——Background

As the 20^th century comes to a close, the health of our Nation has become a high priority. The United States Congress has addressed this priority in the past decade by directing the Department of Defense (DOD) to manage appropriations totaling $1.1B for intramural and extramural grant programs directed toward targeted research initiatives. The U.S. Army Medical Research and Materiel Command¹ (USAMRMC) has been responsible for administering appropriations made in fiscal years 1992-1999 (FY92-99) for research on breast cancer, prostate cancer, ovarian cancer, neurofibromatosis, defense women’s health, osteoporosis, and other specified areas. Together, these programs are managed by the office of the Congressionally Directed Medical Research Programs² (CDMRP), a scientific research directorate within the USAMRMC. This report has been prepared to address frequently asked questions about the CDMRP.

——Appropriations

The CDMRP originated from a unique partnership among the public, Congress, and the DOD. Grass roots advocacy organizations provided much of the impetus that led to a FY92 DOD appropriation of $25M targeted toward breast cancer research. In response to continuing public requests, Congress appropriated $210M in the FY93 DOD budget for extramural peer-reviewed breast cancer research. Congress has continued to appropriate funds each year for DOD peer-reviewed research managed by the CDMRP. Through FY99 the CDMRP has been responsible for approximately $1.1B in appropriations. Currently, five peer-reviewed research programs are active: the Breast Cancer Research Program, the Neurofibromatosis Research Program, the Ovarian Cancer Research Program, the Prostate Cancer Research Program, and the Specified Appropriations Program (BCRP, NFRP, OCRP, PCRP, and SAP, respectively). While the Defense Women’s Health and the Osteoporosis Research Programs are no longer considered active, the CDMRP will manage the research funded by these programs throughout the life span of each project.

——Program Management

To accomplish the multiple program administration tasks, several established science management methods have been adapted and new innovations have been developed. An overview of the CDMRP can be found in Section I. Work is coordinated by the CDMRP Program Staff, a team of skilled, multidisciplinary military and civilian scientists and clinicians. Additionally, the CDMRP utilizes support contractors for assistance in program management and evaluation, scientific and programmatic evaluation of research proposals, and management of funded research grants. For each appropriation, the CDMRP utilizes a flexible multi-year execution and management cycle to accommodate all stages from development of an investment strategy through the completion of research grants. Each program’s investment strategy is critical to the success of the CDMRP in that it encourages research that will impact the health of all people. By identifying gaps in funding, the CDMRP provides award opportunities that will satisfy research objectives without duplicating existing funding efforts. To establish an appropriate investment strategy that meets the current needs of both the research and advocacy communities, the Program Staff seeks the advice of expert panels (Integration Panels) composed of leaders in scientific and clinical research and consumer advocacy organizations. Each program then utilizes a variety of award mechanisms to execute the investment strategy (see Appendix A).

The CDMRP recognizes the importance of stewardship in the management of Congressionally directed programs funded with taxpayer dollars. Congressional directives for each appropriation are interpreted with rigor and integrity, and the resulting programs are responsive to the needs of the scientific and advocacy communities. Descriptions of Congressional appropriations and funding summaries for the CDMRP are provided in Section II and Appendix B.

——Capacity Building

The CDMRP is committed to building and/or enhancing the research capacity of our nation. These capacity-building initiatives support investment in infrastructure, the development of shared resources, the training and career development of scientists, and equity in access to program resources and research funding (Section III). Community outreach is achieved by addressing the needs of underserved populations and Historically Black Colleges and Universities/Minority Institutions (HBCU/MI). Scientists from all demographic and ethnic backgrounds are recruited to participate, and the CDMRP staff strives to disseminate information in multiple formats for optimal public accessibility.

——Partnerships

The unique public/private partnerships formed among the military, government, scientists, and consumer advocates affect multiple aspects of program execution. Since the FY95 BCRP appropriation, consumer advocates have been involved in all levels of the process across all programs. Scientists and clinicians from diverse professional backgrounds working in the military, government, private sector, and academic environments have provided important insight to meet the needs of the research and advocacy communities. The partnerships formed between scientists and consumer advocates are important components in the development of investment strategies and the two-tiered review process. The USAMRMC CDMRP will continue to develop these effective partnerships in the hope that they will augment the comprehensive national health effort and benefit all through scientific innovation and technology transfer.

——Program Evaluation Strategies

In concordance with the recommendations of the 1997 Institute of Medicine (IOM), Review of the Department of Defense’s Program on Breast Cancer Research, the CDMRP is initiating efforts to evaluate the success of their management and investment strategies. Several CDMRP research programs and initiatives are of sufficient maturity to warrant a thorough review of outcomes, especially as they relate to the initial intent and goals of the mechanisms under evaluation. Some efforts under way are: categorical analysis of the CDMRP research portfolio; review of research accomplishments, publications, and presentations; evaluation of the impact of CDMRP funding strategies on the future endeavors of its funded scientists; and assessment of the status of the CDMRP mission to eradicate disease.

——Information Management

The maintenance of accurate and accessible program records, as well as dissemination of research results, is another important function of the CDMRP. To fulfill this requirement, the CDMRP has employed a variety of research information management and dissemination methods. Of particular note is the DOD BCRP Era of Hope meeting that was held in the fall of 1997. This multidisciplinary meeting brought together over 1,100 scientists and consumer advocates to discuss recent developments in breast cancer research and announce the results from 543 DOD grants funded in the FY92-95 BCRPs. The Second Era of Hope meeting will be held on 8-12 June 2000 in Atlanta, Georgia. Current information about the CDMRP such as press releases, program announcements, publications, important dates, and funded research and abstracts can be accessed by the public at http://cdmrp.army.mil.

Summary information on all research programs of the CDMRP can be found in Sections V-XII of this report. These chapters include Congressional directives, program execution, and research accomplishments for each program. Research accomplishments are reported primarily through FY97. FY98 awards were obligated by September 1999, and most of these projects are currently in start-up phases. Program Announcements for the FY99 appropriations have been released, proposals have been received, proposal review is ongoing, and grant negotiations are in progress. Although the research programs share common management methods, each program is unique, with its own individually tailored goals and visions. These features allow the programs to meet the unique needs of their research and consumer advocate communities.

——Program Management Innovations

The CDMRP has been a pioneer in exploring innovative program management strategies that are now being piloted by other funding agencies. Examples of innovative program features born within the CDMRP are the participation of consumer advocates in all aspects of program development and research evaluation, the two-tiered review process, and the criterion-based scoring system used in the scientific review of research proposals. In addition, the Idea Award was first developed in the CDMRP with the hope of funding higher risk, but potentially higher gain ideas that would strategically advance the given field of study.

——Building the Infrastructure

CDMRP-funded development of shared resources (registries, cell/tissue banks, databases, transgenics), cancer centers, and research consortia has enhanced the infrastructure of the research community. The tissue and cell repositories funded by the CDMRP have supported landmark telomerase studies and the establishment of a BRCA1 mutant cell line. Computer-aided decision support systems are being developed, as is an extensive computerized database of detailed genetic information on over 1,000 neurofibromatosis type-1 patients.

The research infrastructure of our nation has also been fortified by the talented scientists trained within the CDMRP. From FY93-98 the CDMRP has supported 23 new institutional training programs in breast cancer, 494 Pre-and Postdoctoral Fellowships, and 123 Career Development Awards and Sabbaticals. Each program managed by the CDMRP has invested a portion of appropriations to draw new investigators into research fields of Congressional interest through the New Investigator Award mechanism. Many of these funded scientists have gone on to successfully compete for further funding through other agencies. Moreover, senior investigators have benefited from CDMRP support. For example, two DOD Ovarian Cancer Research Program Program Project Award recipients were able to initiate work that allowed them to successfully compete for a National Cancer Institute Specialized Program of Research Excellence award.

——Advances in Biomedical Research

The research accomplishments of the CDMRP are very impressive. They can be gauged, in part, by information reported in scientific peer-reviewed journals. FY92-97 awardees have self-reported over 2,300 publications, 1,800 presentations, and 30 patent/license applications on work accomplished with DOD funding. Individual research projects have made significant contributions to our understanding of disease processes, the development of therapeutics, and the improvement of quality of life. Summary information on specific program accomplishments can be found in Sections V-XII of this report.

Many studies across the research programs are examining proteins, genes, and genetic alterations to identify key elements underlying the development and spread of cancer. For example, the research on HER-2/neu oncogene expression has led to the development of Herceptin, an anti-HER-2/neu breast cancer therapeutic agent currently used in some treatment protocols. Similar studies are being conducted to elucidate prostate cancer-specific oncogenes. The study of matrix metalloproteases has provided clues into the mechanisms of metastases and may lead to interventions in early stage tumor development. Researchers are also targeting the process of angiogenesis as a potential area for early intervention in both breast and ovarian cancers.

Advances have also been made in prevention and early detection of breast, prostate, and ovarian cancers. A new vaccine targeted against ductal carcinoma in situ has proven to be effective in protecting mice against tumor development. A novel imaging technique that combines 2-D and 3-D digital mammographic images may help reduce the number of unnecessary breast biopsies. Research scientists at the Veterans Affairs Medical Center are examining risk factors for prostate cancer in African American Veterans in order to better understand the racial differences in prostate cancer incidence and mortality.

Epidemiological studies have shown that a variety of environmental factors such as diet, micronutrients, hormones, and occupational exposures can influence the development of cancers (both positively and negatively). CDMRP-supported investigators are identifying micronutrients (such as vitamin D, selenium, and naturally occurring phytochemicals) that slow the growth and inhibit the spread of breast and prostate cancer. Funded investigators at the National Institute for Occupational Safety and Health are currently analyzing data relating occupational exposure to ethylene oxide or polychlorinated biphenols and breast cancer risk.

Recently, Congress announced that $277M in FY00 will be directed toward the DOD breast cancer, prostate cancer, ovarian cancer, and neurofibromatosis research programs. Thanks to the tireless efforts of CDMRP staff, consultants, collaborators, consumers, and funded scientists, the CDMRP mission is coming to fruition. Each discovery broadens the knowledge base and brings us closer to the eradication of disease and improves the health of our nation.