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

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	Comment
Child accidentally took grandmother’s pills and experienced projectile vomiting	Accidental drug intake by child Vomiting projectile
Father applying topical steroid to his arms accidentally exposed his child to the drug by carrying her	Accidental exposure to product by child Exposure via skin contact	The “exposure to” term captures the agent of exposure, i.e., a product, and the “exposure via” term captures the route/vehicle of exposure, i.e., skin contact

        3.15.2.2 Occupational exposures

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

Example

Reported	LLT Selected	Comment
Physical therapist developed a photosensitivity rash on hands after exposure to an NSAID-containing pain relief cream that she 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” (euphoria). 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	Dependence on cocaine
Patient became addicted to a deliberately ingested topical medication for its psychoactive effect	Drug addiction Intentional use by incorrect route

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

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

Example

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

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

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, the preferred option is to select only a term for the overdose. Alternatively, a term for the overdose and the additional LLT No adverse effect can be selected. (See Section 3.21).

Example

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

3.19 – Device-related Terms

        3.19.1 Device-related event reported with clinical consequences

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

Example

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

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

Example

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

        3.19.2 Device-related event reported without clinical consequences

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

Example

Reported	LLT Selected
Medical device breakage	Device breakage
My patch is leaking on my arm	Leaking patch
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. (See Appendix, Section 4.2.)

        4.1.2 – Timing of version implementation

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

Date of New Reporting Version for Individual Case Safety Reporting

A new release version of MedDRA should become the reporting version on the first Monday of the second month after it is released. To 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

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
•  MSSO's Recommendations for Clinical Trial Versioning
•  Transition Date for the Next MedDRA Version

* Requires user ID and password to access

4.3 Membership of the ICH Points to Consider Working Group

        4.3.1 Current members of the ICH Points to Consider Working Group

Affiliation	Member
Commission of the European Communities	Sarah Vaughan
	Maria Luisa Casini
European Federation of Pharmaceutical Industries Associations	Hilary Vass*
	Christina Winter†
Health Canada	Alison Bennett
	Lynn Macdonald
Japanese Maintenance Organization	Yutuka Nagao
	Kazuyuki Sekiguchi
	Reiji Tezuka
Japan Pharmaceutical Manufacturers Association	Yo Tanaka
MedDRA MSSO	Judy Harrison
Ministry of Health, Labour and Welfare/Pharmaceuticals and Medical Devices Agency	Sonoko Ishihara
	Makiko Isozaki
	Yuuhei Fukuta
Pharmaceutical Research and Manufacturers of America	Anna-Lisa Kleckner
	JoAnn Medbery
US Food and Drug Administration	Sonja Brajovic
	Christopher Breder

* Current Rapporteur
† 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	Osamu Handa; Akemi Ishikawa; Yasuo Sakurai; Yuki Tada
Japan Pharmaceutical Manufacturers Association	Takayoshi Ichikawa; Akemi Ishikawa; Satoru Mori; Yasuo Sakurai; Kunikazu Yokoi
MedDRA MSSO	JoAnn Medbery; Patricia Mozzicato
Ministry of Health, Labour and Welfare/Pharmaceuticals and Medical Devices Agency	Tamaki Fushimi; Wakako Horiki; Kazuhiro Kemmotsu; Tatsuo Kishi; Chie Kojima; Emiko Kondo; Hideyuki Kondou; Kemji Kuramochi; Tetsuya Kusakabe; Kaori Nomura; Izumi Oba; Shinichi Okamura; Yoshihiko Sano; Nogusa Takahara; Kenichi Tamiya; Daisuke Tanaka; Shinichi Watanabe; Takashi Yasukawa; Go Yamamoto; Manabu Yamamoto; Nobuhiro Yamamoto
Pharmaceutical Research and Manufacturers of America	David Goldsmith; Sidney Kahn; Susan M. Lorenski; Margaret M. Westland†
US Food and Drug Administration	Miles Braun; Andrea Feight; John (Jake) Kelsey†; Brad Leissa; Toni Piazza-Hepp

† Former Rapporteur