MedDRA® BEST PRACTICES
Maintenance and Support Services
Organization’s (MSSO)
Recommendations for
Implementation and Use of
MedDRA2018

Acknowledgements

ACKNOWLEDGEMENTS
MedDRA® trademark is owned by IFPMA on behalf of ICH.

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Table of Contents

Table of Contents
1.

INTRODUCTION..................................................................................................... 1

2.

PRIMARY SYSTEM ORGAN CLASS (SOC) ALLOCATION IN MedDRA ............ 2
2.1 PURPOSE ........................................................................................................ 2
2.2 MedDRA AS AN ICH STANDARD .................................................................... 2
2.3 THE REASON FOR A PRIMARY SOC ............................................................. 2
2.4 CAN A PRIMARY SOC ALLOCATION BE CHANGED? ................................... 33.

SINGLE CASE REPORTING USING SEMI-ANNUAL VERSION CONTROL........ 4
3.1 PURPOSE ........................................................................................................ 4
3.2 OVERVIEW....................................................................................................... 4
3.3 RECOMMENDATION ....................................................................................... 4

4.

MedDRA IMPLEMENTATION AND VERSIONING FOR CLINICAL TRIALS ........ 6
4.1 PURPOSE ........................................................................................................ 6
4.2 OVERVIEW....................................................................................................... 6
4.3 OPTIONS CONSIDERED ................................................................................. 6
4.4 RECOMMENDATION ....................................................................................... 8

5.

VERSIONING METHODOLOGY ............................................................................ 9
5.1 PURPOSE ........................................................................................................ 9
5.2 OVERVIEW....................................................................................................... 9
5.3 OPTIONS CONSIDERED ................................................................................. 9

6. RECOMMENDATIONS FOR THE IMPLEMENTATION OF MedDRA
SUPPLEMENTAL TERMS ........................................................................................... 11
6.1 PURPOSE ...................................................................................................... 11
6.2 OVERVIEW..................................................................................................... 11
6.3 RECOMMENDATIONS ................................................................................... 11
LIST OF TABLES
Table 5-1 Types of Versioning Methods ............................................................ 10

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Introduction

1. INTRODUCTION
The purpose of this MedDRA Best Practices document is to provide therecommendations of the MedDRA Maintenance and Support Services Organization(MSSO) for the implementation and use of MedDRA. Its objective is to promote theaccurate and consistent use of MedDRA by users worldwide.
The document provides best practice considerations on several topics pertaining to theuse of MedDRA. It does not specify regulatory requirements, nor does it address
database issues. Organizations are encouraged to document their own best practices inorganization-specific guidelines which should be consistent with this MedDRA Best
Practices document.
This MedDRA Best Practices document has five sections:•Primary System Organ Class (SOC) Allocation in MedDRA•

Single Case Reporting Using Semi-annual Version Control•

MedDRA Implementation and Versioning for Clinical Trials•

Versioning Methodology•

Recommendations for the Implementation of MedDRA Supplemental Terms

Users are invited to contact the MSSO Help Desk with any questions or comments
about the MedDRA Best Practices document.

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Primary System Organ Class (SOC) Allocation in MedDRA

2. PRIMARY SYSTEM ORGAN CLASS (SOC) ALLOCATION IN MedDRA
2.1

PURPOSEThis section explains the concept of the primary System Organ Class (SOC) allocationin MedDRA and why the primary SOC should not be individually selected by MedDRA
users. To do so undermines one of the main goals in using MedDRA as a regulatory
standard.
2.2

MedDRA AS AN ICH STANDARD

MedDRA was developed by an ICH Expert Working Group to address many of thelimitations of older adverse event terminologies. In the past, organizations that used
these terminologies freely “edited” them (e.g., added custom terms) to suit specificneeds and to overcome their limitations. The result was a lack of any real standard
terminology in the adverse event reporting regulatory environment at that time. The
intent of ICH, in developing MedDRA, was to have a standard, medically rigorous, andwell-maintained terminology to facilitate communication.
Specifically, some of the applications for MedDRA are:
•
•
•
•
•

To aggregate reported terms in medically meaningful groupings for review,
analysis and/or summary of safety data
To facilitate identification of common data sets for evaluation of clinical andsafety information
To facilitate consistent retrieval of specific cases or medical conditions from a
database
To improve consistency in comparing and understanding safety signals andaggregated clinical data
To facilitate electronic data interchange of clinical safety information.

The ICH also authorized a group of drug safety experts (from regulatory authorities andindustry) to draft the “MedDRA Term Selection: Points to Consider” document as
guideline for MedDRA usage in coding adverse events, medical and social history, andindications. This ICH-endorsed document states (bold added for emphasis):“MedDRA is a standardized terminology. It is considered essential that ad hoc
structural changes in MedDRA not occur. The assignment of terms across SOCs is
pre-determined within the terminology and should not be altered by users.”
2.3

THE REASON FOR A PRIMARY SOC

MedDRA is a multi-axial terminology meaning that a Preferred Term (PT) may be linked
to more than one SOC. For example, PT Dyspnoea has a link to both SOC Respiratory,
thoracic and mediastinal disorders (its organ system of manifestation) and to SOC
Cardiac disorders (because of its connection to heart disease). Each PT is assigned a
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Primary System Organ Class (SOC) Allocation in MedDRA

primary SOC to avoid “double counting” while retrieving information from all SOCs (i.e.,a cumulative SOC-by-SOC data output). The other SOCs to which a multi-axial PT is
linked are called “secondary” SOCs.
In most instances, PTs relating to diseases or signs and symptoms are assigned to theprime manifestation site SOC. So, for PT Dyspnoea, the primary SOC is SOC
Respiratory, thoracic and mediastinal disorders. However, there are exceptions for three
types of terms:•

Terms for congenital and hereditary anomalies are assigned to SOC Congenital,familial and genetic disorders as the primary SOC.

•

Terms for benign and malignant neoplasms are assigned to SOC Neoplasms
benign, malignant and unspecified (incl cysts and polyps) as primary SOC. This
does not apply to cyst and polyp terms. These terms have as their primary SOC
assignment their site of manifestation SOC•

Terms for infections are assigned to SOC Infections and infestations as theprimary SOC.

These primary SOC assignment rules were instituted as MedDRA was being developedin order to aggregate certain critical issues (congenital anomalies, neoplasms, andinfections) into specific places in MedDRA to facilitate safety signal detection. Note thatthe primary SOC allocations are “hard-wired” into the MedDRA ASCII files.
2.4

CAN A PRIMARY SOC ALLOCATION BE CHANGED?

Yes, any MedDRA Commercial, Non-profit/Non-commercial, or Regulatory subscriber
may submit a proposal to change the primary SOC assignment for any given term
through the usual Change Request process. In considering a subscriber’s request, theMSSO will carefully review the justification provided along with the already establishedallocation rules.
The MSSO is aware that coders and dictionary managers are sometimes asked to reassign the default primary SOC allocation for specific PTs to one of the organization’s
choosing. As noted above, the MSSO strongly discourages this practice as we believe it
undermines the intent of MedDRA as a standard terminology. For example, a reviewer
at regulatory authority would find it difficult to compare the safety data of similar
products from two different organizations if one freely assigned the PTs to SOCs of theirchoosing and the other used the standard primary SOC allocations.

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Single Case Reporting Using Semi-annual Version Control

3. SINGLE CASE REPORTING USING SEMI-ANNUAL VERSION CONTROL
3.1

PURPOSEThe purpose of this section is to provide the MSSO’s recommendations regarding theissue of MedDRA versions and their implementation for spontaneous single casereports and pre-market single case reports.
3.2

OVERVIEWThe updated versions of MedDRA are both the strength of the terminology and one ofits greatest challenges. Earlier terminologies were not properly maintained nor were
there timely releases of these terminologies to address errors or medical advances.
The MedDRA MSSO was created to address both of these issues. MedDRA is currently
provided to subscribers on a semi-annual basis utilizing a rigorous medical andtechnical review for each change request. MedDRA versioning is an issue that affects
the reporting of spontaneous single case reports and pre-market single case reports.
Based on comments the MSSO has received on this issue from users of theterminology, the MSSO is making the following recommendations. These
recommendations should not be viewed as official guidelines approved by regulatory
authorities, however the MSSO hopes that these recommendations are taken into
consideration when regulatory agencies draft guidelines regarding this issue in the
future.
3.3

RECOMMENDATIONThe MedDRA MSSO makes the following recommendations to the users of MedDRA in
the reporting of spontaneous single case reports and pre-market single case reports:
1) MedDRA should be used for spontaneous postmarketing single case reports andpremarket single case reports for serious adverse event reports.
2) All reporting should be done using the most recently released version of MedDRA.
The version number of the MedDRA release used to code the report data should be
included in all reports.
3) The decision to re-code historical data is left to the discretion of each individualorganization.

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Single Case Reporting Using Semi-annual Version Control

4) A new release version of MedDRA should become the reporting version on the firstMonday of the second month after it is released. To synchronize this event over thethree ICH regions, the MSSO recommends midnight GMT, Sunday to Monday, forthe switchover. For example :••1 March – MedDRA X.0 released

First Monday of May – MedDRA X.0 becomes the reporting version•

1 September – MedDRA X.1 released

First Monday of November – MedDRA X.1 becomes the reporting version
The stated change over date and time are used to allow all users enough time toprepare their systems to switch to the new MedDRA version.
For single case reporting, the sender and receiver of the data need to be in synchrony
regarding MedDRA versions. Users who are able to quickly update and validate theirsystems with each release of MedDRA need be aware that if they submit a report using
the updated MedDRA release prior to the receiving party switching to the updated
version, the submission may be rejected or at least kicked out of automated processing
and into a manual process and potential recoding, which will slow the processing of thesubmission.

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MedDRA Implementation and Versioning for Clinical Trials

4. MedDRA IMPLEMENTATION AND VERSIONING FOR CLINICAL TRIALS
4.1

PURPOSEThe purpose of this section is to provide the MSSO’s recommendation regarding theissue of MedDRA versions and their implementation in clinical trials.
4.2

OVERVIEWThe updated versions of MedDRA are both a strength of the terminology and one of its
greatest challenges. Earlier terminologies were not properly maintained nor were there
timely releases of these terminologies to address errors or medical advances. The
MedDRA MSSO was designed to address both of these issues. MedDRA is currently
provided to subscribers on a semi-annual basis utilizing a rigorous medical andtechnical review for each change request. MedDRA versioning is an issue since mostclinical trials run for extended periods of time (i.e., greater than 6 months) andregulatory reports also cover extended periods of time (e.g., Integrated Safety
Summary).
4.3

OPTIONS CONSIDERED

For coding with MedDRA in clinical trials, it is understood that many organizations may
not want to re-code data as frequently as MedDRA updates are available. As such, it isassumed that a project or a trial will “freeze” (i.e., utilize the same version of MedDRA
for the entirety of the project or trial) on a version of MedDRA and then optionally recode at a later milestone in the project/trial.
For purposes of this sectiondocument, a project is defined as a series of related
individual clinical trials. Therefore, when the term project is used in this section it isreferencing all of the subordinate clinical trials as a group.
There are several options available for versioning with relative merits and issues. A brief
discussion of the options follows:
Option 1 – “Freeze” at the initiation and for the life of a project and report with sameversion of MedDRA.
• All trials within the project would be coded with the same version of MedDRA.
• All reports would be generated with the same version of MedDRA.
• Supports consistency of coding and analysis within related trials.
• Reports and analyses performed are done within the context of the same versionof terminology in which the data were coded.
• Causes issues, especially for longer running projects, for the development of thelabel that will utilize a more recent version of MedDRA as well as not taking
advantage of MedDRA improvements with subsequent releases.
• Requires the storage of multiple versions of MedDRA and the maintenance of anorganization’s MedDRA coding conventions with each version of MedDRA.
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MedDRA Implementation and Versioning for Clinical Trials

Option 2 – “Freeze” at the initiation of a project and report with most recent version of
MedDRA.
• All trials within the project would be coded with the same version of MedDRA.
• All reports would be generated with the same version of MedDRA.
• Supports consistency of coding and analysis within related trials.
• The most recent version of MedDRA would be used for reporting utilizing thestructure of the most recent version. For example, if a PT moved from one HLT
to another in the version used for reporting, it would be output to a different HLT
than it was originally coded.
• Depending upon the length of the trials or project, the differences in versions
used to code and report could become more significant.
Option 3 – “Freeze” at the initiation of each trial within a project, and report with themost recent version of MedDRA.
• Coded trial data is coded in the most recent version of MedDRA.
• Less of a difference in time between the significant volume of trial data (Phase
III) and label development.
• Takes advantage of MedDRA improvements in subsequent versions.
• Depending upon the length of the trials or project, the differences in versions
used to code and report could become more significant.
Option 4 – Hold all coding to the completion of each trial and utilize the most recent
version of MedDRA for coding and reporting.
• Coding for the trial would likely be more consistent.
• Loads a significant workload stress at the end of each trial.
• Does not allow for any analysis of coded data to be performed prior to thecompletion of the trial.
Option 5 – “Freeze” at the beginning of each trial within a project and optionally re-code
data with the latest version at the conclusion of the trial based on criteria defined withinproject plan. Always output the data utilizing the most recent version of MedDRA.
• The organization would review the collection of changes against thresholds
developed and documented in the project plan. If there is a medical benefit to recoding the data, the data would be re-coded to the most recent version of
MedDRA. Otherwise, the reports are generated with the most recent version of
MedDRA.
• Long running trials would be updated and better analyzed with the latest version
of MedDRA.
• Less of a difference in time between the most significant volume of trial data
(Phase III) and label development.
• Project level reports would utilize the current version of MedDRA.
Option 6 – Re-code the trial data for all trials in a project on an ongoing basis with themost recent version of MedDRA.

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MedDRA Implementation and Versioning for Clinical Trials

•
•
•

4.4

All trial data would be updated with each version and would provide consistency
for reporting.
Removes reconciliation issues with post-market data since post-market data willreport with the current version of MedDRA.
Requires re-coding of all trials to be updated to the current version of MedDRA.

RECOMMENDATIONFor clinical trial data, the MSSO recommends Option 5 or 6 (described above). These
options are the feasible from an implementation standpoint and allow organizations tochoose which option is best for their process.

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Versioning Methodology

5. VERSIONING METHODOLOGY

5.1

PURPOSEThe purpose of this section is to describe the various versioning methods that may be
applied to data when an organization implements a new version of MedDRA.
5.2

OVERVIEW

Each organization should have a versioning strategy that should be documented. The
versioning strategy may differ between safety databases and clinical trial databases.
For example, there may be no need to update clinical trial data from older trials if thedata are not presently used or will not be used in the future. On the other hand,
postmarketing safety data may be required to be reported in the current (or nearcurrent) version of MedDRA, and version update recommendations then apply.
5.3

OPTIONS CONSIDERED

Users should choose the most optimal approach based on their organization’s
characteristics. The optional methods described below can be used to document theextent to which an organization has applied a new version of MedDRA. These methods
should not be interpreted as regulatory requirements but may be used to communicate
effectively between and within organisations.
The table below summarizes the types of versioning methods:

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Versioning Methodology

MethodDescription

Resource
Intensity

Data
Accuracy

1

Begin to use new version for coding new data;no recoding of existing data

Least

Least

2

Identify verbatim terms linked to non-current
LLTs and recode existing data

3

Identify verbatim terms linked to non-current
LLTs and recode existing data
andRecode verbatim terms to new LLTs that are
direct or lexical matches

4

Identify verbatim terms linked to non-current
LLTs and recode existing data
andRecode verbatim terms to new LLTs that are
direct or lexical matches
andRecode verbatim terms to new LLTs that are
more accurate concepts

↓↓
Most

Most

Table 5-1 Types of Versioning Methods
This list may not be inclusive; other versioning methods may be used. Depending on
how MedDRA data are stored in the database, additional steps may be needed toensure consistency in data retrieval and reporting, including medical review of the data
after the version method has been applied.
Note that Method 4 is the most resource intense and Method 1 is the least. There are
additional points to consider: recoding to LLTs that are new direct matches or moreaccurate concepts (Method 4) provides the most accurate data compared to the othermethods.
The MSSO and the Japanese Maintenance Organization (JMO) provide tools to assist
the user in comparing the changes between MedDRA versions. The Version Report(provided by the MSSO and JMO) is a spreadsheet listing all changes between thecurrent version of MedDRA and the one previous to it; this spreadsheet is provided witheach new release of MedDRA. The MSSO also provides the MedDRA Version Analysis
Tool (MVAT) that facilitates identification and understanding of the impact of changes
between any two MedDRA versions, including non-consecutive ones.

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Recommendations for the Implementation of MedDRA Supplemental Terms

6. RECOMMENDATIONS FOR THE IMPLEMENTATION OF MedDRA
SUPPLEMENTAL TERMS
6.1

PURPOSEThe purpose of this section is to provide the MSSO’s recommendations regarding theissue of utilization of MedDRA supplemental terms.
6.2

OVERVIEW

The maintenance of MedDRA by the MSSO was designed, and has been implemented,
to provide a rapid and accurate response to subscriber Change Requests. When
Change Requests are received by the MSSO, the subscriber receives an initialacknowledgement of the receipt of the request within 48 hours of receipt by the MSSO.
The Change Request is then processed through an international medical team, and a
final disposition is sent to the subscriber within 7-10 calendar days from initial receipt by
the MSSO. Approved Change Requests are designated as supplemental changes to
MedDRA and are posted on the MSSO website for review by all users. In the originalplan of the MedDRA Change Request process, it was anticipated that a situation mightoccur where, following a final pre-release review of the terminology, a supplemental
term may not be included in the next official MedDRA release; this has not happened todate. The MSSO has modified it processes so that, once a supplemental term is added,
it is considered part of the MedDRA terminology and will not be deleted.
There is, however, an issue with using supplemental MedDRA terms. Supplemental
releases are not considered “official” MedDRA releases. Organizations that use
supplemental MedDRA terms do so at risk. The risk is not that the term will not be
included in the next release of MedDRA, but that not all organizations and regulators
are able to accept them as current valid terms. From a regulator standpoint, the risk fora submitting organization will be a possible slow down in processing because thesubmission will be viewed as an exception. Exception processing may include manual
recoding or rejection of the submission. One needs to take into consideration thevalidation processing that is implemented as part of the acceptance of e-submissions
when forming a policy on the use of supplemental MedDRA terms in a filing.
6.3

RECOMMENDATIONSThe MSSO makes the following recommendations:
1. Organizations should use supplemental terms internally based on their businessneeds.
2. Organizations that share data with other organizations need to have a clear
understanding of the other organization’s position on the use of supplemental
terms.
3. Organizations submitting regulatory reports need to be aware of the receiving
regulatory agency’s position on the use of supplemental terms

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Recommendations for the Implementation of MedDRA Supplemental Terms

4. If a regulatory agency does not use supplemental terms, an organization should
limit use of supplemental terms for reporting.
5. If the use of supplemental terms is necessary, the organization should
coordinate its reporting with the regulator.

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