The Biomedical Translational Research Information System (BTRIS)

1. The Biomedical Translational Research Information System (BTRIS) James J. Cimino Chief, Laboratory for Informatics Development National Institutes of Health Clinical Center Senior Scientist, Lister Hill Center for Biomedical Communications National Library of Medicine Adjunct Professor, Department of Biomedical Informatics Columbia University College of Physicians and Surgeons September 12, 2008

2. Learning Objectives • An introduction to the compilation and integration of clinical and research data from multiple disparate sources • Understanding the authorization issues related to reuse of patient clinical data • Understanding the terminology issues related to the reuse of coded clinical and research data • Familiarity with the approach being taken at the National Institutes of Health to collect, integrate, and code clinical and research data into a single repository, for authorized resuse in biomedical research.

3. No Relevant Financial Relationships with Commercial Interests Disclosures

4. The Clinical Center, 1981

5. What Was the Problem? • Patients in the NIH Clinical Center were on research protocols, but… • …their data were in a clinical information system • Needed to extract individual data for analysis • Needed cross-patient queries for additional analysis

6. Patient Information Graphics System (PIGS) • Integration of a desktop computer (pre-PC) to mainframe clinical information system (TDS) • Download vital sign and drug administration data • Various graphical displays • SCAMC, 1981

10. The Columbia University Medical Center Clinical Data Warehouse • Clinical data repository to collect data from ancillary systems • Coded with the Medical Entities Dictionary

11. MED Structure Substance Laboratory Specimen Event Chemical Anatomic Substance Plasma Specimen Diagnostic Procedure Substance Sampled Plasma Laboratory Test Laboratory Procedure Has Specimen Carbohydrate Bioactive Substance Part of Glucose Substance Measured Medical Entity CHEM-7 Plasma Glucose Test

12. Using the MED for Summary Reporting Lab Test Chem20 Display Intravascular Glucose Test Lab Display Fingerstick Glucose Test Serum Glucose Test Plasma Glucose Test

13. The Columbia University Medical Center Clinical Data Warehouse • Back end for clinical information systems (CIS, WebCIS, PatCIS, PalmCIS, QingCIS, MendonÇIS…) • Reorganized for use as Clinical Data Warehouse • Clinical data repository to collect data from ancillary systems • Coded with the Medical Entities Dictionary

14. How often are patient with the diagnosis of myocardial infarction started on beta blockers?

15. How often are patient with the diagnosis of myocardial infarction started on beta blockers? Find all patients with Diagnosis in class MYOCARDIAL INFARCTION Find all patients with Diagnosis in class MYOCARDIAL INFARCTION AND with Medication in class BETA BLOCKER

16. The Clinical Center, 2008

17. The Clinical Center, 2008 • Patient data stored in EHR (Eclipsys) • Need to extract individual data for analysis • Need cross-patient queries for additional analysis • Data may require transformation: • De-identification and Re-identification • Indexing • Aggregation by time • Abstraction by classification • Conversion to relevant concepts

18. What is BTRIS? • Biomedical data • Research data collected using clinical information systems • Clinical data collected using clinical information systems • Research data from research information systems • Non-human data • Reuse of data to support translational research • Hence: Biomedical Translational Research Information System

19. The NIH, 2008

20. What is BTRIS? BTRIS

21. What is BTRIS? BTRIS

22. What is BTRIS? Data Analysis Tools Subject RecruitmentHypothesis GenerationHypothesis Testing Data Acquisition Processes CodingIndexingDe-IdentifyingPermission Setting O n t o l o g y Data Retrieval Functions AuthorizationSubject-OrientedCross-SubjectRe-IdentificationNLP Data Repository BTRIS

23. BTRIS Issues • Data sources • Data model integration • Research Entities Dictionary • Access policies • User requirements • User access and user Interface • Terminology-based queries

24. Data Sources • Order entry system • Ancillary systems • Institute and Center (IC) systems • Individual researchers’ systems • Notebooks

25. Data Model Integration • Events and details • Entity-relation vs entity-attribute-value • Denormalization

26. Research Entities Dictionary • Apelon’s Terminology Development Editor • NCI/caBIG Thesaurus

27. Research Entities Dictionary (RED)

28. Research Entities Dictionary • Apelon’s Terminology Development Editor • NCI/caBIG Thesaurus • Content • Organization

29. Access Policies • Privacy Act, not HIPAA • Policy Working Group • Intellectual property vs. public domain • Identifiers • Unlinked, coded data

30. Active Protocols Inactive Protocols BTRIS Data Storage Policy 1. All clinical and research data, whether from active or inactive protocols, are stored in BTRIS in a timely manner.

31. PIs BTRIS Data Use Policy Active Protocols Inactive Protocols 2. PIs can see data collected on their patients as part of their active protocols

32. PIs BTRIS Data Use Policy Blocked By PI Active Protocols Inactive Protocols 3. PIs may indicate that some of their data should be blocked to avoid unmasking their study subject assignment.

33. PIs BTRIS Data Use Policy Coded Data Identifiers Blocked By PI Active Protocols Inactive Protocols 4. It is helpful to consider data to consist of identifiers vs. other (“coded”) data linked to those identifiers. PIs can get to coded data in their own active protocols, but not those in inactive protocols.

34. BTRIS Data Use Policy Coded Events Identifiers Coded Results Active Protocols Inactive Protocols 5. It is also helpful to consider that coded data can be further divided into recorded events (such as a medication order or a lab result report) and results (such as the medication ordered or the value of the test result).

35. BTRIS Data Use Policy Coded Events Identifiers Coded Results Restricted By PI PI Only Active Protocols Sharable Through PI PI Only Inactive Protocols 6. Identifiers in active protocols are restricted to PIs but other data are generally be sharable with some PI control. The PI may designate some events, and perhaps their data, as completely restricted while the protocol is active.

36. BTRIS Data Use Policy Coded Events Identifiers Coded Results Restricted By PI PI Only Active Protocols Sharable Through PI PI Only Unencumbered By PI No Access Inactive Protocols 7. When a protocol becomes inactive, the identifying information is inaccessible, but the other (coded) data (events and results) become generally available.

37. BTRIS Data Use Policy Coded Events Identifiers Coded Results Restricted By PI PI Only Active Protocols Sharable Through PI PI Only Unencumbered By PI No Access Inactive Protocols Collaborative with PI 8. A PI may restrict use of some data from inactive protocols, for example requiring other users of the data to work in collaboration with the PI.

38. BTRIS Data Use Policy Coded Events Identifiers Coded Results Restricted By PI PI Only Active Protocols Sharable Through PI PI Only Unencumbered By PI No Access Inactive Protocols Collaborative with PI 9. Data may move back to be considered active if a PI (not necessarily the original PI), gets approval to use the data, including (as per the IRB), identifying information.

39. PIs BTRIS Data Use Policy Coded Events Identifiers Coded Results Restricted By PI PI Only Active Protocols Sharable Through PI PI Only Unencumbered By PI No Access Inactive Protocols Collaborative with PI 10. To summarize, PIs have access to data in their own active protocols, subject to any blocking that may be required.

40. BTRIS Data Use Policy Coded Events Identifiers Coded Results Restricted By PI PI Only Active Protocols Sharable Through PI PI Only NIH Community Unencumbered By PI No Access Inactive Protocols Collaborative with PI 11. The NIH community will have access to all data, except identifiers, with restrictions on data (active or inactive) by PIs. Restrictions may differ for events versus results.

41. User Requirements • 2006 study of user requirements

42. User Requirements • Provide Medication lists at time of patient encounters. Include drug diaries for inpatient, outpatient and in-between encounters in the patient medical record. Include all chemo and non-chemo drugs from CRIS and IC systems • Provide Medication administration documentation (drug diaries) with times as part of patient record • Provide ability to compare patient results, Medication Administration Records between dates and/or encounters • Provide drug randomization info, compliance records and drug accountability info for all investigational, study and prescription drugs • Provide all Clinical Center lab results with times of specimen draws • Provide external lab results • Provide archival images • Provide demographics data including age, BMI, race, gender, contact info, etc • Provide access to genomics and bio-markers data • Provide cumulative blood volumes, research drugs and radiation for subject over a given period • Provide ability for ICs to feed expanded diagnosis/problem lists • Provide searching and filtering patients' data by all diagnosis, tests, procedures, protocol & protocol classifications • Standardize medication and lab test codes. • Provide integration of adverse events data in the data warehouse, • Provide integration of protocol census, status and subject accrual tracking data from Protrak in the data warehouse • Provide ability to attribute different events to protocols, viz., consent signed, protocol activated, orders, observations, adverse events, etc • Provide integration of staff, patient and user index data across source systems in data warehouse. • Provide original informed consent, and updated consents for re-contact of patients for research for all protocols. Provide searchable consents and image of consents in database. Provide answers to: • Can tissues be used for cancer/genetic research, other research, germ line testing • Can patient be re-contacted for questions? • Provide single patient amendments • Provide access and track biological specimen data • Provide access to Appointment Data • Provide “Review of Systems” info for each patient visit. • Provide patient de-identification services • Standardize Units Of Measure

43. User Requirements • 2006 study of user requirements • Investigator User Group • Demos: • To user group • One-on-One • Town hall meeting

44. User Access/User Interface • Canned reports (e.g., recruitment for IRB) • Reports with prompts (e.g., sets of lab results) • Ad hoc queries (whatever you want!) • Selected Business Objects

45. Terminology-Based Queries • Hripcsak G, Allen B, Cimino JJ, Lee R. Access to Data: Comparing AccessMed to Query by Review. Journal of the American Medical Informatics Association; 1996;3(4):288-299.

47. Terminology-Based Queries • Hripcsak G, Allen B, Cimino JJ, Lee R. Access to Data: Comparing AccessMed to Query by Review. Journal of the American Medical Informatics Association; 1996;3(4):288-299 • Business Objects prompt with hierarchy

49. Terminology-Based Queries • Ancestor-descendant join with filtering • Hripcsak G, Allen B, Cimino JJ, Lee R. Access to Data: Comparing AccessMed to Query by Review. Journal of the American Medical Informatics Association; 1996;3(4):288-299. • Business Objects prompt with hierarchy

50. Ancestor-Descendant Joinwith Filtering • Start with parent-child table • Transitive closure produces ancestor-descendant table • Designate subset of “searchable” classes (ancestors) • Display flat list (no tree walk) • Let user select desired classes • Query selects ancestor-descendant rows and joins data tables based on descendants