CDASH Initiative: Status Update Bay Area CDISC Implementation Network Meeting - May 29, 2008 Rhonda Facile, Project Director, CDISC Dorothy B. Dorotheo, InterMune Mark Wheeldon, Formedix

Snapshot Overview CDASH Purpose & Scope Who Participated in CDASH How CDASH Developed? CDASH Domains – Where are we? CDASH Domains – New Ideas CDASH Variable Metadata CDASH Core Designations Practical Implementation of CDASH within CDISC ODM CDASH Goals

Snapshot Critical Path Opportunity #45 – Streamline data collection at investigative sites. Continuation of ACRO’s Initiative Started October 2006 Supported by a Collaborative Group of 17 organizations Core team of 15 members manages.. 11 working groups Groups with between 8-40 volunteers ~190 work group volunteers + additional reviewers (both nationally and internationally) 16 Safety data domains developed.. organized in 4 “Packages” Draft consolidated document now out for public review – April 2008

CDASH Purpose & Scope To develop a set of ‘content standards’ (element name, definition, metadata) for a basic set of global industry-wide data collection fields that support clinical research. The initial scope - ‘safety data/domains’. These safety domains cut across all therapeutic areas (TA independent). Follow CDISC Operating Procedure for Standards Development (COP-001).

Who Participated in CDASH? Team membership: Statisticians Medical Monitors/Clinical Scientists Regulatory Affairs Drug Safety Data Managers Clinical Study Coordinators Clinical Research Associates Investigators Clinical Program Managers Statistical Programmers Database programmers More multi-national input welcome. Participants in the CDASH Initiative Other = Academic Research Organizations, Government (NIH, NCI), Hospitals, Universities.

How was CDASH Developed? Start with Study Data Tabulated Model (SDTM) Focus on CRF Content, not CRF Layout Refer to ACRO CRF Samples (where available) Collect CRF samples Evaluate commonalities/differences of CRF samples Document data points included/excluded with justifications

How was CDASH Developed? Agree on basic data collection fields Map to SDTM Terminology - proposals shared with the Terminology Team Write definitions and completion instructions for clinical site and Sponsors Proceed to the next step in the Consensus Process

CDASH Domains – Where we are Package-1: AE CM DM SC Started Oct 06 Package 3: DA EX CO DV DS Started Mar 07 Package-2: IE MH SU PE VS Started Dec 06 Package-4: LB EG Started Jul 07 Consensus (Initial) Version Harmon- ized Released (Production) 1.0 Review TLC Collaborative Group OK Public Published & Out for Public Review – April 2008

CDASH Variable Metadata Question text for collection on the CRF. How to implement the CRF data collection variable Describes the purpose of the data collection field SDTM-IG conforming variable name (CDASH variables shaded) Aka CRF Completion Instructions CDASH Core Designations

CDASH Core Designations Highly Recommended A data collection field that should be on the CRF (e.g., a regulatory requirement (if applicable)). (e.g. Adverse Event Term) Recommended/Conditional A data collection field that should be collected on the CRF for specific cases (may be recorded elsewhere in the CRF or from other data collection sources). (e.g. AE Start Time) Optional A data collection field that is available for use if needed. (e.g. Were there any AE Experienced?) In SDTM, there are also 3 categories, REQUIRED, EXPECTED & PERMISSIBLE The two standards initiatives do not have same purpose/goal: SDTM is for submission, and CDASH is for data collection. There is not a one to one match in most cases. Highly recommended —fields that really need to be collected; basic fields that are or need to be collected on a CRF Recommended/conditional —collected on the CRF for specific cases e.g. collecting time for precision like in a phase 1 study when patients are confined in the study unit and it is impt. in analysis or it may be derived from other fields…less strong a recommendation Optional —a fields available for your use if your protocol needs it.

CDASH Domain – New Ideas Physical Examination (PE) Use PE form to record only whether or not exam was done Instruct Sites to record, Baseline Abn.: MH, Targeted MH or Baseline Conditions CRFs. Post baseline abn. or baseline conditions that worsened on AE CRF Inclusion/Exclusion (IE) Use IE form to collect only the criterion or criteria NOT MET for Inclusion/Exclusion criteria

CDASH Domain – New Ideas Protocol Deviations (DV) Avoid creating a protocol Deviations CRF because this information can often be derived from other CRF domains or system functionalities. Comments (CO) Avoid the creation of a General Comments CRF which collects unsolicited comments.

“Practical Implementation of Clinical Data Acquisition Standards (CDASH) in the CDISC Operational Data Model” Mark Wheeldon, CEO, Formedix Bay Area User Group, 29th May, 2008

Who are we? Involved with Standards since 2001 All our solutions are based on Open CDISC Standards CDISC Products and Consultancy Company Planning, Preparation and Implementation CDISC Services Products so you can use CDISC in house! Product Focus is on Study Specification and Design Tools Origin™ authoring tools to streamline Protocol to Submission Process Database Specification uses CDISC Operational Data Model Origin Study Modeller™ Submission Specification uses CDISC Define.xml Origin Submission Modeller™ Must work with and around existing processes/technologies Operational Data Model for EDC auto generation Existing internal analysis and reporting structures New or existing extract, transfer and load tools

How could CDASH be used today? Use as a Content Standard Off the shelf Case Report Form content Describes relationship between Operational Data and Submission Datasets CDASH represented within a proprietary file format Excel, Word, Proprietary EDC system format Potentially unstructured Use within Machine Readable Metadata CDASH represented in CDISC Operational Data Model Vendor neutral system independent format Hierarchical structure is ideal for re-usable library of Components

Benefits of using CDASH within the CDISC Models Library Development CDASH forms represented in CDISC Database Standard Safety Domains in CDISC Submission Standard Study Specification Using CDISC metadata to reduce study set-up time Automation of Electronic Data Capture Build Using CDISC ODM to reduce study build times Optimize Downstream Dataflow Operational data to submission Reduces mapping complexity Makes mappings re-usable

What is a CDASH-ODM Form Composed Of?

What is CDASH? What is it Not? Content Standard NOT a Model Database Variable Name, Definition, Question Text Instructions to the Site, SDTM Variable Mapping Core Designations is a killer feature Give clinical context on why something is collected Highly Recommended, Recommended/Conditional, Optional Clinical Perspective on data collection What is it not? One to one mapping with the SDTM AEYN not in SDTM AEBODSYS not in CDASH

ODM Building Blocks How does CDASH Relate? Clinical Database Variable Name Controlled Terminology CDASH CRF Label/Question CDASH Core (Highly Recommended)

CDASH Adverse Event Form in ODM No more hand building of this…

A Dedicated Authoring Environment for Each Standard… Origin Study Modeller™ Origin Submission Modeller™

Role Centric Visualizations – Clinician’s eCRF

Role Centric Visualizations – Data Manager’s Tabular Specification

Multi-Vendor Visualizations – PhaseForward

Multi-Vendor Visualizations - Medidata

Multi-Vendor Visualizations - Paper

Optimal Solution from Standardized Content to any EDC System I have an alternative to this diagram – this is new. Good because it brings in libraries ……

Optimizing Downstream Dataflows CDASH vs. Non CDASH Form Differences 1 1 2 2 3 3 4 4 5 5 6 6

Optimizing Downstream Dataflows CDASH vs Non CDASH SDTM Differences 1 1 5 4 5 4 6 6 2 2 3 3

Conclusions CDASH-ODM Delivers Today Library Development CDASH brings clinical perspective CDASH links to SDTM to bring a submission perspective Quickly settle disputes over content Streamline Study Set-up and EDC Build Process Eliminate manual study specification Study Spec from 492 hrs down to 158 hrs (3x shorter) 30-40% build time reductions Downstream Raw Data to Submission Dataflow Optimisation Consistency between Operational Data and Submitted Datasets Reduction in mapping complexity – quick to create Mappings easier to maintain

CDASH Goals Finalize and Post CDASH final draft for public review CDASH Roadshow & Training program. Finalize and Post CDASH V. 1.0 on CDISC.org. Develop and Publish CDASH-ODM metadata Establish subgroup, Scope, Deliverables, Participants and Timelines Identify and Collect feedback from “Early Implementers” “CDASH” New SDTM Domains as required.

Strength through collaboration. PLEASE VOLUNTEER!!! 32 32