Clinical and Translational Research at Vanderbilt

1. Clinical and Translational Research at Vanderbilt Gordon Bernard MD Professor of Medicine Assistant Vice-Chancellor for Clinical Research

2. Clinical and Translational Research to Improve Health Basic Science Content of Care Process of Care Structure/Barriers Outcomes Health Policy* Safe* In vitro studies Feasibility and safety Effective* Patient Health: Morbidity* Mortality* Satisfaction* Cost* Insurance System* Patient-Centered* In vivo/ animal models Efficacy and safety* Access to Care* Timely* Behaviors: Patient* Provider* System* Equitable* Potential Clinical Application Effectiveness and safety* Community Health* Efficient* Epidemiology: Surveillance of System & Outcomes* *Research results trigger assessment for change in care content/process/structure

3. S.E.1 GCRC: Inpatient and OutpatientUtilization Diversity: 2000-2006 S.E.2 GCRC: Pediatric Research (N= 69, most recent 12 months) S.E.3 GCRC: Inpatient and Outpatient Clinical Research Portfolio By Category

4. CTSA – A roadmap initiative “It is the responsibility of those of us involved in today’s biomedical research enterprise to translate the remarkable scientific innovations we are witnessing into health gains for the nation.”

5. Vanderbilt Institute for Clinical and Translational Research(VICTR)

6. Industry Other Institutions NIH CTSA Awards: A Home for Clinical and Translational Science Clinical Research Ethics Trial Design Advanced Degree-Granting Programs Biomedical Informatics CTSA HOME Participant & Community Involvement Clinical Resources Biostatistics Regulatory Support

7. Impediments to translation Current Situation Small proportion translated Large number of ideas T1 and T2 blocks are psychological, organizational, procedural and physical

8. Organizational Chart for VICTR Administration

9. COMMUNITY!

10. 1. Access to pilot funds 2. Biostatistics core support 3. Synthetic derivative 4. Database of collaborators % very beneficial N=575

11. Voucher System • Designed to facilitate support for innovation. • Funds pilot type interactions • Scientific consultations (medical model) • Pilot assays • Statistical/informatics imput • Study design assistance • Vouchers • Small – web based request and approval • Medium – Administrative review • Large – GCRC Advisory Comm (GAC) • Automatic tracking of funds provided, completion, value.

12. Hypothesis Studio Design Studio Implement Studio AnalysisStudio TranslationStudio Clinical Epidemiology Core Behavioral Research Core Quality Improvement Research Core Surveillance Epidemiology Core Community Research Core Structure for Support of Study Development

13. Grassroots Clinical Research:A case study

14. Building a strong clinical trials program: - creates a national reputation that attracts patients - allows us to compete as a center for the study of various patient populations for large NIH trials

15. Interstitial Pulmonary Fibrosis Program • Created by James Loyd • Directed by Lisa Lancaster • Evaluates patients for: • Healthcare options • Clinical trials • Lung transplantation • Large referral base • Closest IPF centers a distance away – Duke, Emory, UAB, U. Colorado

16. Growth of IPF Research Center In 2006 became part Of the NIH IPF Clinical Trials Network

17. Vanderbilt DNA Databank

18. Genomics In Full Force • Senator Bill Frist (1/05, NEJM): “in the next decade, the practice of medicine will change dramatically through genetically based diagnostic tests and personalized, targeted pharmacologic treatments …” • Francis Collins (2/05): Personalized Medicine: How the Human Genome Era Will Usher in a Health Care Revolution

19. Vanderbilt DNA Databank: Background • Uses left-over clinical samples to create a centralized, cost-efficient genetic research resource • associate genetic information with disease susceptibility and variable drug responses across populations • improve patient safety and reduce adverse drug reactions • Patients have the option to opt-out of participation

20. Most Vanderbilt Patients Support DNA Databank project:Local Survey Results • General favorability apparent* • ~80% think the project is very important • ~90% think the hospital should be able to use leftover blood for medical research if personal information is removed • ~4-5% Oppose this type of genetic research • Scientific aims generate support • Prefer direct notification methods; but a fine line with IRB * Patient Survey To Assess Attitudes and Opinions (N=1,005)

21. Distinct Attitudinal Groups (Among Respondents Who Could Be Segmented) Allow opt outs

23. One-way Hash ID “HIPAA” identifiers (name, address…) removed Techniques to prevent re-identification based on specific queries Linked to genetic markers The Synthetic Derivative Medical Information System Identified Clinical data (1.3M records) Replaced record numbers Random social security numbers Shifted birthdates, adm dates, etc Substituted names

24. Comparison to the worlds largest existing DNA bank • Iceland database: • 125,000 records • Genealogy • Homogenous population • Paper medical records • Commercialized • Vanderbilt database: • 300,000 planned records* • No genealogy • Heterogeneous population • Electronic medical records • Academic/shared genotypes • *out of 1.5 million possible

25. What Could Be Done? Short term Long term Confirmation of role of known polymorphisms in causing disease Hypothesis Generation Rapid assessment of areas suitable for further study Discovery of new meaningful SNP’s, haplotypes, targets/pathways Prediction Development of statistical models for decision making Healthcare Paradigm Shift Personalized medicine • Focus on common, but genetically complex diseases: • Cancer, heart disease, diabetes, Alzheimer’s, macular • degeneration, arthritis, Parkinson’s, hypertension…. • As well as the dugs used widely to treat those diseases

26. Personalized Medicine September 5th, 2005 “Doctors might be able to screen patients’ DNA and predict not only whether they are likely to have a heart attack but which type of heart disease to expect and which drug or procedure might work.”

27. Artist’s conception of the Vanderbilt Institute for Clinical and Translational Research (VICTR)