Introduction to the Medical Community The Measurement to Understand Reclassification of Disease Of Cabarrus

1. Introduction to the Medical Community The Measurement to Understand Reclassification of Disease Of Cabarrus/Kannapolis Study

2. Agenda Welcome and introductory comments Andrew Conrad PhD - CSO LabCorp and NCRC Lynne Scott Safrit - President Castle & Cooke Allan Dobson MD � VP Clinical Practice Development, CFM Overview of study plan - Rob Califf MD Overview of -omics study tools � Jessie Tenenbaum PhD Example of liver project - John McHutchison MD Community�engagement plan - Lloyd Michener MD Discussion - All Timeline and next steps - Victoria Christian�

3. NCRC collectively improving human health

4. In 20 years� All people in developed nations will have � An electronic health record Biological samples Digitized images Healthcare will be personalized using an individual�s images, samples and clinical data. The health of a community will be monitored using aggregate records. Kannapolis � as hub of the Carolinas � could define this future through a public-private partnership.

5. Build value using assets already in our reach. Sub-classify major diseases into populations with specific risks and optimal therapy. Apply new knowledge to the study of community health. Re-define clinical research using the power of genomics and biomedical informatics. Re-write the textbook of medicine. The MURDOCK Study will �

6. The MURDOCK Study will ... Fuel the financial success of the DHMRI Core Laboratory and Biorepository. Foster breakthrough collaborations between NCRC schools with diverse and interconnected perspectives and expertise Quickly increase the visibility and scientific impact of the DHMRI Lab. Attract the scientific community. Attract the biotechnology community. Engage the local population in a high-impact, internationally recognized project. The modern equivalent of the Framingham Heart Study

7. Current data assets & DHMRI tools:Powerful once-in-a-lifetime value proposition

8. A new era of biomedical research Novel research technologies have enabled the study of thousands of molecules at a time Referred to as �high throughput� approach These novel methods enable �-Omics� scale research

9. What is �-Omics�? The study of the totality of a type of biological data All genes: Genomics All transcribed genes: Transcriptomics All proteins: Proteomics All metabolites: Metabolomics Omics scale research has enabled patient profiling at the molecular level

10. Continuum of -Omics Genomics

11. Genomics and the media

12. An example: DNA Microarrays

13. DNA Microarray visualization: heatmaps

14. An opportunity For the first time, diseases can be defined by molecular fingerprints or profiles Mechanistic pathways of diseases can be elucidated Symptomatic descriptors can be replaced by meaningful tools for stratification ? These tools will enable truly personalized medicine

15. Medicine today Drugs are developed to treat all patients with the same clinical diagnosis - �one size fits all� Many drugs only work in less than half of the patients for which they are prescribed Over 100,000 people die annually from drug related adverse events - a �top 10� cause of death

16. �-Omics� technologies can help predict treatment response.

17. Combining clinical and molecular data will redefine disease management. Quantify risks of developing diseases.? Apply preventive measures more effectively. Establish diagnosis earlier. ? Prevent disability by treating earlier. Predict death and disability. ? Use healthcare resources strategically.

18. Three horizons of MURDOCK Study

19. Outcomes of Hepatitis C virus infection

20. Reclassification of HCV disease Use genomic technologies to subset patients based on their molecular signature This signature may become a useful marker of: Treatment response � therapeutic decision-making Development of fibrosis or steatosis - non-invasive diagnostic alternative Insulin resistance or dyslipidemia � may have broader relevance for diagnosing and treating non-HCV patients with these conditions

21. Selection of biomarkers for HCV profiling Standard available assays: inflammatory, lipid metabolism, glucose metabolism, etc.

22. Novel biomarker discovery strategies Proteomic discovery

23. Molecular profiling of HCV patients Type large number of biomarkers in ~1000 chronic HCV patients from the Duke Hepatology Research Clinic cohort

24. Deploy assets for maximum potential benefit to communities. Uncover new knowledge in diseases that afflict large patient populations. Epidemics � obesity, diabetes, depressionDiseases of aging � arthritis, dementia Use this new knowledge in clinical practice. Make decisions based on breakthroughs in the individualized treatment of breast cancer and depression Make new discoveries with commercial potential. Contributory drug-able pathwaysNovel biomarkers

26. Groundwork for successful community engagement Transparency of efforts Advice from appropriate community groups Questions to ask: how are citizens best reached? where do they gather? how do they prefer to receive information? Preparation of documents and study plans in iterative process with feedback from community Communication strategy based on community groups� advice Formation of Community Advisory Group

27. Possible modes of engagement Interactive website Community surveys Posters, brochures, other written materials Educational presence at community events (e.g., health fairs) Targeted cable television programs Local physician and patient with 15 min on specific topic (living with osteoarthritis, managing diabetes, etc.) Videos for doctors� offices Interactive kiosks Open communication with local media outlets Meetings with community groups (health related and non-health related)

28. Community Registry Accelerating Discovery:  Suppose we identify a Biomarker that distinguishes a sub-population of patients correlating with new insulin resistance If this is true, we�d treat differently to achieve better patient outcomes We need to test this to assure improved patient outcomes Positive result would drive creation of the diagnostic and care guidelines.

29. Community Registry Allow patients to declare interest in research participation Store information People interested in research participation Summary level health information Permission to contact Primary physician Accelerate discovery by having this information when discoveries are ready to be tested

30. Summary We are committed to building transparent, open partnership with local community. We will seek to maximize opportunities to have meaningful impact on local human health and local economy. The MURDOCK Study offers an opportunity for the local community to have global impact by generating knowledge that improves health and alleviates disease.