff t
LLT Drug name
confusion could be an
optional additional term
to select. Note: this
example is a potential
medication error.
93
MSSO-DI-6017-16.0.1
Overdose, Toxicity and Poisoning
If overdose, poisoning or toxicity is explicitly
p
, select the appropriate
pp p
term
reported,
• Overdose with clinical consequences
Reported
LLT Selected
Stomach upset from study drug
overdose
Stomach upset
Overdose
• Overdose
O d
without
ith t clinical
li i l consequences
Reported
LLT Selected
Patient received an
overdose of medicine
without any adverse
consequences
Overdose
No adverse effect
MSSO-DI-6017-16.0.1
Comment
LLT No adverse
effect can also be
selected
94
What Term to Select?
•
Doctor prescribed the wrong drug. The
pharmacist noticed the error before
p
giving the drug to the patient.
Wrong drug administered?
Drug prescribing error?
Intercepted drug prescribing error?
•
Unintentionally took more than
maximum recommended
d d dose
d
d to
due
dispensing error
MSSO-DI-6017-16.0.1
Accidental overdose?
Incorrect dose administered?
Drug dispensing error?
95
Medication Errors Reported to
EudraVigilance (EV)
• Examined selected medication error terms from MedDRA
(Overdose terms excluded)
• Grouped medication error terms related to medicines by
Anatomical Therapeutic Chemical (ATC) classification system
• Retrieved individual cases reported to EV in postphase (includes
(
non-serious adverse reactions
authorisation p
reported periodically for centrally authorised products (CAPs)
in accordance with previous Volume 9A)
MSSO-DI-6017-16.0.1
Acknowledgement: Dr. Sabine Brosch, EMA
96
Medication Error Cases in
EudraVigilance
Proportion of medication error reports ~ double from outside EEA
MSSO-DI-6017-16.0.1
Acknowledgement: Dr. Sabine Brosch, EMA
97
Medication Errors by ATC Class
*
Examples:
Medication errors associated with ATC Group Nervous System refer mainly to treatment non-compliance with antipsychotics
** Incorrect dosing
*** Problems injecting immunosuppressant leading to incomplete dosing (No ADR)
MSSO-DI-6017-16.0.1
Acknowledgement: Dr. Sabine Brosch, EMA
98
Medication Errors Associated with
Serious ADRs
% used as some products
fall into more than one category
MSSO-DI-6017-16.0.1
Acknowledgement: Dr. Sabine Brosch, EMA
99
Medication Errors by
EMA Internal Groupings
MSSO-DI-6017-16.0.1
Acknowledgement: Dr. Sabine Brosch, EMA
100
Misuse, Abuse and Addiction
New MTS:PTC Section
101
MSSO-DI-6017-16.0.1
Coding Exercises
• Narratives and short verbatims
• Assess
A
the
th reported
t d terms
t
– Identify what concepts are reported (diagnosis,
death, investigations, etc.)
• Refer to the appropriate sections of the
MTS:PTC for guidance on term selection
– For example, Section 3.2 for death terms
• Use MTS:PTC preferred options (forget your
organization’s conventions)
• Use browser to search for and select LLTs
(also record PT and primary SOC)
MSSO-DI-6017-16.0.1
102
Specific Tips for Narrative Exercises
• Overall,, coding
g principles
p
p
are the same
as for short verbatim exercises
• Code all of the following:
– Events (including procedures and
investigations as needed)
– Indications
I di ti
– Medical history
– Social history
103
MSSO-DI-6017-16.0.1
Sample Narrative
A 75-year-old male receiving Drug X for
f
rheumatoid arthritis developed an area
of darkened skin on his chest. The
patient’s medical history is significant
for p
peripheral
p
vascular disease and
cigarette smoking. The skin lesion was
excised; it was revealed to be a
seborrhoeic wart.
MSSO-DI-6017-16.0.1
104
Course Summary
• In this course,, we covered:
– A review of MedDRA’s scope and structure,
including primary SOC allocation rules
– Coding conventions, synonym lists, and
coding QA
– Introduction to the MedDRA Term
S l ti
Selection:
Points
P i t to
t Consider
C id document
d
t
– Coding exercises
105
MSSO-DI-6017-16.0.1
MSSO Contacts
• Web site
– www.meddramsso.com
• E-mail
– [email protected]
• Telephone
– International AT&T Toll Free: 877.258.8280
– Direct Dial (USA): +1 571.313.2574
• Fax (USA)
– +1 571.313.2345
MSSO-DI-6017-16.0.1
106