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

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Employees Funding

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

Clinical Research

Hospital Administration

Rethink silos

PharmaClinical

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…

• Mandated reporting• Manual chart abstraction• Limited variables• Question of generalizability from ward to ward

Current QI efforts

Kaleid Project1. Data from all available sources2. Collaborative exploration of the data3. 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

Cohort Identification

Enroll & Consent Randomize Intervention

Data Capture

Study DB Analysis

ClinicalDecision Support

Care providers using EMR

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 Actionable ResultsBuild a cohort

Make data accessible Discover Validate Implement

Million Veteran Program & GenISIS

Point of Care Research & Kaleid

Shifting from Histologic to Histo-Molecular 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)

TxDx

Current ‘Local Learning’

Time

Providers

POP Data Base

Cancer genomic test results

Tumor Board recommendations

No Sx Sx

TxDx

Local Learning Through Observations

Time

Providers

POP Knowledge Base with ‘Prediction Engine’

N+1 cancer genome

N+1 patient

Prior N patients

Tumor Board recommendations

Patients Like Me (n+1)

TxDx

Local Learning Through Experiments

Time

Providers

POP Knowledge Base with Predictive Engine

N+1 cancer genome

N+1 patient

Prior N patients

If equipoise exists Tumor Board offers randomization

within routine care

higher weight on randomized outcomes

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

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VISN 1 Clinical Trials Network (CTN) Committee Structure

Executive Leadership Board

Director of VISN 1 CTN

CTN Field Advisory & Management Committee

External Advisory 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. Mayo-Smith:

• 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 AccomplishmentsOncology 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 AccomplishmentsPrecision 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 AccomplishmentsCardiology 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 AccomplishmentsOther 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 AccomplishmentsProgram-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

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Current State of Research in the VISN

Investigators pursuing CTs by specialty

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Other = Prostate Cancer, Infection Control, Pulmonology, Epidemiology, Gastroenterology

Current State of Research in the VISNCurrent VA-funded Portfolio (Clinicaltrials.gov)

BOS WH WRJ PRO CWM MAN BED TOG0

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New Trials Trials Open

“New trials” = trials added since 4/20/2014

Current State of Research in the VISNCurrent 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 – mary.brophy@va.gov857-364-4201

Colleen Shannon: colleen.shannon@va.gov857-364-6132

Sara Turek – sara.turek@va.gov857-364-5556