1. Presentations from Subject Matter Experts Precision Medicine Task Force August 5, 2015 Leslie Kelly Hall, Co-Chair Jon White, Co-Chair

2. Agenda Call to Order/Roll Call Welcome, Opening Remarks Presentations from Subject Matter Experts – Intel Corporation – Intermountain Healthcare – National Library of Medicine (NLM), National Center for Biotechnology Information (NCBI) Q & A Recap & Next Steps Public Comment Adjourn 1

3. Precision Medicine Task Force Membership MemberOrganization Co-Chairs Leslie Kelly HallHealthwise Jon WhiteONC / Agency for Healthcare Research and Quality (AHRQ) Members Mary BartonNational Committee for Quality Assurance (NCQA) Lisa GallagherHealthcare Information and Management Systems Society (HIMSS) David McCallie, Jr.Cerner Corporation Andrey OstrovskyCare at Hand Eric RoseIntelligent Medical Objects Andrew WiesenthalDeloitte Consulting, LLP Federal Ex Officio James BreelingVeterans Health Administration (VHA) Josh DennyNational Institutes of Health (NIH) Betsy HumphreysNational Library of Medicine (NLM) Mitra RoccaFood and Drug Administration (FDA) Linda SanchesHHS Office for Civil Rights (OCR) Christina HeideHHS Office for Civil Rights (OCR) Invited Guests Mina HsiangUnited States Digital Service (USDS) / Office of Management and Budget (OMB) Claudia WilliamsWhite House Office of Science & Technology Policy ONC Staff Maya UppaluruONC – Federal Staff Lead Debbie BucciONC - Technical Advisor 2

4. Task Force Charge Identify opportunities for innovative collaboration around pilots and testing of standards that support health IT interoperability for precision medicine Recommend existing standards that are currently ready to support PMI Identify emerging standards and reference implementations that may require further pilot testing in order to support PMI Identify gaps in available data standards related to PMI 3

5. 2015 Q32015 Q4 JunJulAugSepOctNovDec FACA Workplan Kick-off Joint HITPC/HITSC Meeting Quality Measure TF (QMTF) - PFS NPRM Standards Advisory (ISA) Task Force P&S Big Data Recommendations ISA Recommendations Milestone Interoperability Task Force (ITF) Precision Medicine Task Force QMTF - PFS NPRM Feedback Precision Medicine Recommendations ITF Recommendations

6. MeetingsTask July 17, 2015 11:00 am - 1:30 pm ET Kick-off Meeting Review charge, work plan Overview of the Precision Medicine Initiative o White House Office of Science & Technology Policy o National Institutes of Health Wednesday July 29, 2015 1:30 - 3:00 pm ET Presentations from experts o 23andme o NIH Precision Medicine Workshop o Genetic Alliance, Institute of Medicine  Wednesday August 5, 2015 12:00 - 1:30 pm ET Presentations from experts o Intel Corporation o Intermountain Healthcare o NLM / dbSNP / dbGaP o Written comment: Jonathan Sheldon, MD, Oracle Wednesday August 19, 2015 12:00 - 1:30 pm ET Presentations from experts o Duke Me Tree Project o Google Baseline o PCORI o ResearchKit / Sage o Written comment from physicians: Joan Elmore, Nancy Keating, Justin Starren Monday August 31, 2015 12:00 - 1:30 pm ET Develop Preliminary Task Force Recommendations Prep for Sept. HITSC presentation. Thursday September 10, 2015 1:30 - 3:00 pm ET Finalize recommandations to HITSC September 22, 2015 – HITSC Meeting Present final recommendations Precision Medicine Task Force Workplan 7/27/15 5

7. Questions for Presenters Your Organization 1.What role does your organization provide with regard to precision medicine? 2.How do genomics and other “omics” play a part in that work? 3.How important is interoperability to your organization? Standards 1.Will data standards help you? 2.What standards, if any, do you currently use? Both HIT and other? a)Taxonomy or vocabulary standards? b)Data? c)Transport? 3.How committed are you to standards use? 4.Are standards you may be using fit for purpose or for regulatory recommendations or both? Roles 1.What roles should actors play? a)Government? b)Consumers / Patients? Challenges 1.What are the biggest barriers to interoperability that you have experienced with respect to data and systems? 2.What makes it hard or easy to use the following data for population analytics or research: EHR data, genomics data, mHealth data? 3.What other data, gathered from patients, are needed in order to make genomics data as useful as possible in care? 6

8. Intel Corporation 7 Ketan Paranjape, Director Healthcare and Life Sciences Matt Quinn, Managing Director, Life Sciences Ashley Rees, Marketing & Business Strategist, Intel Corporation Yentram Huyen, Innovation Leader in Healthcare & Life Sciences Ecosystems

9. CLINICAL GENOMICS ISSUES AND STANDARDS PERSONALIZED MEDICINE INITIATIVE Marc Probst, Stan Huff, Grant Wood August 5, 2015

10. Challenges Implementing Precision Medicine Prioritization of HIT resources (MU requirements, EHR implementation, business strategy for an ‘Omic repository and clinical genomics platform, etc.) Storing and using family health history and genetic/genomic tests results in the HER Infrastructure to support molecular clinical decision making Data interfaces with labs, data at the source not in structured format Lack of true interoperability, getting there is hard, terminology, information models, process for adopting standards, etc.

11. Standards for Precision Medicine HL7 Clinical Genomics activities - Version 2, Version 3, Clinical Document Architecture, for Family Health History and Clinical Genetics/Genomics HL7 moving towards Fast Healthcare Information Resources (FHIR) for genomic information SMART on FHIR apps (HSPC) API’s to access genomic databases (GA4GH, etc.) IOM Digitize - Genetic results from lab to EHR WEDI, ASCO HIT WG NIH multi-center grants - eMerge network, IGNITE Building from this Foundation

12. A Few Questions IOM Digitize pilot to include Intermountain, Cerner, ARUP, Invitae. Other pilots involve Partners Healthcare and EPIC. Allscripts has been part of discussions. However, how the clinicians will view the data in the EHR is another matter. Clinical genomic interpretation services. Is HL7 genomics standards inadequate for PMI? We should have a discussion with the HL7 workgroup – identify if there is a gap in standards that are not finished. dbSNP a standard for genomic/proteomic data? If the question is about a database schema to store genomic/proteomic data, we can ask the genomic database vendors. What are the challenges with family history data in the EHR? Getting people to collaborate/share data with family members and back to their physician. Looking at issues that support a pedigree in the EHR.

13. Genomics for PMI Task Force August 5, 2015 James Ostell National Center for Biotechnology Information US National Institutes of Health, Bethesda, MD, 20894-6513 12

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15. DANGER! 14

16. “GenBank” Today DANGER! 15

17. Trace and SRA are part of GenBank

18. Submitted BAM Read IDs as strings Original quality & recalibrated quality scores Additional analysis tags Read IDs as integers 40-level read qualities using recalibrated quality scores 8 level qualities for all sites Uniform binning of recalibrated quality scores Variant Call Format (VCF) Genotype likelihoods for all variants Total Project Size SRA-40SRA-8Analysis Genotypes Size (Terabytes) What is the Big Data Problem in Biology? Example: Reducing the 1000 Genome Dataset 250TB 85TB 30TB 0.1TB SRA reads Reads and placement only 17

20. The human reference genome assembly represents multiple individuals 19

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26. dbSNP

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36. The Problem with Human Data 35

37. Secure Hybrid Cloud User Actions Obtains security certificate from dbGaP or other Access Control system Launches FUSE with Security certificate Encryption Key Local Disk Area Local mount point Reads and writes data from mount point as if it is a local filesystem Shutdowns FUSE when work is completed FUSE Server Actions Gets the list of remote files based on security certificate Gets the list of local files from Work Area Returns and decrypts already downloaded pages Decrypts local files Requests missing pages from HTTP Saves delivered pages to local disk Encrypts Writes before saving them to the disk After FUSE is shutdown all data on local disks including newly created is secured NCBI dbGaP DataStore Encrypted Volume C Volume B Volume A HTTP Client Instance Encrypted at rest Page1 Page2 Page3 Page4 Page5 Page6 Local Disk Cache Page1 Page3 Page6 File FooBar Sparse File FooBar FUSE Server Implementation Virtual Image of Remote And Local Data User application Network Access Control Write Local Disk Work Area Read 36

38. Using Beacons to Discover Data Repository Discovery Does the data exist? Role of Public Beacons Query: Do you have any genomes with an “A” at position 100,735 on chromosome 3? Reply: ‘Yes’ or ‘No’ Data context Does the data have the properties I require? Role of Registered Access Beacons Shows details of studies with data and provides link for requesting access Data Preview Does the metadata have the properties I require? Requires approved access Permits users to narrow the search and access the precise sets of data needed. 37

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40. Registration example: NIH eRA 39

41. Registered Access Beacon: dbGaP

42. Recap & Next Steps 41