MedDRA ® is a registered trademark of the International Federation of Pharmaceutical Manufacturers...

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

© 2011 Northrop Grumman Corporation. All Rights Reserved. 2

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


What is MedDRA?

Med = Medical D = Dictionary for

R = Regulatory A = Activities

© 2011 Northrop Grumman Corporation. All Rights Reserved.

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

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Result of an ICH initiative (M1) To provide:

© 2011 Northrop Grumman Corporation. All Rights Reserved. 5 5

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):


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.


MedDRA Subscribers Worldwide

8

2847 organizations as of 31 March 2011


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


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


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


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


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


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

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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


• 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


MedDRA Desktop Browser

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MedDRA Desktop Browsers (Cont)

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MedDRA Web-Based Browser


• 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


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)


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


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


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)


How to “Run” SMQs

Query

Browser Demonstration

SMQ View


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


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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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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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.


Discussion

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