Million Veteran Program: What is it & how will it be developed - PowerPoint PPT Presentation

Million Veteran Program: What is it & how will it be developed John B. Harley, MD, PhD Staff Physician, US Department of Veterans Affairs Medical Center, Cincinnati Director, Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center Professor of Pediatrics & Medicine, University of Cincinnati Genomics and Ethics Conference 2015 10:40 AM, March 13, 2015, Kingsgate Marriott, Cincinnati

Nesting Population Research in the VA Healthcare System VA ideal setting for nested large‐scale population research – Stable and willing veteran population of 8 million using the system each year – Outstanding electronic medical record; fully integrated; data from 2 decades; access to CMS and NDI data – Research infrastructure with diverse expertise – Prototypes for health system based research: – Pragmatic clinical trials of HCTZ vs chlorthalidone – Million Veteran Program VETERANS HEALTH ADMINISTRATION

Large‐Scale Biobanks • Europe • North America – Icelandic Biobank and deCODE – Vanderbilt University – UK Biobank BioVU – Banco Nacional de ADN [Spain] – Canadian Consortium [Canada] – GenomEUtwin – dbGaP, NIH [US] – Finnish biobank – National Children's Study [US] – Swedish biobank – Marshfield Clinic [US] – German biobank, KORA – National Health and Nutrition – UK DNA Banking Network & British biobank Examinations Surveys [US – Estonian biobank: ‐ Kaiser Permanente – Family‐based collections [Nordic] – Generation Scotland Northern CA [US] – HUNT (cardiovascular)& Biohealth [Norway] – Howard University African – EPIC, European (cancer) Diaspora [US] – Danubian Biobank Consortium – Mayo Clinic – GATiB Genome Austria Tissue Bank – ACS – Biobank Hungary VETERANS HEALTH ADMINISTRATION

Million Veteran Program (MVP) Enroll up to one million veterans into an observational mega‐ cohort – Blood collection for biorepository for future research – Collect self‐reported health and lifestyle information – Access to electronic medical record – Ability to recontact participants Million Veteran Program VETERANS HEALTH ADMINISTRATION

Distribution of MVP Sites = Actively Recruiting = Closed to Recruitment ANS HEALTH ADMINISTRATION VETER

MVP Organizational Structure VETERANS HEALTH ADMINISTRATION

MVP Recruitment and Enrollment • Invitational Mailing/Appointment Mailing – Invitation letter, Baseline Survey, MVP Brochure – Appointment letter, Informed consent language • Walk‐in recruitment Study visit – Informed consent/HIPAA • – Blood collection • Thank You Mailing – Thank you letter, Lifestyle Survey • Specimens sent daily

Automated Specimen Processing VETERANS HEALTH ADMINISTRATION 6

VA Central Biorepository VETERANS HEALTH ADMINISTRATION 7

MVP Recruitment to Date (February 20150 Invitation mailings sent 2.9 Million Expressed interest by mail 19.4% (11.2%/8.2%) Optout 13% Completed Baseline Surveys 456,000 Consented Veterans 349,000 Specimens in Lab 345,000 Unscheduled (proportion) 40% Upcoming appointments 5,000 Call volume Over 500,000 VETERANS HEALTH ADMINISTRATION

Current Lab Activities (February 2015) • Receiving and Processing ‐ 400‐600 per day • Shipping Samples for Sequencing and Genotyping: Assay Type Shipments to‐date Targeted Shipments Whole Genome 1886 1370 + 516 sequencing Whole Exome 24260 24126 sequencing SNP Genotyping 206,603 ~200,000 VETERANS HEALTH ADMINISTRATION 10

Axiom MVP Biobank Array 2/13 /201 11 5

Million Veteran Program (MVP) Data Universe Biospecimen Self‐reported MVP surveys MVP Molecular Participan t Data VA ‐ Clinical VINCI, VIReC Non‐VA NDI, CMS, etc. VETERANS HEALTH ADMINISTRATION 12

Other Data Sources MVP Data Other Data • Self‐Reported Survey Data: • VA Healthcare System Data – Lifestyle Survey Data • Other Data (Personal Information, Well‐Being, Activity, Health, – National Death Index Military Experience, Dietary Intak, Medication, Habits) (NDI) – Baseline Survey (Health, – Centers for Medicare Military Experiences, family medical history) and Medicaid Services • Genetic Data (CMS) – Genotype data – State Mortality Data – Sequence data 13 VETERANS HEALTH ADMINISTRATION

VA Data Sources • • Clinic Inpatient and Outpatient Visits Corporate Data Warehouse Databases • Diagnosis (ICD‐9) codes • National Patient Care • Procedure (CPT) codes Databases • National Pharmacy data and laboratory data • Vital Status Data • Systems Decision Support System • Pharmacy Benefit Management (NDS) • National Data Extract (PBM) system database • Beneficiary Identification • OEF/OIF and OND Roster Special Records Locator (BIRLS) death • VA Clinical Assessment Reporting Data file and Tracking (CART) Access w/ • New England VISN‐1 Pharmacy • Veterans Affairs Surgical Quality Data files Improvement Program (VASQIP) Steward • Outpatient Clinic File (OPC) • Veterans Affairs Central Cancer • Patient Treatment File (PTF) Registry (VACCR) • Inpatient and Outpatient Hospitalizations VETERANS HEALTH ADMINISTRATION 14

System Architecture Data Warehouse Study Mart Vendor Survey Data Analysis Study Environment Mart VA Clinical Data Study Mart Consent NDI, CMS Non VA Manager Query Query Molecular Mart Portal Molecular data Lab Access Authorization by Governance System Researcher VETERANS HEALTH ADMINISTRATION 15

MVP Phenotyping Activities Complex Phenotypes – Myocardial infarction (MI) – Stroke – Unstable angina, revascular tx Core Variables – Acute congestive heart failure • Demographics – Death from cardiovascular disease – Age, Sex, Race – Vascular procedure • Laboratory values – Posttraumatic stress disorder (PTSD) – Total cholesterol – Schizophrenia – HDL, LDL – Bipolar disorder – Albumin – Traumatic brain injury – Serum creatinine – Depression – Triglycerides – Vascular dementia • Medications – Cognitive impairment • Other characteristics – Type 2 diabetes mellitus – Blood pressure – Height/weight/BMI – Creatinine trajectory – Smoking – Glucose tragectory – Alcohol consumption – Combat exposure 16 Algorithm Development Validation Methods VETERANS HEALTH ADMINISTRATION

Step 1: Define initial working algorithm (T1A) Step 5: Derive T2A Step 2: Create study cohort and apply T1A Step 6: Evaluate T2A to formulate T3A Step 3: Create Annotation Data Set Step 7: Develop probabilistic model and assign caseness Step 4: Create Phenomic Database through Deposit resulting algorithms to a central Phenotype Data Processing Pipelines Library

The Genomic Information System for Integrated Science (GenlSIS) ....------ - - - - - - . R&E Data Sources , - - - - - - - - - - - - - - Applications I I I Site VistA CSP Studies I I (CDW, MOWS, I SAS Files) I I I I I I I I I Genis s I I I I I I I I -------------------- I Reporting Env LIMS System Enrollment Dashboards Scientific • accessible 1 L_ _ _ _ _ _ ' _ _ _ _ _ _ I

Ongoing alpha and beta test projects • Core MVP descriptive projects – Characterization of the cohort – Race: EHR v. self report v. genes • Alpha Test projects – Schizophrenia/bipolar: Cases collected separately; controls from MVP – PTSD, Post Traumatic Stress Disorder • Beta test RFA – LOIs – Full proposals submitted this week, due March 11. Ours is on Chronic Obstructive Pulmonary Disease (COPD) • Projects in planning VETERANS HEALTH ADMINISTRATION