VA Research and Development Program Joel Kupersmith, MD Chief Research & Development Officer

VA Research and Development Program

VA Research and Development Program

Joel Kupersmith, MDJoel Kupersmith, MDChief Research & Development OfficerChief Research & Development Officer

Rich 85 Year History

• Mission: “To discover knowledge and create innovations that advance the health and care of Veterans and the nation.”

• 3 Nobel Laureates, 6 Lasker Award Winners

• Many important discoveries and inventionso Cardiac Pacemakero First liver transplanto Radioimmunoassayo CT Scannero First large scale clinical trial – TBo 1st multisite RCT of antihypertensive Rxo Lithium and Biologic Psychiatry

Secretary's 13 Transformational Initiatives

• Eliminate Veteran homelessness

• Enable 21st century benefits delivery and services (e.g., backlog)

• Automate GI Bill benefits

• Implement virtual lifetime electronic records (VLER)

• Improve Veteran mental health

• Build Veteran relationship management (VRM) capability to enable convenient, seamless interactions

• Design a Veteran-centric healthcare model and right-sized infrastructure to help Veterans navigate the healthcare delivery system and receive coordinated care

• Expand healthcare access for Veterans, including women and rural populations

• Ensure preparedness to meet emergent national needs (e.g., hurricanes, H1N1 Virus)

• Develop capabilities and enabling systems to drive performance and outcomes

• Establish strong VA management infrastructure and integrated operating model

• Transform human capital management• Perform Research and Development to enhance the long-term health and well-being of Veterans

Presidential Directive on Peer Review

“When scientific or technological information is considered in policy decisions, the information should be subject to well-established scientific processes, including peer review where appropriate, and each agency should appropriately and accurately reflect that information in complying with and applying relevant statutory standards”

Barack Obama, March 9, 2009

White House OSTP* Themes and Initiatives*Office of Science and Technology Policy

• A Healthy Americao Translational research to turn discovery

into better practice (from bench to bedside)o Boosting clinical researcho Improving care for the wounded warrioro Achieving a promise of personalized

medicine o Assisting in the broader priority of

improving health care access

OIG Report on VA Research

• OIG Report on VA research, February 27, 2009• Initiated by MilCon, VA Subcommittee of House of Rep.

Appropriations Committee

• Conclusions of OIG Report

• Appropriated funds for VA research address the broad spectrum of medical issues with which Veterans contend

• VHA’s reporting of how research funds are utilized could be more detailed and transparent

General Characteristics of VA Research

Intramural Research Program

• VA Research connected directly to nation’s largest health system (being “Intramural”)o >70% of investigators are clinicianso Links researchers directly Veterans’ needso Facilitates implementation of research

results

• Broad, extensive research portfolio that balances the needs of all Veterans• ≈ 2100 ORD funded projects

Intramural Research Program

116 VAMCs have capacity for research (FWA)• ≈100 are funded by ORD at any time

Community of ≈3000 VA researchers with a long history of significant research o Published 65,158 articles in past 9 yearso Publish in the best journals

Research Services

• Basic Laboratory R & D

• Clinical Science R & Do Cooperative Studies Program – Large clinical trials

• Rehabilitation R & D

• Health Services R & Do Quality Enhancement Research Initiative (QUERI) –

Implementation research in which VA is the pioneer

VA ResearchPoints to Remember

• Office of Research and Development does not oversee all VA researcho RECC’s, etco Epidemiology sectiono Program offices

• Many interests in VA research o Considerable input on what research to

do

Budgets

Research funding (million $)

0

200

400

600

2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

VA

0

10,000

20,000

30,000

40,000

NIH

Research funding (% increase per year)

VA NIH

0%

4%

8%

12%

16%

2002 2003 2004 2005 2006 2007 2008 2009 2010

VA Budget• 4 components

o Congressional appropriationo VERA $so NIH o Other – Mainly industry

• NIH and CDMRP awardso NIH funding VA competitively awarded to

investigators exceeds the VA research appropriation

o 44% of TBI/PTSD Congressionally Directed Medical Research Program $s awarded to VA investigators

Creating a Culture of Research Compliance

in VAMCs

Principles for Medical Centers

VA commits that in the conduct of research VA willo Ensure that members of the research team will conduct

themselves as professionals conducting themselves in the highest standards of quality and ethics in their work

o Undertake research only if it is reviewed, approved and monitored by the appropriate VA committees that ensure that the research trial is properly designed, does not involve undue risks and includes safeguards for participants

o Clearly explain that research is voluntary, only occurs with written consent and that patient’s have a right to change her mind at any time without affecting their VA healthcare or benefits

o Educate individuals were considering enrolling in the research study about the study and its possible benefits and risks

o Safeguard each participant’s information

Stakeholders in VA Research

• Stakeholders includeo Veteranso Veteran Service Organizationso Other Veterans advocacy groups (e.g. related to

Gulf War)o Academic Medical Centerso Medical specialty societieso Congressional Committeeso Department of Veterans Affairs

E.g., Other program offices, VISNs, VAMCso White House

• Each stakeholder has different agendas as to what type of research VA should do

• Need to maintain balance in the research program

Stakeholder Support for ORD

• Recent increases in research appropriation• VSO support

o E.g. Support of Research Week and others• Friends of VA

o Group includes Association of American Medicinal Colleges, medical specialty societies, VSO’s, research organizations

• Veterans’ survey (below)

Challenges

22

• Others mandate research that is not part of ORD investment strategy

• Maintenance of a research portfolio that reflects Veterans’ needs as well as consideration of strong stakeholder interests

• Bureaucratic obligations

• Physical infrastructure - addressed in budget submission

• Compliance

Challenges

23

• Maintenance of human capital resources - issues related to protected time and bureaucracy

• Continuance of internal integration/communication with VISNs and VAMCs

Challenges (cont’d)

Advances and Initiatives

Facilities• Facilities Infrastructure

o Outdated physical structureo Research facilities ages average 49 yrs

• Limited funding• Formal congressionally mandated

infrastructure assessment process has been underwayo Review of previous surveys, site visits, etc

• Recent improvement

• Improved collaborations within ORD & VHA and with DoD, other federal agencies and the private sector

• Organizational Improvements

o Second Deputy CRADO – for Field

o Program Manager changes

• On-line grant submission (eRA Commons)

• Central IRB

Administrative Advances

• Communications• Internal integration/communication with VISNs

and VAMCso Research Accountability Meeting 2009 included

MCD, COSo ORD leadership plans to visit each VISN Director

• ACOS/AO/RCO meeting• Research Administrative Review• Blue Ribbon Panel

Administrative Advances (cont’d)

Blue Ribbon Panel

The Report of the Blue Ribbon Panel on VA-Medical School AffiliationsTransforming an Historic Partnership for the 21st Century

“…VA and its academic partners redouble their efforts to develop new knowledge through collaborative research.”

..VA review and, whenever possible, modify policies and procedures that limit effective collaboration with its academic affiliate in patient care, education, and research.”

Blue Ribbon Panel

• Accepted by the Secretary

• Implementation Plan drafted

• External (FACA) Advisory Committee being assembled

VA Research Administrative Review

• Purpose – Address issues regarding administration of research in Medical Centers and VISNs o Governanceo Complianceo Researchers and research implementationo Maintaining human capital resources

• Structureo Membership - VISN Directors, MCDs, CMOs, COS,

ACOS/Rs, AOs, RCOs and researcherso Steering Committee

Governance Subcommittee - Chair, Randy Petzel Human Capital Subcommittee – Chair, Jack Hetrick

VA Research Administrative Review

• First reporto Roles of VISN and Medical Center leadership positions in

research o Research performance expectations of VHA leaderso Responsibility of R & D Committeeo Mentoring and training

• Second Report approved by HSC Committee of NLBo ACOS/R, AO responsibilitieso R & D Committee specificso Role of ACOS/R in MCD leadershipo Recruitment, retention and support of investigatorso Time allocation for research effortso VA research principles

Health Services Research Work Group

• Work Group consists of VHA clinical, health system and research leaders

• To address questions includingo How can HSRD best serve to improve the healthcare

system?o How can HSRD do so using the highest quality,

unbiased methods?o How does HSRD play a role in emerging changes

such as the Medical Home?o How can research & the Health Care System better

collaborate?

• Important future impact

IT Projects

• Workgroup including VHA, OIT and universities convened by AAMC o Policies and procedure for sharing datao Consented & Non-consented researcho Checklist

• On-line grants submission implemented – eRA

• NIH IT reporting tool is undergoing evaluation

•Comparative Effectiveness Research

•Genomic Medicine•Post-Deployment Research

A Look to the Future

Comparative Effectiveness Research

Comparative effectiveness research (CER) is the generation and synthesis of evidence that compares the benefits and harms of alternative methods to prevent, diagnose, treat and monitor a clinical condition or to improve the delivery of care.

National Priorities for Comparative Effectiveness ResearchInstitute of Medicine Report BriefJune 2009


Randomized comparisons of treatments, which could be very different from each other

Drugs vs. surgerySurgery vs. deviceBehavioral therapy vs. pharmacological

therapy

Real world experiments applicable to clinical practice

Community based medical centersLarge numbers of patientsBroad eligibility criteriaPatient centered outcomes: mortality,

morbidity

Typical of the conducted by VA CSP


• Interest in and movement to Comparative Effectiveness Research will change the way we approach and do research

o Evaluation via CER will be more prominento How research projects are identified and choseno What research methodology is accepted

Moving beyond the Randomized Controlled Trial

• VA has already made progress in these areas

Influence of CER on the Research Establishment

VA Infrastructure Reflects Needs in FCC CER Report

• FCC CER report outlined infrastructure needs for CER: These infrastructure capabilities already exist in VA o Clinical research networko Registries, surveillance databases, research-quality

observational datasetso Administrative databaseso EHRs & distributed data networkso Tools for dissemination and translation of research

findingso Human and scientific capital

Clinician/Researchers – 70% of VA researchers Training (e.g. Research Career Development Awards) Patient/consumer engagement

VA Cooperative Studies Program • Large VA clinical trials program

o Major vehicle for Comparative Effectiveness Research• Method of funding projects

o Letter of intent submitted Ideas based on clinical practice observations, gaps in literature, etc

o Project review by experts who collaborate with the proposer Include clinicians, clinical researchers, trialists, biostaticians,

pharmacists, others

• Review considerations include clinical and policy considerations

o Clinical relevance and importance to VHA population, methodology, feasibility (testable hypothesis, sample size), ethics, resources needed, investigator qualifications

• Central IRB approval• CSP Center expertise – fixed structure for every

projecto Economics, project management, informatics, etc

• Quality Research Enhancement Initiative

• Evidence Synthesis Programo Policy oriented synthesis of evidence to inform

medical practice and health systems planning Informed by policy considerations with input by

Patient Care Services

o Recent topics Drug management of BPH – Led to Formulary change Osteoporosis – Incorporated into Guideline on

screening male Veterans Pain in Polytrauma – Need more research

Implementation/ Translation

Results of Comparative Effectiveness Research• Informed choices for Patients, Providers,

Healthcare system• Informed choices will involve a complex of

interacting and coalescing research vehicles o Comparative Effectiveness Research o Research related to Personalized/Individualized

Medicine Genomics and other approaches to examine the individual in

his person and setting (genetic make-up, coexisting conditions, location, etc)

• Comparative Effectiveness Research will continue to be a major VA endeavor

Genomic Medicine Program

• Collect and link genetic information with VA Electronic Health Record and thereby:

o Discover genetic predispositions, causes and mechanisms of disease

o Better define treatments Pharmacogenomic & interventional customization

o Via research, advance understanding in all these areas

• Establish how genetic information will be used in clinical medicine

o Translational research to link genotype to phenotype

o Complex, adult, multi-gene diseases possibly with strong environmental influences

Goals of VA Genomic Medicine Program

• Enlarge infrastructureo Pharmacogenomic laboratory, Enlargement of

genetic storage capacity, IT projects (GeniSIS)

• Collaborations – NIH, HHS

• Translation into clinical practiceo Educational programs for health professional with

Nat'l Coalition for Health Prof Educ in Genetics

• Address privacy/ethical issueso Veterans Consultation Projecto Consent process

• Large scale projects

Genomic Medicine Initiative Steps in Implementation

• Veterans consultation projecto Collaboration with VSOso Consulting group engaged to establish Focus

Groups to solicit opinions, beliefs, and values of individual Veterans

• Veterans recruited through:o Local VSOs chapterso VAMCs, VA Community-Based Outpatient Clinics and

VET Centers (Readjustment Counseling Centers)

• Focus Groups met Sept-Nov, 2007• Internet survey performed April 24 – May 5,

2008o N = 931

Veterans Consultation Project

Definitely Yes

ProbablyYes

DefinitelyNo

Probably No

29 53 12 6

Confidential. N=931. Weighted. GPPC 2008

Based on what you’ve just learned, do you think the Genomic Medicine Program should be done?

I am curious about the influence of genes on health

Participating would make me feel like a guinea pig

37%

83%

When thinking about participating in the program, do you agree or disagree with the following statements?

Strongly Disagree Disagree Agree Strongly Agree

78%Participating would be easy

Participating would make me feel I was helping Veterans

86%

48%

63%

17%

22%

14%

52%I would be concerned

info could be used against me

50%50%I would be concerned about govt having my samples


AgreeDisagree

Receiving information about my health

Knowing what kind of research being done using the database

Knowing who to go to with a question or complaint

Having my privacy protectedHaving a mechanism to change my

mind and withdraw my sample and information at a later time

Monetary compensation for my time

In deciding whether to participate or not, how important would the following be to you?

96%

95%

94%

93%

86%

60%

%


Academic or medical centers in other countries

US academic or medical centers

No Yes

80%

Do you think the following types of researchers outside of the VA should be able to use the GMP db and samples?

54%

US pharmaceutical companies

43%

70%

20%

46%

57%

30%Other health-related govt. agencies


Serious consequences for researchers who violate my research agreement

VA have safeguards to protect information from misuse and disclosure

There would be a research agreement signed by researchers and participants

It would be illegal for insurers and employers to get my information

It would be illegal for law enforcement to get my information

If you were a participant, how important would the following be to you?

98%

98%

97%

95%

87%

%


• 83% said program should be done• 71% would participate• Participation associated with

o Attitudes about researcho Attitudes about helping and history of

previous “altruistic behaviors”o Curiosity about geneticso Satisfaction with VAo Demographic differences

Summary of Genomics Survey Findings

36

58

87

89

94

96

31

77

82

88

90

91

91

95

0 50 100

VA

US

Cloning


Stem cell research

Athletic ability

Suscept. to env. exp.Alcoholism

PTSD

Mental illness

Cancer

Do you think research should be allowed or prohibited on: (% allowed)

• Focus group results – Quote"The fact that they have people sitting

around talking about this in advance of even starting to build it tells me that they're paying attention...This right here is oversight, you know, at the get-go. So I think that that's a really good thing; and I think ultimately it's going to be one more way that Veterans give something from themselves to make this country better."

Veteran Attitudes

• Discoverieso Schizophrenia & the alpha-7-Nicotinic acid geneo Alzheimer’s - Presenilin and Tau geneso HIV susceptibility - Immune-response gene CCL3L1o Type-2 Diabetes genes (6) in Mexican Americanso Childhood anxiety disorders

• Ongoing projectso PTSD - Serotonin and Dopamine transporter

genetics o Cholesterol disorderso Alcohol consumption and withdrawalo Bipolar Disordero Coronary disease in Mexican-Americanso Gulf War Veterans Illness

VA Genomics Project Discoveries and Projects

• Large scale Studies/Databaseso Serious Mental Illness - Schizophrenia and Bipolar

Disordero Deployment-related mental illness - PTSD resilienceo Amyotrophic Lateral Sclerosis

• Million Veteran Project (MVP)o Start of large Population (Non disease-specific)

Genomic Databaseo Comprehensive, interdisciplinary data collection and

analysis on 1,000,000 Veteranso Will change the way research is conductedo Will change the way medicine is practiced

Genomic Medicine Initiative Large Scale Projects

IT Projects

• VINCI – Veterans’ Informatics, Information & Computing Infrastructure

o Development of de-identified Corporate Data Warehouse for storing and managing clinical (and genomic) data

o Surveillance – capture of early trends post deployment

• CHIR – Consortium for Healthcare Informatics Research

o Electronic text interpretation of HER

• GenISIS – Genomic Information System for Integrative Science

o Incorporation of genomic data into the HERo Repurpose data and results for secondary analyseso Validate genomic medicine findingso Integrate findings into clinical medicine

OEF/OIF and Other Post-Deployment

Research

• Deployment-related research – current and all conflicts

o Prostheticso Hearing and vision researcho PTSD o Rehabilitation o Environmental exposures

• Deployment-related research highlighting specifics for current conflicts

o Traumatic Brain Injury and other Neurotraumao Polytraumao Accesso Chronic care and the new Veterano Homelessness

• Collaborations with DoD

OEF/OIF and Other Post-Deployment

• Homelessnesso Initiative to eliminate homelessness of

Veterans in 5 yearso Research agenda involves medical

research plus social signs, economics, etc.

o Collaborations will be important• Environmental exposures

o Agent Orangeo Gulf Waro Burn pits

Secretarial Initiatives

Modular Upper LimbVA, DARPA and Industry

Stage 1: “Strap and go” device that operates Stage 1: “Strap and go” device that operates with advanced gyroscope technology with advanced gyroscope technology

Stage 2: Arm controlled by brain-computer Stage 2: Arm controlled by brain-computer interfaceinterface

Electronic Ankle-Foot Prosthesis May Improve Mobility of Veteran Amputees

Dr. Hugh HerrDr. Hugh Herr

Hearing and Vision

• VA Center of Excellence in Hearing Loss Rehabilitation o Unique resource addressing the single largest

cause of disability among Veterans

• VA Center on Aging and Vision Loss o Examines the role of environment in visually

impaired Veterans and conducts clinical trials to improve vision

• VA Center of Excellence in Advanced Vision Rehabilitation o Developing a prosthetic retinal implant for

retinal disorders

TBI/Polytrauma Research

• Developing adult stem cell technology to protect and reverse effects of brain trauma

• Nerve damage repair after brain injury & effectiveness of interventions

• Impact of rehab strategies on the brain after TBI• Pain management• Effects of concurrent PTSD on TBI outcomes• Magnetic brain stimulation to improve rehabilitation• Gate, balance and attention demands and TBI

Mechanisms to enhance cognitive rehabilitation• Various imaging studies• Identifying and screening for mild TBI


Post Traumatic Stress Disorder

• Neurophysiology• Imaging• Treatments (Prazocin for nightmares, respiridone,

cycloserine)• Comparison of virtual reality graded exposure therapy

with cognitive behavioral group therapy• Approaches to PTSD post military sexual trauma• Developing models of care including telemedicine and

collaborative care approaches to increase access• Cohort to examine PTSD & TBI established prior to

deployment and followed post deployment • Biomarkers – genetic, CNS structural and reactivity• PTSD complicated by substance abuse• Vocational rehabilitation• Genetic database

Post Traumatic Stress Disorder

VA Leadership Role in PTSD

• Congressionally Directed Medical Research Programs (CDMRP)o Substantial funding for TBI and PTSDo VA has considerable involvement in

planning and study sections and has won numerous awards (44%)


• Access to Care o ORD has a well established portfolio in access which been

applied to OEF/OIF Veterans

• Interventions to improve community and family reintegrationo Including pro-active case management, mental health, social

and occupational functioning and the needs of care giverso Vocational rehabilitation

• OEF/OIF Advisory Committee to NRACo Includes DoDo Review and advise re OEF/OIF portfolio including gaps

between and overlaps with DoD

Other Programs for the Returning Veterans

Documents

VA Research and Development Program Joel Kupersmith, MD Chief Research & Development Officer