1. Cancer Care Engineering: A Collaborative Transformational Project Indiana University School of Medicine Purdue University

2. Cancer Care Engineering Project Leaders: Stephen Williams, MD HH Gregg Professor of Oncology Director, IU Cancer Center Associate Dean of Cancer Research Indiana University School of Medicine Bradley Doebbeling, MD Director VA CIEBP IU Cancer Center Director (RI, RCHE) Indiana University School of Medicine Joseph Pekny, PhD Professor of Chemical Engineering Director, e-Enterprise Center Founder, Regenstrief Center for Healthcare Engineering Purdue University Marietta Harrison, PhD Professor of Medicinal Chemistry Director, Oncological Sciences Center Associate Director Purdue Cancer Center Purdue University VA/IU Center for Implementing Evidence Based Practice, RI/IU Center for Health Services & Outcomes Research

3. Vision: Goal-oriented cancer research Approach: “Systems Analysis” for cancer prevention, detection, treatment and care delivery & project management Team: Over seventy physicians, caregivers, engineers, scientists and staff drive the CCE vision Cancer Care Engineering

4. CCE Strategy Indiana Cancer Care Understand Goal Oriented Improvement Model, Analyze, Communicate System Awareness Decision Support Tools CCE Hub Animal Models

5. CCE Pillars & Hierarchy The Integrated Pillars Mathematical Models Patient OMIC Analysis Health Services Research Cancer as a Managed Disease Cancer Care System Projects The Integrated Hierarchy Cancer Care Best Practice Projects Physician Tools Projects OMICS Projects

6. CCE Enablers

7. Modeling the Indiana Cancer Care System: A What-If Tool for the Big Picture Regulatory Agents Organizational & Regulatory Agents Patient Agents CRC Care System Indiana Cancer Care System Indiana Cancer Care Model What If Questions validate data What is the impact of screening rate improvement? Caregiver Agents What is the best strategy for using OMICS advances? What is the best strategy for colonoscopy screening? How can all patients with colonoscopy orders to follow-up get them? What resources are required?

8. Indianapolis CRC Quality Improvement Initiative Implementing evidence-based practices, including psycho- social services, and guidelines to deliver high quality care and outcomes – last step in translational research Within CRC care, screening, treatment, and surveillance tests after treatment are studied within primary and specialty care Interventions within two healthcare systems with well- integrated EMRs: Wishard / IUMG and VA (links to VA national initiative) Main project components and outcomes: –Cancer prevention and care process maps –Quality reports for Indianapolis clinics –Application of implementation research methods –Building a Cancer Care – Technical Assistance Program (CC- TAP), patterned after RCHE Healthcare TAP, to help implement best practices in one or more clinics –Understanding the barriers to best practice care

9. Connecting Research to Practice: Mechanistic modeling of polyp & CRC development Methods –Mutation network –Stochastic cell growth Predictions –Likely incidence with age Growth characteristics Transformation rates Applications –Adaptive modeling to individual patients Connection to “omics” measurements –Decision tree hypothesis testing –Identification of heterogeneous sub-populations

10. Personalizing Cancer Care: Data Driven Prevention/Treatment, “Omics”, & Measurement Driven Medicine Genetic Information Proteomics and metabolomics Normal Trajectory Cancer Trajectory malignancy What markers presage cancer? What markers are present with cancer? What markers indicate risk? Develop markers based on all information – integrated omics, clinical data What markers differentiate people? What resolution is possible? On which patient groups does Drug X work? Patient groups are indistinguishable with respect to treatment What dosage is best?

11. Patient Blood Genomic Analysis Lipidomic Metabolomic Glycoproteomic CCE Predictive Molecular Signatures

12. Personalizing Cancer Care: Data Driven Prevention/Treatment, “Omics”, & The Role of Dog Models Genetic Information Proteomics and metabolomics Normal Trajectory Cancer Trajectory malignancy What markers presage cancer? What markers are present with cancer? What markers indicate risk? What markers differentiate dogs? What resolution is possible? Well understood & controlled lineage Companion animals get care & study registration typical IT infrastructure prototype usable for humans Rapid knowledge acquisition cycle Insight to more genetically diverse humans, established animal model

13. 9/05 3/0611/06 9/065/07 6/07 7/074/08 WCCE-1 3/08 IU IRB SRC-1IU IRB SRC-2 6/08 DOD IRB 11/08 CCE Milestones 10/08 Initial DCCE Results Regenstrief CCE Funded Regenstrief CCE Proposal WCCE Proposal Washington WCCE Presentation Indy Foundations Presentation First NIH Proposal CCE is “Born” in Lebanon, IN

14. Cancer Care Engineering Current Funding Initiatives Walther Cancer Institute Foundation Engineering the Cancer System (R-CCE) Funded: $1.35M Regenstrief Institute 7/1/07-2009 Focused on Health Services Research Cancer Care Delivery, Modeling & Data Visualization, CCEHub Warfighter CCE (W-CCE) Funded: $2.4M DOD, 12/1/07-2011 Focused on Prevention, Molecular Signatures Sample Acquisition, OMIC Analysis, Data Modeling, Data Visualization, Literature Mining Funded: $0.2M 2007-2009 Dog-CCE (D-CCE) Regenstrief, PCC, DP, Engineering, Vet School Funded: $0.2M 2007-2009

15. CCE Future Harvest CCE Seed Projects –First Wave of Results Papers & Proposals Present Status & Plans to Indy Foundations –Presentation Proposal (August 14) –Presentation (Fall 2008) Take Results to Foundations & Expand Partnerships Iterative Refinement Evolve According to Results & Funding Realize Results in Care System