Washington, D.C. February 19, 2004

1. caBIG Workspace Clinical Trial Management Systems Washington, D.C. February 19, 2004

2. C3D Requirements (in no particular order) • Rapid study implementation using Library of template CRFs based on caDSR CDEs and EVS terminology • Patient centric view of clinical data via C3PR • Select patient by name • Longitudinal view of patient data across studies • Eliminate duplicate data entry & maintain data integrity • Ensure data security and patient confidentiality • Web based remote data entry • Automated clinical (lab) loading process • Automated lab grading according to CTC • Automated generation/extraction for electronic submission to monitors and regulators • Robust data cleaning • Data entry validation • Post entry discrepancy management

3. Library of Template CRFs Built with CDEs • Forms and CDEs defined in caDSR • Template CRF layouts defined as PDF

4. Oracle Clinical Facts (or Why Oracle Clinical?) • Fully web-based internet architecture: Study definition & Data collection • Built in test environment – eliminate need for redundant development • Build study once • Test/train simultaneously with production data entry • Best of breed COTS solution • Used by 8 of top 10 pharma (Merck, J&J, Glaxo, Pfizer, Bristol, Roche …) • Used by 75% of CROs (Quintiles, PPD, Omnicare, ICON …) • 21 CFR part 11 compliant • Username and password protected • Complete time (and user) stamped audit trail including (soft) deletes • Verbatim data collection supported • Study, site, role, user level security • Standards enforcement via Global Library • Questions and Discrete Value Lists must be defined here before use in study

5. Oracle Clinical Facts - Continued • Flexible data entry from single form definition (PDF) • Electronic PDF data entry • Hand entry on printed PDFs • Batch data loading from electronic sources • Published Workflow, Image and Data Capture APIs • Interface for “Programmerless” validations, edit checks and derivations • Point of entry validation: bounds, LOVs, data type, precision, etc.. • On-line validation: multi question checks preformed on commit by form • Off-line validation: run nightly, complex validation (multi question, form, visit) • Robust discrepancy management • Discrepancy reports categorize by site, investigator and/or CRF • Data changes sensed and validations rerun to automatically resolve discrepancies • Negotiations/partnership with Oracle allow extension of HHS 80% discount to cover: • caBIG participants • Specialized Programs of Research Excellence (SPORES) • North American Brain Tumor Consortium (NABTC) • American College of Radiology Imaging Network (ACRIN)

6. C3D Limitations • Built around proprietary technology – Oracle, 9iAS, Forms, PL/SQL • NCICB is pushing Oracle to provide complete metadata APIs • Currently not supported on Apple Mac OS • No JInitiator for Mac • All data stored as character – limited to 200 characters • No database level support for data types • Date and Numeric type checking at data entry – can be overridden by “verbatim” data • No notion of HL7 – yet • Oracle newly released Healthcare Transaction Base (HTB) • HTB persist HL7 v3 XML messages in Oracle relational DB • NCICB is considering pilot project with Oracle to “integrate” HTB and caCORE • NCICB working with Oracle to define integration of HTB and OC

7. C3D Integration of caDSR Metadata with OC Global Library • Questions asked on OC Study CRFs are restricted by metadata specifications contained in the Global Library (GLIB) • NCI has its own metadata repository in the caDSR • OC has been integrate with caDSR metadata via open source scripts and procedures caDSR ObjectGLIB Component • Common Data Elements Questions • Enumerated Value Domains Discrete Value Groups (DVG) • Enumerated by reference Thesaurus DVG (external sources) • Permissible Values Discrete Value Short Values • Value Meanings Discrete Value Long Values • Form TBD Data Collection Module (DCM) • Form Module/Block TBD Question Group • New OC API added to base product to allow connection to central patient registry

8. Oracle Clinical 4.5 RDC CRF Matrix • Header identifies Database, User, Site & Study • Tabs identify Visits/Phases • Planned CRF pages for each visit define column headers • Unplanned pages can be added • Left column identifies Patients by position number and initials • Matrix cells indicated state of CRF page for each patient • Colors indicate discrepancy status • Red - this user’s problem • Yellow - other user’s problem • Checks indicate Verification and Approval status • Lower section of screen provides access to Summary, Discrepancy details &Audit Trail

9. RDC 4.5 Graphic Layout PDF Style Data Entry • It looks like paper • Less training • PDF globally accepted • PDF endorsed as submission vehicle • Available on wireless tablet

10. RDC 4.5 Graphic Layout (PDF) • Combs • Images • Logos • Adobe plug-in • RDC Toolbar • PDF is background • Only requires Reader • Data stored the same way

11. C3D CDE Compliance Review • View distinct responses collect by Study • Provides visibility of data compliance • Row 13, Response “0” is not compliant • This value is flagged by OC as a Univariate DVG discrepancy because the value is not in the list of acceptable values • Discrepancy can be resolved automatically by audited change of data (with change reason and comment)

12. C3D GLIB Questions linked to caDSR CDEs • Dynamic report implements link to CDE Browser details • Provides CDE Id and Version • Double click CDE Link column opens new CDE Browser with CDE Details

13. C3D Deployment/Development Status • Deployed into production January 2003 • ~30 existing studies with ~500 patients implemented to date – still working on back log • All new studies implemented as approved by the IRB • ~40/year expected • ~4 so far this year • 4 accruing studies (and data) migrated from legacy systems (netTrials) • 3 extramural studies in various states on implementation • NIH lab data automatically loaded daily using generalizable process • Source labs mapped to LOINC like OC lab test names • Specific lab tests placed on CRFs as required by study • Patients matched by MRN across studies and labs loaded to more than one study depending on date window (Pre-study -> Off study + 30 days) • Labs accurately graded according to Common Toxicity Criteria (v2 & 3) • Automatic extraction/generation of data for electronic submission to monitors (CTMS, CDUS) • Access to study data in unified template based reports • ~10 new CDE based CRF templates added to library

14. caBIG Adoption Scenarios • Scenario 1 – Central NCI hosted ASP Model • No license or maintenance fees for caBIG pilot participants • No server hardware costs • No application support costs • Protocol building services provided at no cost for caBIG pilot participants • Client hardware required - Windows PCs • Scenario 2 – Local center installation • 80% discount on license fee - $3000/named user • Annual maintenance 80% of license - $600/year/named user • Hardware & application support costs • Protocol building service costs TBD (per hour, per form, per study?)

15. Questions?