TRANSCEND

1. TRANSCEND caBIG CTMS and Imaging Workspace F2F March 19th, 2009 Translational Informatics Sorena Nadaf, M.S., M.MI Director Translational Informatics, CIO

2. TRANSCEND project TRANslational Informatics System to Coordinate Emerging Biomarkers, Novel Agents, and Clinical Data … “Informatics Integration”

3. Key Partners and Stakeholders UCSF • SorenaNadaf – PI • Laura Esserman – PI • Kathy Hajopolous – Project Lead • Sarah Davis – Project Mgt & I-SPY 2 • Meg Young – Project Manager • Nola Hilton – Imaging • Laura van' Veer – I-SPY 2 UC Davis • Mike Hogarth – Design Lead • Davera Gabriel - Ontologist UPenn • AngiDeMichele – Oncologist Georgetown • SubhaMadhavan – Tech Consultant MD Anderson • Kyle Wathen – Randomization Service Duke • PankajAgarwal – Architect Mentor SAIC-F • Nancy Roche – COTR Manager • Liming Shen - caTISSUE NCI • John Speakman – CTMS PO • Ian Fore – TBPT PO • Christo Andonyadis – CTMS • Denise Warzel – Program Mgt • John Koisch – Architect, COPPA • Anan Basu – caINTEGRATOR FDA • Linda Doody – CRO Regulatory 3rd Millennium • Brian Davis – VCDE Consultant CCSA • Dan Milgram – CRO Informatics • DonyaBaghari – CRO Mgt Tolven • John Churin – Architect • Tom Jones – CMO • Neil Cowles – Strategy Pure InfoDesign • Michael Moore – UI Consultant Ekagra • Kalpesh Patel – Integrations

4. TRANSCEND’s Top 10 Develop and deploy a nationally scalable Informatics Infrastructure to meet multi center adaptive design clinical trials Utilize NCI caBIG compatible tools and architecture in the design of the Informatics Infrastructure Demonstrate the use of web-based case report forms (CRFs) to facilitate data collection and transmission to the NCI Demonstrate how electronic clinical data collection can automate CRF generation Demonstrate the integration of an electronic health record system with an caBIG based translational research infrastructure

5. TRANSCEND’s Top 10 Continued Demonstrate the use of caBIG standards in the integration of a clinical care system with other caBIG tools (caINTEGRATOR, caTISSUE) Extend the caBIG standards for clinical data elements, using coded, controlled vocabularies Connect system interfaces in constructing a translational research platform spanning genomic / proteomic, radiographic, and clinical data Evaluate the efficacy of the TRANSCEND infrastructure in collecting high quality, real-time, and complete structured phenotypic data from next generation clinical trials Be “Adaptive” in Clinical Trials – Smart Clinical Trials

6. Being “adaptive” in trialsrequires technology to be “adaptive” • An iterative approach to evaluating therapeutic interventions/agents • Differs from traditional trials • Adaptive functional requirements • Study participants can be excluded from arms based on biological characterization of their tumors • Treatment Arms (ie, agents) added/removed throughout the trial – a “running trial” • Outcome “measures” can be modified as technology advances – leverage new biomarker assays as they are validated and become available

7. TRANSCEND Informatics • Key requirements for TRANSCEND • Fast and correct information capture • minimize ‘data cleaning’/scrubbing • Expedient access to study information • manage a multi-site trial as a single enterprise, not “multiple sites” • Facilitated information sharing • analysis of trial data by anyone who can connect…(after appropriate vetting and authentication / authorization)

8. TRANSCEND Requirements Manage the registration lifecycle Manage eligibility determination Randomize patients Track study participants Manage bio-specimens Capture clinical data at the point of care and render CRF’s using automated methods Provide most sites with Web-based traditional CRFs Manage patient calendars and treatment planning (CCP) Manage the Severe Adverse Event (SAE) lifecycle Provide for storage and retrieval of raw and interpreted data in a repository (caINTEGRATOR)

9. TRANSCEND Primary Components Automated transformation of data captured at the point of care to CRF-based reportable data Web Based CRF Clinical Data Capture within an electronic health record system Integration from electronic health record to Biospecimen Management and Tracking (caTISSUE) Integration to Adaptive Design Randomization Engine through a web-service AE / SAE Reporting and Management Storage of Array Data Storage and analysis of trial data

10. TRANSCEND caBIG Tools • caTISSUE Suite – Biospecimen Management and Tracking • caINTEGRATOR – Data Analysis Portal • caXchange – Facilitate Electronic Messaging • caARRAY – Micro Array data repository • ? caAERS ? – Adverse and Serious Adverse Event Reporting • caDSR – Where we will derive core set CDE’s required in the CRF’s • BRIDGE* – • HL7 Messaging System Interfaces • Using caXchange and HL7 friendly enterprise bus • When possible, align TRANSCEND information model with BRIDGE

11. TRANSCEND Vision & Primary Case Study • Encompasses: • Clinical Trial Patient Management • Patient Trial Registration • Biospecimen Management • Storage of raw test result data • Provisioning of a data analysis portal for Investigators to analyze trial results on an ongoing basis • Developed in Unison with I-SPY 2 • Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging And molecular analysis • Innovative multi-center adaptive breast cancer clinical trial • Studying use of Novel Agents, Biomarkers, and MRI in neo-adjuvant therapy for women who have locally advanced Breast Cancer • IDEAL test case for TRANSCEND

12. Background Summary for I-SPY1 2 Anthracycline Taxane ClinicalStudy I-SPY 1: (2002–Present) Surgery I-SPY 2: (2009–2012) I-SPY 1 evaluated biomarkers and imaging for predicting response to std neoadjuvant chemotherapy I-SPY 2 will evaluate phase II drugs in combination with standard chemotherapy in a neoadjuvant setting I-SPY 2 will use biomarkers to stratify patients based on their predicted likelihood of response to treatment I-SPY 2 will use imaging to measure response

13. caBIG’s CCTS

14. TRANSCEND Trial Infrastructure Mike Hogarth

15. TRANSCEND Deployment View Mike Hogarth

16. TRANSCEND Deployment View Mike Hogarth

17. TRANSCEND

18. Translational Informatics Program Enable the HDFCCC to optimize the translation of basic discoveries into practical clinical applications Deliver suite of services to support translational, biomedical, clinical research and clinical care improvement

19. System Design Michael Hogarth Laura Esserman Sorena Nadaf Subha Madhava Architecture Mike Hogarth John Koich Clinical Team Angie DeMichele Mary Lou Ernest Michael Moore Laura Esserman Project Management Kathy Hajopoulos Meg Young Trial Support Team Sarah Davis Meredith Buxton Technical Teams Tolven Team John Churrin Tom Jones Neil Cowles NCI caBIG teams caTISSUE, ca INTEGRATOR Subha Madhava Component Acknowledgments

20. Plug: 1st Annual Cancer Center Translational Informatics Conference University of California San Francisco Helen Diller Family Comprehensive Cancer Center October 2010

21. Questions and Answers