THE VISN 1 CLINICAL TRIALS NETWORK

1. Non-Profit Corporation Strategy Meeting JUNE 25TH2014 THE VISN 1 CLINICAL TRIALS NETWORK

2. Meeting Purpose and Goals • Present the VISN1 Strategic Plan and research vision for the Clinical Trials Network • Present an overview of the Clinical Trials Network • Discuss the role of the NPCs in creating an effective and sustainable model for collaborative research in the VISN

3. VISN1 Strategic Plan • VA New England Healthcare System Strategic Plan for FY2013-2017 • Objectives established in five key areas • Goal I: Excellence in population health • Build a culture of improvement • Goal II: Excellence in patient experience • Fix the phones • Goal III: Excellence in financial stewardship • Expand our patient base • Goal IV: Excellence in work force • Manage retirement surge • Goal V: Excellence in Contributions to our national well-being • Enhance research

4. VISN1 Strategic Plan: Enhance Research • Long term strategic target – to be the leading VISN in annual research funding • Establishing academic affiliations and research programs at all eight VISN1 Medical Centers. • Aim to attract and retain high quality researchers within the Network through: • Career Development Awards • Research Enhancement Fund

5. VISN1 RFP: Aligning with MAVERIC’s Vision • RFP: Creation of a Clinical Trials Network in VISN1 • Expresses importance of innovative and groundbreaking work • References: • Co-operative clinical research groups (Children’s Oncology Group) • NEJM article: Looking beyond translation – Integrating Clinical Research with Medical Practice • IOM: Envisioning a Transformed Clinical Trials Enterprise in the US • IOM: A National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program • MAVERIC’s Vision: • To create a Learning Healthcare System within VA through application of research resources and methodologies to important clinical problems.

6. MAVERIC • Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC) • Interdisciplinary research and development organization established in 1996 with continuous growth • CSP Epidemiology Research Center, VA Research Biorepository, CSP Clinical Trials Coordinating Center (ISO 9001), Informatics Core • VA Research Transformational Initiatives: Million Veteran Program, GenISIS, Point of Care Research • Established model for collaborative research: umbrella IRB, feasibility studies prior to trials, administrative support team, site monitoring algorithms, informatics tools, data cores, statistical expertise

8. Beyond traditional clinical trials – Engineering a learning healthcare system

9. Problem Statement • Healthcare system’s research needs are not fully met by the current research enterprise • Designed for basic science inquiry and drug discovery • There is no scalable model for: • Clinical Effectiveness Research • research comparing known treatments • Biomarker validation (Personalized Medicine) • For diagnostics, prognostic or therapeutic indications

10. The Healthcare Value Gap

11. The Pharmaceutical Innovation Gap R&D in the Pharmaceutical Industry, A Congress of the US Budget Office Study, Oct 2006

12. Rethink silos Clinical Hospital Administration Clinical Research Pharma

13. A Solution • Creation of a Learning Healthcare System that creates locally applicable knowledge • Identifies its’ own needs • Uses its’ own infrastructure • Adapts available research methodology • Directly implements research results • The knowledge gained is thus not generalizable (thus not ‘research’) but rather is ‘locally selfish’.

14. The Learning Healthcare System

15. Opportunity – Why now? • Digitization of medical care information • Reimbursement for quality not volume • Accountable care organization needs • Development of healthcare intelligence tools • Need for comparative effectiveness research • Power shift from pharma to clinical care • Increasing costs of clinical trials

16. Learning from medical record data

17. …to improve healthcare delivery…

18. Current QI efforts • Mandated reporting • Manual chart abstraction • Limited variables • Question of generalizability from ward to ward

19. Kaleid Project • Data from all available sources • Collaborative exploration of the data • Automatically learn the most significant correlates to an outcome • By hospital, ward, clinician, etc • Deploy custom interventions • Dashboards

21. Kalied Status • Pilot deployment - CAUTI • NLP outperforms nurse chart abstractors for Foley day extraction • Chosen as pilot project for VA’s next EMR • Foundational project of a new VA Patient Safety Center

22. Integrating clinical research & care

23. Point of Care Clinical Trial • A clinical trial with a substantial portion of its operations conducted by clinical staff in the course of providing patient/subject’s routine clinical care and where the choice of treatment is between two “equivalent” options

24. Care providers using EMR Cohort Identification Enroll & Consent Randomize Intervention Clinical Decision Support Data Capture Study DB Analysis Study team using traditional scientific tools

26. POCR Advantages • Pragmatic qualities address issues of Clinical Effectiveness • Faster (immediate) Integration of results into practice thereby lowering the T2 translation barrier • Enhanced acceptance by providers (locally selfish) • Conversion to a decision support node • Improved logistics – scalable

27. Integrating genomics

28. Million Veteran Program (MVP) • MVP is a major research initiative that will create a longitudinal cohort of one million users of the VA Healthcare System to study genes and health • Designed to provide a better understanding of how genes affect health and illness • Goal of improving health care for Veterans and the nation

29. GenISIS

30. Translating genomics into Personalized Medicine

31. The Challenge of Personalized Medicine ‘OMICS Actionable Results Build a cohort Make data accessible Discover Validate Implement Point of Care Research & Kaleid Million Veteran Program & GenISIS

32. Shifting from Histologic to Histo-Molecular Dx

33. Precision Oncology Objectives • To create a robust precision oncology program in VISN 1 to: • Reduce disparities in cancer treatment • Enhance clinical care through systematic learning • Provide opportunities for clinical trial participation • Provide a platform for biomarker discovery and validation

34. What is Precision Oncology? • Perform genomic test on a cancer specimen • Determine driver mutations in the cancer • Deliver therapy based on identified target • Several targets in a given patient • Different targets across patients • Same targets in different cancer types • Few patients with any given target at one site

35. Clinical Care Component – All Patients • Routine molecular profiling for NSCLC patients as routine care • Longitudinal patient data collected in standardized format • Clinical Data Warehouse created • Track program metrics • Make available to researchers with HIPAA waiver • Referral into clinical trials • Data mining • Analyze outcome data to inform clinical care for ‘patients like me’ (Virtual Molecular Tumor Board)

36. Current ‘Local Learning’ Cancer genomic test results POP Data Base No Sx Dx Tx Sx Tumor Board recommendations Providers Time

38. Local Learning Through Observations Prior N patients POP Knowledge Base with ‘Prediction Engine’ Tumor Board recommendations N+1 cancer genome Dx Tx N+1 patient Providers Time

39. Patients Like Me (n+1)

40. Local Learning Through Experiments Prior N patients POP Knowledge Base with Predictive Engine If equipoise exists Tumor Board offers randomization within routine care N+1 cancer genome Dx Tx higher weight on randomized outcomes N+1 patient Providers Time

41. Research Component – Treated Patients • Patients with treatment plans asked for consent and HIPAA authorization to: • Collect longitudinal outcome data in standardized format to create a research data warehouse • For creation of generalizable knowledge • Sharing through CRADA mechanism • Allow for additional testing of tissue specimens • Implications for tissue management • Allow for re-contact for research purposes including clinical trial consideration

42. Phase II/III Biomarker-Driven Master Protocol for 2nd Line Therapy of Lung Squamous Cell Carcinoma • Lung SCCA remains an “orphan” disease – significant developments in therapeutics has yet to be seen • Multi-Arm Master Protocol can improve operational efficiency with homogeneous patient population and consistent eligibility • Grouping multiple studies reduces screen failures – broad-based platform allows for high “hit rate” • Designed to allow for FDA approval of new drugs

43. Rollout • Fall2014 regional prototype • 5 VISN 1 Centers: Boston (Harvard, BU), West Haven (Yale), Providence (Brown), White River Junction and Togus (Dartmouth) • 3 additional Centers: New York (NYU, Cornell), Ann Arbor (U of Mich) and Durham (Duke) • Summer 2015 expanded pilot • 20-24 sites • Summer 2016 national rollout

45. OK! So Now Are We Ready to Select Drugs for Patients in an even more Personalized Way? Hello, here is my tumor sequence

46. Overview Of The Clinical Trials Network • Mission • To create infrastructure and process to expand clinical trials within VISN 1 facilities that will contribute towards traditional and novel research objectives. • Goals • To increase the number of clinical trials in the VISN • To increase the numbers of Veterans enrolled in clinical trials • To increase annual research funding

48. Overview of the Clinical Trials Network • Goal to develop a full-service, sustainable and scalable research enterprise • Operations Core • Serve as the operational system for the Scientific Core and Field Component • Capitalizes on existing experience and infrastructure • Field Component • Provide resources necessary to execute studies at each site. • One full time site coordinator hired at each facility in the network to execute protocols initiated or expanded through the CTN • Establish a network of sites to collaborate on research protocols • Increase research opportunities in the VISN • Scientific Core • Assist in the development of disease specific consortia and facilitate investigator initiated projects • Create collaboration across facilities in specific disease areas • Increases patient base allowing greater opportunity (consortium vs. single-site approach)

49. Program Governance and Committee Structure

50. Purpose of the Field Advisory and Management Committee (FAMC) • Committee Role and Responsibilities • Identification, development, and expansion of protocols across the VISN • Oversight for field activities • Policy development and review • Field resource management • Fostering a culture of excellence and safety