Introduction to the Medical Community The Measurement to Understand Reclassification of Disease Of Cabarrus/Kannapolis Study The M.U.R.D.O.C.K.
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Introduction to the Medical Community The Measurement to Understand Reclassification of Disease Of Cabarrus/Kannapolis Study The M.U.R.D.O.C.K. Study 22 Oct 2007 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 NCRC collectively improving human health Farming Practices Effective Healthcare Public Health Food Sciences Disease Management Population Health Nutrition Health Maintenance Productivity Medical Education Global Health 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. The MURDOCK Study will … 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. Improve human health. 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 Current data assets & DHMRI tools: Powerful once-in-a-lifetime value proposition Aging Arthritis Heart Disease Obesity Diabetes Liver Disease Brain Disorders Mental Illness Alzheimers Genomics, Proteomics, Metabolomics DHMRI Core Lab Image Analysis DHMRI Core Lab Massive patient database to be mined Cancer Breast Prostate Lung 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 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 Continuum of -Omics Genes mRNA Proteins Metabolites Genomics Transcriptomics Proteomics Metabolomics Genomics and the media An example: DNA Microarrays Cells of interest Known DNA Isolate mRNA, label Glass slide Dr. Russ Altman, Stanford Univ. Reference sample DNA Microarray visualization: heatmaps Expt 1 Experiment 1 (e.g. Patient X) 2 3 4 5 6 Gene 1 Gene 2 Gene 3 Gene 4 Gene 5 Gene 6 Gene 7 Gene 8 Gene 9 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 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 ‘-Omics’ technologies can help predict treatment response. Cancer Diabetes -Omics Technologies Excercise Responder+ Diet A Adverse Exercise event + Diet B Non-responder Exercise + Diet + Medication 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. Three horizons of MURDOCK Study Horizon 2 •Validate hypotheses prospectively •Apply new knowledge to local community through partnership with local medical community •Improve human health Horizon 1.5 •Engage community •Build community registry Horizon 1 •Use assets on hand to generate molecular data •Generate hypotheses by leveraging bioinformatics Outcomes of Hepatitis C virus infection Spontaneous clearance (~25%) Chronic infection Treatment Responders Hepatic Fibrosis Steatosis Non-responders (>50%) Insulin resistance Dyslipidemia Increased risk of diabetes Unknown consequences 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 nonHCV patients with these conditions Selection of biomarkers for HCV profiling Standard available assays: inflammatory, lipid metabolism, glucose metabolism, etc. Novel protein biomarkers – proteomic discovery Novel protein biomarkers – genetic approaches Novel biomarker discovery strategies Proteomic discovery gt1 gt2 Genetic discovery gt3 R NR Open discovery platform allows for discovery of novel protein biomarkers (host or viral-specific) that may be associated with treatment response and/or HCV genotype These biomarkers, along with others, will be typed in a large HCV patient cohort Unbiased discovery platform tests for association of >500,000 gene variants with HCV outcomes and/or quantitative traits (protein markers) Genes discovered in this way may become useful protein biomarkers or remain as DNA diagnostics Molecular profiling of HCV patients Tx response Fibrosis Steatosis Diabetes Dyslipidemia Type large number of Use statistical biomarkers in ~1000 modeling to subset chronic HCV patients HCV patients based from the Duke on common Hepatology Research biomarker signatures Clinic cohort Correlate molecular signatures with outcomes in HCV patients and similar traits in non-HCV patients Deploy assets for maximum potential benefit to communities. Uncover new knowledge in diseases that afflict large patient populations. Epidemics — obesity, diabetes, depression Diseases 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 pathways Novel biomarkers Challenge of biomedical informatics: Turning data into knowledge Knowledge DATA 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 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) Community Registry Accelerating Discovery: Finding Suppose we identify a Biomarker that distinguishes a sub-population of patients correlating with new insulin resistance Application If this is true, we’d treat differently to achieve better patient outcomes Confirm We need to test this to assure improved patient outcomes Translation Positive result would drive creation of the into Practice diagnostic and care guidelines. 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 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.