1. Vertex and CDISC / MBC / 12March2008 1. Vertex and CDISC Accomplishments and Strategy 12 March 2008 Lynn Anderson Associate Director Statistical Programming/Biometrics Pam Ryley, Associate Director Scott Moseley, Senior Director

2. Vertex and CDISC / MBC / 12March2008 2. Vertex and CDISC - Overview SDTM, ADAM (and CDASH) Operations and Submissions In-House and Out-Source Business Processes and Quality Architecture Technology and Tools

3. Vertex and CDISC / MBC / 12March2008 3. Vertex and CDISC - Overview CDASH – Clinical Data Acquisition Standards - FUTURE SDTM – Study Data Tabulation Model ADAM – Analysis Dataset Model

4. Vertex and CDISC / MBC / 12March2008 4. Vertex- CDISC – 2008 Goals - 50,000 ft Raw Data (If possible, close to SDTM/CDASH) SDTM Includes trial design and define.xml ADAM Operations  SDTM  ADAM  SDTM & ADAM  TFLs  SDTM loaded into WebSDM Submissions  SDTM  Annotated eCRF  Define.xml  ADAM  ADAM and Key Tables Programs

5. Vertex and CDISC / MBC / 12March2008 5. CDASH - 5,000 ft 1.Take CDASH into account when building clinical database Extracted ‘raw’ data is standardized for ‘easy’ transformation into the SDTM model Enabled by standardized eCRFs Applies to external data sources also (either integrated into the clinical database or not)

6. Vertex and CDISC / MBC / 12March2008 6. SDTM and ADAM - 5,000 ft SDTM datasets Specification – automation drives datasets development, review, and submission metadata Development – (In-House) SDLC – automation Review – WebSDM plus outside WebSDM Use for data review Use for developing ADAM datasets Use for analysis (with ADAM datasets) Submit to regulatory agency

7. Vertex and CDISC / MBC / 12March2008 7. SDTM and ADAM - 5,000 ft CDASH eCRF SDTM Study Data Clinical Database CDASH Study Data Build DB Extract Raw Data Transform To SDTM ADAM Study Data Analysis (TFL’s) Submit: Annotated eCRFs SDTM Datasets ADAM Datasets TFL’s Metadata (define)

8. Vertex and CDISC / MBC / 12March2008 8. SDTM Datasets Specification– 500 ft CDISC Master Domains Metadata Template (Enhanced with Vertex domains, columns, suppqual standards, and mapping logic) Plus CDISC Controlled Terminology Template Are Customized and Then Drive Specification of Conversion of Raw data into SDTM format Development of SDTM Datasets from Raw Data Review of SDTM Datasets for correctness against the standard and against the raw data Submission Metadata

9. Vertex and CDISC / MBC / 12March2008 9. SDTM Datasets Specification– 500 ft

10. Vertex and CDISC / MBC / 12March2008 10. SDTM Datasets Development – 500 ft Independent QC is incorporated into development whether in-house or outsource At Vertex this is an automation in progress – mapping and logic columns in the specification driver workbook also drive macro programming to create these datasets

11. Vertex and CDISC / MBC / 12March2008 11. Review of SDTM Datasets – 500 ft Review plan talks about strategy for review – this will differ between when we are outsourcing (more extensive) versus when we are developing datasets in-house (since tools in this case are validated and trusted by us) Use of WebSDM in this process gives added benefit of providing a single repository for our clinical trials data – AND gives an opportunity to conduct WebSDM-style safety review on single and pooled studies

12. Vertex and CDISC / MBC / 12March2008 12. Review of SDTM Datasets With WebSDM

13. Vertex and CDISC / MBC / 12March2008 13. Create ADAM datasets from SDTM 5.Develop ADAM datasets from SDTM datasets (and Protocol/SAP of course) 6.Develop TFL’s from SDTM and ADAM (Programming specifications) 7.Submission: SDTMs, SDTM annotated CRF, define.xml, ADAMs, TFLs, Key Programs for ADAMs and Tables

14. Vertex and CDISC / MBC / 12March2008 14. Out-Source versus In-House We want a single set of logical and consistent processes (supported by thorough repetitive training) but where does outsource versus in- house present a challenge? Anything about CDASH Development of SDTM Datasets Review of SDTM Datasets Other

15. Vertex and CDISC / MBC / 12March2008 15. SOP and Working Instruction Framework We are committed to develop & maintain a quality and business process framework that makes sense. While CDISC adoption is a unique effort from TFL’s production and FDR support and FDA submissions, we need these activities to all reference the same Systems Development Lifecycle Inversely, we need our Vertex Statistical Programming Systems Development Lifecycle to support all our departmental responsibilities

16. Vertex and CDISC / MBC / 12March2008 16. SOP and Working Instruction Framework Definition of Departments Biometrics = Biostats and Stat Programming Quality Software/System Development Life Cycle (SDLC) TFLsSAPS Interims Blinding CDASH SDTMs ADAMs Submissions WI’s Specification of SDTM SDTM Review WebSDM App & Study Config Macro Library Dev WebSDM App & Study Config

17. Vertex and CDISC / MBC / 12March2008 17. Future Directions Standardize processes more: revisit, improve Automate processes more: specification, raw data transformation to SDTM, more data review tools based on SDTM, create ADAMs, create metadata (define) Integrate processes and tools across the larger process more tightly Timings: create SDTM (including Trial Design) and define.xml earlier

18. Vertex and CDISC / MBC / 12March2008 18. Future Directions Extend training and distribute the CDISC understanding and tasks Continue improving quality framework – processes that are supported sufficiently by official documentation and that are clear and work across outsource scenarios