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Dalton presentation Dalton presentation Presentation Transcript

  • Transformation to Value-Based Personalized Healthcare: Cancer as a Model
    William S. Dalton, PhD, MDPresident, CEO & Center DirectorMoffitt Cancer Center & Research InstituteTampa, Florida
  • Total Cancer Care: A Personalized Approach to a Patient’s Health Journey
    Populations at Risk
    Intervention
    Diagnosis
    Survivorship
    Prognosis
    Relapsed Disease
    Treatment
    – Behavioral Research
    – Psychosocial & Palliative Care
    – Family Needs
    – Health Outcomes
    – Risk Factors
    – Genetics
    – Early Detection
    – Health Disparities
    – Recurrence Therapy
    – Drug Discovery
    – Adaptive Trial Design
    – Prevention
    – Lifestyle/Nutrition
    – Education
    – Genomics/Proteomics
    – Imaging Modalities
    – Nanotechnology
    – Primary Therapy
    • Multimodality
    • Target Based
    – Post Therapy
    • Surveillance
    – Clinical Trials Matching
    – Molecular Oncology
    – Biomarker Analysis
    (http://www.hhs.gov/myhealthcare/news/phc_2008_report.pdf; pg 243)
  • The Necessary Components
    Clinically annotated bio-repository for tumor and normal specimens
    Partnership among researchers, clinicians, regulators, policy makers, and patients to design an integrated information network system
  • The Approach for Cancer
    The Total Cancer Care Protocol
    • Can we follow you throughout your lifetime?
    • Can we study your tumor using molecular technology?
    • Can we recontact you?
  • Electronic Consenting System
    Consists of IRB Approved:
    • Introductory Video
    • Consent Video by PI
    • Informed Consent
    • Signature Capture
    • Demographics Survey
    Wireless touch- screen tablet
    Connects via secure interface and forwards HIPAA-compliant information to database
  • Partners in the Fight Against Cancer
  • Nexus Biostore
    • Four unit capacity of 2.4 Million samples
    • Stores samples in a -80°C environment
    • Handles samples in a -20°C environment
    • Retrieves samples using NEXUS proprietary ‘Cool Transition’ technology
    • Flexibility to accommodate a wide variety of samples, vessels and labware
    • Automated 24/7 monitoring system in place
    • Automated Inventory functionality provides real-time inventory tracking of stored biospecimens
  • As of August 16, 2011
    Total Cancer Care To Date
    Patients Consented
    78,615
    Tumors Collected
    28,146
    Tumors Profiled
    14,604
    8
    8
    8
    Confidential and Proprietary
  • M2Gen Offices, Bio-repository 100,000 sqft in Tampa, FL
  • The Approach
    Improved
    Medical
    Practice
    Create a delivery system that will integrate new technologies into the standard of care and develop evidence-based guidelines for the treatment of cancer.
  • Four Portals to Total Cancer Care™
    Researcher View
    Next Generation Health and Research Informatics Platform
    • Cohort Identification
    • Molecular Profiling
    • Comparative Effectiveness
    Patient View
    • Personal Health Record
    • Longitudinal Follow-up
    • Personalized Search
    Administrators View
    • Operational Dashboards
    • Quality & Safety Reporting
    • Meaningful Use
    • Decision Support
    • Clinical Pathways
    • Clinical Trial Matching
    • Access for Affiliate Network
    Clinician View
  • The HRI Platform Defined
    An integrated information platform that will create real-time relationships and associations from disparate data sources needed to create new knowledge for improved patient treatments, outcomes and prevention.
  • Core
    Data Aggregation andStorage
    Source Systems
    Some representative examples of business level data domains
    Patient Cohort Examples
    Demographics
    Cancer Stage
    Diagnosis
    Treatment
    Labs
    Drugs
    Integrated Data Warehouse
    Data Factory Implementation
    Data
    Mapping
    Data
    Sourcing
    Data
    Profiling
    Data
    Modeling
    Data Linkage
    HRI Solution: Conceptual Architecture
    Front End
    Information Delivery
    Newly Diagnosed, Primary Pancreatic, having CEL File
    Cancer Registry
    LabVantage
    Capstone
    Primary Breast Cancer, Survival Time >30 months, Disease Stage 1-4, Diagnosed with Type 2 Diabetes, currently on Metaformin
    Female with myelodysplastic syndrome, currently taking vidaza as Ist course chemotherapy, initially diagnosed in 2007-2008
    CEL Files
    Galvanon
    3M
  • HRI Demonstration   
  • Number of patients in the HRI today & growing
  • Patient data available – drill down capabilities to 5 levels of detailed data elements.
  • Tissue specimen data available – drill down capabilities to 5 levels of detailed data elements.
  • The Need for Linked Queries
    Patient 1
    Patient 2
    1-1-2009
    Lung Upper Lobe
    1-1-2010
    Lung
    Upper Lobe
    1-1-2010
    Adenocarcinoma
    NOS
    LINK
    6-30-2010
    Adenocarcinoma
    NOS
    6-30-2010
    Skin Trunk
  • Venn Diagrams
  • Four Portals to Total Cancer Care™
    Researcher View
    Next Generation Health and Research Informatics Platform
    • Cohort Identification
    • Molecular Profiling
    • Comparative Effectiveness
    Patient View
    • Personal Health Record
    • Longitudinal Follow-up
    • Personalized Search
    Administrators View
    • Operational Dashboards
    • Quality & Safety Reporting
    • Meaningful Use
    • Decision Support
    • Clinical Pathways
    • Clinical Trial Matching
    • Access for Affiliate Network
    Clinician View
  • Stakeholders as Partners
    Researcher View
    Total Cancer Care Multi-Dimensional Data Warehouse
  • How is Moffitt Benefiting from the RIE?
    Using the TCC Database to match patients to clinical trials
    Right treatment for the right patient using molecular markers for patient selection
    Development of Comparative Effectiveness Research Infrastructure
    What works best for whom
    Integration of molecular, clinical, biospecimen and patient self-report data
    Gene expression data, Exome sequencing data, SNP/CNV data for new diagnostics, prognostic response and new drug discovery
  • Radiochemotherapy
    Validation of a Predictive Model of Clinical Response to Concurrent Radiochemotherapy
    Javier Torres-Roca, MD
    (R21 CA135620)
    Eschrich SA, et al., Int J Radiat Oncol Biol Phys, 2009
    • TCC database: validation of clinical response
    Figure 1
    Defining the pathway scale by mathematical modeling
    A linear regression algorithm is used to model the pathway/network scale in the radiosensitivity continuum. Biological variables (ras status, p53 status and TO) known to influence radiosensitivity along with gene expression are included in the model
  • High-Throughput Sequencing
    Exome Sequencing
    361 breast and ovary biospecimens sequenced at BGI
    Whole exome sequencing (Agilent SureSelect 38MB kit )
    Raw and analyzed data currently available
    4,000 samples being sequenced at BGI
    ~1,400 genes
    500 lung, 400 kidney, 300 colon
    150 each: uterus, pancreas, ovary, endometrium
    100 each: heme malignancies, melanoma, breast
    50 each: stomach, esphagus, liver, cervix, soft tissue, rectum, anus
    650 undecided
    Whole genome sequencing: Melanoma
    13 match pairs at Wash U Genome Inst.
  • Melanoma Comprehensive
    Research Center
    Melanoma whole genome sequencing
    • 15 melanomas and matched normal pairs chosen from TCC bio-repository
    • Linked to TCC gene expression array and clinical follow-up databases
    • Completed in only 2 months
    • Further analysis by MCC Cancer Informatics Core
    • Funded by MCC and a gift from Donald A. Adam
  • Immunology
    Classification into high and low NF-kB
    Correlation of NF-kB Signature
    with Ras Signature
    Ras Signature
    r=0.692 (p<0.001)
    NF-kB and K-ras Signatures in lung cancer
    Amer Beg, PhD
    Initial Study:
    400 Lung Patients
    TCC database validating signatures
    P50 CA121182
  • Cancer Epidemiology
    Insulin-Like Growth Factor Axis & Colon Cancer Outcomes
    300 Patient Cohort Study
    Erin Siegel, PhD
    Outcomes:
    • Treatment Toxicity & response
    • Quality of Life & symptoms
    • Recurrence & survival
    Recruitment at Surgery
    • Tumor Tissue
    • Gene expression Profile
    • Pre-surgery blood
    • New Patient Questionnaire
    • Physical Activity
    • Anthropometrics
    • Quality of Life (QOL)
    Treatment Information
    Follow-up
    3M
    12M
    6M
    Toxicity & QOL
    • Blood draws
    • Anthropometrics
    • Questionnaires (health behaviors, symptoms & QOL)
    *Green = utilizing TCC infrastructure
    State of Florida, 09BN-13
  • Health Outcomes & Behavior
    Patient Centered Outcomes Research (PCOR)
    David Fenstermacher, PhD
    • New information infrastructure to support PCOR or Comparative Effectiveness Research (CER)
    • Metadata-driven data model
    • Natural language processing algorithms
    • Developed novel data dictionary and metadata tools
    • Generated additional descriptive tool to understand differences in patient response and validation for exponential failure.
    • CER analyses to guide developing CER infrastructure
    • 3 CER studies on myelodysplastic syndrome completed(Alan List, et al., submitted in Blood)
    UC2 CA148332 (NCI Grand Opportunity grant)
  • Clinical Trial Matching
    Using TCC Warehouse to Accrue Patients Jonathan R. Strosberg, MD
    Phase 2 trial of single agent Roche gamma secretase inhibitor in metastatic CRC (PI, Jonathan Strosberg, MD)
    • Trial (NCI 8537) supported by CTEP N01 contract
    • Re-contacted Moffitt TCC patients using general eligibility criteria
    • Enrolled 37 patients in 4 months
    • Time from LOI submission to last patient treated just over 10 months
    • OEWG/IOM expectation for N01 trial activation is 210 days
  • Four Portals to Total Cancer Care™
    Next Generation Health and Research Informatics Platform
    Patient View
    • Personal Health Record
    • Longitudinal Follow-up
    • Personalized Search
  • Four Portals to Total Cancer Care™
    Next Generation Health and Research Informatics Platform
    • Decision Support
    • Clinical Pathways
    • Clinical Trial Matching
    • Access for Affiliate Network
    Clinician View
  • Clinical Pathways: Decision Support
    • Decision support tools available at point-of-care that leverage:
    • Clinical outcomes studies
    • Comparative effectiveness data
    • Comprehensive disease models
    • Evidence-based clinical pathways
  • Clinical Pathways
  • Pathways Approach
    Clinical Priorities in Pathway development
    Efficacy
    Toxicity
    Cost
    Comprehensive Clinical Coverage
  • Fixing Clinical Trials?
  • Current Clinical Trial Challenges
    • Trial activation too slow
    • Trial accrual too slow
    • Patients do not want to leave home
    • 80% of cancer care delivered locally
    • Novel investigational trials performed in Academic Medical Centers
    • Trials are searching for patients
  • Current Clinical Trial Challenges
    • Cancer patients enrolled: 2-3 % in community and 10-12 % in cancer centers
    • Early phase trials’ response rates too low
    • Early enrollers on Phase I trials are under-treated
    • Small incremental benefits in large later phase trials
    • Regulatory burden is increasing
  • Clinical Trials Vision
    • Develop a consortium network for clinical trials (practices and hospitals)
    • Obtain molecular data from patients’ tumors
    • Maintain real-time clinical data on patients
    • Match drugs to patients using molecular and clinical data
    • Faster and smaller trials with increased response rates
  • Paradigm Shift
    TODAY
    Trials searching for patients
    TOMORROW
    Trials designed for and directed to patients
  • 344
    275
    220
    209
    167
    134
    107
    42
    30
    Molecular Mapping to Produce Dynamic Pool of Trial-Ready Patients
    (Many Mapped to Pre-Selectively Enroll a Few)
    Newly Diagnosed Metastatic/Locally-Advanced Patients
    Assumptions Reducing Sample Size
    • Starting sample sizeY
    • Availability of biopsy* (-20%)
    • Adequacy of biopsy (-20%)
    • Assay failure (-5%)
    • Death/Morbid/Toxicity (-20%)
    • Temporal Readiness within 1 yr of the Bx (TTP < 1yr) (-20%)
    • Performance Status or inadequate Labs (-20%)
    • Prevalence of Mutation (-60%)
    • Pt/MD Choice of Rx (-30%)
    One Tumor Type
    Diminishing
    # of Patients
    Potential “Positive” Factors:
    • Could also limit to specific diseases (such as colon, lung, breast, pancreas) to ensure proper final mix
    * Could allow primary biopsies for brain, prostate, pancreas, ovary, bladder, pancreas where distant metastases hard to access;
    * Could also assume physicians might consider a “diagnostic” Bx in a situation when otherwise they might pass
    Trial-Ready
  • Ultimate Goal of New Trials
    To incorporate molecular characteristics
    of the tumor, as well as the patient’s genetic
    background, into an individualized treatment
    plan to maximize clinical benefit to the
    patient from specific anti-tumor agents.
  • Biomarker-driven trials at Moffitt
    • Phase 3 RRM1/ERCC1 directed chemo in advanced NSCLC (completed)
    • Phase 2 R115777 in elderly AML with specific 2-gene ratio (active)
    • Phase 2 Notch inhibitor in mCRC (completed)
    • Planned TCC consortium trials
    • CY 2011 Pharma Trials
  • Designing a New Research & Healthcare Network Model
    Hospitals & Healthcare Networks
    Offices & Clinics
    Insurers
    Research
    Information
    Exchanges
    Personal
    Health
    Records
    Researchers Centers
    & Networks
    Genomic Data &
    Annotation
    Services
    Patients
    Researchers
    Dalton, Fenstermacher, et al, Clin Cancer Res; 16 (24) December 15, 2010
  • Rapid Learning Information System for Cancer Care & Research
  • Thank You