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

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

S.E.2 GCRC: Pediatric Research S.E.1 GCRC: Inpatient and Outpatient Utilization 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

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.”

Vanderbilt Institute for Clinical and Translational Research (VICTR)

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

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

Organizational Chart for VICTR Administration

COMMUNITY!

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

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.

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

Grassroots Clinical Research: A case study

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

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

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

Vanderbilt DNA Databank

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

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

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)

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

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

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

What Could Be Done? Focus on common, but genetically complex diseases: 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

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.”

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