Advancing Clinical and Transformational Research with Informatics at the University of Kansas Medical Center

Lemuel Russell Waitman1, Gerald Lushington2, Judith J. Warren3

iomedical Informatics accelerates scientific discovery and improves patient care by converting data into actionable information. Pharmacologists and biol- B ogists receive improved molecular signatures; translational scientists use tools to determine potential study cohorts; providers view therapeutic risk models indi- vidualized to their patient; and policy makers can understand the populations they serve. Informatics methods also lower communication barriers by standardizing terminology describing observations, integrating decision support into clinical systems, and connecting patients with providers through telemedicine. The University of Kansas Medical Broadly the initiative would: a) Center’s (KUMC) decision to pursue a adopt methods which facilitate collabo- National Institutes of Health (NIH) Clin- ration and communication both locally ical and Translational Science Award and nationally, b) convert clinical sys- (CTSA)1 in partnership with other re- tems into information collection systems gional academic medical centers, univer- for translational research, c) provide in- sities, and health systems catalyzed the novative and robust informatics drug development and integration of infor- and biomarker discovery techniques, d) matics capabilities to specifically sup- work with state and regional agencies to port translational research in our region provide infrastructure and data man- and to address issues and needs like agement for translational outcomes re- those identified above. Headquartered at search in underserved populations, and KUMC, the NIH-CTSA-supported Fron- e) measure clinical information systems’ tiers program, also called The Heartland ability to incorporate translational re- Institute for Clinical and Translational search findings. Research (HICTR), is a network of scien- The specific aims for informatics tists from institutions in Kansas target translational needs requiring fur- and the Kansas City region ther investment and complement the (www.FrontiersResearch.org). The vi- novel methods and technologies of our sion for the informatics section is to pro- region: a) the Institute for Advancing vide rich information resources, services, Medical Innovation’s (IAMI)2 effort in and communication technologies across drug discovery and b) the Personalized the spectrum of translational research. Medicine Outcomes Center at the Uni-

1 Director Medical Informatics, Department of Biostatistics, University of Kansas Medical Center 2 Associate Scientist and Director of Laboratories, Molecular Structures Group, University of Kansas 3 Christine A. Hartley Centennial Professor, School of Nursing, University of Kansas Medical Center

versity of Missouri- Kansas City neered the use of telemedicine since the (UMKC) which seeks to understand the early 1990s, providing inter-state con- determinants of health systems’ out- nectivity at over 100 sites and conduct- comes and develop methods to deliver ing thousands of clinical consultations evidence based practice. Four aims were and hundreds of educational events for articulated: health care professionals, researchers, 1. Provide a portal for investigators and educators. to access clinical and translational re- The Center for Health Informatics’ search resources, track usage and out- Simulated E-hEalth Delivery System, a comes, and provide informatics consul- jointly funded program between the tation services. University of Kansas and Cerner Corpo- 2. Create a platform, HERON ration, creates an equitable partnership (Healthcare Enterprise Repository for to fully integrate applied clinical infor- Ontological Narration), to integrate clin- matics into an academic setting and ical and biomedical data for translational supports over 40 international academic research. clients. These existing efforts are com- 3. Advance medical innovation by plemented by more recent investments linking biological tissues to clinical phe- in clinical research informatics and med- notype and the pharmacokinetic and ical informatics. pharmacodynamic data generated by Starting in 2005, KU selected Velos research in phase I and II clinical trials e-Research for our Clinical Research In- (addressing T1 translational research). formation System (CRIS). CRIS is a web 4. Leverage an active, engaged application, supports Health Level 7 statewide telemedicine and Health In- messaging for systems integration, and formation Exchange (HIE) to enable complies with industry and federal community based translational research standards (CFR Part 11) for FDA regu- (addressing T2 translational research). lated drug trials. It consists of a man- This article will focus on Frontiers’ agement component for patients, case plan and progress in achieving these report forms, and protocols, and allows aims since the grant was awarded in financial management for conducting June 2011. studies with administrative dashboards Background and milestones for measuring research The University of Kansas has a wide effectiveness. KU’s support and staffing range of informatics capabilities, devel- serves not only support KU investigators oped over decades of research and ser- but also to provide enterprise licensing vice. Through the National Center for for Frontiers’ investigators to conduct Research Resources (NCRR) IDeA Net- multi-center, cooperative group, and in- works for Biomedical Research Excel- vestigator-initiated research with CRIS lence (INBRE), the Kansas’ KINBRE has across unlimited participating locations created a ten campus network of collab- without additional license fees. CRIS has orative scientists using common bioin- been deployed throughout our institu- formatics resources. Kansas has pio- tion and the team has experience sup-

porting multicenter trials across the na- mation technology. Like many funded tion. CTSA programs, KU is a founding Bioinformatics is a critical technolo- member of the American Medical In- gy for translational (T1) research that formatics Association’s (AMIA) Aca- systematically extracts relevant infor- demic Forum. Graduate health informat- mation from sophisticated molecular ics education, continuing education, interrogation technologies. Analytical AMIA 10x10 program, consultation, and techniques–such as microarray experi- staff development workshops/seminars ments, proteomic analysis and high designed to advance health informatics throughput chemical biology screening– are sponsored or co-sponsored through can probe disease etiology, aid in devel- KU-CHI. Graduate education in health opment of accurate diagnostic and informatics began in 2003 in the School prognostic measures, and serve as a ba- of Nursing and is now a multidiscipli- sis for discovering and validating novel nary master’s degree program offered by therapeutics. HICTR institutions benefit the Office of Graduate Studies and man- from strong molecular bioinformatics aged by the KU-CHI. Helen Connors, research expertise distributed across PhD, RN, FAAN (executive director of three synergistic entities: the Center for KU-CHI) chairs the State of Kansas E- Bioinformatics at KU-Lawrence (CBi), Health Advisory Council that oversees the Bioinformatics and Computational the development of the state’s health in- Life Sciences Research Laboratory formation exchange strategic and opera- (BCLSL), and the K-INBRE (Kansas tional plans and is a board member of IDeA Network for Biomedical Research the Kansas City Bi-state Health Infor- Excellence) Bioinformatics Core (KBC). mation Exchange, the metropolitan ar- Over time, CBi (an internationally rec- ea’s Regional Health Information Organ- ognized structural biology modeling re- ization. search program, focusing on computa- Under the direction of Dr. Ryan tional structural biology) and BCLSL (a Spaulding, The University of Kansas research program, led by the School of Center for Telemedicine & Telehealth Engineering at KU-Lawrence and focus- (KUCTT) is a leader in telehealth ser- ing on development of sophisticated al- vices and research. The program began gorithms for mining biological data) in 1991 with a single connection to a should grow into collaborative partners community in western Kansas. The Kan- for Frontiers investigators. sas telehealth network now is used to The University of Kansas Center for connect 60 health facilities in Kansas Health Informatics (KU-CHI), estab- each year. It also is the basis for several lished in 2003, is an interdisciplinary national and international collabora- center of excellence designed to advance tions, demonstrating significant poten- health informatics through knowledge tial of telehealth technologies to elimi- integration, research, and education of nate distance barriers. Over the last 19 faculty and students in the expanding years, nearly 30,000 clinical consulta- field of biomedical science and infor- tions have been conducted across nu-

merous allied health, nursing and medi- sity of Kansas Physicians began adop- cal specialties, making the KUCTT one tion of Epic across all ambulatory clinics. of the earliest and most successful tele- Planned Program Objectives and health programs in the world. In 2009, Progress. over 5000 Kansas patients benefited Aim #1: Provide a Frontiers portal from telemedicine services that included for investigators to access clinical and clinical consultations, community educa- translational research resources and tion, health screenings and continuing provide informatics consultative ser- education for health professionals. vices. Through the Midwest Cancer Alliance As shown at the top of Figure 1, a (MCA) alone, the KUCTT supported web application to link research re- numerous second opinion cancer consul- sources and foster communication was tations, multidisciplinary tumor board seen as an underlying need. It provides conferences, chemotherapy administra- investigators access to request services tion courses and routine patient consul- from the Translational Technologies and tations. Other specialties facilitated by Resource Center, the Participant & Clini- the KUCTT include cardiology, psychol- cal Interactions Resources, the Commu- ogy, psychiatry, neurology, wound care, nity Partnership for Health, and the Eth- etc. The KUCTT also has been very ac- ics section. It also allows investigators to tive integrating numerous technologies obtain targeted internal and extramural to support clinical and research activi- funding opportunities, request biostatis- ties, including telehealth systems, elec- tics support and clinical research data- tronic health records, data registries and base construction, request and access patient management systems. informatics resources, and explore edu- In 2010, KU committed $3.5 million cational offerings. dollars over the next five years towards A key component of the portal is the medical informatics academics and ser- adoption of REDCap4 (Research Elec- vice, and established the Division of tronic Data Capture), to create databases Medical Informatics in the Department to manage requests and triage review of Biostatistics, to integrate clinical re- and tracking of requests. Medical Infor- search informatics, and to provide over- matics implemented REDCap in January all leadership for the Frontiers Biomedi- 2011 to provide a self-service database cal Informatics program. Coincidental management system for clinical and with establishing the division, the Uni- translational research. Since users be- versity of Kansas Hospital completed come familiar with the ease of use and their five-year, $50 million investment to development of forms, it was a natural implement the Epic Electronic Medical approach to also extend the use of RED- Record, concluding with Computerized Cap to manage research request activi- Provider Order Entry in November 2010. ties. Thus, the user focused portal is This effort has transformed the inpatient complemented by using REDCap to help environment. Subsequently, the Univer- Frontiers management track projects, distribute resources, and facilitate evalu-

ation similar to efforts at Vanderbilt process for submitting data requests and University3. Frontiers adoption of RED- receiving data and complementary Cap has been dramatic with over 700 methods to support Data Request Over- users of over 500 projects either under sight Committee activities. Finally, we development or in production. REDCap provided a request management infor- usage has ranged from student research matics consult service and training de- projects as part of a fourth year Health scribed below. of the Public medical school course to With the award of the CTSA, we an- providing the data management infra- ticipated the need to dedicate a clinical structure for a $6.3 million NIH funded informaticist to match investigators’ Alzheimer’s Disease Core Center grant. needs against current information avail- In addition to the existing capabilities of able in Frontiers resources, specifically the CRIS, there are several informatics the HERON repository described in Aim specific components have been devel- 2. By early 2012, we had recruited Tama- oped to provide better integration for ra McMahon to serve in this role as the clinical and translational researchers. clinical informatics coordinator. She as- Integrated authentication between the sists users with tools like i2b2 and will portal, the campus Central Authentica- recommend alternative approaches tion Service, CRIS, and i2b2 streamlines when required data are not integrated.

Figure 1. Conceptual Model of Biomedical Informatics and Specific Aims access to our clinical data repository de- She and the larger team’s experience scribed in the second aim. REDCap was from front-line consulting with transla- used to develop secure methods for the tional researchers drives prioritizing ad-

ditional data sources, terminology and cal trial data capture, outcomes research, ontology development and guides the and evaluation of T2 interventions for adoption of new technologies for data translating research into practice. While retrieval and analysis. As we’ve matured initially focused on integrating data be- as a team these consultative services, tween the KU Medical Center, the KU while lead by the coordinator, are Hospital, and KU affiliated clinics, our staffed and addressed by the combined methods are designed to subsequently biomedical informatics personnel. Addi- integrate information among all Fron- tionally, informatics clinics have been tiers network institutions. established biweekly for investigators, Beginning in April 2009, the Fron- staff, and students to attend and discuss tiers started piloting a participant regis- needs and solutions in an informal try in the clinics which allows patients to group setting. Requests for bioinformat- quickly consent to be contacted by clini- ics and computational biology capabili- cal researchers. The registry contains the ties are facilitated by the Bioinformatics consented patients’ demographics, con- Resources section of the portal and sup- tact information, diagnoses, and proce- port by the bioinformatics assistant di- dure codes. From April to July 2010, the rector (initially Dr. Gerald Lushington; medical center, hospital and clinics re- currently Dr. Paul Terranova). viewed comparable practices5,6,7,8 and Aim #2: Create a platform, HERON drafted a master data sharing agreement (Healthcare Enterprise Repository for between the three organizations that was Ontological Narration), to integrate signed September 6, 2010. The HERON clinical and biomedical data for transla- executive committee is composed of sen- tional research. ior leadership (e.g. chief operating, fi- Transforming observational data in- nancial, executive officers and chief of to information and knowledge is the staff) from the hospital, clinic and medi- cornerstone of informatics and research. cal center and provides governance for The opportunity for data driven institutional data sharing. Establishing knowledge discovery has exploded as business processes and servicing re- health care organizations embrace clini- search requests is conducted by the Data cal information systems. However, when Request Oversight Committee (DROC) dealing with confidential patient infor- which reports to the HERON executive mation, science and technology are de- committee. The repository’s construc- pendent on law, regulation, organization, oversight process, system access tional relationships, and trust. HERON agreement, and data use agreement for provides Frontiers with secure methods investigators were approved by the In- for incorporating clinical data into stitutional Review Board. Since HERON standardized information aligned with is currently funded by KU and contains national research objectives. It facilitates medical center and affiliated clinics and hypothesis generation, allows assessing hospital data, access requires a medical clinical trial enrollment potential, and center investigator. As additional institu- minimizes duplicate data entry in clini- tions and health care organizations pro-

vide support and contribute data, they separate de-identified repository (See will be incorporated with multi- Figure 2). We recognize that certain re- institutional oversight provided by the search requires access to identified data HERON executive committee and but our approach streamlines oversight DROC. when needs are met with de-identified As agreed upon by the HERON ex- data. We adopted the NIH funded i2b29 ecutive committee, HERON has four us- software for user access, project man- es: cohort identification, de-identified agement, and hypothesis exploration data, identified data, and participant and chose Oracle as our database be- contact information: cause of existing site licensing and i2b2 After signing a system access compatibility. Transformation and load agreement, cohort identification queries activities are written in the python lan- and view-only access is allowed and ac- guage and deployed onto SUSE LINUX tivity logs are audited by the DROC. servers. Servers are maintained in the Requests for de-identified patient medical center and hospital’s data center data, while not human subjects research, which complies with HIPAA standards are reviewed by the DROC. for administrative, technical and physi- Identified data requests require ap- cal safeguards. proval by the Institutional Review Board Maximizing data sharing to adhere prior to DROC review. After both ap- to NIH guidelines has been a key goal provals, medical informatics staff will for the development of HERON. Our generate the data set for the investigator. goals are to make scientific data and in- Investigators who request contact formatics methods available as widely as information for cohorts from the HICTR possible while safeguarding the privacy Participant Registry have their study re- of our patients. Our data sharing agree- quest and contact letters reviewed for ments were developed at an organiza- overlap with other requests and adher- tional level to streamline requests for de- ence to policies of the Participant and identified data. Our repository’s use of Clinical Interactions Resources Program i2b2 and UMLS terminologies facilitate Data Request Committee. national collaboration. By using open The utility of data for clinical resource development tools and languages search is proportional to the amount of all new software developed using sup- data and the degree to which it is inte- port from the NIH grant is then made grated with additional data elements available to others through our divi- and sources. However, as additional da- sion’s research and development web- ta are integrated and a richer picture of site: http://informatics.kumc.edu. the patient is provided, privacy concerns Access to the identified repository is increase. HERON receives and preserves highly restricted and monitored. Data data into an identified repository, links exchange between source systems, and transforms those data into de- HERON, and user access is handled via identified, standardized concepts, and security socket layer communications, allows users to retrieve data from this https with digital certificates, and 128-bit

or higher public key cryptography (ex: MITRE Identification Scrubber Toolkit SSH-2). We will continue to monitor versus only extracting concepts) prior to federal guidance regarding appropriate incorporating narrative text results security measures for healthcare infor- which have greater risk for re- mation10. User access, activity logs, and identification11,15. project management for the de- Arvinder Choudhary, our medical identified repository is managed via the informatics project director, and Daniel i2b2 framework and is integrated with Connolly, our lead biomedical informat- the medical centers’ open source Jasig ics software engineer, were responsible Central Authentication Service and the for the initial construction of HERON. HICTR portal. Account creation and ac- Starting in April 2010, the team has de- cess control is provided by the medical ployed a data repository with i2b2 inte- center. Audit logs are maintained for gration, contributed to the i2b2 commu- both the identified and de-identified re- nity code for integration with the Cen- positories. Intrusion detection mecha- tral Authentication Service (an open nisms are used and monitored by medi- source project used by many universities cal center Information Resources securi- for “single sign-on”), worked with other ty personnel who also conduct HIPAA CTSA institutions to use the UMLS as a Security Rule reviews of the systems. source terminology for i2b2, and estab- Current literature highlights chal- lished a software development envi- lenges with providing anonymity after ronment for the team using Trac and de-identifying data11,12,13,14. While we re- Mercurial. Initial pilot use began as early move all 18 identifiers to comply with as April for access to the Frontiers Par- HIPAA Safe Harbor, the de-identified ticipant Registry (diagnoses, de- repository is treated as limited data set, mographics, and procedures based on reinforced by system access and data use clinic billing systems). The current archi- agreements. Initially, HERON will only tecture was deployed in August 2010 incorporate structured data. We will stay and populated with production data abreast of best practices (e.g., De-ID, the from IDX and Epic in September 2010.

Figure 2. HERON Architecture

Initial extract, load, and transform pro- approach is to rely on the National Li- cesses obtain data files from the source brary of Medicine Unified Medical Lan- system via secure file transfer methods. guage System (UMLS) as the source for The repository was available as a proof ontologies and to use existing or develop of concept in December 2010 and en- new update processes for the i2b2 On- tered beta mode for all faculty in March tology Management Cell and other sys- 2011. HERON has been updated with tems. The National Center for Biological new data and functionality every month Ontologies is also working with the i2b2 since August 2011 (updates advertised development team to create methods on our blog: that can assist organizations using i2b2 http://informatics.kumc.edu/work/blog). with building appropriate ontologies As of August 2012, HERON is using an based on the UMLS or other source on- i2b2 version 1.6 and it contains approx- tologies. This may play a greater role as imately 850 million facts for 1.9 million we bridge clinical data towards bioin- patients. formatics domains and to incorporate From its inception, HERON has more recently authored ontologies that benefitted from i2b2 community exper- are not fully supported by the NLM. As tise and the team works with other aca- we develop new mapping for going demic medical centers to align our ter- from UMLS into i2b2 and from source minology with CTSA institutions. Our systems such as Epic, we have shared

Figure 3. HERON Progress on Incorporating Data Sources and Ontologies 98

our code and processes with the i2b2 assessments, social status) from the Epic community via our website. Figure 3 electronic medical record. Judith War- illustrates our current progress in build- ren, PhD, RN, BC, FAAN, FACMI (Di- ing a rich picture of our patient popula- rector of Nursing Informatics, the Center tion and highlights places where the for Health Informatics) serves as assis- HERON repository also serves to ad- tant director of health informatics for vance KUMC’s goal to become a Nation- Frontiers and has extensive experience al Cancer Institute designated Cancer developing health informatics standards Center. and terminologies, teaching informatics, The team’s approach leveraged and developing national policy for methods outlined by several CTSA or- health information technology. She has ganizations that shift mapping inside led several initiatives, especially regard- i2b2 instead of in database transfor- ing nursing observations, to adopt mation and load processes16. This pre- standards that will maximize data inte- serves the original data side by side with gration and reuse. the transformed information allowing Our hope is that standardizing in- easier review by investigators and do- formation for research strengthens our main experts. We applied these methods relationship with the hospital and clin- when we incorporated nursing flow- ics. Reusing information for clinical sheet information17 (vital signs, nursing quality improvement also requires

Figure 4. Richness of Phenotype in HERON using Frontier Participants as an example

standardization. Translational research We saw two points where Frontiers’ using HERON has highlighted areas informatics must bridge between basic needing terminological clarity and con- science resources and clinical activities sistency in the electronic medical record. to enhance our region’s ability to con- Going forward, we are partnering with duct translational research. Our region Dr. Ator, Chief Medical Information Of- provides a wealth of biological and ana- ficer, and the University of Kansas Hos- lytical capabilities but struggles at times pital’s Organizational Improvement to understand if our clinical environ- (which has two of their leaders on the ments see enough patients to support DROC) to develop a data driven process research. This leads to clinical trials for improving standardization. Research which fail to accrue enough subjects22. and quality improvement goals also Accurately annotating biological tissues align with achieving “meaningful use”18 and routine clinical pathology specimens and Health Information Exchange activi- with the patients’ phenotypic character- ties. We will gradually build relation- istics (such as diagnosis and medications ships by initially focusing on linking da- from the clinical records) would provide ta sources from KU Hospital and affiliat- a more accurately characterized clinical ed clinics. Figure 4 provides an illustra- research capacity. Our second targeted tion of how today, patients who volun- area is designed to support the Drug teer to be contacts for research in the Discovery and Development activities of clinic based upon a clinic billing system Frontiers’ Institute for Advancing Medi- indicator are linked to medication expo- cal Innovation’s (IAMI) initiative in sure and laboratory results, allowing managing information in phase I and II more targeted recruitment for prospec- clinical trials. Molecular biomarker and tive clinical trials19. The majority of these pharmacokinetics/pharmacodynamics patients have diagnoses, demographics, research activities provide high quality procedure codes, laboratory results, and analysis, but their results are not easily medications in HERON. As capabilities integrated with other records main- of the team develop we plan to expand tained in clinical research information to other Frontiers affiliated network in- systems. Reciprocally, if clinical charac- stitutions, state agencies, and our rural teristics could be provided with samples practice networks (outlined in aim 4). in a standardized manner it would allow This may require centralized and/or dis- improved modeling and analysis by the tributed data integration20,21. core laboratories. Collaboration between Aim #3: Advance medical innova- the bioinformatics and biomedical in- tion by linking biological tissues to formatics specifically targeted at bio- clinical phenotype and the pharmaco- specimens, pharmacokinetic /pharmacokinetic and pharmacodynamic data dynamic results and clinical trials will generated by research in phase I and II provide a foundation for subsequent in- clinical trials (addressing T1 transla- tegration and our final goal of providing tional research). molecular bioinformatics methods.

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Aligning CTSA capabilities with our cal relevance. We need to improve our Cancer Center’s pursuit of national des- characterization of these samples to ignation was a top T1 priority for the maximize our investment in maintaining informatics team. Our ability to incorpo- them for clinical research. By integrating rate clinical pathology based infor- clinical pathology derived characteristics mation and the biological tissue reposi- and research specimens with clinical in- tories with HERON could improve co- formation in HERON, researchers can hort identification, clinical trial accrual, quantify samples belonging to patients and clinical trial characterization. Pa- (e.g. aggregating all breast cancer diag- tients’ tissue specimens are a fundamen- noses using the i2b2 clinical concept tal resource that links the majority of “malignant neoplasm of the breast” and basic biological science analysis to clini- treated with the adjuvant therapy Trastuzumab). On July 12, 2012, KU was awarded NCI Cancer Center Designation, the highest priority strategic objective for the university. Informatics contributed by enhancing i2b2 for cancer research by incorporating key data sources and developing methods for conducting real time survival analysis. Our first step towards supporting T1 research was integrating the Biological Tissue Reposito- ry (BTR) in the Translational Technologies and Resource Center (Section 8) and HERON. The BTR, built upon the existing KU Can- cer Center Biospecimen Shared Resource, plays a vital role in collecting and distributing high quality human biospecimens es- sential to research. Improv- ing specimen management for clinical research has Figure 5. Initial ontology for Biospecimen Tissue Repository been identified as a high Integration within HERON 101

priority initiative for KU. Integrating the systems. The tumor registry was incor- BTR allows users to exploit the pheno- porated with collaboration from Kimmel typic data in HERON to characterize the Cancer Center (PA) and Group Health samples. BTR personnel can also use this Cooperative (WA) and leveraged using linkage to provide investigators request- the national standard for tumor registry ing samples with clinical phenotype data specified by the North American from HERON via a data use request ap- Association for Central Cancer Registries proved by the oversight committee. Fig- (NAACCR). We also incorporated the ure 5 demonstrates the ontology for bio- social security death index from the Na- specimens within HERON’s i2b2 appli- tional Institutes for Standards and Tech- cation. We are currently migrating the nology to provide support for long term BTR to reside within the Comprehensive outcomes and survival analysis across Research Information System (CRIS). all clinical conditions and health services This will enhance analysis and charac- research. Finally, we created rgate – an terization of data from clinical trials and improved method to integrate R with also improve inventory management, i2b2 and Oracle23. Figure 6 provides a retrieval, and quality assurance process- summary of HERON workflow for hy- es for the BTR staff. potheses generation and preliminary Our second step was to incorporate visualization using the interactive analy- the hospital’s Tumor Registry within sis tools. Future work will focus on gen- HERON since the validated tumor regis- eralizing plugins for multiple cohorts try provides additional tumor character- beyond cancer and extending the use of istics for the cancer population, out- R analysis within HERON so that initial comes, and follow up information that validation can be conducted without are not maintained in surgical pathology needing to request data from HERON.

Figure 6. HERON providing interactive survival analysis

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That in turn reduces the risk of acci- Aim #4: Leverage an active, en- dental data disclosure. gaged statewide telemedicine and Going forward, we plan to support Health Information Exchange (HIE) to IAMI clinical trials by integrating and enable community based translational standardizing information between the research (addressing T2 translational bioinformatics and pharmacokinet- research). ic/pharmacodynamic (PK/PD) program In the latter years of the grant we and CRIS. The Institute for Advancing plan to leverage regional informatics ca- Medical Innovation (IAMI) builds upon pabilities to complement the long histo- the region’s significant drug discovery ry of engaging the community through capabilities and creates a novel platform outreach via telemedicine, continuing for medical innovations. Members of the medical education, and our extensive K-INBRE Bioinformatics Core (KBC) community research projects in urban provide bioinformatics analysis across rural and frontier settings. We will high- the spectrum of target discovery, com- light the initial areas where Frontiers is pound screening, lead identification and deploying informatics in support of T2 optimization, and preclinical develop- community based research. ment. As drug candidates successfully Under the leadership of Dr. Helen transition to a new investigational drug Connors, the Center for Health Informat- application, we will continue bioinfor- ics has been instrumental for advancing matics support into clinical trials. HIE for Kansas and the Kansas City bi- Through Frontiers we hope to estab- state region. As chair of the eHealth Ad- lish stronger bridges between analytical visory Council, Dr. Connors guided the resources and clinical information which process to establish the Kansas HIE will allow phenotypic variables to be (KHIE)23; a non-profit corporation incor- exploited by bioinformatics expertise in porated by the governor in response to data mining by the K-INBRE Bioinfor- the federal HITECH Act. Allen Greiner, matics Core (KBC) and the Bioinformat- MD, director of the Community Partner- ics and Computational Life Sciences Re- ship for Health (Section 5), participates in search Laboratory. Over time, Frontiers selecting electronic health records for the T1 translational research efforts may be Kansas Regional Extension Center and enhanced by providing data mining al- Dr. Russ Waitman has participated in gorithms that extract key information activities on behalf of Kansas Medicaid from data-intensive wet lab studies and and technical subcommittees responsible integrating those results with phenotype for the development of Health Infor- derived from clinical applications. This mation Exchange in the state. The shared bridge between molecular-level analysis goal is to keep Frontiers engaged in state and clinical studies is a potent model for and regional infrastructure capabilities biomarker prediction and validation, for translational research and facilitate PK/PD studies, and the prospective re- identifying other collaborating organiza- finement of personalized medicine. tions.

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The University of Kansas Center for Biomedical informatics works with Telemedicine and TeleHealth (KUCTT) KUCTT to provide a telemedicine clini- provides enormous reach into diverse cal trials network connected by CRIS for communities for implementing clinical remote data collection via study person- trials and other research across the state. nel or direct data entry through a patient Telemedicine has figured prominently in portal. a number of clinical research programs Additionally, in March 2011, Kansas (e.g. studies of diagnostic accuracy, cost City, Kansas “won” a nationwide Re- effectiveness, and patient and provider quest for Information (RFI) solicitation satisfaction with telemedicine) as well as for construction of a next generation studies that employ telehealth for ran- broadband network by Google achieving domized control trial interventions. upload and download speeds of 1 giga- Complementing KUCTT, the Midwest bit per second (Google 2011). Google Cancer Alliance (MCA) is a member- subsequently announced the expansion ship-based organization bringing cancer of service to Kansas City, Missouri for a research, care and support professionals potential deployment of 500,000 indi- together to advance the quality and viduals. Through Frontiers, the Univer- reach of cancer prevention, early detec- sity of Kansas Medical Center’s (KUMC) tion, treatment, and survivorship in the early support led to a collaborative heartland. The MCA links the University working relationship between KUMC of Kansas Cancer Center with the hospi- Medical Informatics and the Google Fi- tals, physicians, nurses and patients bat- ber team to explore leveraging the tech- tling cancer throughout Kansas and nology to further health care delivery, Western Missouri. The MCA advances education, and research. On July 26, access to cutting-edge clinical trials as 2012, Google unveiled their services and well as professional education, network- began preregistration throughout the ing, and outreach opportunities. These Kansas City metropolitan area. KUMC is clinical trials use our Comprehensive actively participating by providing nu- Research Information System (CRIS). tritional consults via telepresence as part Notably, the MCA critical access and of the Google Fiber Space located a few rural referral centers are also the most blocks from the medical center campus. active participants in telemedicine. The Building on the strength of telemedicine medical director of the MCA, Dr. Gary and informatics Drs. Waitman and Doolittle is a pioneer user and has pub- Spaulding are collaborating with the lished telemedicine research with Dr. School of Nursing and the School of En- Ryan Spaulding, the director of the tel- gineering to develop a research proposal emedicine network24,25. The network has for the National Science Foundation’s been successfully used to facilitate clini- US Ignite (www.nsf.gov/usignite) initia- cal research and to support special needs tive to develop next generation applica- populations; especially in the area of tions that can exploit ultra-fast networks smoking cessation. such as Google Fiber.

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In the coming year, Frontiers plans to stracted measures might be automatically build upon investment in electronic medi- derived from a mature clinical information cal records by consulting with Frontiers system, and (c) data integration will allow investigators to optimize the use of clinical hypotheses to be explored that suggest systems for disseminating translational ev- methods for improving care. Finally, we idence and recording measures to verify aim to collaborate with Frontier’s Personal- adoption. This work is also foundational to ized Medicine and Outcomes Center to medical informatics and will allow the provide complex risk models for decision evaluation of native clinical information support to a variety of clinical specialties. system “signals” against manual processes Those investigators have developed meth- used to report measures to government, ods that translate complex risk models into regulatory agencies, and national registries. fully functional decision-support tools for Working with the hospital to develop ca- physicians as well as personalized educa- pabilities to acquire user activity data to tional and informed consent documents for measure the systems’ impact on workflow patients. and clinical decision making (e.g. drug- Acknowledgements drug interaction overrides, time to com- Large portions of this text were previ- plete medication administration task) will ously used in the university CTSA applica- also help us overcome translational re- tion’s biomedical informatics section by the search’s last mile: implementation into clin- coauthors Lemuel Waitman, Judith Warren ical workflow. and Gerald Lushington. We would like to Longer term objectives for Frontiers acknowledge the participation of Frontiers will look to develop methods to engage leadership and numerous investigators with community providers regarding elec- throughout the Kansas City region who tronic health record adoption and those have contributed to the development and systems’ capacity to support translational ongoing progress of Frontiers. research. As mentioned previously, we References have also made initial inroads regarding 1. Zerhouni EA. Translational and clinical science– incorporating state and national data time for a new vision. NEJM 2005, 353:1621-23. sources into HERON as illustrated by our 2. The University of Kansas Medical Center 2012. Institute for Advancing Medical Innovation. Re- incorporation of the Social Security Death trieved from http://www.kumc.edu/iami.html Index. Over time, we hope to work with 3. Pulley JM, Harris PA, Yarbrough T, Swafford J, Edwards T, Bernard GR. Acad Med. 2010 the Kansas Medicaid program to investi- Jan;85(1):164-8. An informatics-based tool to assist gate methods to link health data main- researchers in initiating research at an academic tained by the state as claims against the medical center: Vanderbilt Customized Action Plan. clinical data in HERON. This will further 4. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez three objectives: (a) national data may pro- N, Conde JG. Research electronic data capture vide outcome measures lacking in acute (REDCap) - A metadata-driven methodology and workflow process for providing translational re- care clinical information systems, (b) na- search informatics support, J Biomed Inform. 2009 tional registries, such as the National Data- Apr;42(2):377-81. base of Nursing Quality Indicators, can 5. Sears CS, Prescott VM, McDonald CJ. The Indiana Network for Patient Care: A Case Study of a Suc- evaluate the degree to which manually ab- cessful Healthcare Data Sharing Agreement.

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