Air Force Medical Support Agency Integrity Service Excellence

Air Force Medical Support Agency Integrity - Service - Excellence Building a Digital Biobank Technology Platform for Military Precision Medicine 6 November 2018

Disclaimer The views expressed in this presentation are those of the speaker, and do not necessarily reflect the official policy or position of the Air Force, the Joint Program Committee 1, the Defense Health Agency, the Department of Defense, or the U. S. Government. Integrity - Service - Excellence 1

Precision Operational Health and Performance (POHP) Introduction Integrity - Service - Excellence 2

Precision Medicine Ecosystem Patient Advocates Pharma Researchers Healthcare Professionals Payors Regulators Integrity - Service - Excellence 3

Precision Medicine Program Comparison Military Shared Use Cases Medical Readiness Human Performance Force Health Protection Injury treatment Pharmacogenomics Cancer and genetic disease treatment and prognosis Data Types Deployment Training Fitness Exposures Electronic Medical Records ‘Omics Biomarkers International Traffic of Arms Regulations (ITAR) Reporting secondary findings Policies Integrity - Service - Excellence Civilian Genetic Information Nondiscrimination Act (GINA) 4

Air Force Medical Service (AFMS) Precision Medicine Focus n Air Force Medical Service (AFMS) Vision: “Our supported population is the healthiest and highest performing segment of the U. S. by 2025. ” n Air Force (AF) Global Horizons Final Report: “The game changer for the AF is personalized health and performance. ” Personalized Medicine Program Transition Phase I Research to Demonstrate Clinical Utility Clinical Phase II Transition of Research, Policy, & Bioinformatics Program Elements Phase III Clinical Policy & Bioinformatics Integration Clinical Bioinformatics Research Bioinformatics Integrity - Service - Excellence 5

Research Projects and Data Integrity - Service - Excellence 6

Research Projects and Data Projects Data • Clinical Utility Study – Collaboration with the Coriell Institute to evaluate the clinical utility of personal genomic information • Targeted genotyping + Surveys on 6, 500 individuals • Mil. Seq Project – Collaboration with Brigham and Women’s Hospital to evaluate exome sequencing informed personalized medicine in the Air Force • Whole Exome Sequencing + EMR integration on 75 individuals • Human Performance • Targeted Genotyping of 1. 2 million SNPS + performance phenotypes on 300 individuals Integrity - Service - Excellence 8

Challenges Management of Sequencing Data Sharing Data Reuse Data Security Scalable storage of increasing volumes of genetic data Securely share data with academic and industry collaborators Enable researchers to reuse data for further research Protect service members’ data Integrity - Service - Excellence Policies Protect service members from harmful use of their data 9

Digital Biobank Technology Platform Integrity - Service - Excellence 10

Digital Biobank: ‘Omics Storage and Analytics n The AFMS Digital Biobank is a precision medicine research technology platform that allows researchers and clinicians to: n upload and store ‘omics data for further research n automate bioinformatics workflows n efficiently query large disparate data sets n integrate ‘omics, clinical, exposure, and military-specific data n enable precision medicine analytics on large volumes of disparate data n visualize data and analysis results Integrity - Service - Excellence 11

Digital Biobank Impacts n Scalable storage for siloed ‘omics datasets n Cost savings enabled by reuse of stored ‘omics data n Military-relevant precision medicine research for performance and readiness n Development of research partnerships n Advancement of pharmacogenomics into clinical practice Integrity - Service - Excellence 12

Overall Approach Integrity - Service - Excellence 13

Product Roadmap 2017 -2018 2019 -2020 -Beyond Pre-production Production Other ‘Omics Use Cases Clinical Use Cases • Upload and store genomics data and enable bioinformatics workflows • Upload phenotypes • Query genotypes and phenotypes • Provide a coding notebook for running research-use analytics • Administrative controls • Administrative framework for: • Patient consent • Data sharing • Data deidentification • IRB review • EHR integration • User-friendly analytical capabilities • Storage and analytics support for nongenomics ‘omics such as metagenomics and RNA-seq • Increased analytical capabilities Integrity - Service - Excellence • Storage of clinical ‘omics data for use in the clinical workflow • Integrate clinical genomic reporting with the EHR 14

Previous Schedule Q 1 2017 Q 2 2017 Q 3 2017 Q 4 2017 Q 1 2018 Q 2 2018 Q 3 2018 Q 4 2018 Requirements Gathering Design and Discovery Analysis of Alternatives Technical Exchanges Development Testing Integrity - Service - Excellence 15

Requirements Gathering High Performance Team • Gathered a diverse team or SMEs, IT managers and cost analysts to define the requirements • Requirements were reviewed and validated by the Air Force Surgeon General Requirements for Operational Capabilities Council (SGROCC) Stakeholder Interviews • Stakeholders included: leaders, researchers, clinicians, information technologists, IRB representatives, and Precision Care Advisory Panel (PCAP) representatives • Completed 14 interviews with 18 stakeholders 106 Requirements • • Integrity - Service - Excellence High-level Features: User authentication and authorization Uploading ‘omics data Querying Requesting data IRB interactions Data management Analytics Administrative functionality 16

Design Principles n Secure and scalable ‘omics data storage n Seamless ‘omics data ingestion n Standardized metadata n Data de-identification n User-friendly efficient querying for data sets n IRB permissioning n Scalable analytics n Role-based user access management Integrity - Service - Excellence 17

Analysis of Alternatives Understand Design Analyze Recommend Conduct Research Performed an environmental scan to develop a comprehensive catalog of solutions that address Digital Biobank requirements. Evaluation Criteria Developed evaluation and scoring criteria to analyze alternatives. Alternative Analysis Analyzed alternatives based on criteria developed, and assigned appropriate score to each alternative. Develop Recommendations Reviewed final overall ranked alternatives to develop a recommended course of action. Key Milestone Identified comprehensive precision medicine and genomic analysis systems. Key Milestone Evaluation criteria included: (1) business fit, (2) functional capabilities, (3) cost, (4) security, (5) ease of implementation, and (6) technical performance. Key Milestone Developed scorecards to compare alternatives. Key Milestone Recommended a course of action in a full report and executive summary. Genome Analysis Toolkit 4 (GATK 4) was selected because it is open source, supports distributed computing and has optimizations for the cloud, and has extensive documentation and an active community support forum. Integrity - Service - Excellence 18

Technical Exchanges Overview n Technical exchange forums included government, academic, and industry experts n Insights, lessons learned, and recommendations were shared Key Benefits Architectural Approach Guidance to embrace cloud computing directly led to a change in the technical architecture approach from onpremises computing to a cloud computing approach. Policy Guidance Identification of clinical genomics policy issues and recommendations, including accession and occupational impacts of genetic testing results, will inform guidance for service members. Integrity - Service - Excellence Feature Prioritization Feedback from technical exchange forum attendees was used to improve features and prioritize development, including supporting precision operational health and performance use cases. 19

Initial Release SSO-enabled Login Ingest ‘Omics Data Upload ‘Omics and Metadata Query Data Analyze Data Administrative Controls Query on Genotypes Cohort Building New Accounts Identify Variants Query on Phenotypes GWAS User Roles View Uploaded Files Query on Metadata Ad Hoc Analytics Audit Logs @SEQ_ID GATTACA + CCCCC 65 Security and Encryption Integrity - Service - Excellence 20

Innovation Integrity - Service - Excellence 21

Forward-Looking Applications Prevent noise induced hearing loss – Develop models of the complex polygenic noise induced hearing loss trait using genetic variants and noise exposure data to identify at risk individuals. Precision performance research for special operators – identify biomarkers associated with adaptations to exercise training and predisposition to exercise-related injuries. Biothreat detection – Identify biothreat microorganisms in metagenomic sequencing samples for improved infectious disease detection, treatment, and surveillance Pharmacogenomics – Select pharmaceuticals based on genetic variation to reduce costs and improve health outcomes Traumatic Brain Injury (TBI) treatment – Utilize genetics to inform the selection of the appropriate treatment for service members with TBI. Integrity - Service - Excellence 22

Acknowledgements n Maj Jameson Voss, MD, MPH, FACPM, Co-PI n Lt Col Michael Holmes, MSC, PMP, CPHIMS, Retired n Lt Col Ruth Brenner, MD n Loretta Schlachta-Fairchild, Ph. D, RN n Caterina Lasome, Ph. D, RN n Pavithra Shivakumar, Ph. D n Alex Wisely n Joint Program Committee-1 n Precision Care Advisory Panel (PCAP) Col Albert Bonnema MD, MPH Chief, Applied Technology and Genomics Wright-Patterson AFB Principal Investigator Ezekiel Maier Ph. D Senior Lead Scientist Booz Allen Hamilton This study #B 0900 -1074/0010 was funded/supported by the Defense Health Agency/US Army Medical Research and Materiel Command (USAMRMC) Joint Program Committee-1, Medical Simulation and Information Sciences, and the Health Information Technology & Informatics Steering Committee. Contract support provided by Booz Allen Hamilton and i. ON Informatics, LLC. Integrity - Service - Excellence 23

Questions Integrity - Service - Excellence 24