AAMC Reporter: June 2008

The VA Cooperative Studies Program

Grant D. Huang, Ph.D., Cooperative Studies Program Headquarters, VA Office of Research and Development

Peter Peduzzi, Ph.D., Cooperative Studies Program Coordinating Center

The Cooperative Studies Program (CSP) is a division of the Department of Veterans Affairs (VA) Office of Research and Development. CSP specializes in large-scale clinical research studies within the VA, across the nation, and around the world. Its mission is to advance the health and care of veterans and the nation through collaborative research studies that produce innovative, effective solutions to national health care problems. From its inception, the CSP has completed many landmark studies and continues to help advance emerging areas of clinical research, such as genomic medicine.

The CSP has an extensive history that dates to the 1940s, when the VA initiated drug treatment studies on tuberculosis, a prevalent disease among veterans. Researchers John Barnwell and Arthur Walker were concerned about caring for thousands of veterans with tuberculosis. In 1946, they launched a study to test the efficacy of various drugs, including the antibiotic streptomycin, in patients with this disease. The study results not only revolutionized how tuberculosis was treated, but also led to development of an innovative method for evaluating the effectiveness of new treatments: the multisite VA cooperative study.

In advancing the cooperative study approach, the VA developed a program for conducting further high-caliber research in the 1950s at the Perry Point (Maryland) VA Medical Center. This effort emphasized the design and conduct of randomized trials for treating mental illnesses. Other noteworthy cooperative studies begun in the 1950s and 1960s included the use of long-term anticoagulants after myocardial infarction, the use of lipid lowering drugs to prevent heart attack and stroke, gastric ulcer disease treatments, the efficacy of gamma globulin in post-transfusion hepatitis, analgesics to reduce postoperative pain, surgical treatments for coronary artery disease, and treatments for prostate cancer. In 1970, Edward Freis and the VA Cooperative Study Group on Antihypertensive Agents published the results of a landmark cooperative study showing that use of antihypertensive drugs prevented or delayed serious cardiovascular events. Freis won the Lasker Award in 1971 and received two Nobel Prize nominations for his work.

In 1972, the VA clinical trials program was officially reorganized by James A. Hagans, M.D., Ph.D., as the Cooperative Studies Program. Over the past 35 years, CSP study findings have significantly influenced the practice of medicine, including ones that showed:

• coronary artery bypass surgery prolongs life in patients with left main coronary artery disease,
• warfarin helps prevent stroke,
• aspirin reduces heart attacks and death,
• benign prostatic hyperplasia can be relieved by terazosin,
• septic shock should not be treated with steroid therapy (a commonly used practice at the time), and
• insulin pump therapy improves the quality of life for diabetics.

Recently, one of the largest adult vaccine trials ever, the Shingles Prevention Study, was completed by the CSP in collaboration with the National Institutes of Health and Merck and Co. More than 38,500 subjects were followed for an average of nearly three years. This study convincingly demonstrated that the Oka-Merck shingles vaccine reduced the incidence and severity of shingles. These findings were the basis for the Food and Drug Administration's decision to license the drug, and for the Centers for Disease Control and Prevention's recommendation that it be used in patients over age 60.

The ability to achieve high-impact research is based on an established infrastructure for conducting multisite clinical trials and observational studies. This extensive network of professional biostatisticians, epidemiologists, clinicians, health economists, clinical research pharmacists, computer programmers, administrators, and support staff is organized into 11 centers across the United States. These centers include statistical coordinating centers, a clinical research pharmacy, and a health economics resource center. The CSP has also expanded its genomic medicine capabilities with a DNA coordinating center, biospecimen repository, and pharmacogenomics analysis laboratory. This CSP infrastructure not only maintains expertise in conducting VA-based clinical research, but also has become a leader in trials involving academic health centers, other federal agencies, private industry, and international collaborators.

A hallmark of CSP research is its collaboration with VA clinical investigators on designing, initiating, conducting, and analyzing cooperative studies. Established policies, guidelines, and standard operating procedures for all phases of a clinical research study also provide a critical structure for these efforts. Unique to the CSP are human rights committees that help review study protocols for matters on patients' rights and welfare, in addition to local institutional review boards. These committees also perform site visits to evaluate the attention to and conduct of activities related to study-subject protections.

About 40 cooperative studies on a range of topics are ongoing at any one time. Current studies are addressing key questions in cardiovascular disease and surgery, diabetes, mental health (including post-traumatic stress disorder), neurological disorders (Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis), cancer, and rheumatoid arthritis, among other conditions.

As part of the largest integrated health care system in the United States, the CSP is a dynamic organization continually growing to accomplish its mission. Presently, it is building the capacity to conduct early-phase trials and studies in genomic and pharmacogenomic medicine and pharmacoepidemiology, integrating informatics in research activities, and developing new clinical trial methodologies. Through these efforts, the CSP continues to seek ways to produce innovative and important findings that benefit our veterans and the nation as a whole.