Goal and objectives. Uppsala Monitoring Centre

Transcription

1 Goal and objectives To expand the knowledge of the WHO Drug Dictionaries The different formats Codes and ID:s ATC and SDG classification Different entries Best Practice WHO Drug Dictionaries Support information Uppsala Monitoring Centre The Uppsala Monitoring Centre is the WHO Collaborating Centre for International Drug Monitoring A network och national pharmacovigilance centres (regulators) Collects, analyses and communicates drug safety information 1

2 The WHO Drug Dictionaries First created in 1968 The WHO Drug Dictionary was created to code and analyse medication information First used in drug safety now mainly in clinical trials NCs, pharma, CROs, academia The WHO Drug Dictionaries A relational database unique Trade Names from >100 countries ingredients/combination of ingredients Up to date Produced quarterly and sent to you in text files in ASCII format 2

3 Dictionary types Dictionary types: WHO Drug Dictionary WHO Drug Dictionary Enhanced WHO Drug Dictionary Enhanced extended with WHO Herbal Dictionary Drug Dictionary China Fastum 法斯通 Fa si tong 酮洛芬 Ketoprofen M02AA - Antiinflammatory preparations 局部用抗炎非类固醇类药物 3

4 Verbatim How is the data collected? IMS health FDA EMA MAHolder Official national authority drug lists Quarterly data collection 4

5 How is the data validated? How is the data validated? 5

6 Quality assurance Technical quality assurance Weekly Quarterly Regular Quality Assurance projects Vitamins (2014) Shortened names (2013) Vaccines (2011) Changes in the dictionaries Changes made once a year: March release Other quarters additions only Cumulative changes list is a help to follow the changes made Changes are not made on existing records Alegra Allegra 6

7 From file production to customer Quality Assurance Database lock Reminder sent out one week before release Files available for 14 days Files uploaded on website Attention letter sent out The Dictionary Formats The B Format The C Format Drug Code Drug Name Ingredient Salt ATC code Medicinal Product ID Name Specifier Country Marketing Authorisation Holder Strength Dosage form 7

8 Formats B & C B-format: Tradolan (Tramadol hcl) N02AX C-format: Tradolan Tramadol hydrochloride Sweden, Finland, Norway, Austria Nordic Drugs, Lannacher Tablets, Ampoules, Liquids, Supp. 100 mg, 150 mg, 200 mg N02AX Information levels B Trade name Ingredient Country MA-holder Form Strength Seroquel Seroquel Quetiapine fumarate Quetiapine fumarate Sweden C Seroquel Quetiapine fumarate Sweden AstraZeneca Seroquel Quetiapine fumarate Sweden AstraZeneca Coated Tablets Seroquel Quetiapine fumarate Sweden AstraZeneca Coated Tablets 25 mg Seroquel Quetiapine fumarate Sweden AstraZeneca Coated Tablets 100 mg 8

9 When is the C format needed? Non-unique names the name appears more than once in the B format with different active ingredients The B format doesn t contain the data fields that explains the difference When Form or strength information is relevant in analysis Codes and IDs 9

10 The Drug Code The Drug Code is the unique key in the B format and it is used also in the C format. Unique identifier of a Product name The code gives you information about the Active ingredient(s) Salt or ester variants of the ingredient The Drug name The Drug Code The code can be used as a key in the case report or clinical data The Drug Code is an aggregation of Drug Record Number (Drecno), Sequence Number 1 and Sequence Number 2. 10

11 Drug Record Number The first six characters in the Drug Code The Drug record number (drecno) is the same for all entries containing the same active ingredient or unique combination of active ingredients. Drecno Seq 1 Seq 2 Name Ampicillin Paracetamol Sequence Number 1 Character 7-8 in the Drug Code The Sequence Number 1 (Seq1) identifies the salt or the ester of the active ingredient in single ingredient product. The number 01 identifies the base substance, without any salt or ester, and values above 01 will identify salts and esters. Drecno Seq 1 Seq 2 Name Ampicillin Ampicillin sodium Ampicillin trihydrate 11

12 Sequence Number 2 Character 9-11 in the Drug Code The Sequence Number 2 (Seq2) identifies trade names and in some cases a synonym to a generic name The entry with Sequence Number 2 value 001 identifies the preferred name Preferred base number XXXXXX Preferred salt name XXXXXX XX 001 Seq 2 - example Drecno Seq 1 Seq 2 Name Ampicillin Ampicin Binotal Ampicillin sodium Binotal Polycillin-n 12

13 The Medicinal Product ID The ID is just a numeric name of the medicinal product and it has no intrinsic meaning in the C format. All drugs in the C format is also given a Drug Code The code can be used as a key in the case report or clinical data What is ATC? Anatomical Therapeutic Chemical (ATC) Originally created for drug statistics Maintained by WHO Collaborating Centre for Drug Statistics Methodology Each product in the WHO Drug Dictionaries is coded with at least one ATC code 13

14 ATC classification A B C D G H J L M N P R S V Alimentary tract and metabolism Blood and blood forming organs Cardiovascular system Dermatologicals Genito-urinary system and sex hormones Systemic hormonal preparations, excluding sex hormones and insulins Antiinfectives for systemic use Antineoplastic and immunomodulating agents Musculo-skeletal system Nervous system Antiparasitic products, insecticides and repellents Respiratory system Sensory organs Various 5 ATC levels A A10 A10B A10B A A10B A02 Alimentary tract and metabolism (1st level, anatomical main group) Drugs used in diabetes (2nd level, therapeutic subgroup) Oral blood glucose lowering drugs (3rd level, pharmacological subgroup) Biguanides (4th level, chemical subgroup) Metformin (5th level, chemical substance) 14

15 ATC in the WHO Drug Dictionaries Drugs in the WHO Drug Dictionaries are coded on the fourth level. The Drug Record number in the WHO Drug Dictionaries has the corresponding meaning as the fifth level, but with higher precision. Example Acetyl Salicylic Acid: A01AD LOCAL ORAL TREATMENT B01AC PLATELET AGGREGATION N02BA ANALGESICS AND ANTIPYRETICS Unofficial in WHO Drug Dictionaries: M02AC Preparations with salicylic acid derivatives 15

16 Example Paracetamol and codeine < 20 mg Codeine N02BE (Anilides) > 20 mg Codeine N02AA (Natural Opium alkaloids) ATC vs indictations Medicinal products are classified according to the main therapeutic use of the main active ingredient Not all indications of use! In the WHO Drug Dictionaries many products have additional ATC classes 16

17 SDG An SDG is any grouping of medicines having one or several properties in common. The individual grouping can be based on indication, chemical properties, pharmacodynamic properties and/or pharmacokinetic properties as well as any other property of interest. How can SDGs be used? 1. Protocol violation drug lists 2. Interactions analysis 3. For active surveillance of certain riskgroups within a trial 4. Safety analysis 5. Efficacy analysis 6. etc 17

18 Development of an SDG Expert working group Defintion created Based on in-house list for medications of interest - or Made from scratch Searches in publications and otherrelevant sources List reviewed by UMC staff List peer reviewed by another group member SDG Maintenance Updated quarterly along with dictionary versions UMC staff review each new substance entered UMC staff communicates with SDG responsible for approval Continous QA controls are run either automated, where applicable, or manual 18

19 Protocol violation Existing SDGs Antihypertensives Estrogens Hormone replacement therapy DMARDs (Disease Modifying AntiRheumatic Drugs) Diuretics Intended for analysis CYP interacting substances Analgesia producing opioids Hierarchy CYP3A4 Group Substrates Inducers Inhibitors Subgroup Broad Narrow Broad Narrow Broad Narrow Scope Narrow = Clinically relevant Broad = Clinical relevance unknown 19

20 Different entries in the WHO Drug Dictionaries Different entries Trade names Generic names Preferred names Umbrella entries 20

21 Trade name The name on the Package Alvedon Generic name The ingredient in a Trade name Paracetamol 21

22 Preferred names The Drug Code ends with 001 In single ingredient products the generic name , 001 In multi ingredient products it will be the name of the first entered product name that was entered into the WHO Drug Dictionaries , , 26 Umbrella entries The reported term is not a Drug name but a type or class of drugs Choices in this category should be used if: - Drug terms can t be coded to a more specific term. - Drug terms can t be identified or further clarified. 22

23 Umbrella entries Drug Codes that starts with a 9 refers to Umbrella entries drug classes Based on the ATC text Ex Anilides Sometimes NOS - Not Otherwise Specified Ex Electrolytes nos Sometimes used as place holder Name Specifier Old form Products change composition without changing trade name. - /Old form/ is added in the Name specifier field. Both old and new entry must be included in the dictionary 23

24 Old form flag In the C format the old entry is flagged as old form in the name specifier field In the B format this is available as an additional table from 2010 The information is available in the browser Ex Topisolon ,

25 Non-unique names Sometimes the same name is used in different countries with different active ingredients Sometimes different pharmaceutical forms have different active ingredients even within a country A product can change its composition B format Dolmen / / - contains Acetylsalicylic acid/ascorbic acid/codeine phosphate Dolmen / / - contains Tenoxicam Dolmen / / - contains Dexketoprofen trometamol 25

26 Comparison view in the Browser C format as a reference Many organsiations have implemented the B format often due to software limitations The WHO Drug Dictionary Browser is used as a reference to access C format information to investigate omission lists Information about why a specific code is selected is lost since the Drug Code doesn t de-code to country/form/etc. 26

27 Coding principles Company specific (trial specific) Best Practices to be developed by the user community Set up own SOPs Support Questions about the dictionary structure and the dictionary types Questions about the downloading of files Questions about individual drug entries and ATC assignments Do you miss anything? You can request new entries to WHO Drug Dictionaries 27

28 User Group Access documents and important notices at the WHODDUG portal Thank you for attending the User Group meeting. West coast, Europe, Japan, India Thank You! 28