The document discusses the need for personalized health care as the key to meaningful health care reform. It outlines how medicine has progressed from focusing on single factors to understanding disease as complex with multiple interacting factors. Personalized health care involves using tools like genomics, biomarkers and clinical risk models to quantify individual health risks, monitor disease progression, select targeted therapies, and create personalized health plans and treatment timelines. The document provides an example of how this approach could be used to create a personalized cancer care plan.

1. Personalized Health Care: The Key to Meaningful Health Care Reform Ralph Snyderman, MD Chancellor Emeritus, Duke University Johanna and Ralph DeStefano Personalized Health Care Conference Ohio State Medical Center October 6, 2011 ©2011 RALPH SNYDERMAN

2. Medicine Pre-1900 ©2011 RALPH SNYDERMAN

3. Science and Medicine 1900s Germ Theory Chemistry Physiology Pathology Physics 2000s Genomics Proteomics Metabolomics Systems Biology Informatics Micro/Nano Processing Find It Fix It Predict It Personalize It Understanding Disease Understanding Health, Disease and Complexity ©2011 RALPH SNYDERMAN

4. Concepts of Disease Emergence: Multiple factors Reductionism: Single factor Baseline Risk Environmental Factors Preclinical Progression Disease Initiation Disease Progression Irreversible Damage Causative Factor Disease ©2011 RALPH SNYDERMAN

5. Concepts of Disease Emergence: Multiple factors Reductionism: Single factor Baseline Risk Environmental Factors Causative Factor Disease Enhance Health and Well-Being ©2011 RALPH SNYDERMAN

6. Initiating Events Disease Burden Time Cost 1/reversibility Typical Current Intervention Earliest Clinical Detection Earliest Molecular Detection Baseline Risk Personalized, Predictive, Prevention Personalized Medicine Tools Development of Disease ©2011 RALPH SNYDERMAN Personalized Health Planning

7. Health Risk Assessments Genomic Predictors (e.g.) SNPs Gene Sequencing Haplotype Mapping Biomarkers Gene Expression Tests Proteomics Tests Metabolic Profiles Clinical Risk Models Clinical Decision Support Adverse Outcome Models Drug Metabolism Indicators Companion Diagnostics Targeted Therapies Emerging Medical Capabilities Personalized Medicine Tools Applications Quantify Health Risks Monitor Disease Progression Define Disease Mechanisms Select Therapies ©2011 RALPH SNYDERMAN

8. Shift to Personalized Health Planning Traditional Medical Evaluation and Record Chief Complaint History of Illness Past Medical History Family History Social History Physical Exam Diagnostic Tests Assessment and Plan Personalized Wellness Plan Current Health Status Clinical Risk Assessment Tracking Wellness and Pathogenesis Clinical Event Prediction Wellness Plans Patient Engagement Personalized Treatment Plan Mechanistically Defined Pathology Level of Disease Activity Best Therapeutic Intervention Tracking Factors Therapeutic Timeline and Plan Patient Engagement ©2011 RALPH SNYDERMAN

9. Hallmarks of Cancer Self sufficiency of growth signals Insensitivity to growth inhibition Evasion of programmed cell death Limitless replication potential Sustained angiogenesis Invasion/metastasis potential Immune evasion Stress response phenotype ©2011 RALPH SNYDERMAN

10. Targeted Cancer Therapies Block Oncogene Addiction Inhibitors of BCR–ABL, c-KIT, HER, B-RAF Enhance Tumor Suppressors Inhibitors of DNA methyl transferase, HDAC Promote Apoptosis Inhibitors of Bcl-2; IAPs antisenses Inhibit Angiogenesis Inhibitors of VEGF, EGFR, Notch Abrogating Limitless Replication Inhibitors of CDK, CHK, MTK Inhibit Invasion and Metastasis Inhibitors of TGFb, IGF-1R, FAK Enhance Immune Surveillance Immunomodulatory drugs Examples ©2011 RALPH SNYDERMAN

11. Personalized Diagnostics Diagnostic Testing Overview Source: Company websites, L.E.K. analysis ©2011 RALPH SNYDERMAN

12. Consider a 28 year-old man with a mass in his neck Personalizing Cancer Care ©2011 RALPH SNYDERMAN

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15. Personalized Cancer Care Plan Advanced Clinical Decision Support Personalized Diagnosis Risk Models Companion Diagnostics Targeted Therapies Adverse Reaction Indicators Disease Activity Indicators Dx Evaluation Rx Selection Onset Remission Tracking and Refining Therapies ©2011 RALPH SNYDERMAN

16. New Model Validation Biocausality Engine Clinical Decision Support Diagnostics Selectors Clinical Risk Predictors Therapeutic Predictors Payer Adjudication CPOE CDS TM PDx TM Personalized Cancer Care Plan EHR Clinical Decision Support at the Point of Care ©2011 RALPH SNYDERMAN

17. Personal Care Plan Risks Clinical Therapy Individual Tracking Tools Therapeutic Plan Patient Physician Advanced Clinical Decision Support Clinical Workflow and Guidelines Risk Models Molecular Diagnostics Coordinated Care Patient Centered Medical Home Accountable Care Organization Disease Management Personalized Data Base Personalized Health Care ©2011 RALPH SNYDERMAN

18. Coordination of Care Patient Centered Medical Home Accountable Care Organizations Disease Management Programs Health Care Innovation Zones Reimbursement for Performance Pay for Performance Best Practice Pricing Bundled Payments Personalized Health Planning PPACA – Elements of Health Care Reform ©2011 RALPH SNYDERMAN