Pharmacovigilance Unit 2 PDF

# UNIT-2 ## Drug and disease classification ### Points to be covered in this topic - Anatomical, Therapeutic and Chemical Classification of Drugs - International Classification of Diseases - Daily defined Doses - International Nonproprietary Names for Drugs ## Drug and disease classification ### DRU...

# UNIT-2 ## Drug and disease classification ### Points to be covered in this topic - Anatomical, Therapeutic and Chemical Classification of Drugs - International Classification of Diseases - Daily defined Doses - International Nonproprietary Names for Drugs ## Drug and disease classification ### DRUG AND DISEASE CLASSIFICATION - A classification of diseases can be defined as a system of categories to which morbid entities are assigned according to established criteria. - The purpose of the ICD is to permit the systematic recording analysis, interpretation and comparison of mortality and morbidity data collected in different countries or areas and at different times. - The ICD is used to translate diagnoses of diseases and other health problems from words into an alphanumeric code, which permits easy storage, retrieval and analysis of the data. - The ICD can be used to classify diseases and other health problems recorded on many types of health and vital records. Its original use was to classify causes of mortality as recorded at the registration of death. - Later, its scope was extended to include diagnoses in morbidity. - The WHO Family of International Classifications (WHO-FIC) attempts to serve as the framework of international standards to provide building blocks of health information systems. ### There may be other related classifications: - Reference classification - Derived classifications - Related classifications - Diagnosis-related classifications Non-diagnostic classifications - The International Classification of Functioning, Disability and Health ## ANATOMICAL, THERAPEUTIC AND CHEMICAL CLASSIFICATION OF DRUGS ### Structure and nomenclature - In the Anatomical Therapeutic Chemical (ATC) classification system, the activ substances are divided into different groups according to the organ or system on which they act and their therapeutic, pharmacological and chemical properties. Drugs are classified in groups at five different levels. The drugs are divided into fourteen main groups (1st level), with pharmacological/therapeutic subgroups (2nd level). - The 3rd and 4th levels are chemical/pharmacological/therapeutic subgroups and the 5th level is the chemical substance. The 2nd 3rd and 4th levels are often used to identify pharmacological subgroups when that is considered more appropriate than therapeutic or chemical subgroups. - The complete classification of metformin illustrates the structure of the code: | Code | Organ or system | |---|---| | A | Alimentary tract and metabolism (1st level, anatomical main group) | | A10 | Drugs used in diabetes (2nd level, therapeutic subgroup) | | A10B | Blood glucose lowering drugs, excl. insulin (3rd level, pharmacological subgroup) | | A10BA | Biguanides (4th level, chemical subgroup)| | A10BA02 | Metformin (5th level, chemical substance) | - Thus, in the ATC system all plain metformin preparations are given the code A10BA02. ### Nomenclature - International non-proprietary names (INN) are preferred. If INN names are not assigned, USAN (United States Adopted Name) or BAN (British Approved Name) names are usually chosen. - WHO's list of drug terms (Pharmacological action and therapeutic use of drugs: List of Terms) is used when naming the different ATC levels. - ATC main groups: | Abbreviation | Explanation | |---|---| | A | Alimentary tract and metabolism | | B | Blood and blood forming organs | | C | Cardiovascular system | | D | Dermatologicals | | G | Genito urinary system and sex hormones | | H | Systemic hormonal preparations, excl. sex hormones and insulin | | J | Anti-infectives for systemic use | | L | Antineoplastic and immune modulating agents | | M | Musculo-skeletal system | | N | Nervous system | | P | Anti-parasitic products, insecticides and repellents | | R | Respiratory system | | S | Sensory organs | | V | Various | ### Inclusion and exclusion criteria - The WHO Collaborating Centre in Oslo establishes new entries in the ATC classification on requests from the users of the system. These include manufacturers, regulatory agencies and researchers. The coverage of the system is not comprehensive. A major reason why a substance is not included is that no request has been received. - Active ingredients which fulfill one of the following criteria will normally be included in the ATC system: - They are new chemical entities (active ingredients) or biologicals proposed for licensing in a range of countries. A new chemical entity is normally not included in the ATC system before an application for marketing authorization is submitted in at least one country. - They are existing well defined chemical entities used in a variety of countries. An INN should preferably be established for the active ingredient. Alternatively other official names, e.g. USAN or BAN names should be available. - They are herbal medicinal products assessed and approved by regulatory authorities based on dossiers including efficacy, safety, and quality data (e.g. the well-established used procedure in EU). - Other medicinal products are considered on a case by case basis. Complementary, homeopathic and herbal traditional medicinal products are in general not included in the ATC system. ## Principles for classification ### General Principles - Medicinal products are classified according to the main therapeutic use of the main active ingredient, on the basic principle of only one ATC code for each route of administration (i.e. pharmaceutical forms with similar ingredients and strength will have the same ATC code). - Immediate and slow release tablets will normally have the same ATC code. - A medicinal product can be given more than one ATC code if it is available in two or more strengths or routes of administration with clearly different therapeutic uses. Two examples of this are as follows: - Sex hormones in certain dosage forms or strengths are only used in the treatment of cancer and are thus classified under L02 - Endocrine therapy. Remaining dosage forms/strengths are classified under G03 - Sex hormones and modulators of the genital system. - Clonidine is available in two different strengths. One strength, which is used mainly in the treatment of hypertension, is classified under CO2 - Antihypertensive. Another strength mainly used in the treatment of migraine is classified under N02C - Antimigraine preparations. - Different pharmaceutical forms for topical and systemic use are also given separate ATC codes. ### Example: - Prednisolone in single ingredient products is given several ATC codes due to different therapeutic use and different local application formulations. | Code | Type of drug | Type of dosage form | |---|---|---| | A07EA01 | Intestinal anti-inflammatory agents | Enemas and foams | | C05AA04 | Antihemorrhoidals for topical use | Suppositories | | D07AA03 | Dermatological preparations | Creams, ointments and lotions | | H02AB06 | Corticosteroids for systemic use | Tablets, injections | | R01AD02 | Nasal decongestants | Nasal sprays/drops | | S01BA04 | Ophthalmologicals | Eye drops | | S02BA03 | Otologicals | Ear drops | ## Classification of plain products - Plain products are defined as: - Preparations containing one active component (including stereo-isomeric mixtures). - Medicinal products which in addition to one active component contain auxiliary substances intended to increase the stability of the preparations (e.g. vaccines containing small amounts of antibacterials), increase the duration (e.g. depot formulations) and/or increase the absorption (e.g. different solvents in various dermatologicals) are also considered as plain products. Plain products are classified according to the general principles outlined in section II C1. ## Classification of combination products - Products containing two or more active ingredients are regarded as combination products. Combination products are classified according to three main principles. - (a) Combination products containing two or more active ingredients belonging to the same 4th level is normally classified using the 5th level codes 20 or 30. ### Example: - NO1BB02 lidocaine - N01BB04 prilocaine - N01BB20 combinations (e.g. lidocaine and prilocaine) - (b) Combination products containing two or more active ingredients not belonging to the same 4th level is classified using the 50-series. ### Example: - RO6AA02 diphenhydramine - RO6AA52 diphenhydramine, combinations - Different combination products sharing the same main active ingredient are usually given the same ATC code. - Thus, products containing phenylpropanolamine + brompheniramine and phenylpropanolamine + cinnarizine are both given the code R01BA51. - Packages comprising two or more different medicinal products marketed under a common brand name are also considered as combination products. e.g.: Sotalol tablets and aspirin tablets in one combination package are classified inC07AA57 sotalol, combinations. ## Principles for changes to ATC classification - As the drugs available and their uses are continually changing and expanding, regular revisions of the ATC system will always be necessary. ### Principle - Changes in the ATC classification should be kept to a minimum. Before alterations are made, difficulties arising for the users of the ATC system are considered and related to the benefits achieved by the alteration. - Alterations in ATC classification are made when the main use of a drug has clearly changed, and when new groups are required to accommodate new substances or to achieve better specificity in the groupings. - When it is decided to make an alteration, the following principles are used: - Space is provided for possible future extension of an ATC group. - The ATC code assigned to combination products should correspond as far as possible with the classification of the single substances in question. - Previous ATC codes for deleted products are not used for new substances. - Obsolete drugs or drugs withdrawn from the market are kept in the ATC system, since exclusion of substances from the ATC system may create difficulties for the users of the system when considering historical data. - Changes of currently valid codes are kept to a minimum. A gap in the sequence is preferred to changing codes. ## The EphMRA classification system - The ATC classification system was originally based on the same main principles as the Anatomical Classification (AC-system) developed by the European Pharmaceutical Market Research Association (EphMRA) and the Pharmaceutical Business Intelligence and Research Group (PBIRG). - In the EphMRA system, the drugs are classified in groups at three or four different levels. The ATC classification system is modified and extended from the EphMRA system by the addition of a therapeutic/pharmacological/chemical subgroup as the fourth level and a fifth level for the chemical substance. ## International classification of diseases - The first international classification edition known as the International List of Causes of Death was adopted by the International Statistical Institute in 1983. - WHO with the ICD was entrusted in 1948 and the 6th version was published as ICD-6 that included morbidity for the first time. - The WHO Nomenclature Regulations, adopted in 1967, stipulated that Member States use the most current ICD revision for mortality and morbidity statistics. - The ICD has been revised and published in a series of editions to reflect advances in health and medical science over time. ICD-10 was endorsed in May 1990 by the Forty-third World Health Assembly. It is cited in more than 20,000 scientific articles and used by more than 100 countries around the world. - Across the World the ICD is the foundation for the identification of health trends and statistics and international standard for reporting diseases and health conditions. It is the diagnostic classification standard for all clinical and research purposes. ICD defines the universe of diseases, disorders, injuries and other related health conditions, listed in a comprehensive, hierarchical fashion that allows for: - Easy storage, recovery and analysis of health information for evidenced-based decision-making; - Sharing and comparing health information between hospitals, regions, settings and countries; and - Comparison of data in the same location across different time periods. - These include monitoring of the incidence and prevalence of diseases, observing reimbursements and resource allocation trends, and keeping track of safety and quality guidelines. - There are many diseases, and one needs to establish a common language for reporting and data analysis. - Standard grouping of diseases by a set of principles is called classification, and it allows: - Easy storage, retrieval and analysis of data - Comparison and transmission of data between hospitals, provinces and countries - Comparison in the same location across different time periods. - ICD is a classification. Classifications are essential. They define, study and they highlight the relevant aspects of the information that have been collected. - Internationally endorsed classifications facilitate the following: - Storage, - Analysis, and - Retrieval, - Interpretation of data and - their Comparison - within populations over time and - between populations at the same point in time as well as - compilation of internationally consistent data. - Populations may be nations, states and territories, regions, minority groups or other specified groups. - The WHO Family of International Classifications in health consists of reference classifications, derived classifications and related classifications. - The reference classifications cover the areas of disease and related health problems (ICD), disability (ICF) and health interventions (ICHI, under development). - Other members of the Family cover fields like drugs, causes of injury and reasons for encounter, or provide more detail, for example for use in oncology. - These classifications are the building blocks of health information used for measures to help provide the best possible health to all people. ### Related Classifications - International Classification of Primary Care (ICPC) - International Classification of External Causes of Injury (ICECI) - The Anatomical, Therapeutic, Chemical (ATC) classification system with Defined Daily Doses (DDD) - ISO 9999 Technical aids for persons with disabilities -Classification and Terminology - International Classification for Patient Safety (ICPS) - International Classification of Nursing Practice (ICNP) ### Reference Classifications - International Classification Of Diseases (ICD) ### Derived Classifications. - International Classification of Diseases for Oncology, Third Edition (ICD-0-3). - The ICD-10 Classification of Mental and Behavioral Disorders. - Application of the International Classification of Diseases to Dentistry and Stomatology, Third Edition (ICD-DA). - Application of the International Classification of Diseases to Neurology(ICD-10-NA). - International Classification of Functioning, Disability and Health, Children & Youth Version (ICF-CY). ## DAILY DEFINED DOSES (DDD) ### Definition and general considerations - The basic definition of the unit is: The DDD is the assumed average maintenance dose per day for a drug used for its main indication in adults. - A DDD will only be assigned for drugs that already have an ATC code. It should be emphasized that the defined daily dose is a unit of measurement and does not necessarily reflect the recommended or Prescribed Daily Dose. Doses for individual patient and patient groups may often differ from the DDD and will necessarily have to be based on individual characteristics such as age, weight and pharmacokinetic considerations. - For the optimal use of drugs, it is important to recognize that genetic polymorphism due to ethnic differences can result in variations in pharmacokinetics of drugs. - However, only one single DDD is assigned per ATC code and route of administration. The DDD should reflect global dosage irrespective of genetic variations. - Drug consumption data presented in DDDs only give a rough estimate of consumption and not an exact picture of actual use. ### Principles for DDD Assignment - The basic principle is to assign only one DDD per route of administration within an ATC code. - DDDs for plain substances are normally based on monotherapy. Exceptions to this rule are given in the guidelines. - A DDD will normally not be assigned for a substance before a product is approved and marketed in at least one country. - For substances indicated for rare disorders with individual dosing, the Working Group could decide not to assign a DDD. ### Plain Products - Plain products contain one active ingredient (including stereo isomeric mixtures). When a new DDD is assigned, various sources are used to get the best overview of the actual or expected use of a substance. - The assigned DDD is based on the following principles: - The average adult dose used for the main indication as reflected by the ATC code. When the recommended dose refers to body weight, an adult is considered to be a person of 70 kg. It should be emphasized that even special pharmaceutical forms mainly intended for children (e.g. mixtures, suppositories) are assigned the DDD used for adults. Exceptions are made for some products only used by children, e.g. growth hormones and fluoride tablets. - The maintenance dose (long term therapeutic dose) is usually preferred when establishing the DDD. The initial dose may differ but this is not reflected in the DDD. If the approved dose recommendation provides limited information about maintenance dose, the DDD will usually be the average of the maintenance dose range. Examples of interpretation of approved dose titration recommendations: - "Titrate up to a high dose if it is tolerated": the high dose would normally be chosen as the DDD. - "Consider to increase the dose only if efficacy is not satisfactory with initial dose": ### Combination Products - The DDDs assigned for combination products are based on the main principle of counting the combination as one daily dose, regardless of the number of active ingredients included in the combination. If a treatment schedule for a patient includes e.g. two single ingredient products, then the consumption will be measured by counting the DDDs of each single ingredient product separately. ### Example I: - Treatment with two products, each containing one active ingredient: - Product A: Tablets containing 20 mg of substance X (DDD = 20 mg) - Product B: Tablets containing 25 mg of substance Y (DDD = 25 mg) The dosing schedule 1 tablet of A plus 1 tablet of B daily will be calculated as a consumption of 2 DDDs. ### Example II: - Treatment with a combination product containing two active ingredients: - Product C: Tablets containing 20 mg of substance X and 12.5 mg of substance Y. - The DDD of the combination products is assigned as 1 UD = 1 tablet. The dosing schedule 1 tablet of C daily will be calculated as 1 DDD (even though it will be equivalent to 1.5 DDD of the single active ingredients). ### Other factors - (a) Fixed dose groups - For some groups of products, it has been considered most appropriate to estimate the average use for products within a group instead of establishing accurate doses for every product, such as cough mixtures and multivitamins. For the multivitamins the composition of various products may differ, but the average recommended dose is usually the same. Such DDDs are called "fixed dose". - (b) Depot formulations - Depot formulations (e.g. sustained release formulations) are usually assigned the same DDDs as the ordinary dosage forms. Exceptions to this main rule are described in the guidelines for the different ATC groups. - (c) Intermittent dosing - In certain therapeutic groups, such as hormones, many of the products are administered intermittently. In such cases, the dose administered is divided by the number of days in the treatment period to obtain the average daily dose. This means that medicament free periods in between courses are included in the treatment period. - This also applies to such drugs as depot antipsychotics and contraceptive pills, which are given intermittently. - (d) Duration of treatment - The duration of treatment is normally not considered when assigning a DDD, even if the drugs are used mainly in short periods. Exceptions from this main rule are explained in the respective ATC groups. ### Selection of units - For plain products, DDDs are as far as possible given in amount of active ingredients, using the following units: g (gram), mg (milligram), mcg (microgram), mmol (millimole), U (unit), TU (thousand units) and MU (million units). The abbreviation U for unit as well as other units are used internationally. - (A) Combination products or products where a DDD for various reasons cannot be given in amount of active ingredient, the unit UD (unit dose) is used: - Tablets, suppositories, pessaries, etc: - 1 UD equals 1 tablet, 1 suppository, 1 pessaries, etc. Powder for oral use: - 1 UD equals 1 gram of powder. If the DDD for an oral powder is given in grams, this refers to the content of active ingredient. - Powder in single dose units for oral use: 1 UD equals 1-unit dose powder. - Powder for injection: - 1 UD equals 1 gram of powder. If the DDD for powder for injection is given in grams, this refers to the content of active ingredient. - Powder for inhalation: - 1 UD equals 1-unit dose powder, e.g. 1 capsule. - Liquid preparations for oral use (mixtures, syrups etc.): - 1 UD equals 5 ml of the preparation. - Liquid preparations for parenteral use (injections): - 1 UD equals 1 ml of the preparation. Liquid preparations for rectal use: - 1 UD equals 1 ml of the preparation. - Liquid preparations for inhalation: - 1 UD equals 1 ml of the preparation. - Liquid preparations for inhalation in single dose units (unit dose): 1 UD equals 1-unit dose inhal. sol - Enemas: - 1 UD equals 1 enema. - Plaster for transdermal application: - 1 UD equals 1 plaster. - Vaginal cream: - 1 UD equals 1 dose, 1 application. - (B) Route of administration - The route of administration is indicated by the following codes: - Inhal Inhalation R = Rectal - N = Nasal - 0 = Oral - SL = Sublingual/buccal - TD = Transdermal - P = Parenteral - V = Vaginal - (C) Pediatric DDD - DDDs are normally assigned based on use in adults. For medicinal products approved for use in children, the dose recommendations will differ based on age and body weight. Many medicinal products used on children are not even approved for such use, and documentation regarding dose regimens is not available. - Thus the WHO International Working Group for Drug Statistics Methodology has concluded that pediatric DDDs are impossible to assign and problems related to drug utilization research in children cannot be solved by such means. - (D) Principles for reviewing and changing DDD - As the dosages used may change over time, it will always be necessary to make some alterations. The International Working Group for Drug Statistics Methodology may review a DDD whenever the Group finds it appropriate. - Changes in DDDs should be kept to a minimum and avoided as far as possible. Too many alterations will always be disadvantageous for long-term studies on drug utilization. Before alterations are made, difficulties arising for the users are weighed against the benefits achieved by the alteration. - The same principles used to assign new DDDs also apply when DDDs are reviewed. - Changes are generally not made unless they are at least in the order of 50%. - This rule is not used for the three-year revision of DDDs, where smaller alterations are allowed. Further, minor alterations are allowed for important drugs, which are frequently used (e.g. the DDD for cimetidine was changed from 1.0 g to 0.8 g). ### DDD review after three years - All newly assigned DDDs are reviewed during the third year after inclusion in the ATC Index with DDDs. The DDDs are reviewed at the first semi-annual meeting of the International Working Group for Drug Statistics Methodology. - The following are considered: - Recommended dosages as listed in drug catalogues in different countries and/or published in peer reviewed scientific journals or major international textbooks. - Data on prescribed daily doses (PDDs) from a range of countries. Figures showing the prescribed daily dose (PDD) are important when reviewing an assigned DDD. Usually more data concerning PDDs are available after a three years period than at the time of marketing. - Established main indication and therapy profile of the preparation (i.e. has the main indication changed?) - Existing DDDs in the ATC group. - Written objections to the DDD which have been received. - When reviewing combination products, changes in the DDDs for the different active ingredients are an important consideration. ### Further reviews of DDDS - After the first three years' period, the DDD normally remains unchanged for at least five years unless the WHO Working Group decides to make a total revision of all DDDs assigned in an ATC group. Proposed DDD changes from users of the system, based on new information will always be considered, but only after the three years' revision has been performed. - (E) Description of other drug utilization metrics Cost - Drug use can be expressed in terms of costs (e.g. national currency). - Cost figures are suitable for an overall cost analysis of drug expenditure. - National and international comparisons based on cost parameters are often misleading and of limited value in the evaluation of drug use. ### Volume - Common physical units (e.g. grams, kilos, litres), numbers of packages or tablets and numbers of prescriptions are also used for quantifying drug consumption. - These units can be applied only when the use of one drug or of well-defined products is evaluated. Problems arise, however, when the consumption of whole drug groups is considered. ### Prescribed daily dose - The prescribed daily dose (PDD) can be determined from prescription studies, medical- or pharmacy records and patient interviews. It is important to relate the PDD to the diagnosis on which the dosage is based. - The PDD will give the average daily amount of a drug that is actually prescribed. When there is a substantial discrepancy between the PDD and the defined daily dose (DDD), it is important to take this into consideration when evaluating and interpreting drug consumption figures. - For drugs where the recommended dosage differs from one indication to another (e.g. the antipsychotics) it is important that diagnosis is linked to the prescribed daily dose given. - The PDD can vary according to both the illness treated and national therapy traditions. ## International nonproprietary names for drugs - The International Nonproprietary Name (INN) is an official generic and non-proprietary name given to a pharmaceutical drug or an active ingredient which has been coordinated by the World Health Organization (WHO) since 1953. It aids in precise communication by providing a unique standard name for each active ingredient which helps in avoiding the prescribing errors. - Unambiguous standard names for each drug is important because drugs sold have different brand names, or a branded medication may contain more than one drug. - Every drug's INN is unique but may contain a word stem that is shared with other drugs of the same class. - The WHO issues INNs in English, Latin, French, Russian, Spanish, Arabic, and Chinese, and a drug's INNs are often cognate across most or all of the languages, with minor spelling or pronunciation differences. - An established INN is known as a recommended INN (rINN), while a name that is still being considered is called a proposed INN (PINN). ### Name stems - Drugs from the same therapeutic or chemical class are usually given names with the same stem. Stems are mostly placed word-finally, but in some cases word-initial stems are used. They are collected in a publication informally known as the Stem Book. - The Indian Law Section 13 (b) of the Trade Marks Act, 1999 states that no word that is declared as an INN by WHO and is notified by the Registrar of Trade Marks, or which is deceptively similar to such names, can be registered as trademarks. However, no INN has been notified by the Trade Marks Registrar. There is also no requirement under the Trade Marks Rules for conducting a search of INNs while examining new trademark applications in class 5 (pharmaceutical substances come under class 5). Moreover, there is no mandatory requirement of registering a trademark in India. - The drug regulatory system in India is highly decentralized with a limited role being played by the Central Drug Regulatory Authority. The State Drug Regulatory Authorities do not have the capacity to control this effectively in a decentralized system. Hence there is need for a specific policy guideline on the use of INNS in India. It is therefore, desirable to develop a centralized database of brands that are approved by State Drug Regulatory Authorities. # UNIT-2 ## Drug dictionaries and coding in pharmacovigilance ### Points to be covered in this topic - WHO Adverse Reaction Terminologies - MedDRA and Standardized MedDRA Queries - WHO Drug Dictionary - Eudravigilance Medicinal Product Dictionary ## Drug dictionaries and coding in pharmacovigilance ### INTRODUCTION - The purpose of the dictionary is to bring order to apparent chaos. - They are intended to bring some discipline to the vast number of descriptive terms that health professionals and patients use for medical conditions, and to the enormous collection of medicines that the former impose on the latter. ## WHO ADVERSE REACTION TERMINOLOGIES - Over more than 30 - 40 years this terminology has been developed to serve as a basis for rational coding of adverse reaction terms. - The structure of the terminology is flexible enough, because new drugs and new indications produce new terms which are incorporated. - At the same time it is necessary to maintain the structure of the terminology without losing previous relationships. The basic logic behind such flexibility is a hierarchical structure starting with body system/organ level, within which there is grouping (general or high level) terms which is useful with respect to drug problems. - Within these broad categories the specific, frequently used 'preferred terms' provide for precise identification of drug problems. As such preferred terms means exact terms; but everyday experience shows that adverse reaction reports contain colloquial terms. - For this reason, the WHO 'included terms' closest to preferred term, but still allows the actual reported term to remain unaltered. Many users simply make up the list with own included terms on the basis of their own experience. Users are encouraged to let the Uppsala Monitoring Centre know about any useful "included terms" so that they can be incorporated in the official WHO-ART with appropriate relationship to "preferred terms". ## The complete list of system-organ classes and codes | Organ/Class of Organ | Code | |---|---| | Skin and appendages disorders | 0100 | | Musculo-skeletal system disorders | 0200 | | Collagen disorders | 0300 | | Central & peripheral nervous system disorders | 0410 | | Autonomic nervous system disorders | 0420 | | Vision disorders | 0431 | | Hearing and vestibular disorders | 0432 | | Special senses other disorders | 0433 | | Psychiatric disorders | 0500 | | Gastro-intestinal system disorders | 0600 | | Liver and biliary system disorders | 0700 | | Metabolic and nutritional disorders | 0800 | | Endocrine disorders | 0900 | | Cardiovascular disorders, general | 1010 | | Myo-, endo-, pericardial & valve disorders | 1020 | | Heart rate and rhythm disorders | 1030 | | Vascular (extra cardiac) disorders | 1040 | | Respiratory system disorders | 1100 | | Red blood cell disorders | 1210 | | White cell and RES* disorders | 1220 | | Platelet, bleeding & clotting disorders | 1230 | | Urinary system disorders | 1300 | | Reproductive disorders, male | 1410 | | Reproductive disorders, female | 1420 | | Foetal disorders | 1500 | | Neonatal and infancy disorders | 1600 | | Neoplasms | 1700 | | Body as whole - general disorders | 1810 | | Application site disorders | 1820 | | Resistance mechanism disorders | 1830 | | Secondary terms - events | 2000 | | Poison specific terms | 2100 | ## WHO-ART Hierarchy - System organ class Group of preferred terms pertaining to the same body organ - High level term Group of similar preferred terms - Preferred term Principal terms for coding and presentation - Included term Terms similar to preferred terms ## MedDRA AND STANDARDIZED MedDRA QUERIES - Standardized MedDRA Queries (SMQs) are groupings of MedDRA terms, generally at the Preferred Term (PT) level that relate to a defined medical condition or area of interest. - SMQS help to identify and recover the potentially relevant individual case safety reports. The included terms may relate to signs, symptoms, diagnoses, syndromes, physical findings, laboratory and other physiological test data, etc. - The Lowest Level Terms (LLTs) represented in an SMQ are those that link to a PT used in the SMQ. All others are excluded. - SMQS come out of a recognized need of the MedDRA user community for standard tools to assist in the identification and recovery of safety data. The original MedDRA Special Search Categories (SSCs) were intended for a similar purpose. - But after several years of MedDRA use, the biopharmaceutical community (regulators and industry) informed that these tools did not adequately address the need. - As a result, in early 2002 the MedDRA Maintenance and Support Services Organization (MSSO) began to develop MedDRA Analytical Groupings (MAGS). - MAGS were defined as collections of terms from any level of the MedDRA hierarchy (except, in general, LLTs) and from any of the MedDRA SOCS that relate to the medical condition or area of interest defined by the name of the MAG. - This includes signs, symptoms, physical findings, laboratory and other physiologic test data, and associated social circumstances related to the medical condition or area of interest. - At the same time, when MAGS were developed at the MSSO, an independent initiative by the Council for International Organizations of Medical Sciences (CIOMS) was started to address the need for special queries/groupings using MedDRA-coded data. These groupings were called Standardized Search Queries (SSQs). - It was clear that the concepts of MAGS and SSQs were quite similar to one another and were both intended to fulfil the need for a recovery tool to accompany MedDRA. - Since May 2003, the joint efforts of the CIOMS Working Group and MSSO have been designated Standardized MedDRA Queries (SMQs). - In November 2003, the ICH MedDRA Management Board endorsed the cooperative effort, and the ICH process was adopted for the development of SMQS. - The CIOMS Working Group is composed of senior scientists from several drug regulatory authorities, international pharmaceutical companies, the MSSO, the Japanese Maintenance Organization (JMO), the World Health Organization, and other institutions. ## Development of SMQS - A focus of the early phase of SMQ development was to identify which areas of interest were candidates for development. - Close to 100 possible topics were initially identified. The CIOMS Working Group continually reviews this list and prioritizes topics for development. - Sub teams work on each candidate SMQ prior to review and approval by the entire CIOMS Working Group. The definitions, inclusion and exclusion criteria, hierarchy (if applicable), and algorithm (if applicable) for each SMQ are included in this introductory Guide. - Much of this information was derived from the anonymized SMQ CIOMS Working Group detailed documentation. The general methodological approach to the development and use of SMQs was published in a document by CIOMS. The reader is referred to the CIOMS web site for further information: ### Design Concepts for SMQ Content - (a) Narrow and broad scope - (b) Algorithm - (c) Category - (d) Wealth - (e) Hierarchy - (f) PT/LLT - (g) Term status ## WHO DRUG DICTIONARY - The WHO Drug Dictionary contains data from 1968 onwards. The content today is originating mostly from IMS and National Drug names References. - No entries are deleted even though they are withdrawn from the market, since old case reports might be coded with these products. They are marked as OLD FORM. - A database with information about medicinal products from all over the world, it contains medicinal products and information related to them in a relational database system. Information is provided in a consistent and structured way. - It provides useful groupings of data, useful for both data input and output. It is continuously updated. - A source of international drug names: - (a) Substance names according to International Non Proprietary Names (INN) - (b) Drugs classified according to the Anatomical-Therapeutic-Chemical (ATC) classifications system - (c) Information on companies and reference sources - The majority of the entries refer to conventional (chemical substance) medicinal products, but the WHO-DD also includes - (a) Herbal remedies - (b) Vaccine - (c) Blood products - (d) Homeopathic remedy - (e) Dietary supplement ### WHO-DD is available in several ways: - (a) As text files to download and load in local tools, which requires in-depth technical knowledge of the WHO-DD structure. - (b) Through online tools: - Integrated in VigiSearch, - Integrated in VigiFlow, - WHO DD browser. - (c) The method for access is somewhat different depending on the needs for each specific tool. ## EUDRAVIGILANCE MEDICINAL PRODUCT DICTIONARY - EudraVigilance is the European Union pharmacovigilance database and data-