1. Accelerate define.xml
using
defineReady
- Saravanan
June 17, 2015

2. Agenda Introduction – define.xml Current situation Why defineReady?
defineReady Stages
Process Flow
Key features
defineReady - Reports
defineReady – Mile stones
Questions and Answers

3. Introduction - Define.XML
The FDA reviewer requires a document which navigates through the study data presented in individual dataset. CDISC define.xml is the one such document which describes the structure and content of clinical data in a machine readable format for electronic submissions of CDISC datasets, such as SDTM and ADaM.
The define.xml describes metadata in 5 Levels:
Table Level Metadata
Variable Level Metadata
Value Level Metadata
Controlled Terminology
Computational Algorithm

4. Current situation
Daunting and time consuming job in terms of collecting the CRF pages, handling the Origin, codelists, valuelists and study specific derivations.
Requires multiple eyes on each area like metadata repository building, handling sponsor defined data along with standards
Also it requires a lot more in-depth understanding in terms of other technologies like XML, Style Sheets, SAS®, interacting with PDF/RTF/XLS and also important to adhere standards of CDISC/FDA.

5. Current situation (contd…)
Receive files from Sponsor
Run OpenCDISC for xpt files
Convert XPT to SAS datasets
Split Dataset if XPT size > 1 GB
Create destination in CRF
Input sheet preparation
Generate Define XML
Review Define XML
Run OpenCDISC for define XML package
Sign-off

6. Why defineReady?
defineReady is an automated solution that will help generate the define.xml to meet the FDA requirement in a regulated environment with greater accuracy and integrity.
Predefined process with the minimal user interaction.
Ease of use.
No need of technology experts to generate a define.xml.

7. Setup and Configuration
defineReady Stages
The automated process involves three main stages
Setup and Configuration
Build and Generate
Reporting
Setup and Configuration
Reporting
Verification / Review Step
Build
Generate

8. Process Flow

9. Process Flow (contd..) Project and Study setup configurations
Setup and Configuration
Project and Study setup configurations
Study setup
Datasets (XPTs/Dataset)
Annotated Blank CRF*
Data Guide & Supplemental document*
Derivation Document*
Codelist files*
Study related files
Submission Configurations
Submission Type(SDTM/ADaM)
Metadata Version
Define XML version
External Dictionaries

10. Setup and Configuration
Process Flow (contd..)
Setup and Configuration
System will execute the pre-loaded confirmation rules (Level 1 – Metadata Checks) to ensure the submission data meet the standards
System will generate the exception report grouped by domain and severity
Identifies a column that was described in the domain description but not included in the SAS dataset for that domain
Identifies a column where the expected datatype inferred from the description file does not match the actual datatype in the dataset
Identifies a column listed in the domain description as Required ('Req') but not included in the SAS dataset for that domain
Identifies a column listed in the domain description as Expected ('Exp') but not included in the SAS dataset for that domain
Identifies a column that appears in the SAS dataset but is not listed in the domain description
Identifies a variable where datatype in (study specific) description is not consistent with datatype implicit in SAS dataset
Identifies a variable present in SAS dataset but not present in (study specific) description file
Identifies a domain that is referenced in a description file but for which there is no source data
Identifies a variable whose description does not match the standard label
Identifies a variable that has been deprecated according to the CDISC SDTM standard
Identifies a domain for which metadata has not been provided

11. Process Flow (contd..) Build Computation External Codelist QNAM Build
Domain
Metadata
Pre-loaded Codelist
Code List Name
Coded Value
Decoded Value
Sponsor-Defined
Extended
Codelist
Computation
Dataset
Variable Name
Computation Name
Computation Method
Study Metadata
Variable Level Metadata
--TESTCD --
PARAMCD
CAT
QNAM
<< USER >>
Build
Configure External Dictionary
Configure Value Level Metadata
External Codelist
Variable Name
External Codelist Name
Dictionary
Version
Configure Computation methods
Configure Codelists
Domain
Domain Label
Purpose
Repeating
Is Reference Data
Structure
Domain Keys
Class
Is Custom Domain
Domain
Variable
Label
Order Number
Data Type
Length
Significant Digits
Display Format
Origin
Comment
Mandatory
Role
Dataset
Where
Element
Derivation
Origin

12. Process Flow (contd..) Build GMD CT DD CRF Study Specific Derivations
Codelists
Computation
Origin
Code list & Decoded values
Role
Comments
GMD CT DD
CRF

13. Process Flow (contd..) Build
System will generate the combined metadata information, which user could be extracted in the form of Excel (Input sheet)
Input sheet includes Domain Level Metadata, Variable Level Metadata, Value Level Metadata, Control Terminology, Computational Algorithms and External Codelists

14. Process Flow (contd..) Generate
The XML generation engine will read the information from Input sheet and generate the define.xml and exception report (Level 2 Report)
The Level 2 exception report is reviewed by the Analyst and study specific documents are updated. The system will then generate a versioned Input sheet
System will generate the define.xml based on the updated/provided inputs
Also it will generate the Validation report to ensure that the generated XML matches with the standards, in terms of structure and content.

15. Process Flow (contd..) Reporting
Final submission package is ready along with the required supporting files
Generating Define.PDF to get a printable version of define.xml
Generate management reports

16. Key features
Pre-loaded Global Metadata repository to support all SDTM/ADaM versions.
Able to handle the multiple versions of define.xml (various versions of style sheets for the respective submissions of ADaM and SDTM).
System will support the sponsor defined code lists along with pre-loaded standard codelist provided by National Cancer Institute.
System will auto import the derivation documents and annotated CRFs.
System will support CUSTOM domains and SPLITTING of large datasets.

17. Key features (contd..)
System can read the CRF origin from the annotated CRFs and cross check against the origins provided.
Provided standards to reference Data guide & Supplemental document
Handling pre-loaded standard codelists, Sponsor defined codelists and Extended codelists
System will automatically populate the Value level and codelist level information
Able to support multiple versions of Input excel and also multiple versions of define xml.
System will also help us to generate the printable version of define XML where known as printable PDF

18. defineReady - Reports
System will generate the reports at each stages to ensure or give the flexibility to the user to make a decision
Overview of the reports generated by each stage
Configure
Level 1 Reports
Report
Printable
PDF
Build
User Friendly Reports (Domain Level, Variable Level, Value Level and Codelist )
Generate
1. Metadata INPUT EXCELS (Versioned)
2. Level 2 Reports

19. defineReady – Reports (contd..)
System will also generate the reports which will be used for audit trial purpose and help us to identify the project status
Overview of the generated Reports by System Level
Project-wise
Study-wise
Stage-wise
User-Wise

20. defineReady – Mile Stones
List of features will be added to the defineReady in a near feature, where it will help and support our submission package in an effective manner
CRF Auto Annotator
Reviewer Guide Generator
Validation
Checks

22. Thank You