1. Clinical and Translational Research: Expectations and Goals Daniel E. Ford, M.D., M.P.H. Director, Institute for Clinical and Translational Research Vice Dean for Clinical Investigation

2. Clinical Research at Johns Hopkins Comprehensive in Scope Cancer Center Research in children Neurosciences Drug abuse Investigator Initiated Large Discovery Pipeline Expertise in Moving Discoveries to Population Fortunate to Have Large Number of Trainees Interested in Research

3. Research at ClOffJohns Hopkins Medicine By Calendar Year Last updated 4/5/2010 New Applications 200720082009 NHSR354899 New Exempt443364311 New Expedited561688830 New Convened418520569 Total New145716201809 Applications 200720082009 Active eIRB Applications 155221982890 Active Paper Applications 1051859554 Active SOM IRB 260330573444 WIRB Active Applications 405297200 CIRB Active Applications 325863 Total Active 304034123707 Randomized Clinical Trials 200720082009 Active Randomized Clinical Trials 724815854 New Randomized Clinical Trials 247376405

4. Commercial Applications 200720082009 Active Commercial 550543487 New Commercial 262322270 Commercial Clinical Trials 200720082009 Active Commercial Clinical Trials 385 360 New Commercial Clinical Trials 181202243 Using Drugs/Devices 200720082009 Active Applications Using Drugs 86910241091 New Applications Using Drugs 282346386 Active Applications using Devices 288327245 New Applications using Devices 104118102 IDE/INDs Applications 200720082009 Investigator/Sponsor HeldActive Applications using INDs 383496523 New Applications using INDs 157198156 Active INV Held INDs 74118162 New INV Held INDs 135582 Active Applications using IDEs 122944 New Applications using IDEs 92120 Active INV Held IDEs 71314 New INV Held IDEs 332

5. Sponsored Project Sources Johns Hopkins SOM – Prorated Awards

6. Translational Medicine T1 – “the transfer of new understandings of disease mechanisms gained in the laboratory into the development of new methods for diagnosis, therapy, and prevention and their first testing in humans.” T2 – “the translation of results from clinical studies into everyday clinical practice and health decision making.” IOM Clinical Research Roundtable

7. Translational Research Activities T1 activities included: 1) the translation of basic discovery into mechanistic studies in cell lines or animals, 2) the translation of mechanistic studies into initial human testing, and 3) the translation of initial human testing into proof of efficacy. The T2 activities included 1) the translation of proof of efficacy into proof of effectiveness in a usual care setting, and 2) research aimed at enhancing the adoption of best practices in the community

8. Conclusions 69% responded they are translational researchers (9% other survey but different definition) PhD and fellows report less translational activity Barriers to translational research are as expected but substantial

9. 84 44 43 33 30 20 11 5 0102030405060708090 Translational research is not part of my research agenda or is not central to the goals of my research program. I don’t have the resources (funding, space, equipment, technology) for making my research more translational. I have not yet identified an appropriate translational research question to pursue. I am not sure what the next translational step would be for my research. I haven’t identified or secured the colleagues or collaborators I need to make my work more translational. I don’t have the guidance or mentorship I need to make my research more translational. I don’t have the training or expertise I need to make my work more translational. I have methodological obstacles to making my research more translational. It is premature for me to consider translational research. Number of Respondents (n=205) It is premature for me to consider translational research. I have methodological obstacles to making my research more translational. I don’t have the training or expertise I need to make my research more translational. I don’t have the guidance or mentorship I need to make my research more translational. I haven’t identified or secured the colleagues or collaborators I need to make my work more translational. I am not sure what the next translational step is I have not yet identified an appropriate translational research question to pursue. I don’t have the resources (funding, space, equipment, technology) for making my research more translational. Translational research is not part of my research agenda or is not central to the goals of my research program. Barriers to Translational Research (n=205)

10. Translational Pathway Basic Discovery Mechanistic Studies Initial Human Testing Proof of Efficacy Proof of Effectiveness Diffusion to All Health Care Settings 2 1

11. Institute for Clinical and Translational Research Influence on Scientific Discovery Institute Programs Enhancing Formulation ofCreation of Development Conduct Analysis of Publication Observation Scientific Question Research Team Study Protocol of Study Study Data Impact Study Advisory Boards Protocol Review Translational Science Forums Science Cores Innovation Groups Biostatistical Support Regulatory Support ATIP Research Ethics Clinical Research Units Clinical Research Participant Core Data/Safety Monitoring Community Engagement Program Biomedical Informatics Navigator Program Research Education and Training

12. Impetus for the CTSA Program  Implementing biomedical discoveries made in the last 10 years demands an evolution of clinical science.  New prevention strategies and treatments must be developed, tested, and brought into medical practice more rapidly.  CTSA awards will lower barriers between disciplines, and encourage creative, innovative approaches to solve complex medical problems.  These clinical and translational science awards will catalyze change -- breaking silos, breaking barriers, and breaking conventions.

13. Johns Hopkins and Translational Medicine Need to support researchers at all career levels Progress in translational medicine requires development of teams of researchers that appreciate all phases Clinical and translational researchers will continue to develop more technical and specialized approaches. Handoffs require active coordination (project coordinators). Do to increasing regulations, researchers will need to rely more on systematized solutions at institutional or national level Academic organizations need to partner better with other organizations to increase efficiency (industry, payers, patient groups) Need to balance resources/support for early and late translation Academic centers need better management structure to systematically monitor research process and barriers

14. MT WY ID WA OR NV UT CA AZ ND SD NE CO NM TX OK KS AR LA MO IA MN WI IL IN KY TN MS AL GA FL SC VA WV OH MI NY PA MD DE NJ CT RI MA ME VT NH AK HI Building a National CTSA Consortium Since 2006 Since 2007 Participating Institutions

15. CTSAWeb.org

16. Consortium Governance & Organization Governance Manual available at http://ctsaweb.org/Docs/CTSA_Governance_Manual.pdf http://ctsaweb.org/Docs/CTSA_Governance_Manual.pdf

17. Institute for Clinical and Translational Research Goals –Academic Home for Clinical and Translational Researchers –Expand the Working Relationships of Clinical Investigators with Basic Scientists and Population-oriented Scientists –Coordinate Translational Research Activities to Increase Innovation and Speed of Translation

18. Institute for Clinical and Translational Research Goals –Support Training of Clinical and Translational Research Faculty and Staff –Provide Centralized Support for Research Where Efficient –Measure and Track Efficiency of Human Subjects Research to Address Barriers Director – Daniel Ford, MD, MPH Vice Dean for Clinical Investigation

19. Deputy Directors of the Institute for Clinical and Translational Research Dr. Charles Balch Dr. Stephen Desiderio Dr. Charles Flexner Dr. Elizabeth Jaffee Dr. Pete Miller Dr. Pamela Ouyang Dr. Jeff Rothstein Dr. Pamela Zeitlin

20. Trial Design Advanced Degree-Granting Programs Participant & Community Involvement Regulatory Support Biostatistics Clinical Resources Biomedical Informatics Research participant Recruitment office Johns Hopkins ICTR ICTR NIH & other government agencies Healthcare organizations Industry Johns Hopkins Institute for Clinical and Translational Research

21. Johns Hopkins ICTR Progams Translational research training –K junior faculty/fellows –Medical students –Research staff and community physicians Clinical Research Units –1200 inpatient research bed days –Over 10,000 outpatient research visits –Pediatric and adult beds including Bayview

22. Johns Hopkins ICTR Progams Biostatistical Consultation Innovative Methodology Workgroups Clinical Research Ethics Consultations Data and Safety Monitoring Services Translational Research Navigators (project managers) Clinical Research Management Database

23. Johns Hopkins ICTR Progams Basic Discovery Translational Forum Clinical Sciences Translational Forum Accelerated Translational Incubator Program (ATIP) support pilots Research Participant Recruitment and Retention Program Community Research Networks Office Secondary Translation or Knowledge Transfer Office

24. Clinical Research Management System Budgeting Sponsor Billing InvestigatorsResearch Nurse Data Manager Insurance Clearance Budgeting by Dept. Admin. Program Manager Patient/ Protocol Registry PharmacyCore Facilities Labs SoM Leadership Billing Compliance IRB Eligibility Screening EPR/Labs Integration IRB Integration Protocol Schema / Patient Calendar Billing Compliance External Recruiting Website JHED/Site Minder Integration Data Warehouse Library Research Forms Work In Progress Currently In Use Possible Future Functionality Key:

25. Translational Cores Genetics Core Proteomics/Biomarker Core Drug and Vaccine Development Core