MedDRA Term Selection:
Points to Consider

Section 1. Introduction
1.1 Objectives of this Document
1.2 Uses of MedDRA
1.3 How to Use this Document
1.4 Preferred Option
1.5 MedDRA Browsing Tools
Section 2. General Term Selection Principles
2.1 Quality of Source Data
2.2 Quality Assurance
2.3 Do Not Alter MedDRA
2.4 Always Select a Lowest Level Term
2.5 Select Only Current Lowest Level Terms
2.6 When to Request a Term
2.7 Use of Medical Judgment in Term Selection
2.8 Selecting More than One Term
2.9 Check the Hierarchy
2.10 Select Terms for All Reported Information, Do Not Add Information
Section 3 Term Selection Points
3.1 Definitive and Provisional Diagnoses with or without Signs and Symptoms
3.2 Death and Other Patient Outcomes
3.2.1 Death with ARs/AEs
3.2.2 Death as the only reported information
3.2.3 Death terms that add important clinical information
3.2.4 Other patient outcomes (non-fatal)
3.3 Suicide and Self-Harm
3.3.1 If overdose is reported
3.3.2 If self-injury is reported
3.3.3 Fatal suicide attempt
3.4 Conflicting/Ambiguous/Vague Information
3.4.1 Conflicting information
3.4.2 Ambigious information
3.4.3 Vague information
3.5 Combination Terms
3.5.1 Diagnosis and sign/symptom
3.5.2 One reported condition is more specific than the other
3.5.3 A MedDRA combination term is available
3.5.4 When to “split” into more than one MedDRA term
3.5.5 Event reported with pre-existing condition
3.6 Age vs. Event Specificity
3.6.1 MedDRA term includes age and event information
3.6.2 No available MedDRA term includes both age and event information
3.7 Body Site vs. Event Specificity
3.7.1 MedDRA term includes body site and event information
3.7.2 No available MedDRA term includes both body site and event information
3.7.3 Event occurring at multiple body sites
3.8 Location-Specific vs. Microorganism-Specific Infection
3.8.1 MedDRA term includes microorganism and anatomic location
3.8.2 No available MedDRA term includes both microorganism and anatomic location
3.9 Modification of Pre-existing Conditions
3.10 Exposures During Pregnancy and Breast Feeding
3.10.1 Events in the mother
3.10.2 Events in the child or foetus
3.11 Congenital Terms
3.11.1 Congenital conditions
3.11.2 Acquired conditions (not present at birth)
3.11.3 Conditions not specified as either congenital or acquired
3.12 Neoplasms
3.12.1 Do not infer malignancy
3.13 Medical and Surgical Procedures
3.13.1 Only the procedure is reported
3.13.2 Procedure and diagnosis are reported
3.14 Investigations
3.14.1 Results of investigations as ARs/AEs
3.14.2 Investigation results consistent with diagnosis
3.14.3 Investigation results not consistent with diagnosis
3.14.4 Grouped investigation result terms
3.14.5 Investigation terms without qualifiers
3.15 Medication Errors, Accidental Exposures and Occupational Exposures
3.15.1 Medication errors
3.15.2 Accidental exposures and occupational exposures
3.16 Misuse, Abuse and Addiction
3.16.1 Misuse
3.16.2 Abuse
3.16.3 Addiction
3.16.4 Drug diversion
3.17 Transmission of Infectious Agent via Product
3.18 Overdose, Toxicity and Poisoning
3.18.1 Overdose reported with clinical consequences
3.18.2 Overdose reported without clinical consequences
3.19 Device-related Terms
3.19.1 Device-related event reported with clinical consequences
3.19.2 Device-related event reported without clinical consequences
3.20 Drug Interactions
3.20.1 Reporter specifically states an interaction
3.20.2 Reporter does not specifically state an interaction
3.21 No Adverse Effect and "Normal" Terms
3.21.1 No adverse effect
3.21.2 Use of “normal” terms
3.22 Unexpected Therapeutic Effect
3.23 Modification of Effect
3.23.1 Lack of effect
3.23.2 Do not infer lack of effect
3.23.3 Increased, decreased and prolonged effect
3.24 Social Circumstances
3.24.1 Use of terms in this SOC
3.24.2 Illegal acts of crime or abuse
3.25 Medical and Social History
3.26 Indication for Product Use
3.26.1 Medical conditions
3.26.2 Complex indications
3.26.3 Indications and genetic markers or abnormalities
3.26.4 Prevention and prophylaxis
3.26.5 Procedures and diagnostic tests as indications
3.26.6 Supplementation and replacement therapies
3.26.7 Indication not reported
3.27 Off Label Use
3.27.1 Off label use when reported as an indication
3.27.2 Off label use when reported with an AR/AE
3.28 Product Quality Issues
3.28.1 Product quality issue reported with clinical consequences
3.28.2 Product quality issue reported without clinical consequences
3.28.3 Product quality issue vs. medication error
Section 4 Appendix
4.1 Versioning
4.1.1 Versioning methodologies
4.1.2 Timing of version implementation
4.2 Links and References
4.3 Membership of the ICH Points to Consider Working Group
4.3.1 Current members of the ICH Points to Consider Working Group
4.3.2 Former members of the ICH Points to Consider Working Group




 

MedDRA® TERM SELECTION:

POINTS TO CONSIDER

ICH-Endorsed Guide for MedDRA Users

Release 4.13
Based on MedDRA Version 20.0

 

 

 

1 March 2017


Disclaimer and Copyright Notice
This document 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's copyright in the document is acknowledged at all times. In case of any adaption, modification or translation of the document, reasonable steps must be taken to clearly label, demarcate or otherwise identify that changes were made to or based on the original document. Any impression that the adaption, modification or translation of the original document is endorsed or sponsored by the ICH must be avoided.
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MedDRA® trademark is owned by IFPMA on behalf of ICH

 


Section 1 – INTRODUCTION

The Medical Dictionary for Regulatory Activities terminology (MedDRA) was designed for sharing regulatory information for human medical products. In order for MedDRA to harmonise the exchange of coded data, users should be consistent in the assignment of terms to verbatim reports of symptoms, signs, diseases, etc.

This MedDRA Term Selection: Points to Consider (MTS:PTC) document is an ICH-endorsed guide for MedDRA users. It is updated in step with new MedDRA versions and is a companion document to MedDRA. It was developed and is maintained by a working group charged by the ICH Steering Committee. The working group consists of regulatory and industry representatives of the European Union, Japan, and the United States, as well as representatives from the Canadian regulatory authority, the World Health Organization, the MedDRA Maintenance and Support Services Organization (MSSO) and the Japanese Maintenance Organization (JMO) (see Appendix, Section 4.3 for list of members).

1.1 – Objectives of this Document

The objective of the MTS:PTC document is to promote accurate and consistent term selection.

Organisations are encouraged to document their term selection methods and quality assurance procedures in organisation-specific coding guidelines which should be consistent with the MTS:PTC.

Consistent term selection promotes medical accuracy for sharing MedDRA-coded data and facilitates a common understanding of shared data among academic, commercial and regulatory entities. The MTS:PTC could also be used by healthcare professionals, researchers, and other parties outside of the regulated biopharmaceutical industry.

The document provides term selection considerations for business purposes and regulatory requirements. There may be examples that do not reflect practices and requirements in all regions. This document does not specify regulatory reporting requirements, nor does it address database issues. As experience with MedDRA increases, and as MedDRA changes, there will be revisions to this document.

1.2 – Uses of MedDRA

Term selection for adverse reactions/adverse events (ARs/AEs), device-related events, product quality issues, medication errors, exposures, medical history, social history, investigations, misuse and abuse, off label use, and indications is addressed in this MTS:PTC document.

MedDRA’s structure allows for aggregation of those reported terms in medically meaningful groupings to facilitate analysis of safety data. MedDRA can also be used to list AR/AE data in reports (tables, line listings, etc.), compute frequencies of similar ARs/AEs, and capture and analyse related data such as product indications, investigations, and medical and social history.

1.3 – How to Use this Document

The MTS:PTC document does not address every potential term selection situation. Medical judgment and common sense should also be applied.

This document is not a substitute for MedDRA training. It is essential for users to have knowledge of MedDRA’s structure and content. For optimal MedDRA term selection, one should also refer to the MedDRA Introductory Guide (see Appendix, Section 4.2).

Users are invited to contact the MSSO Help Desk with any questions or comments about this MTS:PTC document.

1.4 – Preferred Option

In some cases, where there is more than one option for selecting terms, a “preferred option” is identified in this document. Designation of a “preferred option” does not limit MedDRA users to applying that option. Users should always first consider regional regulatory requirements. An organisation should be consistent in the option that they choose to use and document that option in internal coding guidelines.

1.5 – MedDRA Browsing Tools

The MSSO and JMO provide two browsers (a Desktop browser and a Web-Based browser) that allow for searching and viewing the terminology (see Appendix, Section 4.2). Users may find these browsers useful aids in term selection.

Section 2 – GENERAL TERM SELECTION PRINCIPLES

2.1 – Quality of Source Data

The quality of the original reported information directly impacts the quality of data output. Clarification should be obtained for data that are ambiguous, confusing or unintelligible. If clarification cannot be obtained, refer to Section 3.4.

2.2 – Quality Assurance

To promote consistency, organisations should document their term selection methods and quality assurance procedures in coding guidelines consistent with this MTS:PTC document.

Clear initial data can be promoted through careful design of data collection forms, and training of individuals in data collection and follow-up (e.g., investigators, drug sales representatives). 

Term selection should be reviewed by a qualified individual, i.e., a person with medical background or training who has also received MedDRA training.

Human oversight of term selection performed by IT tools (such as an autoencoder) is needed to assure that the end result fully reflects the reported information and makes medical sense.

2.3 – Do Not Alter MedDRA

MedDRA is a standardised terminology with a pre-defined term hierarchy that should not be altered. Users must not make ad hoc structural alterations to MedDRA, including changing the primary SOC allocation; doing so would compromise the integrity of this standard. If terms are found to be incorrectly placed in the MedDRA hierarchy, a change request should be submitted to the MSSO.

Example

Change Request to Re-Assign Primary SOC
In a previous version of MedDRA, PT Factor VIII deficiency was incorrectly assigned to primary SOC Blood and lymphatic system disorders.  By means of a Change Request, the PT was re-assigned to primary SOC Congenital, familial and genetic disorders (making SOC Blood and lymphatic system disorders its secondary SOC assignment).

2.4 – Always Select a Lowest Level Term

MedDRA Lowest Level Term(s) (LLT) that most accurately reflects the reported verbatim information should be selected.

The degree of specificity of some MedDRA LLTs may be challenging for term selection. Here are some tips for specific instances:

•  A single letter difference in a reported verbatim text can impact the
   meaning of the word and consequently the term selection

Example

Reported LLT Selected
Lip sore Lip sore (PT Lip pain)
Lip soresSores lip (PT Cheilitis)
Sore gums Sore gums (PT Gingival pain)
Sores gum Sores gum (PT Noninfective gingivitis)

•  Gender-specific terms

MedDRA generally excludes terms with demographic descriptors (age, gender, etc.), but some terms with gender qualifiers are included if the gender renders the concept unique.

Example

Distinct Gender-Specific Terms
In MedDRA, there are separate LLTs/PTs for
Infertility, Infertility female and Infertility male

Organisation-specific coding guidelines should address instances when it is important to capture gender-specific concepts.

MedDRA users should also consider the impact of gender-specific terms when comparing current data to data coded with a legacy terminology in which such gender specificity may not have been available.

Example

Gender Specificity – Legacy Terms vs. MedDRA
Consider the impact of selecting gender-specific MedDRA terms for breast cancer (e.g., LLT Breast cancer female) when comparing data coded in a legacy terminology with only a single “Breast cancer” term.

• Postoperative and post procedural terms

MedDRA contains some “postoperative” and “post procedural” terms. Select the most specific term available.

Example

Reported LLT Selected
Bleeding after surgeryBleeding postoperative
Sepsis occurred after the procedure Post procedural sepsis

• Newly added terms

More specific LLTs may be available in a new version of MedDRA. See Appendix, Section 4.2.

2.5 – Select Only Current Lowest Level Terms

Non-current LLTs should not be used for term selection.

2.6 – When to Request a Term

Do not address deficiencies in MedDRA with organisation-specific solutions. If there is no MedDRA term available to adequately reflect the reported information, submit a change request to MSSO.
Example

Change Request for a New Term
LLT HBV coinfection was added to MedDRA
following a user’s request.

2.7 – Use of Medical Judgment in Term Selection

If an exact match cannot be found, medical judgment should be used to adequately represent the medical concept with an existing MedDRA term.

Example

ReportedLLT Selected Comment
Brittle hairHair breakageThere is no MedDRA term for “brittle hair”.  LLT Hair breakage more accurately reflects the reported concept than the less specific LLT Hair disorder

2.8 – Selecting More Than One Term
When a specific medical concept is not represented by a single MedDRA term, consider requesting a new term through the change request process (see Section 2.6). Whilst waiting for the new term, select one or more existing terms using a consistent approach with careful consideration of the impact on data retrieval, analysis, and reporting.

In some cases, it may be appropriate to select more than one MedDRA LLT to represent the reported information. If only one term is selected, specificity may be lost; on the other hand, selecting more than one term may lead to redundant counts. Established procedures should be documented.

Example

More Than One LLT Selected
There is no single MedDRA term for “metastatic gingival cancer”.  Therefore,
the options are:
1. Select LLT Gingival cancer OR LLT Metastatic carcinoma
2. Select LLT Gingival cancer AND LLT Metastatic carcinoma

2.9 – Check the Hierarchy

When considering selecting an LLT, check the hierarchy above the LLT (PT level and further up the hierarchy to HLT, HLGT and SOC) to ensure the placement accurately reflects the meaning of the reported term.

2.10 – Select Terms for All Reported Information, Do Not Add Information

Select terms for every AR/AE reported, regardless of causal association. In addition, select terms for device-related events, product quality issues, medication errors, medical history, social history, investigations, and indications as appropriate.

If a diagnosis is reported with characteristic signs and symptoms, the preferred option is to select a term for the diagnosis only (see Section 3.1 for details and examples).

When selecting terms, no reported information should be excluded from the term selection process; similarly, do not add information by selecting a term for a diagnosis if only signs or symptoms are reported.

Example

ReportedLLT SelectedComment
Abdominal pain, increased
serum amylase, and
increased serum lipase
Abdominal painIt is inappropriate to
assign an LLT for
diagnosis of
“pancreatitis”
Serum amylase increased
Lipase increased

Section 3 – TERM SELECTION POINTS

3.1 – Definitive and Provisional Diagnoses with or without Signs and Symptoms

The table below provides term selection options for definitive and provisional diagnoses with or without signs/symptoms reported. Examples are listed below the table.

A provisional diagnosis may be described as “suspicion of”, “probable”, “presumed”, likely”, “rule out”, “questionable”, “differential”, etc.

The preferred option for a single or multiple provisional diagnosis(es) is to select a term(s) for the diagnosis(es) and terms for reported signs and symptoms. This is because a provisional diagnosis may change while signs/symptoms do not.

SUMMARY OF PREFERRED AND ALTERNATE OPTIONS
SINGLE DIAGNOSIS
DEFINITIVE DIAGNOSIS PROVISIONAL DIAGNOSIS
Single definitive diagnosis
without signs/symptoms

•  Diagnosis (only possible option)


Single provisional diagnosis
without signs/symptoms

•  Provisional diagnosis (only
possible option)

Single definitive diagnosis
with signs/symptoms

•  Preferred: Diagnosis only
•  Alternate: Diagnosis and
signs/symptoms


Note: Always include signs/symptoms
not associated with diagnosis

SEE EXAMPLE 1

Single provisional diagnosis
with signs/symptoms


•  Preferred: Provisional diagnosis
and signs/symptoms

•  Alternate: Signs/symptoms only

Note: Always include signs/symptoms
not associated with diagnosis

SEE EXAMPLE 2

MULTIPLE DIAGNOSES
DEFINITIVE DIAGNOSESPROVISIONAL DIAGNOSES
Multiple definitive diagnoses
without signs/symptoms


•  Multiple diagnoses (only possible
option)

Multiple provisional diagnoses
without signs/symptoms


•  Multiple provisional diagnoses
(only possible option)

Multiple definitive diagnoses
with signs/symptoms

•  Preferred: Multiple diagnoses only
•  Alternate: Diagnoses and signs/
symptoms


Note: Always include signs/symptoms
not associated with diagnosis

SEE EXAMPLE 3

Multiple provisional diagnoses
with signs/symptoms

•  Preferred: Multiple provisional
diagnoses and signs/symptoms

•  Alternate: Signs/symptoms only

Note: Always include signs/symptoms
not associated with diagnosis

SEE EXAMPLE 4

 

EXAMPLES
ExampleReportedLLT SelectedPreferred Option
1 Anaphylactic reaction, rash
dyspnoea, hypotension,
and laryngospasm

Anaphylactic reaction
Anaphylactic reaction
Rash
Dyspnoea
Hypotension
Laryngospasm
 

2Possible myocardial infarction
with chest pain,
dyspnoea, diaphoresis
Myocardial infarction
Chest pain
Dyspnoea
Diaphoresis
Chest pain
Dyspnoea
Diaphoresis
 
3 Pulmonary embolism,
myocardial infarction, and
congestive heart failure with
chest pain, cyanosis, shortness
of breath, and
blood pressure decreased
Pulmonary embolism
Myocardial infarction
Congestive heart failure
Pulmonary embolism
Myocardial infarction
Congestive heart failure
Chest pain
Cyanosis
Shortness of breath
Blood pressure decreased
 

4 Chest pain, cyanosis, shortness
of breath, and blood pressure decreased. Differential
diagnosis includes pulmonary
embolism, myocardial
infarction, and congestive
heart failure.
Pulmonary embolism
Myocardial infarction
Congestive heart failure
Chest pain
Cyanosis
Shortness of breath
Blood pressure decreased
Chest pain
Cyanosis
Shortness of breath
Blood pressure decreased
 
Always include signs/ symptoms not associated with diagnosis Myocardial infarction, chest
pain, dyspnoea, diaphoresis, ECG changes and jaundice
Myocardial infarction
Jaundice (note that jaundice is
not typically associated with myocardial infarction)
 

3.2 – Death and Other Patient Outcomes

Death, disability, and hospitalisation are considered outcomes in the context of safety reporting and not usually considered ARs/AEs. Outcomes are typically recorded in a separate manner (data field) from AR/AE information. A term for the outcome should be selected if it is the only information reported or provides significant clinical information.

(For reports of suicide and self-harm, see Section 3.3).

        3.2.1 Death and ARs/AEs

Death is an outcome and not usually considered an AR/AE. If ARs/AEs are reported along with death, select terms for the ARs/AEs. Record the fatal outcome in an appropriate data field.

Example

Reported LLT Selected Comment
Death due to
myocardial infarction
Myocardial infarction Record death as
an outcome
Constipation, ruptured
bowel, peritonitis, sepsis;
patient died
Constipation
Perforated bowel
Peritonitis
Sepsis

        3.2.2 Death as the only reported information

If the only information reported is death, select the most specific death term available. Circumstances of death should not be inferred but recorded only if stated by the reporter.

Death terms in MedDRA are linked to HLGT Fatal outcomes.

Example

Reported LLT Selected
Patient was found dead Found dead
Patient died in childbirth Maternal death during childbirth
The autopsy report stated that the
cause of death was natural
Death from natural causes

        3.2.3 Death terms that add important clinical information

Death terms that add important clinical information should be selected along with any reported ARs/AEs.

Example

Reported LLT Selected
Patient experienced a rash and had
sudden cardiac death
Rash
Sudden cardiac death

        3.2.4 Other patient outcomes (non-fatal)

Hospitalisation, disability, and other patient outcomes are not generally considered ARs/AEs.

Example

Reported LLT Selected Comment
Hospitalisation due to
congestive heart failure
Congestive heart failure Record hospitalisation
as an outcome

If the only information reported is the patient outcome, select the most specific term available.

Example

Reported LLT Selected
Patient was hospitalised Hospitalisation

3.3 – Suicide and Self-Harm

Accurate and consistent term selection for reports of suicide attempts, completed suicides, and self-harm is necessary for data retrieval and analysis. If the motive for reported injury is not clear, seek clarification from the source.

        3.3.1 If overdose is reported

Do not assume that an overdose – including an intentional overdose – is a suicide attempt. Select only the appropriate overdose term (see Section 3.18).

        3.3.2 If self-injury is reported

For reports of self-injury that do not mention suicide or suicide attempt, select only the appropriate self-injury term.

Example

Reported LLT Selected Comment
Self slashing Self inflicted laceration LLT Self inflicted
laceration
is linked to
PT Intentional
self-injury
Cut her own wrists
Cut wrists in a suicide attempt Self inflicted laceration
Suicide attempt
 
Took an overdose in an attempt to commit suicide Intentional overdose
Suicide attempt
If overdose is reported in the context of suicide or a suicide attempt, the more specific LLT Intentional overdose can be selected (see also Section 3.18)

        3.3.3 Fatal suicide attempt

If a suicide attempt is fatal, select the term that reflects the outcome instead of the attempt only.

Example

Reported LLT Selected Comment
Suicide attempt resulted in death Completed suicide Record death as
an outcome

3.4 – Conflicting/Ambiguous/Vague Information

When conflicting, ambiguous, or vague information is reported, term selection to support appropriate data retrieval may be difficult. When this occurs, attempt to obtain more specific information. If clarification cannot be achieved, select terms as illustrated in the examples below (Sections 3.4.1 through 3.4.3).

        3.4.1 Conflicting information

Example

Reported LLT Selected Comment
Hyperkalaemia with a serum potassium of 1.6 mEq/L Serum potassium abnormal LLT Serum potassium
abnormal
covers both
of the reported
concepts (note: serum
potassium of 1.6 mEq/L
is a low result,
not high)

        3.4.2 Ambiguous information

Example

Reported LLT Selected Comment
GU pain Pain Effort should be made to obtain clarification of the meaning of "GU" from the source so that more specific term selection may be possible. “GU” could be either “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

        3.4.3 Vague information

For information that is vague, attempt to obtain clarification. If clarification cannot be achieved, select an LLT that reflects the vague nature of the reported event.

Example

Reported LLT Selected Comment
Turned green Unevaluable event “Turned green” reported
alone is vague; this
could refer to a patient condition or even to a product (e.g., pills)
Patient had a medical problem of unclear type Ill-defined disorder Since it is known that there is some form of a medical disorder, LLT Ill-defined disordercan be selected

3.5 – Combination Terms

A combination term in MedDRA is a single medical concept combined with additional medical wording that provides important information on pathophysiology or aetiology. A combination term is an internationally recognised, distinct and robust medical concept as illustrated in the examples below.

Example

MedDRA Combination Terms
PT Diabetic retinopathy
PT Hypertensive cardiomegaly
PT Eosinophilic pneumonia

A combination term may be selected for certain reported ARs/AEs (e.g., a condition “due to” another condition), keeping the following points in mind (Note: medical judgment should be applied):

        3.5.1 Diagnosis and sign/sympton

If a diagnosis and its characteristic signs or symptoms are reported, select a term for the diagnosis (see Section 3.1). A MedDRA combination term is not needed in this instance.

Example

Reported LLT Selected
Chest pain due to myocardial infarction Myocardial infarction

        3.5.2 One reported condition is more specific than the other

If two conditions are reported in combination, and one is more specific than the other, select a term for the more specific condition.

Example

Reported LLT Selected
Hepatic function disorder
(acute hepatitis)
Hepatitis acute
Arrhythmia due to atrial fibrillation Atrial fibrillation

        3.5.3 A MedDRA combination term is available

If two conditions are reported in combination, and a single MedDRA combination term is available to represent them, select that term.

Example

Reported LLT Selected
Retinopathy due to diabetes Diabetic retinopathy
Rash with itching Itchy rash

        3.5.4 When to "split" into more than one MedDRA term

If “splitting” the reported ARs/AEs provides more clinical information, select more than one MedDRA term.

Example

Reported LLT Selected
Diarrhoea and vomiting Diarrhoea
Vomiting
Wrist fracture due to fall Wrist fracture
Fall

Exercise medical judgment so that information is not lost when “splitting” a reported term. Always check the MedDRA hierarchy above the selected term to be sure it is appropriate for the reported information.

Example

Reported LLT Selected Comment
Haematoma due to an animal bite Animal bite
Traumatic haematoma

LLT Traumatic
haematoma
is more
appropriate than LLT
Haematoma (LLT
Traumatic haematoma
links to HLT Non-site
specific injuries NEC

and HLT Haemorrhages
NEC
while LLT
Haematoma links
only to HLT
Haemorrhages NEC)

        3.5.5 Event reported with pre-existing condition

If an event is reported along with a pre-existing condition that has not changed, and if there is not an appropriate combination term in MedDRA, select a term for the event only (see Section 3.9 for pre-existing conditions that have changed).

Example

Reported LLT Selected Comment
Shortness of breath due to
pre-existing cancer
Shortness of breath In this instance,
“shortness of breath”
is the event; “cancer” is
the pre-existing
condition that
has not changed

3.6 – Age vs. Event Specificity

        3.6.1 MedDRA term includes age and event information

Example

Reported LLT Selected
Jaundice in a newborn Jaundice of newborn
Developed psychosis at age 6 years Childhood psychosis

        3.6.2 No available MedDRA term includes both age and event information

The preferred option is to select a term for the event and record the age in the appropriate demographic field.

Alternatively, select terms (more than one) that together reflect both the age of the patient and the event.

Example

Reported LLT Selected Preferred Option
Pancreatitis in a newborn Pancreatitis
Pancreatitis
Neonatal disorder
 

3.7 – Body Site vs. Event Specificity

        3.7.1 MedDRA term includes body site and event information

Example

Reported LLT Selected
Skin rash on face Rash on face

        3.7.2 No available MedDRA term includes both both site and event information

Select a term for the event, rather than a term that reflects a non-specific condition at the body site; in other words, the event information generally has priority.

Example

Reported LLT Selected Comment
Skin rash on chest Skin rash In this instance, there
is no available term for
a skin rash on the chest

However, medical judgment is required, and sometimes, the body site information should have priority as in the example below.

Example

Reported LLT Selected Comment
Cyanosis at injection site Injection site reaction Cyanosis implies a
generalised disorder.
In this example,
selecting LLT Cyanosis
would result in loss of
important medical
information and
miscommunication

        3.7.3 Event occurring at multiple body sites

If an event is reported to occur at more than one body site, and if all of those LLTs link to the same PT, then select a single LLT that most accurately reflects the event; in other words, the event information has priority.

Example

Reported LLT Selected Comment
Skin rash on face
and neck
Skin rash LLT Rash on face,
LLT Neck rash,
and LLT Skin rash
all link to PT Rash
Oedema of hands
and feet
Oedema of extremities LLT Oedema hands and
LLT Oedematous feet
both link to PT Oedema
peripheral
. However,
LLT Oedema of
extremities
most
accurately reflects the
event in a single term

3.8 – Location-Specific vs. Microorganism-Specific Infection

        3.8.1 MedDRA term includes microorganism and anatomic location

Example

Reported LLT Selected Comment
Pneumococcal pneumonia Pneumococcal pneumonia In this example, the
implied anatomic
location is the lung

        3.8.2 No available MedDRA term includes both microorganism and anatomic location

The preferred option is to select terms for both the microorganism-specific infection and the anatomic location.

Alternatively, select a term that reflects the anatomic location or select a term that reflects the microorganism-specific infection. Medical judgment should be used in deciding whether anatomic location or the microorganism-specific infection should take priority.

Example

Reported LLT Selected Preferred Option Comment
Respiratory chlamydial infection Chlamydial infection Respiratory infection Represents both microorganism-specific infection and anatomic location
Respiratory infection   Represents location-specific infection
Chlamydial infection   Represents microorganism-specific infection

3.9 – Modification of Pre-existing Conditions

Pre-existing conditions that have changed may be considered ARs/AEs, especially if the condition has worsened or progressed. (see Section 3.5.5 for pre-existing conditions that have not changed, and Section 3.22 for an unexpected improvement of a pre-existing condition).

Example

Ways That Pre-existing Conditions May Be Modified
Aggravated, exacerbated, worsened
Recurrent
Progressive

Select a term that most accurately reflects the modified condition (if such term exists).

Example

Reported LLT Selected
Exacerbation of myasthenia gravis Myasthenia gravis aggravated

If no such term exists, consider these approaches:

Ø  Example 1: Select a term for the pre-existing condition and record the modification in a consistent, documented way in appropriate data fields

Ø  Example 2: Select a term for the pre-existing condition and a second term for the modification of the condition (e.g., LLT Condition aggravated, LLT Disease progression). Record the modification in a consistent, documented way in appropriate data fields.

Example

Examples Reported LLT Selected Comment
Example 1 Jaundice
aggravated
Jaundice Record “aggravated”
in a consistent,
documented way
Example 2 Jaundice
aggravated

Jaundice

Condition
aggravated

Record "aggravated"
in a consistent,
documented way.
Select terms for the
pre-existing condition
and the modification.

3.10 – Exposures during Pregnancy and Breast Feeding

To select the most appropriate exposure term (or terms), first determine if the subject/patient who experienced the event is the mother or the child/foetus.

        3.10.1 Events in the mother

        3.10.1.1 Pregnant patient exposed to medication with clinical consequences

If a pregnancy exposure is reported with clinical consequences, select terms for both the pregnancy exposure and the clinical consequences.

Example

Reported LLT Selected
Pregnant patient receiving drug X experienced a pruritic rash Maternal exposure during pregnancy
Pruritic rash

        3.10.1.2 Pregnant patient exposed to medication without clinical consequences

If a pregnancy exposure report specifically states that there were no clinical consequences, the preferred option is to select only a term for the pregnancy exposure. Alternatively, a term for the pregnancy exposure and the additional LLT No adverse effect can be selected (see Section 3.21).

Example

Reported LLT Selected Preferred Option
Patient received drug X while pregnant (no adverse effect) Maternal exposure
during pregnancy
Maternal exposure during pregnancy
No adverse effect
 

        3.10.2 Events in the child or foetus

Select terms for both the type of exposure and any adverse event(s).

Example

Setting/Patient Reported LLT Selected
Foetus with AE;
exposed in utero; mother took product
Pregnant woman taking drugX;
foetal tachycardia
noted on routine
examination
Drug exposure in utero
Foetal tachycardia
Baby with AE;
exposed in utero; father took product
Baby born with cleft palate;
father had been taking
drug X at time of
conception
Paternal drug exposure
before pregancy
Cleft palate
Newborn with AE;
exposed to product via breast milk
Mother exposed to drug X;
nursing newborn
experienced vomiting
Drug exposure via
breast milk
Vomiting neonatal

3.11 – Congenital Terms

“Congenital” = any condition present at birth, whether genetically inherited or occurring in utero (see the MedDRA Introductory Guide).

        3.11.1 Congenital conditions

Select terms from SOC Congenital, familial and genetic disorders when the reporter describes the condition as congenital or when medical judgment establishes that the condition was present at the time of birth.

Example

Reported LLT Selected Comment
Congenital heart disease Heart disease congenital  
Child born with heart disease
Newborn with phimosis Phimosis A “congenital” term is not available but LLT/PT Phimosis links to primary SOC Congenital, familial and genetic disorders

        3.11.2 Acquired conditions (not present at birth)

If information is available indicating that the condition is not congenital or present at birth, i.e., it is acquired, select the non-qualified term for the condition, making sure that the non-qualified term does not link to SOC Congenital, familial and genetic disorders. If a non-qualified term is not available, select the “acquired” term for the condition.

Example

Reported LLT Selected Comment
Developed night blindness
in middle age
Night blindness LLT/PT Night blindness
links to primary SOC
Eye disorders. Do not
assume the condition is
congenital (LLT/PT
Congenital night
blindness
).
Developed phimosis
at age 45
Acquired phimosis LLT/PT Phimosis should not be selected because it links to primary SOC Congenital, familial and genetic disorders
34 year old patient with cholangiectasis Cholangiectasis acquired A non-qualified term “Cholangiectasis” is not available. It cannot be assumed that the condition was present at birth so it is appropriate to select the acquired term.

        3.11.3 Conditions not specified as either congenital or acquired

If a condition is reported without any information describing it as congenital or acquired, select the non-qualified term for the condition. For conditions or diseases existing in both congenital and acquired forms, the following convention is applied in MedDRA: the more common form of the condition/disease is represented at the PT level without adding a qualifier of either “congenital” or “acquired”.

Example

Reported LLT Selected Comment
Pyloric stenosis Pyloric stenosis Pyloric stenosis is more commonly congenital than acquired; LLT/PT Pyloric stenosis links to primary SOC Congenital, familial and genetic disorders
Hypothyroidism Hypothyroidism Hypothyroidism is more commonly acquired than congenital; LLT/PT Hypothyroidism links to primary SOC Endocrine disorders

3.12 – Neoplasms

Due to the large number of neoplasm types, specific guidance cannot be provided for all situations. The MedDRA Introductory Guide describes the use and placement of neoplasm terms and related terms in MedDRA.

Keep in mind the following points:

Neoplasms Terms in MedDRA
“Cancer” and “carcinoma” are synonyms (Appendix B of Introductory Guide)
“Tumo(u)r” terms refer to neoplasia
“Lump” and “mass” terms are not neoplasia

If the type of neoplasia is not clear, seek clarification from the reporter. Consult medical experts when selecting terms for difficult or unusual neoplasms.

        3.12.1 Do not infer malignancy

Select a malignancy term only if malignancy is stated by the reporter. Reports of “tumo(u)r” events should not be assigned a “cancer”, “carcinoma” or another malignant term unless it is clear that malignancy is present.

Example

Reported LLT Selected
Tumour growing on skin Skin tumour
Cancer growing on tongue Malignant tongue cancer

3.13 – Medical and Surgical Procedures

Terms in SOC Surgical and medical procedures are generally not appropriate for ARs/AEs. Terms in this SOC are not multiaxial. Be aware of the impact of these terms on data retrieval, analysis, and reporting.

Keep in mind the following points:

        3.13.1 Only the procedure is reported

If only a procedure is reported, select a term for the procedure.

Example

Reported LLT Selected
Patient had transfusion of platelets Platelet transfusion
Patient had tonsillectomy in childhood Tonsillectomy

        3.13.2 Procedure and diagnosis are reported

If a procedure is reported with a diagnosis, the preferred option is to select terms for both the procedure and diagnosis. Alternatively, select a term only for the diagnosis.

Example

Reported LLT Selected Preferred Option Comment
Liver transplantation
due to liver injury
Liver transplantation
Liver injury
Selecting term
for the
procedure may
indicate
severity of
the condition
Liver injury    

3.14 – Investigations
SOC Investigations includes test names with qualifiers (e.g., increased, decreased, abnormal, normal) and without qualifiers. Corresponding medical conditions (such as “hyper-” and “hypo-” terms) are in other “disorder” SOCs (e.g., SOC Metabolism and nutrition disorders).

SOC Investigations is not multiaxial; always consider the terms in this SOC for data retrieval.

        3.14.1 Results of investigations as ARs/AEs

Keep in mind the following points when selecting terms for results of investigations:

Ø  Selecting terms for a medical condition vs. an investigation result

Example

Reported LLT Selected Comment
Hypoglycaemia Hypoglycaemia LLT Hypoglycaemia links
to SOC Metabolism and
nutrition disorders
Decreased glucose Glucose decreased LLT Glucose decreased
links to SOC
Investigations

Ø  Unambiguous investigation result

Example

Reported LLT Selected Comment
Glucose 40 mg/dL Glucose low Glucose is clearly below
the reference range

Ø  Ambiguous investigation result

Example

Reported LLT Selected Comment
His glucose was 40 Glucose abnormal In this example, no
units have been
reported. Select LLT
Glucose abnormal if
clarification cannot
be obtained

        3.14.2 Investigation results consistent with diagnosis

When investigation results are reported with a diagnosis, select only a term for the diagnosis if investigation results are consistent with the diagnosis.

Example

Reported LLT Selected Comment
Elevated potassium, K 7.0 mmol/L, and hyperkalaemia Hyperkalaemia It is not necessary to
select LLT
Potassium increased

        3.14.3 Investigation results not consistent with diagnosis

When investigation results are reported with a diagnosis, select a term for the diagnosis and also select terms for any investigation results that are not consistent with the diagnosis.

Example

Reported LLT Selected Comment
Alopecia, rash,
and elevated
potassium 7.0 mmol/L
Alopecia
Rash
Potassium increased
Elevated potassium is
not consistent with the
diagnoses of alopecia
and rash. Terms for all
concepts should
be selected.

        3.14.4 Grouped investigation result terms

Select a term for each investigation result as reported; do not “lump” together separate investigation results under an inclusive term unless reported as such.

Example

Reported LLT Selected Comment
Abnormalities of liver
function tests
Abnormal liver function
  tests
 
Increased alkaline
phosphatase, increased
SGPT, increased SGOT and elevated LDH
Alkaline phosphatase
increased
SGPT increased
SGOT increased
LDH increased
Select four individual
terms for the
investigation results. A
single term such as LLT
Liver function tests
abnormal should not
be selected

        3.14.5 Investigation terms without qualifiers

Terms in SOC Investigations without qualifiers are intended to be used to record test names when entering diagnostic test data in the ICH E2B electronic transmission standard.

Example

Information/Reported
(Verbatim)
LLT Selected for Test Name Comment
Cardiac output
measured
Cardiac output  
Haemoglobin 7.5 g/dL Haemoglobin LLT Haemoglobin decreased
should not be
selected as it is both a
test name and a result*

*MedDRA is used only for test names, not test results, in the E2B data elements for Results of Tests and Procedures.

Test name terms without qualifiers are not intended for use in other data fields capturing information such as ARs/AEs and medical history. The use of the Unqualified Test Name Term List is optional and may be used to identify the inappropriate selection of these terms in data fields other than the test name data element. It is available for download from the MedDRA and JMO websites.

3.15 – Medication Errors, Accidental Exposures and Occupational Exposures

        3.15.1 Medication errors

Medication errors are defined as any preventable event that may cause or lead to inappropriate medication use or patient harm while the medication is in the control of the health care professional, patient or consumer.

Appendix B of the MedDRA Introductory Guide contains descriptions of the interpretation and use of certain medication error terms (e.g., “Dispensing error”).

Reports of medication errors may or may not include information about clinical consequences.

        3.15.1.1 Medication errors reported with clinical consequences

If a medication error is reported with clinical consequences, select terms for both the medication error and the clinical consequences.

Example

Reported LLT Selected Comment
Patient was administered wrong drug and experienced hypotension Wrong drug administered
Hypotension
 
Because of similar sounding drug names, the wrong drug was dispensed; as a result, the patient took the wrong drug and experienced a rash Drug name confusion
Wrong drug dispensed
Wrong drug administered
Rash
It is important to select terms for all medication error concepts, i.e., do not subtract information
Insulin preparation was given using the wrong syringe resulting in the administration of an overdose. The patient developed hypoglycaemia. Drug administered in wrong device
Accidental overdose
Hypoglycaemia
If an overdose is reported in the context of a medication error, the more specific term LLT Accidental overdose can be selected (see also Section 3.18)

        3.15.1.2 Medication errors and potential medication errors reported without clinical consequences

Medication errors without clinical consequences are not ARs/AEs. However, it is important to record the occurrence or potential occurrence of a medication error. Select a term that is closest to the description of medication error reported.

Intercepted medication error. For the purposes of term selection and analysis of MedDRA-coded data, an intercepted medication error refers to the situation where a medication error has occurred, but is prevented from reaching the patient or consumer. The intercepted error term should reflect the stage at which the error occurred, rather than the stage at which it was intercepted.

If a medication error report specifically states that there were no clinical consequences, the preferred option is to select only a term for the medication error. Alternatively, a term for the medication error and the additional LLT No adverse effect can be selected (see Section 3.21).

Example

Reported LLT Selected Preferred Option
Medication was given intravenously instead of intramuscularly but the patient did not experience any adverse effects Intramuscular formulation administered by other route
Intramuscular formulation administered by other route
No adverse effect
 

Example

Reported LLT Selected Comment
Pharmacist notices that the names of two drugs are similar and is concerned that this may result in a medication error Drug name confusion
Circumstance or information capable of leading to medication error
Note: this example is a potential medication error and LLT Drug name confusion provides additional information about the nature of the potential medication error
The physician prescribed the wrong dose of the drug; the error was identified at the time of dispensing Intercepted drug prescribing error The intercepted error terms reflect the stage at which the error occurred, rather than the stage at which the error was intercepted
The pharmacist dispensed the wrong drug but the patient realised the error and did not take the drug Intercepted drug dispensing error
Patient forgot to take his scheduled dose of drug X Drug dose omission Dose omission is failure to administer an ordered dose but excludes patient’s refusal, clinical decision or other objective reason not to administer. It is a medication error. See Concept Description in Appendix B of the MedDRA Introductory Guide.
Patient’s scheduled dose of drug X was not administered because he was undergoing surgery that day Intentional dose omission This is an example of an intentional dose omission/missed dose. It is not a medication error.

        3.15.1.3 Medication monitoring errors

For the purposes of term selection and analysis of MedDRA-coded data, a medication monitoring error is an error that occurs in the process of monitoring the effect of the medication through clinical assessment and/or laboratory data. It can also refer to monitoring errors in following instructions or information pertinent to the safe use of the medication.

Example

Reported LLT Selected Comment
The patient’s liver enzymes were measured every six months instead of the recommended monthly schedule Drug monitoring procedure incorrectly performed The monthly monitoring schedule is in the label for this drug. This is an example of incorrect monitoring of laboratory tests recommended in the use of a drug.
Patient taking lithium-based drug did not have his lithium levels measured Therapeutic drug monitoring analysis not performed This is an example of not monitoring the therapeutic drug level to ensure that it is within the therapeutic range as recommended in the label for this drug

If the label describes known effects when the product is co-administered with specific drugs, with specific foods, or to patients with specific disease states, and if the report does not indicate that this is intentional misuse or intentional off label use, then select a medication error term for the type of interaction, such as those listed below:

Medication Error Terms – Labelled Interactions
Labelled drug-drug interaction medication error
Labelled drug-food interaction medication error
Labelled drug-disease interaction medication error
Documented hypersensitivity to administered product

Example

Reported LLT Selected Comment
Patient became pregnant
whilst taking an antifungal drug and an oral contraceptive
Labelled drug-drug
interaction medication error
Pregnancy on oral
contraceptive
Product is labelled for this drug-drug interaction
(see also
Section 3.20)
Patient drank grapefruit
juice whilst taking a calcium channel blocker
Labelled drug-food
interaction
medication error
Product is labelled for this drug-food interaction with grapefruit juice
Patient with renal failure is accidentally prescribed a drug that is contraindicated in renal failure Labelled drug-disease interaction
medication error

Contraindicated drug prescribed
Product is labelled for this drug-disease interaction. LLT Contraindicated drug prescribed provides additional information about the nature of the labelled interaction medication error and the stage at which the error occurred
Patient with known sulfa allergy is administered a sulfonamide-based drug and experienced wheezing Documented
hypersensitivity to administered drug
Wheezing
See Concept Description in Appendix B of the MedDRA Introductory Guide. This medication error refers to the situation when a patient is administered a drug that is documented in the patient's medical file to cause a hypersensitivity reaction in the patient.

        3.15.1.4 Do not infer a medication error

Do not infer that a medication error has occurred unless specific information is provided. This includes inferring that extra dosing, overdose, or underdose has occurred (see Section 3.18).

Example

Reported LLT Selected Comment
Patient took only half the prescribed dose Underdose
Based on this report, it is not known whether the underdose is intentional or accidental. If information is available, select the more specific LLT Accidental underdose or LLT Intentional underdose as appropriate.

        3.15.2 Accidental exposures and occupational exposures

        3.15.2.1 Accidental exposures

The principles for Section 3.15.1 (Medication errors) also apply to accidental exposures.

Example

Reported LLT Selected Comment
Child accidentally took grandmother’s pills and experienced projectile vomiting Accidental drug intake
by child
Vomiting projectile

 
Father applying topical steroid to his arms accidentally exposed his child to the drug by carrying her Accidental exposure to product by child
Exposure via skin contact
The “exposure to” term captures the agent of exposure, i.e., a product, and the “exposure via” term captures the route/vehicle of exposure, i.e., skin contact

        3.15.2.2 Occupational exposures

For the purposes of term selection and analysis of MedDRA-coded data, occupational exposure encompasses the “chronic” exposure to an agent (including therapeutic products) during the normal course of one’s occupation, and could include additional scenarios in specific regulatory regions. For example, occupational exposure may additionally relate to a more acute, accidental form of exposure that occurs in the context of one’s occupation. In these regions, occupational exposure for healthcare workers could be of particular interest.

Example

Reported LLT Selected Comment
Physical therapist developed a photosensitivity rash on hands after exposure to an NSAID-containing pain relief cream that she applied to a patient Occupational exposure to drug Exposure via skin contact
Photosensitive rash
 
Pathologist chronically exposed to formaldehyde developed nasopharyngeal carcinoma Occupational exposure
to toxic agent
Nasopharyngeal carcinoma

Exposure to formaldehyde is a known risk factor for this type of malignancy
Nurse splashed injectable drug in her own eye resulting in excessive tearing Inadvertent exposure to drug Excess tears
An additional term for occupational exposure – e.g., LLT Occupational exposure to drug – could also be selected, if applicable to regional requirements

3.16 – Misuse, Abuse and Addiction

The concepts of misuse, abuse and addiction are closely related and can pose challenges for term selection since the terms may overlap to some extent; the specific circumstances of each case/reported event may help in consideration for term selection of these concepts. Medical judgment and regional regulatory considerations need to be applied.

It may also be useful to consider these concepts as shown in the table below

Concept Intentional? By Whom? Therapeutic Use? Additional Sections in this Document
Misuse Yes Patient / consumer Yes* 3.16.1
Abuse Yes Patient / consumer No 3.16.2
Addiction Yes Patient / consumer No 3.16.3
Medication error No Patient / consumer or healthcare professional Yes 3.15
Off label use Yes Healthcare professional Yes 3.27

* Definitions of misuse may not always include the concept of therapeutic use; misuse may be similar to the concept of abuse in some regions.

Select the most specific term available and always check the MedDRA hierarchy above the selected term to be sure it is appropriate for the reported information. In some cases, it may be appropriate to select more than one MedDRA LLT to represent the reported information.

        3.16.1 Misuse

For the purposes of term selection and analysis of MedDRA-coded data, misuse is the intentional use for a therapeutic purpose by a patient or consumer of a product – over-the-counter or prescription – other than as prescribed or not in accordance with the authorised product information.

Example

Reported LLT Selected
Patient deliberately took the medication twice daily instead of once daily Intentional misuse in dosing frequency

        3.16.2 Abuse

For the purposes of term selection and analysis of MedDRA-coded data, abuse is the intentional, non-therapeutic use by a patient or consumer of a product – over-the counter or prescription – for a perceived reward or desired non-therapeutic effect including, but not limited to, “getting high” (euphoria). Abuse may occur with a single use, sporadic use or persistent use of the product.

Example

Reported LLT Selected Comment
Athlete used anabolic steroid preparation to enhance performance Steroid abuse  
Patient occasionally uses opioid product
to get high
Opioid abuse, episodic use
Patient deliberately ingested the topical medication for its psychoactive effect Drug abuse
Intentional use by incorrect route
LLT Intentional use by incorrect route (PT Intentional product use issue) provides additional information about the nature of the drug abuse

See Section 3.24.1 and 3.24.2 for additional references to "abuse" terms in MedDRA.

        3.16.3 Addiction

For the purposes of term selection and analysis of MedDRA-coded data, addiction is an overwhelming desire by a patient or consumer to take a drug for non-therapeutic purposes together with inability to control or stop its use despite harmful consequences. Addiction can occur because drug induces physical dependence and consequently a withdrawal syndrome, but this is not an essential feature; and addiction can occur because of a desire to experience the drug's psychological, behavioral or physical effects.

Example

Reported LLT Selected
Patient became dependent on
crack cocaine
Dependence on cocaine
Patient became addicted to a
deliberately ingested topical medication for its psychoactive effect
Drug addiction
Intentional use by incorrect route

See Section 3.24.1 for additional references to "addict/addiction" terms in MedDRA.

        3.16.4 Drug diversion

For the purposes of term selection and analysis of MedDRA-coded data, drug diversion means that a drug is diverted from legal and medically necessary uses toward illegal uses.

Example

Reported LLT Selected
Pharmacist stole medications from the pharmacy and sold them to others for recreational use Drug diversion
A person put a sedative into the patient’s drink Drug diversion
Inadvertent exposure to drug


3.17 – Transmission of Infectious Agent via Product

If a report of transmission of an infectious agent via a product is received, select a term for the transmission. If the infection is identified, select a second term for the specific infection; if appropriate, a product quality issue term can also be selected (see Section 3.28).

Example

Reported LLT Selected
Patient received a nasal spray product
and later developed a severe nasal
infection with Burkholderia cepacia.
Cultures of unopened containers of the
nasal spray grew B. cepacia
Transmission of an infectious agent
via product
Product contamination bacterial
Burkholderia cepacia infection
Patient received a blood transfusion and developed Hepatitis C Transfusion-transmitted infectious disease Hepatitis C

Medical judgment should be used if the reporter does not explicitly state transmission of an infectious agent via a product but this could be implied by other data within the report. In this instance, select LLT Suspected transmission of an infectious agent via product.

3.18 – Overdose, Toxicity and Poisoning

Accidental overdose terms are grouped under HLT Product administration errors and issues; other overdose terms are grouped under HLT Overdoses NEC. Toxicity and poisoning terms are grouped under HLT Poisoning and toxicity. For more information, refer to the MedDRA Introductory Guide.

For the purposes of term selection and analysis of MedDRA-coded data, overdose is more than the maximum recommended dose (in quantity and/or concentration), i.e., an excessive dose (see Appendix B, MedDRA Introductory Guide).

If overdose, poisoning or toxicity is explicitly reported, select the appropriate term.

Example

 

Reported LLT Selected Comment
Patient took an overdose Overdose Based on this report, it is not known whether the overdose is intentional or accidental. If information is available, select the more specific LLT Accidental overdose or LLT Intentional overdose as appropriate.
A child was accidentally
poisoned when she ingested a chemical cleaning product
Accidental poisoning
Chemical poisoning
 
Patient deliberately took
an overdose of analgesic pills to treat his worsening arthritis
Intentional overdose LLT Arthritis aggravated can be selected as the indication for treatment
The dose taken
was above the recommended
maximum dose in the label
Overdose Based on this report, it is not known whether the overdose is intentional or accidental. If information is available, select the more specific LLT Accidental overdose or LLT Intentional overdose as appropriate.

        3.18.1 Overdose reported with clinical consequences

Select terms for overdose and for clinical consequences reported in association with an overdose.

Example

Reported LLT Selected
Stomach upset from
study drug overdose
Overdose
Stomach upset

        3.18.2 Overdose reported without clinical consequences

If an overdose report specifically states that there were no clinical consequences, the preferred option is to select only a term for the overdose. Alternatively, a term for the overdose and the additional LLT No adverse effect can be selected (see Section 3.21).

Example

Reported LLT Selected Preferred Option
Patient received an overdose
of medicine without any
adverse consequences
Overdose
Overdose
No adverse effect
 

3.19 – Device-related Terms

        3.19.1 Device-related event reported with clinical consequences

If available, select a term that reflects both the device-related event and the clinical consequence, if so reported.

Example

Reported LLT Selected
Patient with a vascular implant developed an infection of the implant Vascular implant infection
Patient noted the prosthesis
caused pain
Medical device pain

If there is no single MedDRA term reflecting the device-related event and the clinical consequence, select separate terms for both.

Example

Reported LLT Selected
Ventricular tachycardia due to
malfunction of device
Device malfunction
Ventricular tachycardia
Partial denture fractured leading to
tooth pain
Dental prosthesis breakage
Tooth pain

        3.19.2 Device-related event reported without clinical consequences

If a device-related event is reported in the absence of clinical consequences, select the appropriate term.

Example

Reported LLT Selected
Medical device breakage Device breakage
My patch is leaking on my arm Leaking patch

3.20 – Drug Interactions

This term includes reactions between drugs and other drugs, food, devices and alcohol. In this document, “drug” includes biologic products.

Labelled drug interactions may be medication errors (see Section 3.15.1.3).

        3.20.1 Reporter specifically states an interaction

Select an interaction term and additional term(s) for any reported medical event.

Example

Reported LLT Selected
Torsade de pointes with suspected
drug interaction
Drug interaction
Torsade de pointes
Patient drank cranberry juice which
interacted with anticoagulant drug
causing an INR increase
Food interaction
INR increased

        3.20.2 Reporter does not specifically state an interaction

Two products may be used together, but if the reporter does not specifically state that an interaction has occurred, select terms only for the medical events reported.

Example

Reported LLT Selected
Patient was started on an anti-seizure
medication and a heart medication and developed syncope
Syncope
Patient was already on an anti-seizure medication and was started on a heart medication, and anti-seizure medication levels increased Anticonvulsant drug level increased

3.21 – No Adverse Effect and "Normal" Terms

        3.21.1 No adverse effect

LLT No adverse effect can be used when absence of an AR/AE is specifically reported, despite exposure to a product (see Sections 3.15.1.2 and 3.18.2).

Some organisations may want to record LLT No adverse effect for administrative purposes (e.g., pregnancy registries, overdose and medication error reports).

        3.21.2 Use of "normal" terms

Terms for normal states and outcomes can be used as needed.

Examples of Terms for “Normal” States and Outcomes
Sinus rhythm
Normal baby
Normal electrocardiogram

3.22 – Unexpected Therapeutic Effect
Some organisations may want to record LLT Unexpected therapeutic effect for reports of a beneficial effect of a product apart from the reason it had been given. (Such effects are not usually considered ARs/AEs).

Example

Reported LLT Selected
A bald patient was pleased that he grew hair while using a product Unexpected therapeutic effect
Hair growth increased

3.23 – Modification of Effect
It is important to record modification of effect (e.g., increased, prolonged) although it is not always an AR/AE.

        3.23.1 Lack of effect

The preferred option is to select only the “lack of effect” term even if consequences are also reported. However, terms may also be selected for events associated with the lack of effect.

Example

Reported LLT Selected Preferred Option
Patient took drug for a
headache, and her
headache didn’t go away
Drug ineffective
Drug ineffective
Headache
 
Antibiotic didn’t work Lack of drug effect  

        3.23.2 Do not infer lack of effect

Example

Reported LLT Selected Comment
AIDS patient taking anti-
HIV drug died

Death Do not assume lack of
effect in this instance.
Select only a term for
death (see Section 3.2)

        3.23.3 Increased, decreased and prolonged effect

Example

Reported LLT Selected
Patient had increased effect
from drug A
Increased drug effect
Patient had decreased effect
from drug A
Drug effect decreased
Patient had prolonged effect
from drug A
Drug effect prolonged

3.24 – Social Circumstances

        3.24.1 Use of terms in this SOC

Terms in SOC Social circumstances represent social factors and may be suitable to record social and medical history data. Such terms are not generally suitable for recording ARs/AEs; however, in certain instances, terms in SOC Social circumstances are the only available terms for recording ARs/AEs or may add valuable clinical information.

Example

Reported LLT Selected
Patient’s ability to drive was impaired Impaired driving ability

Terms in SOC Social circumstances are not multiaxial and, unlike terms in other “disorder” SOCs in MedDRA (e.g., SOC Gastrointestinal disorders), they generally refer to a person, not to a medical condition.

Be aware of the impact that terms in SOC Social circumstances may have on data retrieval, analysis and reporting as illustrated in the table below:

Term in SOC Social circumstances
(“person”)
Similar term in “Disorder” SOC
(“condition”)
Alcoholic Alcoholism
Drug abuser Drug abuse
Drug addict Drug addiction
Glue sniffer Glue sniffing
Smoker Nicotine dependence

Note that “abuse” terms not associated with drugs/substances are in this SOC*, regardless of whether they refer to the person or to the condition, as illustrated in the table below:

LLT PT
Child abuse Child abuse
Child abuser
Elder abuse Elder abuse
Elder abuser

(See Section 3.24.2 concerning illegal/criminal acts.)

        3.24.2 Illegal acts of crime or abuse

Terms for illegal acts of crime and abuse (excluding those related to drug/substance abuse) are in SOC Social circumstances, such as LLT Physical assault.

LLTs representing the perpetrator are linked to PTs describing the unlawful act committed. PTs representing the victim of unlawful acts generally begin with “Victim of… ”.

Example

Reported LLT Selected Comment
Patient’s history indicates
that patient is a known
sexual offender
Sexual offender Perpetrator; LLT
Sexual offender links
to PT Sexual abuse
in SOC
Social circumstances
Patient was a childhood
sexual assault victim
Childhood sexual assault
victim
Victim; LLT Childhood
sexual assault victim

links to PT Victim of
sexual abuse
in SOC
Social circumstances

3.25 – Medical and Social History

Example

Reported LLT Selected
History of gastrointestinal bleed
and hysterectomy
Gastrointestinal bleed
Hysterectomy
Patient is a cigarette smoker with
coronary artery disease
Cigarette smoker
Coronary artery disease

3.26 – Indication for Product Use
Indications can be reported as medical conditions, prophylaxis of conditions, replacement therapies, procedures (such as anesthesia induction) and verbatim terms such as “anti-hypertension”. Terms from almost any MedDRA SOC – including SOC Investigations – may be selected to record indications.

Regulatory authorities may have specific requirements for certain aspects of term selection for indications (e.g., for indications within regulated product information). Please refer to the regulatory authority’s specific guidance for such issues.

        3.26.1 Medical conditions

Example

Reported LLT Selected
Hypertension Hypertension
Anti-hypertensive
Chemotherapy for breast cancer Breast cancer
I took it for my cold symptoms Cold symptoms

If the only information reported is the type of therapy, select the most specific term.

Example

Reported LLT Selected
Patient received chemotherapy Chemotherapy
Patient received antibiotics Antibiotic therapy

It may not be clear if the reported indication is a medical condition or a desired outcome of therapy. The term selected in either case may be the same.

Example

Reported LLT Selected Comment
Weight loss Weight loss Unclear if the purpose
is to induce weight loss
or to treat an
underweight patient
Immunosuppression Immunosuppression Unclear if the purpose
is to induce or to treat
immunosuppression

        3.26.2 Complex indications

Term selection for some indications (e.g., in regulated product information) may be complex and require selection of more than one LLT to represent the information completely, depending on the circumstances.

Example

Reported LLT Selected Comment
Treatment of aggression in autism Aggression
The products do not treat the underlying autism, thalassaemia, or myocardial infarction, but they do address the associated signs/symptoms (aggression, chronic iron overload, atherothrombosis). It may be necessary to select LLT Autism, LLT Thalassaemia major, or LLT Myocardial infarction based on regional regulatory requirements.
Treatment of chronic iron overload in thalassaemia major Chronic iron overload
Prevention of atherothrombotic events in patients with myocardial infarction Atherothrombosis prophylaxis

        3.26.3 Indications with genetic markers or abnormalities

For indications that describe a genetic marker or abnormality associated with a medical condition, select a term for both the medical condition and the genetic marker or abnormality.

Example

Reported LLT Selected
Non small cell lung cancer
with K-ras mutation
Non-small cell lung cancer
K-ras gene mutation

        3.26.4 Prevention and prophylaxis

When an indication for prevention or prophylaxis is reported, select the specific MedDRA term, if it exists. (Note: the words “prevention” and “prophylaxis” are synonymous in the context of MedDRA.)

Example

Reported LLT Selected
Prophylaxis of arrhythmia Arrhythmia prophylaxis
Prevention of migraine Migraine prophylaxis

If there is no MedDRA term containing “prevention” or “prophylaxis”, choose one of the following options The preferred option is to select a general prevention/ prophylaxis term and a term for the condition. Alternatively, select a term for the condition alone or a prevention/prophylaxis term alone.

Example

Reported LLT Selected Preferred
Option
Comment
Prevention of
hepatotoxicity
Prevention
Hepatotoxicity
Represents both the
prevention/prophylaxis concept
and the condition
Hepatotoxicity   Represents
the condition
Prevention   Represents the
prevention/prophylaxis
concept

        3.26.5 Procedures and diagnostic tests as indications

Select the appropriate term if the product is indicated for performing a procedure or a diagnostic test.

Example

Reported LLT Selected
Induction of anaesthesia Induction of anaesthesia
Contrast agent for angiogram Angiogram
Contrast agent for coronary angiogram Coronary angiogram

        3.26.6 Supplementation and replacement therapies

Terms for supplemental and replacement therapies are in SOC Surgical and medical procedures (see Section 3.13). If the product indication is for supplementation or replacement therapy, select the closest term.

Example

Reported LLT Selected
Testosterone replacement therapy Androgen replacement therapy
Prenatal vitamin Vitamin supplementation

        3.26.7 Indication not reported

If clarification cannot be obtained, select LLT Drug use for unknown indication.

Example

Reported LLT Selected
Aspirin was taken for an unknown
indication
Drug use for unknown indication

3.27 – Off Label Use

For the purposes of term selection and analysis of MedDRA-coded data, the concept of “off label use” relates to situations where a healthcare professional intentionally prescribes, dispenses, or recommends a product for a medical purpose not in accordance with the authorised product information. When recording off label use, consider that product information and/or regulations/requirements may differ between regulatory regions.

        3.27.1 Off label use when reported as an indication

If a medical condition/indication is reported along with “off label use”, the preferred option is to select terms for the medical condition/indication and off label use. Alternatively, select a term for the medical condition/indication alone. Select LLT Off label use alone only if it is the only information available.

Example

Reported LLT Selected Preferred Option
Hypertension; this is off
label use
Off label use
Hypertension
Hypertension
 

Example

Reported LLT Selected
Used off label Off label use

Example

Reported LLT Selected Preferred Option
Drug indicated for use in
adults used off label to treat
a 6 year old child
Off label use

Adult product
administered to child
LLT Adult product administered to child (PT Drug administered to patient of inappropriate age, HLT Product administration errors and issues)provides additional information about the specific type of off label use. The term is not an off label use term itself; it is a general product use issue term that can be used in combination with other terms to capture detail about off label use, misuse, medication errors, etc.

        3.27.2 Off label use when reported with AR/AE

If an AR/AE occurs in the setting of off label use for a medical condition/indication, the preferred option is to select a term for off label use, and a term for the medical condition/indication in addition to a term for the AR/AE. Alternatively, select a term for the medical condition/indication and a term for the AR/AE.

Example

Reported LLT Selected Preferred Option
Patient was administered a drug off label for pulmonary hypertension and suffered a stroke Off label use
Pulmonary hypertension
Stroke
Pulmonary hypertension
Stroke
 

3.28 – Product Quality Issues

It is important to recognise product quality issues as they may have implications for patient safety. They may be reported in the context of adverse events or as part of a product quality monitoring system.

Product quality issues are defined as abnormalities that may be introduced during the manufacturing/labelling, packaging, shipping, handling or storage of the products. They may occur with or without clinical consequences. Such concepts may pose a challenge for term selection.

Familiarity with HLGT Product quality, supply, distribution, manufacturing and quality system issues (in SOC Product issues) is essential for term selection. Under this HLGT are categories of specific product quality issues such as HLT Product packaging issues, HLT Product physical issues, HLT Manufacturing facilities and equipment issues, HLT Counterfeit, falsified and substandard products, etc. Navigating down to the appropriate LLTs from the MedDRA hierarchy is the optimal approach for term selection.

Explanations of the interpretations and uses of certain product quality issue terms (e.g., “Product coating incomplete”) are found in the MedDRA Introductory Guide (Appendix B, MedDRA Concept Descriptions).

        3.28.1 Product quality issue reported with clinical consequences

If a product quality issue results in clinical consequences, term(s) for the product quality issue and the clinical consequences should be selected.

Example

Reported LLT Selected Comment
New bottle of drug tablets have unusual chemical smell that made me nauseous Product odour abnormal
Nauseous
 
I switched from one brand to another of
my blood pressure medication, and I
developed smelly breath
Product substitution issue
brand to brand
Smelly breath
 
Consumer noted that the toothpaste they had purchased caused a stinging sensation in the mouth. Subsequent investigation of the product lot number revealed that the toothpaste was a counterfeit product. Product counterfeit
Stinging mouth
 
Patient reported severe burning in his nose after using nasal drops that had a cloudy appearance. An investigation by the manufacturer revealed that impurities were found in the batch of nasal drops and that these had been introduced by a faulty piece of equipment. Nasal burning

Product appearance cloudy

Product impurities found

Manufacturing equipment issue
Specific product defects and issues with manufacturing systems may be reported subsequently as part of a root cause analysis

        3.28.2 Product quality issue reported without clinical consequences

It is important to capture the occurrence of product quality issues even in the absence of clinical consequences.

Example

Reported LLT Selected
Sterile lumbar puncture kit received
in broken packaging
(sterility compromised)
Product sterile packaging disrupted

        3.28.3 Product quality issue vs. medication error

It is important to distinguish between a product quality issue and a medication error.

Product quality issues are defined as abnormalities that may be introduced during the manufacturing/labelling, packaging, shipping, handling or storage of the products. They may occur with or without clinical consequences.

Medication errors are defined as any preventable event that may cause or lead to inappropriate medication use or patient harm while the medication is in the control of the health care professional, patient or consumer.

Explanations of the interpretations of product quality issue terms are found in the MedDRA Introductory Guide (Appendix B, MedDRA Concept Descriptions).

Example

Reported LLT Selected Comment
Pharmacist dispensing Drug A inadvertently attached a product label for Drug B Wrong label placed on medication during dispensing Medication error
The drug store clerk noted that the wrong product label was attached to some bottles in a shipment of mouthwash Product label
on wrong product
Product quality issue
The mother administered an underdose of antibiotic because the lines on the dropper were illegible Product dropper calibration unreadable
Accidental underdose
Product quality issue and medication error. If underdose is reported in the context of a medication error, the more specific LLT Accidental underdose can be selected.

Section 4 – APPENDIX

4.1 – Versioning

        4.1.1 – Versioning methodologies

Each organisation should have a versioning strategy that should be documented. The versioning strategy may differ between safety databases and clinical trial databases. For example, there may be no need to update clinical trial data from older trials if the data are not presently used or will not be used in the future. On the other hand, postmarketing safety data may be required to be reported in the current (or near-current) version of MedDRA, and version update recommendations then apply.

Users should choose the most optimal approach based on their organisation’s characteristics. The optional methods described below can be used to document the extent to which an organisation has applied a new version of MedDRA. These methods should not be interpreted as regulatory requirements but may be used to communicate effectively between and within organisations.

The table below summarises the types of versioning methods.

Method Description Resource
Intensity
Data
Accuracy
1 Begin to use new version for coding new data; no
recoding of existing data
Least Least
2 Identify verbatim terms linked to non-current
LLTs and recode existing data
3 Identify verbatim terms linked to non-current
LLTs and recode existing data
and
Recode verbatim terms to new LLTs that are
direct or lexical matches
4 Identify verbatim terms linked to non-current
LLTs and recode existing data
and
Recode verbatim terms to new LLTs that are
direct or lexical matches
and
Recode verbatim terms to new LLTs that are more
accurate concepts
Most Most

This list may not be inclusive; other versioning methods may be used. Depending on how MedDRA data are stored in the database, additional steps may be needed to ensure consistency in data retrieval and reporting, including medical review of the data after the version method has been applied.

Note that Method 4 is the most resource intense and Method 1 is the least. There are additional points to consider: recoding to LLTs that are new direct matches or more accurate concepts (Method 4) provides the most accurate data compared to the other methods.

The MSSO and JMO provide tools to assist the user in comparing the changes between MedDRA versions. The Version Report (provided by the MSSO and JMO) is a spreadsheet listing all changes between the current version of MedDRA and the one previous to it; this spreadsheet is provided with each new release of MedDRA. The MSSO also provides the MedDRA Version Analysis Tool (MVAT) that facilitates identification and understanding of the impact of changes between any two MedDRA versions, including non-consecutive ones (see Appendix, Section 4.2.)

        4.1.2 – Timing of version implementation

For single case reporting, the sender and receiver of the data need to be in synchrony regarding MedDRA versions. There are MSSO recommendations for the timing of the implementation of a new MedDRA release for both individual case safety reporting and clinical trial data. Specific transition dates for single case reporting for the next MedDRA versions are provided (see Appendix, Section 4.2).

Date of New Reporting Version for Individual Case Safety Reporting
A new release version of MedDRA should become the reporting version on the first Monday of the second month after it is released. To synchronise this event over the three ICH regions, the MSSO recommends midnight GMT, Sunday to Monday, for the switchover.  For example :

•1 March – MedDRA X.0  released
•First Monday of May – MedDRA X.0 becomes the reporting version

•1 September – MedDRA X.1 released
•First Monday of November – MedDRA X.1 becomes the reporting version

4.2 – Links and References

The following documents and tools can be found on the MedDRA website (www.meddra.org):

•  MedDRA Introductory Guide
•  MedDRA Change Request Information document
•  MedDRA Web-Based Browser *
•  MedDRA Desktop Browser
•  MedDRA Version Report (lists all changes in new version) *
•  MedDRA Version Analysis Tool (compares any two versions) *
•  Unqualified Test Name Term List
•  MSSO's Recommendations for Single Case Reporting using Semi-annual Version Control
•  MSSO's Recommendations for MedDRA Implementation and Versioning for Clinical Trials
•  Transition Date for the Next MedDRA Version

* Requires user ID and password to access

4.3 Membership of the ICH Points to Consider Working Group

        4.3.1 Current members of the ICH Points to Consider Working Group

Affiliation Member
Commission of the
European Communities
Maria Luisa Casini
Kavita Chadda
European Federation of
Pharmaceutical Industries and
Associations
Hilary Vass*
Christina Winter†
Health Canada Dwana Pritchett
Lynn Macdonald
Japanese Maintenance Organization Yutaka Nagao
Kazuyuki Sekiguchi
Mitsuru Takano
Tomoko Narita
Japan Pharmaceutical
Manufacturers Association
Yo Tanaka
Hitomi Takeshita
Miyako Shionoiri
MedDRA MSSO Judy Harrison
Ministry of Health, Labour and Welfare/Pharmaceuticals and
Medical Devices Agency
Daisuke Inoue
Miki Ohta
Daisuke Sato
Yasuko Inokuma
Kiyomi Ueno
Pharmaceutical Research and
Manufacturers of America
Milbhor D’Silva
US Food and Drug Administration Sonja Brajovic#
Christopher Breder
World Health Organization Daisuke Tanaka

* Current Rapporteur
# Regulatory Chair
† Former Rapporteur

        4.3.2 – Former members of the ICH Points to Consider Working Group

Affiliation Member
Commission of the
European Communities
Dolores Montero; Carmen Kreft-Jais; Morell David; Sarah Vaughan
European Federation of
Pharmaceutical Industries and Associations
Barry Hammond†; Reinhard Fescharek†
Health Canada Alison Bennett; Valérie Bergeron;
Heather Morrison;
Polina Ostrovsky; Michelle Séguin; Stephanie Silva;
Heather Sutcliffe; Bill Wilson
Japanese Maintenance Organization Osamu Handa; Akemi Ishikawa;
Yasuo Sakurai; Yuki Tada; Reiji Tezuka
Japan Pharmaceutical
Manufacturers Association
Takayoshi Ichikawa; Akemi Ishikawa;
Satoru Mori; Yasuo Sakurai;
Kunikazu Yokoi
MedDRA MSSO JoAnn Medbery; Patricia Mozzicato
Ministry of Health, Labour
and Welfare/Pharmaceuticals and
Medical Devices Agency
Yuhei Fukuta; Tamaki Fushimi; Wakako Horiki;
Sonoko Ishihara; Makiko Isozaki;
Kazuhiro Kemmotsu; Tatsuo Kishi; Chie Kojima;
Emiko Kondo; Hideyuki Kondou;
Kemji Kuramochi; Tetsuya Kusakabe;
Kaori Nomura; Izumi Oba;
Shinichi Okamura; Yoshihiko Sano;
Nogusa Takahara; Kenichi Tamiya;
Daisuke Tanaka; Shinichi Watanabe;
Takashi Yasukawa; Go Yamamoto;
Manabu Yamamoto; Nobuhiro Yamamoto
Pharmaceutical Research
and Manufacturers of America

David Goldsmith; Sidney Kahn;
Anna-Lisa Kleckner;
Susan M. Lorenski; JoAnn Medbery;
Margaret M. Westland†
US Food and Drug Administration Miles Braun; Andrea Feight;
John (Jake) Kelsey†; Brad Leissa;
Toni Piazza-Hepp

† Former Rapporteur