APPENDIX B:  MedDRA CONCEPT DESCRIPTIONS

This appendix provides a list of MedDRA concept descriptions.  A concept description is a description of how a concept is interpreted, used, and classified within the MedDRA terminology and is not a definition.  The concept descriptions are intended to aid the consistent and accurate use of MedDRA in coding, retrieval, and analysis and to overcome the differences of medicine practice worldwide.  The MSSO expects this appendix to be a working document and grow as subscribers request additional concepts to be documented.

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z

A

Abuse           

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

Acute             

                   For use in medicine, the word means “reaching a crisis rapidly.”  In some instances, an “acute” condition may be interpreted as more severe than a “chronic” one.  This was considered during the processing of proposed modified terms to assure that terms expressing only severity were not included.

Addiction      

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

Aggravated   

                   From “aggravate”: To make worse, e.g., “bronchitis aggravated by smoking.” For the purposes of term placement in MedDRA, the use of modifiers exacerbated, aggravated and worsened is interchangeable

Application site

For the purposes of MedDRA, an application site is considered to be the surface that contacts a topical medication in the form of a cream, lotion, or patch (e.g., an estrogen hormone patch).  It does not pertain to other methods of drug delivery such as injection or infusion by catheter or other means.

Angina         

                   “Angina” exists in MedDRA as a non-current LLT because of the ambiguous nature of the term.  Angina is interpreted as a variant expression for acute tonsillitis (angina tonsillaris) in certain languages. However, based on the popular usage of this term in English language for Angina pectoris, in MedDRA it is linked to PT Angina pectoris. 

Arthritis/Arthrosis
In MedDRA, any inflammation of a joint is considered “arthritis.”  In contrast “arthrosis” is interpreted as a non-inflammatory degenerative joint disease and is linked to PT Osteoarthritis.

C

Cancer/Carcinoma
"Cancer" is a disease in which abnormal cells divide uncontrollably and can spread to other parts of the body (metastasize).  "Cancer" can be one of several histologic types including those derived from epithelial tissues (carcinomas), those derived from mesenchymal tissue (sarcomas), and those arising from hematopoietic and lymphoid tissues (leukemia, lymphomas, and multiple myeloma).  In the context of MedDRA, "carcinoma" and "cancer" are considered synonymous. “Carcinoma" terms are generally subordinate to "cancer" terms (e.g., LLT Skin carcinoma is linked to PT Skin cancer).

Cell marker

                   A cell marker is a biochemical or genetic characteristic of a cell which discriminates between different cell types.

Chronic          

                   Of long duration; subject to a disease or habit for a long time.  In some instances, a “chronic” condition may be interpreted as milder than an “acute” one.  This was considered during the processing of proposed modified terms to assure that terms expressing only severity were not included.

Closure         

                   Closure is the cap, lid, stopper or other feature which is the primary mechanism for protecting the product from spill, air etc.

 Cold               

                   For purposes of MedDRA, the mention of “cold” without addition of any prefix of feeling signifies the catarrhal disorder associated with nasopharyngitis. “Coldness” and “feeling cold,” are body temperature perceptions of uncomfortably low

                   temperature for humans.

 Compounding

                    Compounding refers to products that are usually made by a pharmacist or physician.

Compounding issue
Compounding issue refers to quality problems associated with those  products.

Contributing factor

                   A contributing factor is a circumstance, action or influence which is thought to have played a part in the origin or development of a medication error or to increase the risk of a medication error.

Coring
A small piece of the stopper is sometimes sheared off (known as coring); an example could be after a needle is inserted through the stopper of a medication vial. 

Crystal formation
Crystals are symmetrically arranged formations created by the solidification of a chemical element, a compound, or a mixture found in or on the dosage form which is not normal for the product.  

D

Device capture

PT Device capturing issue refers to a situation where a device fails capture signal input or output, or captures the wrong signal input or output.

Device use error

An act or omission of an act that results in a different medical device response than intended by the manufacturer or expected by the operator.

Diaphragm 
For purposes of MedDRA, diaphragm is considered a respiratory structure.

Dispensing Error 
Dispensing errors are not limited to pharmacists.  It can include nurses and physicians.  For example, physicians can dispense sample products in their office.

Dissolution

                   Dissolution is the process in which one substance is dissolved in another. Dissolution and solubility are considered synonyms in MedDRA.

Dosage       

                  The determination and regulation of the size, frequency, and number of doses. 

Dosage Form
The physical form in which a drug is produced for administration to recipient (tablets, capsules, cream etc.).

Dose            

                  A quantity to be administered at one time, such as a specified amount of medication. 

Dose Omission 

Dose omission refers to an event where an ordered dose is not administered before the next scheduled dose, if any.  

 Documented hypersensitivity to administered drug
This medication error refers to the situation when a patient is administered a drug that is documented in the patient's medical file to cause a hypersensitivity reaction in the patient.  Example:  Despite the fact that the patient's medical record indicated "sulfa allergy," the physician prescribed a sulfa antibiotic. Subsequently, the patient took the antibiotic and experienced hives. A related term, PT Documented hypersensitivity to administered product, applies to similar situations involving known hypersensitivity to other types of products, not specifically drugs.

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.

Drug Formulation 
Refers to both active and inactive ingredients.

Duration      

Includes duration of therapy/length of therapy.

E

Exacerbation
See “Aggravated.”  For the purposes of term placement in MedDRA, the use of modifiers exacerbated, aggravated and worsened is interchangeable

Exposure      
For the purposes of MedDRA, the concept of “exposure”:

· Is not limited to drugs; it can include exposure to chemicals, toxins, radiation, communicable disease, etc.

· Can occur through various pathways (via blood, direct contact, etc.)

Extension     
When paired with a product or a device, an extension is a component of a device that carries the impulses from the implant site of a device to the lead.

G

Gel Formation
A product has formed into a gelatinous matter, a colloid in a more solid form than a solution which is not normal for the product.

H

High Blood Pressure
“High” and “low” terms in MedDRA are generally considered to be laboratory/investigation type of terms and are found in the SOC Investigations.  However, because of the synonymous use of expression blood pressure high and hypertension in common usage, the LLT Blood pressure high is linked to PT Hypertension in SOC Vascular disorders. 

Hypertension vs. Hypertonia
Hypertonia” may be synonymous for “hypertension” in some languages.  However, for purposes of MedDRA, hypertonia is defined as a condition marked by an abnormal increase in muscle tension and a reduced ability of a muscle to stretch. Hence, it is placed in muscle tone disorders.

Hy's Law
Hy's law is used as an indicator for potential drug-induced liver injury. To be considered a potential “Hy's law” case, the following three components must all be met:

· Elevation of aminotransferases, e.g., alanine aminotransferase (ALT) and aspartate aminotransferase (AST), of >3x upper limit of normal (ULN)

· Alkaline phosphatase (ALP) <2x ULN

· Increase in total bilirubin ≥2x ULN

Please refer to the July 2009 FDA Guidance for Industry – “Drug-Induced Liver Injury: Premarketing Clinical Evaluation” for additional information.

I

Inappropriate Schedule     
Includes all deviations from the prescribed dosage schedule.

Intercepted medication error

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

Issue             
The word “issue” for the purpose of MedDRA is used as a general term, which does not necessarily point to a failure or defect when paired with a product or a device. 

L

Label
Label refers to display of written, printed, or graphic matter upon the container or packaging.

Labelled drug-disease interaction medication error
This medication error refers to the situation when a patient is prescribed, dispensed, or administered a drug that is documented in the drug label as having the potential to exacerbate or worsen the patient's pre-existing disease(s).  Example: A patient has a medical history of having bleeding gastric ulcers. However, the patient was inadvertently prescribed and dispensed several doses of aspirin.

Labelled drug-drug interaction medication error
This medication error refers to the situation when a patient is prescribed, dispensed, or administered a drug that is documented in the drug label to cause a drug to drug interaction with the patient's existing medication(s).  Example: Patient became pregnant whilst taking an antifungal drug and an oral contraceptive.  This interaction is clearly stated in the product data sheet.

Labelled drug-food interaction medication error
This medication error refers to the situation when a patient is prescribed, dispensed, or administered a drug that is documented in the drug label to cause an expected adverse event with patient's consumed food.  Example: Patient drank grapefruit juice whilst taking a calcium channel blocker and the calcium channel blocker is labeled for grapefruit juice interaction.

Labelled drug-genetic interaction medication error

This medication error refers to the situation when a patient is prescribed, dispensed, or administered a drug that is documented in the drug label to cause an interaction in patients with particular genetic variants. Example: Patient was inadvertently given a drug that is contraindicated in patients who are cytochrome P450 2D6 poor metabolisers.

Lower gastrointestinal tract
For purposes of MedDRA, the following constitute the lower gastrointestinal tract: small intestine (duodenum, jejunum, ileum) and large intestine which includes cecum (and the vermiform appendix attached to the cecum), colon (ascending colon, transverse colon, descending colon and sigmoid flexure), rectum, and anus.

Lower respiratory tract
For purposes of MedDRA the lower respiratory tract is comprised of  bronchi, bronchioles, alveoli and lungs.

M

Manufacturing stability testing

For the purposes of term selection and analysis of MedDRA-coded data, manufacturing stability testing refers to the stage of the manufacturing process where testing is performed to provide evidence on how the quality of a drug substance or drug product varies with time under the influence of a variety of environmental factors such as temperature, humidity, and light. Stability testing permits the establishment of recommended storage conditions, retest periods and shelf lives.

Medication error
For the purposes of term selection and analysis of MedDRA-coded data, medication errors are defined as any unintentional and 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.  Such events may be related to professional practice, health care products, procedures and systems, including prescribing, order communication, product labeling, packaging and nomenclature, compounding, dispensing, distribution, administration, education, monitoring and use.

Medication monitoring error
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.

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

O

Occupational exposure
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. 

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

Out of specification test results

For the purposes of term selection and analysis of MedDRA-coded data, out of specification test results refers to test results performed during the pharmaceutical product manufacturing process that fall outside the specifications or acceptance criteria established in drug applications, drug master files, official compendia, or by the manufacturer. It also applies to all-in process laboratory tests that are outside of established specifications.

Overdose
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.

P

Precipitate                          

                  Precipitate is substance separated from a solution or suspension by chemical or physical change usually as an insoluble solid which is not normal for the product.

Preparation  

                  A medicinal substance that is ready for use (e.g., a preparation for colds).

http://www.merriam-webster.com/medical/preparation

Prescribing error      
Prescribing errors may be made in the hand of physicians or other healthcare professionals who have the prescription authority.

Procedure
This term relates to concepts currently in SOC Injury, poisoning and procedural complications under HLGT Procedural related injuries and complications NEC and in SOC Surgical and medical procedures.

Product
In the context of MedDRA, "product" can refer to various types of products intended for human use such as drugs (prescription and over the counter), biologics, vaccines, combination products, devices, nutraceuticals, dietary supplements, etc. 

Product coating incomplete
Product coating incomplete refers to the outer coating of a product when it does not entirely cover the product and can appear blotchy, splattered or speckled.

Product colour issue
Product color issue is when the product color is not uniform; color has faded or turned to a different color/shade.

Product dosage form confusion
Product dosage form confusion is a misinterpretation of the dosage form of a product which may potentially result in a medication error.

Product label confusion
Product label confusion is a misinterpretation of the appearance and/or content of a product label which may potentially result in a medication error. This may be due to similarity with another product's label or due to confusing information on a single product label.

Product name confusion
Product name confusion is a misinterpretation of the correct name of a product which may result in a medication error. This may be due to a misleading name, or due to similar-looking or sounding product names.

Product odour abnormal    

                      A change in the normal odor of the product.

Product packaging confusion
Product packaging confusion is a misinterpretation of the appearance of a product's packaging which may potentially result in a medication error. This may be due to similarity with the appearance of another product's packaging or due to confusing appearance or presentation of a single product's packaging.

Product quality issues 
Product quality issues are abnormalities that may be introduced during the manufacturing/labeling, packaging, shipping, handling or storage of the products.

Product storage

                   HLT Product distribution and storage issues in SOC Product issues is intended to cover issues with the storage of products by manufacturers, distributors, wholesalers, etc. In contrast, product storage issues by end-users such as healthcare professionals, patients, and consumers are considered to be medication errors and are represented by the appropriate medication error terms in HLT Product storage errors and issues in the product use system in SOC Injury, poisoning and procedural complications.

Product taste abnormal     

                    A change in the normal taste of the product.

Progression of 
Movement forward; advancement.  Continuously spreading or increasing in severity.

Prophylaxis of 
Protective treatment for or prevention of disease.  For the purposes of term placement in MedDRA, the use of modifiers “prophylaxis” and “prevention of” is interchangeable.

R

Rate              

                   The amount of drug (dose) administered per unit of time

Recurrent     

Occurring or appearing again or repeatedly.  For the purposes of term placement in MedDRA, the modifiers “relapse” and “recurrent” are synonymous.

S

Seal
A seal refers to an outer wrap on the closure or a liner attached to the container underneath the closure to either protect the product or act as a tamper evident feature.

Sedimentation
Sedimentation is the settling of product or foreign material to the bottom of a vial/container which is not normal for the product.

Sore/soreness/sores
For purposes of MedDRA, “sore” and “soreness” terms are used  for pain.  “Sore” terms, unless clearly addressed to a concept e.g. LLT Bed sore linked to PT Decubitus ulcer – are mainly placed under either pain related PTs or PTs indicating inflammation. “Sores” are considered lesions of the skin or mucous membrane frequently associated with pain, inflammation etc., depending on the context.

Solubility      

                  See the concept description for dissolution.

Strength        

Refers to a concentration of active ingredient found in a particular dosage form.

Subacute       

Between acute and chronic: course of a disease of moderate duration or severity. Please see definitions of “acute” and “chronic.”

T

 Technique   

The manner of performance, method, operation, procedure, or details (e.g.,   pharmaceutical technique, aseptic technique) used to prepare a product. 

Tenderness  

For purposes of MedDRA tenderness terms are defined as sub-concepts of pain and mainly subordinated to “Pain” or to “-algia” PTs unless they clearly address a single concept (e.g., PT Abdominal rebound tenderness).

Thrombophlebitis
Inflammation of a vein (phlebitis) associated with thrombus formation (thrombosis). The MSSO acknowledges the international use of thrombophlebitis/phlebothrombosis/vein thrombosis interchangeably, but MedDRA recognizes them as separate unique concepts. MedDRA also makes a distinction between superficial and deep vein thrombosis. When thrombosis occurs in the lower extremity, it is often called deep venous thrombosis/thrombophlebitis (DVT); when superficial vessels are involved, it is superficial thrombosis/thrombophlebitis.

U

Underdose   

For the purposes of term selection and analysis of MedDRA-coded data, underdose is the administration of less than the minimum recommended dose (in quantity and/or concentration).

Upper gastrointestinal tract
In MedDRA the following organs constitute the upper gastrointestinal tract: mouth (buccal cavity; including salivary glands, mucosa, teeth, and tongue), oesophagus and stomach which includes the cardia, fundus, body, and pylorus.

Upper respiratory tract
In MedDRA the upper respiratory tract is comprised of nose, paranasal sinuses, pharynx, larynx and trachea.

W

Worsened/worsening 
See “aggravated.”  For the purposes of term placement in MedDRA, the use of modifiers exacerbated, aggravated, and worsened is interchangeable.