Presentation is loading. Please wait.

Presentation is loading. Please wait.

1. 2 Better Prevention and Management of Chronic Disease are Critical to Improving Health Outcomes and Lowering Healthcare Costs Source: DeVol, R, Bedroussian,

Similar presentations

Presentation on theme: "1. 2 Better Prevention and Management of Chronic Disease are Critical to Improving Health Outcomes and Lowering Healthcare Costs Source: DeVol, R, Bedroussian,"— Presentation transcript:

1 1

2 2 Better Prevention and Management of Chronic Disease are Critical to Improving Health Outcomes and Lowering Healthcare Costs Source: DeVol, R, Bedroussian, A, et al. An Unhealthy America: The Economic Burden of Chronic Disease. The Milken Institute. October An Unsustainable Path

3 3 Our Leaders Agree In the future, when doctors can truly prescribe the right treatment, to the right person, at the right time, we will have a new level of precision and effectiveness that will provide the knowledge-driven power that is necessary to achieve our highest goals in healthcare reform – including more effective disease prevention and early disease detection. HHS Secretary Kathleen Sebelius Senate confirmation hearings, April 2, 2009

4 4 IGNITE is a unique non-profit medical research institute in the national capital area aimed at alleviating human suffering and transforming the health care system using a new strategy: Personalized Medicine

5 5 Strategy Chronic disease R&D focus – align program with market needs from outset Deep molecular sub-classification of chronic disease (all heritable risk identified) Identify at-risk individuals from across the population via genetic risk factor testing Run distributed primary prevention trials facilitated by HIT network Apply results rapidly back to at-risk individuals via a robust translational infrastructure – including a captured health care system Integrate health information technology to allow heritable risk information to be incorporated into point-of-care with clinical decision support Empower change across the personalized medicine ecosystem through policy, education, health economics, regulation Outcome: Alleviate or delay the onset of chronic disease and decrease the time individuals are sick at the end of life and allow resources to care for more


7 Alzheimers Disease 7

8 8 How AD Contributes to the Crisis In Boomer Diseases, such as Alzheimers, Impact and Costs Will Escalate Dramatically Without New Interventions $0 $500 $1000 $1500 $ Baseline Estimate Estimated Number of People With AD (in millions) Delayed Onset & Slowed Progression (~6 yrs) Adapted from The Lewin Group Report, June 2004, Saving Lives. Saving Money: Dividends for Americans Investing in Alzheimer Research, The Alzheimers Association (


10 Molecular Scanning Technologies –Chairman of NIH Microarray Consortium (15 NIH) –10 years of experience with Affymetrix platform –5 years experience with Illumina –>60,000 expression profiles run –>100,000 SNP arrays run (10k, 100k, 500k, 1M) –Data warehousing –First Genomics Collaborators, Center of Excellence, and TransMed site of Affymetrix –NHLBI Programs in Genomic Applications –NEI intramural contract site –NIH Neuroscience Array Consortium –NCI funded ALL catalog –NIA funded Alzheimers disease catalog –ADNI Consortium hub –International Autism Genome Project Genotyping Site –TCGA Biospecimen repository –High throughput sequencing (Solexa, 454, ABI, Pacific Biosiences)

11 The Shop

12 NIH Neuroscience Microarray Consortium 1650 registered users 455 proposals submitted from about 114 institutions around the country and from over 287 different investigators 455 Total Projects: 455 (45,400 arrays)






18 Population-based Genetic Risk Factor Screening David Agus, MD Dietrich Stephan, PhD SAB: Isaac Kohane, MD PhD David Botstein, PhD Spencer Wells, PhD

19 Navigenics CONFIDENTIAL Extract the Total Heritable Risk for Chronic Disease Customer Acquisition LaboratoryBioinformatics Personalized Web Portal Ongoing Service ATACCGCTGGCCCTT TGGCATTACCTATGA AGATTGCTTCAGCCA GCGTCAGTTTCAACC TGTACGCTAGTGTGT TTCTACTCACGTGTC TCAGCATTGATCGAT ACCTGGCTATTGTTC ACCCAATGAAGTCCC FUTURE: Full genome sequencing, copy number analysis, methylation status leading to personalized exposure mitigation strategies and biomarker monitoring programs fully integrated into the established health care system.

20 Non-Invasive DNA Collection Kit February 13, 2014

21 GMP-compliant, ISO-certified Array Manufacturing PhotolithographyChemistry

22 QUALITY CLIA and stringent QC lab Captured perfectly Per SNP algorithm checks Per SNP concordance H-W equilibrium checks

23 Navigenics CONFIDENTIAL What we do 23Navigenics CONFIDENTIAL Review world class academic and clinical research published in leading peer-reviewed journals… …and provide personalized, preventative, health and wellness information

24 Stringent Curation Criteria Replication in the same ethnic group –Once for GWAS, twice for candidate gene studies –>60% independent sample sets show same statistically significant effect with same allele (after trimming underpowered samples) Study design - An effort was made to sample controls from the same source population as the cases, e.g. ethnicity, gender, age, or other risk factors. Reasonable sample size to detect weak effects. OR <1.5 needs 250 cases/250 controls at least. Significance level - Exact value depends on magnitude of the study (e.g. GWAS or candidate gene) Sound statistical design - correction for multiple testing, population stratification, confounding Sound laboratory practice - independent genotyping platforms, replicated samples Functional data and magnitude of effect are also taken into account, but studies are not automatically excluded if functional data is unavailable or the effect estimate is small.

25 Finding the Relative Risk - see full details at OR (RR) (RN) Prevalence We normally get genotypic odds ratios RR/NN, RN/NN OR (RN) Genotype Freq Using genotype frequencies and prevalence, we derive a set of quadratic equations – the solution provides the relative risks. (RN) ? ?

26 Distribution of effect sizes for genetic and environmental risk factors Risk factors determined from literature using strict curation guidelines risk factorcondition effect size Ex-smoker T2D 1.15 PPARG genotype T2D 1.53 HDL<35mg/dl CHD 2.08 MHC genotype RA 5 APOE genotype AD 18 BMI>35 T2D 42

27 Google, Microsoft, MDVIP, Cisco, etc…

28 Distribution of fold change in lifetime risk by individual patient Across the entire population: –98% of patients showed at least condition with >1.2X increase in average lifetime risk –45% of patients showed at least condition with >3X increase in average lifetime risk Fold ALTR Average lifetime risk for this condition = 0.06% Individuals estimated lifetime risk = 0.37% Fold change in ALTR= 0.37/0.06 = 6.2 Orange (>1.2X) Gray (<1.2X) Individual Patient Number

29 Conditions with >3X ALTR risk by individual patient Fold ALTR Individual Patient Number Alzheimers disease Celiac disease Crohns disease Glaucoma Graves disease Macular degeneration Multiple sclerosis


31 Alzheimers Disease: Homozygous or Orange 31 30% APOE4 Heterozygous 3.3% APOE4 Homozygous

32 Clinical Decision Support - Prevention


34 fMRI in at-risk Individuals as a Surrogate for Clinical Efficacy (BAI) push loaded patients to BAI via Navigenics baseline imaging performed patients go on drug and placebo periodic functional imaging use imaging as surrogate measure of clinical efficacy PROS: hundreds of patients vs. thousands years vs. decades millions vs. hundreds of millions within patent life of compound CONS: imagining not endpoint for approval no biomarker associated with imaging


36 Health Information Technology Accelerates Personalized Medicine Embed the genome into the electronic medical record (EMR) Role-based access to genome data (insurance companies excluded) Connect to a consumer-facing portal (PCHR, patientslikeme, Healthvault) Allow HIPAA-compliant messaging and interventional distributed trials Secure and authenticate transactions and data flow Undergird the clinical information system with a research database that can connect to other regional HIT systems (MS Amalga) Build a flexible clinical decision support module that allows physicians to understand molecularly-guided strategies Enable a learning CDS that constantly refines itself with the data flows to optimize clinical care 36

37 Summary of Solution – Alzheimers Identify genes that classify the population into high and low risk Build a broad-based CLIA genetic testing infrastructure to classify individuals across the world (Navigenics) Incorporate pointers to push high risk individuals into our clinical trial at BAI Develop functional brain imaging strategy that can detect the earliest brain changes associated with AD that can be used as a surrogate measure of clinical efficacy in slowing AD pathology Run a series of small trials drawing on a national base and fMRI to develop primary prevention drugs for AD in the next decade Work with the FDA so that fMRI and associated biomarkers are robust enough for approval of primary prevention therapies Use HIT vehicle to disseminate approved therapies back to population 37

38 Learning Health Care System 38 Results of Personalized Medicine in Chronic Disease Genomic Profile / Predisposition / Environmental Risks Personal Health / Wellness (Disease pre-emption) Interaction with Health Care Provider (Early diagnosis if needed) Interventions (Targeted treatment individualized to my molecular profile and that of my disease) Post-Disease Management Family Members Health Care

39 39 What Does Success Look Like? Americans living longer without disease American health care delivering value at reduced cost Connected information from bench to bedside Robust pipeline of diagnostics and targeted therapeutics moving toward approval Growing portfolio of emerging, innovative companies $ $


Download ppt "1. 2 Better Prevention and Management of Chronic Disease are Critical to Improving Health Outcomes and Lowering Healthcare Costs Source: DeVol, R, Bedroussian,"

Similar presentations

Ads by Google