Application for 2015 University of California Larry L. Sautter Award for

Innovation in Information Technology

Date: May 15, 2015

Project Title: UC-ReX Data Explorer

Submitted by: Kent Anderson, Division Manager, Research IT / Associate Director, CTSC Biomedical Informatics /

kander@ucdavis.edu / (925) 408-6416

On Behalf of: University of California Health:

UC Davis

UC Irvine

UC Los Angeles

UC San Diego

UC San Francisco

I. Project Leaders and Team Members

UC Health strongly promotes a team science approach as a methodology for translational work. The key elements leading to

the success of this project has been the consistent partnering of individual staff and faculty experts throughout UC

institutions, a well-defined governance structure, and a commitment towards leveraging the collective power of UC Health

data through standardization and meticulous quality checking.

UC ReX Team Kent Anderson, UCD Nick Anderson, UCD Lattice Banks-Armstead, UC ReX Douglas Bell, UCLA Douglas Berman, UCSF Lisa Dahm, UCI Pralav Dessai, UCLA Robert Follett, UCLA Davera Gabriel, UCD Mike Hogarth, UCD Justin Jay, Sr., UCI Dana Ludwig, UCSF Lucila Ohno-Machado, UCSD Ayan Patel, UCI Paulina Paul, UCSD Leslie Yuan, UCSF Additional UC ReX team members

UC Davis UC Irvine UCLA UC San Diego UC San Francisco

Albert "Bill" Riedl Christine Hotz Momeena Ali Samuel Morley

Ray Pablo Yi-Cheng "Andrea" Hwang

Marianne Zachariah Yi "Ruby" Wan

Antonios Koures Carol Johnson Claudiu Farcas Elizabeth Bell Hyeon-Eui Kim Jim Graczyk Tony Chen Wendy Zhu

Bhuwan Karki Jocel Dumlao Kimberly Romero Martha Michel Robert Hink Vijay Rayanker

Executive Summary

The UC Research Exchange (UC ReX) consortium is an informatics collaboration based on the Clinical Translational

Research Awards (CTSA) Biomedical Informatics Cores. Formed in 2010, the UC ReX collaborative built upon the

existing research data warehousing investments at each UC medical campus. Key to the collaboration was an

understanding that, even though most campuses employed the same type of electronic health record system,

data from the 5 campuses (Davis, Irvine, Los Angeles, San Diego and San Francisco) was not comparable, and thus

not useful for research, clinical quality improvement (QI), and administrative inquiries.

Our first step was to harmonize the data from the research data warehouses into a common format so simple

queries could be conducted across all 5 campuses. We successfully implemented the “UC ReX Data Explorer1”

using i2b2 Shared Health Research Information Network (SHRINE)2 technology from Partners Healthcare in Boston

so that end users (researchers, clinicians, administrators) could start exploring these data themselves, without the

need for a dedicated database analyst. The UC ReX Data Explorer allows authorized UC researchers, clinicians, and

administrators to query de-identified demographics, diagnoses, procedures, laboratory orders, medications, and

vital signs data across all 13.6 million patient records of the five UC academic medical centers, typically in less

than 10 seconds (Figure 1).

Figure 1 - A user is able to query the electronic medical record at each of the 5 UC Health sites for prospective research cohort identification and study feasibility analysis in seconds using our first deployed application, Data Explorer, without the need for a database analyst.

The governance employed by UC ReX to achieve this level of success has become a model for governance of shared data resources and cooperation among medical centers. National networks of clinical data & informatics, including the National Institutes of Health (NIH) National Center for Advancing Translational Science (NCATS) Accrual to Clinical Trials (ACT) and Patient Centered Outcomes Research Institute (PCORI) pSCANNER projects, have evolved data governance structures modeled after UC ReX, and extended them to several other institutions.

UC ReX enhances the competiveness and impact of clinical research and healthcare quality improvement initiatives at the University of California by enabling the use of big data and promoting the implementation of multi-campus applications like Data Explorer. UC ReX receives strategic guidance from the UC Biomedical Research Acceleration, Integration and Development (BRAID)3 leadership and is supported by the Health System CIOs and by a grant from the UC Office of the President (UCOP).

1 https://www.ucrex.org

2 https://www.i2b2.org/work/shrine.html

3 http://www.ucbraid.org/

The technology infrastructure behind UC ReX Data Explorer In just the last decade, the five UC Health sites have invested over $500 million implementing electronic health record systems. Leveraging the data collected in these records presents a significant opportunity to improve our ability to work together to complete clinical studies and clinical quality improvement projects. UC ReX provides a framework for consolidating data across campuses and creates a venue for collaboration among managers and investigators. Clinical studies are a critical component of the research programs at the UC Health centers, but recruitment of subjects is chronically difficult; far too many studies fail for not enrolling an adequate number of participants. Traditionally, identifying patients required manual chart reviews, which are laborious and costly.

UC IrvineUC San Francisco

UC San Diego

UC Los Angeles

UC Davis

Clarity

Data ExplorerEpic

i2b2

Clarity

Data ExplorerEpic

i2b2 Clarity

Data ExplorerEpic

i2b2

Clarity

Data ExplorerEpic

i2b2 Data Ware- house

Data ExplorerAllScripts

i2b2

Central Management Node (CMN)

Each of the five UC Health sites has implemented an i2b2 data warehouse instance derived from clinical data in their electronic medical record systems. Data Explorer employs Harvard’s SHRINE technology to distribute queries against these federated data instances, which returns a count of patients in each system that match the cohort selection criteria. A basic diagram of the systems in use at each site and the interactions is shown in Figure 2. Not shown are the security measures employed to maintain privacy of the patient information.

Figure 2 - Federated i2b2 database at each site unified by a Central Management Node (CMN).

The UC ReX Data Explorer is a secure, web-based system that enables UC investigators to identify potential research study cohorts at the five UC medical centers. This technical resource contains records for over 13.6 million patients with nearly 700 million clinical observations across California (Table 1). Data Explorer allows researchers to explore whether a population of suitable patient exists for their studies within minutes. Data Explorer helps researchers assess the feasibility of studies, permits clinicians to explore associations among phenotypes of interest, and fosters collaboration among campuses. Alongside existing campus services, it has enabled pilot studies for individual researchers at several campuses. Total Observations

Demographics Diagnoses Distinct Patients Labs Medications Procedures Vital Signs Vital Status Observations

UCD 15,160,538 14,854,022 2,181,279 58,921,929 12,842,458 444,840 17,680,764 63,183 102,286,970

UCI 10,908,111 14,027,831 1,559,070 21,594,379 8,367,547 875,595 7,251,652 14,997 44,880,349

UCLA 30,632,221 34,336,485 4,375,712 120,205,477 10,734,430 1,389,854 13,741,495 45,295 211,085,257

UCSD 8,237,067 16,636,522 2,323,234 59,027,137 110,581,964 90,150 22,876,604 2,825 217,452,269

UCSF 12,697,792 8,088,649 3,249,612 92,365,008 8,766,599 396,462 20,484,099 36,523 122,351,033

Grand Total 77,635,729 87,943,509 13,688,907 352,113,930 151,292,998 3,196,901 82,034,614 162,823 698,055,878 Table 1 - Count of Patients and Clinical Facts in UC-ReX (March 2015)

Data Explorer –UC ReX’s First Tool In its initial 18 months, UC ReX successfully implemented “UC ReX Data Explorer” (i2b2 SHRINE). The resulting “UC ReX Virtual Clinical Data Repository” became one of the largest federated clinical data repository systems in the world. UC ReX Data Explorer initially allowed authorized UC researchers and quality improvement administrators

to query de-identified demographics, diagnosis and procedure data across all 13.6 million patient records of the five UC academic medical centers. These queries typically took less than 10 seconds. Available data has been subsequently been expanded to include vital status, laboratory orders, medications and vital signs.

Clinical data exchange for research and QI is a complicated because of clinical data heterogeneity, loosely documented clinical data practices, and stringent regulatory protections surrounding patient information. UC ReX Data Explorer was made possible only through the diligent efforts of a core of semanticists, informaticists, and specialized technical personnel, all focused on providing users with a tool that leverages the substantial UC investment in electronic medical records for secondary use.

The UC ReX Program Governance Structure The five UC Medical Campus Informatics program leaders recognized the opportunity to provide users with a query tool based on clinical data warehousing initiatives using a tested software developed by Harvard/Partners Healthcare in Boston, called SHRINE. SHRINE is an automated software platform which manages queries across a federated network of databases and displays the results from each participating site. Using lessons learned from an NIH NCRR grant-funded proof-of-concept project with University of Washington, UC Davis and UC San Francisco that had ended in 2010, the group crafted a proposal to UCOP to create the University of California Research Exchange (UC ReX), a SHRINE network among the five UC medical campuses.

Project Structure and Governance The success of UC ReX can be greatly attributed to its project and Governance structure (Figure 3). This structure brings together translational research and technology functions from all campuses. The UC ReX organization is comprised of an Executive and a Leadership Implementation Committee and five workgroups that develop, plan and implement program goals.

Figure 3. The UC ReX program is comprised of a leadership committee and a series of working groups that drive much of the programs efforts. It is overseen by the UC Biomedical Research Acceleration, Integration, and Development (UC BRAID) initiative and includes the informatics teams for the 5 health science campuses.

UC BRAID The UC Biomedical Research Acceleration Integration and Development (BRAID) group, comprised of the leaders of UC’s Clinical Translational Science Award (CTSA) programs, are oversee UC ReX activities and facilitate collaborative partnerships.

UC BRAIDUC ReX Executive

Committee

UC ReX Implementation

Leadership Committee

Technology Strategy

Data(Harmonization/Quality)

Technical Implementation

User Support

Marketing

CTSA, Informatics & CIO Leaders Stakeholder liaison; determines strategy, defines scope & budgets; provisions resources; makes decisions; campus implementation owner

Workgroup Chairs & Program Leads Details scope; define requirements & identifies dependencies; resolves escalated issues and risks; oversees delivery

CTSA PI’s Scope and budget oversight; funding and collaborative project partner

Subject Matter Experts Executes site plans; resolves site issues; informs planning and decisions

UC ReX Executive Committee Each participating campus is represented by a principal investigator/voting member and a discretionary CIO representative/non-voting member. These members and the Program Associate Director comprise the Executive Committee. Decisions are made by simple majority of the voting membership. The Executive Committee Chair role rotates between voting members.

UC ReX Workgroups Five workgroups bring together subject matter experts and implementation skills from each campus to create solutions which support shared data and ensure meaningful and seamless unification of data sets. Each of the five workgroups meets regularly to facilitate planning and delivery of UC ReX goals. Workgroup Role

Strategy Conducts technology assessments and recommends solutions for prioritized demonstration projects.

Data Harmonization and Quality

Ensures the semantic interoperability across the institutions (e.g. concepts have the same meaning) and continually characterizes and improves the fitness of data represented in UC ReX resources.

Technical Implementation

Ensures that the infrastructure and critical software are deployed and maintained.

User Support Ensures the definition and implementation of a user support model across campuses and maintains ucrex.org

Marketing develops and promotes branding and marketing strategies to identify and engage users to maximize tool utilization.

Table 2. Workgroups in UC-ReX execute the vision set forth by the Executive Committee

Impact and Outreach UC ReX is currently launching its initial marketing campaigns to expand utilization, but even without concerted communications efforts, UC ReX is already making contributions to UC research outcomes. 70% of UC ReX Data Explorer users indicated intent to apply for a research grant and 30% engaged the tool with intent to conduct prospective research.

UC ReX gained national attention in 2013 when its governance and collaborative approach to promoting standardization of its clinical data and cross-campus use for research and QI was leveraged by a team of investigators that included most UC ReX leaders. The Patient-Centered Outcomes Research Institute (PCORI) awarded $7M to the patient-centered Scalable National Network for Effectiveness Research (pSCANNER), a federated clinical data research network that includes data from electronic records of 21 Million patients (UC ReX Institutions, the VA national enterprise data warehouse, and three Los Angeles community clinics led by USC). The proposal was led by UC ReX’s first steering committee chair, who is currently a member of its Executive Committee. The UC ReX governance model, data standardization, Data Explorer, and BRAID alignment were important factors for the success of the proposal. In pSCANNER, data were transformed into a Common Data Model that included many items in addition to those covered initially for use in Explorer. The goal is to go beyond count queries into multivariate analytics and permit expansion to the national clinical data research network sponsored by PCORI, PCORnet. Additionally, other successful awards by non-UC ReX team members originated from initial queries in UC ReX (Table 3).

Title Agency Sites Status Funding

Integrated Molecular, Cellular and Imaging Characterization of Screen-Detected Lung Cancer

NCI UCLA Pending review

$3,931,346

COMPARE-UF – Comparing Options for Management: Patient-Centered Results for Uterine Fibroids

PCORI/AHRQ UCSF, UCD, UCLA, UCSD, UCI

Funded One of 8 “sites” in $20,000,000 overall project

Mapping Immune Responses to CMV in NIH/NIAID UCLA, UCSF Pending $10,600,000

Table 3. In addition to $8.2M in informatics projects, UC ReX has helped non-UC ReX investigators obtain over $6M from grants awarded by different funding agencies.

Recently, BRAID and UC ReX have leveraged their partnership and have collaborated to bring over $1.2 million in funding (total $7 million national award) for participation in the National Center for Advancing Translational Science (NCATS) – Accrual to Clinical Trails (ACT) grant. UC ReX campuses represent five of the twenty-one CTSA’s participating in Phase One of ACT which builds upon the UC ReX network and allows new national academic medical center partners to collaboratively design large clinical trials requiring cohort identification. ACT builds upon UC ReX’s governance, harmonization and technical implementation models. UC ReX’s expert technical, data harmonization, regulatory, and governance representatives serve as key contributors to the national program, via participation in every ACT work group.

In summary, UC ReX was a pioneering effort in bringing together all UC health science campuses in sharing informatics best practices, developing a governance structure in which the executive committee chair rotates across all campuses, and standardizing a large volume of data collected in the process of healthcare for secondary use in research, QI, or administration. UC ReX, established in 2010, showed that informatics leaders across the UC campuses were correct in anticipating future needs of national initiatives such as big data (2012) and precision medicine (2015), by promoting standardization, improving quality, and integrating clinical data from a large number of patients.

Publications and Presentations Ohno-Machado L, Agha Z, Bell DS, Dahm L, Day ME, Doctor JN, Gabriel D, Kahlon MK, Kim KK, Hogarth M, Matheny ME, Meeker D, Nebeker JR; pSCANNER team. pSCANNER: patient-centered Scalable National Network for Effectiveness Research. J Am Med Inform Assoc. 2014 Jul-Aug;21(4):621-6. doi:10.1136/amiajnl-2014-002751. Epub 2014 Apr 29. PMID: 24780722 <http://www.ncbi.nlm.nih.gov/pubmed/24780722>

Gabriel,D, Anderson, N, Hogarth,M, A Best Practice Developed to Harmonize Distributed Research Data Resources, AMIA Annual Conference, November 14-15, 2013 Washington DC

Anderson, N, Abend, A, Mandel, A, Geraghty, E, Gabriel, D, Wynden, R, Kamerick, M, Anderson, K, Rainwater, J, Tarczy-Hornoch, P, Implementation of a De-identified Federated Data Network for Population-based Cohort Discovery, JAMIA, 1 June 2012 vol. 19 no. e1e60-e67

Wynden, R ,Weiner,M, Sim,I, Gabriel, D, Casale,M, Carini, S,Hastings,S, Ervin,D, Tu,S, Gennari, J, Anderson,N Mobed, K, Lakshminarayanan,P Massary, M, Cucina, R, Ontology Mapping and Data Discovery for the Translational Investigator, AMIA Clinical Research Informatics Summit 2010, San Francisco,CA

Anderson - 1. Invited Speaker: ³UC-ReX:Federated Multi-Site Clinical Data Repositories for Population Studies² PCOR-Net Grand Rounds, March 14, 2014

Anderson 1. Panel Speaker ³Data Management in Patient Centered Outcomes Network² HealthDataPalooza, Washington DC, May 24, 2014

Transplant Recipients review

Effects of Exercise Training on Cardiac Structure and Function in Prediabetes Using 3D Cardiac MRI Technology

AHA UCLA Pending review

$43,700

Complex Contraception Registry – UC Family Planning Collaborative Study

NIH K12 UCSD, UCLA, UCSF, UCI, UCD

Funded $40,000

Developing Population-Scale Analytics to Evaluate Long-Term Health Care Utilization and Associated with Autism Spectrum Disorders

Center for Behavioral Health Excellence

UCD $200,000

Community engaged Network for all UCD, UCSF Pending review

$150,000