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Introduction to MedDRA® and its useKathryn HuntleyHuntley Consulting, LLCDAIDS ContractorFebruary 21, 2006 1

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MedDRAMed= MedicalD = Dictionary forR = RegulatoryA = Activities 2

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MedDRA DefinitionMedDRA is a clinically-validatedinternational medical terminology used byregulatory authorities and the regulatedbiopharmaceutical industry. The terminologyis used through the entire regulatory process,from pre-marketing to post-marketing and fordata entry, retrieval, evaluation andpresentation 3

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Scope OUT Drug product terms IN Diseases Population-level qualifiers Diagnoses Signs SymptomsPatient demographic Therapeutic indications Numerical values for terms Investigation names & qualitative results results Medical & surgical procedures Medical, social, family history Terms from: COSTART Device failure terms WHO-ART Severity descriptors HARTS Equipment, device, diagnostic product terms Clinical trial study design terms

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MedDRA Structure and GrowthVersion 2.1 Version 7.0 Version 8.0 26 26 26 System Organ Class 334 332 332 High-Level Group Term 1,663 1,681 1,683 High-Level Term 11,193 16,449 16,751 Preferred Term 35,065 44,755 45,597 Lowest-Level Term 5

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MedDRA Structure and Growth Version 8.0 Version 8.1 26 26 System Organ Class 332 332 High-Level Group Term 1,683 1,683 High-Level Term 16,751 16,976 Preferred Term 45,597 45,974 Lowest-Level Term 6

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System Organ Class Highest level of the hierarchy SOCs identified by Anatomical or physiological system Etiology Purpose 7

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System Organ ClassBlood and lymphatic system Musculoskeletal and connectivedisorders tissue disordersCardiac disorders Neoplasms benign, malignant andCongenital, familial and genetic unspecified (incl cysts and polyps)disorders Nervous system disordersEar and labyrinth disorders Pregnancy, puerperium andEndocrine disorders perinatal conditionsEye disorders Psychiatric disordersGastrointestinal disorders Renal and urinary disordersGeneral disorders and Reproductive system and breastadministration site conditions disordersHepatobiliary disorders Respiratory, thoracic andInfections and infestations mediastinal disordersImmune system disorders Skin and subcutaneous tissue disordersInjury, poisoning and procedural Social circumstancescomplicationsInvestigations Surgical and medical proceduresMetabolism and nutrition disorders Vascular disorders 8

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High Level Group Term Subordinate only to System Organ Classes and superordinate descriptor for one or more HLTs SOC Gastrointestinal disorders HLGT HLGT HLGT Dental and Gastrointestinal Gastrointest gingival infections inal vascular conditions conditions

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High Level Term Subordinate to HLGTs and superordinate descriptors for the PTs linked to it SOC Gastrointestinal disorders HLGT Gastrointestinal infections HLT HLT Gastrointestinal HLT Intestinal infections, site Peritoneal infections infections unspecified

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Preferred Term Each Preferred Term represents a single medical concept: • SOC Gastrointestinal disorders – HLGT Gastrointestinal infections – HLT - Gastrointestinal infections, site unspecified - PTs Abdominal sepsis, Amoebic dysentery, Tuberculosis gastrointestinal, Gastrointestinal anthrax . . . 11

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Preferred Term PT Characteristics • No limit to the amount of LLTs that can be associated with a single PT • An identical LLT is created for every PT • Each path to a SOC from a PT should have exactly one HLT and HLGT (one route) PT → HLT → HLGT → SOC • PTs can be represented in multiple SOCs (multiaxality) 12

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Lowest Level Term LLT Characteristics: Developed to support consistent coding • An LLT has one or more of the following relationships to a PT: – Synonym – Lexical variant – Quasi-synonym (colloquial terms) • Many terms from included terminologies are represented at the LLT level 13

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Lowest Level Term LLT Characteristics cont. • Constitutes the entry level of the terminology and is linked to a single PT • Can have current or non-current status • Culturally unique terms are found at this level 14

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NEC = Not Elsewhere Classified For specific, yet miscellaneous, terms that do not readily fit into hierarchical classifications, used only at the HLT and HLGT levels HLT Congenital disorders NEC PT PT HereditaryCongenital PT PT PT angioedemaabnormality Conjoined Hereditary Umbilical twins disorders malformation

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MedDRA Codes Each MedDRA term assigned an 8-digit numeric code The code is non-expressive Codes can fulfill a data field in various electronic submission types (e.g., E2b) Initially assigned alphabetically by term starting with 10000001 New terms are assigned sequentially Codes are never reused Supplemental terms are assigned codes 16

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Anatomy (Body System) Blood and lymphatic system disorders Cardiac disorders Ear and labyrinth disorders Endocrine disorders Eye disorders Gastrointestinal disorders Hepatobiliary disorders Immune system disorders Musculoskeletal and connective tissue disorders Nervous system disorders Psychiatric disorders Renal and urinary disorders Reproductive system and breast disorders Respiratory, thoracic and mediastinal disorders Skin and subcutaneous tissue disorders Vascular disorders 17

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Other (Cause/Association) Congenital, familial and genetic disorders General disorders and administration site conditions Infections and infestations Injury, poisoning and procedural complications Investigations Metabolism and nutrition disorders Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pregnancy, puerperium and perinatal conditions Social circumstances Surgical and medical procedures 18

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General disorders and administration siteconditions SOC specific topics: SOC includes terms that are very general in nature e.g.. Pain, Mass, Tenderness etc. Administration site conditions all grouped here (also in Injury SOC). • Application • Injection • Implant Much of this SOC is not multi-axial 19

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Congenital, familial and geneticdisorders SOC specific topics: Primary SOC for all congenital conditions Primary SOC for all congenital conditions Congenital = any condition present at birth, whether genetically inherited or acquired in utero definition used for placement into this SOC HLGTs categorized either by an anatomical basis following the naming conventions of the SOCs Look here for the congenital condition, look in the anatomy SOC for grouping with non-congenital conditions 20

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Injury, poisoning and proceduralcomplications SOC specific topics: Can be considered the “due to SOC” HLGTs are representing either the agent that caused the injury or anatomy Only SOC where cardiac and vascular are considered together (cardiovascular injuries) Overdose, poisoning, misadministrations etc are located here 21

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Investigations SOC specific topics: Single axial SOC Represents only the results of tests (no interpretation) HLGTs represent various large groupings of tests PTs naming convention is: Test identifier, specimen type, qualifier • Qualifiers include: normal, increased, decreased, abnormal NOS (no direction of abnormality specified) – There will always be an investigation term without any qualifier to be used when no value is given (e.g., PT: Hematocrit) 22

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Infections and infestations SOC specific topics: All infections are primary to the Infection SOC HLGTs categorized either infectious agent or on an anatomical basis under pathogen class unknown. HLGT refers to taxonomy of pathogen e.g.. Bacterial, Fungal etc. HLT references the genus PT refers to genus plus anatomy LLT references the species 23

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Metabolism and nutrition disorders SOC specific topics: HLGTs represent metabolic disorders divided by substance being metabolized or nutritional disorders This SOC is based upon substance, cause would be represented in anatomical or congenital SOCs 24

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Neoplasms benign, malignant andunspecified (incl cysts and polyps) SOC specific topics: Primary SOC for all Neoplasms Secondary SOC for all Cysts and Polyps Developed with the help of National Cancer Institute (CTEP) Applies international naming conventions HLGTs classify anatomy HLTs distinguish staging Includes very specific as well as very general terms 25

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Pregnancy, puerperium and perinatalconditions SOC specific topics: Contains terms for classifying disorders as well as normal conditions Age is important in using this SOC e.g.. Neonatal Topics of mother and child are covered within this SOC The HLGT Abortion and stillbirth includes spontaneous and abnormal conditions, procedures and complications 26

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Social circumstances SOC specific topics: Contains terms for categorizing life style factors Does not contain disorders Single axial Drug and chemical abuse does not include alcohol Coding with this SOC requires full understanding of the SOC and its interpretation 27

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Surgical and Medical Procedures SOC specific topics: HLGTs are broken down by anatomy or procedural type Only section of the terminology where Ear, nose and throat are grouped. Single axial Represents only procedures, complications are represented in the Injury, poisoning and procedural complications SOC, the reason for the procedure is represented in the disorders SOC 28

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In what SOC would you find thefollowing: Hypoglycemia Decreased heart rate Drug addict Bacterial infection Pneumonitis Broken leg Injection site pain 29

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Using MedDRA’s Hierarchy Important functions of a hierarchy are as follows: Provides a grouping scheme for data analysis Defines the meaning of word and its relationship to terms associated with it Defines/limits the meaning of lateral terms Serves as a pre-developed method of grouping data for analysis Supports consistent data representation Supports standardized data reporting. MedDRA is NOT a taxonomy. Be careful to understand the interaction of the hierarchy and multiaxiality. 30

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A Multi-Axial Terminology Multi-axial = the representation of a medical concept in multiple SOCs Allows terms to be grouped by different classifications Allows retrieval and presentation via different data sets Allows an automatic assignment of pre-defined term groupings 31

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Primary SOC Allocation Every PT is assigned to a Primary SOC Purpose of Primary SOC – Determines which SOC will represent a PT during cumulative data outputs – Is used to support consistent data presentation for reporting – Secondary SOCs are used for additional scientific analysis 32

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Rules forPrimary SOC Allocation PTs relating to diseases or signs and symptoms are assigned to the SOC that best represents the primary manifestation site PT: Appendicitis = Primary SOC: Gastrointestinal disorders PT: Dry Skin = Primary SOC: Skin & subcutaneous tissue disorders PT: Nausea = Primary SOC: Gastrointestinal disorders 33

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Exceptions forPrimary SOC Allocation All congenital and hereditary anomalies are placed in the Congenital, familial and genetic disorders SOC as their Primary SOC 34

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Exceptions forPrimary SOC Allocation Primary SOC Congenital and familial/genetic disorders Example PT Congenital rubella infection Secondary SOC Pregnancy, puerperium and perinatal conditions Infections and infestations 35

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Exceptions forPrimary SOC Allocation All neoplasms are placed in the Neoplasms benign and malignant (including cysts and polyps) SOC as their Primary SOC 36

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Exceptions forPrimary SOC Allocation Primary SOC Neoplasms benign,malignant and unspecified (including cysts and polyps) Example PT Benign lung neoplasm Secondary SOC Respiratory, thoracic and mediastinal disorders 37

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Exceptions forPrimary SOC Allocation Exception: Cysts and polyps are placed in the prime manifestation site as their Primary SOC 38

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Exceptions forPrimary SOC AllocationPrimary SOC Ear and labyrinth disorders Example PT Secondary SOC Aural polyp Neoplasms benign, malignant and unspecified (including cysts and polyps) 39

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Exceptions forPrimary SOC Allocation All infections and infestations are placed in the Infections and infestations SOC as their Primary SOC 40

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Exceptions forPrimary SOC AllocationPrimary SOC Infections and infestationsExample PTs Secondary SOCHepatitis C Hepato-biliary disorders Nervous system disordersEncephalitis Respiratory, thoracic andPneumonia mediastinal disorders 41

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A Multiaxial Terminology PTs in the following SOCs only appear in that particular SOC: Investigations Social circumstances Surgical and medical procedures. 42

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Multiaxial Terminology SOC = Respiratory, thoracic and SOC = Infections and mediastinal disorders infestations HLGT = Upper respiratory HLGT = Viral infectious tract infections disorders HLT =Viral upper respiratory HLT = Influenza viral tract infections infections PT = Influenza 43

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A Multiaxial Terminology SOC = Endocrine SOC = Metabolism and disorders nutrition disorders HLGT = Glucose metabolism disorders (including diabetes mellitus) HLT = Diabetes mellitus (including subtypes) PT = Diabetes mellitus 44

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Using MedDRA to Your BenefitMultiaxiality SOC= Infection and SOC = Hepatobiliary infestations disorders HLGT = Viral HLGT = Hepatic disease disorders HLT = Hepatic viral infection PT = Hepatitis C 45

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Using MedDRA to Your BenefitMultiaxiality (Continued) SOC = Hepatobiliary disorders HLGT = Hepatic disorders HLT = Hepatic HLT = Hepatic signs viral infection and symptoms PT = Hepatitis C PT = Hepatomegaly 46

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Using MedDRA to Your BenefitMultiaxiality (Continued) Impact of multiaxiality on analysis: PTs are represented in more than one SOC. Secondary path is used in SOC analysis. Use of multiaxiality. Double counting is prevented. Multiple data representation is supported. Related terms in different SOCs are revealed. 47

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In what SOC would the followingterms be primary: Community acquired pneumonia Congenital HIV infection Kaposi’s Sarcoma HIV wasting syndrome Wasting Intestinal polyp Endometrial sarcoma 48

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Special Search Category Standardizes frequently used searches Helps define the syndromes/diseases Facilitates analysis across SOCs Groups PTs at the PT level (horizontally) Will be retired with MedDRA version 10 49

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Special Search Categories Anaphylaxis (SSC) Arrest (Cardiac) (SSC) Blood dyscrasias/bone marrow depression (SSC) Cardiac ischaemia (SSC) Haemorrhage (SSC) Hypersensitivity reactions (SSC) Oedema (SSC) Pain (SSC) Premalignant lesions (SSC) Secondary immunocompromised state (SSC) Thrombosis (SSC) Upper GI bleeding/perforation (SSC) Vasculitis (SSC) 50

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Standardized MedDRA Query Standardizes frequently used searches Helps define the syndromes/diseases Facilitates analysis across SOCs Allows for broad and narrow searches (sensitivity vs. specificity) Is tested by MedDRA subscribers Is maintained by the MedDRA MSSO 51

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Acknowledgement MedDRA® is a registered trademark of the International Federation of Pharmaceutical Manufacturers & Associations (IFPMA) 52