The Department of Veterans Affairs* MVP and GenISIS

Report
THE VISN 1 CLINICAL
TRIALS NETWORK
Non-Profit Corporation Strategy Meeting
JUNE 25TH 2014
Meeting Purpose and Goals
• Present the VISN1 Strategic Plan and research
vision for the Clinical Trials Network
• Present an overview of the Clinical Trials
Network
• Discuss the role of the NPCs in creating an
effective and sustainable model for
collaborative research in the VISN
VISN1 Strategic Plan
• VA New England Healthcare System Strategic Plan for FY2013-2017
– Objectives established in five key areas
– Goal I: Excellence in population health
• Build a culture of improvement
– Goal II: Excellence in patient experience
• Fix the phones
– Goal III: Excellence in financial stewardship
• Expand our patient base
– Goal IV: Excellence in work force
• Manage retirement surge
– Goal V: Excellence in Contributions to our national well-being
• Enhance research
VISN1 Strategic Plan: Enhance Research
• Long term strategic target – to be the leading
VISN in annual research funding
• Establishing academic affiliations and research
programs at all eight VISN1 Medical Centers.
• Aim to attract and retain high quality
researchers within the Network through:
– Career Development Awards
– Research Enhancement Fund
VISN1 RFP: Aligning with MAVERIC’s Vision
• RFP: Creation of a Clinical Trials Network in VISN1
• Expresses importance of innovative and groundbreaking work
• References:
– Co-operative clinical research groups (Children’s Oncology Group)
– NEJM article: Looking beyond translation – Integrating Clinical
Research with Medical Practice
– IOM: Envisioning a Transformed Clinical Trials Enterprise in the US
– IOM: A National Cancer Clinical Trials System for the 21st Century:
Reinvigorating the NCI Cooperative Group Program
• MAVERIC’s Vision:
– To create a Learning Healthcare System within VA through application
of research resources and methodologies to important clinical
problems.
MAVERIC
• Massachusetts Veterans Epidemiology Research and
Information Center (MAVERIC)
– Interdisciplinary research and development organization
established in 1996 with continuous growth
– CSP Epidemiology Research Center, VA Research Biorepository,
CSP Clinical Trials Coordinating Center (ISO 9001), Informatics
Core
– VA Research Transformational Initiatives: Million Veteran
Program, GenISIS, Point of Care Research
– Established model for collaborative research: umbrella IRB,
feasibility studies prior to trials, administrative support team,
site monitoring algorithms, informatics tools, data cores,
statistical expertise
Employees and Funding Per Year
140
$25,000,000
120
$20,000,000
100
$15,000,000
80
60
$10,000,000
40
$5,000,000
20
0
$0
1997
1998
1999
2000
2001
2002
2003
2004
2005
Employees
2006
2007
Funding
2008
2009
2010
2011
2012
2013
Beyond traditional clinical trials –
Engineering a learning healthcare
system
Problem Statement
• Healthcare system’s research needs are not
fully met by the current research enterprise
– Designed for basic science inquiry and drug
discovery
• There is no scalable model for:
– Clinical Effectiveness Research
• research comparing known treatments
– Biomarker validation (Personalized Medicine)
• For diagnostics, prognostic or therapeutic indications
The
Healthcare
Value Gap
The
Pharmaceutical
Innovation Gap
R&D in the Pharmaceutical Industry, A Congress of the US Budget Office Study, Oct 2006
Rethink silos
Clinical
Hospital
Administration
Clinical
Research
Pharma
A Solution
• Creation of a Learning Healthcare System that creates locally
applicable knowledge
– Identifies its’ own needs
– Uses its’ own infrastructure
– Adapts available research methodology
– Directly implements research results
• The knowledge gained is thus not generalizable (thus not
‘research’) but rather is ‘locally selfish’.
The Learning Healthcare System
Opportunity – Why now?
• Digitization of medical care information
• Reimbursement for quality not volume
• Accountable care organization needs
– Development of healthcare intelligence tools
– Need for comparative effectiveness research
• Power shift from pharma to clinical care
• Increasing costs of clinical trials
Learning from medical record data
…to improve healthcare delivery…
Current QI efforts
•
•
•
•
Mandated reporting
Manual chart abstraction
Limited variables
Question of generalizability from ward to ward
Kaleid Project
1. Data from all available sources
2. Collaborative exploration of the data
3. Automatically learn the most significant
correlates to an outcome
– By hospital, ward, clinician, etc
4. Deploy custom interventions
– Dashboards
Kalied Status
• Pilot deployment - CAUTI
• NLP outperforms nurse chart abstractors for Foley day
extraction
• Chosen as pilot project for VA’s next EMR
• Foundational project of a new VA Patient Safety Center
Integrating clinical research & care
Point of Care Clinical Trial
• A clinical trial with a substantial portion of its operations
conducted by clinical staff in the course of providing
patient/subject’s routine clinical care and where the choice
of treatment is between two “equivalent” options
Care providers using EMR
Cohort
Identification
Enroll
& Consent
Data Capture
Study DB
Randomize
Intervention
Clinical
Decision Support
Analysis
Study team using traditional scientific tools
POCR Advantages
• Pragmatic qualities address issues of Clinical Effectiveness
• Faster (immediate) Integration of results into practice
thereby lowering the T2 translation barrier
• Enhanced acceptance by providers (locally selfish)
• Conversion to a decision support node
• Improved logistics – scalable
Integrating genomics
Million Veteran Program (MVP)
• MVP is a major research initiative that will create a
longitudinal cohort of one million users of the VA
Healthcare System to study genes and health
• Designed to provide a better understanding of how
genes affect health and illness
• Goal of improving health care for Veterans and the
nation
GenISIS
Translating genomics into
Personalized Medicine
The Challenge of Personalized
Medicine
‘OMICS
Build a
cohort
Actionable Results
Make data
accessible
Discover
Million Veteran Program
& GenISIS
Validate
Implement
Point of Care Research &
Kaleid
Shifting from Histologic to HistoMolecular Dx
Precision Oncology Objectives
• To create a robust precision oncology
program in VISN 1 to:
– Reduce disparities in cancer treatment
– Enhance clinical care through systematic learning
– Provide opportunities for clinical trial
participation
– Provide a platform for biomarker discovery and
validation
What is Precision Oncology?
•
•
•
•
•
•
•
Perform genomic test on a cancer specimen
Determine driver mutations in the cancer
Deliver therapy based on identified target
Several targets in a given patient
Different targets across patients
Same targets in different cancer types
Few patients with any given target at one site
Clinical Care Component – All Patients
• Routine molecular profiling for NSCLC patients as
routine care
– Longitudinal patient data collected in
standardized format
– Clinical Data Warehouse created
• Track program metrics
• Make available to researchers with HIPAA waiver
– Referral into clinical trials
– Data mining
• Analyze outcome data to inform clinical care for
‘patients like me’ (Virtual Molecular Tumor Board)
Current ‘Local Learning’
Cancer genomic
test results
POP Data Base
No
Sx
Sx
Dx
Tx
Tumor Board
recommendations
Providers
Time
Local Learning Through Observations
Prior N patients
POP Knowledge Base
with ‘Prediction Engine’
N+1 cancer
genome
Tumor Board
recommendations
Dx
Tx
N+1 patient
Providers
Time
Patients Like Me (n+1)
Local Learning Through Experiments
Prior N patients
POP Knowledge Base
with Predictive Engine
If equipoise exists Tumor Board
offers randomization within
routine care
N+1 cancer
genome
Dx
Tx
higher weight on
randomized outcomes
N+1 patient
Providers
Time
Research Component – Treated
Patients
• Patients with treatment plans asked for
consent and HIPAA authorization to:
– Collect longitudinal outcome data in standardized
format to create a research data warehouse
• For creation of generalizable knowledge
• Sharing through CRADA mechanism
– Allow for additional testing of tissue specimens
• Implications for tissue management
– Allow for re-contact for research purposes
including clinical trial consideration
Phase II/III Biomarker-Driven Master Protocol for 2nd Line
Therapy of Lung Squamous Cell Carcinoma
• Lung SCCA remains an “orphan” disease – significant developments in
therapeutics has yet to be seen
• Multi-Arm Master Protocol can improve operational efficiency with
homogeneous patient population and consistent eligibility
• Grouping multiple studies reduces screen failures – broad-based platform
allows for high “hit rate”
• Designed to allow for FDA approval of new drugs
Rollout
• Fall2014 regional prototype
– 5 VISN 1 Centers: Boston (Harvard, BU), West
Haven (Yale), Providence (Brown), White River
Junction and Togus (Dartmouth)
– 3 additional Centers: New York (NYU, Cornell), Ann
Arbor (U of Mich) and Durham (Duke)
• Summer 2015 expanded pilot
– 20-24 sites
• Summer 2016 national rollout
OK! So Now Are We Ready to Select
Drugs for Patients in an even more
Personalized Way?
Hello, here is my tumor sequence
Overview Of The Clinical Trials Network
• Mission
– To create infrastructure and process to expand clinical
trials within VISN 1 facilities that will contribute
towards traditional and novel research objectives.
• Goals
– To increase the number of clinical trials in the VISN
– To increase the numbers of Veterans enrolled in
clinical trials
– To increase annual research funding
Overview of the Clinical Trials Network
• Goal to develop a full-service, sustainable and scalable
research enterprise
– Operations Core
• Serve as the operational system for the Scientific Core and Field
Component
• Capitalizes on existing experience and infrastructure
– Field Component
• Provide resources necessary to execute studies at each site.
• One full time site coordinator hired at each facility in the network to
execute protocols initiated or expanded through the CTN
• Establish a network of sites to collaborate on research protocols
• Increase research opportunities in the VISN
– Scientific Core
• Assist in the development of disease specific consortia and facilitate
investigator initiated projects
• Create collaboration across facilities in specific disease areas
• Increases patient base allowing greater opportunity (consortium vs.
single-site approach)
Program Governance and Committee Structure
VISN 1 Clinical Trials Network (CTN) Committee Structure
Executive Leadership Board
Director of
VISN 1 CTN
External Advisory
Committee
CTN Field Advisory &
Management Committee
Purpose of the Field Advisory and Management
Committee (FAMC)
• Committee Role and Responsibilities
– Identification, development, and expansion of
protocols across the VISN
– Oversight for field activities
– Policy development and review
– Field resource management
– Fostering a culture of excellence and safety
Purpose of the External Advisory Committee
(EAC)
• Provide support in strategic planning
• Assures state-of-the-art clinical research within
the CTN
• Integration of research within the VHA systems
Expanding Research Across The Network
– Broad long-range goals suggested by Dr. MayoSmith:
• Double the number of clinical trials within the network
from 87 to 174 by end of FY16
• Double the number of veterans enrolled in clinical trials
within the network by end of FY16
• Support new research activities that would result in an
estimated annual $4 million VERA revenue across the
network by end of FY16
Expanding Research Across The Network
• Program Funding and Sustainability
– Funds appropriated for the CTN to support the infrastructure and facilitate
the expansion of clinical trials within the network
– Newly initiated projects will require funding from sponsors to support the
core and field activities at each participating facility
– Goal for each facility to establish local infrastructure to efficiently support
incoming protocols
– Operations Core infrastructure eliminates the need for full-scale expertise
and experience to be reinvented at each facility
• data operations, RACC, informatics, project management, statistical expertise,
biorepository services, study design expertise
Clinical Trials Network Accomplishments
Oncology Consortium
• Representation from each VISN facility with oncologists
– 7 trials have been reviewed by the consortium.
• 3 are currently open at WRJ site
• In application process for 4 studies
– Engaged the NCI’s Southwest Oncology Group who
enthusiastically endorsed the consortium’s application
as a VA network
• Applying for SWOG membership as a consortium
• Storefront arrangement
Clinical Trials Network Accomplishments
Precision Oncology Program
• Program has morphed into clinical and research
components
• Clinical program allows for routine molecular profiling tumors
of NSCLC patients with results returned to EHR
• Research component designed to match patients to research
protocol for targeted therapies (e.g., NCI master protocol)
– Buy-in from clinical obtained (oncology, pathology,
pharmacy)
– Engaging PBM and pharmaceutical sponsors to discuss
drug costs, management and distribution
– Currently working with contracting to secure vendor
for analysis
Clinical Trials Network Accomplishments
Cardiology Consortium
– Representation from each facility with cardiologists
– Strategic plan has been created to approach collaborative
networks and sponsors
– Sponsored Trials Activity
• Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and
Mortality in Heart Failure Patients With Preserved Ejection Fraction
(PARAGON-HF) – Novartis trial approved in Boston, currently
submitting IRB paperwork. 2 additional sites are in application process
• Effect of Serelaxin Versus Standard of Care in Acute Heart Failure
Patients – trial approved in Boston
• Two sites applying for an additional Novartis trial (Fourier)
Clinical Trials Network Accomplishments
Other Projects
– Multiple Myeloma trial: Dr. Nikhil Munshi working with
pharmaceutical company to establish VA-specific myeloma
protocols
– Working with Dr. Vickie Driver (VA Providence) on expanding her
extensive research in wound healing across the network
– Potential for additional consortia (Mental Health, Palliative Care,
Women’s Health) in the future
Clinical Trials Network Accomplishments
Program-wide
– Regular discussions and engagement with ACOS-Rs across the
VISN
– Working toward hiring field staff
– Identification of local investigators with projects for possible
expansion
– Discussions regarding streamlining IRBs; planned meeting in
September with IRB Chairs
– Discussions with co-chair of Central IRB
Clinical Trials Network Accomplishments
• ORD/CSP Engagement
– Expansion of MVP across the network (NNERC)
– VA FIT (CSP #593) to be launched in WH and NNERC with
Boston and Providence as dual back-up sites
– Suicide Prevention trial (CSP #590) to be launched in
Boston with Togus, WH, and Providence as back-up sites)
– Use of ORD infrastructure/resources to support CTN
– Interest in the concept of a Learning Healthcare System
with possible financial backing
– Agreement to use NCI Central IRB based on expected policy
changes (~4-6 months)
Current State of Research in the VISN
CRADAs by type
60
50
40
30
20
Active CRADAs
Pending CRADAs
10
0
Current State of Research in the VISN
Investigators pursuing CTs by specialty
Investigators by Specialty
50
45
40
35
30
25
20
15
10
5
0
Other = Prostate Cancer, Infection Control, Pulmonology,
Epidemiology, Gastroenterology
Current State of Research in the VISN
Current VA-funded Portfolio (Clinicaltrials.gov)
70
60
50
40
New Trials
Trials Open
30
20
10
0
BOS
WH
WRJ
PRO
CWM
MAN
“New trials” = trials added since 4/20/2014
BED
TOG
Current State of Research in the VISN
Current VA-funded Portfolio (Clinicaltrials.gov)
Wide range of trials:
• Mental Health: PTSD, Stress Disorders, Memory Disorders, Traumatic Brain
Injury
• Depression, Suicide Prevention, Pain Management
• Schizophrenia, Bipolar Disorder
• Substance Abuse, Alcohol Abuse, Tobacco Dependence
• Cardiovascular: Coronary Artery Bypass Grafting, Coronary Heart Disease
• Cancer: Leukemia, Multiple Myeloma, NSCLC, Colorectal
• Chronic Disease: COPD, Hypertension, Diabetes, Kidney Disease
• Sleep Apnea
• HIV and AIDS
• Osteoporosis
• Orthopedic Injury, Spinal Cord Injury, Prosthesis Usage
• Wound Healing
• Spinal Cord Injuries
• GERD and Gastrointestinal Diseases
• Women’s Health issues
Discussion
• How do we create a sustainable model to support and grow
infrastructure for research?
• How do we structure and manage CRADAs for multi-site research
projects?
• What is the role of the STAR Attorneys and how we can help develop
processes for supporting multi-site CRADAs?
• What tools are available to support and standardize processes
across NPCs?
• How to we inform local investigators of the network and availability
of the core infrastructure? How do we communicate across facilities
and NPCs to strengthen and grow the VISN research enterprise?
• What are the risks, barriers, and threats to success of a research
network?
Thank you!
Contact info:
Mary Brophy – [email protected]
857-364-4201
Colleen Shannon: [email protected]
857-364-6132
Sara Turek – [email protected]
857-364-5556

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