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

Your ResearchJeffrey M. Burns, MD, MS

Edward H. Hashinger Professor of NeurologyDirector, Clinical and Translational Science Unit

Associate Director, KU Alzheimer’s Disease Center

Russ Waitman, PhDAssociate Professor, Department of Internal Medicine

Associate Vice Chancellor for Enterprise AnalyticsDirector of Medical Informatics

Patricia Kluding, PT PhDAssociate Professor, Dept of Physical Therap & Rehab Sciences

Director, Georgia Holland Health Exercise and Aging LabAssociate Director, Clinical and Translational Science Unit

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

KU Clinical Research Center

http://www.youtube.com/watch?v=zsMBazY31S0

Clinical SpaceClinical 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

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)

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

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

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

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

Participant Recruitment

• Frontiers Registry• Pioneers program

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

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

KUMC Biomedical Informatics Resources for your Research: a focus on HERON

Russ Waitman, PhDDirector of Medical Informatics,

Director, Frontiers Biomedical InformaticsAssistant Vice Chancellor, Enterprise Analytics

Associate Professor, Internal MedicineUniversity of Kansas Medical Center

Kansas City, Kansas

This project is supported in part by NIH grant UL1TR000001 and NSF Award CNS-1258315

• “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

• 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

Bennett Spring Trout Park, Lebanon Missourihttp://mdc.mo.gov/regions/southwest/bennett-spring

You’re that fisherman: wanting to land data to answer your research hypothesis

The Fish: Diagnoses, Demographics, Observations, Treatments

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

Photo Credit: HuntFishGuide.comhttp://www.flickr.com/photos/huntfishguide/5883317106/

Second Goal: If you need help fishing, get a guide

Photo Credit: S. Klathillhttp://www.flickr.com/photos/sklathill/505464990/

Prepare and Analyze Data

Photo Credit: Steve Velo http://www.flickr.com/photos/juniorvelo/259888572/

Our shared goal: a tasty publication

• 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

• 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

http://www.flickr.com/photos/wiccked/185270913/lightbox/

REDCap: think Fish Tank you manage

Bonneville Hatchery: Trout, Salmon, Sturgeon, Columbia River, Oregon

I want to go fishing, not fill a fish tank (REDCap) Use HERON: a managed fishery

• 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

• 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

Single sign-on using your email username

Real-time check

for current human subjects training

HERON: Getting a Fishing License

The i2b2 “Fishing Rod”: build Diabetes cohort

Drag concepts from upper left into panels on the right

Types of “fish” in folders

i2b2 : AND in Frontiers Research Registry

Dragging over the second condition

i2b2: AND a high Hemoglobin A1C

When you add a numeric concept,i2b2 asks if you want to set a constraint

i2b2 Result: 497 patients in Cohort

Run the QueryQuery took 4 seconds497 patient in cohort

I2b2: Explore Cohort, Visualize

http://www.oregon.com/columbia_gorge_attractions/bonneville_hatchery

Catch the data for JAMA, NEJMpublication

The dream: landing the big one

Without getting bit

HERON as Central Aim to CTSA

“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?

• 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

https://informatics.kumc.edu/work/blog - world viewhttps://bmi-work.kumc.edu/work/blog - internal KUMC view: latest breaking developments

Monthly ReleaseBlog highlights:- Features- Size- Dates of sources

HERON’s Data Sources, Types of Data

https://bmi-work.kumc.edu/work/wiki/HeronProjectTimeline#July2013Planning - contains current plan for next several monthly releases

• 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

“Who’s Using HERON” and collaboration approaches

• 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 13th patient’s offset might be -192.

HERON De-identification: Remove HIPAA 18 identifiers -> non human subjects research

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

• 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

• 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

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Steering CommitteeScientific Advisory Board

Special Expert Group

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Patient-Centered Outcomes Research InstituteClinical 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

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

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

Community Research Recruitment Registrywww.pioneersresearch.org

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

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

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

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

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

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

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)

Community Research Recruitment Registrywww.pioneersresearch.org