Mayo Site Report. emerge phase II Steering Committee meeting. New York City, NY June 30, 2015

Transcription

1 Mayo Site Report emerge phase II Steering Committee meeting New York City, NY June 30, 2015

2 Mayo emerge Team Iftikhar J. Kullo, MD Christopher G. Chute, MD, DrPH Phenotyping Chris Chute, MD, DrPh; Jyoti Pathak, PhD; Sue Bielinski, PhD; Kevin Bruce, BA; Sean Murphy, MS; John Heit, MD; Hayan Jouni, MD, Adelaide Arruda-Olson, MD; Carol Ye MD, Iftikhar Kullo, MD Genomics Mariza de Andrade PhD, Erin Austin, PhD; Tim Lesnick, MS, Kent Bailey, PhD EHR integration Chris Chute, MD; Jim Buntrock, MS; Pedro Caraballo, MD ROR Iftikhar Kullo, MD; Jennifer McCormick, PhD; Richard Sharp, PhD CERC Jen McCormick, PhD, Richard Sharp, PhD emerge PGx S Bielinski, J Pathak, Jen McCormick PhD, R Weinshilboum, C Chute, I Kullo Project Management Chandra Hutchens Angie Dalenberg

3 Mayo emerge II Aim 1 Aim 2 Phenotyping Based on structured EHR data and NLP of unstructured text Cardiorespiratory fitness Venous thromboembolism Heart failure Response to statins Genomics Genetic risk scores for CHD (28 SNPs related to CHD risk) Develop tools to convey genetic component of risk (pictograms) Aim 3 Aim 4 EHR integration Incorporate CHD GRS into EHR Decision aid to enable shared decision making Return of results Randomized clinical trial to evaluate comprehension and response to GRS for CHD

4 Phenotyping highlights Harmonize phenotype data dictionaries across the consortium Alignment of emerge with PhenX elemap tool Open-source NLP resource ctakes PhEMA

5 Phenotypes implemented Phenotypes Cases Controls AMD Colon Polyps MACE on statins Atopic Dermatitis CAAD CKD GERD BPH

6 2014 MFMER slide-6

7 Mayo Clinic Biobank 51,908 QN and DNA consented 47,655 completed Female 58% Male 42% Mean Length of EHR: 15.6 y Median length of EHR: 18.6 y Range: 0 to 23.8 y IA 6% WI 4% Dakotas 2% Other US 20% Rest of MN 16% SE MN 15% Olmsted 37% Age at consent

8 CHD N= % HTN DM HLP Smoking COPD CKD AAA N=1095, 9% PAD N=3384, 29% CAS N= % Comorbidities Mayo Vascular Disease Major diseases Age, years 66.2 (11.9) Men, % 61.6 Rare vascular diseases FMD, vasculitis Genotyped ~10,000 Biorepository Ancillary data N=11,814 till 7/22/2014 Laboratory ~99% ECHO 71% ECG 96% Rx 100%

9 Genomics highlights QC for the network-wide high-density genotype dataset for dbgap submission GWAS of VTE, HF and CRF Genetic risk scores Structural and null variant projects PheWAS projects Encode collaboration (RBC & platelet traits)

10 Genomic association analyses SNP MAF OR P GENE Cases Controls VTE-EA* rs E-14 F5 2,537 9,625 rs E-14 LOC VTE-EA** rs E-07 GPNMB 2,537 9,625 rs E-07 KLHL7 VTE-AA*** rs E-08 LEMD ,941 rs E-08 LY86 CRF rs E-07 SH3RF3 2,756 no gene rs E-07 associated HF rs E-08 ANAPC1 2,612 9,380 rs E-08 LOC HFpEF rs E-07 PPARGC1A 853 9,380 rs E-07 HMGB3P18 HFrEF rs E-08 CLCNKA 676 9,380 rs E-08 ZBTB17

11 Genetic risk score for CHD

12 ROR highlights MIGENES clinical trial Myresults.org website ROR instruments repository Manuscripts describing ROR activities in the Network Consent form for emerge PGx ROR template for PGx actionable events Contribution to Network-wide projects

13 MIGENES highlights Feasibility of incorporating genomic risk information for a common disease in the EHR o Risk report placed in EHR o Shared decision making using an EHR-embedded decision aid Disclosure of a GRS for CHD led to lower LDL-C levels Increased perceived personal control and genetic counseling satisfaction Genetic knowledge, numeracy, and risk perception Does not affect participants satisfaction with shareddecision making Increased information seeking and sharing

14 CERC highlights Participated in several CERC working committees, including informed consent, IRB interaction, data sharing, community consultation, and ROR Co-lead of the IRB committee for the national survey on ROR project as well as an active member of the survey development committee

15 Other Mayo CERC Activities Community Advisory Board Survey asking participants about preferences for handling sample and data after their death Collaborating with CIM re Education on patient PGx survey and provider PGx survey CERC/CSER and CERC/RoR papers Participating in Mayo Clinic s next phase of the emerge initiated RIGHT PGx study (10K expansion)

16 EHRI highlights EHR-based genomic decision aid to facilitate shared decision-making after disclosure of CHD risk Contributed to development of Info button resource for PGx CDS usable among multiple sites Shared our CDS logic for simvastatin, clopidogrel, and warfarin

17 EHR-based Genomic decision aid

18 Clinical Decision Support process Enterprise-wide team of physicians, pharmacists, informaticians, IT experts, laboratorians, and education staff Met weekly to collaborate with clinical champions and informaticians to o define rules and garner support across the enterprise o develop new IT processes for implementing drug-gene rules o build consensus among the laboratory, clinical and pharmacy practices o create and update supporting point-of-care education

19 Drug-gene rules that are live Tested Clopidogrel, Citalopram, Escitalopram: CYP2C19 Simvastatin: SLC01B1 Warfarin: CYP2C9/VKORC1 (used in dosing algorithm) Abacavir: HLA-B*5701 Carbamazepine: HLA-B*1502 Thiopurines (4 drugs): TPMT (enzyme/ phenotype test) Codeine, Tramadol, Tamoxifen, Paroxetine, Fluoxetine, Fluvoxamine, Venlafaxine: CYP2D6 Allopurinol: HLA-B*5801 In process Tacrolimus: CYP3A5 Carbamazepine: HLA-B* Fluorouracil: DPYD/TYMS Maintenance of existing rules

20 emerge PGx highlights Rapid and efficient recruitment Consent form for the project widely adopted Sequencing of the 84 pharmacogenes + conventional genotyping for CYP2D6 in a CLIA setting, enabling direct deposition of variants in the EHR with linkage to CDS CDS for tamoxifen, simvastatin, clopidogrel, codeine, tramadol and warfarin is currently live in the Mayo HER 10k expansion 2011 MFMER slide-20

21 CENTER FOR INDIVIDUALIZED MEDICINE Genomic Medicine: From Promise to Practice 2012 MFMER

22 Center for Individualized Medicine emerge- PGx Supplement Dr. Christopher Chute (Co- PI) Dr. Iftikhar Kullo (Co-PI) Dr. Jyotishman Pathak Dr. Suzette J. Bielinski Dr. Richard Weinshilboum Dr. Liewei Wang Dr. Pedro Caraballo Dr. Robert Freimuth Dr. Janet Olson Dr. Karen Maschke RIGHT Protocol Ms. Kiley Johnson Ms. Jody Morrisette Ms. Kelly Lyke Dr. Jennifer McCormick Ms. Tamra Velduizen Ms. Cloann Schultz Pharmacogenomics Network (PGRN) Dr. Richard Weinshilboum (Co-PI) Dr. Liewei Wang (Co-PI) Center for Individualized Medicine Dr. Gianrico Farrugia Mr. Scott Beck Pharmacogenomics Dr. Richard Weinshilboum Dr. Liewei Wang Clinomics Dr. Eric Wieben Dr. Matt Ferber Dr. Konstantinos Lazaridis Dr. Eric Klee Mr. James Buntrock Ms. Tammy McAllister Education Dr. Petra Casey Dr. Jerry Swanson Dr. Christine Formea Ms. Caer Vitek Personalized Genomics Laboratory (PGL) Dr. John Logan Black III Dr. Linnea Baudhuin Clinical Genome Sequencing Laboratory (CGSL) Dr. Matthew Ferber Dr. Eric Klee 2011 MFMER

23 Patients at risk for being started on: Warfarin Clopidogrel Simvastatin Sequence 84 VIPs Variant annotation Place actionable variants in EHR Linkage to CDS that provides guidance at point of care Assess outcomes placing PGx information in EHR

24 CDS for 3 commonly used drugs CYP2C19: Poor metabolizer for clopidogrel Alternative antiplatelet (e.g. Ticagrelor) Genotypes at VKORCI and CYPC29 Precise dosing SLCOB1 polymorphism Lower dose of simvastatin or use another statin

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26 Drug Gene Alerts Between January, 2013 and May, drug order alerts fired Drug Codeine/Tram adol/tamoxifen Gene Alert Live date n Pgx CYP2D6 10/26/ Simvastatin SLCO1B1 4/24/ Warfarin CYP2C9/V KORC1 9/18/ Clopidogrel CYP2C19 9/18/ MFMER slide-26

27 Education links: AskMayoExpert

28 LDL cholesterol levels and 82 VIPs N=~ individuals Marshfield Clinic, Mayo Clinic, NW University, UW/GH, Vanderbilt University Targeted Seq data Lipid panel Male 1582 (49%) Mean age: 56.5±9.8 years Mean LDL-C: 114.3±29.3 years MAF 0.05 LD r2 <0.50 Adjustments for age, sex, population stratification Sequencing with PGRNeq, including 5 lipid genes (LDLR, HMGCR, NAT2, ABCA1, and APOA1) Adaptive sum of powered score aspu test P-value: HMGCR LDLR TCL1A* NR3C1* CRHR1* NAT ABCA APOA

29 Acknowledgements Mayo Center for Individualized Medicine National Human Genome Research Institute (HG-06379)

30 Thank you to the emerge network. It has been a great four years!