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MedDRA OverviewICH M Initiatives Training, Beijing, 25‐26 October 2012

Anna Zhao‐Wong  MD  PhD

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Anna Zhao‐Wong, MD, PhDDeputy DirectorMedDRA MSSOanna.zhao‐wong@meddra.org

International Conference on Harmonisation of Technical Requirementsfor Registration of Pharmaceuticals for Human Use

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ICH Overview

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Test Your Knowledge• MedDRA is

MedDRA Overview

• MedDRA iso 1. A list of drug nameso 2. A list of adverse eventso 3. A classification for a wide range of clinical informationo 4. I have no idea

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Test Your Knowledge (cont)• All MedDRA users pay for their MedDRA

MedDRA Overview

• All MedDRA users pay for their MedDRA subscription.

o 1. Trueo 2. False

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Test Your Knowledge (cont)• MedDRA is a product of

MedDRA Overview

• MedDRA is a product ofo 1. MSSO (Maintenance and Support Services

Organization)o 2. JMO (Japanese Maintenance Organization)o 3. ICHo 4. Regulatory authorities

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Topics• What is MedDRA?

MedDRA Overview

• What is MedDRA?• Advantages of using MedDRA• How do I plan for the transition to MedDRA?• How do I get access to MedDRA?• Whom do I contact for MedDRA questions?

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q

• MedDRA information on the web

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What is MedDRA?• Medical Dictionary for Regulatory Activities

MedDRA Overview

• Medical Dictionary for Regulatory Activities• An ICH standard product• A classification for a wide range of clinical

informationo Diseases, signs, symptoms, laboratory, procedures,

medication errors, product quality issues…

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, p q y

• Support for multiple regulated product areaso Drugs, vaccines, biologics, food, cosmetics …

Advantages Of Using MedDRA• To speak the same language in product safety

MedDRA Overview

• To speak the same language in product safetyo Before ICH – back track 20+ years

Country/Region Examples of TerminologyEuropean Union

Clinical trial ICD-9Post-marketing WHO-ART

Japan Clinical trial MEDISPost-marketing J-ART

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Post marketing J ARTUnited States Clinical trial ICD-9-CM

Post-marketing COSTARTCanada Post-marketing WHO-ART

Many homegrown terminologies

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Advantages Of Using MedDRA (cont)• To speak the same language in product safety

MedDRA Overview

• To speak the same language in product safetyo “based on recent experiences from eight different companies and

showed that ten months were needed to convert a US/NDA into an EU/MAA! ” – Françoise Augier de Crémiers “THE BIRTH OF ICH E3 AND HOW IT LED TO THE CTD”, DIA Global Forum April 2011

o There must be a better way to communicate within and

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cross country/region in order to protect patient safety

Advantages Of Using MedDRA (cont)• To speak the same language in product safety

MedDRA Overview

o ICH solution – Harmonization: MedDRA was first released on 1 March 1999

- 13 years after MedDRA was first releasedCountry/Region Terminology

European Union* Clinical trial MedDRAPost-marketing MedDRA

Japan* Clinical trial MedDRA

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Japan Clinical trial MedDRAPost-marketing MedDRA

United States Clinical trial MedDRAPost-marketing MedDRA

Canada Clinical trial MedDRAPost-marketing MedDRA

*MedDRA is mandated

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Advantages Of Using MedDRA (cont)• To speak the same language in product safety –

l b l M dDRAArgentinaAustraliaAustriaBelgiumBrazilBulgariaCanadaChileChinaChinese TaipeiCroatia

GreeceHong KongHungaryIcelandIndiaIrelandIsraelItalyJapanLatviaLithuania

PhilippinesPolandPortugalRomaniaRussian FederationSaudi ArabiaSerbiaSingaporeSlovakiaSloveniaSouth Africa

global MedDRA users

CroatiaCyprusCzech RepublicDenmarkDominican RepublicEstoniaEthiopiaFinlandFranceGermany

LithuaniaLuxembourgMalaysiaMaltaMauritusMexicoMontenegroNetherlandsNew ZealandNorway

South AfricaSouth KoreaSpainSwedenSwitzerlandThailandUkraineUnited Arab EmirateUnited KingdomUnited States

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Advantages Of Using MedDRA (cont)• To speak the same language in product safety

MedDRA Overview

• To speak the same language in product safety –numerous regulatory authorities using MedDRAincluding

o EMA and National Competent Authorities (EU)o FDA (United States)o Health Canada (Canada)

MHLW (Japan)

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o MHLW (Japan)o TGA (Australia)o SFDA (Saudi Arabia)o HSA (Singapore)

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Advantages Of Using MedDRA (cont)• To speak the same language in product safety Multi

MedDRA Overview

• To speak the same language in product safety – Multi-lingual

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Advantages Of Using MedDRA (cont)• Designed and developed by ICH M1 Expert Working

MedDRA Overview

• Designed and developed by ICH M1 Expert Working Group for

o Adverse event coding and reporting (free text to controlled vocabulary)

- Wide range of granularity to meet the needs of clinical trial study and post-marketing report

- Work with E2B and eCTD系统

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o To facilitate signal detection and pharmacovigilance – 系统性综合归纳信息

- MedDRA hierarchy- Standardised MedDRA Queries

• Single terminology used through a product life cycle

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Advantages Of Using MedDRA (cont)o OMOP recent study on ICD 9 CM SNOMED CT and

MedDRA Overview

o OMOP recent study on ICD-9-CM, SNOMED CT, and MedDRA – “We found that MedDRA is a good compromise between size and coverage”

C Reich, et al, Evaluation of alternative standardized terminologies for medical conditions within a network of observational healthcare databases, J. Biomedical Informatics, June 2012

o OMOP is a project under US FDA Sentinel Initiative

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o OMOP is a project under US FDA Sentinel Initiative

Advantages Of Using MedDRA (cont)• Practical example (1):

MedDRA Overview

• Practical example (1):Basaria, S et al. Adverse events associated with testosterone

administration

In this study of elderly men with limited mobility and low serum testosterone, subjects were randomly assigned to receive placebo or testosterone for 6 months. Adverse events were categorized using MedDRA. Based on analysis of specific groups of

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g y p g pcardiovascular event MedDRA terms, the data and safety monitoring board for this study recommended that the trial be discontinued early because of a higher rate of adverse cardiovascular events in the testosterone group than in the placebo group.

N Engl J Med 2010;363:109-22

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Advantages Of Using MedDRA (cont)• Practical example (2):

MedDRA Overview

• Practical example (2):Vellozzi, C et al. Adverse events following influenza A (H1N1) 2009

monovalent vaccines reported to the Vaccine Adverse Event Reporting System, United States, October 1, 2009–January 31, 2010.

In this study, reports to the vaccine adverse event reporting system (VAERS), a US spontaneous reporting system, were reviewed to identify potential rare events or unusual adverse event (AE) patterns after 2009 H1N1 vaccination

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events or unusual adverse event (AE) patterns after 2009-H1N1 vaccination. These AE reports are coded using MedDRA. Analysis of these MedDRA-coded data showed that the adverse event profile after 2009-H1N1 vaccine in VAERS (over 10,000 reports) was consistent with that of seasonal influenza vaccines, although the reporting rate was higher after 2009-H1N1 than seasonal influenza vaccines.

Vaccine 2010 Oct 21;28(45):7248-55

Advantages Of Using MedDRA (cont)• Actively maintained centralized and governed

MedDRA Overview

• Actively maintained – centralized and governedo ICH has established an ICH MedDRA Management Board

to:- Oversee financial and technical operations of the MSSO- Ensure the continued development and viability of MedDRA- Ensure that MedDRA is easy to use and accessible to all- Ensure MSSO is meeting the needs of users

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Advantages Of Using MedDRA (cont)• Actively maintained to meet user needs

MedDRA Overview

• Actively maintained to meet user needs

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Advantages Of Using MedDRA (cont)• Actively maintained centralized and governed

MedDRA Overview

• Actively maintained – centralized and governedo Centralized maintenance organization – MSSO partnered

with JMO- One international standard

• No country or regional modification of MedDRA• No company modification of MedDRA

o Governed maintenance by the ICH MedDRA Management B d

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Board

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Advantages Of Using MedDRA (cont)• Actively maintained Governance structure

MedDRA Overview

• Actively maintained – Governance structure

MSSODevelopment Maintenance JMO

MedDRAManagement Board

(Six ICH parties, Canada, UK MHRA & WHO as Observer)

ICH SteeringCommittee

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User CommunitiesRegulatory Authorities Regulated Industries

WHO Others

Others (Future)

Development MaintenanceImplementation User Support

CommunicationJMO

(MedDRA Japanese)

Advantages Of Using MedDRA (cont)• Increase efficiency

MedDRA Overview

• Increase efficiency

Paper Reporting

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Advantages Of Using MedDRA (cont)• Increase efficiency – MedDRA support electronic

MedDRA Overview

• Increase efficiency – MedDRA support electronic submission (从手工劳动中解脱出来)

Regulatory Authority 电子报告Firewall

医院

诊所电子表格

CROE2B (LLT)

药厂

病人

表格

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Regulatory Authority 电子报告Gateway - ICH E2B 电子表格

药物不良反应

生物制品不良反应

用药错误 产品质量问题

检索分析

编码不良反应数据库

药品监管部门

MedDRA 编码

Advantages Of Using MedDRA (cont)• MedDRA an integral part of ICH e submission standards

MedDRA Overview

• MedDRA – an integral part of ICH e-submission standardso E2B - MedDRA LLT code is used for (E2B R3)

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Advantages Of Using MedDRA (cont)• MedDRA an integral part of ICH e submission standards

MedDRA Overview

• MedDRA – an integral part of ICH e-submission standardso E2B - MedDRA LLT code is used for (E2B R3)

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Advantages Of Using MedDRA (cont)

MedDRA Overview

• MedDRA – an integral part of ICH e-submission standards

o eCTD – Module 5: Clinical Study Reports Foldero M4E Guideline: MedDRA is recommended in adverse

event summary tables

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Advantages Of Using MedDRA ‐Summary

MedDRA Overview

• Use of MedDRA provides standardization in coding, retrieval and communication of safety data

• This has the benefit ofo Consistencyo Accuracy

Effi i

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o Efficiencyo Transparency

How Do I Plan For The Transition To MedDRA?• A transition plan and a team to e ec te the plan

MedDRA Overview

• A transition plan and a team to execute the plan• Legacy data conversion: strategy, conventions

o WHO-ART to MedDRA mappingo Software tools

• IT infrastructureo Hardware – such as server

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o Software – such as application, database- MedDRA Browsers- How to better design safety database, e.g.,

• To minimize the impact of MedDRA versioning• To facilitate analysis: term, code, primary link, secondary

link• To define fields coded in MedDRA – E2B guidance

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How Do I Plan For The Transition To MedDRA? (cont)• Policy and guidance

MedDRA Overview

• Policy and guidanceo Overall Workflow process

- Coding process- Medical review process – quality control- Decision making process

o Regulatory authorities: policy and guidance for industry• Coding processes and conventions based on ICH Point to Consider

(PTC) guidanceo MedDRA Term Selection: PTCo MedDRA Data Retrieval and Presentation: PTC

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o ed ata et e a a d ese tat o Co Creation and maintenance of in house conventions – consistent with PTC

guide• Staffing

o Coder, QA, data management team, safety reviewer… • Training needs

o Type of courseo Who should attend? – coder, reviewer, data manager, statistician, QA

How Do I Plan For The Transition To MedDRA? (cont)

MedDRA Overview

• Communication, communication, and communicationo Communication transition to internal organizations, partners,

regulated industry…- Timeline- Implications to relevant parties

o Ongoing communication: versioning dateso Communication of other changes over time e.g. changes to

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coding guidelines

• Whom to contact for helpo ICH Secretariat: http://www.ich.org/, Email: admin@ich.orgo MSSO: http://www.meddramsso.com/,

Email:mssohelp@mssotools.com

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How Do I Get Access To MedDRA?• Becoming a MedDRA subscriber

MedDRA Overview

o Regulatory authority – freeo Non-profit organization – free

- Healthcare provider, research institute, academiao Pharmaceutical company, CRO – paid

- Sliding scale subscription rates for commercial organizationso System developer – paido Special license

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p- To further facilitate MedDRA’s use, the ICH MedDRA Board has

also granted a number of Special Licenses – example: EudraVigilance

• Allows a Regulator to make MedDRA available to low revenue companies in an electronic reporting tool

• Allows companies to meet their reporting requirements without taking a MedDRA subscription – free of charge

How Do I Get Access To MedDRA?• Download MedDRA files from the MSSO web site:

MedDRA Overview

• Download MedDRA files from the MSSO web site: http://www.meddramsso.com/subscriber_download.asp

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Whom Do I Contact for MedDRA Questions?• MSSO Help Desk: mssohelp@mssotools com

MedDRA Overview

• MSSO Help Desk: mssohelp@mssotools.como Accepting English and Chinese inquirieso How to subscribe?o Who is my company MedDRA point of contact?

- One subscription for the entire organizationo Forgot my company’s userID and password

What type of training should I take?

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o What type of training should I take?o How do I register for MSSO MedDRA User Group

meeting?o How to register for the free training course?

MedDRA Information On The Web• MedDRA documentation

MedDRA Overview

• MedDRA documentationo MedDRA library on MSSO web:

http://www.meddramsso.com/subscriber_library.asp

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MedDRA Information On The Web (cont)• MedDRA training

MedDRA Overview

• MedDRA trainingo Course description and slides:

http://www.meddramsso.com/public_training.asp

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MedDRA Information On The Web (cont)• MedDRA training videos

MedDRA Overview

• MedDRA training videoso http://www.meddramsso.com/public_videos.asp

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MedDRA Information On The Web (cont)• MedDRA User Group meetings

MedDRA Overview

• MedDRA User Group meetingso http://www.meddramsso.com/subscriber_events_usergrou

p.asp

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MedDRA Information On The Web (cont)• MedDRA Tools

MedDRA Overview

• MedDRA Toolso http://www.meddramsso.com/subscriber_download.asp

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MedDRA Information On The Web (cont)• Frequent asked questions

MedDRA Overview

• Frequent asked questionso http://www.meddramsso.com/public_about_faq.asp

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MedDRA Information On The Web (cont)• Frequent asked questions about MedDRA

MedDRA Overview

• Frequent asked questions – about MedDRAo http://www.meddramsso.com/public_faq_meddra.asp

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Glossary

COSTART Coding Symbols for a Thesaurus of Adverse Reactions TermsCTD Common Technical DocumentCRO Contract Research OrganizationEMA European Medicines AgencyEU European UnionFDA Food and Drug Administration (United States)HSA Health Sciences AuthorityICD‐9 International Classification of Diseases ‐ 9th Revision

International Classification of Diseases ‐ 9th Revision ClinicalICD‐9‐CM

International Classification of Diseases  9th Revision Clinical Modification

ICHInternational Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use

J‐ART Japanese Adverse Reaction TerminologyJMO Japanese Maintenance OrganizationMAA Marketing Authorization Application MedDRA Medical Dictionary for Regulatory ActivitiesMEDIS MEDical Information SystemMHLW Ministry of Health, Labour and WelfareMSSO M i t d S t S i O i ti

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MSSO Maintenance and Support Services OrganizationNDA New Drug ApplicationOMOP Observational Medical Outcomes PartnershipSNOMED CTSystematized Nomenclature of Medicine‐‐Clinical TermsSMQ Standardised MedDRA QueryTGA Therapeutic Goods AdministrationUMC Uppsala Monitoring CentreWHO‐ART World Health Organization Adverse Reaction Terminology

谢谢!

International Conference on Harmonisation of Technical Requirementsfor Registration of Pharmaceuticals for Human Use