The Future is now: Using Big Data in Precision Medicine. Penn Medicine

Transcription

1 The Future is now: Using Big Data in Precision Medicine Penn Medicine

2

3 Penn Medicine Geography

4 Precision Medicine - Use of an individual s genetic profile to guide decisions made in regard to the prevention, diagnosis and treatment of disease. Jameson JL, Longo DL. N Engl J Med DOI: /NEJMsb

5 Strategy - focus on high acuity patients needing advanced diagnostic, therapeutic and procedural services Serve a region by being the destination for tertiary and quaternary care Top Priority of Penn Medicine s 5-Year Strategic Plan Lead in Delivering Individualized Medicine Actions to Achieve Goal Center for Personalized Diagnostics in-house oncology diagnostic lab for liquid / solid tumors Institute for Biomedical Informatics Large bio-bank focused on disease-based initiatives Precision Medicine Initiative focused investment in demonstration of personalized medicine approach beyond oncology Significant investment in advanced IT infrastructure

6 Antiplatelet inhibitors are administered to majority of patients post- Percutaneous Coronary Intervention (PCI) Plavix / clopidogrel (prodrug) activated by CYP2C19 ~15% carriers of the CYP2C19*2 LOF allele poor metabolizers of clopidogrel, increased risk of recurrent CV events Approach SPARTAN POC device for 1-hour CYP2C19 genotype assay of 700 PCI patients Observe impact on prescribing patterns and outcomes post-pci compared with historical controls Data and interpretation incorporated into EMR and pharmacy order sets Drug Clopidogrel (generic) Effient (prasugrel) Price $0.33 / pill $8.90 / pill

7 Familial Hypercholesterolemia (FH) prevalence = 1:250 Under diagnosed / under treated (<1% FH prospectively diagnosed in US) Cascade screening of extended family of diagnosed patients most effective way to identify other patients for early treatment ID ~2000 patients (in Penn Data Store) with LDL NGS LDL receptor Subjects to receive mutation results or not, encourage and facilitate probands in both groups to actively recruit extended family members for screening

8 Transforming Data into Value

9

10 Precision Medicine Technology Ingredients

11 Senior IT Governance SOM IT Governance Clinical IT Governance Business IT Governance Analytics Governance Research Advisory Education Advisory Administrative Advisory IP EMR Oversight OP EMR Oversight Business IT Committee Revenue Cycle Committee Data Governance IP EMR Operations OP EMR Operations Inpatient Enterprisewide Prioritization Committee

12 Widely Adopted Integrated EMR

13 Somatic Genetics Tumor specific Germline Genetics Inherited Highly identifiable Rare diseases in a population Ancestors Siblings Descendants More sensitive than PHI Outsource and insource Innovation and intellectual property Turnaround time Access to the results data Accuracy? Network bandwidth HPC? (see next slide) Illumina NextSeq 500 Desktop Sequencer - 23 x 21 x lbs V - Dual 1.8 GHz Xeon CPUs - 96 GB RAM GB hard drive - $250,000-1 Whole genome - 30 hours GB output per sample - $9,000 in materials and labor

14 Used to align the DNA sequence 3 billion base pairs in a full sequence Compare to a reference genome to identify variants Pattern matching jobs run for weeks Like comparing two texts on the Revolutionary War looking for common phrases Major infrastructure issues Storage, compute, retention, bandwidth, physical security, redundancy Penn Medicine HPC Center 2,500 high memory cores 2 PB of fast disk 1.8 PB of mirrored tape with robotic library Slow disk 10 GB network to campus

15 Remove 18 HIPAA Identifiers Including dates!? Makes the data almost useless Date shifting by a random (negative) number of days per patient Unstructured data cannot be reliably de-identified Need an honest broker human being Vet IRB approval Track data delivery Educate requester on best practices and accepted liability Ensure Data Use Agreements are signed Ideally spawn a VM for each data request and trap the data there A valid medical identity is worth $50 - $100 each vs. $1 for simple identity theft Opt-in research consent require per IRB

16 PennOmics Research focused Fully de-identified (3 million patients) 6,000 genetic sequences, 1.7 trillion variants Self-service access Competition underway

17 PennSeek 98 million unstructured notes, scripts & documents Productivity 10x to 100x 29 IRB-approved studies

18 Contains over 1 million samples (human or otherwise) Tissue Saliva Blood Adding 400 a week DNA Stored in Large freezers -20 to -80 degrees Indexed in a central LIMS by Building, Floor, Freezer, Shelf, Box, X-Y coordinate Feed into PennOmics if linked to a patient

19 Specimen Management Workflow

20 Implement Document Management System Integrate Epic with Clinical Trial Management System (Velos) ADT Feed to ease enrollment Enrollment feed to automate Epic subject identification / status Budgets and Scheduling grid in 2017 Capture clinical trial specific research data from within Epic Improve research billing Migrate to all Epic based in 2017

21 Define Genetic Indicators one at a time BRCA1, BRCA2, EGFR, BRAF V600E, etc. Clinicians can check off predefined Indicators Need an automated way to turn indicators on or off Epic considering for a future release Can then establish Best Practice Advisories

22 250,000+ patients enrolled in MyPennMedicine patient portal Web and mobile 30% use it regularly Engaging patients in their care Surveys Biometrics EQ-5D SINO-NASAL OUTCOME TEST (SNOT-22) HISTORY OF PRESENT ILLNESS - OTO KENNEDY OSWESTRY DISABILITY (ODI) QUESTIONNAIRE ACHD MEDICAL HISTORY QUESTIONNAIRE PROMIS PHQ2 MPM TRAVEL MED PRE-TRAVEL WORKSHEET GIM WELLNESS SURVEY PAIN MED NEW PATIENT MPM PAIN SURVEY PENN SLEEP CENTER QUESTIONNAIRE [409] AMC QUESTIONNAIRE CARDIAC SURGERY FOLLOW UP UROLOGY NEW PATIENT MEDICAL HISTORY QUESTIONNAIRE [5508] PATIENT SATISFACTION INDEX (PREOP) SURGERY MPM POV1 QUESTIONNAIRE KOOS HOOS Short Sleep TCE Derm Research Rheum Research PROMIS 29 Pain Disability Index PMR Post Procedure OPHTHALMOLOGY HVC Close Encounter Neuro Close Encounter PHQ4 MPM PSYCH MU QUESTIONNAIRE [869] Neurosurgery Otolaryngology Otolaryngology ACHD Pain Med Sleep Coumadin Clinic Cardiac Surg Urology Neurosurgery Surgery Ortho Ortho Sleep ONC DERM RHEUM Rehab Rehab Rehab Oph HVC Neurology Onc Psych

23 View Alerts and Results Data Flow mypennmedicine Receive Order Data Flow via Bluetooth Place Patient Order Acquire and Pair with Device IS Defines Flowsheet and Order Details

24 Body Measurements Vitals Results Fitness Height Heart Rate Oxygen Saturation Step Count Active Energy Burned Body Temperature Peripheral Perfusion Index Distance Walking Running Lean Body Mass Blood Pressure Systolic Blood Glucose Distance Cycling Body Mass Index Blood Pressure Diastolic Electrodermal Activity Basal Energy Burned Body Fat Percentage Respiratory Rate Blood Alcohol Content Active Energy Burned Weight Lung Function Values Floors Climbed Inhaler Usage Number Of Times Fallen NikeFuel Plus 38 Nutrition items such as Dietary Fat Total, Dietary Fat Polyunsaturated, Dietary Fat Monounsaturated, Dietary Fat Saturated, Dietary Cholesterol, Dietary Sodium, Dietary Carbohydrates, Dietary Fiber, Dietary Sugar, etc.

25 Why We Do This The Value of Precision Medicine 12/10/2012

26 Brian P. Wells Penn