MedDRA^® TERM SELECTION:

POINTS TO CONSIDER

ICH-Endorsed Guide for MedDRA Users

1 March 2016

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 harmonising 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 and Korean regulatory authorities, 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).

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

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

•  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

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

• Postoperative and post procedural terms

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

Example

• 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

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

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

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

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.

EXAMPLES
Example	Reported	LLT Selected	Preferred Option
1	Anaphylactic reaction, rash dyspnoea, hypotension, and laryngospasm	Anaphylactic reaction
		Anaphylactic reaction Rash Dyspnoea Hypotension Laryngospasm
2	Possible 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

        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

        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

        3.2.4 Other patient outcomes (non-fatal)

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

Example

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

Example

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

        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

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

        3.4.2 Ambiguous information

Example

        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

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

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

        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

        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

        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

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

        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

Ø  Unambiguous investigation result

Example

Ø  Ambiguous investigation result

Example

        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

        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

        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

        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 in the ICH E2B electronic transmission standard.

Example

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

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

        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.

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

        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

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:

Example

        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

        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

        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

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

* 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 and inappropriate use of a product – over-the-counter or prescription – other than as prescribed or not in accordance with the authorised product information.

Example

        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” (euphoria). Abuse may occur with a single use, sporadic use or persistent use of the product.

Example

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

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

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

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 Maladministrations; 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

        3.18.1 Overdose reported with clinical consequences

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

Example

        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

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

Example

        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

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

        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

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.

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

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

        3.23.3 Increased, decreased and prolonged effect

Example

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

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:

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:

(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

3.25 – Medical and Social History

Example

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

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

Example

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

        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

        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

        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

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

        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

        3.26.7 Indication not reported

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

Example

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 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

        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 LLT Off label use, or other appropriate LLTs linked to PT 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

        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

        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

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).

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) *
•  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

* Current Rapporteur
# Regulatory Chair
† Former Rapporteur

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

† Former Rapporteur