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 fetus
3.11 Congenital Terms
3.11.1 Condition described as congenital
3.11.2 Condition not congenital/not present at birth
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/Administration Errors, Accidental Exposures and Occupational Exposures
3.15.1 Medication/administration 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
3.17 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 4.5 Based on MedDRA
Version 16.0

 

 

 

1 April 2013


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.  However, unless users achieve consistency in how they assign terms to verbatim reports of symptoms, signs, diseases, etc., use of MedDRA cannot have the desired harmonizing effect in the exchange of coded data.

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 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.

Organizations are encouraged to document their term selection methods and quality assurance procedures in organization-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 professional, researchers, and other parties outside of the regulated biopharmaceutical industry.

The document provides term selection advice 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 analyze 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).

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. An organization should be consistent in the option that they choose to use.

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, organizations 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 collections 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 standardized 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 Gingival inflammation)

•  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

Organization 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 organization-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). While 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.

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

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

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

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

EXAMPLE 4

 

ExampleReportedLLT SelectedPreferred Option
1 Anaphylactic reaction, rash
dyspnea, hypotension,
and laryngospasm

Anaphylactic reaction
Anaphylactic reaction
Rash
Dyspnea
Hypotension
Laryngospasm
 

2Possible myocardial infarction
with chest pain,
dyspnea, diaphoresis
Myocardial infarction
Chest pain
Dyspnea
Diaphoresis
Chest pain
Dyspnea
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, dyspnea, 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 hospitalization 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)

Hospitalization, 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 Suicide attempt In addition, LLT Self
inflicted laceration
can be selected

        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
Hyperkalemia 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 etiology. A combination term is an internationally recognized 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
Diarrhea and vomiting Diarrhea
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
Hematoma due to an
animal bite
Animal bite
Traumatic hematoma

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

and HLT Haemorrhages
NEC
while LLT
Hematoma 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 Comment
Pancreatitis in a
newborn
Pancreatitis Record patient
age in a
demographic field
Pancreatitis   In addition,
LLT Neonatal
disorder

can be selected

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
generalized 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 and
LLT Neck rash both
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 options (Note: keep in mind possible database limitations):

Ø  Option 1: Select a term for the pre-existing condition and record the modification in a consistent, documented way (narrative, check box on data collection form, etc.)

Ø  Option 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)

Example

Options Reported LLT Selected Comment
Option 1 Halitosis worsened Halitosis Record “worsened”
in a consistent,
documented way
(e.g., check box
on data
collection form)
Option 2 Progression of
Addison’s disease
Disease progression
Addison's disease
Use 2 terms to
record pre-existing
condition and
modification
Jaundice aggravated

Condition aggravated
Jaundice

3.10 – Exposures during Pregnancy and Breast Feeding
To select the most appropriate term (or terms), first determine if the subject/patient who experienced the event is the mother or the child/fetus.

        3.10.1 Events in the mother

Ø  Patient became pregnant while receiving product

Pregnancy is not normally considered an adverse event, but organizations may wish to record this information in their databases.

Example

Reported LLT Selected Comment
Pregnancy (no adverse effect) Pregnancy
No adverse effect
Select LLT
No adverse effect
(in addition to LLT
I) if no
adverse event has
occurred. (See
Section 3.21)
Pregnancy (outcome
unknown)
Pregnancy Select LLT Pregnancy
only if neither outcome
nor occurrence of
AE is known

Ø  Pregnant patient receiving medication experienced adverse event

Example

Reported LLT Selected Comment
Pregnant patient receiving
drug X experienced a
pruritic rash
Maternal exposure
during pregnancy
Pruritic rash
LLT Pregnancy can be selected for
medical history,
concomitant
medical condition

        3.10.2 Events in the child or fetus

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

Example

Setting/Patient Reported LLT Selected
Fetus with AE;
exposed in utero; mother
took product
Pregnant woman taking drug
X; fetal tachycardia
noted on routine
examination
Drug exposure in utero
Fetal 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. (MedDRA Introductory Guide, Version 16.0; see Appendix, Section 4.2 for a link to the MedDRA Introductory Guide).

        3.11.1 Condition described as congenital

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
Congenital heart disease Heart disease congenital
Child born with heart disease

        3.11.2 Condition not congenital/not present at birth

If the condition is not described as congenital or present at birth, select the non-qualified term for the condition; if a non-qualified term is not available, select the “acquired” term for the condition.

Example

Reported LLT Selected Comment
Night blindness Night blindness LLT/PT Night blindness
(links to primary SOC
Eye disorders). Do not
assume the condition is
congenital (LLT/PT
Congenital night
blindness
)
Cholangiectasis Cholangiectasis acquired  

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 multi-axial. 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 multi-axial; 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
Hypoglycemia Hypoglycemia LLT Hypoglycemia 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 hyperkalemia
Hyperkalemia 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 may be used to record test names when entering diagnostic test data.

Example

Information/Reported
(Verbatim)
LLT Selected for Test Name Comment
Cardiac output
measured
Cardiac output  
Increased blood sugar Blood glucose LLT Blood glucose
increased
should not be
selected as it is both a
test name and a result*

*Enter a qualifier (e.g., "increased") or a numeric result (if available) into the "Result" data field.

3.15 – Medication/Administration Errors, Accidental Exposures and Occupational Exposures
.

        3.15.1 Medication/administration 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
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

        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.

Also, if specifically reported that no adverse effect has occurred, it is acceptable to select LLT No adverse effect.

In instances where the medication did not reach the patient, it is acceptable to select LLT Drug not taken in context of intercepted medication error.

Example

Reported LLT Selected Comment
Medication was given
intravenously instead of
intramuscularly
Intramuscular formulation
administered by
other route
 
Medication was given
intravenously instead of
intramuscularly
without sequelae
Intramuscular formulation
administered by
other route
No adverse effect
See Section 3.21
Patient was dispensed the
wrong drug.  The error
was detected prior to
patient administration
Intercepted drug
dispensing error
 
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
LLT Drug name
confusion
could be an
optional additional term
to select (for tracking
purposes). Note: this
example is a potential
medication error
Drug inadvertently
administered. The error
was noticed soon
afterwards
Drug administration error  

        3.15.1.3 Medication errors in the context of labeled instructions

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, then select a medication error term for the type of interaction, such as those listed below:

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

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
Interaction must be
stated in product data
sheet (See also
Section 3.20)
Patient drank grapefruit
juice whilst taking a calcium
channel blocker
Labelled drug-food
interaction
medication error
Product is labeled for
grapefruit juice
interaction
Patient with renal failure is
prescribed a drug that is
contraindicated in renal
failure
Labelled drug-disease
interaction
medication error
 
Patient is administered a
sulfonamide-based drug

Documented
hypersensitivity to
administered drug
Medical file clearly
indicates patient has a
sulfa allergy

        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
Antibiotic was prescribed
for a week, and the patient
stopped treatment after 2
days because of bitter
taste
Prescribed dosing duration
not completed
Taste bitter
LLT Taste bitter
represents a sensory
perception issue. LLT
Medication after taste
refers to a product
quality issue
Incorrect dosing by patient Incorrect dose
administered
Do not select Extra
dose administered or
Overdose
based on this
information alone
Patient took only half the
prescribed dose
Underdose
 

        3.15.2 Accidental exposures and occupational exposures

        3.15.2.1 Accidental exposures

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

Example

Reported LLT Selected
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 Exposure via 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 spplied 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 provider Yes 3.15
Off label use Yes Healthcare provider Yes 3.27

        3.16.1 Misuse

For the purposes of term selection and analysis of MedDRA-coded data, misuse is the intentional and inappropriate use of a product – over-the-counter or prescription – other than as prescribed or not in accordance with the authorized product information.

Example

Reported LLT Selected
Patient deliberately ingested the topical medication Intentional use by incorrect route
Patient deliberately took the medication for two days longer than instructed on the product label Intentional use beyond labeled duration

        3.16.2 Abuse

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

Example

Reported LLT Selected
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

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 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
Cocaine dependencee
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.

3.17 – Transmission of Infectious Agent via Product
If a report of transmission of an infectious agent via medicinal 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 a
medicinal 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 medicinal product but this could be implied by other data within the report. In this instance, select LLT Suspected transmission of an infectious agent via a medicinal product.

3.18 – Overdose, Toxicity and Poisoning
Overdose terms are grouped under HLT Overdoses. Toxicity and poisoning terms are grouped under HLT Poisoning and toxicity. For more information, refer to the MedDRA Introductory Guide, v16.0. (See Appendix, Section 4.2 for a link to the MedDRA Introductory Guide).

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

Example

 

Reported LLT Selected Comment
Overdose of pills Overdose  
A child was accidentally
poisoned when she ingested
a chemical cleaning product
Accidental poisoning
Chemical poisoning
 
Patient intentionally took
many more than the
prescribed number of pills
Intentional overdose  
The dose of drug X taken
was above the recommended
maximum dose in the label
Drug overdose  
Nurse inadvertently
administered an additional
vaccine dose to an already
vaccinated child
Inappropriate dose of vaccine administered Please note that LLT Inappropriate dose of vaccine administeredis a maladministration term, not specifically an overdose term

        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, select LLT Overdose and the additional LLT No adverse effect can be selected. (See Section 3.21).

Example

Reported LLT Selected Comment
Patient received an overdose
of medicine without any
adverse consequences
Overdose
No adverse effect
LLT No adverse
effect
can also
be selected

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
My patch is not sticking to my skin Medicinal patch adhesion issue

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

Labeled 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 organizations 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 organizations 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 multi-axial 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, thalassemia, 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 Thalassemia major, or LLT Myocardial infarction based on regional regulatory requirements.

Treatment of chronic iron overload in thalassemia 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 (Note: the preferred option is to select a general prevention/ prophylaxis term and a term for the condition):

Example

Reported LLT Selected Preferred
Option
Comment
Prevention of
hepatotoxicity
Prevention
Hepatotoxicity
Select the closest
term for
both concepts
Hepatotoxicity   Select a term for
the condition
Prevention   Select the closest
prevention/prophylaxis
term

        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 anesthesia Induction of anesthesia
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

The concept of “off label use” relates to situations where the product is intentionally used for a medical purpose not in accordance with the authorized product information.

        3.27.1 Off label use when reported as an indication

If a medical condition is reported as an indication along with “off label use”, the preferred option is to select terms for the medical condition and LLT Off label use or other appropriate LLTs linked to PT 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 Comment
Used off label Off label use  
Off label use in paediatric patients Drug use in unapproved population Refers to a population of patients
Drug X given to a 10 year old boy; the drug is not indicated for use below 18 years Adult product administered to child LLT Adult product administered to child is linked to PT Off label use

        3.27.2 Off label use when reported with AR/AE

If an AR/AE occurs as a result of off label use, the preferred option is to select LLT Off label use, or other appropriate LLTs linked to PT Off label use, and a term for the medical condition in addition to a term for the AR/AE. Alternatively, select a term for the medical condition 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
Stroke
Pulmonary hypertension
Stroke
Pulmonary hypertension
 

3.28 – Product Quality Issues

It is important to recognize 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/labeling, 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 issues (in SOC General disorders and administration site conditions) is essential for term selection. Under this HLGT are categories of specific product quality issues such as HLT Product packaging issues, Product physical issues, 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
New bottle of drug tablets have unusual
chemical smell that made me nauseous
Product odor 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 had a mouldy odour  Subsequent investigation of the product lot number revealed that the toothpaste was a counterfeit product Product counterfeit
Product odour abnormal

        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/labeling, 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
insufficient amount of
prescribed antibiotic
because the lines on the
dropper were hard to read
Product dropper calibration
unreadable
Insufficient dosage
Product quality issue
and medication error

Section 4 – APPENDIX

4.1 – Versioning

        4.1.1 – Versioning methodologies

Each organization 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 organization’s characteristics. The optional methods described below can be used to document the extent to which an organization 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 organizations.

The table below summarizes 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. Links to these tools are in the 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 synchronize 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

Document Link
MedDRA Introductory Guide http://meddramsso.com/files_acrobat/intguide_16_0_English_update.pdf
MedDRA Change Request Information document http://meddramsso.com/subscriber_download_change_request.asp
MedDRA Web-based Browser https://meddramsso.com/subscriber_download_tools_wbb.asp
MedDRA Desktop Browser https://meddramsso.com/subscriber_download_tools_browser.asp
MedDRA Version Report (lists all changes in new version) * https://meddramsso.com/secure/subscriber_download_translations.asp
MedDRA Version Analysis Tool (compares any two versions) * http://www.meddramsso.com/subscriber_download_tools_mvat.asp
MSSO’s Recommendations for Single Case Reporting http://meddramsso.com/files_acrobat/VCGuide_semiannual.pdf
MSSO’s Recommendations for Clinical Trial Versioning http://meddramsso.com/files_acrobat/clinicaltrialversioning.pdf
Transition Date for the Next MedDRA Version http://www.meddramsso.com/index_subscriber.asp

* 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
Sarah Vaughan
Maria Luisa Casini
European Federation of
Pharmaceutical Industries
Associations
Hilary Vass**
Christina Winter*†
Health Canada Alison Bennett
Lynn Macdonald
Japanese Maintenance Organization Osamu Handa
Kazuyuki Sekiguchi
Reiji Tezuka
Japan Pharmaceutical
Manufacturers Association
Yo Tanaka
MedDRA MSSO Judy Harrison
Patricia Mozzicato
Ministry of Health, Labour
and Welfare
Shinichi Okamura
Makiko Isozaki
Hideyuki Kondou
Shinichi Watanabe
Pharmaceutical Research and
Manufacturers of America
Anna-Lisa Kleckner
JoAnn Medbery
US Food and Drug Administration John (Jake) Kelsey*
Sonja Brajovic

* Current co-Rapporteurs
† 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
European Federation of Pharmaceutical
Industries Associations
Barry Hammond†; Reinhard Fescharek†
Health Canada Heather Morrison; Michelle Séguin;
Heather Sutcliffe; Bill Wilson
Japanese Maintenance Organization Akemi Ishikawa; Yasuo Sakurai;
Yuki Tada
Japan Pharmaceutical
Manufacturers Association
Takayoshi Ichikawa; Akemi Ishikawa;
Satoru Mori; Yasuo Sakurai;
Kunikazu Yokoi
MedDRA MSSO JoAnn Medbery
Ministry of Health, Labour
and Welfare
Tamaki Fushimi; Wakako Horiki;
Kazuhiro Kemmotsu; Tatsuo Kishi;
Chie Kojima; Emiko Kondo; Kemji
Kuramochi; Tetsuya Kusakabe;
Kaori Nomura; Izumi Oba;
Yoshihiko Sano; Nogusa Takahara; Kenichi Tamiya; Daisuke Tanaka; Takashi Yasukawa; Go Yamamoto; Manabu Yamamoto;
Nobuhiro Yamamoto
Pharmaceutical Research
and Manufacturers of America

David Goldsmith; Sidney Kahn;
Susan M. Lorenski;
Margaret M. Westland†
US Food and Drug Administration Miles Braun; Andrea Feight;
Brad Leissa; Toni Piazza-Hepp

†  Former Rapporteur