1. Confidential - Property of Navitas - 2015 Accelerate define.xml using defineReady - Saravanan June 17, 2015

2. Confidential - Property of Navitas - 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. Confidential - Property of Navitas - 2015 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. Confidential - Property of Navitas - 2015 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. Confidential - Property of Navitas - 2015 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. Confidential - Property of Navitas - 2015 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. Confidential - Property of Navitas - 2015 7 defineReady Stages The automated process involves three main stages – Setup and Configuration – Build and Generate – Reporting Setup and Configuration Reporting Verification / Review Step BuildGenerate

8. Confidential - Property of Navitas - 2015 8 Process Flow

9. Confidential - Property of Navitas - 2015 9  Project and Study setup configurations Process Flow (contd..)  Study related files  Submission Configurations Submission Type(SDTM/ADaM) Metadata Version Define XML version External Dictionaries Datasets (XPTs/Dataset) Annotated Blank CRF * Data Guide & Supplemental document * Derivation Document * Codelist files* Study setup Setup and Configuration

10. Confidential - Property of Navitas - 2015 10 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 Process Flow (contd..)

11. Confidential - Property of Navitas - 2015 11 Build Study Metadata Domain Metadata Variable Level Metadata Configure Value Level Metadata Configure Codelists Configure Computation methods Configure External Dictionary -- TESTCD -- PARAMCD -- CAT QNAM > Pre-loaded Codelist Code List Name Coded Value Decoded Value Sponsor-Defined Code List Name Coded Value Decoded Value Extended Codelist Code List Name Coded Value Decoded Value Computation Dataset Variable Name Computation Name Computation Method External Codelist Variable Name External Codelist Name Dictionary Version Process Flow (contd..)

12. Confidential - Property of Navitas - 2015 12 Study Specific Derivations Codelists Computation Origin Code list & Decoded values Role Origin Comments GMDCT DDCRF Build Process Flow (contd..)

13. Confidential - Property of Navitas - 2015 13 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 Process Flow (contd..)

14. Confidential - Property of Navitas - 2015 14  The XML generation engine will read the information from Input sheet and generate the define.xml and exception report (Level 2 Report) Generate Process Flow (contd..)  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  Also it will generate the Validation report to ensure that the generated XML matches with the standards, in terms of structure and content.  System will generate the define.xml based on the updated/provided inputs

15. Confidential - Property of Navitas - 2015 15  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 Process Flow (contd..) Reporting

16. Confidential - Property of Navitas - 2015 16 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. Key features

17. Confidential - Property of Navitas - 2015 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. Confidential - Property of Navitas - 2015 18 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 defineReady - Reports Configure Level 1 Reports Build User Friendly Reports (Domain Level, Variable Level, Value Level and Codelist ) Generate 1. Metadata INPUT EXCELS (Versioned) 2. Level 2 Reports Report Printable PDF

19. Confidential - Property of Navitas - 2015 19 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 defineReady – Reports (contd..) Project-wise Study-wise Stage-wise User-Wise

20. Confidential - Property of Navitas - 2015 20 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 defineReady – Mile Stones CRF Auto Annotator Reviewer Guide Generator Validation Checks

21. Confidential - Property of Navitas - 2015 21

22. Confidential - Property of Navitas - 2015 22 Thank You