Implementing a Vision for Clinical Research

1. Implementing a Vision for Clinical Research Peter D. Emanuel, M.D. July, 2009 1

2. Who We Are • The University of Arkansas for Medical Sciences (UAMS) is part of the University of Arkansas system • The flagship campus (Univ. of Arkansas) is located in the Northwest corner of the state, whereas UAMS is located in Little Rock which is in the center of the state and also home of the state capitol. • UAMS is the sole medical school for the UA system and also the only medical school in the state. The UAMS campus is strictly a health sciences campus composed of six Colleges: Medicine, Pharmacy, Nursing, Public Health, Health Related Professions, and Graduate Studies. Interwoven into the Colleges are six Institutes: Cancer, Aging, Psychiatry, Myeloma, Eye, and Spine & Neurosciences.

3. Who We Are The University of Arkansas for Medical Sciences (UAMS) • UAMS recently established a satellite medical school, and also operates 8 Area Health Education Centers (AHECs) and 6 satellite Aging Clinics dispersed throughout the state. • On 07/14/2009 UAMS was awarded a nearly $20 million NIH CTSA grant, based upon its strength in telemedicine and community programs, amongst other initiatives. This made Arkansas only the 2nd small state to be awarded a CTSA grant (Iowa was the first).

4. Who We Are • The Winthrop P. Rockefeller Cancer Institute at UAMS • The Rockefeller Cancer Institute began in 1984 as the Arkansas Cancer Research Center. In 2004 it was proclaimed as the official cancer institute for the state of Arkansas by then Governor Mike Huckabee. • The Cancer Institute’s first tower, named in honor of Willard & Pat Walker, was constructed in 2 stages and was fully complete in 1994. It included both outpatient clinical space as well as clinical and bench research space. • By 2004, it was decided that an expansion tower would be needed.

5. Who We Are • The Winthrop P. Rockefeller Cancer Institute at UAMS • In 2007, ground was broken for building a 12-story 350,000 sq ft expansion tower, which is twice the size of the Walker Tower. The new tower adjoins the Walker Tower such that the two towers will work as one. The first phase will be completed in the summer of 2010. • Also in 2007, the Cancer Institute adopted the name Winthrop P. Rockefeller. Winthrop Rockefeller was one of John D. Rockefeller, Jr.’s five sons and served as Arkansas Governor from1967-1971 before succumbing to pancreatic cancer. Winthrop P. Rockefeller was Winthrop’s only child and served as Lieutenant Governor of Arkansas for 10 years before dying of a blood cancer in 2006.

6. Who We Are • Some of the strengths of the Rockefeller Cancer Institute at UAMS include: molecular epidemiology, cancer control, disparities, bone metastases, multiple myeloma, immunotherapy, behavioral oncology, radiation injury and radiation biology, and laser detection of circulating tumor cells.

7. Implementing a Vision for Clinical Research How Much Longer Until We Get There? Laura Hutchins, M.D. July, 2009

8. Where Have We Been? • 1990 • Paper medical record • Paper flow sheets • Paper case report forms • Paper IRB function • No system • Budget development • Database production • Tissue banking

9. Where Have We Been? • 1992 • ADAMS (Arkansas Data Management System) • Mainframe, MUMPS • Vendor went out of business 2 months after purchase • Interfaced to clinical lab, pathology, blood bank • Added vital signs, problem list, medications, past oncology treatment, referring physicians • History and physical information dictated • Inpatient Physician Order Entry initiated

10. Where Have We Been? • 2001 • Failed attempt to implement an outpatient EMR • 2002 • Developed and implemented ARIA (Automated Research Information Administrator • 2004 • Customized existing primary care EMR for oncology • All history and physical documentation done in the system • Developed electronic chemotherapy electronic orders and charting • Developed electronic toxicity grading forms using NCI CTAE 3.0 • Developed electronic response form using RECIST criteria • Developed past therapy log • Developed order protocol specific order forms

11. NCI CTCAE 3.0

12. RECIST Form

13. Chemotherapy Order Form

14. Clinical Trial Order Form

15. Where Have We Been? • 2002 • POST (Protocol Management: registrations, logs) • Not interfaced • Outdated • ARIA (Protocol Submission: IRB) • 2005 • ARIA (Grant Submission: ORSP) • 2007 • CRIMSON (Clinical Research Online Budgeting Module) • Added to ARIA • Real – time access to the charge-master

16. IRB Submission Form

17. Where Have We Been? Budgets were not prepared in a standard format, fees were inconsistent, approvals were not documented, billing compliance difficult to track: Chaos!!

18. CRIMSON Budget Form

19. Where Have We Been? • Benefits • Helps with protocol compliance • Helps with monitoring visits and audits • Helps bill correctly • More efficient than paper overall • Ongoing Issues • Not all applications fully running • CRF’s largely paper • No interfaces from clinical to research systems

20. “Every Man for Himself” • Issues that may develop when individual investigators are left to devise methods to accomplish their research without central support or structure: • Multiple unlinked, poorly annotated, unbacked-up tissue banks • Multiple unlinked, unbacked-up databases • Increased risk of unsuccessful research • Increased risk of regulatory violations • Overall decreased productivity

21. Where Are We Going? The vision for translational research utilizing the new techniques of genomics, proteomics, genome-wide association studies, etc. to result in personalized medicine will not work in the “every man for himself” environment. • Options for IT support include: • Build your own • Buy it • Collaborate (caBIG )

22. Where Are We Going • We could build our own but: • Issues of time • Issues of how to allow data sharing (data definitions, etc.) • We could buy some: • Cost • Interfaces • Licenses • Customization • Vendor support • Implementing caBIG by far the best option

23. Where Are We Going? • 2006 • Became a C3D adopter • 2008 • Converted the tissue bank to caTissue • Developed Single Sign-On Dashboard • 2009 • C3PR • OpenClinica • Patient Study Calendar • caXchange Developed Event Tracker TrialSearch Contracts

24. Where We Want to Be

25. Implementing a Vision for Clinical Research The Rollout Cheryl Lane July, 2009

26. Clinical Trials - What We Have Implemented

27. UAMS Single Sign-On • Single sign-on • Domain Username and Password • Future enhancement to provide secure access by outside users • Fall 2008

28. UAMS Dashboard • Fall 2008

29. UAMS ARIA, CRIMSON, & Contracts Protocol and Grant Admin CRIMSON Protocol Budget Research Contracts • Spring 2009

30. UAMS Event Tracker (ET) • Spring 2009

31. UAMS TrialSearch • Spring 2009

32. caBIG Cancer Central Clinical Participant Registry • Summer 2009

33. OpenClinica – Open Source Trial Management • Summer 2009

34. caBIG Patient Study Calendar • Summer 2009 – Pending Release

35. Clinical Trials - What We Have Implemented C3PR Patient Study Calendar OpenClinica caXchange Single Sign-on Dashboard TrialSearch Event Tracker

36. Biospecimen Implementation - caTissue Suite • Winter 2008

37. What’s Next? caTissue caAERS caArray Integration caXchange REDCap LabViewer

38. The IT Effort • ARIA (Protocol and Grant Administration) • Project Management (.25) Institution • Developers (2.0) Institution • CRIMSON, Dashboard, TrialSearch, Event Tracker • Project Management (.5) Institution • Technical Advisor (.25) Institution + Grant Funding • Developers (2.5) Institution + Grant Funding • caBIG Clinical Trial Management, etc. and Open Source • Project Management (.5) Institution • Part-time Interns (1) Grant Funding • Part-time Developers (2.5) Grant Funding • Technical Advisor (.25) Institution + Grant Funding • caBIG caTissue Suite, caArray • Technical Advisor (.25) Institution + Grant Funding • Developers (2) Institution

39. Implementing a Vision for Clinical Research a Technical Perspective Umit Topaloglu Ph.D. July, 2009

40. What a Developer Needs to Know * caBIG developer…

41. Tools we are Working on • caBIG • C3PR • PSC • caXchange • Labviewer • caTissue Suite • caTIES • caArray • Other • OpenClinica • LifeRay Portal • EventTracker • Trial Search • Aria/CRIMSON/Contracts

42. Integration via caXchange caTissue UAMS ADT UAMS Lab SOFTLAB Interface Engine C3PR ARIA IRB Protocol/Grants Submission / approval caXchange (Integration via grid and non-grid services) PSC CRIMSON Budget Submission / approval OpenClinica UAMS TrialSearch Search Potential Candidates LabViewer Event Tracker Regulatory Compliance

43. Assessment of caXchange • Provides integration for CCTS applications over caGrid interface • Based on ESB platform allowing for integration with non-grid applications • Provides SOA based integration of systems • Provides integration over other protocols (ftp, WS, etc.) • Provides many infrastructure services • Documented process for integrating non-CCTS systems

44. CCTS Integration Scenario with OC Patient visits the Physician Cancer Central Clinical Participant Registry (C3PR v2) Patient Study Calendar (PSC) Tracks the patient schedule throughout the study Lab Viewer Eligibility is verified and patient is registered to a study caXchange (Hub) Identifies labs, loadsthem into the CDMSand AE system OpenClinica Cancer Adverse Event Reporting System (caAERS) Clinical data is captured Identifies and tracks adverse events and any associated schedule changes

45. How caXchange Facilitates the Integration Scenario 5 1 6 2 1 1 2 2 7 7 3 3 HL7 V3 4 Lab Data 1 2 5 HL7 v2,3 • Study Creation Message (BRIDG based) • Register Subject Message (BRIDG based) • CT Lab Message (HL7 V3) • Load Lab in CDMS Message (BRIDG based) • Schedule Modification Message (BRIDG based) • Adverse Event Notification (BRIDG based) • Get Patient Demographic From EMR based on MRN Open Clinica caAERS UAMS ADT 2 caXchange Hub 2 C3PR 4 Lab Data Multiple Myeloma Database CTODS Data Service CCHC Outside LABS 6 AE Notification CTODS DB 4 Lab Data CTODS Lab Viewer PSC UAMS Lab SOFTLAB

46. CCTS and OpenClinica Integration • We have implemented OpenClinica integration with CCTS • OpenClinica changes • Implement service to accept ‘Register subject’ message • Develop mapping • Define Interface(s) • Implement security • Integrate the service with caXchange • caXchange • Configure routing for OpenClinica • Integration testing

47. OpenClinica Integration with caXchange caXchange C3PR UAMS Register Subject XML Message is Generated by C3PR 2. ServiceMix caXchange Inbound Component (Grid Service On Tomcat) caXchange Client Register Subject XML 1. Eligibility is verified and patient is registered to a study Content Based Routing The caXchange Request Processor Grid Service receives the XML 3. Service Orchestration Distributed Transactions Based on Routing Rules caXchange routes to the caXchange Consumer Service 4. Message Aggregation Message Tracking caXchange Consumer Service (process, rollback, commit) OpenClinica Consumer Service maps payload and calls the OpenClinica Web-Service 5. Tomcat OpenClinica Web Service 6. OpenClinica Web-Service Calls OpenClinica API’s and subject is registered in OpenClinica

48. SSO and Portal • We integrated caBIG and other tools Single Sign On that was incorporated with the UAMS LDAP • We have also customized LifeRay portal to create a single point of access to the tools

49. OpenClinica Integration with WebSSO • Objective: Enable OpenClinica to participate in single sign-on with the CCTS suite while preserving the authorization/permissions that are configured in OpenClinica. • Challenge: OpenClinica uses the Tomcat Declarative Security for Authentication as well as Access Control • Approach:The Ekagra and UAMS teams developed a custom soulwing CAS client. This client allows OpenClinica to support webSSO.

50. Security: WebSSO and OpenClinica CAS Server OpenClinica Database 5. Retrieve Roles JDBCRealm 3. Assertion (Attributes) 5. User Roles 2. Authn using User Credentials 4. Mock Authn & Roles Request 6. User Roles OpenClinica Web Application SoulWing CAS Client Soulwing Realm Wrapper 1.Request 7. Req 8. Res 9. Response