Demystifying Define-XML Codelist Handling for Nonclinical Studies

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Project Overview

The goal of this project is to provide recommendations for specific problems/questions encountered, when fulfilling the define.xml codelist section for a nonclinical study.

The project will be initiated by defining a specific list of issues/concerns/questions/challenges related to nonclinical codelist in define.xml to be explored.

It will then include an exploration of published general information (clinical or nonclinical) about implementing codelists in define.xml and relating this to specific challenges expressed by nonclinical data stakeholders. It will also include exploration of how codelists are used by the FDA as a consumer of the nonclinical define.xml file.

The result of this project is expected to be recommendations to the public on best practices for fulfilling codelist section of the define.xml for SEND study submissions.

Deliverables are expected to be poster(s) for the 2018 CSS; published recommendation on the SEND Implementation Wiki and a white paper may be warranted as well.

This project will not include education in the define-xml standard, generally how to create define.xml files, or any survey or analysis of define-xml tools. It will focus solely on codelist content. Participants should have a working knowledge of the define-xml standard.

Project Leads

Jennifer Feldmann Co-Lead Epreda
Kathy Brown Co-Lead Sanofi

Project Members

Anne Cecilie Engsig Nordisk
Melissa Rowley GSK
Joanne Hudson Covance
Steve Polley GSK
Susie Lendal Antvorskov Data Standards Decisions
Christy Kubin MPI Research
Jose Orellana Nordisk
Tim Gartner Lilly
Matt Hayes Genentech
Ying Li CRL
Anne Lindberg Roche
Carrie Neeley Covance
Michael Rosentreter Bayer
Catherine Roy Merck
Audrey Harris Charles River
Florence Halbert Novartis
Gitte Koch Ullman Novo Nordisk
Jessica Hawes FDA
Wenxian Wang Xybion
Tania Strimple Covance

Project Updates

Provide project updates in this section.
Date: Description of Update

Objectives and Timelines

List proposed project deliverables and timelines.

Objective Timeline
Call for Participation 13 Sep 2017
Kick-Off Meeting 29 Sep 2017
Establish list of issues to be addressed 10 Nov 2017
Identify Research Material Timeline 4
Establish subteams to identify potential recommendations for each issue Timeline 5
Full Team Review/Acceptance of all recommendations complete Timeline 6
Coordinate with SEND Implementation Wiki subteam for publication of recommendations Timeline 7
Complete Poster for 2018 PhUSE CSS Timeline 8

Project Activities

This section can document project activities or serve as a jumping off point to other pages in the project.

Published Resources

CDISC Define-XML Specification Version 2.0

CDISC Define.xml Implementation Wiki - Working with Controlled Terminology

FDA Study Data Business Rules
Note specifically FDAB035 The definition of datasets, variables, and codelists in define.xml should reflect the actual study data.

Understanding the define.xml File and Converting It to a Relational Database
Lex Jansen, Octagon Research Solutions, Wayne, PA
SAS Global Forum 2010

PharmaSUG 2016 - Paper DS16 Codelists Here, Versions There, Controlled Terminology Everywhere
Shelley Dunn, Regulus Therapeutics, San Diego, California

From the November 2017 Study Data Technical Conformance Guide: "For variables for which no standard terms exists, or if the available terminology is insufficient, the sponsor should propose its own terms. The sponsor should provide this information in the define.xml file and in the SDRG."


From CDISC Define-XML Specification Version 2.0, Section 4.3

The term “Controlled Terminology” in the context of a study refers to the set of all allowable values across all variables that have finite sets of allowable values in the study. A “Codelist” is a unique subset of the controlled terminology to which one or more variables are subject. Beginning with SDTM Version 1.2, the SDTM-IG requires controlled terminology for many SDTM variables. For some variables, sponsor-specific controlled terminology is recommended. All controlled terminology used in a study must be provided within the Define-XML document. Each codelist referenced by a study item shall be represented in the Define-XML document using a CodeList element.

Questions about Define.xml Codelists

Member Questions

A. General Questions to Address

1. How is the define.xml file currently being used in nonclinical (by FDA, Sponsors, CROs, system vendors)? What are possible uses (and thus valid reasons for providing codelists in define.xml)?

2. What variables, other than those that have associated CDISC codelists in the SENDIG, must/should have user-defined codelists in define.xml? What are the criteria for determining this?

3. What are the criteria for determining what terms are included in a codelist? Is the criteria different when a published codelist is referenced?

  • When are all possible terms included? Consider scoring scales such as are used in FOBs, dermal and ocular observations; pH scale; semi-quantitative urinalysis results; severities that use CDISC CT like MISEV; severities that do not use CDISC CT such as CLSEV; subsets of the NY codelist.
  • When are only terms used on the study included?
  • If some codelists contain all possible terms (rather than just the terms used on the study) should the rationale be documented somewhere (define.xml comments and/or nSDRG)?
  • Is there a case where only user-defined extensions of CDISC terminology are included, and published CDISC terms are excluded?
  • Should the codelist included in define.xml align with the menu selections available during data collection (which would be the "allowed" terms?
  • Is a free-text term added during collection represented any differently than a selected from a menu during collection?
  • Can you include user-define terms that are used on the associated study, but may be used on a different study, in a codelist? It may be that it is more convenient when creating the define.xml to always include a specific list of terms whether or not they were used on the study.
  • When should user defined codelists (nonCDISC codelists) be included in the define file?
  • Are the criteria "shoulds" or "musts"?

4. How should published CDISC CT codelists associated with multiple variables be referenced in define.xml (UNIT, NY for example)? More specifically, when can a codelist be shared across multiple variables and when should a unique codelist be referenced?

  • For example, if body weights, body weight gains and food consumption are all in grams, can BWORRESU, BWSTRESU, BGORRESU, BGSTRESU and FWORRESU all reference a codelist UNIT_G that contains only "g"?
  • If the protocol list of required tissues for gross and micro are different, should there be two different codelists referenced, each with only the list of required tissues for the type of observation? If so, how are required tissues related to a specific sex and death status represented? How are tissues added to the required tissue list (due to findings present) represented? Since the CDISC SPEC codelist contains tissues for any species and sex, presumably the entire SPEC codelist can never be used on a stud?
  • When a variable entry contains more than one value (separated by a semi-colon) do you include two entries in the codelist? or one entry with both terms?

5. Is there any specific naming convention that should be used for codelists? Are there any restrictions on naming (special characters)?

  • for codelists that contains a subset of published controlled terminology?
  • for user-defined codelists

6. When should a Display Value (Decode) be included with each codelist term? Codelist entries that have a decode are included in the define.xml with CodeListItem rather than EnumeratedItem

  • When should CodelistItem be used and when should EnumeratedItem be used?

  • What should be in the Decode field?

7. If a term is entered via free text during data collection (i.e., it was not an "allowable" term predefined for selection) is it represented in the codelist any different than terms that were in an allowable list?

8. Should user defined codes use the CDISC code if it exists in a future CT package, or should it use a nonstandard code? It is understood that this would still be an extended term to the CT package used to generate the dataset.

9. If abbreviations are included as findings in a report, should be abbreviations be in ORRES, then included in a codelist with a definition (decode), which would be similar to how the report is presented (abbreviations in the body of the report with a separate explanations page/key)? Or should the abbreviations be replaced with the meanings in the ORRES? What about abbreviations in modifiers that do not have controlled terminology or in comments?

10. Is there a list of know issues or help with troubleshooting Pinnacle21 checker results?

11. What is the appropriate way to indicate that no external codelists were used?

12. What guidance for industry can we give for use of information in the define.xml file that is associated with a SEND dataset?

13. Can an original term that has been translated to controlled terminology, be included in the define file to aid in traceability to the study report? Is that a decode or something else?

Use Cases for Codelists in a Nonclinical Define.xml

1. As a reference to determine what different codes, terms and acronyms mean (Jessica)

2. To check conformance, comparing the terms in a define.xml codelist with terms in a published codelist to identify errors such as failure to use a required codelist, systematic capitalization errors, or extending a nonextensible list (Elaine)

3. To identify extensions to published terminology to ensure that the definition of each extension is provided and is clear (Jen)

4. To ensure definitions of terms in user-defined codelists are provided and clear

5. To see the relationship between collected terms and published controlled terminology that the collected term has been translated to (Jen)

6. To make the SEND datasets clearer

Meeting Minutes

29 September 2017 Minutes

13 October 2017 Minutes

27 October 2017 Minutes

10 November 2017 Minutes

8 December 2017 Minutes

05 January 2018 Minutes

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