Vertex and CDISC / MBC / 12March2008 .

1

Vertex and CDISC Accomplishments and Strategy

12 March 2008

Lynn AndersonAssociate Director

Statistical Programming/BiometricsPam Ryley, Associate DirectorScott Moseley, Senior Director

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

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

Vertex and CDISC / MBC / 12March2008 .

4

Vertex- CDISC – 2008 Goals - 50,000 ft

Raw Data(If possible, close to SDTM/CDASH)

SDTMIncludes 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

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)

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

Vertex and CDISC / MBC / 12March2008 .

7

SDTM and ADAM - 5,000 ft

CDASH eCRF

SDTM Study Data

Clinical Database

CDASH StudyData

Build DB Extract Raw Data

Transform ToSDTM

ADAMStudy Data

Analysis (TFL’s)

Submit:

•Annotated eCRFs•SDTM Datasets•ADAM Datasets•TFL’s•Metadata (define)

Vertex and CDISC / MBC / 12March2008 .

8SDTM 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

Vertex and CDISC / MBC / 12March2008 .

9

SDTM Datasets Specification– 500 ft

CDISC_spec SAS Macro

Part 1 General SDTM

Specification

Part 2 Study

Specific SDTM

Specification

CDISC Master

Domains Workbook

PLUS

CDISC Master

Terminology Workbook

PLUS

WriteSpec.SAS

Part 3 Detailed SDTM

Specification

Vertex CDISC SDTM

Specification

Put pieces together into one document

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

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

Vertex and CDISC / MBC / 12March2008 .

12Review of SDTM Datasets With WebSDM

Data ReviewYesDatasets

Readyfor Review?

Augment Checks in

Accordance with Review

Plan

Create StudyCreate

Application

Review SDTM Errors

Load datasets

Assign Error Details to SDTM

Errors

Copy Datasets to Load Area

Create Directories in

Load Area

Receive Datasets

Yes

Preprocess Datasets

Feedback to SDTM

Dataset Developers

No

Download SDTM Errors

Successful Load?

Specify CDISC SDTM Datasets

Develop CDISC SDTM Datasets

Develop Review Plan for CDISC SDTM Datasets

21

No

3

4 5 6 7 8 9 10 11

14 16 1712 1513

18Accept

Datasets?

No

Yes

Assign Error Details to

SDTM Errors

19

Accept Datasets

20 21

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

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

Vertex and CDISC / MBC / 12March2008 .

15SOP 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

Vertex and CDISC / MBC / 12March2008 .

16SOP and Working Instruction Framework

Definition of DepartmentsBiometrics = Biostats and Stat Programming

Quality

Software/System Development Life Cycle (SDLC)

TFLsSAPS

Interims

Blinding

CDASH

SDTMs

ADAMsSubmissions

WI’s

Specification of SDTM

SDTM Review

WebSDM App & Study Config

Macro Library Dev

WebSDM App & Study Config

Vertex and CDISC / MBC / 12March2008 .

17Future 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

Vertex and CDISC / MBC / 12March2008 .

18Future 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