University of Pittsburgh Clinical and Translational Science Institute Update: 2012

1. University of PittsburghClinical and Translational Science Institute Update: 2012 Steven E. Reis, MD

2. Zerhouni 2005: CTSA Objectives • Distinct disciplineof clinical and translational science • Opportunities and resources for original research • Develop translational technologiesfor full spectrum of CTS • Synergize partnerships(industry, foundations, community) • Train interdisciplinary teamswho will conduct the clinical and translational research of the future

3. 2006: NCRR- “It’s all about infrastructure”

4. CTSI Scope: NIH Support

5. CTSI Scope: Who Are We? From 46 disciplines • Discipline of CTS requires a cadre of scientists to advance CTSI mission • 162 faculty with secondary appointments in CTS

6. CTSI Scope:Who do we support? Surgery Psychiatry Pediatrics Medicine (Other)

7. CTSI Scope: Supported Studies by Year

8. Impact of CTSI Research:NIH Metrics NIH Grant Funding Resulting from CTSI-supported projects ($millions)

9. Impact of CTSI Research: ROI

10. Examples of CTSI Programs • Cores focusing on: • Education and Career Development • Novel and Collaborative Research • Research Support for CTS • Community Partnered Research

11. CTSI Education, Training & Career Development

12. CTSI Mobile Lab: Teach the Scientific MethodEngaged >9,000 high school students

13. Organization of Overview • Cores: • Education and Career Development • Novel and Collaborative Research • Research Support for CTS • Community Partnered Research

14. CTSI Novel Technologies Core Goals: • Develop Diamond for clinical use • Identify incipient engineering technologies • Year 6: Biosensors  • Computational modeling and systems biology core (Bahar)

15. CTSI Novel Core: Diamond(CTSI, CMU, Intel) Diamond(Interactive Search Assisted Diagnosis)

16. Diamond: Melanoma (Pathology)(Satya, Jukic, Ferris) • Diamond PathFind melanoma • Pathologists mark up pagetoid melanocytes • Machine Learning algorithm developed • Clinical trial: SPIRiT: • Pitt, Chicago, Penn, Yale (WashU)

17. Diamond: Melanoma (Dermatology)(Satya, Ferris) • Diamond DermShare • Clinical evaluation of pigmented lesions • Provide to PCPs and general dermatologists • Facilitate expert dermatopathology evaluation

18. CTSI Pilot Studies Core:>$3 million awarded • Pilot funding programs that: • Establish new collaborations • Generate preliminary data/experimental refinement • Promote new directions

19. Pilots Across the SPIRiT Consortium Initial Interpretation of Sociogram: - 1-12 pilot projects between institutions -high density/cohesion by establishing at least one tie between all institutions. -Centrality (measure of network activity and highlights which institution is most/least active in the network.) Penn=43, JHU=31, Pitt=30, WashU=30, Yale=28, UC=16. --Pitt, Penn, JHU, and Wash U were most proximal accumulating a high frequency of projects between institutions.

20. Organization of Overview • Cores: • Education and Career Development • Novel and Collaborative Research • Research Support for CTS • Community Partnered Research

21. IT Support for CTS-CARe: BridgingResearchers & Clinical Data • Data extraction and de-identification • Research requirements • Data model design • Service and fast turnaround • Compliance • Financial planning dbMotion Cerner Epic Transplant MARS Other Data

22. CARe Services Data Needs? Research Request Self-Extract CARe Analyst Review Costs Covered by UPMC Regulatory Consultation Cost Covered by CTSI or OSPARS TBD OSPARS Process CARe UPMC Programming Programming Charges at Standard Hourly Rates Data Extract Data Extract Existing Policy

23. Janice Zgibor, PhD Assistant Professor Epidemiology and Medicine

24. TIES Supports Tissue Sharing Across SPIRiT:Pitt, Penn, Wash U and Chicago

25. Clinical Research Resources & Facilities Core

26. CRRF Accomplishments:Year 6 Data

27. CRRF Participant Recruitment:Scope of Problem

28. Outpatient Office Information Technology Clinical Researchers Step 1 Investigators/ Coordinators Clinic Registrars Registry Studies Step 3 Step 2 Matching Step 4 UPMC Patients Investigators/ Coordinators

29. CTSI Research Registry Goal: Develop a “Research Informed Community”

30. Registry Goal: Recruit Participants for Specific Studies >33,000 Participants Dear Mr. Reis: On 11/17/2008, you enrolled in the Research Participant Registry. At this time, either you, or someone you know, may be eligible to participate in the following research studies.   EFADA Study: University of Pittsburgh_PRO11010186Are you a non-smoker between the ages of 18 and 60? Do you have a diagnosis of asthma? If so, you may be eligible to participate in a study to collect bronchial samples. Study participation includes 3-4 office visits over a two-week period. Participants will be compensated for their time and travel expenses. APRIL OCELOT Research Study: University of Pittsburgh_PRO10120319Does your child have a cough and/or wheeze? Is he/she between the ages of 1 year to almost 6 years old (12-71 months)? Has your child had repeated wheezing the past year? Researchers at Children’s Hospital of Pittsburgh of UPMC are currently studying ways to prevent coughing and wheezing in preschool aged children. This study will last about 12 months, and participants will be compensated.

31. CTSI Translational Technologies Core

32. Carol Feghali-Bostwick, PhDAssociate ProfessorMedicine and Pathology

33. CTSI Design, Biostatistics, and Epidemiology Core Stephen Wisniewski, PhD Professor of Epidemiology • Study design, biostatistics , epidemiology support • ≈200-300 requests/year

34. CTSI Comparative Effectiveness Research Data Center • CER data and IT infrastructure (CCM) • Datasets: • Medicare Provider Analysis and Review (MedPAR) • Medicare Healthcare Cost Reporting Information System (HCRIS) • AHRQ Healthcare Costs and Utilization Project Nationwide Inpatient Sample (NIS) • AHRQ Healthcare Costs and Utilization Project Emergency Department Sample (NEDS) • AHRQ Healthcare Costs and Utilization Project State Inpatient Databases (SID) • Medicare 20% sample (both inpatient, outpatient and Part D) • US Census data

35. CTSI Regulatory Knowledge and Support Core Hands-on assistance (IRB, IACUC, etc.) Responsible Conduct of Research training center Institutional DSMB (n=21)

36. Regulatory Plans IMPLEMENTATION OF FINDINGS RESEARCH IDEA -Map out processes -Identity Barriers -Address Challenges and Identified Needs Regulatory efficiency project Industrial Engineering Approach

37. Organization of Overview • Cores: • Education and Career Development • Novel and Collaborative Research • Research Support for CTS • Community Partnered Research

38. CTSI Community PARTners Core • Led by Pediatrics, Family Medicine, GSPH • Educational opportunities • Centralized consulting services: CBPR • Expand engaged and partnered research

39. Community Core: Educational Programs for Community

40. CTSI 2012

41. NIH’s Evolutionary Transformation:From NCRR to… NCATS:“It’s all about drug discovery (repurposing?)”

42. Novel Core Plans:CTSInnovation Program • Consulted with Xprize leadership • CTSI Goal: Ecosystem of Innovators • Stimulate creative approaches to broad translational research questions • Diverse groups of innovators coalescing around ideas • Application of ‘prize theory’ Ansari Xprize: SpaceShipOne

43. Prize Theory: Drivers of Innovation(“Radical Departure from Accepted Theory”) • Motivation to forge teams of innovators: • Curiosity • Fear/Defense (?loss of NIH funding) • Wealth Creation/Greed (?Grants, Patents) • Significance/Fame (?Tenure)

44. CTSInnovation: Mechanism Unsolvable Problems? Teams Coalesce Around Ideas It’s Not All About the Money

45. Unexplained Family OGT OGTT test Gliburide Insulin level variance in history OGT Random Diabetes plasma diagnosis Sex glucose Type 1 Insulin Diabetes Amount Glucose feature Joint uptake by Race/ Diabetes muscle ethnicity feature Type 2 FPG Diabetes Glucose HbA1c feature Age production by liver Urine ketone test Normal liver BMI Metformin glucose production Diabetes Propensity HDL LDL Triglyceride Blurred blood Smoking cardiac risk to blurred pressure cholesterol cholesterol s vision factor vision factor These coefficients vary by gender, race and age Memory Mean Systolic Propensity Peripheral Polyuria arterial blood Coronary to polyuria resistance pressure pressure artery FPG stenosis Perception Cardiac Propensity Arterial Pulse \ Fatigue to fatigue output compliance pressure To the To the To the To the CAD Propensity Retinopathy Nephropath Neuropathy Thirst model to thirst model y model model Drug Discovery/in silico clinical trials: Archimedes Model Insulin treatment Random plasma glucose test Random FPG test error and variation Efficiency of insulin use HbA1c test Untreated Care Age, sex, insulin level processes race/ To ethnicity treatment Fractional models Keto- change in acidosis Insulin Height Weight Diet and Hypo- FPG exercise glycemia Patient takes action Diabetes PITT/UPMC/Archimedes

46. CTSI: Beyond 2012 The NIH Centers for Accelerated Innovations (U54)RFA-HL-13-008 Due September 19, 2012 $24m/7 years

47. Goals • Develop Centers that: • Solicit and select emerging technologies • Facilitate their translation to commercialized products • Early stage technologies • Industry partnerships & non-federal funds • Create cultural changes

48. CTSI Supports Clinical and Translational Scientists