HERON, Frontiers, and Pioneers: Database and Recruitment Resources to Advance Your Research

1. HERON, Frontiers, and Pioneers: Database and Recruitment Resources to Advance Your Research Russ Waitman, PhD Associate Professor, Department of Internal Medicine Associate Vice Chancellor for Enterprise Analytics Director of Medical Informatics Jeffrey M. Burns, MD, MS Edward H. HashingerProfessor of Neurology Director, Clinical and Translational Science Unit Associate Director, KU Alzheimer’s Disease Center 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 • 9exam 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 This project is supported in part by NIH grant UL1TR000001 and NSF Award CNS-1258315

15. Overview • “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

16. Biomedical Informatics Can Help Your Research • 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.

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

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

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

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

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

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

23. Nightmare: looks like a nice river, but can’t catch fish • 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

24. Sometimes, You’re willing to enter data/buy fish: REDCap: ResearchElectronicDataCapture • 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”

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

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

27. Central CTSA Informatics Aim: Create a data “fishing” platform: HERON, https://heron.kumc.edu • 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.

28. HERON: Getting a Fishing License Single sign-on using your email username Real-time check for current human subjects training • 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.com • Check http://frontiersresearch.org/frontiers/HERON-Introduction for more information, status, and training videos

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

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

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

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

33. I2b2: Explore Cohort, Visualize

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

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 #2: Computer + Clinical Process-> Better Health? Hypothesis #1: Admin + Clinical -> Better Knowledge?

38. How the Team Works: HERON Evolves Every Month • 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

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

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. “Who’s Using HERON” and collaboration approaches • Find a colleague • Talk with hospital, clinic to understand workflow • Attend bi-weekly clinics • Watch the videos: http://frontiersresearch.org/frontiers/informatics-training-videos • Request a consult 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=3SBkPg&tool=1

42. HERON De-identification: Remove HIPAA 18 identifiers -> non human subjects research • 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 bornAugust 13, 1968, had their blood pressure measured on November 28, 2012. • Each month dates shifted, ex: to -15 for January release: Newbirthday 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 13th patient’s offset might be -192.

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. Aligning Clinical Research Informatics for Quality: Registry Abstraction and Data Delivery • 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

45. Next Steps: A Learning Healthcare System • 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.

46. Patient-Centered Outcomes Research Institute Clinical Data Research Network Announcement Scientific Advisory Board PCORI Steering Committee • 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 Special Expert Group PPRN Coordinating Center PPRN CDRN PPRN PPRN PPRN PPRN PPRN PPRN CDRN CDRN PPRN CDRN CDRN CDRN PPRN • Selby JV, Krumholz HM, Kuntz RE, Collins FS. Network news: powering clinical research. • SciTransl Med. 2013 Apr 24;5(182):182fs13. doi: 10.1126/scitranslmed.3006298. Epub 2013 Apr 23.

47. What Do They Want the Network to Do? 18 MONTHS LATER COOPERATIVE AGREEEMENT AWARD 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 • > 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 • 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 Joe V. Selby, MD, MPH, Executive Director ONC HITCP June 5, 2013

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