COMPARATIVE EFFECTIVENESS RESEARCH IN THE

VA COOPERATIVE STUDIES PROGRAM

Grant D. Huang, MPH, PhD

30 Years of Comparative Effectiveness Research Conference

Washington, DCSeptember 23, 2009

OUTLINE

• Cooperative Studies Program (CSP): A national clinical research infrastructure

• CSP study development process

• Lessons from CSP comparative effectiveness research efforts

CSP OVERVIEW

• CSP is a national infrastructure for sponsoring, developing & executing: Multi-site clinical trials Epidemiological & population research Genomic medicine research

• First Cooperative Study conducted in 1940s on streptomycin for treating tuberculosis in WWII veterans Program formally established in 1972

• Over 175 clinical trials and observational studies completed including landmark studies in cardiovascular disease / cardiovascular surgery, infectious diseases, surgery, gastroenterology, mental health, oncology, and endocrinology

CSP COMPARATIVE EFFECTIVENESS RESEARCH

• CSP #494 – Prolonged exposure therapy vs. patient-centered therapy for Post-Traumatic Stress Disorder in women Journal of the American Medical Association, Feb 28, 2007

• CSP #424 (COURAGE) – Percutaneous coronary intervention/optimal medical therapy vs optimal medical therapy alone New England Journal of Medicine, March 27, 2007

• CSP #530 – Intensive vs less intensive renal replacement therapy for acute kidney injury New England Journal of Medicine, May 20, 2008

• CSP #468 – Deep brain stimulation vs. best medical therapy for improving motor symptoms in Parkinson’s Disease patients Journal of the American Medical Association, January 7, 2009

On-going / planned studies address areas of:- Stroke rehabilitation, rheumatoid arthritis, diabetes, cardiovascular

surgery, prostate cancer, depression, low back pain

CSP RESOURCES & EXPERTISE

• CSP is comprised of: 5 data/statistical coordinating centers 4 epidemiological research centers 1 clinical research pharmacy coordinating center 1 health economics resource center Pharmacogenomics analysis lab; DNA/tissue repository

• Center expertise includes: Biostatistical / epidemiological expertise Clinical expertise Safety and regulatory oversight Health economics expertise Pharmaceutical management Clinical research project & fiscal management Genomics Informatics

• CSP studies go through VA Central IRB

CSP RESEARCH

• VA clinician-investigators partner with CSP experts to develop and conduct national studies of high clinical relevance

• Close integration with patient care provides an environment for both identifying key clinical questions and an ability to execute studies 82 VA medical centers involved in FY09 VA sites/study: 4 to 43; Average # of VAMCs/study = 17

• CSP & VA network provides strong experience base for continual generation of CER-related inquiries Investigators interact in multiple scientific & clinical forums Tradition of CER-based inquiry passed on to other VA investigators

COOPERATIVE STUDIES PROGRAM SCIENTIFIC REVIEW PROCESS

Medical Center

Local VA Research

Office

External Review

External Review

Study Proponent

CSRD Director

approval for planning

CSRD Director

Decision / approval

Study planning meetings (2+)

Cooperative Studies Scientific Evaluation Committee Review

Study ProponentClinical & Biostatistical

reviewers

Study team+

Central Office

Admini-

strative

Review External Review

CSP Central Office

CSP Coordinating

Centers

VAMC

VAMC

VAMC

VAMC

Study sites

Planning Committee

CSP Coordinating

Center(s)

Study Proponent

Clinical Experts

Score & Comments

Score & Recommendation

Letter of Intent

Research Proposal

STUDY INITIATION

• Study ideas are generated from VA clinician-investigators based on: observations from clinical practice; efforts to address gaps in the literature; priorities identified at scientific conferences and/or among the clinical

community; research needs expressed by VHA Patient Care Services leaders; responses to Office of Research & Development solicitations or service

directed projects.

• Study proponents include VA national program directors, VA and NIH research center directors, VA clinical chiefs, and other leading clinical experts

• Multiple treatment options available to practicing clinicians help lead to questions involving head-to-head comparisons of treatments and/or strategies.

• Intensive planning process helps to refine the clinical question and methodological approach for definitively answering it. VA Central Office is involved from early stages in study development

• All studies focus on enhancing care to Veterans

SCIENTIFIC REVIEW

• Clinical relevance To Veteran population To general public Timeliness

• Methodology• Feasibility

Testable hypothesis Sample size

• Ethical considerations• Resources needed• Investigator qualifications

Will the study change clinical practice?

Face-to-face review with a diverse group of clinicians and biostatisticians/epidemiologists plays a critical role in

study approval.

CSP MISSION

To advance the health and care of Veterans through collaborative research studies that produce innovative and effective solutions to national healthcare problems.

TEAM EFFORT

ALL are key to the success of the study

Study TeamStudy Team

StudyStudy DevelopmentDevelopment

Organizational Organizational & Start-up& Start-up

ExecutionExecution

EnrollmentEnrollment -- -- Follow-upFollow-up

Analyses & Analyses & Close-outClose-out

Study Chair

Biostatistician

Research Pharmacist

Health Economist

Project Manager

Site investigators

Nurse/Site Coordinators

Programmers

Executive Committee

Scientific / Scientific / EthicalEthicalreviewreview

Scientific Scientific peerpeer

reviewreview

Scientific / Scientific / EthicalEthicalreviewreview

IRB / R&D

FDA

Human Rts Cmte

IRB / R&D Cmte

FDA

Human Rts Cmte

Data Monitoring Cmte

COLLABORATORS

• National Institutes of Health NIDA, NIDDK, NINDS, NCI, NHLBI, NIMH, NIDCD

• Department of Defense• Universities• Industry• International

Canadian Institutes of Health Research United Kingdom Medical Research Council

SUMMARY & LESSONS

• Stable clinical research infrastructure enables the establishment of expertise that focus on developing and conducting high impact clinical studies.

• Integration of clinical and methodological researchers within a health care system provides a strong environment for continual development of CER

• Rigorous planning and review process leads to critical refinement of a study question that seeks to change practice. Contributions from a diverse group of clinicians, biostatisticians,

epidemiologists, and leadership enhance overall research product.

• Culture of collaboration and commitment to a common mission are key to all efforts. Shared desire to improve Veteran and national health plays a central role in

program activities.

ACKNOWLEDGEMENTS

Thanks to all of the of Veterans who have participated in CSP studies.

QUESTIONS?QUESTIONS?