Accelerating Precision Medicine for All of Us

1. Accelerating Precision Medicine for All ofUs CSR Council September 24th2018 Joni L. Rutter,PhD Director of ScientificPrograms All of Us ResearchProgram

2. PrecisionMedicine Righttreatment. Rightperson. Righttime. Rightdose. Pharmacogenetics (PharmGKB Drug Labels) https://www.pharm gkb.org/labels Prescription Eyeglasses Blood Transfusions More research is needed to bring precision medicine to mostdiseases Precision medicine research PrecisionMedicine

3. The cost of ImpreciseMedicine Patients Providers Researchers Health care is often targeted to the average patient, not the individual Health problems can take years to unravel, with significant trial anderror Not enough research todraw on for clinical evidence, especially in diverse populations Medical records scattered in differentplaces Not enough time for analysis one patient at atime Enormous time and cost spent building IT systems vs. doing research Siloed data resources and funding opportunities Challenges acquiring large sample sizes Slow translation of datainto knowledge ⦿ ⦿ ⦿ ⦿ ⦿ ⦿ ⦿ ⦿ ⦿ 3

4. Now is the time for precision medicine research – a revolutionary approach for disease prevention and treatment that takes into account individual differences in lifestyle, environment, andbiology. Click to edit Master textstyles

5. 21st Century CuresAct H.R.34, 21st Century Cures Act,enacted December 13, 2016 (Pub.L.114-255) Broad bi-partisan support Provisions relevant to All ofUs: Provides the Precision Medicine Initiative with $1.455 billion over 10years Provides flexible funding mechanism, Other TransactionAuthority Language on diversity, whole genome sequencing, data sharing,privacy Provides important privacy protections critical for engenderingtrust ⦿ ⦿ ⦿

6. All of Us Research Program – A New Initiative Gets a NewMechanism Portfolio 19 OtherTransaction (OT) Awards HPOs, Community EngagementPartners, Comms, Outreach, & GenomeCenters 6

7. Other TransactionsAuthority ⦿ The Other Transactions (OT) award mechanism is not a grant, cooperative agreement orcontract. ⦿ Only a few NIH Institutes/Centers have thisauthority. ⦿ For the All of Us Research Program, the National Center for Advancing Translational Sciences (NCATS) manages the OT awards, NHLBI manages the Cooperative agreements ⦿ All applicants (PI, AOR, Project Team) should read and be familiar with the Other Transaction Award Policy Guide for NIH Precision Medicine Initiative Research Programs. (The NIH Grants Policy Statement and the FAR does not apply to OT awards.) ⦿ OT allows NIH the flexibility to alter the course of projects in real-time to meet the overarchingprogrammaticgoal. This means awarded activity can be expanded, modified, partnered, not supported, or later discontinued based on programneeds. ⦿ If selected for award, applicants should expect significant ongoing involvement from NIH. 7

8. All of Us Research Program: Mission andObjectives Nurture relationships with 1 Million ormore participant partners, fromall walks of life, for decades Ourmission To accelerate health research and medical breakthroughs, enabling individualized prevention,treatment, and care for all ofus Deliver the largest, richest biomedical datasetever that is easy, safe, and free toaccess Catalyzea robustecosystem of researchers and funders hungry to use and supportit 1. Diversity of people at scale with participants at the center; 2. Diversity ofdata; 3. Open resource forall 8

9. Major building blocks of the All of Us Research Program consortium -1 PARTICIPANT TECHNOLOGY SYSTEMSCENTER Web and phone-based platforms forparticipants DATA ANDRESEARCH CENTER Big data capture, cleaning, curation, & sharing in secureenvironment BIOBANK Repository for processing, storing, and sharing biosamples (35+Mvials) Vanderbilt, Verily, BroadInstitute VibrentHealth MayoClinic Wenchi Liang,PhD ValerieBartlett,ESA Sam Butler,ESA Delia Olufokunbi Sam,PhD Valerie Bartlett,ESA Sam Butler,ESA Valerie Durrant, PhDand Denise Wiesch, PhD Thyra Mack,ESA U24:PTSC SEP 5/23/2016 U24:Biobank SEP 4/18/2016 U2C:DRC SEP 5/5/2016 9

10. Major building blocks of the All of Us Research Program consortium -2 HEALTHCARE PROVIDERORGS NETWORK HPOs with clinical & scientific expertise, enrollment & retention of participants THEPARTICIPANT CENTER/ DIRECTVOLUNTEER Direct volunteer participant enrollment, digital engagement innovation, and consumer healthtechnologies COMMUNICATIONS & COMMUNITYNETWORK Communications, marketing, and design expertise; engagement coordination and community partners network 10 regional medical centers,6 FQHCs, VA, totaling165 enrollmentsites Scripps Research Institute (with multiplepartners) Lisa Steele,PhD Colin Fraser, ESA UG3: HPO (1)5/25/2016 Wenchi Liang,PhD ValerieBartlett,ESA Sam Butler,ESA Wondros, HCM, 34 community partner orgs, and future awards to grownetwork Michael Bloom, PhDand Noni Byrnes, PhD Zohra Rasuli,ESA OT: HPO (2)9/27/2016 U24:TPC SEP 5/23/2016 10

11. Two Paths toParticipation Joinallofus.org “all ofus” Health CareProvider Organizations(HPO) Direct Volunteers(DV) 11 (inclEHR)

12. Current Enrollment Centers and Zip-codeCatchment

13. Invent Network of Direct VolunteerPartners Potential capacity of the DVNetwork ⦿ Quest: 2000locations. Reach 90% where all people live, within 20 – 45 minutes o Not all at once--Cycle up or down locations depending on need (~50 attime) Convenientlocations In-Home enrollment (EMSI) AoU on wheels – JourneyBus 13 Once proven, this capability— “to go where the people are”—may prove valuable for futureresearch

14. Two pathways for EHR datasharing FOR DIRECTVOLUNTEERS FORHPOs Start with pilot of Sync for Science program with top EHR vendors with the goal to “donate your EHR at touch of a button” patient-initiated using an industry-adopted, standard API technology to read data from a PatientPortal Exploring partnership opportunities with aggregators to bring in more data – Need to betested • Using OMOP v5 Common DataModel Starts with limited EHR fields • Labs, Dx, medications,etc. ⦿ ⦿ ⦿ Focus on quality improvement and mappingto ⦿ standards Will grow over time to include expanded datatypes ⦿ ⦿ HITECH and CURES Acts: making progress on provider access and use of health information, with individuals at the center of their care, and S4S enabling patient’s sharing EHR withresearchers 14

15. AoU Genomics Platform AoU Genome Centers(GCs) Genotyping and WGSplatforms Analysis pipeline includes variant calling and clinical interpretation (in program- definedregions) 1. Biobank ClinicalAssay GC2 L GC1 CV CLIA CLIA Clinical Validation Laboratory (CVL) CLIA/CAP validation assay w/sign-off 2. GCR DRC Genetic Counseling Resource (GCR) Responsible return of actionable results Case workapproach 3. Opt-in consent Research Portal Participant Portal ResearchWorkflow Return ofInformation

16. Ongoing scientific requirements gathering to drive precision medicineresearch Participant advocacy, community & providergroups • * • Researchers andScientists  +Data * +Surveys Tools mHealth  +Data +Surveys +Tools +mHealth +Analyses Moreresearch MoreValue  … • NIHICs • ▲ AoUConsortium +Data +Features +Value Research * * ● ● ●  Data Surveys Biosample ▲ ▲ ▲ * ● Consortium BrainTrust ▲ Version2 Version3 Version4 Version1 16

17. What is the promise forparticipants? An opportunity to help fight disease and improve the health of futuregenerations. A chance to learn about your own health, including personalized risk factors or exposures. The ability and choice to access your own data, including increasingly rich healthrecords. An opportunity to ensure that your community is included in the studies that lead to new understanding and new treatments. A chance to learn about additionalresearch opportunities that may interestyou. The choice to meet others like you, perhaps even joining some of them to propose & do research. ⦿ ⦿ ⦿ ⦿ ⦿ ⦿ 17 This is a long-term relationship and the value to participants (and researchers) will grow overtime.

18. Participants are ourPartners Steering and Executive Committees and AdvisoryPanel Provide participant perspectives to oversight and governance Help set strategicdirection ParticipantAmbassadors Co-create and provide input on ongoing work and AoURP programimplementation Serve on select Working Groups andTask Forces Director’s ThinkTank Small group of mid-level professionals/ community members from DMV area to provide feedback to AoURPleadership ⦿ ⦿ ⦿ Help shape and co-create newapproaches 18

19. What is the Promise for Researchers:researchallofus.org The opportunity to save time and resources and accelerate your research breakthroughs byleveraging: ⦿ A rich resource of data, including biospecimens and increasingly robust electronic healthrecords. A longitudinal dataset that will follow participants as theymove, age, develop relationships, get sick, and trytreatments. A diverse cohort of participants, including people bothhealthy and sick, from all walks of life and all parts of thecountry. Both raw data and data that is already cleaned and curated. Robust computing and analytic tools to support complex data analyses in a secure dataenvironment. A group of engaged participants who may be eager toparticipate in ancillarystudies. 19 We are collecting, evaluating, and curating initial datasets; availability in2019

20. Data Access | Principles andFramework Data available to all types of users ⦿ Employ a secured, cloud-based, analysis platform (no dataremoval), ⦿ Access will betiered ⦿ Users will be granted datapassports ⦿ Project information will be made public andauditable ⦿ Controlleddata individual-level health dataand genetics 20

21. Approach to Privacy andSecurity Data warehouse built with the most advanced securityavailable ⦿ Continuous rigorous security testing (HackerOne, Bug Bashes, 3rd Party Penetration Testing,etc) ⦿ Data is encrypted and personal identifiersremoved ⦿ Committed to transparency in the event of a data breach ⦿ Researchers must go through identity proofing, ethics training, agree to a code ofconduct ⦿ Protected by a Certificate ofConfidentiality ⦿ 21

22. https://www.researchallofus.org/ Learn more about the All of Us Research Program protocol > 22

23. Grand Challenges & Opportunities for all ofus… Risk Populations – Need prevalent, incident, and pre-onset age groups (precursors, EHR, medications, lifestyles, demographics,etc); Participants from existing cohorts can -- and are-- invited toparticipate ⦿ Access to data -- and translating the findings to knowledge that can betested EHR - Syntactic harmonization – driving towards the use of the same schema to represent the same values (e.g. cognitive tests, brainscans). We're leaning heavily on existing standards and vocabularies; with someheterogeneity EHR - Semanticharmonization-- ability to compare values across sources (e.g. reference ranges, medication names, prescribing and codinghabits). This will be a long and ongoing challenge, need lots of data in place and ready for analysis Use what we learn to feed back into thesystem ⦿ ⦿ ⦿ 23 GrandOpportunity: moving from observing outcomes, to predicting them and then changingthem

24. TODATE… National launch: Sunday May 6,2018 >110,000 Participants registered; >60,000 core participants 76% are under-represented in biomedicalresearch 150+ sites now enrolling in 19 states Biobank > 1M tubes (capacity for35M) Developed data warehouse to collect, clean, curate, de-identify thedata COMINGSOON: Research Portal to be open with initial public dataset in2019 Begin enrolling children once plans and protocol approved Genomics to begin in late 2018/early2019

25. Thefuture of health begins withyou - NIH