1. MedDRA® Version Updates
MedDRA® is a registered trademark of the International Federation
of Pharmaceutical Manufacturers and Associations (IFPMA)

2. Course Objectives To provide an understanding of:
MedDRA versioning: timing and extent of updates
Impact of MedDRA versioning in your organization
Practical approaches to MedDRA versioning

3. Background of Versioning

4. MedDRA Maintenance MedDRA is a user responsive terminology
Subscribers may submit change requests
100 change requests maximum per month
Twice yearly official updates
1 March X.0 release (all levels)
1 September X.1 release (LLT and PT levels only)

5. MedDRA Growth Trend Number of Implemented Changes per Release
Updated v13.0

6. Versioning Background
An issue to be addressed by all MedDRA users
Changes that can occur:
New terms added
Terms can change position in hierarchy
Primary SOC allocations can change
LLT currency can change
SMQ maintenance 6

7. Rationale for Version Update
Electronic submissions:
Individual Case Safety Reports (ICSRs)
Suspected unexpected serious adverse reactions (SUSARs)
Signal detection
Standardised MedDRA Queries (SMQs)
Periodic reviews, including PSURs
Data monitoring committees

8. Rationale for Version Update (cont)
Regulatory submissions
Clinical study reports
Safety summary reports
Marketing applications
Labeling (package insert)

9. Type of Data to Update Safety reports (pharmacovigilance)
Clinical study data (adverse events, medical history)
Legacy data (e.g., from prior mergers)
Data from contract research organizations
Synonym lists

10. Frequency of Data Update
Other versioning considerations:
Global regulatory requirements
Budget/resources
Availability of software tools/upgrades

11. Resources for Version Updates

12. “What’s New” Document
Contains detailed information on source, types of changes between versions
Highlights changes related to new initiatives, SMQs
Other information
Term history
Tables showing impact of this version on MedDRA
Impact on records in MedDRA files
MedDRA term counts
List of modified LLT names
List of LLTs with currency status change
MSSO “What’s New” webinars

13. MedDRA Version Reports
Developed by MSSO to provide list of changes between latest version and previous version
Detailed record-by-record report
Included in the MedDRA terminology download

14. MedDRA Version Reports (cont)
Summary table
New LLTs including new PTs
New PTs
Promoted LLTs
Demoted PTs
LLTs moved to different PTs
LLT and PT primary SOC changes
LLT and PT text changes
LLT currency changes
Hierarchy term changes (HLT, HLGT, SOC)
SMQ changes
PTs added to SMQs

15. MedDRA Version Reports (cont)
Note this is an example (from v12.0) and will not be updated with each version of this course.

16. MedDRA Version Reports (cont)
Note this is an example (from v12.0) and will not be updated with each version of this course.

17. Sequential Files
ASCII files that identify changes between latest version and previous version
Distributed with MedDRA release
Files with “.seq” suffix

18. Points to Consider Documents
Both “MedDRA Term Selection” and “Data Retrieval and Presentation” PTC documents are updated
Each document has associated “Summary of Changes”
Organization coding and data analysis/retrieval conventions should be reviewed, updated as needed with each new MedDRA version

19. Timing of Version Updates

20. Goals of Version Updates
Most organizations have version update processes in place
May vary among departments
Goals of versioning
Implement current version of MedDRA
Stay current with regulatory authorities and partners
Harmonize use of MedDRA to optimize communication of data

21. Timing of Version Update
MSSO “Best Practice” documents
“Recommendations for MedDRA Implementation and Versioning in Clinical Trials” (
Six options involving either “freezing” a version or re-coding at various points
MSSO recommends Options 5 or 6
Updated v13.0. JH Updated weblink.

22. Option 1
“Freeze” at initiation and for life of a project (all trials, reports); report with same version
Supports consistency of coding and analysis within related trials
For longer running projects, impact on development of label that uses a more recent version
Does not take advantage of improvements with subsequent releases
Requires storage of multiple MedDRA versions and maintenance of coding conventions with each version

23. Option 1 – Use a Single Version for All Trials for Life of Program

24. Options 2 - 4
Option 2 - “Freeze” at initiation of project; report with most recent version
Option 3 - “Freeze” at initiation of each trial within project; report with most recent version
Option 4 - Hold coding until completion of each trial
Use most recent version for coding and reporting

25. Option 5 – Recommended by MSSO
“Freeze” at beginning of each trial within project
Optionally re-code data with latest version at conclusion of each trial based on project-defined criteria

26. Option 5 - Recommended by MSSO (cont)
Always output data using most recent version
Review collected changes against thresholds documented in project plan
If there is medical benefit to re-coding, re-code to most recent version; otherwise, generate reports with most recent version of MedDRA
Long running trials would be updated and better analyzed with latest version
Less time difference between significant volume of trial data (Phase III) and label development
Project level reports use current version

27. Option 6 - Recommended by MSSO
Ongoing re-coding of all trial data in a project to most recent version
All trial data updated with each version; provides consistency for reporting
Removes reconciliation issues with post-marketing data which is reported with current version of MedDRA
Requires re-coding of all trials to be updated to current version of MedDRA

28. Options 6 – All Trial Program Data Updated with Each Release

29. Timing of Update (cont)
MSSO “Best Practice” documents (cont)
“The MedDRA MSSO’s Recommendations for Single Case Reporting using Semi-annual Version Control” (
Recommendations
MedDRA should be used for spontaneous post-market single case reports and pre-market single case reports for serious adverse events
All reporting should be done using most recently released version. Version number of MedDRA release used to code report data should be included in all reports
V13.0 Updated weblink

30. Timing of Update (cont)
Recommendations (cont)
The decision to re-code historical data is an organizational decision
The newly released version of MedDRA should become the reporting version on the first Monday of the second month after it is released. To synchronize this event over the three ICH regions, the MSSO recommends midnight GMT, Sunday to Monday, for the switchover

31. Timing of Update (cont)
Recommendation 4 applied to MedDRA Version 13.0
MedDRA Version 13.0 released 1 March 2010
First Monday in May is 3 May 2010
MedDRA Version 13.0 becomes reportable version on 3 May 2010 at 00:01 GMT
v13.0 Updated dates and versions.

32. Timing of Update
1 March 2010 – MedDRA 13.0 Released
Updated v13.0

33. Timing of Update (cont)
Impact limited to data that are being transmitted
Internal data (i.e., some clinical trial data) could follow a different schedule
EMA and MHLW will accept current version plus previous version for ICSRs and SUSARs
FDA has no version requirement
Follows MSSO recommendation for versioning
Will re-code if a submitted PT not recognized
13.0 Updated EMEA to EMA

34. Timing of Update (cont)
Typically, individual National Competent Authorities support one version of MedDRA
One EU regulatory agency implemented the recommendation as follows:
“Electronic reports submitted prior to 7 May 2007 using version 10.0 will be rejected by the [Agency].”

35. 60 Day Implementation Period
Issues with Timing
Currently, organizations are implementing on different dates
On release date
During implementation period
At end of implementation period
13.0. Updated to May 3
May 3
March 1 1 2 3
60 Day Implementation Period

36. Issues with Timing (cont)
Differences in implementation date negatively impact communication of ICSRs
EMA issued letter supporting original MSSO recommendation
MSSO is working with regulatory authorities to coordinate implementation for all MedDRA users
MSSO recommendation is to transition on transition date
Not by transition date
13.0. Changed EMEA to EMA

37. Extent of Version Updates

38. Extent of Update
What does it mean to implement latest version of MedDRA?
Since coding terms in MedDRA (LLTs) are not deleted, an organization could simply apply latest version with no data changes
What does your organization do?
Data coded to LLTs that become non-current
Data that have direct matches to new terms
Medically “better” terms available in new version

39. Extent of Update (cont)
Many approaches to versioning by industry and regulators
No real regulatory mandate
MSSO has drafted a versioning “Best Practice” document

40. Versioning “Best Practice” (cont)
Implementation levels

41. Version Change – LLT Non-Current
Automated approach
Example:
Verbatim Term
Previous Version LLT
Version Change
New Version LLT (Re-coded)
Swelling (extensive) of arm that was vaccinated
Extensive limb swelling
LLT Extensive limb swelling became non-current in new version
Extensive swelling of vaccinated limb

42. Version Change – New LLTs Direct/Lexical Match
Automated approach
Example:
Verbatim Term
Previous Version LLT
Previous Version PT
Version Change
New Version LLT (Re-coded)
New Version PT
Urinary calculus, migrating
Urinary calculus
Calculus urinary
LLT Migrating urinary calculus was added to the new version
Migrating urinary calculus

43. Version Change – New LLTs Better Medical Match
Requires manual medical review
Example:
Verbatim Term
Previous Version LLT
Previous Version PT
Version Change
New Version LLT (Re-coded)
New Version PT
Darkened surface of tongue (new finding)
Tongue discolora-tion
Tongue discolouration
LLT/PT Tongue pigmentation was added to new version
Tongue pigmentation

44. Supplemental Terms
Defined as approved change requests between releases of MedDRA
Posted on MSSO Web site
Assigned MedDRA code
Available for use

45. Supplemental Terms (cont)
Most organizations wait for official release
Many will review supplemental terms to be aware of what is coming in next release
In general, regulatory authorities do not accept supplemental terms
13.0 Updated last bullet to state that most regulators don’t accept supplemental terms. (Previously stated that EMEA supports their use).

46. Blue Ribbon Panel Meeting on Versioning
V 13.0 New slide. Summary of BRP.

47. Versioning BRP Blue Ribbon Panel (BRP) Topics of this BRP
Goal: develop recommendations on an issue
Panel members represent ICH regions
Observers play important role
MSSO presents recommendations to Board for approval
Topics of this BRP
Extent of MedDRA versioning
Frequency of MedDRA releases
Hosted by Schering-Plough, Kenilworth, NJ May 2009.
V 13.0 New slide. Summary of BRP. 47

48. BRP Panel Members Barry Hammond (GlaxoSmithKline)
JoAnn Medbery (Johnson & Johnson)
Tom Paternoster (European Medicines Agency)
Toni Piazza-Hepp (US Food and Drug Administration)
Yasuo Sakurai (Japanese Maintenance Organization)
V 13.0 New slide. Summary of BRP. 48

49. Extent of MedDRA Versioning
Proposed implementation levels
V 13.0 New slide. Summary of BRP. 49
MSSO-DI © 2006 Northrop Grumman Corporation. All Rights Reserved.

50. Frequency of MedDRA Releases
Can MedDRA be released once a year instead of two times a year?
V 13.0 New slide. Summary of BRP. 50

51. Recommendations – Extent of Versioning
1. Content to be added as appendix to “MedDRA Term Selection: Points to Consider” (TS: PTC). PTC WG should further develop content, align it with existing versioning language
2. Add recommendation that organizations document upversioning strategy
V 13.0 New slide. Summary of BRP. 51

52. Recommendations – Extent of Versioning (cont)
3. Emphasis on communication of version extent; not to be interpreted as regulatory requirement
4. Include impact, positive and negative, of each method of version updates (e.g., recoding non-current LLTs)
V 13.0 New slide. Summary of BRP. 52

53. Recommendations – Feasibility of Annual Release
Remain biannual for now; revisit in 2011
How to assist small, new subscribers:
To implement a new version without recoding is acceptable
Develop tool to assess impact of new version and facilitate upversioning task (MSSO)
Additional training on version update processes (MSSO)
3. Add to TS: PTC MSSO’s recommendation for implementation date/time (00:00 GMT on 1st Monday of 2nd month after release)
V 13.0 New slide. Summary of BRP. 53

54. Recommendations – Feasibility of Annual Release (cont)
4. MSSO to collate the versioning requirements of ICH regulatory authorities and post on MSSO website
5. Regulatory authorities should consider future use of supplemental terms
All recommendations endorsed by Management Board
V 13.0 New slide. Summary of BRP. 54

55. Impact of Version Updates

56. Impacts of New Versions
Key point – LLTs/PTs are never deleted in MedDRA
Type of Change
Impact
LLT/PTs are moved
Be aware of change, not necessary to change coding
LLTs change currency
Probably need to re-code
LLT/PTs change primary SOC
Understand impact on summary reporting
LLT/PTs are added
May cause re-coding

57. Impacts of New Versions (cont)
Type of Change
Impact
Revisions, additions to hierarchy
Be aware of change, not necessary to change coding
Understand impact on summary reporting
Addition of new SMQs
No impact on coding
Useful information for data analysis and reporting
Changes to existing SMQs. PTs added or made inactive
No change to coding but be aware of impact on data analysis

58. Sample Version Impact (cont)58

59. Sample Version Impact (cont)
New PT
added in MedDRA 59

60. Sample Version Impact (cont)
Identify potential impact on existing MedDRA-coded data
Significant number of cases are coded under this HLT
Some existing verbatim terms/synonym list entries may directly match new PTs or LLTs
Some existing verbatim terms/synonym list entries may be medically better terms to use 81 27 60

61. Focused MedDRA Impact Analysis
120 AEs
350 AEs
18 AEs
17 AEs
950 AEs
535 AEs
26 Changes
257 Changes
415 Changes
756 Changes
310 Changes
0 Changes

62. Software Tools
For versioning, software tools can be a great time saver
Use the tools to focus your review
Link MedDRA changes to your organization’s coded data
Easily identifies LLTs that changed currency
Lists areas of MedDRA your organization uses that have possibly useful new terms
Simple queries can be developed using SQL tools to support these standard reports

63. MedDRA Version Analysis Tool
Concept from BRP 6 on versioning
MSSO tasked to develop a tool to assist in MedDRA version upgrade
Current working title for this project is the MedDRA Version Analysis Tool (MVAT)
13.0 New slide. MVAT summary.

64. MSSO Actions MSSO developed an initial set of requirements
Requirements refined by MedDRA Expert Panel input
Release plan and costs to MedDRA Management Board for approval
13.0 New slide. MVAT summary.

65. Basic Assumptions Tool will generate a series of reports
Intended to aid all MedDRA users
Free with a MedDRA subscription
MVAT will not perform coding tasks
Difficult to meet different user requirements
Could be seen as MSSO or ICH coding guidance
Automated tool cannot replace expert human coders
13.0 New slide. MVAT summary.

66. Basic Assumptions (cont)
All MVAT reports should be considered informational and not a requirement
User decides whether to re-code based on information provided
Reports can compare any two MedDRA versions
MVAT will have two modes of operation
Static Reports
Interactive Reports (optional)
13.0 New slide. MVAT summary.

67. Basic Assumptions (cont)
Static Reports
MedDRA changes that require no user input (based on current Version Report spreadsheet format)
Identify changes between any two MedDRA versions
MSSO will continue to produce Version Report spreadsheet (two consecutive versions)
13.0 New slide. MVAT summary.

68. Report Menu
13.0 New slide. MVAT summary.

69. Basic Assumptions (cont)
Interactive Reports
Require input from the user
Verbatim (optional)
LLT/PT code (required)
Company database identifier (i.e., record number - optional)
Provide more of a “tuned” list of changes
New MedDRA LLTs directly matching verbatims
Currently used LLTs with a currency change
Changes in hierarchy for currently used terms
13.0 New slide. MVAT summary.

70. Sample Interactive Report Output
13.0 New slide. MVAT summary.

71. Impact of Version Updates on Data Analysis
Version used in data retrieval and presentation should be documented
Terms used for queries should be in same version as data being queried
Core slide

72. MedDRA Versioning - Effect of PT Demotion
Number of Events at PT Level
Pacemaker complication (PT) 15
Medical device complication 5
MedDRA Version 13.0
Pacemaker complication (no longer a PT) 20
Core slide.
Updated demotion example for v13.0.Also good to show how specific devices are under general device terms at PT level. 72 72

73. MedDRA Versioning (cont) - Effect of Primary SOC Change
Number of Events
SOC Neoplasms benign, malignant and unspecified (incl cysts and polyps)
PT Ectopic hormone secretion 20
MedDRA Version 13.0
SOC Endocrine disorders
Core slide.
Updated primary SOC change example for v13.0. PT is not a neoplasm per se but a malignancy-related condition, therefore the primary SOCs were swapped. Now primary to Endocrine with secondary link to Neoplasms. 73 73

74. SMQ Versioning
It is recommended that organizations utilize the SMQs with data coded with the same version of MedDRA
Match the MedDRA version of the SMQ with the MedDRA version of the coded data
Mismatches of SMQ and MedDRA coded data could produce unexpected results
Core slide

75. SMQ Versioning (cont)
Examples of PTs added to SMQs in MedDRA Version 13.0:
PT Spinal column injury in SMQ Accidents and injuries
PT Subclavian artery occlusion in SMQ Embolic and thrombotic events, arterial
Using version 12.1 SMQs which do not contain these PTs would fail to identify cases coded to these terms in a database using MedDRA Version 13.0
Core slide. Updated with new examples of terms added to SMQs in v13.0.JH. 75

76. Synonym List Maintenance
For new MedDRA versions, run synonyms against new MedDRA LLTs
Identify new non-current LLTs that are on synonym list; flag for recoding
Run synonyms against new MedDRA LLT list
Identify possible new current direct matches

77. Synonym List Maintenance (cont)
Remaining challenge is to determine if “better medical matches” have been added (essentially, a manual process)
Communicate results to users of synonym list

78. Conclusions MedDRA version updates can be reduced to reasonable tasks
Focus on what impacts your data
Take advantage of data and reports available
Communicate changes
Some updates may not change coding but may impact data analysis and reporting

79. Summary In this course, we:
Reviewed MedDRA maintenance, growth, and types of version changes
Learned about resources available to assist in version updates
Learned about the timing and extent of MedDRA version updates
Considered the impact of version updates on coded data, including data analysis

80. QUESTIONS ?

81. MSSO Contacts Mail Telephone Fax Products and Services
MedDRA MSSO
3975 Virginia Mallory Drive
Chantilly, VA, USA 20151
Telephone
Toll-free Worldwide (AT&T)
Fax
Products and Services 81

82. MSSO Contacts (cont) To Subscribe by Help desk E-mail Web site Phone
Web site
click on “Subscribe to MedDRA”
Help desk
Phone
International AT&T Toll Free:
Direct Dial (USA): 82