Association of GCRC Statisticians August 7, 2004

1. “Information Integration -The Next Frontier” Association of GCRC StatisticiansAugust 7, 2004 Joyce C. Niland, Ph.D. Professor and Chair, Information Sciences City of Hope National Medical Center

2. Executive Summary:October 2003 GCRC Workshop

3. Outline • Why This Workshop, and Why Now? • Overview of Workshop Presentations • Vision of the GCRC Informatics Cores • Group Discussion

4. Challenges in Clinical Research • Efforts to mount clinical research are enormous • Data rarely can be effectively exchanged, integrated • Lack of standards hampers efficient trial design, decision support, analysis

5. D H H S National Health Information Infrastructure NIH Roadmap NCI National Strategic Initiativesin Support of Biomedical Research

6. 30,000 Foot View: National Health Information Infrastructure (NHII) • Department of Health and Human Services (HHS) initiative to improve effectiveness, efficiency, and overall quality of health care • Stemmed from April 2004 executive order to establish interoperable electronic health records within 10 years • Kickoff session July 21-23, 2004 in Wash DC • DHHS Secretary Tommy Thompson • Health Information Technology (HIT) Coordinator David Brailer, MD, PhD • Honorable Bill Frist, Rep Nancy Johnson, Newt Gingrich • Heads of FDA, CDC, VA, NIH, DoD, AHRQ, OPM

7. National Health Information Infrastructure (NHII) • Four main goals of HIT initiative: • National electronic health records • Interoperable infrastructure to promote patient record portability across clinicians and practice sites • Facilitating patient participation and personalized care • Using HIT to improve population health • Estimated that completed project will save $130Bin health care costs • Other tangible benefits include: • Decreased medical errors • Earlier detection of bioterrorism • Improved local health care systems • Increased efficiency in medical research

8. Clinical Research SIG: Preamble We the people . . . . hereby recommend that the NHII ensure that clinical and translational research needs are interwoven through the NHII strategic plan, in order to form a more perfect Union between clinical care and research endeavors. Be it known that we also urge our nation’s government to articulate the long-term vision and mission for research within the NHII, in addition to the short-term actionable articles set forth herein.

9. Clinical Research SIG: Preamble The NHII should be concerned with all facets of research related to human health and well-being, including but not limited to:clinical research, basic science, population research, environmental sciences, bioengineering, and informatics. . . . . These truths we hold self-evident.

10. NIH Roadmap NIH Roadmap

11. Dr. Zerhouni’s NIH Roadmap • Speed biomedical research by: • Building on strengths • Identifying best practices • Increasing collaboration among researchers

12. New Pathways to Discovery Research Teams of the Future Re-engineering the Clinical Research Enterprise NIH Three Arteries of the NIH Roadmap

13. Dr. Zerhouni’s NIH Roadmap • Speed biomedical research by: • Building on strengths • Identifying best practices • Increasing collaboration among researchers • Build the National Electronic Clinical Trials & Research Systems (NECTAR) • Enhance clinical research through informatics tools • Standardize data, software tools, and network infrastructure for seamless data and sample sharing • Maximize connectivity among existing and newly created clinical research networks

14. Roadmap Will Require the Full Scope of the Discipline of Informatics Research,development, and application of tools and approaches for measurement, collection, annotation, analysis, and interpretation of patient care / clinical research data <---BIOMEDICAL INFORMATICS---> Basic Science Clinical Research Bioinformatics Clinical Research Informatics Genotype Phenotype Measurement, collection, annotation, analysis and interpretation of biological data, often at the genome level. (Employs tools / techniques from Computational Biology and Biostatistics)

15. Contributing to the Global Solution • GCRCs represent a substantial investment in biomedical research and data • Major opportunity and potential to contribute to the NIH Roadmap and NECTAR • Informatics Cores operating independently • Often inventing their own informatics toolsto meet these challenges (of necessity) • General lack of communication /consensus on informatics approaches • Rationale for two-day workshopat the NCRR last October

16. Organizing Committee Composed of NCRR, AGITP, BIRN, and FIRST representatives: • Dr. Elaine Collier • Dr. Bob DiLaura • Dr. Randy Gollub • Dr. David Ikle • Dr. Joyce Niland • Dr. Bob Rice • Dr. Hemant Shah • Dr. Doug Stahl

17. Substantial Interest from GCRC Cores • Evidenced by over 100 attendees from 54GCRC institutions • Excellent abstract submissions and active participation in two-day meeting • Objective: Identify approaches to make GCRC Informatics Core most effective contributor to biomedical research through IT approaches

18. Day One Agenda • Welcome Dr. Judith Vaitukaitis Dr. Anthony Hayward • National Initiatives BIRN caCORE FIRST GCRC Survey • Local GCRC Initiatives Clinical Research Management Tools for Research Collaboration • The Future A Standards Perspective

19. Day Two Agenda • Moderated Panel I Vocabulary & Data Standards • Moderated Panel II Open Source Development • Poster Sessions • Breakout Sessions Role of the GCRCs in Developing and Adapting Informatics Tools • Wrap-up & Discussion

20. Informatics InitiativesPresented

21. Survey of GCRC Informatics Cores (B. DiLaura) • Excellent response rate (95%) • Some key findings: • Many one-off solutions in place • Mixed levels and types of technologies • Lack of current cross-GCRC interactions • Many unmet needs: scheduling, SAE reporting, etc.

22. Local GCRC Initiatives Presentations and posters on GCRC Informatics Cores’ roles in: • Clinical research management tools • Web-services suite of technologies • Barriers to data sharing and integration • Web-based applications to integrate heterogeneous data sources • Facilitating research through the AGITP

23. BIRN: Biomedical Informatics Research Network (R. Gollub) • Testbed for a biomedical knowledge infrastructure • Creation and support of federated bioscience databases • Data integration and interoperable analysis/data mining tools • Scalable and extensible • Driven by research needs pull, not technology push

24. FIRST: Fully Integrated Research Standards & Technology (J. Niland) • 3-year GCRC supplement grant conducted at COH • Input from USC and CHLA • Collaboration from Los Alamos National Laboratory(Dr. David Forslund) • Goal: Develop a fully integrated scalable information management and decision support environment • Creation of a unified informationarchitecture with standard: • Data Model • Vocabularies • Data Interfaces • Informatics Training Program

25. Functionality to be Supported in FIRST Results Research Idea Protocol Tracking Outcome Measures Eligibility Screening Protocol Monitoring Patient Tracking

26. Position Available: Senior Statistician and Section Head, Hematology/Bone Marrow Transplantation DEPARTMENT OF BIOSTATISTICS City of Hope NationalMedical Center, located 25 miles northeast of Los Angeles in Duarte, California, is seeking an experienced senior statistician to join the Department of Biostatistics. City of Hope, begun over 90 years ago, has grown into an international medical center and research institute known for research in cancer, diabetes and AIDS, and has been designated a Comprehensive Cancer Center by the National Cancer Institute. City of Hope has a large portfolio of investigator-initiated and cooperative- group clinical trials, across many excellent biomedical research programs, including a world -renowned BMT program. For the second year in a row US News and World Report has named City of Hope one of the top cancer hospitals in the nation. The Division of Information Sciences at City of Hope is an innovative group of 136 professionals collaborating in all phases of basic and clinical research, encompassing Departments of Biostatistics, Clinical Research Information Management, and Biomedical Informatics. We are seeking an experienced clinical trials statistician who will be responsible for collaborative research in the areas of BMT for leukemia/ lymphoma, serving as Section Head and Senior Statistician for the BMT Program Project Grant, Lymphoma SPORE grant, and the national Islet Cell Data Coordinating Center. This individual will supervise 3 Masters- level statisticians and 1 Ph.D. statistician, overseeing data analyses, preparing manuscripts, and participating in grants. Department of Biomedical Informatics (26 Members) Department of Biostatistics (30 Members) Department of Clinical ResearchInformation Mgmt (74 Members) Supporting Biomedical Research at City of Hope Division of Information Sciences (136 Members) Protocol Design Project Mgmt Data Analysis Systems Biology Data Collection Applications Study Management Architecture Database Modeling

27. Incorporating Standards • Standardized Unified Modeling Language (UML) models for clinical research functions • Use of standardized vocabularies, and semantic analysis to map among vocabularies • SNOMED • LOINC • NCI CDEs • Data interexchange standards • eXtensible Markup Language (XML)

28. Incorporating Standards • Health Level 7 (HL7) standard for clinical data interchange: Reference Information Model (RIM) • V3.0 includes standardized class and block diagrams to represent healthcare information • HL7 Regulated Clinical Research Information Model (RCRIM) • Evolving a standardized model for research • City of Hope participating as HL7 institutional member • Also participating in ‘CDISC’ modeling

29. Clinical Data Interchange Standards Consortium (CDISC) • An open, multi-disciplinary, non-profit organization • Began in 1997 • Mission: lead the development of global, vendor-neutral, platform independent standards to improve data quality and speed product development • Development of industry standards to support electronic acquisition, exchange, submission, and archiving of clinical trials data

30. Where CDISC Fits in the “World of Standards” International Conference on Harmonization (ICH) Japan MHW US FDA EU EMEA Pharmaceutical Industry EU USA Japan EFPIA PhRMA JPMA REGULATORY AUTHORITIES Health Care Providers & Pharmacies - NCPDP CDISC Clinical Trials Models: NCI, OMG Standards: HL7, XML Dictionaries: MedDRA, LOINC

31. Standards Perspective from the Experts Health Level 7- V3.0(Dr. Gunther Schadow) • Reference Information Model (RIM) • Entities (people, animals, devices) in their roles • Participate in acts (clinical trial) • Utilizes UML standards • Block diagrams to save screen real estate • A ‘grammar’ to construct medical information • Emerging RCRIM: Regulated Clinical Research Information Model • CDISC to submit their model to RCRIM for ‘ballot’

32. HL7 RIM Class Diagram

33. FIRST Block Diagram:Protocol Registration

34. A Standards Perspective Distributed, Service-Based Architecture(Dr. Forslund) • Interoperable components (“plug and play”) • Standardized components that separate specification from implementation through interfaces • Service-oriented architecture approach • Define fundamental capabilities around an object model (UML) • Data models are fully extensible and independent of any database representation • Use of common services would allow GCRCs to work together

35. Significance of CORBA Technology • Advantages through flexibility and reusability of CORBA services • Minimizes additional development • E.g. built-in security, audit trail • Places emphasis on knowledge representation,rather than database construction • Database created automatically via XML Data Type Definition (DTD)

36. CORBA Graphical Representation Defines relationships among data elements XML configuration files <Trait Type = "HL7" Name="Patientt”<Value> Hasman^Arie^^^^ </Value></Trait> <Trait Type="HL7" Name="PhoneNumber_Home"> <Value>(505)672-1200 </Value> </Trait> <Trait Type="HL7" Name="SSNnumber"> <Value>111-222-3333 </Value> </Trait> Tells service what the data is CORBA Data Base • Data • patient CORBA Service Entity-Attribute-Value (EAV) structural independence Stores data & preserves relationships defined by the configuration file, maintained by PIDS service Can be HL-7, flat files, etc

37. A Standards Perspective Standard Terminologies(Dr. James Cimino) • Standards support merging of data, reuse of information • Several established standards (LOINC, SNOMED-CT) • Many have shortcomings (CPT, ICD-9) • Emerging standards show great promise (Rx-NORM) • Unified Medical Language System (UMLS) • Not created as a terminology • Subsumes other terminologies, maps among them

38. Moderated Panels Vocabulary & Data Standards(Cimino, Covitz) • Experiences and problems in implementing vocabulary standards • Motivations for utilizing, successes, removing impediments Open Source Development(Forslund, Ho, Schadow) • Development of national healthcare initiatives • Potential for collaborative development within GCRCs

39. Biomedical Objects Common Data Elements Enterprise Vocabulary NCI’S caCORE: Infrastructure for Clinical Research Scientific Applications

40. Biomedical Information ‘Tsunami’ • Overwhelming data volume • Multitude of sources

41. NCI caBIG • Goal: A virtual web of interconnected data, individuals, and organizations redefines how research is conducted, care is provided, and patients/participants interact with the biomedical research enterprise • Cited by DHHS Secretary Tommy Thompson as potential precursor to NIH “NECTAR”

42. caBIG ‘Desiderata’ • Open access, open source • Derived from common information models • Standards for data exchange formats • Data and metadata following ISO 11179 • Consume appropriate public, open access standards when available • (Note: These same principles followed in FIRST)

43. Timeline: • Phase I – (summer 2003) • Meetings to discuss caBIG initiative • NCI-designated Cancer Center needs/capability/interest presented at cooperative development meetings • Extensions to NCICB infrastructure • Phase II – (fall 2003) • Selected pilot participants • Established working groups • Established communications portal • Phase III – (spring 2004) • Establishment of master contracts • Assessment of pilot statements of work

44. The graph below shows the frequency of needs identified by Cancer Centers duringthe Cooperative Development Meetings to select the final participants for the caBIG pilot. Leading priority

45. NCI caBIG Award Announcement (December 19, 2003) City of Hope selected as Developer sitefor caBIGclinical trial management systems(with Universityof Pittsburgh)

46. WorkshopBreakout Sessions

47. Breakout Sessions • Created 4 Teams • Mission - • Key themes, issues or priorities? • Significant challenges/barriers to progress? • Changes required or helpful to get started? • (include human, IT, other resources) • Where do we go from here - recommendations? • Support – • * Assigned each Team a Facilitator • * Team picked a Scribe and Spokesperson

48. Wrapping It Up:Summary ofTeam Deliberations GCRC Informatics Meeting October 30, 2003

49. Vision for Future GCRC Collaboration • Remarkable consensus among participants to work cohesively and cooperatively in future • Transform GCRCs into powerful facilitatorsof biomedical research • Vision kindled excitement and energyacross all four Working Groups • Integration theme was embraced by all four Breakout Groups