Geisinger s Precision Health Initiative

Transcription

1 Geisinger s Precision Health Initiative June 28, 2017 David H. Ledbetter, PhD, FACMG Geisinger Health System dhledbetter@geisinger.edu 1

2 3.5% Expected to get results 8,700+ Participants MyCode Footprint MyCode Patient Impact It means hope. Lynn Yost Battled breast, ovarian & melanoma cancer I really never thought they would find anything. Kim Mummert Lynch Syndrome mutation 152,000+ Participants * * I feel like I cheated cancer. Dina Harringon BRCA2 mutation identified It s my responsibility as a parent. Loudon Connelly First newborn enrolled in MyCode 92,000+ Lynch Syndrome Mutation Exomes BRCA2 Mutation sequenced

3 The Learning Healthcare System, is the first publication of the IOM Roundtable on Evidence-Based Medicine, >12 volumes published since (now NAM). - Research and clinical care should not be separate. Advanced EHR/clinical data warehouses at LHS offer opportunities for massive amounts of free phenotypic data.

4 Building a Genomic Medicine Clinical/Research Team (2010-present) Genetic Clinical Lab MD Clinical Counselors Directors Geneticists (>25) (2) (4) Bioethics (3) Bioinformatics (4) 4

5 Community Health Initiative MyCode began in 2007 High consent rate (90%) Goal >250,000 sequenced 152,000+ consented MyGeisinger (online) AtlantiCare (NJ) 8,700+ Holy Spirit (Harrisburg) Launched May 2017 *As of 1/23/2017 5

6 Geisinger-Regeneron Foundational Collaboration to Sequence >250,000 People in the Geisinger Health System Scientifically and medically, it s pretty exciting, said Dr. Leslie G. Biesecker, chief of the genetic disease research branch at the government s National Human Genome Research Institute, who is familiar with the project. As far as I m aware, it s the largest clinical sequencing undertaking in this country so far by a long shot. He added that the move of sequencing into general health care is going to change medicine. Goal: build the world s most comprehensive genotype-phenotype resource combining deidentified genomic and clinical data from >250,000 people to aid drug development and genomic medicine Geisinger: >2.5 million patient health system with cradle to grave records; amongst earliest adopters of EHRs and leaders in clinical informatics Two organizations focused on making genomic data medically actionable and translating genetic discoveries into improved patient outcomes and therapeutics 6

7 Clinical Engagement Cohort Value >150,000 Consented cohort (>92,000 sequenced) years of EHR data 47 clinical encounters 455 lab test values 94 vital measurements Geisinger Health Plan (GHP) sweet spot 56,847 GHP coverage at some point 30,989 GHP coverage now (38.7%) 7

8 Critical Consent Features Opt-in consent Re-contact Longitudinal EHR data Longitudinal samples Return of clinically actionable results Online consent 8

9 American College of Medical Genetics and Genomics ACMG Recommendations for Reporting of Incidental Findings in Clinical Exome and Genome Sequencing Robert Green, Jonathan Berg, Wayne Grody, Sarah Kalia, Bruce Korf, Christa Martin, Amy McGuire, Robert Nussbaum, Julianne O Daniel, Kelly Ormond, Heidi Rehm, Michael Watson, Marc Williams, Leslie Biesecker We thank the following individuals for their review and comments on drafts of this paper, many of which were adopted by the Working Group. Margaret Adam, Jeffrey Botkin, Wendy Chung, David Dimmock, Christine Eng, Madhuri Hegde, Gail Jarvik, Stephen Kingsmore, Michael Murray, Katherine Nathanson, Sharon Plon, Reed Pyeritz, Cheryl Reid, V. Reid Sutton, Benjamin Wilfond. The final version of this paper and its recommendations do not necessarily reflect the views of these individuals. 9

10 Predicting Clinical Volume From First 250K Participants (2-4% in healthy adults) Patients Identified Participants with pathogenic variants from Geisinger 76 Estimates 5-10,000 At risk relatives identified 15-30,000 Total 20-40,000 10

11 The DiscovEHR Research Cohort (Science, Dec. 23, 2016) Regeneron and Geisinger first 50K exomes 11

12 Top Three Most Prevalent Conditions in the G76 Expected to Compose Half of those Returned GENOMIC CONDITION POPULATION PREVALENCE CLINICAL RISK DISEASE-ALTERING INTERVENTION Familial Hypercholesterolemia Hereditary Breast and Ovarian Cancer Syndrome 1 in in 400 Lynch Syndrome 1 in 440 TOTAL > 1 in 100 Early-onset Coronary Artery Disease and Stroke Early-onset Breast, Ovarian, and Prostate Cancers Early-onset Colon and Uterine Cancers Multiple Cancers and Cardiovascular Diseases Targeted screening and aggressive medical management Targeted screening with prophylactic medical and surgical intervention Targeted screening and management of precancerous changes Life-saving screening and intervention before development of disease Responsible genes to be screened: BRCA1, BRCA2, MLH1, MSH2, MSH6, PMS2, LDLR, APOB, PCSK9

13 The DiscovEHR Research Cohort (Science, Dec. 23, 2016) Regeneron and Geisinger first 50K exomes 13

14 14

15 Barbara Barnes MyCode Story 57 Year old grandmother bringing up three grandchildren ages 3, 5, and 14 Found to have a pathogenic BRCA1 mutation Okay, so what do we do next? I have 15 more years to go until they re raised. Genetic counseling and workup Negative mammogram Elected to have preventive bilateral salpingooophorectomy Stage 1 cancer found in one fallopian tube Completing chemotherapy with expected excellent outcome 15

16 Lessons Clinical Outcomes Early-stage cancer diagnoses in 3 patients with pathogenic BRCA variant 56yo woman: fallopian tube cancer detected on RRSO 57yo woman: DCIS detected on surveillance breast MRI 55yo man: elevated PSA & positive prostate biopsy Each diagnosis prompted by clinical work-up that followed results disclosure Highlights importance of link to clinical support 16

17 Short-term/long-term goals Find every patient & family member in GHS system with FH; determine optimum age/method of tx w/ statins or PCSK9 inhibitors to prevent CVD. Find every person with BRCA1/2 mutation for early monitoring/detection breast/ovarian cancer. Early detection by ctdna sequencing? Move on to other diseases! 17

18 Summary of DBD CNVs in general adult population Significant proportion of individuals (0.8%) in our health systembased cohort have a DBD CNV 40-50% of all individuals with a DBD CNV have a DBD diagnosis Many have a diagnosis consistent with known CNV phenotype, however most do not have an EHR-documented genetic etiology We are initiating a return of results program to provide this clinically relevant information back to patient-participants 18

19 W. Andrew Faucett, MS, LGC Christa L. Martin, Ph.D., FACMG Marc Williams, MD, FACMG Adam Buchanan, MS, MPH, LGC Amy Sturm, MS, LGC Karen Wain, MS, LGC Marci Schwartz, MS, LGC Miranda Hallquist, MSc, LGC Janet Williams, MS, LGC Heather Rocha, MS, LGC Cara McCormick, MPH Loren Gorgol, MS Amanda Lazzeri, BS Lauren Frisbie, BS Michael Murray, MD, FACMG Murugu Manickam, MD, FACMG Marylyn D. Ritchie, Ph.D. Carroll Flansburg, MA, MPH MyCode Genomics Team David C. Carey, Ph.D. Dan Davis, Ph.D. Jennifer Wagner, Ph.D., J.D. Michelle Meyer, Ph.D., J.D. Ethics Advisory Council members Clinical Oversight Committee members Focus group participants Precision Health Patient Advisory Board GEISINGER PATIENTS Regeneron Genetics Center Aris Baras, M.D. Rick Dewey, M.D. Omri Gottesman, M.D. John Overton, Ph.D. Jeffrey Reid, Ph.D. Alan Shuldiner, M.D. George Yancoploulos, M.D., Ph.D. Laboratory for Molecular Medicine Matthew S. Lebo, Ph.D. Christina Austin-Tse, Ph.D. Heather M. Mason-Suares, Ph.D. Heidi Rehm, Ph.D., FACMG

20 Still growing our team! Looking for outstanding: Genetic counselors (ABGC) Molecular Genetics Lab Directors (ABMGG) Clinical Geneticists (ABMGG) Clinical Informatics/Bioinformatics Bioethics/Health Care Policy Health Economists Help translate >250,000 exomes into improved health and well-being at Geisinger and beyond! 20 20