1. March 6, 2012: I. Sim APEX, etc. at UCSF Epi 206 — Medical Informatics Ida Sim, MD, PhD March 6, 2012 Division of General Internal Medicine, and Center for Clinical and Translational Informatics UCSF APEX and Clinical Research at UCSF Copyright Ida Sim, 2011. All federal and state rights reserved for all original material presented in this course through any medium, including lecture or print.

2. March 6, 2012: I. Sim Research Informatics Epi 206 — Medical Informatics Outline Systems for Traditional Clinical Research –sharing research meaning UCSF clinical research information systems –REDCap –MyResearch –IDR Cohort Selection Tool

3. Big Picture of Health Informatics Virtual Patient Transactions Raw data Medical knowledge Clinical research transactions Raw research data Decision support Medical logic PATIENT CARE / WELLNES RESEARCH Workflow modeling and support, usability, cognitive support, computer-supported cooperative work (CSCW), etc. CRMSs

4. March 6, 2012: I. Sim Research Informatics Epi 206 — Medical Informatics IRBFunding Agency Study DB Data analysis Results reporting Contract Research Organization (CRO) Protocol Trial Design Sponsors Academic PIs ? Site 1Site 2 Site 3 Site Management Organization (SMO) Clinical Research Today >80% on paper

5. March 6, 2012: I. Sim Research Informatics Epi 206 — Medical Informatics Clinical Trial Management Systems Clinical Trial Management Systems (CTMS) are for running/managing a study –document management (protocol, case report forms) –finances, IRB –study calendar (what to do to whom when) and data entry –data management and analysis –reporting

6. March 6, 2012: I. Sim Research Informatics Epi 206 — Medical Informatics EHR vs. CTMS Contents EHR Patient demographics Chart notes –problem list Visit and assessment Lab and other orders Lab and other results Clinical decision-making Discharge summary CTMS Title, NCT #, IRB # Protocol document –interventions, design, outcomes, etc. Study assessment Outcomes assessment Case report forms Data analysis Trial reporting/publication

7. March 6, 2012: I. Sim Research Informatics Epi 206 — Medical Informatics Just Like Need for EHR… Clinical trials are becoming very complex –avg 460 days (2002) to 780 days (2006) –avg # of participants: 1700 to 3400 over 30 yrs –# of study procedures: 70% increase to 85 procedures, from 2000 to 2005 Fragmented, global industry –estimated 1100 organizations involved in clinical research in 2009 in US (Sponsors, CROs, SMOs, AHCs...) –“43% big pharma FDA trials were conducted abroad... projecting as much as 65% within 3 years” [Tufts Outlook 2008] Can we afford to do this all in paper?? Tufts Center for the Study of Drug Development, “Growing Protocol Design Complexity Stresses Investigators, Volunteers,” Impact Report 10, no. 1 (January/February 2008).

8. March 6, 2012: I. Sim Research Informatics Epi 206 — Medical Informatics IRB Trial Design Protocol Funding Agency Site 1Site 2 Site 3 Site Management Organization (SMO) Study DB Data analysis Results reporting Contract Research Organization (CRO) Sponsors Academic PIs ? Need to Interoperate Multiple Systems

9. March 6, 2012: I. Sim Research Informatics Epi 206 — Medical Informatics Interoperation Ability of two or more systems or components to exchange information and to use the information that has been exchanged [IEEE Standard Computer Dictionary, 1990] –syntactic: grammar, composition of what is said e.g., using an exchange protocol over networks e.g., HL7, DICOM, XML Document Type Definition (DTD) –semantic: meaning of what is said e.g., using a controlled vocabulary aka dictionary e.g., SNOMED, ICD-9

10. March 6, 2012: I. Sim Research Informatics Epi 206 — Medical Informatics MICU Finance Research QA Clinical / Research Data Repository Internet ADT ChemEHRXRayPBMClaims How do the machines “talk” to each other? Networking Basics

11. March 6, 2012: I. Sim Research Informatics Epi 206 — Medical Informatics Internet = Network of Networks itsa medicine ucsf.edu nci.nih.gov “ the cloud ” myhome.com Main Trunk Cables local trunk cable through Berkeley amazon.com at home dial-in to itsa.ucsf.edu via modem pacbell.net aol.com Internet Service Provider (ISP) via DSL or cable LAN

12. March 6, 2012: I. Sim Mobile and Internet-Based Research Epi 206 – Medical Informatics Clients and Servers itsa medicine ucsf.edu nci.nih.gov “ the cloud ” myhome.com Main Trunk Cables local trunk cable through Berkeley amazon.com at home dial-in to itsa.ucsf.edu via modem pacbell.net aol.com Internet Service Provider (ISP) via DSL or cable LAN Server Client

13. March 6, 2012: I. Sim Mobile and Internet-Based Research Epi 206 – Medical Informatics What Happens over the Cables Internet = network of networks –computers and cables all linked to one another and talking to one another using protocols –supports lots of different internet protocols Protocol = “grammar” for machines talking to each other –e.g., hypertext transfer protocol http for web http://www.epibiostat.ucsf.edu/courses/schedule/med_infor matics.htmlhttp://www.epibiostat.ucsf.edu/courses/schedule/med_infor matics.html –e.g., ftp file transfer protocol, smtp, https, etc. etc. –all sit on top of basic networking protocol TCP/IP

14. March 6, 2012: I. Sim Research Informatics Epi 206 — Medical Informatics Web is the internet traffic that uses http –servers send out information in HTML Hypertext Markup Language –web browsers can decode HTML and display it Health-specific protocols needed “on top of” http or TCP/IP –a “grammar” for how to exchange health-related data Internet vs. Web

15. March 6, 2012: I. Sim Research Informatics Epi 206 — Medical Informatics Health Data Interchange Protocols HL7, “containers” for data packages, e.g., lab DICOM, “containers” for radiology studies –machine used, type of study, # of images, etc. CCD (Continuity of Care Document) for EHR data interchange (official standard under Meaningful Use) –e.g., problem list, allergies, family history –supplanted by NHIN Direct? “Containers” do not address the data naming issue –e.g., Na, sodium, serum sodium -- need to standardize to a SNOMED code MSH|… message header PID|… patient identifier OBX|1|ST|84295^NA||150|mmol/l|136-148|H||A|F|19850301

16. March 6, 2012: I. Sim Research Informatics Epi 206 — Medical Informatics Interoperation Over the Stack AdministrativeClinical CareResearch ClinicalBilling Physical Networking Communications Protocols (e.g., HL-7) Standard Vocabulary Practice Management Systems Medical Business Data Model Electronic Medical Record Clinical Care Data Model Clinical Res. Management Systems Clinical Study Data Models Syntactic Semantic and Workflow

17. March 6, 2012: I. Sim Research Informatics Epi 206 — Medical Informatics Sharing Research Meaning AdministrativeClinical CareResearch ClinicalBilling Physical Networking Communications Protocols (e.g., HL-7) Standard Vocabulary Practice Management Systems Medical Business Data Model Electronic Medical Record Clinical Care Data Model Clinical Res. Management Systems Clinical Study Data Models Syntactic Semantic and Workflow

18. March 6, 2012: I. Sim Research Informatics Epi 206 — Medical Informatics Computable Protocol Study protocol is core essence of a research study –the investigational plan, including the actions to be undertaken, the measurements, and the analysis procedures to be followed –is not the same as the study protocol document (i.e., the Word or PDF file) If this protocol is made computable, and standardized, then all clinical studies can be described in the same way so that clinical research systems can interoperate

19. March 6, 2012: I. Sim Research Informatics Epi 206 — Medical Informatics Components of a Study Protocol Who –participants: eligibility criteria, recruitment, followup –investigators: PI, sponsors, advisors, etc. What –interventions or exposures: experimental, control –study outcomes: primary, secondary, baseline When –dates of enrollment, timing of assessments Where –study sites Why –background, objective, hypothesis How –analytic approach, study monitoring, outcomes adjudication, etc.

20. March 6, 2012: I. Sim Research Informatics Epi 206 — Medical Informatics Computable Protocol AdministrativeClinical CareResearch ClinicalBilling Physical Networking Communications Protocols (e.g., HL-7) Standard Vocabulary Practice Management Systems Medical Business Data Model Electronic Medical Record Clinical Care Data Model Clinical Res. Management Systems Computable Protocol Syntactic Semantic and Workflow

21. March 6, 2012: I. Sim Research Informatics Epi 206 — Medical Informatics Need Standardization To... Common computable study protocol –the study plan: e.g., eligibility criteria, treatment, outcomes Ontology of Clinical Research 1, SDTM, BRIDG, etc. etc. Common variables (aka common data elements, CDEs) –see Clarke M, Trials 2007,e.g., “menopause” definition to standardize enrolled population common outcomes for data pooling, meta-analysis (e.g., “MI”) Terminologies/vocabularies –base terms used to describe biomedical concepts e.g., SNOMED, NCI Thesaurus Common interchange standards –e.g., CDISC (“HL7 for clinical research”) 1 http://rctbank.ucsf.edu/home/ocre

22. March 6, 2012: I. Sim Research Informatics Epi 206 — Medical Informatics Sharing and Standardization …of research variables –PhenX Toolkit https://www.phenxtoolkit.org/https://www.phenxtoolkit.org/ a catalog of high-priority measures (e.g., MI) for genome-wide association studies (GWAS) and other studiesMI NIDA requires Tier 1 substance abuse measures –PROMIS http://nihpromis.org/http://nihpromis.org/ –NCI library of Common Data Elements (CDEs)library of Common Data Elements –CDISC SHARE: industry, NCI, FDA http://www.cdisc.org/cdisc-share http://www.cdisc.org/cdisc-share –AHRQ Registry of Patient Registries CDE outcome measuresRegistry of Patient Registries …of case report forms (NCI, OpenClinica, etc.)

23. March 6, 2012: I. Sim Research Informatics Epi 206 — Medical Informatics Summary: Sharing Research Data Interoperation = meaningful exchange of data among computers –syntactic: how things are said, the grammar – semantic: what is said, the meaning Semantic standardization a greater challenge in research than clinical care –need a common computable protocol model –need to be very precise, research needs change as knowledge grows, researchers very individualistic Moving towards standardized, coded variables

24. March 6, 2012: I. Sim Research Informatics Epi 206 — Medical Informatics Outline Systems for Traditional Clinical Research –sharing research meaning UCSF clinical research information systems –REDCap –MyResearch –IDR Cohort Selection Tool New Models of Clinical Research

25. March 6, 2012: I. Sim Research Informatics Epi 206 — Medical Informatics via iMedRIS Funding Agency MyResearch Data analysis Results reporting Oncor CRMS Protocol Trial Design Sponsors Academic PIs IRB Site 1Site 2 Site 3 Site Management Organization (SMO) UCSF Research Info Systems Integrated Data Repository REDCap APEX

26. March 6, 2012: I. Sim Research Informatics Epi 206 — Medical Informatics REDCap Web-based tool for building study databases and defining data entry forms –https://redcap.ucsfopenresearch.org/https://redcap.ucsfopenresearch.org/ –https://redcap.ucsfopenresearch.org/index.php?ac tion=traininghttps://redcap.ucsfopenresearch.org/index.php?ac tion=training –is HIPAA-compliant (unlike Survey Monkey) Available to you for free

27. REDCap Demo https://redcap.ucsfopenresearch.org/ March 6, 2012: I. Sim Research Informatics Epi 206 — Medical Informatics

28. March 6, 2012: I. Sim Research Informatics Epi 206 — Medical Informatics via iMedRIS Funding Agency MyResearch Data analysis Results reporting Oncor CRMS Protocol Trial Design Sponsors Academic PIs IRB Site 1Site 2 Site 3 Site Management Organization (SMO) Where Should REDCap Data Go? Integrated Data Repository REDCap APEX

29. March 6, 2012: I. Sim Research Informatics Epi 206 — Medical Informatics No More Lax Storage Storing Protected Health Information (PHI) on laptops, unsecured desktops is bad –VA example, cancer registry theft CA law: you can be fined up to $250,000 for PHI breach –recent $1 million MGH penalty PI #2 PI #1

30. March 6, 2012: I. Sim Research Informatics Epi 206 — Medical Informatics PHI stored in FISMA level secure database Data never physically leaves MyResearch Your browser is a “dumb” window onto the MyResearch computer –SAS, etc. runs on data on MyResearch –you see pixels only, no local caching on your computer MyResearch Secure location with backup SAS, R Firewall Pixels only Secure Global Desktop

31. March 6, 2012: I. Sim Research Informatics Epi 206 — Medical Informatics Using MyResearch Satisfies CHR criteria for secure data storage Works on PC, Mac with Leopard, Unix Gives you free access to SAS, SPSS, Microsoft Access/Project, etc. http://oaais.ucsf.edu/OAAIS/networking/research _data/1034-DSY.htmlhttp://oaais.ucsf.edu/OAAIS/networking/research _data/1034-DSY.html –90-100 weekly users, expecting totals up to 3000 –4-5 monthly users of Cohort Selection Tool About to be completely retooled to something more user-friendly (for $150,000)

32. MyResearch Demo Go to MyAccess http://myaccess.ucsf.eduhttp://myaccess.ucsf.edu Go to MyResearch March 6, 2012: I. Sim Research Informatics Epi 206 — Medical Informatics

33. March 6, 2012: I. Sim Research Informatics Epi 206 — Medical Informatics via iMedRIS Funding Agency MyResearch Data analysis Results reporting Oncor CRMS Protocol Trial Design Sponsors Academic PIs IRB Site 1Site 2 Site 3 Site Management Organization (SMO) Accessing Clinical Data Integrated Data Repository REDCap APEX

34. March 6, 2012: I. Sim Research Informatics Epi 206 — Medical Informatics MICU Finance Research QA Integrated Data Repository Internet ADT ChemEHRXRayPBMClaims autofeed nightly, data stored securely with backup Data from UCare to IDR

35. March 6, 2012: I. Sim Research Informatics Epi 206 — Medical Informatics UCSF IDR First version: all UCare data from July 1, 2005 (Ucare roll-out) to mid-2011 –2.875 million records (not all unique) –5 Million encounter records -- manual refresh –Included inpatient data, Dentistry, some billing data, never got STOR/VA/Kaiser/THREDS data yet; IDR of Ucare data now retired Transitioning to IDR with APEX data instead

36. APeX-IDR Information Flow Shadow Server Clarity (Microsoft SQL Server) IDR (HIPAA Limited Data Set*) Epic Production Server (Chronicles Caché) MyResearch (Data Marts / Ontologies) Operational and financial reports Government-mandated reporting Research Patient care Staging Server (Microsoft SQL Server) Medical Center Network (Requires CHR Approval for Access) MyResearch Network (No CHR Approval Required) * “HIPAA Limited Data Set” = No PHI Except Dates of Service

37. MyResearch/IDR Roadmap February 2012 – –IDR 1.1 APeX demographic data loaded. biweekly refresh –Cohort Selection Tool available (in MyResearch) March 2012 – –De-identified views available for self-service April 2012 – –Usability enhancements –APeX diagnostic Information available in the IDR Spring 2012 – –Infrastructure refresh and upgrade –Replace Sun Global Desktop with Citrix Xenapp –Create virtual server clusters to improve performance of statistical software –Upgrade i2b2 environment to Oracle-based version 1.5 to support UC ReX and additional data Summer 2012 –IDR Version 1.2 – Extended APeX Dataset –Orders –Procedures –Results Additional data sources – (e.g. dental data) 37

38. IDR Demo Go to MyAccess (myaccess.ucsf.edu) Go to MyResearch Launch Cohort Selection Tool –need to sign up for account first March 6, 2012: I. Sim Research Informatics Epi 206 — Medical Informatics

39. IDR User Interface UCare Cohort Selection Tool

40. March 6, 2012: I. Sim Research Informatics Epi 206 — Medical Informatics Limitations Search option limitations –Race: only Asian, Black, Native American, Other are searchable in UCare (no “Hispanic”) –Can search by specific ICD9 code under “GE Centricity” –“ICD9 Diagnoses” lists diagnoses in English (maps ICD9 to a proprietary Harvard ontology) Other limitations –Diagnoses include both primary and secondary –Queries are for entire time period since 2005 I.e., can’t ask for only 2003-2005 –Data is whatever comes out of UCare, errors exist (e.g. married children under 10) Beware!

41. March 6, 2012: I. Sim Research Informatics Epi 206 — Medical Informatics Research Informatics at UCSF RedCAP available for secure surveys Must keep all data/analyses in MyResearch environment –heavy penalties for data breaches Beta version of Cohort Selection Tool for identifying UCare patient data Use of APEX for research is lower priority than clinical roll-out

42. March 6, 2012: I. Sim Research Informatics Epi 206 — Medical Informatics Summary: Research Informatics Clinical research fragmented, global, essentially separate from clinical care Clinical research informatics ongoing in two worlds –most still paper, commercial CTMSs mostly document centered (PDFs) rather than data or concept-centered –moving towards modular component approach with standard data elements (CDEs) and case report forms (CRFs) common computable protocol models (OCRe) and interchange exchange standards (CDISC) Still very very early in design and use of clinical research information systems