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MedDRA® is a registered trademark of the International Federation
of Pharmaceutical Manufacturers and Associations (IFPMA)
MedDRA® Overview
NCI Vocabulary and Common Data Elements WorkspacePresented by: Ann Setser, MSSO
June 16, 2011
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Agenda
• Background of MedDRA• Regulatory status of MedDRA• Introduction to MedDRA’s structure and
scope• Demonstration of MedDRA Desktop
Browser• Standardised MedDRA Queries (SMQs)• Examples of NCI’s use of MedDRA
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What is MedDRA?
Med = Medical D = Dictionary for
R = Regulatory A = Activities
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Objectives for MedDRA Development
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• An international multi-lingual terminology
• Standardized communication between industry and regulators
• Support of electronic submissions• Application through all phases of the
development cycle
4
Result of an ICH initiative (M1) To provide:
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Objectives for MedDRA Development (cont)
• Classification for a wide range of clinical information
• Support for multiple medical product areas
• A terminology that saves time and resources
To provide (cont):
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MedDRA and the MSSO• International support and development of
terminology• Foster use of MedDRA through
communications and educational offerings• “Custodians”, not owners, of the
terminology• JMO (partner organization for Japanese-
language MedDRA)• Governed by a Management Board
(industry, regulators, multi-national, other interested parties)
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MedDRA Definition
MedDRA is a clinically-validated international medical terminology used by regulatory authorities and the regulated biopharmaceutical industry. The terminology is used through the entire regulatory process, from pre-marketing to post-marketing, and for data entry, retrieval, evaluation, and presentation.
© 2011 Northrop Grumman Corporation. All Rights Reserved.
MedDRA Subscribers Worldwide
8
2847 organizations as of 31 March 2011
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Regulatory Status of Mandate• US FDA
– Used in several FDA databases (AERS, VAERS, and CAERS)
– Proposed Rule for Safety Reporting Requirements (2003): MedDRA for postmarketing safety reports
• Japanese Ministry of Health, Labour and Welfare– Mandatory use for electronic reports– Used in Periodic Infection and Safety Reports– For medical devices with biological components,
infections to be described with MedDRA terms
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Regulatory Status of Mandate (cont)
• European Union– Clinical trials
• SUSARs (Suspected Unexpected Serious Adverse Reactions) – use MedDRA LLTs (current or previous version)
– Volume 9A (all authorized medicinal products, including OTC) • Individual Case Safety Reports (ICSRs) – use
MedDRA LLTs (current or previous version) • For adverse reactions in Periodic Safety Update
Report• Standardised MedDRA Queries (SMQs)
recommended for signal detection
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ICH Standard
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• Work together with other ICH standards for electronic submission:o ICH E2B form: data elements for transmission of ICSR
MedDRA
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MedDRA and E2B MedDRA-coded fields• B.1.7.1 Structured information on relevant medical history including onset and
resolution date as well as relevant comments• B.1.7.1a.1 MedDRA version for medical history• B.1.7.1a.2 Structured information• B.1.8 Relevant past drug history• B.1.8f.1 MedDRA version for indication• B.1.8f.2 Indication• B.1.8g.1 MedDRA version for reaction• B.1.8g.2 Reaction• B.1.9.2 Reported cause(s) of death • B.1.9.2.a MedDRA version for reported causes(s) of death• B.1.9.2.b Reported cause(s) of death (repeat as necessary)• B.1.9.4 Autopsy-determined cause(s) of death• B.1.9.4a MedDRA version for autopsy-determined cause(s) of death• B.1.9.4b Autopsy-determined cause(s) of death (repeat as necessary) • B.1.10.7 Relevant medical history and concurrent conditions of parent• B.1.10.7.1a.1 MedDRA version for parent medical history• B.1.10.7.1a.2 Structured information
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MedDRA and E2B (cont)• B.1.10.8 Relevant past drug history• B.1.10.8f.1 MedDRA version for indication• B.1.10.8f.2 Indication• B.1.10.8g.1 MedDRA version for reaction• B.1.10.8g.2 Reactions (if any and known)• B.2 Reaction(s)/Event(s)• B.2.i.1.a MedDRA version for reaction/event term LLT• Reaction/event in MedDRA terminology (LLT)• B.2.i.2.a MedDRA version for reaction/event term PT• Reaction/event in MedDRA terminology (PT )• B.3 Results of tests and procedures relevant to the investigation of the patient• B.3.1c Structured information (tests) relevant to the investigation of the patient • B.4.k.11 Indication for use in the case• B.4.k.11a MedDRA version for indication• B.4.k.11b Indication for use in the case• B.4.k.17.2 Effect of rechallenge (or re-exposure), for suspect drug(s) only• B.4.k.17.2a MedDRA version for reaction(s)/event(s) recurred• B.4.k.17.2b If yes, which reaction(s)/event(s) recurred?• B.4.k.18.1 Relatedness of drug to reaction(s)/event(s)• B.4.k.18.1a MedDRA version for Reaction assessed• B.4.k.18.1b Reaction assessed• B.5.3 Sender's diagnosis/syndrome and/or reclassification of reaction/event
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Regulatory Status of Mandate (cont)• European Union (cont)
– Interface between EudraVigilance and EU Risk Management Plan• To code indications, risks, interactions
(potential and Summary of Product Characteristics guideline
• MedDRA to be used throughout; in particular for Contraindications, Special warnings and precautions for use, and Undesirable effects sections
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Regulatory Status of Mandate (cont)• ICH M4E Guideline on Common Technical
Document– Recommended in adverse event summary tables
• Canada– Guidance Document for Industry - Reporting
Adverse Reactions to Marketed Health Products• Recommended as standard for adverse reaction reports
– Guidance for Industry - Product Monograph (labeling)
• Preferred terminology for adverse drug reactions
15
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• MedDRA implemented in WHO’s Global Safety Database (Vigibase)– WHO National Centres can review data,
conduct analyses in both WHO-ART and MedDRA
• Vigibase (>5.5 million ICSRs) provides a global repository of MedDRA-coded safety data– Substantial pharmacovigilance tool– Significant benefit to global patient safety– WHO receives most of its ICSRs coded in
MedDRA
WHO and MedDRA
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Scope of MedDRA
DiseasesDiagnoses
SignsSymptoms
Therapeutic indicationsInvestigation names &
qualitative resultsMedical & surgical
proceduresMedical, social, family
historyMedication errors
Product quality, device issues
Not a drug dictionary
Not an equipment, device,diagnostic product dictionary
Clinical trial study design terms
Patient demographicterms
Frequency qualifiers
Numerical values forresults
Severity descriptors
INOUT
Terms from other terminologies
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MedDRA Structure
System Organ Class (SOC) (26)
High Level Group Term (HLGT) (335)
High Level Term (HLT) (1,710)
Preferred Term (PT) (19,086)
Lowest Level Term (LLT) (69,019)
MedDRA Version 14.0
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• MedDRA Desktop Browser– Download from MSSO Web site– View/search MedDRA and SMQs– Export functionality
• MedDRA Web-Based Browser– https://www.meddrabrowser.org/dsnavigator/– Requires specific user ID and password– Access to all MedDRA versions in English and
available EU languages (and Chinese, if subscribed)
– View/search MedDRA and SMQs– Export functionality
MSSO’s MedDRA Browsers
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MedDRA Desktop Browser
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MedDRA Desktop Browsers (Cont)
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MedDRA Web-Based Browser
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• MedDRA is a user responsive terminology • Subscribers may submit change requests to
the MSSO for consideration• Twice yearly official updates
– 1 September X.1 release (Simple changes only)– 1 March X.0 release (Complex and simple
changes)• Resources:
– “What’s New” document– Version report– Recommendations for MedDRA Implementation
and Versioning for Clinical Trials
MedDRA Maintenance
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ICH-Endorsed Guides for MedDRA Users
Developed by a working group of the ICH Steering Committee• Regulators and industry representatives• EU, Japan, USA• Canadian observer, MSSO, JMO
1. MedDRA Term Selection: Points to Consider– Developed to promote medically accurate and consistent use of MedDRA
in exchange of data (ultimately, for “medically meaningful” retrieval and analysis)
2. MedDRA Data Retrieval and Presentation: Points to Consider– Objective is to promote understanding of implications that various
options for data retrieval have on accuracy and consistency of final output
Current versions available on MedDRA MSSO Web site (http://www.meddramsso.com/subscriber_library_ptc.asp)
© 2011 Northrop Grumman Corporation. All Rights Reserved. 25 25
Standardised MedDRA Queries (SMQs)
• Result of cooperative effort between CIOMS and ICH (MSSO)
• Groupings of terms from one or more MedDRA System Organ Classes (SOCs) related to defined medical condition or area of interest
• Included terms may relate to signs, symptoms, diagnoses, syndromes, physical findings, laboratory and other physiologic test data, etc., related to medical condition or area of interest
• Intended to aid in case identification
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SMQs in Production - ExamplesAs of Version 14.0, a total of 85 in production (One is inactive)
• Agranulocytosis• Anaphylactic reaction• Cerebrovascular
disorders• Convulsions• Depression and
suicide/self-injury• Hepatic disorders• Ischaemic heart disease• Lack of efficacy/effect
• Osteonecrosis• Peripheral neuropathy• Pregnancy and neonatal
topics• Pseudomembranous colitis• Rhabdomyolysis/myopathy• Severe cutaneous adverse
reactions• Systemic lupus
erythematosus
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SMQ Benefits and Limitations• Benefits
– Application across multiple therapeutic areas– Validated reusable search logic– Standardized communication of safety information– Consistent data retrieval– Maintenance by MSSO/JMO
• Limitations– Do not cover all medical topics or safety issues– Will evolve and undergo further refinement even
though they have been tested during development
© 2011 Northrop Grumman Corporation. All Rights Reserved.
SMQ Applications• Clinical trials
– Where safety profile is not fully established, use multiple SMQs on routine basis as screening tool
– Selected SMQs to evaluate previously identified issue (pre-clinical data or class effect)
• Postmarketing – Selected SMQs to retrieve cases for suspected or
known safety issue– Signal detection (multiple SMQs employed)– Single case alerts– Periodic reporting (aggregate cases for safety and
other issues, e.g., lack of efficacy)
© 2011 Northrop Grumman Corporation. All Rights Reserved. 29
How to “Run” SMQs
Query
Browser Demonstration
SMQ View
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MedDRA Use for AE Reporting:Industry vs. NCI
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• Industry – Verbatim/text terms coded to MedDRA for regulatory
reporting• Clinical trial data• Post-marketing pharmacovigilance (spontaneous reports by
healthcare professionals, companies, patients; post-marketing studies; literature reports)
• NCI Industry AE Subcommittee: When industry uses CTCAE, generally verbatim terms are also required which are coded to MedDRA
• Some also recode CTCAE terms to MedDRA
• NCI– CTCAE
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MedDRA Use at NCI
List MedDRA Number of terms
% ‘Mapped’ to MedDRA
CTCAE v3 V10.0 ‘Mapped’
- -
CTCAE v4.0 V12.1 LLTs 790 -
Simplified Disease List (SDC)
V10.0 ‘Mapped’
245 94%
Pre-existing conditions
V10.0 ‘Mapped’
38 100%
Therapies V10.0 ‘Mapped’
19 53%
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© 2011 Northrop Grumman Corporation. All Rights Reserved.
CTCAE v4.0 and MedDRASafety Profiler (CTCAE ‘Index’)
• Assistance to identify appropriate CTCAE term
- Utilizes all LLTs associated with CTCAE terms- Example: search for ‘rigors’ or ‘shivering’ returns
CTCAE v4.0 term ‘Chills’
• ‘Other, specify’ assistance to select valid MedDRA term
• http://safetyprofiler-ctep.nci.nih.gov/CTC/CTC.aspx
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CTCAE ‘Other, specify’ andMedDRA
• Verbatim (non-MedDRA)• CTCAE v4.0 revision project analysis of ~450
verbatim– 41% match– 23% algorithm– 36% uncoded
• caAERS pilot MedDRA integration with ‘Other, specify’
• When all AE data is MedDRA (CTCAE + ‘Other, specify’), MedDRA tools can be applied for analysis (hierarchy, SMQs)
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© 2011 Northrop Grumman Corporation. All Rights Reserved.
MedDRA Training Resources
Free Training Open Registration Webinars
Onsite Training
Coding with MedDRA What’s New in MedDRA Coding with MedDRA
MedDRA Safety Data Analysis and SMQs
MedDRA Versioning MedDRA Safety Data Analysis and SMQs
Webinar-MedDRA Coding Basics
Introduction to MedDRA
Webinar-Introduction to MedDRA Data Analysis and SMQs for Physicians
Medication Errors and Product Quality Issue Concepts in MedDRA
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Shorter courses are available upon request. Please contact MSSO Help Desk for details.
© 2011 Northrop Grumman Corporation. All Rights Reserved. 36
Discussion
www.meddramsso.com
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