1. Clinical Research Informatics William G. Adams, MD Associate Professor of Pediatrics Director, BU-CTSI Clinical Research Informatics November 10, 2009

2. Visibility of Translational Research CTSA program By 2012, 60 programs at a cost of $500 million per year Foundations Industry Disease-related organizations Hospitals and health systems Journals

4. What is “translational research”?

6. T1 and T2 T1: “The transfer of new understandings of disease mechanisms gained in the laboratory into the development of new methods for diagnosis, therapy, and prevention and their first testing in humans.” T2: “The translation of results from clinical studies into everyday clinical practice and health decision making.” Sung, N. S. et al. JAMA 2003;289:1278-1287.

7. Copyright restrictions may apply. Sung, N. S. et al. JAMA 2003;289:1278-1287. IOM Clinical Research Roundtable

8. Central Translational Challenges 1.Public Participation 2.Information Systems 3.Workforce Training 4.Funding Sung, N. S. et al. JAMA 2003;289:1278-1287.

9. The Laboratory of T1

10. Resources Needed for T1 Mastery of molecular biology, genetics, and other basic sciences Appropriately trained clinical scientists Strong laboratories Cutting-edge technology Supportive infrastructure within the institution

12. The Laboratory of T2

13. Resources Needed for T2 “Implementation science”: evaluating interventions in real-world settings Clinical epidemiology and evidence synthesis Communication theory Behavioral science Public policy Financing Organizational theory System redesign Informatics Mixed methods/qualitative research

15. Informatics Resources Across the Research Continuum Hypothesis generation, cohort preparation (intra- and inter- institutional), epidemiology IRB protocol preparation and approval Subject Recruitment Research Data Management Research TaskInformatics Resource BMC-CDW i2b2* CliniWorks Consultation Service INSPIR Volunteer* Registry Red-Cap* BMC-CDW * Open-source software available from CTSA community Research Networking Profiles*

17. CRI Systems and Projects Data Repositories (i2b2) BU-i2b2 Massachusetts Health Disparities Repository (MHDR) Shared Research Information Network (SHRINE) Subject Registries (ResearchMatch.org) Research Data Capture (RedCap) Research Networking (Profiles)

18. What is i2b2? “Informatics for Integrating Biology with the Bedside” Open-source software based on the MGH Research Patient Data Repository (RPDR) Collection of modules or “cells” constitute the i2b2 “hive” PHI-free clinical database repository Self-service query and analysis tool

21. Ontologies AttributeDescriptionOntologyCodeSystem WeightBody Weight (kgs)Clinical Obs27113001SNOMET-CT Gender Demographic s 36587300 7 SNOMET-CT cd4 countCD4 cell (# Bld)Lab Tests 8127-3LOINC AttributeIDValueDate Weight61207/12/2009 Gender6M9/12/2009 cd4 count67504/1/2009 Facts Core Tables of the i2b2 Data Repository

24. i2b2 @BU Two installations: BU-i2b2 Core BU-CTSI Resource Installation to be completed next week MA-Health Disparities Repository (MHDR) Kressin/Adams co-PIs NIH Grand Opportunity (GO) Grant Began in October 2009

25. Boston Medical Center Community Health Centers HealthNet Plan Boston-MHDR Researchers have direct access to patient-level data within repository IRB must approve creation of repository and (separately) all research protocols BU-i2b2 Researchers only have access to repository via software that performs aggregate queries (counts > 5) IRB must approve creation of repository Queries are not human subjects research Research Data System Clinical Data System Data Processing Researchers do not have access to clinical data CDW staff or “business associate” creates and transfers Limited Data Set via automated scripts Secure, encrypted Link Table used for updates Clinical Data ( BMC Clinical, CHC Clinical, HealthNet Claims) ETL (Extract, Transform, Load) Limited Dataset(s)* in i2b2 format Covered Entities * Limited data set identifiers limited to registry ID and census tract for Boston-MHDR and registry ID for BU-i2b2 BUMC i2b2-related Research Repositories Overview

26. BU-i2b2 Established using CTSA core resources Currently under evaluation as pilot tool Actively looking for pilot evaluators Expansion plan to include visits and health insurance ontologies

27. Massachusetts Health Disparities Monitoring System Nancy Kressin, PhD, Director, Health/care Disparities Research Program William Adams, MD, Associate Professor of Pediatrics, and Director, Clinical Research Informatics, BU-CTSI

28. Project Team Christopher Shanahan Arlene Ash Amresh Hanchate Michael Paasche-Orlow Emelia Benjamin Joel Weissman (consultant from the state) UMass: Ralph Zottola, Jeroan Allison Recombinant Data Corporation

29. Aims 1.Create infrastructure to monitor CVD risk factors and outcomes large, longitudinal, statewide de-identified database new software tools for “push button” monitoring, data extraction and geo-mapping 2.Explore the effects of health reform and the economic downturn on health disparities in Massachusetts 3.Develop strategies for sharing tools and communicating results to policy makers, health care providers, and the research community

30. Data Sources BMC (clinical data warehouse) BMC affiliated community health centers BMC Health Plan (claims data) UMass Medical Center (clinical data warehouse)

31. Demonstration

35. Receives within minutes qualified results

36. EMR views dashboard is generated on-the- fly out of free text documents only! Click on the found term will get you to the original document source

37. De-identified within text: Visit details, MRN Visit day + month Patient’s name Former Locations Providers names ASSESSMENT: 52-year-old male with poorly-controlled, type 2 diabetes. He is probably maxed out on oral agents. See above conversation. Other problems include uncontrolled hypertension, mild persistent hyperlipidemia, now on a maximal dose of Lipitor. PLAN: He is fasting, so check fasting lipids plus SGPT. Recheck hemoglobin A1c. Work on carb counting and get a diabetes update with our diabetes educators and then transition him to Humalog. At that point, discontinue Glucotrol. Consider him for a pump candidate. Decide on an ARB. Follow up with me in three or four months. ADDENDUM: Triglycerides 54, HDL 37, and LDL 72. Potassium is 3.5, creatinine 1.0. HbA1c 8.8%, and urine microalbumin pending. Dictated by:* ****************, M.D. Assistant Professor Electronically Authenticated - XX/XX/08 LKC/mhm T *** D *** A XX/XX/08

38. i2b2.org 38

39. i2b2 and Shared Health Research Information Networks (SHRINE) Douglas MacFadden Andrew McMurry Shawn Murphy Partners Healthcare http://catalyst.harvard.edu

40. Networks i2b2 clinical databases across the web Aggregates query results across all sites Each site maintains autonomous database What does SHRINE do?

41. SHRINE 5.6M+ Patients 890M+ Facts 3 Ontology Categories, 18k+ Terms 4 major competing hospitals, 3 sites 7,500+ Potential Users 4 IRBs Metrics as of October 2009

42. CTSAs University of Washington UC San Francisco UC Davis IRB approved SHRINE deployments West Coast SHRINE Sites

43. ResearchMatch.org Paul Harris, PhD Director, CTSA Biomedical Informatics Operations Department of Biomedical Informatics, Vanderbilt University

44. What is ResearchMatch.org? A centralized, web-based recruitment registry designed to ‘match’ individuals interested in participating in research with research teams Institution-neutral; Disease-neutral; Study-neutral Complementary, no-cost recruitment tool for research teams CTSA collaboration - 38 participating CTSAs

45. How will ResearchMatch.org work? Step 1: Potential volunteers (or their parents/caretakers) self-register to indicate a willingness to be contacted for research studies. Step 2: Registered researchers search database for individuals (identifiers suppressed) based on study inclusion criteria.

46. How will ResearchMatch.org work? Step 3: Researchers send approved recruitment message to ‘matched’ volunteers. Volunteers may then opt to share identifiable information for direct contact. Step 4: Researchers contact interested volunteers and follow normal study consent procedures.

47. Research Electronic Data Capture (REDCap) Paul Harris, PhD Director, CTSA Biomedical Informatics Operations Department of Biomedical Informatics, Vanderbilt University

48. REDCap Project Overview 2004 Needs Assessment Researchers needed help managing data for small/medium sized non-trial research projects (pilot, R01, PPG) Hypothesis Researchers will do the right thing (secure, audit trails, etc) if provided an easy way to get needed tools Problem Many projects, few resources

49. REDCap Project Overview Solution: Metadata-driven application (no per-project programming) 2004 - First REDCap project operational at VU 2006 - REDCap Consortium Launched REDCap Consortium to share with other universities and foster collaboration for future development 2008 – CTSA Informatics Pilot Project (IPP) Award Increase capacity and streamline processes for collecting and managing data in diverse scientific areas of study

52. REDCap Survey Currently @ 12 Institutions 80,000 Surveys Collected

53. RedCap Features Secure Researcher driven Meta-data library MySQL Export flexibility Inexpensive

54. Collaborating on “Profiles” A case study on sharing a research networking platform & informatics across Harvard & UCSF Maninder Kahlon, PhD (UCSF) CIO, UCSF CTSI Griffin Weber, MD, PhD (Harvard) CTO, Harvard Medical School

55. Harvard Catalyst Profiles – Active & Passive Networking

56. Keyword Cloud CoAuthors: Map View CoAuthors: Radial Graph SNA: Network ReachSNA: ClosenessSNA: Keyword Network

57. A “Boston Common”? Discussions underway to potentially create: BU-Profiles Tufts-Profiles Integrated system (The Boston Common)

58. Informatics Resources Across the Research Continuum Hypothesis generation, cohort preparation (intra- and inter- institutional), epidemiology IRB protocol preparation and approval Subject Recruitment Research Data Management Research TaskInformatics Resource BMC-CDW i2b2* Cliniworks Consultation Service INSPIR Volunteer* Registry Red-Cap* BMC-CDW * Open-source software available from CTSA community Researcher Networking Profiles*

59. Concluding Thoughts Informatics essential component of Clinical/Translational Research Superb open-source opportunities from CTSA Community Small investments could lead to great benefits Clinical Research Informaticians in short supply Contact info: badams@bu.edu