SMART I2b2 Clinical Trials Platform

1. SMART I2b2 Clinical Trials Platform Shawn Murphy MD, Ph.D. Nich Wattanasin Michael Mendis Alyssa Porter Stella Ubaha Lori Phillips MS Josh Mandel MD Ken Mandl MD, MPH Susanne Churchill Ph.D. Isaac Kohane MD, Ph.D.

2. The National Center for Biomedical Computing entitled Informatics for Integrating Biology and the Bedside (i2b2), what is it? Software for explicitly organizing and transforming person-oriented clinical data to a way that is optimized for clinical genomics research Allows integration of clinical data, trials data, and genotypic data A portable and extensible application framework Software is built in a modular pattern that allows additions without disturbing core parts Available as open source at https://www.i2b2.org

3. i2b2 Cell: The Canonical Software Module Business Logic i2b2 Data Access HTTP XML (minimum: RESTful) Data Objects

4. An i2b2 Environment (the Hive) is built from i2b2 Cells “Hive” of software services provided by i2b2 cells B A C local Data Model remote Data Repository Cell

5. I2b2 Software components are distributed as open source

6. CTSA’s Boston University Case Western Reserve University (including Cleveland Clinic) Children's National Medical Center (GWU), Washington D.C. Duke University Emory University (including Morehouse School of Medicine and Georgia Tech ) Harvard University (includingBeth Israel Deaconness Medical Center, Brigham and Women's Hospital, Children's Hospital Boston, Dana Farber Cancer Center, Joslin Diabetes Center, Massachusetts General Hospital) Medical University of South Carolina Medical College of Wisconsin Oregon Health & Science University Penn State MIlton S. Hershey Medical Center Tufts University University of Alabama at Birmingham University of Arkansas for Medical Sciences University of California Davis University of California, Irvine University of California, Los Angeles* University of California, San Diego* University of California San Francisco University of Chicago University of Cincinnati (including Cinncinati Children's Hospital Medical Center) University of Colorado Denver (including Children's Hospital Colorado) University of Florida University of Kansas Medical Center University of Kentucky Research Foundation University of Massachusetts Medical School, Worcester University of Michigan University of Pennsylvania (including Children's Hospital of Philadelphia) University of Pittsburgh (including their Cancer Institute) University of Rochester School of Medicine and Dentistry University of Texas Health Sciences Center  at Houston University of Texas Health Sciences Center at San Antonio University of Texas Medical Branch (Galveston) University of Texas Southwestern Medical Center at Dallas University of Utah University of Washington University of Wisconsin - Madison (including Marshfield Clinic) Virginia Commonwealth University Weill Cornell Medical College Academic Health Centers (does not include AHCs that are part of a CTSA): Arizona State University City of Hope, Los Angeles Georgia Health Sciences University, Augusta Hartford Hospital, CN  HealthShare Montana Massachusetts Veterans Epidemiology Research and Information Center (MAVERICK), Boston Nemours Phoenix Children's Hospital Regenstrief Institute Thomas Jefferson University University of Connecticut Health Center University of Missouri School of Medicine University of Tennessee Health Sciences Center Wake Forest University Baptist Medical Center HMOs: Group Health Cooperative Kaiser Permanente  International: Georges Pompidou Hospital, Paris, France Hospital of the Free University of Brussels, Belgium Inserm U936, Rennes, France Institute for Data Technology and Informatics (IDI), NTNU, Norway Institute for Molecular Medicine Finland (FIMM) Karolinska Institute, Sweden Landspitali University Hospital, Reykjavik, Iceland Tokyo Medical and Dental University, Japan University of Bordeau Segalen, France University of Erlangen-Nuremberg, Germany University of Goettingen, Goettingen, Germany University of Leicester and Hospitals, England (Biomed. Res. Informatics Ctr. for Clin. Sci) University of Pavia, Pavia, Italy University of Seoul, Seoul, Korea Companies: Johnson and Johnson (TransMART) GE Healthcare Clinical Data Services Implementations

7. Aggregating across 4 hospitals, 3 i2b2 instances SHRINE (Shared Research Informatics Network)= Distributed Queries

9. 2012

10. To support Clinical Trials need Identified Data and Patient Centric Views of Data • Problem #1 = Make detailed identified patient data available to the members of the Specific Clinical Trials “project” only for sets of patients that have been previously constrained in de-idientified queries. • This will enable screening and contact of these patients using tools in i2b2 that allow viewing of Identified Data. • The creation and definition of patient sets possible through the Project Request form.

11. Data mart request form

12. To support Clinical Trials need Identified Data and Patient Centric Views of Data • Problem #2 = Need detailed view of patient data available to the members of the Specific Clinical Trials “project” to review and assist selection of patients for a clinical trial. • Review application is most likely going to be staffed by clinicians, clinicians who are most familiar with using EMR’s to look at patient data. • Widgets (“Apps”) written to specifically assist the review would be nice in this theoretical EMR

13. “SMART Enabling” i2b2 CRC ONT PM SMART APP SMART MAPPER SMART APP SMART APP SMART APP

14. What is the SMART project about? Substitutable Medical Apps, reusable technologies supported by the Office of the National Coordinator as SHARP Program 3 Provides a unified mechanism for diverse apps to interact with medical record data – An iPad kind of App that fits into AJAX model of web browsing Enables SMART Apps built against a SMART API to be embedded within any SMART Container A SMART Container can be an EMR system used by physicians, or a PHR system used by patients…or a data-analytics platform such as i2b2used by researchers

15. Substitutable Medical Apps and Reusable Technologies 1. SMART Connect 2. SMART REST

16. An “EMR View” becomes available in i2b2

17. Up close …

18. EMR View can be edited by user

19. Leads us to: • Adopt EMR View that looks familiar to clinicians • Patients can be screened using SMART App’s

20. New Core Cell = Identity Management Cell • Main functions • Converts MRNs to i2b2 patient nums • Holds contact data in tables which themselves do not contain clinical data • Links to enterprise services and converts custom enterprise output to i2b2 standards • Lists of patients with real identifiers are managed and linked to a project

21. Flow for conversion of de-identified patient_num in i2b2 Clinical Research Chart to Medical Record Number PM 1 2 CRC P_num 001 P_num 001 SMART eMGH-fheu eBWH-djifs 3 5 MGH MRN#3234567 IM “Firewall” eMGH-fheu eBWH-djifs 4

22. Contact data through IM Cell • Links to enterprise services and converts custom enterprise output to i2b2 standards • Request for demographics is sent to IM cell • If using i2b2 number converts to MRN • Depending on implementation • Demographics requested from services = most uptodate • Demographics requested from database • Demographics sent back in PDO

23. Patient identified data available through IM cell PM 1 MGH004 CRC SMART 2 MGH004 Enterprise Services IM Contact data is in IM database, but for most current may need to use Enterprise Service. MAPPER 3 MGH004

24. Custom views supports clinical trials in i2b2 • An EMR View is welcomed by clinical researchers when they review patients for clinical trials • The EMR View can be focused to support specific needs of each clinical trial review • New Apps can be written to assist eligibility determination during the viewing of a patient

25. Ultimate Goal = Recruit Patients for Clinical Trials with Shared Health Research Information Network (SHRINE) • SHINE will allow a federated query to be performed across i2b2 SHINE databases, and the resulting patient population can be reviewed and recruited for clinical trials with the involvement of a coordinating center.

26. Privacy assumptions: • 1 – It is permissible for the specific goals of a defined project that is “preparatory to research” for that project to allow LDS access across sites. All queries are audited, an IRB has been approved across sites for the study, DUA’s (or the equivalent) have been signed by all project members. • 2 – At the site where the patients have signed the HIPAA notification, the PHI of a specific set of patients can be made available to the investigators. The specific set of patients will be defined by a patient list created in (1) and “promoted” to the level of PHI by transferring the list to a well defined access control place. Accesses to the PHI of these patients will be reported on all HIPAA audits for the patients. • 3 – Two use cases will be supported, one where the coordinating center can see only the LDS data and one where they can see PHI.

27. I2b2 Related Projects …

29. https://community.i2b2.org/ Shawn Murphy MD, Ph.D. Nich Wattanasin Michael Mendis Alyssa Porter Stella Ubaha Lori Phillips MS Josh Mandel MD Ken Mandl MD, MPH Susanne Churchill Ph.D. Isaac Kohane MD, Ph.D.