Cancer Care Engineering: A Collaborative Transformational Project

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

2. VA/IU Center for Implementing Evidence Based Practice, RI/IU Center for Health Services & Outcomes Research 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

3. CRC Cancer Care Engineering 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

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

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

6. CCE Enablers

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

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

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

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

13. CCE Milestones 9/05 9/06 5/07 7/07 4/08 10/08 3/06 11/06 6/07 3/08 6/08 11/08 WCCE-1 DOD IRB IU IRB SRC-1 IU IRB SRC-2 WCCE Proposal First NIH Proposal Initial DCCE Results Regenstrief CCE Funded Regenstrief CCE Proposal CCE is “Born” in Lebanon, IN Indy Foundations Presentation Washington WCCE Presentation

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

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