1. HERON, Frontiers, and Pioneers: Database and Recruitment Resources to Advance Your Research Jeffrey M. Burns, MD, MS Edward H. Hashinger Professor of Neurology Director, Clinical and Translational Science Unit Associate Director, KU Alzheimer’s Disease Center Russ Waitman, PhD Associate Professor, Department of Internal Medicine Associate Vice Chancellor for Enterprise Analytics Director of Medical Informatics Patricia Kluding, PT PhD Associate Professor, Dept of Physical Therap & Rehab Sciences Director, Georgia Holland Health Exercise and Aging Lab Associate Director, Clinical and Translational Science Unit

2. What is the CTSU? Supports research activity NIH-Funded –A program of Frontiers: Heartland Institute of Clinical and Translational Research –Physical Infrastructure Clinic rooms Infusion center Exercise physiology Sleep lab and beds for extended stays Metabolic kitchen –Nursing –Coordinators –Recruitment Program Registry Pioneers Community Registry –CTSU Satellite / CTSU Without Walls program

3. KU Clinical Research Center http://www.youtube.com/watch?v=zsMBazY31S0

4. Clinical Space Clinical Area 9 exam rooms for multi-purpose outpatient research evaluations 2 cognitive testing rooms 2 Isolation exam rooms, designed for smoking cessation or ID studies Workspace for up to 8 study coordinators Infusion Center 11 infusion suites for drug administration and pharmacokinetic studies Investigational pharmacy

5. Extended Observation Unit / Sleep Lab Extended Observation Unit (EOU) to allow evening stays 3 hospital-style suites Study drug administration, observation & PK lab draws Sleep Program opened in October 2012 (Suzanne Stevens)

6. Exercise Physiology Laboratory  Exercise Physiologist, ACSM Certified  Two Parvo Medics Metabolic Carts  Maximal Graded Exercise Testing with Medical Monitoring  Multiple Modalities and Protocols  Treadmill  Cycle  Recumbent Stepper  Upper Body Ergometer

7. Metabolic and Demonstration Kitchens Assessment of dietary intake Direct or digital photograph observation 24-hour recalls Food records Food frequency questionnaires Screeners Nutrition interventions Recipe Development and Testing Research diets / Controlled feeding protocols Standardized meals

8. CTSU Satellite Space Meet basic needs of investigators on campus Rooms and basic supplies –Delp – shared space with Dr. Moriarty, overflow room. –Hoglund Brain Imaging Center –Swope Health Services

9. Research Coordinator Pool Service  % FTE or $60 per hour  Coordinator may provide services including  Regulatory processing for the trial  Coordinating and conducting study visits  Performing study-required procedures  Documentation  Assisting with monitor visits  Many other tasks and duties

10. Participant Recruitment Frontiers Registry Pioneers program

11. Research Participant Registry Program  Comprehensive registry of KUMC patients willing to be contacted for participation in research studies  4 clinics started in 2009, now active 17 clinics  15,000+ enrolled in registry by September 2012  17 researchers have received participant information for 25 protocols ( 7 PhDs, 8 MDs, 1 PharmD and 1 MSPT)  148 participants identified from the registry have been enrolled in protocols

13. Summary of CTSU The purpose of the CTSU is to support research by providing –Space –Nursing / coordinators –Access to important resources Exercise physiology Overnight stay and sleep lab capabilities Metabolic kitchen –Recruitment tools Frontiers Registry, Pioneers Program

14. KUMC Biomedical Informatics Resources for your Research: a focus on HERON Russ Waitman, PhD Director of Medical Informatics, Director, Frontiers Biomedical Informatics Assistant Vice Chancellor, Enterprise Analytics Associate Professor, Internal Medicine University of Kansas Medical Center Kansas City, Kansas This project is supported in part by NIH grant UL1TR000001 and NSF Award CNS-1258315

15. “Hooking” People on Informatics How We Work: the technology and the team What’s on the Horizon – Enhanced Registry Integration and data delivery with REDCap – Collaboration via CTSAs and PCORI opportunity to generalize your research findings Overview

16. We have tools and expertise to manage data and convert it into information REDCap and CRIS – enter and manage data HERON – fish for data from the hospital/clinic Biweekly Frontiers Clinical Informatics Clinics – Tuesday 4-5 pm in 1028 Dykes Library. – Next session September 17, 2013. Biomedical Informatics Can Help Your Research

17. Bennett Spring Trout Park, Lebanon Missouri http://mdc.mo.gov/regions/southwest/bennett-spring You’re that fisherman: wanting to land data to answer your research hypothesis

18. The Fish: Diagnoses, Demographics, Observations, Treatments

19. Why so many fish? Current Goal: Build Hatchery, Manage the Fishery

20. Photo Credit: HuntFishGuide.com http://www.flickr.com/photos/huntfishguide/5883317106/ Second Goal: If you need help fishing, get a guide

21. Photo Credit: S. Klathill http://www.flickr.com/photos/sklathill/505464990/ Prepare and Analyze Data

22. Photo Credit: Steve Velo http://www.flickr.com/photos/juniorvelo/259888572/ Our shared goal: a tasty publication

23. I’ll just enter everything in Excel…. What if I lose or accidentally sort my spreadsheet? How to I let students only review de- identified data? Hospital/Clinic is making me use this Electronic Medical Record and I get nothing in return... Little White Salmon River, Washington State, last Summer in July Nightmare: looks like a nice river, but can’t catch fish

24. https://redcap.kumc.edu – It uses the same username and password as your KUMC email. – Non-KUMC researchers can request an affiliate account through Frontiers CTSA office – Check out the training materials under videos Case Report Forms – (see left) registries, trials Conduct Surveys – Similar to “SurveyMonkey” Sometimes, You’re willing to enter data/buy fish: REDCap: Research Electronic Data Capture

25. http://www.flickr.com/photos/wiccked/185270913/lightbox/ REDCap: think Fish Tank you manage

26. Bonneville Hatchery: Trout, Salmon, Sturgeon, Columbia River, Oregon I want to go fishing, not fill a fish tank (REDCap) Use HERON: a managed fishery

27. Get a License: Develop business agreements, policies, data use agreements and oversight. Get a Fishing Rod and Bass Boat: Implement open source NIH funded (i.e. i2b2 https://www.i2b2.org/) initiatives for accessing data. Know what your catching: Transform data into information using the NLM UMLS Metathesaurus as our vocabulary source. Stock Different Tasty Fish: link clinical data sources to enhance their research utility. Central CTSA Informatics Aim: Create a data “fishing” platform: HERON, https://heron.kumc.edu

28. Fill out System Access Agreements to sponsor students/staff Fill out Data Use Agreement to request data export No Limit!!! IRB Protocol Not Required to view or pull de- identified data Must be on campus or use VPN or https://access.kumed.comhttps://access.kumed.com Check http://frontiersresearch.org/frontiers/HERON-Introduction for more information, status, and training videoshttp://frontiersresearch.org/frontiers/HERON-Introduction Single sign-on using your email username Real-time check for current human subjects training HERON: Getting a Fishing License

29. The i2b2 “Fishing Rod”: build Diabetes cohort Drag concepts from upper left into panels on the right Types of “fish” in folders

30. i2b2 : AND in Frontiers Research Registry Dragging over the second condition

31. i2b2: AND a high Hemoglobin A1C When you add a numeric concept, i2b2 asks if you want to set a constraint

32. i2b2 Result: 497 patients in Cohort Run the Query Query took 4 seconds 497 patient in cohort

33. I2b2: Explore Cohort, Visualize

34. http://www.oregon.com/columbia_gorge_attractions/bonneville_hatchery Catch the data for JAMA, NEJM publication The dream: landing the big one

35. Without getting bit

36. HERON as Central Aim to CTSA

37. “Signals” of Health: Think of each source electronic system as an EKG, blood pressure cuff, arterial line Hypothesis #1: Admin + Clinical -> Better Knowledge? Hypothesis #2: Computer + Clinical Process-> Better Health?

38. Goal: stable monthly process, minimal downtime Complete rebuild of the repository, not HL7 messaging update based. Two databases: create new DB while old DB is in use. When the new DB is ready, switch over i2b2 to serve customers fresh data. Initial Files from Clinical Organizations Export KUH Epic Clarity relational database instead of Cache/MUMPS. Monthly file from clinic billing system (GE IDX). Demographics, services, diagnoses, procedures, and Frontiers research participant flag. – UHC CDB hospital quality, Tumor Registry, Biospecimens Extract Transform Load (ELT) processes largely SQL (Oracle) Wrapped in python scripts. Goals for a monthly release (21 months in a row so far): – Fresh data. Example: another month of visits = millions of facts – New types of data. Example: microbiology – New functionality: Example: link data by encounter across clinical and financial sources; distinguish medication administration from prescription How the Team Works: HERON Evolves Every Month

39. https://informatics.kumc.edu/work/bloghttps://informatics.kumc.edu/work/blog - world view https://bmi-work.kumc.edu/work/bloghttps://bmi-work.kumc.edu/work/blog - internal KUMC view: latest breaking developments Monthly Release Blog highlights: -Features -Size -Dates of sources

40. HERON’s Data Sources, Types of Data https://bmi-work.kumc.edu/work/wiki/HeronProjectTimeline#July2013Planning - contains current plan for next several monthly releases

41. Find a colleague Talk with hospital, clinic to understand workflow Attend bi-weekly clinics Watch the videos: http://frontiersresearch.org/frontie rs/informatics-training-videos Request a consult http://frontiersresearch.org /frontiers/biomedical- informatics http://frontiersresearch.org /frontiers/biomedical- informatics If you don’t see what you want, or you really like things, let us know: https://redcap.kumc.edu/surveys/?s=3S BkPg&tool=1 “Who’s Using HERON” and collaboration approaches

42. HIPAA Safe Harbor De-identification – Remove 18 identifiers and randomly date shifting by up to 365 days back in time Downside: can’t do seasonal studies without IRB approval to go back and get actual dates In general, tack on 7 months when wanting volume for the last year. – Resulting in non-human subjects research data but treated as a limited data set from a system access perspective. System users and data recipients agree to treat as a limited data set (acknowledging re-identification risk) To be addressed: – For now, we won’t add free text such as progress notes with text scrubbers (DeID, MITRE Identification Scrubber toolkit) Date Shift example: – Patient was born August 13, 1968, had their blood pressure measured on November 28, 2012. – Each month dates shifted, ex: to -15 for January release: New birthday is July 29, 1968 and the blood pressure measurement occurred on November 13, 2012. For another patient, their offset might be -278. Next month the Aug 13 th patient’s offset might be -192. HERON De-identification: Remove HIPAA 18 identifiers -> non human subjects research

43. Repurposing i2b2 Clinical Research Infrastructure for Inpatient Quality Improvement i2b2 “largely” ambulatory or population/genomics focused Is i2b2 version 1.6 with same financial encounter and modifiers now useful for inpatient research? Goal: understand medication timing and antibiotic selection Suspect vancomycin preferred Validate HERON medications – Especially administration timing

44. REDCap registries into i2b2 allows intuitive exploration – Researchers may need less abstraction as data is extracted from the EMR. i2b2 into REDCap: inherit security model, graphical/export tools Aligning Clinical Research Informatics for Quality: Registry Abstraction and Data Delivery

45. Evidence Generation: Trials post Electronic Health Records (EHR) – Learning Healthcare System Institute of Medicine Reports: 2006 onward. – 2011 Report: Digital Infrastructure for the Learning Health System: The Foundation for Continuous Improvement in Health and Health Care “Information Technology (IT) serves as the functional engine for the continuous learning system” Effective Biomedical Research Organizations will integrate Medical Informatics and Clinical Research Informatics capabilities with Operational Clinical Systems of the Healthcare Systems – EHR Standardization and collection of data becomes critical to the cost effective research capacity of the University. – EHRs (Cerner/Epic), clinical research systems like (REDCap/Oncore/Velos), and ultimately translational bioinformatics systems will need to be managed holistically as opposed to siloed. Next Steps: A Learning Healthcare System

46. PCORI Coordinating Center Steering Committee Scientific Advisory Board Special Expert Group CDRN PPRN Patient-Centered Outcomes Research Institute Clinical Data Research Network Announcement Selby JV, Krumholz HM, Kuntz RE, Collins FS. Network news: powering clinical research. Sci Transl Med. 2013 Apr 24;5(182):182fs13. doi: 10.1126/scitranslmed.3006298. Epub 2013 Apr 23. April 23, 2013 Two types of component networks: systems-generated and patient driven networks Active involvement of health care systems, of clinicians and of patients A commitment to establishing inter- operability and data sharing across networks and ready collaboration with the larger research community

47. What Do They Want the Network to Do? Joe V. Selby, MD, MPH, Executive Director ONC HITCP June 5, 2013 COOPERATIVE AGREEEMENT AWARD 18 MONTHS LATER At least two health care systems engaged Willingness and capacity to work toward data standardization with other awardees Willingness to participate in collaborative studies with data sharing as part of a national research infrastructure > 1,000,000 patients enrolled Data standardized within network and with other awardee networks Patients, system, and clinicians engaged in governance & use Capable of implementing clinical trials Capabilities : Rich clinical data from electronic health records and other data sources stored in standardized, interoperable formats. Capacity to conduct both observational studies and randomized trials embedded in clinical settings Rigorous practices for data security and confidentiality Appropriate IRB and human subjects oversight Utility for CER, safety studies, surveillance, etiologic research, and potentially for pre- approval trials

48. The “Greater Plains Collaborative” Letter of Intent Submitted Tuesday KS, the University of Kansas Medical Center (KUMC) MO, Children’s Mercy Hospital IA, University of Iowa Healthcare WI, the University of Wisconsin- Madison, the Medical College of Wisconsin, and Marshfield Clinic MN, the University of Minnesota Medical Center NE, the University of Nebraska Medical Center TX, the University of Texas Health Sciences Center at San Antonio and the University of Texas Southwestern Medical Center. Will learn in July if we can apply in September, award in December – $7 million total costs over 18 months

49. Community Research Recruitment Registry www.pioneersresearch.org

50. Pioneers Development Frontiers / CTSU team – Communications – Frontiers Registry Bioinformatics team – REDcap survey – HERON search – Active studies list Information technology Website development Regulatory / legal Ethics Community Partnership for Health – POW! paPOW! papaPOW! Outreach plan for public and researchers – KU entities – All Frontiers organizations

51. Become a Pioneer! Potential research participants = Entire community – KUH patients – Non-KUH patients – Healthy individuals Online enrollment & informed consent – Enroll self, children, family member/surrogate

52. Become a Pioneer! Email verification Brief survey (redcap) – Demographic and contact info – Medical history info (self report) – Option to link to EMR if KUH patient

53. Pioneers: Universal Research Portal Currently, multiple individual databases Pioneers offers: – Single sign up process for participants – Powerful search options with EMR access – No cost to investigators to manage database, to search for participants, to advertise study – Able to screen by email with study – specific questions

54. Investigator Access Open to all Frontiers investigators – KUH EMR access only available to KUMC investigators Data Request Committee (DRC) approval – Community Partnership for Health – Ethics / Regulatory representative – KU Hospital

55. Current Status Accomplished: HSC approval Website / database fully developed Multiple rounds of user testing with community group “Live” early next week? Pending: Searchable list of all active trials Integrated study-specific surveys

56. Future Plans Spanish language consent Option to search EMR of other health care organizations Link with biospecimen repository Merge with existing Frontiers participant registry (enrollment via checkbox in EMR)

57. Community Research Recruitment Registry www.pioneersresearch.org