In the past decade, heightened public awareness and increased interest in health issues have influenced scientific research. Cancer research has been a particular focus of attention due, in part, to the rising impact of cancer and the work of consumer advocacy organizations. In response to the concerns of the American population, the United States Congress has taken several actions, including directing the Department of Defense (DOD) to manage intramural and extramural grant programs aimed toward targeted research initiatives.

The U.S. Army Medical Research and Materiel Command (USAMRMC) has been responsible for administering targeted appropriations totaling $1.1 billion for fiscal years (FY) 92-99 research on breast cancer, defense women?s health, osteoporosis, neurofibromatosis, prostate cancer, ovarian cancer, and other specified areas. Together, these programs are managed by the office of the Congressionally Directed Medical Research Programs (CDMRP), a scientific research directorate within the USAMRMC. These programs along with their appropriation years are as listed in Table I-1. The remainder of this section will summarize the history of the CDMRP, highlighting unique program features and strategies.

Although each of the research programs within the CDMRP 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 advocacy communities. Program Announcements (PA) that target the individual program requirements are provided to the research community to solicit proposals for each of the seven programs shown in Table I-1. Highlights of each of the active research programs with standing Integration Panels (IPs) follow.

??Breast Cancer Research Program

The vision of the Breast Cancer Research Program (BCRP) is to eradicate breast cancer. The mission of the program is to foster new directions, address neglected issues, and bring new investigators into the field. The program aims to fund a balanced portfolio of scientifically meritorious and innovative research on the prevention, detection, diagnosis, and treatment of breast cancer. Appropriations for the FY92-99 BCRP total $870.1M. Since the inception of the program, 12,009 proposals have been received and 1,806 awards have been made through September 1999. The research accomplishments are impressive and can be gauged, in part, by information reported in scientific peer-reviewed journals. Over 2,300 publications on work accomplished with DOD funds have been self-reported by FY92-96 awardees. More detailed information regarding the BCRP can be found in Section V.

??Neurofibromatosis Research Program

The vision of the Neurofibromatosis Research Program (NFRP) is to decrease the impact of neurofibromatosis. The mission of the NFRP is to support extramural research directed toward the diagnosis, treatment, and understanding of neurofibromatosis types I and II, as well as toward enhancing the quality of life for individuals with the disease. Appropriations for the FY96-99 NFRP total $37.3M. Thirteen Investigator-Initiated Awards and two natural history studies were funded with FY96 and FY97 appropriations for studies on the molecular biology, genetics, neural development, tumor biology, models, and natural history of tumor growth for these disorders. The NFRP funded nine projects in FY98. The research focus in FY98 was on the cell biology of the normal NF type I and II proteins, and how abnormal functioning or lack of these proteins results in pathogenesis. Further details regarding the NFRP can be found in Section VIII of this report.

??Prostate Cancer Research Program

The vision of the Prostate Cancer Research Program (PCRP) is to conquer prostate cancer. The mission of the program is to support innovative and multidisciplinary basic and clinical research relevant to prostate cancer that will result in substantial improvements over current approaches to the prevention, detection, diagnosis, treatment, and basic biology of the disease. Appropriations for the FY97-99 peer-reviewed PCRP total $135M. Due to the desire to increase the efficiency of getting the funds to the scientists, FY97 and FY98 funds were combined and used to fund investigators with highly meritorious proposals submitted to the FY97 program. A total of 168 Dual-Phase Idea Development and New Investigator awards were made in the combined FY97/98 program in the following research categories: prevention and detection; carcinogenesis, etiology, and tumor biology; special populations and behavioral patterns; genetics and molecular biology; and therapeutics. In addition, the program awarded 17 Minority Population Focused Training Awards and a military Tri-Service project. The PCRP is described in greater detail in Section VI of this report.

??Ovarian Cancer Research Program

The vision of the Ovarian Cancer Research Program (OCRP) is to prevent ovarian cancer. The mission of the program is to build a sound research foundation in ovarian cancer that will enhance research on the prevention of ovarian cancer. Appropriations for the FY97-99 OCRP total $27.5M. In FY97, three research awards were made to National Cancer Institute-designated Comprehensive Cancer Centers. In FY98, the OCRP funded five large program projects that aim to (1) advance ovarian cancer prevention strategies through enhanced understanding of ovarian cancer etiology, (2) engage experts from multiple disciplines in collaborative ovarian cancer research efforts, and (3) foster the development of a sustained national ovarian cancer research enterprise. Refer to Section VII for a comprehensive description of the OCRP.

??Specified Appropriations Program

The goal of the Specified Appropriations Program (SAP) is to fund outstanding research that will address topic areas specified by Congress. Appropriations for the FY99 SAP total $5.5M for research in specified topic areas. The FY99 SAP includes two specified topic areas: Advanced Cancer Detection (ACD) and Diagnostic and Surgical Breast Imaging (DSBI). Additional details regarding SAP can be found in Section IX of this report.

??Other Research Programs Managed by the CDMRP

Beginning in FY95, Congress has directed the DOD to manage a number of targeted research initiatives. Appropriations to these initiatives total $22.5M. The other research initiatives managed by the CDMRP include Coastal Cancer Control, Computer Aided Diagnosis, Center for Prostate Disease Research, and Advanced Cancer Detection. Further information about the other research programs managed by the CDMRP can be found in Section XII.

The U.S. Army Medical Research and Development Command (later renamed the USAMRMC) first received $25M for breast cancer research in FY92. The CDMRP office, formerly known as Research Area Directorate VI, was established the following year and assumed management responsibilities for the FY92 awards. At the initiation of the FY93 BCRP, the Army sought the advice of the National Academy of Sciences for recommendations to guide the $210M research appropriation. In response, a 12-member committee of the Institute of Medicine (IOM) issued a report: Strategies for Managing the Breast Cancer Research Program: A Report to the U.S. Army Medical Research and Development Command. For a more thorough discussion of the IOM, refer to the Institute of Medicine Recommendations.

Programs within the CDMRP are managed by a skilled, multidisciplinary team of military and civilian scientists and clinicians, referred to as the Program Staff. Under expert direction of the Program Staff, innovations have been implemented in program development, scientific and programmatic evaluation of proposals, and grants management.

Most federally funded research programs are long-term efforts that receive similar levels of funding from one year to the next, allowing a regular cycle of proposal submission and review over the course of many years. In contrast, programs managed by the CDMRP have no lifetime beyond that allotted by a single Congressional appropriation and tight restrictions regarding how and when funds may be spent. Therefore, management of these programs requires a thorough understanding of Congressional intent and Federal Acquisition Regulations, all other applicable regulations, and a strict adherence to the timeline for obligation of funds. Figure I-1 shows the major milestones for each research program funding cycle.

The timeline begins with the Congressional appropriation, program execution occurs over the first 2 years, and science management takes place over the next 5 years. To accomplish the multiple program administration tasks, several established science management methods have been adapted and new innovations have been developed. For each Congressional appropriation, the CDMRP utilizes a flexible 7-year execution and management cycle to accommodate all stages from development of an investment strategy through the completion of research grants. Each cycle is designated by the year of the appropriation and the name of the program (e.g., FY95 BCRP). The cycle begins with the receipt of a fiscal year appropriation.

The first major milestone in the cycle is the development of an investment strategy. To establish an appropriate investment strategy for each program that meets the current needs of both the research and advocacy communities, the Program Staff seeks the advice of expert panels [i.e., IPs] composed of leaders in scientific and clinical research, and consumers (persons living with the disease targeted by each program?s focus). Each program then utilizes a variety of award mechanisms to execute the investment strategy, which is advertised to the research community in a PA.

By the end of the second fiscal year, proposals are received, scientific and programmatic reviews are conducted, and funds are awarded. During fiscal years 3 through 7, the research is performed and science management of grants is conducted. Science management in years 3 through 7 involves annual and final report reviews, performing selected site visits, and disseminating research findings.

??Stakeholders

The CDMRP is committed to providing a sound investment of public funds and to effectively and efficiently addressing the research needs of targeted diseases. To accomplish these goals, each program?s investment strategy addresses gaps and urgent areas of need in a particular field that are not adequately addressed by other funding agencies.

At the initiation of each new program, the USAMRMC convenes a Stakeholders Meeting that assembles key scientists and consumers in a given field (e.g., prostate cancer and ovarian cancer) from leading government, academic, private, and consumer advocacy organizations. The participants discuss the unique issues and concerns of the disease and the most critical gaps in current research funding. The information is supplied to the IP to provide the initial guidance for development of a program focus and funding strategy that most effectively target the gaps in research while responding to Congressional direction.

Several other benefits are derived from this approach. Communication among scientists from different disciplines, and between scientists and consumer advocates, provides a forum from which fresh perspectives emerge that transcends parochial interests. This networking also catalyzes the team building needed for a shared program vision. In addition, the Stakeholders Meeting provides an opportunity for the CDMRP to solicit nominations for the scientific peer and the programmatic review panels.

??Two-Tiered Review

Critical to the success of the CDMRP is the concept of the two-tiered review of research proposals. The CDMRP adopted the recommendations of the National Academy of Sciences? 1993 IOM Report that recommended a two-tiered peer review process. The IOM concluded that the best course for the CDMRP would be to establish a peer review system that reflects the traditional strengths of existing review systems but is tailored to accommodate the individual program?s goals. The CDMRP has developed a peer review model similar to the National Institutes of Health system to evaluate competitive research and training proposals.

The two tiers of review are complementary. Scientific peer review, the first tier of review, is a criterion-based process whereby proposals are evaluated on their own scientific and technical merit. The process of scientific peer review is currently being executed under contract with United Information Systems, Incorporated.

Programmatic review, the second tier of review, is a comparison-based process in which submissions from multiple disciplines compete within a common pool. Programmatic review is being conducted as part of the contract the CDMRP holds with Science Applications International Corporation (SAIC). Utilizing the input of the scientific review panels provided in the peer review summaries, the IP evaluates scientifically meritorious submissions for programmatic relevance and makes recommendations for funding. Consumers have an equal vote with scientists in both levels of review and provide essential contributions to the CDMRP. Overall, the goal of the two-tiered review process is to develop funding recommendations that balance the most meritorious science across many disciplines and offer the highest promise for fulfilling the programmatic goals set forth in the PA.

??Criterion-Based Scoring

Peer review panels organized by scientific discipline and specialty area conduct the first level of review. The primary responsibility of the panel is to review the scientific merit of each proposal based on the evaluation criteria specified in the PA. Each scientific review panel is composed of a Panel Chairperson, scientific reviewers (usually 11 to 16), consumers (typically 2), and a non-voting Executive Secretary. Panel members have varied qualifications and responsibilities in accordance with their assigned roles.

A two-part scoring procedure is used for the evaluation of proposals in the first tier of the review process. The procedure consists of the assignment of an overall global priority score and individual evaluation criteria scores. A global priority score range of 1 to 5 is used with 1 representing the highest merit and 5 the lowest merit. Reviewer voting is permitted in 0.1 increments. In addition to assigning a global priority score for each proposal, panel members are asked to rate each of the review criteria related to the appropriate award mechanism as published in the PA. The scale used is 1 to 10 with 1 representing lowest merit and 10 representing highest merit using whole numbers only. The evaluation criteria are designed for each award mechanism to emphasize the important elements of a particular mechanism.

The main reasons for rating each of the review criteria separately in addition to the global rating are:

• It places additional emphasis on the published evaluation criteria and provides guidance to reviewers in determining an appropriate global score.
• The evaluation criteria are intended to provide the applicant, the IP, and the CDMRP with a more informed measure of the quality of the proposal in terms of its strengths and weaknesses.
• The ratings have been helpful in focusing panel discussion and conserving valuable meeting time.

??Integration Panels

Integration Panels are the primary advisory committees utilized by the CDMRP Program Staff. Each program of the CDMRP has a separate IP that is composed of a diverse group of research scientists and clinicians, and consumer advocates. Panel members recommend the program vision and investment strategy and participate in the programmatic review of research proposals. The major tasks of the IPs are outlined in Figure I-2.

Integration Panels tasks and duties have been conducted in all programs of the CDMRP in a manner that ensures ethical conduct, e.g., avoidance of conflict of interest and disclosure of confidential or procurement-sensitive information. Panel members have dedicated significant hours in support of programs of the CDMRP. The USAMRMC gratefully acknowledges the intellectual strength, commitment, and passion of these Panel members. Brief biographies of current members of each CDMRP IP are provided in the individual program sections of this report (Sections V-XI).

??Consumer Participation in the CDMRP

A key component of the CDMRP is the inclusion of consumers in all advisory panels utilized by the CDMRP. The value of consumer involvement on these panels is derived from their unique professional and personal histories. Their firsthand experiences with the disease add perspective, passion, and a sense of urgency, ensuring that the human dimensions of disease are incorporated in program policy, investment strategy, and research focus. The goal for consumer participation is to involve a diverse array of consumers to ensure that the perspectives of survivors from all backgrounds are represented. This is consistent with the unique research agenda of the CDMRP, which emphasizes outcomes and a patient-centered focus.

Consumers have been valued participants in the BCRP first serving on the IP in FY93. A meeting was held in FY93 to discuss extending the role of consumers in the BCRP, and the decision was made to also include consumers on peer review panels. The success of this process has led to using consumers on all CDMRP peer review panels.

Consumers on peer review panels are cancer survivors and are active in advocacy for the BCRP, PCRP, and OCRP; NFRP consumers are individuals with neurofibromatosis, their family members, or representatives of consumer organizations who are active in advocacy. The CDMRP now serves as an example for other funding agencies for including consumers in peer review. These consumers must be nominated by an advocacy organization, be fluent in English, possess at least a high school education, and have an interest in extending their scientific knowledge.

During peer review, consumers are asked to examine the relevance of the proposed research to the targeted disease with the following questions in mind:

Today, consumers serve on all CDMRP scientific and programmatic review panels. Additionally, the Program Staff consults ad hoc consumer advisors for their opinions on various issues throughout the review and management process. In the changing world of science management, it is vitally important to foster partnerships among the managers and scientists as well as those who are ultimately affected by policy and science. Consumer participation in key processes of the CDMRP has enhanced the fulfillment of program objectives. The practice is being continually improved and new directions are being undertaken to ensure that those who are ultimately affected by funding decisions have a voice in the process. For more information, see the article "Perspective from the Department of Defense Breast Cancer Research Program," Breast Disease 10:33-45, 1998.

??Award Categories and Mechanisms

One of the hallmarks of the CDMRP is its ability to adapt every program cycle to the individual needs of each program?s research, clinical, and consumer communities. A key means by which the CDMRP addresses these individual needs is to utilize a variety of award categories and mechanisms that will best stimulate research that is considered important in that fiscal year. Three types of award categories have been used by the CDMRP: Training/Recruitment, Research, and Infrastucture. Each category contains between 1 and 11 mechanisms. For a description of all award mechanisms used by the CDMRP, see Appendix A.

The utilization of various award mechanisms and the amount of money invested in each mechanism are key components of each program?s investment strategy. The different award categories and mechanisms used in individual programs for each program cycle have allowed the CDMRP to fill unique niches and complement funding opportunities offered by other agencies. For example, the BCRP has focused on three areas of emphasis. First, the training/recruitment category, which includes numerous mechanisms, has been an area of emphasis since support from other agencies for training has been limited in recent years. Second, Idea Awards are now a major backbone of the BCRP and most other programs within the CDMRP. These awards are designed to stimulate new directions in research that should allow investigators to compete for larger, more traditional grants offered by other agencies. Third, translational research, i.e., bench to bedside research that will involve a clinical trial within the lifetime of the award, has become a recent focus since it is often difficult for investigators to obtain initial funding at this important junction in research.

Other programs, such as the NFRP, have designed mechanisms that meet a specific need. In FY98, the NFRP recognized that there was a need for natural history studies on both neurofibromatosis type-1 and neurofibromatosis type-2. Thus, a mechanism was implemented to facilitate these types of studies and establish consortiums that could also form the foundation for performing future clinical trials. In the last 2 years, both the BCRP and the PCRP have also employed mechanisms to encourage research at Historically Black Colleges and Universities/Minority Institutions (HBCU/MI) (see Minority Health Initiative, for more detailed information).

The IOM committee made two important recommendations in their 1993 Report to the USAMRMC ? an investment strategy for the FY93 BCRP and a two-tiered review mechanism. The investment strategy emphasized the belief that ideas flow most freely from research that is unimpeded and is driven by the investigators? own curiosity and creativity.

The IOM committee recommended an investment strategy that would distribute funding in three areas: investigator-initiated research projects, infrastructure enhancement, and training and recruitment. The IOM also recommended a two-tiered review strategy that has been applied to all CDMRP programs since FY93.

In late 1995, the USAMRMC asked the IOM to review the implementation and progress of the BCRP. The IOM issued a report in 1997: A Review of the Department of Defense?s Program for Breast Cancer Research. The IOM was favorably impressed with the BCRP and supported its continuation.