The Duke Clinical Research Institute: An Academic Research Organization (ARO)

1. The Duke Clinical Research Institute:An Academic Research Organization (ARO) John S. March, MD, MPH, Director, Neurosciences Medicine Duke Clinical Research Institute Durharm, NC

2. My Disclosures • Advisory board: Lilly, Pfizer, BMS • Consultant: Lilly, Pfizer, J&J, Scion, Psymetrix • Drug for NIMH study: Lilly, Pfizer • Research funding: Lilly, Pfizer • Equity: MedAvante • NIMH: POTS, TADS, CAMS, CAPTN, K24 • Foundation: NARSAD • Editor: Biological Psychiatry • Royalties: MHS, OUP, Guilford Press • Promotional activities: None http://www.dcri.duke.edu/research/coi.jsp

3. Topics • What is the DCRI? • Placing the DCRI in context • DCRI facts • Operational advantages

4. What is the DCRI? An academic research organization: Integrates the scientific thought leadership of an academic medical center and the operational capabilities of a CRO Provides a full range of clinical research services conducted to worldwide regulatory standards Provides access to core laboratories and specialized research tools Linked to academic health centers, professional societies, advocacy groups, regulatory agencies Fully oriented to the public private partnership space In operation for over 25 years

5. Our mission . . . to develop and share knowledge that improves the care of patients around the world through innovative clinical research. Duke Clinical Research Institute

7. How Is the DCRI Different….? From other Academic Research Centers... Operational capability to manage trial types from Phase I to global multi-center clinical research Possession of the complete infrastructure to needed to sustain clinical research Compared with Clinical Research Organizations…. Experienced Clinicians as Faculty Researchers dedicated to the Academic mission Extensive Relationships with and appointments at regulatory agencies including the FDA and the NIH institutes Ability to take research from Bedside to Clinical Research to Bedside

8. Topics • What is the DCRI? • Placing the DCRI in context • DCRI facts • Operational advantages

9. Discovery to Care Continuum

10. Current Fragmented System

11. Duke Medicine Model for Translation  

12. DCRU Facilities • 30,000 sq ft professional Phase I Unit • 60 beds, including • -Dormitory rooms accommodating 8 adult or 6 pediatric beds, a 30 bed adult confinement unit, and 10 licensed hospital beds including 2 “infant family rooms”; permits “standard-of-care” services • 30,000 sq ft professional Phase I Unit • Linked to Singapore (30 beds) and Medanta (100 beds)

13. Under the Umbrella or Connected DCRI

14. CTSAs Emphasize Public Private Partnerships • Integrate translational and clinical science by fostering collaboration between ….between institutions and industry • Provide a point of contact for partnerships with industry, foundations and community physicians as appropriate

15. The Biomarkers Factory (BMF) Core Lab Imaging Chemistry Radiochemistry - Omics Immune Monitoring Nonclinical POC Clinical Trial Design & Conduct Clinical Validation DCRI SCRI DCRU SRI Medanta Systems Biology BMF Sample Storage Bio- Informatics Biobank MURDOCK Study Analysis & Interpretation Trials / Registries

16. 2 3 1 4 5 6 7 12 8 11 9 10 Cycle of Quality: Generating Evidence to Inform Policy DataStandards NIH Roadmap NetworkInformation FDACritical Path Early TranslationalSteps EmpiricalEthics Discovery Science Prioritiesand Processes Measurement andEducation ClinicalTrials Outcomes Transparencyto Consumers Inclusiveness ClinicalPracticeGuidelines Pay forPerformance PerformanceMeasures Use forFeedbackon Priorities Conflict of InterestManagement Evaluation of Speedand Fluency Califf RM, Harrington RA, Madre L, et al, Health Affairs, 2007

17. Topics • What is the DCRI? • Placing the DCRI in context • DCRI facts • Operational advantages

18. Over 1000 staff and 200 faculty (~ 90 “A” faculty) Research conducted in 20 therapeutic areas Grants and contracts > $150 million/year Industry; Gov’t; Professional societies; Foundations > 400 clinical trials/outcomes research projects completed in 64 countries with > 579,900 patients > 5,000 publications in peer-reviewed journals Over 500 manuscripts published annually 15-20% in journals with impact factor >10 DCRI – Facts

19. The Duke Clinical Research Institute:An Academic Research Organization (ARO) John S. March, MD, MPH, Director, Neurosciences Medicine Duke Clinical Research Institute Durharm, NC

20. DCRI – Trials Experience by Phase and Size

21. DCRI Global Clinical Site Locations Iceland Finland Norway Russia Estonia U.K. Denmark Latvia Canada Lithuania Ireland Netherlands Poland Germany China Belgium Czech Rep. Ukraine Austria Slovenia Switz. Hungary France Romania Georgia Bulgaria Italy Spain United States Portugal Japan Greece Turkey Israel Egypt United Arab Emirates Mexico Taiwan India Dominica Hong Kong Panama Guatemala Thailand Venezuela El Salvador Malaysia Columbia Singapore Indonesia Brazil Paraguay Australia Chile South Africa Uruguay Argentina New Zealand October 2002

22. Therapeutic Areas of Expertise Anesthesiology Cardiology Cardiothoracic surgery Dermatology Endocrinology Gastroenterology Geriatrics Hematology Infectious disease Nephrology Neurosciences Medicine Oncology Ophthalmology Otolaryngology Pediatrics Pulmonary medicine Primary care Reproductive medicine Rheumatology Transplant medicine

23. DCRI Activities Scientific leadership Project Leadership Biostatistics Data Management (EDC) Clinical Events Classification Safety Surveillance Core laboratories DSMC Clinical Hotline Site Management and Monitoring Site Contracts and Payments Regulatory Affairs Medical Communications Health Economics & Outcomes

24. NSM Division Overview One of four pillars at the DCRI More than 40 Neurology and Psychiatry Faculty engaged with the DCRI 20+ NSM Focused Clinical Operations Staff Therapeutically dedicated support in: Data Management Statistics Currently 24 Active Projects in 9 Indications

25. NSM Therapeutic Areas of Expertise • Neurocognition • Neuromuscular disorders • Obesity • OCD / TS • Pain • Parkinson’s Disease • Schizophrenia • Sleep disorders • Substance Abuse • Stroke • TBI • ADHD • Aggression • Autism / PDD • Alzheimer’s / Dementias • Anxiety Disorders • Bipolar Disorder • Cross-TA CNS • Eating Disorders • Epilepsy • Major Depression • Multiple Sclerosis

26. Neurosciences Medicine Faculty T.K. Li, MD Christine Marks, MD David Marks, MD Joseph McEvoy, MD Mohamed Mikati, MD Ashwin Patkar, MD Rodney Radtke, MD Lesco Rogers, MD Jim Rochon, PhD Jed Rose, PhD Donald Sanders, MD Mark Skeen, MD Mark Stacy, MD David Steffans, MD Warren Strittmatter, MD Warren Taylor, MD Kathleen Welsh-Bohmer, PhD Wei Zhang, MD, PhD Nancy Zucker, PhD • John Beyer, MD • Dan Blazer, MD, PhD • Scott Compton, PhD • John Curry, PhD • James Blumenthal, PhD • James Burke, MD, PhD • Joe DeVeaugh-Geiss, MD • P. Murali Doraiswamy, MB, BS • Kenneth Gersing, MD • Carmelo Graffagnino, MD • Gerald Grant, MD • Mike Hagland, MD, PhD • Atif Husain, MD • Glenn Jaffee, MD • Jan Jiang, MD • Vern Juel, MD • Richard Keefe, PhD • Brad Kolls, MD • Scott Kollins, PhD, MS • Andrew Krystal, MD • Daniel Laskowitz, MD, MHS

27. Professional Core Laboratories / Capabilities Biomarker / Biosignatures -Omics platforms Biospecimen respository Immune monitoring Cell therapies Informatics Neuroimaging—structure, fMRI, MRS, PET Probes: PPI, startle, rTMS Neuropsychology Electroencephalography Neuroopthalmology Abuse liability eECG monitoring / cardiac imaging

28. Topics • What is the DCRI? • Placing the DCRI in context • DCRI • Operational advantages

29. DCRI – The ARO Advantage • Expertise used in trial design • Include real-world understanding of current clinical treatments and gaps • Designs that work within the practice flow and that will answer clinical questions • Include study population-specific endpoints • Integrated approach to data collection tools • Independent statistical analyses assures credibility and “interpretable” results

30. DCRI – The ARO Advantage • Professional relationships leveraged for the success of the trial • Recruitment of appropriate capable sites • PI involvement in site management • Early identification and mitigation of enrollment challenges • Involvement of key thought leaders • Regulatory authority interactions (FDA and EMEA)

31. Clinical Trials Transformation Initiative Mission: To identify practices that through broad adoption will increase the quality and efficiency of clinical trials.

32. DCRI – The ARO Advantage • Operational excellence • Project and faculty leader(s) collaborate on scientific and operational aspects of a project • Tested operational plans • Trained & experienced staff …low turnover • Excellent data quality and data-driven metrics to maximize signal detection • Practical experience in recruiting all patient populations

33. DCRI – The ARO Advantage • Key themes in developing partnerships with industry • True partnership not a pure outsourcing model • Established relationships with IRBs • Dedicated in house contracts group • High credibility and transparency • Right to publish • IP and/or profit sharing • Cost effective

34. Summary • One stop shopping • World renowned faculty • Therapeutic area expertise • High level operational capability • Far reaching network experience • Exceptional scientific technologies • Publication record impacting clinical practice • Commitment to public-private partnerships • Credibility with regulators and medical community

35. Duke Clinical Research Institute