1. N o r t h A m e r i c a E u r o p e A s i a / P a c i f i c L a t i n A m e r i c a A f r i c a 1 Generating Define.xml at Kendle using Definedoc TM Presentation at the CDISC German Speaking User Group Face To Face Meeting Emöke Merli, 11Mar2010

2. N o r t h A m e r i c a E u r o p e A s i a / P a c i f i c L a t i n A m e r i c a A f r i c a 2 Define.xml Generation Process Overview 4 Steps to Define.xml Definedoc TM Software Outline

3. N o r t h A m e r i c a E u r o p e A s i a / P a c i f i c L a t i n A m e r i c a A f r i c a 3 Define.xml Generation Process Overview

4. N o r t h A m e r i c a E u r o p e A s i a / P a c i f i c L a t i n A m e r i c a A f r i c a 4 Kendle SDTM Validation Checks Based upon WebSDM TM edit checks as published on the CDISC website Based upon Janus guideline 'SDTM Validation Specification' as published on the FDA homepage Based upon OpenCDISC Rules Additional SDTM validation checks implemented by Kendle

5. N o r t h A m e r i c a E u r o p e A s i a / P a c i f i c L a t i n A m e r i c a A f r i c a 5 Define.xml Checks and QC Kendle SAS ® macros and programs for check of define.xml specific content (in addition to the Kendle SDTM Validation Checks) Define.xml syntax validation against the CDISC schemas using Eclipse Xerces XML parser Manual check of define.xml file (e.g. hyperlinking)

6. N o r t h A m e r i c a E u r o p e A s i a / P a c i f i c L a t i n A m e r i c a A f r i c a 6 4 Steps to Define.xml

7. N o r t h A m e r i c a E u r o p e A s i a / P a c i f i c L a t i n A m e r i c a A f r i c a 7 1.Include all files in correct directory and run Definedoc TM to generate initial define.xml file 2.Run SAS ® programs to include information from Excel ® metadata specification document into SAS ® working file and to perform checks 3.Run Definedoc TM for the second time to generate an updated define.xml file by including the metadata from the SAS ® working files 4.Run SAS ® programs to modify the layout of the define.xml and define.xsl files and to perform checks 4 Steps to Define.xml

8. N o r t h A m e r i c a E u r o p e A s i a / P a c i f i c L a t i n A m e r i c a A f r i c a 8 Final Define.xml Example

9. N o r t h A m e r i c a E u r o p e A s i a / P a c i f i c L a t i n A m e r i c a A f r i c a 9 Product of MetaXceed Co. Ltd. User interface based on SAS ® Automatically captures metadata available in SAS ® datasets (XPT or SAS7BDAT) Metadata not available in SAS ® datasets is entered manually Creates define.xml (also PDF, RTF and XLS) Definedoc TM - Software

10. N o r t h A m e r i c a E u r o p e A s i a / P a c i f i c L a t i n A m e r i c a A f r i c a 10 Define project and study Define input SAS ® datasets (CDISC order) Define source data path Define output file (e.g. define.xml) Define output library Define order of variables (e.g. natural order) Definedoc TM – Data Definition Screen

11. N o r t h A m e r i c a E u r o p e A s i a / P a c i f i c L a t i n A m e r i c a A f r i c a 11 Define project and study Define input SAS ® datasets (CDISC order) Define source data path Define output file (e.g. define.xml) Define output library Define order of variables (e.g. natural order) Definedoc TM – Data Definition Screen

12. N o r t h A m e r i c a E u r o p e A s i a / P a c i f i c L a t i n A m e r i c a A f r i c a 12 Define text that will appear in define.xml title Define relative link to XPT files Define CRF location and name Define layout Definedoc TM – General Information Screen

13. N o r t h A m e r i c a E u r o p e A s i a / P a c i f i c L a t i n A m e r i c a A f r i c a 13 Define project and study Define input SAS ® datasets (CDISC order) Define source data path Define output file (e.g. define.xml) Define output library Define order of variables (e.g. natural order) Definedoc TM – Data Definition Screen

14. N o r t h A m e r i c a E u r o p e A s i a / P a c i f i c L a t i n A m e r i c a A f r i c a 14 Define dataset metadata Define variable metadata Click on ‘Value Level‘ button to define value-level metadata Definedoc TM – Edit Definition Screen

15. N o r t h A m e r i c a E u r o p e A s i a / P a c i f i c L a t i n A m e r i c a A f r i c a 15 Define dataset metadata Define variable metadata Click on ‘Value Level‘ button to define value-level metadata Definedoc TM – Edit Definition Screen

16. N o r t h A m e r i c a E u r o p e A s i a / P a c i f i c L a t i n A m e r i c a A f r i c a 16 Definedoc TM - Output FileDescription define.xmlXML file define.xslStylesheet corresponding to XML file _define.sas7bdatDefinedoc TM working file containing information (dataset and variable metadata) for define.xml generation _define_bak.sas7bdatBackup of _define.sas7bdat file _definea.sas7bdatAudit trail _definea_bak.sas7bdatBackup of _definea.sas7bdat file _defineco.sas7bdatDefinedoc TM working file containing information (value-level metadata) for define.xml generation icon1.gif, icon2.gif, icon3.gifPictures for navigation bar Definedoc TM generates the following files in defined output library

17. N o r t h A m e r i c a E u r o p e A s i a / P a c i f i c L a t i n A m e r i c a A f r i c a 17 Contact –Emöke Merli: merli.emoeke@kendle.com Tel: +49 (0) 89 99 39 13 - 181 Reference –MetaXceed Home http://www.meta-x.com/definedoc/index.htmlhttp://www.meta-x.com/definedoc/index.html –“Creation of define.xml at Kendle using Definedoc TM : implementation, obstacles and enhancements“ Paper published in Pharmacoutical Programming Journal by Maney, Volume 2, Number 2, December 2009, pp. 65-75(11) Questions?

18. N o r t h A m e r i c a E u r o p e A s i a / P a c i f i c L a t i n A m e r i c a A f r i c a 18 Real people. Real results. ®