1. MedDRA® Overview NCI Vocabulary and Common Data Elements Workspace
Presented by: Ann Setser, MSSO
June 16, 2011
MedDRA® is a registered trademark of the International Federation
of Pharmaceutical Manufacturers and Associations (IFPMA)

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

3. What is MedDRA? Med = Medical D = Dictionary for R = Regulatory
A = Activities

4. Objectives for MedDRA Development
Result of an ICH initiative (M1)
To provide:
An international multi-lingual terminology
Standardized communication between industry and regulators
Support of electronic submissions
Application through all phases of the development cycle 4

5. Objectives for MedDRA Development (cont)
To provide (cont):
Classification for a wide range of clinical information
Support for multiple medical product areas
A terminology that saves time and resources 5

6. 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) 6 6

7. 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. 7

8. MedDRA Subscribers Worldwide
2847 organizations as of 31 March 2011

9. 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

10. 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

11. ICH Standard
Work together with other ICH standards for electronic submission:
ICH E2B form: data elements for transmission of ICSR
MedDRA

12. MedDRA and E2B MedDRA-coded fields
B 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 Reported cause(s) of death
B a MedDRA version for reported causes(s) of death
B b Reported cause(s) of death (repeat as necessary)
B 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 Relevant medical history and concurrent conditions of parent
B a.1 MedDRA version for parent medical history
B a.2 Structured information

13. MedDRA and E2B (cont) B.1.10.8 Relevant past drug history
B f.1 MedDRA version for indication
B f.2 Indication
B g.1 MedDRA version for reaction
B g.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

14. 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 14

15. 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 15

16. WHO and MedDRA
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 16

17. Scope of MedDRA OUT IN Diseases Diagnoses Signs Symptoms
Therapeutic indications
Investigation names & qualitative results
Medical & surgical procedures
Medical, social, family history
Medication errors
Product quality, device issues
Not a drug dictionary
Not an equipment, device,
diagnostic product dictionary
Clinical trial study design terms
Patient demographic
terms
Frequency qualifiers
Numerical values for
results
Severity descriptors IN
OUT
Terms from other terminologies 17

18. 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

19. MSSO’s MedDRA Browsers
MedDRA Desktop Browser
Download from MSSO Web site
View/search MedDRA and SMQs
Export functionality
MedDRA Web-Based Browser
Requires specific user ID and password
Access to all MedDRA versions in English and available EU languages (and Chinese, if subscribed)

20. MedDRA Desktop Browser

21. MedDRA Desktop Browsers (Cont)

22. MedDRA Web-Based Browser22

23. MedDRA Maintenance 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

24. 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 (

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 25

26. SMQs in Production - Examples
As 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

27. SMQ Benefits and Limitations
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

28. 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)

29. How to “Run” SMQs
Query 29

30. Browser Demonstration SMQ View

31. MedDRA Use for AE Reporting: Industry vs. NCI
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

32. 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)
245
94%
Pre-existing conditions 38
100%
Therapies 19
53%

33. CTCAE v4.0 and MedDRA Safety 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

34. CTCAE ‘Other, specify’ and MedDRA
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)

35. MedDRA Training Resources
Free Training
Open Registration Webinars
Onsite Training
Coding with MedDRA
What’s New in MedDRA
MedDRA Safety Data Analysis and SMQs
MedDRA Versioning
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
Shorter courses are available upon request. Please contact MSSO Help Desk for details.

36. Discussion