1. Diabetes Clinical and Translational Research: Rewards and Challenges Ruth S. Weinstock MD PhD Medical Director, Joslin Diabetes Center and Clinical Research Unit Professor of Medicine and Chief, Endocrinology, Diabetes and Metabolism SUNY Upstate Medical University Syracuse NY October 24, 2011

2. Disclosures Research funding: NIH/NIDDK, Helmsley Charitable Trust Speaker bureaus/honoraria: none Multicenter clinical trials: Diamyd, Eli Lilly, Pfizer, Ultradian Diagnostics Inc., GlaxoSmithKline, Macrogenics, MiniMed

3. Prevention and Management of Diabetes: Types of Clinical Research Initiation: –Investigator vs. non investigator Focus: –Medications –Devices –Behavioral interventions –Epidemiology –Quality of life –Health services –Others

4. Sponsors Federal: NIH, DOD, VA, CMS, other Foundations/non-for-profits (ADA, JDRF, others) State health departments (usually limited funding and indirect cost recovery) Industry: Phase I: evaluate safety, determine dose, side effects (n=20-80) Phase II: evaluate effectiveness, further safety (n=100- 300) Phase III: confirm effectiveness, monitor side effects, compare to standard Rx (n=1000-3000) Phase IV: collect more information re: risks, benefits, uses Hybrids

5. Why Participate? Intellectual benefits: contribute to understanding of disease and development of new therapies Academic rewards Early experience with new treatments Free services/medications to the needy

6. Requirements Trained staff For subjects: benefits > risks Adherence to GCP (Good Clinical Practice) principles Compliance with federal regulations (Protection of Human Subjects) IRB approval Ability to meet recruitment and retention goals Meticulous record keeping Sufficient funding (careful budgeting!) Dependent upon study: EMR, statistical/study design support, specific facilities eg Clinical Research Unit Must follow protocol exactly!

7. Considerations for Participate in Clinical Trials Do you have the required? –Patient population –Collaborators –Ancillary services –Equipment –Facilities (e.g. inpatient vs outpatient, pantry, pharmacy, laboratory, specimen processing) –Trained, dedicated staff –Time (P.I. etc) –Other Is budget sufficient? Duration of study?

8. Current Diabetes Grants at Upstate Medical University NIH (n=6) Industry-sponsored multicenter clinical trials (n=13) Foundation (Type 1 Diabetes Exchange) NYS Dept of Health Diabetes Center of Excellence (support community outreach, professional education and pilot projects e.g. school telemedicine)

9. Upstate Clinical Diabetes NIH Grants Investigator-initiated: SHINE, DSP Support salaries (% effort), other costs Highest indirect cost recovery Most difficult to obtain Greatest intellectual/academic gratification SBIR (Small Business Innovation Research) Partner with small business (new CGMS device) Joint federal and industry sponsorship Multicenter trials: TODAY, TrialNet Funding: traditional (% effort) or accrual based

10. Diabetes Industry-Sponsored Multicenter Clinical Trials Usually little input from investigators re: design Competitive enrollment Funding: based on recruitment and retention Indirect cost recovery: 30—50% of NIH Need to meet enrollment and retention goals May be discontinued at any time Need significant number of subjects to break even

11. So…Should We Participate? Carefully consider all factors (budget, patient population, staffing, other support) before committing Once committed, need to perform to expectations ENJOY!

12. THANK YOU!