Vol. 18, No. 19, June 2, 1989 DATED ANNOUNCEMENTS (RFPs AND RFAs) SEER/SURVEILLANCE QUALITY CONTROL UNIT (RFP) ..............(84/124).......... 1 National Cancer Institute Index: CANCER LARGE-SCALE AUTOMATED DNA SEQUENCING OF NEUROTRANSMITTER RECEPTOR GENES (RFP) ......................................(127/184)......... 1 National Institute of Neurological Disorders and Stroke Index: NEUROLOGICAL DISORDERS, STROKE DIABETES CENTERS (RFA) ....................................(187/292)......... 2 National Institute of Diabetes and Digestive and Kidney Diseases Index: DIABETES, DIGESTIVE AND KIDNEY DISEASES MINORITY-BASED COMMUNITY CLINICAL ONCOLOGY PROGRAM (RFA) ..(295/409)......... 3 National Cancer Institute (1124/2381) Index: CANCER NATIONAL COOPERATIVE VACCINE DEVELOPMENT GROUPS FOR THE ACQUIRED IMMUNODEFICIENCY SYNDROME (RFA) .............(412/488, 2384/3254)... 5 National Institute of Allergy and Infectious Diseases Index: ALLERGY, INFECTIOUS DISEASES MURINE IMMUNODEFICIENCY LENTIVIRUS MODEL FOR AIDS (RFA) ...(491/532)......... 6 National Institute of Allergy and Infectious Diseases (3257/3556) Index: ALLERGY, INFECTIOUS DISEASES ONGOING PROGRAM ANNOUNCEMENTS MOLECULAR MECHANISMS OF CELL DEATH DURING AGING ...........(538/818)......... 6 National Institute on Aging Index: AGING THE AGING OF RETARDED ADULTS ..............................(821/1099)........10 National Institute on Aging Index: AGING DATED ANNOUNCEMENTS (RFPs AND RFAs) SEER/SURVEILLANCE QUALITY CONTROL UNIT RFP AVAILABLE: NCI-CN-95124-41 P.T. 34; K.W. 0715035, 0755018 National Cancer Institute The National Cancer Institute will issue RFP No. NCI-CN-95124-41 upon request to the address shown below on or about June 5, 1989, and proposals will be due approximately July 20, 1989. The National Cancer Institute, Division of Cancer Prevention and Control, Surveillance Program, is interested in soliciting proposals from organizations for maintaining a quality control unit (QCU) for the surveillance program. The purpose of the QCU is to assess and insure the completeness, accuracy and timeliness of data that are available to the NCI and are used to measure the progress of cancer control. A secondary purpose of the QCU is to reduce the variability in procedures and interpretations of data collection and abstraction conventions by individuals responsible for collecting and managing cancer surveillance information through education and communications. A third purpose of the QCU is to provide a research and evaluation component focused on assessment of the quality of surveillance data and the efficiency of existing surveillance systems to assure that they continue to serve the NCI program needs. Thus, the QCU makes a significant contribution to the National Cancer Program. This RFP is for recompetition of an ongoing contract with the University of California at San Francisco. The National Cancer Institute expects to make one award. Copies of the RFP may be obtained by sending a written request to: Mrs. Susan K. Hoffman, Contract Specialist National Institutes of Health National Cancer Institute Research Contracts Branch, PCCS Executive Plaza South, Room 635 9000 Rockville Pike Bethesda, Maryland 20892 Telephone: (301) 496-8603 LARGE-SCALE AUTOMATED DNA SEQUENCING OF NEUROTRANSMITTER RECEPTOR GENES RFP AVAILABLE: NIH-NINDS-89-10 P.T. 34; K.W. 0760050, 0760075, 0755045 National Institute of Neurological Disorders and Stroke The National Institute of Neurological Disorders and Stroke has a new requirement which involves research to improve and provide large-scale DNA template production applicable to large-scale automated DNA sequence analysis. The Contractor shall be required to work from established protocols to 1) provide single-stranded DNA templates to the Government and 2) improve upon the methods used to produce these templates. In most cases this shall include restriction endonuclease digest analysis of DNA fragments from lambda or cosmid clones and the use of the resulting information to subclone fragments of the cloned insert DNA into phagemid or plasmid vectors. The next step shall be the production of ordered, unidirectional deletions of DNA fragments from phagemids containing cloned DNA using exonuclease III and the analysis of these deleted subclones. The final step shall be the production of single-stranded DNA templates from phagemids or plasmids for use in automated DNA sequencing. The Contractor may be required to carry out alternate procedures which shall be either subsets of the above procedures or closely related procedures. The Contractor shall be required to develop new procedures to accomplish the goals achieved by carrying out the procedures above or develop variations of the above procedures that allow more rapid sample preparation, greater number of samples to be processed simultaneously, and less variation in experimental results. An example of an improvement that the Contractor may perfect is the use of polymerase chain reaction to prepare single-stranded template DNA. To Vol. 18, No. 19, June 2, 1989 - Page 1 accomplish these goals, offerors shall have expertise and experience in the areas of microbiology, molecular biology and nucleic acids biochemistry. It is anticipated that one contract award will be made under this RFP, for a three-year period. RFP No. NIH-NINDS-89-10 will be issued on or about June l, l989, with a tentative date for receipt of proposals set at August l, l989. To receive a copy of the RFP, please submit a written request and two self-addressed mailing labels to the following address. All responsible sources may submit a proposal which shall be considered by the Government. Contracting Officer Contracts Management Branch, DEA National Institute of Neurological Disorders and Stroke, NIH Federal Building, Room 90l 7550 Wisconsin Avenue Bethesda, Maryland 20892 Attn: RFP-NINDS-89-10 DIABETES CENTERS RFA AVAILABLE: 89-DK-09 P.T. 04; K.W. 0715075, 0785050, 0710030 National Institute of Diabetes and Digestive and Kidney Diseases Application Receipt Date: November 20, 1989 The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) invites applications for a Center grant to be awarded in Fiscal Year 1991. NIDDK anticipates the competitive award of one Diabetes Endocrinology Research Center (DERC) in Fiscal Year 1991. BACKGROUND The NIDDK-supported DERCs are part of an integrated program of diabetes-related research support provided by NIDDK. These centers have provided a focus for increasing collaboration and cost effectiveness among groups of successful investigators at institutions with established comprehensive diabetes research bases. OBJECTIVES AND SCOPE The objectives of the DERCs are to bring together investigators from relevant disciplines in a manner which will enhance and extend the effectiveness of research related to diabetes and its complications. A diabetes center must be an identifiable unit within a single university medical center or a consortium of cooperating institutions, including an affiliated university. The overall goal of the DERC is to bring together on a cooperative basis, clinical and basic science investigators in a manner which will enrich the effectiveness of diabetes research. An existing program of excellence in biomedical research in the area of diabetes and related metabolic and endocrine disorders is required. This research should be in the form of NIH-funded research projects, program projects, or other peer-reviewed research that is in existence at the time of submission of a center application. Close cooperation, communication, and collaboration among all involved personnel of all professional disciplines are ultimate objectives. Applicants should consult with NIDDK staff concerning plans for the development of the center. The DERCs are based on the core concept. Cores are defined as shared resources that enhance productivity or in other ways benefit a group of investigators working in diabetes or diabetes-related areas to accomplish the stated goals of the center. Two other types of activities may also be supported with center funding - a pilot and feasibility program and an enrichment program. The pilot and feasibility program provides modest support for new initiatives or feasibility research studies. This program is directed at new or established investigators in other research disciplines where their expertise may be applied to diabetes research. The center grant may also include limited funds for program enrichment such as seminars, visiting scientists, consultants, workshops, etc. Vol. 18, No. 19, June 2, 1989 - Page 2 MECHANISM OF SUPPORT NIDDK expects to award one DERC Grant in Fiscal Year 1991 on a competitive basis. The receipt of one competitive continuation application is anticipated, which will compete for the award along with other applications received in response to this announcement. Foreign institutions are not eligible to apply. The anticipated award will be for five years and is contingent upon the availability of appropriated funds. The RFA (general description and Guidelines for the DERC) and consultation may be obtained from: Dr. Sanford A. Garfield Diabetes Centers Program Director Division of Diabetes, Endocrinology, and Metabolic Diseases Westwood Building, Room 626 National Institute of Diabetes and Digestive and Kidney Diseases Bethesda, Maryland 20892 Telephone: (301) 496-7418 REVIEW PROCEDURES Applications for a DERC grant will be evaluated in national competition by the NIH grant peer review process. Applications will be reviewed initially by a special review committee convened by the NIDDK and subsequently by the National Diabetes and Digestive and Kidney Diseases Advisory Council. METHOD OF APPLYING Potential applicants are urged to submit a letter of intent regarding their application. The letter of intent is nonbinding and is not a precondition for an award. The letter of intent should include the name(s) of the principal investigator and principal collaborators, descriptive titles of the core facilities and pilot/feasibility projects, and the organization(s) involved. Applications must be submitted using PHS Form 398 (Rev. 10/88). The RFA label contained in the application kit must be affixed to the bottom of the face page of the original copy of the application. Failure to use this label could result in delayed processing and review of your application. Mail the completed application (original and four copies) to: Application Receipt Office Division of Research Grants Westwood Building, Room 240 National Institutes of Health Bethesda, Maryland 20892** Simultaneously submit two copies to Dr. Sanford A. Garfield at the address noted above. The special single receipt date for submissions in response to this announcement is November 20, 1989, with earliest funding December 1, 1991. MINORITY-BASED COMMUNITY CLINICAL ONCOLOGY PROGRAM RFA AVAILABLE: 89-CA-06 P.T. 34, FF; K.W. 0785140, 0785035, 0404004, 0795003 National Cancer Institute Letter of Intent Receipt Date: July 14, 1989 Application Receipt Date: October 13, 1989 The Division of Cancer Prevention and Control (DCPC), National Cancer Institute (NCI), is interested in establishing a cancer control effort, which is designed to link physicians involved in the care of minority cancer patients to the NCI clinical trials program, and to provide minority cancer patients/subjects with state-of-the-art treatment and cancer control research opportunities. DCPC invites applications from domestic institutions with greater than 50 percent of new cancer patients from minority populations for cooperative agreements in response to this Minority-Based Community Clinical Oncology Program (Minority-Based CCOP) Request for Applications (RFA). Vol. 18, No. 19, June 2, 1989 - Page 3 BACKGROUND INFORMATION Overall, survival rates from cancer in minority populations are less than in whites. For example, data from the Surveillance, Epidemiology, and End Results (SEER) Program, NCI, show that the five-year relative survival rate (1975-1984) for all cancer sites in blacks is 39.6 percent compared to 51.3 percent for whites. Site-specific survival rates of black patients with breast, rectal, corpus uteri, and bladder cancers are lower than those for whites by 12, 12, 30, and 22 percents, respectively. In addition to poorer survival outcomes, cancer incidence and mortality rates for selected cancer sites in minority populations are higher compared to whites. One way to develop and implement effective treatment and cancer control strategies in minority populations, and thereby reduce disparities in cancer incidence, morbidity, and survival rates between whites and minority populations, is to provide broader access to clinical research and greater involvement of minority populations in the clinical trials process. In general, there is limited participation in clinical trials research by black, Hispanic, Asian-American, Native-American and other minority cancer patients. A major factor influencing participation in clinical research by minority patients is access to the clinical trials process. The Community Clinical Oncology Program (CCOP), which was first initiated in 1983, has proven to be a successful model for bringing the benefits of clinical research to cancer patients in their communities by providing support for community physicians to enter patients on treatment and cancer control research protocols. During the first phase of CCOP, a patient log record-keeping system on all new cancer patients seen by a participating physician, and for whom protocols were available, showed that 7 percent of CCOP patients were minorities. This compares to 13 percent minority representation in SEER and 20 percent in the general U.S. population. A similar ethnic profile of minority patient participation in clinical trials is seen during the second phase of the CCOP. Through the Minority-Based CCOP, DCPC aims to meet a need of minority cancer patients and individuals at risk for cancer by establishing a system of oncology programs for participation in clinical research trials through the NCI network. RESEARCH GOALS AND SCOPE The Minority-Based CCOP initiative is designed to: o Bring the advantages of state-of-the-art treatment and cancer control research to minority individuals in their own communities by having practicing physicians and their patients/subjects participate in clinical treatment and cancer control research protocols; o provide a basis for involving a wider segment of the community in clinical research by increasing the involvement of primary health care providers and other specialists in treatment and cancer control research; o provide an operational base for extending cancer control, and reducing cancer incidence, morbidity, and mortality in minority populations by accelerating the transfer of newly developed cancer prevention, detection, treatment, and continuing care technology to widespread community application; o facilitate wider community participation in future treatment and cancer control research approved by NCI; and o examine selected issues in Minority-Based CCOP performance and evaluate its impact in the community. MECHANISM OF SUPPORT Awards will be made as Cooperative Agreements. The Cooperative Agreement is an assistance mechanism involving cooperation by NCI staff as described in the RFA. Depending on individual costs and available funds, NCI anticipates making up to eight (8) awards under this RFA with total funding not expected to exceed $1.2 million per year. Awards will be for three (3) years as described in the RFA. Vol. 18, No. 19, June 2, 1989 - Page 4 STAFF CONTACT Additional information and copies of the RFA may be obtained from: Carrie P. Hunter, M.D. Program Director, CCOP, CORB, DCPC, NCI Executive Plaza North, Room 300-G Bethesda, Maryland 20892 Telephone: (301) 496-8541 NATIONAL COOPERATIVE VACCINE DEVELOPMENT GROUPS FOR THE ACQUIRED IMMUNODEFICIENCY SYNDROME RFA AVAILABLE: 89-AI-16 P.T. 34; K.W. 0715008, 0740075, 1002045, 0760080, 1002008, 0710030 National Institute of Allergy and Infectious Diseases Letter of Intent Receipt Date: June 19, 1989 Application Receipt Date: August 10, 1989 The National Institute of Allergy and Infectious Diseases (NIAID) announces the availability of an RFA for the funding of National Cooperative Vaccine Development Groups for the Acquired Immunodeficiency Syndrome (NCVDG). The RFA (available on request) invites applications aimed at the development of effective vaccines for the prevention of AIDS. Scientific approaches to the development of effective AIDS vaccines appropriate to the RFA may range from research on whole virus vaccines, through the production of preparations with recombinant DNA techniques and synthetic approaches, to the use of viral vectors to deliver antigenic materials. Applications directed towards vaccine development for AIDS-associated opportunistic infections are not invited. Otherwise, scientific approaches to the development of effective vaccines appropriate to the RFA are broad and limited only by the creativity and ability of the applying group to exploit leads from basic studies in virology, molecular biology, and immunology. Each NCVDG will be assembled by the Principal Investigator to form a multidisciplinary consortium representing the various skills needed to successfully design and evaluate vaccine entities and strategies for the prevention of AIDS. Inasmuch as it is unlikely that all of the outstanding talents required to exploit fundamental leads from various scientific disciplines will be found in a single institution, each Group is envisioned as being multi-institutional as well. Thus each NCVDG will be assembled by the Principal Investigator and may consist of a number of Laboratory Projects representing the scientific disciplines required to attain the Group's goal and objectives. The various Laboratory Projects, including that of the Principal Investigator, may be mobilized from academic or research institutions, and industry. It is expected that the rationale for design of potential vaccines, the synthesis or production of specific candidates, and the models for evaluation will originate within the Group and be based on leads from their own and others' fundamental research. Awards will be made as Cooperative Agreements. Assistance via a Cooperative Agreement differs from the research grant in that the Government component (in this instance, the NIAID) awarding the Cooperative Agreement anticipates substantial involvement during performance. The nature of NIAID staff participation is described in the RFA. However, the applying Group must define its objectives in accord with its own interests and perceptions of approaches to vaccines for AIDS prevention. It is anticipated that 5 to 7 awards will be made, each averaging $500,000 to $750,000 in direct costs. The proposed applicant institution will be responsible for the Group's application. Awards will be made to the applicant institution on behalf of the group as a whole and not to individual Laboratory Projects within the Group. The applicant institution will provide a Central Operations Office for the Group. The applicant institution will be responsible for the performance of the entire Group and will be accountable for the funds awarded. The participation of the Government through the NIAID extramural staff is aimed at facilitating a concerted effort by the Group. The interaction of academic and non-profit research institutions with commercial organizations and Government is expected to favor efficient development of AIDS vaccines and will facilitate their subsequent refinement and evaluation in clinical trials. Vol. 18, No. 19, June 2, 1989 - Page 5 The RFA is available from: Dr. Dale R. Spriggs NIAID, AIDS Program Vaccine Research and Development Branch 6003 Executive Blvd., Room 234P Rockville, Maryland 20892 Telephone: (301) 496-8200 MURINE IMMUNODEFICIENCY LENTIVIRUS MODEL FOR AIDS RFA AVAILABLE: 89-AI-17 P.T. 34; K.W. 0715008, 0755020, 1002045, 0765033 National Institute of Allergy and Infectious Diseases Letter of Intent Receipt Date: July 14, 1989 Application Receipt Date: August 25, 1989 The National Institute of Allergy and Infectious Diseases (NIAID) announces the availability of an RFA for the development of a murine immunodeficiency lentivirus model for the acquired immunodeficiency syndrome (AIDS). The RFA (available on request) invites applications to develop a murine immunodeficiency lentivirus model for AIDS which would expedite studies of pathogenesis, and evaluation of potential therapies and vaccines. Applicants are encouraged to propose novel strategies for obtaining such a model with a rational approach for the identification, isolation, and molecular and biological characterization of naturally occurring murine lentiviruses. It will be important to address multiple alternatives since there will be no way to guarantee success of a single search strategy. Scientific and technical merit of the zoology/ecology collaborators or contractors will be critical in the evaluation of the applications. Mouse strains and viruses developed in this research must be made available to the AIDS Research and Reference Reagent Program for world-wide distribution to qualified researchers. Awards will be made as individual research (RO1) grants. Investigators from any institution, foreign or domestic, are eligible to apply for this funding. This RFA is available from: Dr. Linda M. Muul Pathogenesis Branch NIAID, AIDS Program 6003 Executive Blvd., Room 214N Rockville, Maryland 20892 Telephone: (301) 496-8378 ONGOING PROGRAM ANNOUNCEMENTS MOLECULAR MECHANISMS OF CELL DEATH DURING AGING P.T. 34; K.W. 0710010, 1002004, 0765010, 0765033, 0790005, 0705055 National Institute on Aging INTRODUCTION Cell death in multicellular organisms takes place in a variety of circumstances. For example, the death of certain cells may occur as part of a developmental program; in connection with organ involution or regression as in the adult thymus; during cell renewal processes where specialized, differentiated, non-dividing effete cells such as granulocytes and erythrocytes are replaced by newly-formed cells; as a consequence of toxic or harmful environmental conditions; when potentially harmful cells such as neoplastic or virus-infected cells are targeted for destruction by surveillance systems; or because of senescence of the cells themselves or the host organism. In an entity as complex as the cell there are processes such as nucleic acid and protein synthesis, transport of ions, nutrients and other metabolites across membranes, and structures such as membranes and cytoskeleton whose function and integrity must be faithfully maintained Vol. 18, No. 19, June 2, 1989 - Page 6 because they are essential for cell viability. Defense mechanisms such as DNA repair and heat shock proteins have evolved which allow the cell to repair, or prevent injury to vital molecules when faced with stressful or potentially harmful environmental conditions. In some cases, the molecular events that lead to cell death are reasonably well known. For example, in complement-mediated lysis the membrane attack complex causes the formation of channels in the target cell's membrane, which therefore becomes leaky and no longer functions as a permeability barrier. In other cases, however, the critical event(s) in cell death is not known; nor is it known which molecular lesions are irreversible and which can be repaired or prevented by the cell's protective mechanisms. Questions such as why and how senescent cells die are relevant to understanding the aging process in complex organisms. Furthermore, the role of cell death in age-related diseases and degenerative conditions is unknown. This question is particularly important in neural tissue, where cell regeneration is either non-existent or at best quite limited. SPECIFIC OBJECTIVES The National Institute on Aging (NIA) wishes to encourage applications for research projects investigating the molecular events that may lead to, or accompany, cell death during aging. While the study of cell death in any circumstance may be appropriate under this program, its relevance to the aging process must be explicit. The following questions illustrate the type of research that this program announcement intends to foster. BASIC MECHANISMS OF CELL DEATH o What intracellular conditions predispose the cells to irreversible damage, e.g., elevation of calcium ion concentration, oxidizing agents, etc.? By what mechanisms? o What are the critical sites or molecules which, when damaged, result in cell death if not repaired? o Which potentially lethal lesions can be repaired by the cell, and which lesions are irreversible? o What are the cellular mechanisms that prevent or reverse potentially lethal lesions, and how do they work? Are these defense mechanisms impaired in senescence? o Do senescent cells die because they are programmed to die, do they die because of damage resulting from the accumulation of damage inflicted by a hostile environment, or both? o What tissues are most sensitive to loss of function due to cell death? o Although cells may die for a variety of reasons, are there common steps in the pathways leading to cell death? o What naturally-occurring molecules are toxic to cells leading to cell death, and how do they function? CELL DEATH IN AGE-ASSOCIATED DISEASES AND DEGENERATIVE CONDITIONS The role of cell death in the pathogenesis of several age-related diseases and degenerative conditions is an intriguing and largely unexplored possibility. Explorations of this possibility are limited by technical difficulties in determining the extent of cell death in many tissues. Important avenues for research thus include the following: o Testing new techniques to determine the rate and extent of in vivo cell loss and/or cell death in tissues susceptible to age-related diseases (e.g. articular cartilage, bone, cardiac muscle, vascular endothelium; cell loss in the CNS is discussed in the next section). o Studies to determine the possible role of cell loss and/or cell death in specific age-associated diseases and conditions. Examples include the possible role of chondrocyte loss in osteoarthritis, loss of osteoblasts or osteoblast progenitor cells in osteoporosis, loss of striated muscle fibers in age-associated degenerative muscular conditions, loss of parietal cells in atrophic gastritis, cell loss associated with disorders of gait and balance, and cell loss in the sinoatrial node in age-associated arrhythmias. Vol. 18, No. 19, June 2, 1989 - Page 7 o Studies to determine the role of cell in age-associated changes in renal, pulmonary, muscular, and other physiologic functions. CELL DEATH IN THE AGING NERVOUS SYSTEM One of the most critical issues in the neurobiology of aging concerns the specific mechanisms of selective cell loss in the brain. Neuronal death is especially critical due to the non-replicative nature of most cells in the central nervous system; CNS structural change and/or loss of neurons is the hallmark of many of the age-associated disorders of the brain such as Alzheimer's disease. The inability of the CNS to replace lost neurons and the complex structure of the brain raise a number of unique research questions. o Is there significant cell loss associated with normal healthy aging of the brain as there is during early development or is it only as a result of incipient disease? o Do the mechanisms of cell loss associated with normal brain aging differ from those associated with diseases of the CNS? o What accounts for the selective vulnerability of specific neurons in various diseases? o What is the role of trophic factors in the survival and death of neurons in the aging CNS? o Is there increased vulnerability to endogenous and environmental toxins in the aging CNS and if so what is the nature of this vulnerability? o Under what conditions do excitatory amino acid neurotransmitters become excitotoxic? o What are the molecular mechanisms by which toxins trigger cell death in the aging CNS? o What role does neuronal connectivity and activity play in the survival or death of neurons in the adult and aging CNS? o What is the role of altered gene expression in neuronal cell death? o How does the aging CNS compensate for cell loss? o What roles do vascular and glial elements play in neuronal survival and death; are changes in the transport mechanisms for glucose, oxygen and other essential elements involved? o Are the quantitative methods used for estimating cell loss in the aging nervous system accurate or are new methods needed? o What role do changes in neuroendocrine and immune factors play in neuronal cell death in the aging nervous system? o What is the role of stress and glucocorticoids in neuronal cell death? o Are intracellular metabolic changes such as modifications in mitochondrial oxidative metabolism primary or secondary causes of neuronal cell death? o How do membrane changes affect inter- and intracellular signal transduction during normal aging and diseases of aging? o How do changes in homeostatic mechanisms that regulate cytosol calcium concentration lead to cell death? Qualified scientists who plan to investigate these issues, or other issues of similar nature, are invited to apply for research grants under this program. APPLICATION AND REVIEW PROCEDURES The primary mechanisms for support of this program are: o Research grant (R01) o Program Project Award (P01) Vol. 18, No. 19, June 2, 1989 - Page 8 o First Independent Research Support and Transition (FIRST) Award (R29) o Career grants, which include: Research career development award (K04) Clinical investigator award (K08) o Training grants (T32) o Fellowships (F32, F33) Research project grant (R01 and R29) applications, fellowships (F32, F33) and research career development awards (K04) will be reviewed for scientific and technical merit by an appropriate study section in the Division of Research Grants. All other applications will be reviewed by an appropriate peer review group. Secondary review will be by an appropriate National Advisory Council. There are no set-aside funds for these applications. Applications compete on the basis of scientific merit with all other applications. The review criteria are the traditional ones underlying scientific merit. Researchers who are considering making an application in response to this announcement are welcome to discuss their project, and the range of grant mechanisms available, with NIA staff in advance of formal submission. This can be done either through a telephone conversation or a brief letter giving the descriptive title of the proposed project and identifying the principal investigator and, when known, other key participants. Applications related to the health of women and minorities are particularly encouraged. Applicants should use the regular research project and program project grant application form 398 (Rev. 9/86) for R01, R29, P01, T32, K04 and K08 applications, and form 416-1 (revised 7/88) for F32 and F33 applications. These are available at the applicant's institution or from: Office of Grants Inquiries Division of Research Grants Westwood Building, Room 449 National Institutes of Health Bethesda, Maryland 20892 Telephone: (301) 496-7441 To expedite the application's routing within NIH, please check "Yes" on item 2 of the face sheet of the application indicating that your proposal is in response to this announcement and print "Mechanisms of Cell Death." In assigning applications to NIA or other Institutes, accepted referral guidelines will be followed. Mail the completed application (with 6 copies) to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, Maryland 20892** Receipt dates for Research Grant, Program Project Grant, Research Career Development Award and First Award applications are February 1, June 1, and October 1; those for Institutional Training Grant and Fellowship applications are January 10, May 10, and September 10. Depending on your particular research interests, correspondence and inquiries should be directed to: Basic mechanisms of cell death Huber Warner, Ph.D. Molecular Biology Program Administrator Biomedical Research and Clinical Medicine Building 31, Room 5C21 National Institute on Aging Bethesda, Maryland 20892 Telephone: (301) 496-6402 Vol. 18, No. 19, June 2, 1989 - Page 9 Role of cell death in age-associated diseases Evan Hadley, M.D. Chief, Geriatrics Branch Biomedical Research and Clinical Medicine Building 31, Room 5C27 Bethesda, Maryland 20892 Telephone: (301) 496-6761 Cell death in the aging nervous system Creighton Phelps, Ph.D. Neuroplasticity Program Administrator Neuroscience and Neuropsychology of Aging Building 31, Room 5C32 National Institute on Aging Bethesda, Maryland 20892 Telephone: (301) 496-9350 THE AGING OF RETARDED ADULTS P.T. 34; K.W. 0710010, 0715130 National Institute on Aging INTRODUCTION The National Institute on Aging (NIA) seeks research applications focused on retarded adults as they grow old. This announcement responds to U.S. Senate Appropriations Report language (Rpt. 100-399) for Fiscal Year 1989 that the NIA should consider conducting studies in the area of social gerontological aspects of aging and mental retardation, as well as the biological and psychological aspects of the aging process among individuals with mental retardation and related conditions. The announcement is part of the broad program of the Institute which was established by law for the "conduct and support of biomedical, social, and behavioral research and training related to the aging process and the diseases and other special problems and needs of the aged." It supplements NIA's broad announcement on HEALTH AND EFFECTIVE FUNCTIONING IN THE MIDDLE AND LATER YEARS. (See NIH GUIDE FOR GRANTS AND CONTRACTS, VOL. 12, NO. 6, JUNE 17, 1983.) It is issued by the Behavioral and Social Research Program in collaboration with the other NIA programs on Neuroscience and Neuropsychology of Aging and on Biomedical Research and Clinical Medicine. BACKGROUND Little is known about retarded adults as they grow older. The problem has become acute as the size of the older retarded population has increased, in part as a result of improved intervention and care. In future years the problem will become still more severe as the aging of the baby boom cohort increases the number of retarded adults whose parents, or other primary caretakers, are themselves old. Research on these adults and their caretakers is incomplete in several ways. It has been hampered by changing definitions of retardation. Moreover, it has relied too heavily on cross-sectional research, a strategy that provides useful data but that compounds the interpretative difficulties brought on by the different definitions of retardation and different medical and social conditions prevailing at different time periods. Useful background reading can be found in Janicki, M.P. & Wisniewski, H.M. (Eds.) (1985). Aging and Developmental Disabilities. Baltimore, Paul H. Brookes, and in Seltzer, M.M. & Krauss, M.W. (1987). Aging and Mental Retardation: Extending the Continuum. Washington: American Association on Mental Retardation. SPECIFIC OBJECTIVES Applications are sought that examine the nature and needs of the middle-aged and older retarded population. Sample topics are described below. However, applications on other related topics are also encouraged. 1. Demographic and Epidemiological Research Data on the characteristics of this population have been plagued by problems created by the changing definition of retardation and by the suspected existence of many retarded adults, living with the help of family members, who are unknown to service agencies. These problems make forecasting the size and future composition of this population hazardous. New analyses of existing Vol. 18, No. 19, June 2, 1989 - Page 10 data bases are needed; in addition, new data are needed that use a consistent definition of retardation and that incorporate effective procedures for sampling retarded adults unknown to service agencies. Illustrative research topics include: o analyses of chronic diseases and co-morbidities o research that yields projections of life expectancy for retarded adults, with and without surviving parents o adaptations of such instruments as Activities of Daily Living and Instrumental Activities of Daily Living questionnaires; assessments of projections of functional ability based on these measures o demography of surviving older people with developmental disabilities other than retardation 2. Adaptive Functioning in Older Retarded Adults Existing standardized tests of intellectual functioning often are inadequate to assess people who are retarded. The nature of particular syndromes, experience, and the existence of informal support networks allow considerable independence of function for which these tests cannot compensate. Such tests are also unlikely to capture changes in competence as people age, as they cope with illness, or as informal supports change. Approaches are needed, therefore, that test older retarded adults in everyday tasks and relate their competence to psychomotor and to cognitive abilities, as well as to existing social and physical aids. For mildly retarded adults who live independently, little is known about how job history, friendships, and social activities alter adaptive functioning as these adults age. Research is needed to track such patterns of activity and to understand how changes in activities affect these retarded adults. Some illustrative topics include: o To what extent do differences in functioning among different-aged older retarded adults reflect the effects of experience and of setting versus the effects of age? o What accounts for the wide variation in adaptive functioning achieved by adults with similar degrees of retardation? Do these individual differences remain stable in the later adult years? o Do older retarded men and women differ substantially in patterns of development and decline? 3. Social Interactions and Family Support Little is known about how the aging of parents and other caregivers of retarded adults affects both the parents themselves and also the retarded adult. Among the likely events in a middle-aged and older retarded individual's life are: transition from parent as caregiver to some other source of care; death of a parent; and change in residence with resulting change in social support and social relations. Research is needed to explore the effects of such changes on these adults and their caregivers. Among mildly retarded individuals, the impact of such life events as death of a spouse or retirement needs particular study. Do the effects of these transitions on mildly retarded adults mirror their effects on the general population? Examples of research include: o What are the factors that predict an orderly and smooth transition from parental care to some other support system? o Do changes in the characteristics of the family support system predict more accurately the need for social services in later adulthood than do changes in the characteristics of the retarded adult? o How do retarded adults' feelings of control, perceptions of changes in competence, and overall assessment of quality of life change as they incur transitions in later life? o What is the role of siblings in providing care and social support for older retarded adults? Vol. 18, No. 19, June 2, 1989 - Page 11 o What beliefs do other adults hold about older retarded people? How do these beliefs affect, or how are they affected by, interactions with older retarded adults? 4. Intervention Strategies Research is needed on interventions to increase the skills mastered by older retarded adults, to foster maintenance of skills, and to decrease dependence on institutional or organizational support. Behavioral interventions (such as training) and environmental interventions (such as altering the accessibility of staff support) might be evaluated for their ability to improve functioning. Technological interventions (e.g., equipment to aid performance or to improve health) and pharmacological interventions can also be investigated to determine whether they improve independent functioning and the quality of life of both older retarded adults and their caretakers. Sample topics include: o Can older retarded adults who live at home learn to manage some of the tasks once assumed by aging parents? o Can the competencies displayed by institutionalized retarded adults be enhanced by changes in setting or by changes in patterns of structured interaction? o How can the burden of care of aging parents of retarded adults be reduced by technological interventions? o How do older and younger retarded adults with the same etiology vary in responsiveness to particular pharmacological and behavioral interventions? 5. Service and Care Research Research is needed on, for example, the problems of matching service and care to aging retarded adults; or, the economics of different service and care solutions. Both the kinds of care necessary (e.g., respite care for aging caretakers, part-time institutional care) and the quality of care, as assessed by its effect on retarded adults and older familial caretakers, need to be addressed. Research is also needed on what services older retarded adults have used in the past. Such research can identify the most frequent causes of service use in early and later adulthood and can identify consequences of the use of services on particular individuals. Some possible research questions include: o What are the advantages and disadvantages of age integrated versus age separated, and ability integrated versus ability separated facilities? o How does respite care affect the quality of relations between older retarded adults and their family caretakers? o How do the economics of different care solutions (e.g., institutional, home support) vary with changing numbers and geographical distribution of the aging retarded population? o What factors predict successful entry of older retarded adults into recreation programs designed for seniors? METHODOLOGY The topics covered by this announcement are diverse and require varied methodological approaches. Nevertheless, research with a cohort-longitudinal component is especially sought. Most current research on older retarded adults is cross-sectional. Adults born in one time period (with particular definitional criteria and institutional practices) are compared against other adults born at other times with very different practices. Studies could trace different cohorts of retarded adults for an extended time. Only by such investigation can intra-individual changes in functioning be differentiated from differences between people of different ages that might reflect cultural change rather than true age-related change. NIA also urges applicants to give added attention to the inclusion of women, as well as men, and minorities in study populations. Investigators are Vol. 18, No. 19, June 2, 1989 - Page 12 reminded that merely including quotas of such participants in a given study is insufficient to guarantee generalization of results. APPLICATION AND REVIEW PROCEDURES Research project grant (RO1, R29) applications, individual fellowships (F32, F33), and research career development awards (KO4) will be reviewed for scientific and technical merit by an appropriate study section in the Division of Research Grants. Other applications will be reviewed by an appropriate institute review group. Secondary review will be by the National Advisory Council of the relevant Institute. Applications assigned to NIA compete on the basis of scientific merit with all other applications assigned to the Institute. The review criteria are the traditional considerations underlying scientific merit. Researchers considering an application in response to this announcement are encouraged to discuss their project, and the range of grant mechanisms available, with NIA staff prior to formal submission. Applicants should use the regular research project grant application form (PHS 398 Rev. 10/88) for RO1, R29, PO1, T32 and KO4 applications, and the PHS 416-1 (Rev. 7/88) form for F32 and F33 applications. These forms are available at the applicant's institutional Application Control Office or from the Office of Grants Inquiries, Division of Research grants, NIH (see address below). In order to expedite the application form's routing within NIH, please check "yes" on item number 2 on the face sheet of the application indicating that your proposal is in response to this announcement and print THE AGING OF RETARDED ADULTS. Mail the completed application (with 6 copies) to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, Maryland 20892** Telephone: (301) 496-7441 Receipt dates for the Research Project Grant, the Research Program Project Grant, Research Career Development Awards, and the First Independent Research Support and Transition Award applications are February 1, June 1, and October 1; those for the National Research Service Awards applications are January 10, May 10, and September 10. Correspondence and inquiries (please indicate Aging of Retarded Adults in your inquiry) should be directed to staff at: Dr. Robyn Barr Behavioral and Social Research National Institute on Aging Building 31C, Room 5C32 Bethesda, Maryland 20892 Telephone: (301) 496-3136 This program is described in the Catalog of Federal Domestic Assistance No. 13.866, Aging Research. Awards will be made under the authority of the Public Health Service Act, Title III, Section 301 (Public Law 78-410, as amended; 42 USC 241) and administered under PHS grant policies and Federal Regulations 42 CFR Part 52 and 45 CFR Part 74. This program is not subject to Health Systems Agency review. **THE MAILING ADDRESS GIVEN FOR SENDING APPLICATIONS TO THE DIVISION OF RESEARCH GRANTS OR CONTACTING PROGRAM STAFF IN THE WESTWOOD BUILDING IS THE CENTRAL MAILING ADDRESS FOR THE NATIONAL INSTITUTES OF HEALTH. APPLICANTS WHO USE EXPRESS MAIL OR A COURIER SERVICE ARE ADVISED TO FOLLOW THE CARRIER'S REQUIREMENTS FOR SHOWING A STREET ADDRESS. THE ADDRESS FOR THE WESTWOOD BUILDING IS: 5333 Westbard Avenue Bethesda, Maryland 20816 Vol. 18, No. 19, June 2, 1989 - Page 13 FULL TEXT OF RFAs FOR ONLINE ACCESS MINORITY-BASED COMMUNITY CLINICAL ONCOLOGY PROGRAM RFA AVAILABLE: 89-CA-06 P.T. 34, FF; K.W. 0785140, 0785035, 0404004, 0795003 National Cancer Institute Letter of Intent Receipt Date: July 14, 1989 Application Receipt Date: October 13, 1989 INTRODUCTION The Division of Cancer Prevention and Control (DCPC), National Cancer Institute (NCI), is interested in establishing a cancer control effort which involves practicing oncologists who serve large minority populations in the NCI clinical trials program. DCPC invites applications from domestic institutions with greater than 50% of new cancer patients from minority populations for cooperative agreements in response to this Minority-Based Community Clinical Oncology Program (Minority-Based CCOP) Request for Applications (RFA). The NCI clinical trials network provides support for clinical research in cancer centers, major university centers, and community programs. The purpose of this program is to utilize as a national resource those physicians involved in the care of minority cancer patients who are available for treatment and cancer control clinical trials research. The linkage of minority cancer patients to the current clinical trials network will facilitate the transfer of new technology in treatment and cancer control practices to minority communities and their physicians. The Minority-Based CCOP should: 1) provide support for expanding clinical research in minority community settings; 2) bring the advantages of state-of-the-art treatment and cancer control research to minority individuals in their own communities by having practicing physicians and their patients/subjects participate in treatment and cancer control research protocols; 3) increase the involvement of primary health care providers and other specialists in cancer control studies; 4) establish an operational base for extending cancer control, and reducing cancer incidence, morbidity, and mortality in minority populations by accelerating the transfer of newly developed cancer prevention, detection, treatment, rehabilitation, and continuing care technology to widespread community application; and 5) examine selected issues in Minority-Based CCOP performance (e.g., patient recruitment, accrual, eligibility) and evaluate its impact in the community. BACKGROUND INFORMATION Overall, survival rates from cancer in minority populations are less than in whites. For example, data from the Surveillance, Epidemiology, and End Results (SEER) Program, NCI, show that the five-year relative survival rate (1975- 1984) for all cancer sites in blacks is 39.6% compared to 51.3% for whites. Site-specific survival rates of black patients with breast, rectum, corpus uteri, and bladder cancers are lower than those for whites by 12%, 12%, 30%, and 22%, respectively. In addition to poorer survival outcomes, cancer incidence and mortality rates for selected cancer sites in minority populations are higher compared to whites. One way to develop and implement effective treatment and cancer control strategies in minority populations, and thereby reduce disparities in cancer incidence, morbidity, and survival rates between whites and minority populations, is to provide broader access to clinical research and greater involvement of minority populations in the clinical trials process. NCI's clinical trials network has evolved over the past 30 years. The major NCI program initiatives supporting this network are the Clinical Cooperative Group Program, the Cancer Centers Program, the Cooperative Group Outreach Program, and the Community Clinical Oncology Program (CCOP). Treatment and cancer control clinical trials research funded through these programs provides patients and their physicians with access to state-of-the-art cancer care management opportunities, and provides oncologists with a source of continuing education on innovations in cancer therapy, diagnostic techniques, and treatment applications. One of the major efforts of NCI has been to design and implement program interventions to assure that patients treated in their own communities have access to the same quality of cancer care and the same technological advances available to patients treated in major centers. The CCOP, which was first initiated in 1983, has proven to be a successful model for bringing the benefits of clinical research to cancer patients in their communities by providing support for community physicians to enter patients on treatment research protocols. In addition to increasing patient accrual to treatment clinical trials, the CCOP stimulated many communities to organize their cancer activities and expedited the development of a local-regional cancer program. Increased numbers of physicians, hospitals, and other health care professionals became involved in CCOP, and quality control standards of the cooperative groups were maintained. In 1987 the CCOP expanded the cancer control effort to include support for research in prevention, health promotion, smoking cessation, chemoprevention, treatment applications, continuing care and rehabilitation. With the development and implementation of cancer control research through the clinical trials network, opportunities exist for the implementation of effective preventive strategies for reducing cancer incidence, morbidity and mortality. In general, there is limited participation in clinical trials research by black, Hispanic, Asian-American, Native- American, and other minority cancer patients. Traditionally, institutions and physicians with access to large minority populations have not been involved in cancer research, and few minority cancer patients and their physicians are impacted by research currently funded through the clinical trials network. During the first phase of CCOP, a patient log record-keeping system on all new cancer patients seen by participating physicians, and for whom protocols were available, showed that seven percent (7%) of CCOP patients were minorities. This compares to 13% minority representation in SEER and 20% in the general U.S. population. A similar ethnic profile of minority patient participation in clinical trials is seen during the second phase of the CCOP. However data from the patient log showed that when access to clinical trials through CCOPs was provided, the proportion of minority patients with protocols available, and who are judged to be clinically eligible and entered on protocol, is similar to that of white patients. These findings suggest that a major factor influencing participation in clinical research by minority patients is access to the clinical trials process. Large numbers of minority cancer patients and populations at risk for cancer are available for participation in clinical trials in community, urban, and university settings. A cadre of university-trained oncologists is involved in treating minority cancer patients in these locations. In some urban settings large municipal hospitals serve for all practical purposes as the community hospital for minority cancer patients. The CCOP model is an effective mechanism for facilitating the linkage of investigators and their institutions with the clinical trials network. The Minority- Based CCOP RFA differs from the currently funded Community Clinical Oncology Program in that applications will be accepted from hospitals that are major teaching institutions for universities, providing they meet the eligibility criteria in ELIGIBILITY REQUIREMENTS. Through this initiative, DCPC aims to meet a need of minority cancer patients and individuals at risk for cancer by establishing a system of oncology programs for participation in clinical research trials through the NCI network. RESEARCH GOALS AND SCOPE The Minority-Based CCOP initiative is designed to: o bring the advantages of state-of-the-art treatment and cancer control research to minority individuals in their own communities by having practicing physicians and their patients/subjects participate in clinical treatment and cancer control research protocols; o provide a basis for involving a wider segment of the community in clinical research by increasing the involvement of primary health care providers and other specialists (e.g., surgeons, urologists, gynecologists) with the Minority-Based CCOP investigators in treatment and cancer control research, thus providing an opportunity for education and exchange of information; o provide an operational base for extending cancer control, and reducing cancer incidence, morbidity, and mortality in minority populations by accelerating the transfer of newly developed cancer prevention, detection, treatment, and continuing care technology to widespread community application; o facilitate wider community participation in future treatment and cancer control research approved by NCI; and o examine selected issues in Minority-Based CCOP performance (e.g., patient recruitment, accrual, eligibility) and evaluate its impact in the community. The Minority-Based CCOP will be developed and supported by DCPC, NCI. Participating programs will be required to enter patients/subjects onto NCI-approved clinical trials through research bases with which the Minority-Based CCOP is affiliated. Consideration will also be given for patients referred to cancer centers and entered onto NCI-approved treatment protocols. Minority-Based CCOPs may relate directly to NCI for assistance and participation in selected cancer control protocols. Research bases approved for CCOP participation will provide clinical research treatment and cancer control protocols to Minority-Based CCOPs. Research bases will be expected to monitor the quality of protocol conduct, follow Minority- Based CCOP accrual, and participate in the performance evaluation of affiliated programs. Participating programs may affiliate with a maximum of one national multi-disease clinical trials cooperative group (research base) having a spectrum of treatment and cancer control clinical trial protocols available, and a maximum of four additional research bases. Research bases may be national or regional multi-disease cooperative groups, specialized cooperative groups, cancer centers, or a public health department currently participating in NCI-approved clinical research protocols and approved as a CCOP research base (See PREPARATION OF APPLICATIONS, Currently Funded Research Bases). Eligible patients in a single disease category should be allocated to one protocol in the case where multiple affiliations have resulted in overlapping protocols. Intervention research in cancer control may include such areas as prevention, early detection, smoking cessation, treatment applications, continuing care and rehabilitation. Minority-Based CCOP applicants must demonstrate the potential for accessing appropriate cancer patients/subjects within their communities for participation in cancer control protocols provided by their research bases. The recruitment and accrual of minority patients from different community health care settings will be evaluated during the course of the program in order to assess the conditions and models which promote minority patient accrual onto clinical research trials. MECHANISM OF SUPPORT Support of this program will be through the Cooperative Agreement. The Cooperative Agreement is an assistance mechanism in which substantial NCI programmatic involvement with the recipient during performance of the planned activity is anticipated. The nature of NCI staff involvement is described in TERMS OF COOPERATION. Applicants will be responsible for the planning, direction, and execution of the proposed project. Except as otherwise stated in this RFA, awards will be administered under PHS grants policy as stated in the Public Health Service Grants Policy Statement, DHHS Publication No. (OASH) 82-50,000, revised January 1, 1987. NCI has determined that there is a continuing program need for minority participation in clinical cancer research. It is expected that, if funds are available, an announcement of the annual receipt date for applications in response to this RFA will be published in the NIH Guide for Grants and Contracts in 1990 and 1991. It is anticipated that up to $1.2 million in total costs per year will be committed to specifically fund applications which are submitted in response to this RFA. It is anticipated that up to eight (8) awards will be made. This is dependent on the receipt of a sufficient number of applications of high scientific merit. The total project period for applications submitted in response to this RFA may not exceed three (3) years. The earliest feasible start date for the initial awards will be June 1, 1990. NCI program staff will take into account demographic and geographic distributions of peer-reviewed and approved Minority-Based CCOPs in the final funding selection process. Multiple Minority-Based CCOP applicants approved for funding but who are competing for the same patient population will be considered, but all may not be awarded unless warranted by the population density. Although this program is provided for in the financial plans of NCI, the issuance of awards pursuant to this RFA is also contingent upon the availability of funds for this purpose. Awards for research bases affiliated with Minority-Based CCOPs will be through Cooperative Agreements under the Community Clinical Oncology Program RFA NO. 89-CA-13. TERMS OF COOPERATION Under the Cooperative Agreement, a partnership will exist between the recipient of the award and NCI, with assistance from NCI in carrying out the planned activity. This assistance will include: clarification of Minority-Based CCOP requirements; review of accrual to clinical trials; monitoring of community efforts to increase minority participation in clinical research; participation in protocol review; and discussions on the continuing needs of the program for enhancing Minority-Based CCOP performance. The following terms and conditions pertaining to the scope and nature of the interaction between NCI and the investigators will be incorporated in the Notice of Award. These terms will be in addition to the customary programmatic and financial negotiations which occur in the administration of cooperative agreements. The "TERMS OF COOPERATION: Nature of NCI Staff Involvement" described in this section are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines; DHHS grant administration regulations 45 CFR 74; other DHHS, PHS, and NIH grant administration policy statements; and other NCI administrative terms of award. 1 Nature of NCI Staff Involvement All research base protocols utilized by the Minority-Based CCOPs must be reviewed and approved for CCOP use by the Cancer Control Protocol Review Committee (CCPRC), Division of Cancer Prevention and Control (DCPC) and/or the Protocol Review Committee (PRC), Division of Cancer Treatment (DCT), NCI, prior to implementation. NCI will not provide investigational drugs, permit expenditure of NCI funds, or allow accrual credit for a protocol that has not been approved, or that has been closed to patient/subject accrual (except for patients already on study). Monitoring There will be periodic on-site monitoring (auditing) of each Minority-Based CCOP by NCI staff, representatives of its research base(s), or an NCI-designee, such as DCT's current Clinical Trials Monitoring Service contractor. Such on-site visits may include monitoring the following: use of investigational drugs; compliance with regulations for Institutional Review Board (IRB) approval and informed consent (compliance with 45 CFR 46); compliance with protocol specifications; quality control and accuracy of data recording; completeness of reporting adverse drug reactions; protocol accrual; fiscal and administrative procedures. Reports of such site visits will be reviewed by the Quality Assurance and Compliance Section (QACS), Regulatory Affairs Branch (RAB), Cancer Therapy Evaluation Program (CTEP), DCT, and by the DCPC program director. Data Management The DCPC program director will have access to all data generated under this award and will periodically review the data management procedures of the Minority-Based CCOPs. Data must also be available for external monitoring, if required by NCI's agreement with other federal agencies, such as the Food and Drug Administration (FDA). Organizational Changes Certain Minority-Based CCOP organizational changes must have the prior written approval of the DCPC program director. These changes include the addition/deletion of a participating physician, affiliate, component, or research base. A change in the principal investigator, or in any key personnel identified on the "Notice of Award," must have the prior written approval of the NCI Grants Management specialist, with the advice of the DCPC program director. Investigational Drug Management The Drug Management and Authorization Section, Investigational Drug Branch (IDB), CTEP, DCT/Chemoprevention Branch (CB), DCPC, will advise investigators of specific requirements and changes in requirements about investigational drug management that the FDA and NCI may mandate, either directly or through the research bases. Program Review Annual progress reports must be submitted to DCPC. A suggested format developed by the DCPC program director for this purpose will be provided. The DCPC program director will review the progress of each Minority-Based CCOP through consideration of the Minority-Based CCOP annual report, program site visits, patient log, and reports from affiliated research base(s). This review may include, but not be limited to, overall accrual credits, number of new cancer patients available to the participating Minority-Based CCOP physicians and the percentage of new cancer patients from minority populations placed on study, eligibility and evaluability of individuals entered on study, and timeliness and quality of data reporting. The Minority-Based CCOP's performance in accruing cancer patients from minority populations will be assessed. The inability of a Minority- Based CCOP to meet the performance requirements set forth in the TERMS OF COOPERATION in the RFA, or significant changes in the level of performance, may result in an adjustment of funding, withholding of support, suspension or termination of the award. Strategy Sessions The DCPC program director will sponsor strategy sessions as needed to review the status, progress, and evolving needs of the Minority-Based CCOP. These meetings may include discussions of overall CCOP performance, minority cancer patient recruitment and retention in clinical research trials, barriers to effective treatment and cancer control implementation, and scientific research required to address specific issues in minority populations. The DCPC program director will assist the Minority-Based CCOP investigators in exploring mutual interests in cancer control research and in establishing and prioritizing goals for evolving cancer programs. Federally Mandated Regulatory Requirements The DCPC program director/DCT representative will review mechanisms established by each Minority-Based CCOP to meet the Department of Health and Human Service (DHHS)/Public Health Service (PHS) regulations for the protection of human subjects and FDA requirements for the conduct of research using investigational agents. At a minimum, these include: o methods for assuring that each institution at which Minority-Based CCOP investigators are conducting clinical trials has a current, approved assurance on file with the Office for Protection from Research Risks (OPRR); that each protocol is reviewed by the responsible IRB prior to patient entry; and that each protocol is reviewed annually by the IRB so long as the protocol is active; o methods for assuring or documenting that each patient (or patient's parent/legal guardian) gives fully informed consent to participation in a research protocol prior to the initiation of the experimental intervention; o a system for assuring timely reporting of all serious and unexpected toxicities to the IDB, CTEP, DCT, according to DCT guidelines and/or to DCPC according to DCPC guidelines; and o implementation of DCPC/DCT requirements for storage and accounting for investigational agents provided under DCPC/DCT sponsorship. Arbitration Process The TERMS OF COOPERATION require that the NCI program director make post-award administrative decisions related to program performance, adjustments in funding, etc. NCI will establish an arbitration process when a mutually acceptable agreement cannot be obtained between the awardee and NCI staff. An arbitration panel (with appropriate expertise) composed of one member of the recipient group, one NCI nominee, and a third member chosen by the other two will be formed to review the NCI decision and recommend a course of action to the Director, DCPC. These special arbitration procedures in no way affect the awardee's right to appeal an adverse action in accordance with PHS regulations 42 CFR Part 50, Subpart D, and DHHS regulations 45 CFR Part 16. 2 Responsibilities of Awardees Accrual Patient accrual to clinical trials is expected to be reflective of the new cancer patient distribution of the participating physicians, that is, greater than 50% of new cancer patients from minority populations. Each Minority-Based CCOP is expected to accrue a minimum of 50 credits* per year in treatment clinical trials that are approved by the PRC, DCT, NCI. (For applicants whose specialty is pediatrics, the 50 credit minimum requirement may be waived for those applicants who are able to place a majority of their eligible patients on protocols.) A Minority-Based CCOP will receive accrual credit for a patient that is referred to a cancer center and placed on an NCI- approved treatment protocol. As one measure of performance, it is expected that at least 10 percent of all new cancer patients for whom protocols are available will be placed on study by Minority-Based CCOP physicians. Each Minority-Based CCOP is expected to accrue a minimum of 20 credits* per year to cancer control protocols that have been approved by the CCPRC, DCPC and/or the PRC, DCT, NCI. * Credits will be based on the complexity of the intervention, the amount of data management required, and the duration of follow-up. For example, each patient accrued to an average Phase II or Phase III protocol will count 1 credit; an NCI-designated high-priority protocol 1.5 credits; and a childhood acute lymphocytic leukemia protocol 2 credits. Cancer control protocols will be assessed for credit using a similar approach. Credit will be assigned following final approval of the protocol. Protocols Research bases are responsible for the development and implementation of high quality treatment and/or cancer control research clinical trials, as applicable, and for evaluation of the results of such studies. To be eligible to receive credit for accrual to a research base protocol, the Minority-Based CCOP must have an affiliation agreement with the research base responsible to NCI for that protocol. All research base protocols utilized by Minority-Based CCOPs must have been reviewed and approved for CCOP use by the CCPRC, DCPC and/or the PRC, DCT, NCI, prior to implementation. NCI will not provide investigational drugs, permit expenditure of NCI funds, or allow accrual credit for a protocol that has not been approved, or that has been closed to patient/subject accrual (except for patients already on study). Research Base Affiliation(s) Each Minority-Based CCOP may affiliate with up to five (5) eligible research bases, only one of which may be a national multi-specialty cooperative group. For a list of currently funded research bases, see PREPARATION OF APPLICATIONS, Currently Funded Research Bases. If participation in the protocols of one group competes with that of another group with which the Minority-Based CCOP is affiliated (e.g., two adjuvant protocols for the same eligible Stage II node positive patient), the Minority-Based CCOP must prioritize the protocols in order to avoid bias in the allocation of patients to competing protocols. Initial affiliations should be maintained during the funding cycle. When circumstances require changes in research base affiliations, prior written approval from the DCPC program director is required. Quality Control The Minority-Based CCOP will follow the procedures required by each of its research bases and the QACS, RAB, CTEP, DCT/DCPC program director. Data Management The Minority-Based CCOP will provide the DCPC program director with access to all data generated under this award for periodic review of its data management procedures. Data must also be available for external monitoring by NCI's agreement with other federal agencies, such as the FDA. Network Participation Minority-Based CCOPs are part of a national network for conducting treatment and cancer control clinical trials. As such, each Minority-Based CCOP is expected to participate in strategy sessions or workshops and in the continuing evaluation of the Minority-Based CCOP and its impact in the community. Patient Log Each Minority-Based CCOP agrees to maintain a new patient log or minimal registry to include age, sex, race, primary site of cancer, stage of disease, and treatment disposition for the potentially eligible patient pool (patients with a protocol available for site and stage) seen by the Minority- Based CCOP investigators. Monitoring Each Minority-Based CCOP agrees to periodic on-site monitoring (auditing) of its program by representatives of its research base(s), NCI, or an NCI-designee, such as DCT's Clinical Trials Monitoring Service contractor. Such on-site visits may include, but not be limited to, monitoring the following: accrual of patients to protocols including the accessioning of minority patients to clinical trials; use of investigational drugs; compliance with regulations for IRB approval and informed consent (compliance with 45 CFR 46); compliance with protocol specifications; quality control and accuracy of data recording; completeness of reporting adverse drug reactions; and fiscal and administrative procedures. Radiotherapy Equipment Radiotherapy equipment must have its calibration verified according to standards set by the Radiologic Physics Center (RPC) in order for institutions to participate in protocols requiring radiation therapy, as required by the affiliated research base(s). Investigational Drug Management Investigators performing trials under Cooperative Agreements will be expected, in cooperation with NCI, to comply with all FDA monitoring and reporting requirements for investigational agents. Reporting Requirements Annual progress reports must be submitted to DCPC. A suggested format provided by the DCPC program director for this purpose will be provided. The DCPC program director will review the progress of the Minority-Based CCOP through consideration of the Minority-Based CCOP annual report, program site visits, patient log, and reports from the affiliated research bases. This review may include, but not be limited to, overall accrual credits, the number of new cancer patients with protocols available and the number entered on clinical trials; the percentage of new cancer patients from minority populations with protocols available and the percentage placed on study; eligibility and evaluability of individuals entered on study; and the timeliness and quality of data reporting. The Minority-Based CCOP's performance in accruing cancer patients from minority populations will be assessed. The inability of a Minority- Based CCOP to meet the performance requirements set forth in the TERMS OF COOPERATION in the RFA, or significant changes in the level of performance, may result in an adjustment of funding, withholding of support, suspension or termination of the award. Audits Cooperative group research bases will be responsible for site visit monitoring (auditing) of affiliated Minority-Based CCOPs according to the established guidelines for monitoring its other members and/or affiliates. Cancer center research bases may initiate their own audit programs following guidelines established by the RAB, CTEP, DCT. Joint audits by representatives of more than one research base may be conducted. Minority-Based CCOPs are expected to participate in audits by their respective research base(s). Mutual collaboration between the Minority-Based CCOP and its research base will include, but not be limited to, a review of medical records, drug logs, and radiographic films and reports of patients entered on protocol. Results of CCOP audits will be reported to the QACS, RAB, DCT, CTEP, DCT, and the DCPC program director. Federally Mandated Regulatory Requirements Each Minority-Based CCOP must establish mechanisms to meet DHHS/PHS regulations for the protection of human subjects and FDA requirements for the conduct of research using investigational agents. At a minimum, these include: o methods for assuring that each institution at which Minority-Based CCOP investigators are conducting clinical trials has a current, approved assurance on file with OPRR; that each protocol is reviewed by the responsible IRB prior to patient entry; and that each protocol is reviewed annually by the IRB so long as the protocol is active; o methods for assuring or documenting that each patient (or patient's parent/legal guardian) gives fully informed consent to participation in a research protocol prior to the initiation of the experimental intervention; o a system for assuring timely reporting of all serious and unexpected toxicities to the IDB, CTEP, DCT, according to DCT guidelines and/or to DCPC according to DCPC guidelines; and o implementation of DCPC/DCT requirements for storage and accounting for investigational agents provided under DCPC/DCT sponsorship. Publications and Presentations Timely publication of major findings is encouraged. Publication or oral presentation of work done under this agreement requires acknowledgement of NCI support. ELIGIBILITY REQUIREMENTS Institutions, organizations and/or physician group applicants for the Minority-Based CCOP must have greater than 50% of new cancer patients from minority populations AND, as a group, the participating physicians listed in the application must have greater than 50% of new cancer patients from minority ethnic groups. The following eligibility requirements then apply. 1 An applicant may be a hospital, a clinic, a group of practicing physicians, a health maintenance organization (HMO), or a consortium of hospitals and/or clinics and/or physicians and/or HMOs, but a single administrative focus is required. 2 A university hospital that is the major teaching institution for that university AND which has greater than 50 percent of new cancer patients from minority populations is eligible to apply. 3 A military or Veterans Administration hospital may be included in an application as a nondominant member of a consortium led by a community institution. An unfunded nonuniversity clinical trials cooperative group member is eligible to apply. 4 Funded Cooperative Group Outreach Program (CGOP) participants are eligible to apply, but should state in the application that CGOP support will be relinquished if a Minority-Based CCOP award is received. 5 Funded Minority Satellite Supplement Program (MSSP) participants are eligible to apply, but should state in the application that MSSP support will be relinquished if a Minority-Based CCOP award is received. Institutions and organizations NOT eligible to apply as a Minority-Based CCOP are: 1 A comprehensive, consortial, or clinical cancer center holding an NCI Cancer Center Support (CORE) grant; 2 A university hospital clinical trials cooperative group member funded by DCT, NCI; and 3 Currently funded CCOPs. PREPARATION OF APPLICATIONS General instructions for the preparation of the cooperative agreement application are contained in the grant application form PHS-398 (revised 10/88). Because the TERMS OF COOPERATION will be included in all awards issued as a result of this RFA, it is critical that each applicant include specific plans for responding to these terms. Plans should describe how the applicant will comply with NCI staff involvement as well as how all the responsibilities of awardees will be fulfilled. Treatment Clinical Trials Each applicant must demonstrate access to a population with greater than 50% of new cancer patients from minority groups. Data from hospital registries, admission, discharge, clinic, and billing records may be utilized to document the minority new cancer patient population available to the applicant organization AND its physician participants. Each applicant must demonstrate the potential and stated commitment to accrue a minimum of 50 credits (see TERMS OF COOPERATION, Responsibilities of Awardees, Accrual) per year to approved clinical research treatment protocols from the research base(s) with which the community program is affiliated. (For applicants whose specialty is pediatrics, the 50 credit minimum requirement may be waived for those applicants who are able to place a majority of their eligible patients on protocol.) Applicants should document experience of participating physicians in treatment clinical research. Such experience may include involvement in clinical research sponsored by NCI, cancer centers, or drug companies. It may also include experience gained from residency, fellowships, postdoctoral training and/or subsequent practice. A list of treatment protocols (from research bases) in which the applicant expects to participate, and the projected accrual to each study should be provided. Cancer Control Studies Each applicant must demonstrate the potential and stated commitment to accrue patients/subjects to cancer control protocols. Each applicant is expected to accrue a minimum of 20 credits (see TERMS OF COOPERATION, Responsibilities of Awardees, Accrual) per year to NCI-approved cancer control research protocols. The applicant should describe experience in cancer control research and related activities (e.g., smoking cessation clinics, screening and early detection projects, tumor boards and conferences, hospice, home care programs). An applicant must describe its capabilities by responding to at least two examples of cancer control intervention protocols currently activated or planned by its affiliated research base(s) which are appropriate for its participation and implementation in community settings. The applicant's ability to access the appropriate physicians and patient/subject populations, and the facilities to participate in the proposed studies, should be described. Multidisciplinary Involvement Each applicant is expected to have a committed multidisciplinary professional group appropriate for its expected protocol participation. This team may include surgeons, radiation oncologists, medical oncologists, pathologists, oncology nurses, data managers, social workers, and other disciplines (e.g., gynecology, pediatrics, internal medicine, family practice) as appropriate. The training and experience of participating physicians should be provided, along with a description of working relationships. Any experience working together as a group, and particularly in implementing clinical treatment and cancer control research and related activities, should be included. An organizational chart showing how the group will function should also be included. Principal Investigator A designated principal investigator is required. An associate principal investigator should also be named to assure continuity in the event of resignation of the principal investigator. The qualifications and experience of both, in terms of ability to organize and manage a community oncology program that includes treatment and cancer control research and related activities, should be described. Patient Resources Each applicant must delineate its patient catchment area. A map of the service area, designating counties or zip codes from which approximately 80% of the patients will be drawn, should be provided. A description of other cancer care resources (i.e., hospitals, clinics, physicians, cancer centers) in the catchment area which are not part of the application should be included. A detailed demographic description, including a distribution of all new cancer patients (including minorities) available for participation in clinical research, should be provided. The applicant must clearly indicate the percentage of new cancer patients from minority populations available to institutions (i.e., hospitals) included in the application AND the percentage of new cancer patients from minority populations seen by the participating physicians included in the application. Organizational Structure Each applicant should describe its organizational structure and the relationship of the administrative unit and its proposed personnel to the participating physicians, institutions (e.g., hospitals, practices), and other affiliates. Information on how the program will be organized and directed to facilitate clinical cancer research should be described. A statement of commitment from each participating institution, organization, and physician should be provided, as appropriate. Data Management Plan The proposed data management plan should be described to include, but not be limited to, the procedures for identifying potential patients/subjects for study, the communication links between the applicant's administrative unit and participating physicians, the data collection and quality control procedures, and interactions with research base affiliates. Research Base Affiliations Through formal affiliations with a maximum of five (5) eligible research bases, only one of which may be a national multi-specialty cooperative group, the applicant must demonstrate access to both treatment and cancer control research protocols. Evidence must be provided that an affiliation has been established with an NCI-funded research base(s) for CCOPs which has the capacity to provide both treatment and cancer control protocols. In addition, affiliations with NCI-funded research bases offering only cancer control protocols (e.g., cancer centers or a public health department) are appropriate. The conditions of affiliation must be provided in the Minority-Based CCOP- research base affiliation agreement(s) submitted with the application. Initial affiliations should be maintained during the three-year funding cycle. Multiple research base affiliations are permitted provided they are not conflicting. The affiliation agreement must state specifically how the problem of competing protocols is to be resolved (see TERMS OF COOPERATION, Responsibilities of Awardees, Research Base Affiliation(s)). To be eligible to receive accrual credit for entry to an NCI- approved protocol, the Minority-Based CCOP must have an affiliation agreement with the research base responsible to NCI for that protocol. Currently Funded Research Bases National Multi-specialty Cooperative Groups: (Applicant may choose only one.) Cancer and Leukemia Group B (CALGB) Eastern Cooperative Oncology Group (ECOG) Southwest Oncology Group (SWOG) Other Cooperative Groups: Children's Cancer Study Group (CCSG) National Surgical Adjuvant Breast and Bowel Project (NSABP) North Central Cancer Treatment Group (NCCTG) Pediatric Oncology Group (POG) Radiation Therapy Oncology Group (RTOG) Cancer Centers and Public Health Department: Cancer Center/Wake Forest University (CC/WFU) Dana-Farber Cancer Institute (DFCI) Fox Chase Cancer Center (FCCC) Illinois Cancer Council (ICC) M.D. Anderson Cancer Center (MDACC) Memorial-Sloan Kettering Cancer Center (MSKCC) Minnesota State Health Department (MNSHD) Northern California Cancer Center (NCCC) University of Rochester Cancer Center (URCC) Research base awards will be recompeted in 1990 under the Community Clinical Oncology Program RFA NO. 89-CA-13. Following this recompetition, other NCI-funded cooperative groups, cancer centers, and public health departments may be eligible as research bases for Minority-Based CCOPs. Quality Control Quality control procedures should be described in detail. Assurance of quality is the joint responsibility of the Minority-Based CCOP and its research base(s). Quality control procedures of the research base will be applied to the Minority-Based CCOPs and should be specified in the Minority-Based CCOP-research base affiliation agreement. Administrative Facility The availability of facilities, including laboratories, inpatient and outpatient resources, cancer registries, etc. should be described. In addition, each applicant must have a defined space for administrative activities and administrative personnel which will serve as a focus for data management, quality control, and communication. Allowable Costs Allocation of funds to support community costs for receipt, handling, and quality control of patient data should be specified. Allowable items in the budget are requests for full or part-time administrative personnel, data managers, and study assistants; supplies and services directly related to study activities (e.g., processing and sending material for pathology review, processing and sending port films for radiation therapy quality control); and appropriate travel to meetings directly related to study activities (e.g., research base meetings, NCI-sponsored strategy sessions/workshops, local travel). Special personnel resource needs to support the recruitment and retention of eligible minority patients on clinical trials may be requested. Funding is not allowed for clinical care provided to patients. Physician compensation is allowable only for time spent on Minority- Based CCOP organizational/administrative tasks. Justification must be provided for personnel time and effort and funds requested. REVIEW PROCEDURES AND CRITERIA 1 Review Procedure Upon receipt, applications will be reviewed (initially) by the Division of Research Grants (DRG) for completeness. Incomplete applications will be returned to the applicant without further consideration. Evaluation for responsiveness to the program requirements and criteria stated in the RFA is the responsibility of the NCI program director. Applications which are judged non-responsive will be returned to the applicant. In cases where the number of applications is large compared to the number of awards to be made, the Division of Extramural Activities (DEA), NCI, may conduct a preliminary scientific peer review to eliminate those which are clearly not competitive for award. DCPC will remove from competition those applications judged to be noncompetitive and notify the applicant and institutional business official. Those applications judged to be both competitive and responsive will be further evaluated according to the review criteria stated below for scientific and technical merit by an appropriate peer review group convened by DEA, NCI. The second level of review by the National Cancer Advisory Board considers the special needs of the Institute and the priorities of the National Cancer Program. 2 Review Criteria o Ability to access through participating Minority-Based CCOP physicians a population with greater than 50% of new cancer patients from minorities. o Ability to accrue a minimum of 50 credits per year to treatment clinical trials (may be waived for applicants whose specialty is pediatrics, as stated in TERMS OF COOPERATION, Responsibilities of Awardees, Accrual). Experience in accruing to treatment clinical trials will be considered. o Potential to accrue a minimum of 20 credits per year to cancer control studies. Experience participating in cancer control activities (e.g., screening and detection projects, cancer education training programs, hospice, etc.) and research will be considered. Each applicant's ability to access the appropriate populations, professional disciplines, and facilities to participate with affiliated research bases in at least two currently approved or planned cancer control protocols from those research bases will be assessed. o Qualifications and experience of the principal investigator and associate principal investigator, related to his/her ability to organize and manage a community oncology program that includes treatment and cancer control research and related activities. o Training, experience, and commitment of participating physicians for accruing patients/subjects to protocols in which the applicant has agreed to participate. The work experience of proposed investigators (gained from residency, fellowships, postdoctoral training and/or subsequent practice) in the entry and treatment of cancer patients on research trials will be considered. Previous involvement by participating physicians and the applicant organization in cancer care management, clinical research, and related activities in minority populations will be assessed. o For multidisciplinary studies, evidence of the availability of appropriate professional resources (e.g., radiotherapy, pediatrics, surgery, gynecology, urology, pathology, nursing, social service, nutrition). Experience or special skills in cancer control studies will be considered, together with the availability of other community resources and personnel for such studies. o Qualifications and experience of all proposed support personnel relative to their position descriptions. The relevant credentials and expected contributions to the program of personnel resources not fiscally supported by the award will be considered. Unique resource needs and requirements to support the proposed organizational structure will be assessed. o The stability of the functional unit or group applying to become a Minority-Based CCOP. Pre-existing organizational affiliations of at least a core of the group applying and evidence of stable working relationships will be appraised. Examples of established consortium arrangements may be submitted. Evidence of previous success as a group in implementing treatment and cancer control activities in the community setting will be considered. o The adequacy of available facilities, including laboratories, inpatient and outpatient resources, cancer registries, etc., and the adequacy of space for administrative activities and personnel. Evidence of commitment to clinical research from participating institutions, organizations, and proposed investigators will be assessed. o The appropriateness of a specific research base affiliation and the treatment and cancer control protocols chosen from that research base. Affiliation agreements with research bases must be provided in the application. o The adequacy of quality assurance mechanisms for both treatment and cancer control interventions; and the adequacy of procedures for investigational drug monitoring and data management. The review group will critically examine the proposed budget and will recommend an appropriate budget and period of support for each approved application. Allowable items in the budget are requests for full or part- time administrative personnel, data managers, and study assistants; supplies and services directly related to study activities (e.g., processing and sending material for pathology review, processing and sending port films for radiation therapy quality control); and appropriate travel to meetings directly related to study activities (e.g., research base meetings, NCI-sponsored strategy sessions/workshops, local travel). Special personnel resource needs to support the recruitment and retention of eligible minority patients on clinical trials will be considered. Funding is not allowed for clinical care provided to patients. Physician compensation is allowable only for time spent on Minority- Based CCOP organizational/administrative tasks. Justification must be provided for personnel time and effort and funds requested. ADMINISTRATIVE REQUIREMENTS o Management of Federal Funds The basic requirements are: 1 A formal organizational structure capable of managing the project and safeguarding the disposition of Federal funds; 2 Adequate cost accounting and bookkeeping procedures, including the capacity to separately monitor Federal funds; 3 Time and effort policies to account for personnel costs; and 4 Accountability for all equipment, supplies, and other necessary project expenditures. o Mandated Assurances Information regarding these may be found in grant application form PHS-398 (revised 10/88) or by contacting the Grants Administration Branch official named in INQUIRIES: 1 Civil Rights 2 Handicapped Individuals 3 Sex Discrimination 4 Protection of Human Subjects If a CCOP application is selected for funding, assurances of compliance with 45 CFR 46 must be negotiated or renegotiated (in the case of existing assurances) prior to receipt of funds or involvement of human subjects. 5 Debarment and Suspension 6 Drug-Free Workplace 7 Misconduct in Science 8 Certification of Non-Delinquency on Federal Debt o Indirect Costs Unless directed otherwise, successful applicants who have not negotiated an indirect cost rate must do so. The negotiation of the indirect cost rate may begin just prior to, or immediately following receipt of the Award Notice. Guidance on this requirement will be made available from the Grants Administration Branch, NCI, upon selection of the application for funding. o Payment Procedures Payments for cooperative agreements awarded by NIH are made through the Payment Management System (PMS) of the Department of Health and Human Services. Guidance for receipt of payment will be provided by the NCI/PMS to successful applicants at the time of the award. LETTER OF INTENT Prospective applicants are asked to submit by July 14, 1989, a letter of intent that includes a descriptive title of the proposed research, the name and address of the principal investigator, the names of other key personnel, the participating institution(s), and the number and title of the RFA in response to which the application is being submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, NCI would like to emphasize the benefits to the applicant of having a principal investigator submit a letter of intent. First, it allows NCI staff to estimate the potential review workload and to avoid possible conflict of interest in the review. In addition, program staff, through subsequent contact, may be able to assist prospective applicants in clarifying scientific content and objectives of an application, size and focus of a research program, organization of an application, and appropriate use of consultants. Should it appear that the potential applicant has misunderstood the requirements and objectives of the RFA or opted for an inappropriate funding mechanism, NCI staff will be able to inform the applicant. The letter of intent should be sent to: Carrie P. Hunter, M.D. Program Director, CCOP, CORB, DCPC, NCI Executive Plaza North, Room 300-G Bethesda, Maryland 20892 (301) 496-8541 METHOD OF APPLYING The regular research grant application form PHS-398 (revised 10/88) must be used in applying for Cooperative Agreements. These forms are available at most institutional business offices; from the Office of Grant Inquiries, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, 5333 Westbard Avenue, Bethesda, Maryland 20892; or from the NCI program director named in LETTER OF INTENT. It is requested that some of the information be submitted in a tabular format. The suggested format will be sent to applicants submitting a letter of intent or may be obtained from the program director named in the LETTER OF INTENT section. Applications should be as concise as possible. The RFA label available in the 10/88 revision of Application Form 398 must be affixed to the bottom of the face page. Failure to use this label could result in delayed processing of your application such that it may not reach the review committee in time for review. The title of the RFA, "MINORITY-BASED COMMUNITY CLINICAL ONCOLOGY PROGRAM," and the RFA number, "89-CA-06," should be typed on line 2 of the face page of the application form. Submit a signed, typewritten original of the application, including the Checklist, and four (4) signed, exact photocopies of the application, in one package to the Division of Research Grants, NIH, at the address below. The photocopies must be clear and single sided. DIVISION OF RESEARCH GRANTS National Institutes of Health Westwood Building, Room 240 Bethesda, Maryland 20892** At the time of submission, send two (2) additional copies of the application to: REFERRAL OFFICER Division of Extramural Affairs National Cancer Institute Westwood Building, Room 848 5333 Westbard Avenue Bethesda, Maryland 20892 Applications must be received by October 13, 1989. If an application is received after that date, it will be returned. Also, DRG will not accept any application in response to this announcement that is the same as one currently being considered by any other review group or NIH awarding unit. INQUIRIES Written or telephone inquiries concerning the objectives and scope of this RFA or inquiries about whether or not specific proposed research would be responsive are encouraged and should be directed to Dr. Carrie P. Hunter at the address provided in LETTER OF INTENT. The program director welcomes the opportunity to clarify any issues or questions from potential applicants. Questions pertaining to business matters should be directed to: Ms. Eileen Natoli Grants Administration Branch Office of the Director, NCI Executive Plaza South, Room 243 Bethesda, Maryland 20892 (301) 496-7800 This program is described in the Catalog of Federal Domestic Assistance No. 13.399, Cancer Control. Awards are under authorization of the Public Health Service Act, Title IV, Part A (Section 301, Public Law 78-410, 42 USC 241, and Section 412, as amended by Public Law 99-158, 42 USC 285a-1) and administered under PHS grant policies and Federal Regulations 42 CFR Part 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. REQUEST FOR COOPERATIVE AGREEMENT APPLICATIONS: RFA-NIH-NIAID-89-AI-16 P.T. 34; K.W. 0715008, 0740075, 1002045, 0760080, 1002008, 0710030 NATIONAL COOPERATIVE VACCINE DEVELOPMENT GROUPS FOR THE ACQUIRED IMMUNODEFICIENCY SYNDROME NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES Letter of Intent Date: June 19, 1989 Application Date: August 10, 1989 The NIAID invites applications to establish additional National Cooperative Vaccine Development Groups for the Acquired Immunodeficiency Syndrome (NCVDG). This is a re- issuance of a previous request for applications (RFA 88-AI-06). There are no plans to reissue this Request for Applications at any future time. I. SUMMARY AND BACKGROUND The National Institutes of Health and other agencies in the Public Health Service are currently supporting extramural and intramural projects for the study of the etiology, natural history, and demographics of the Acquired Immunodeficiency Syndrome (AIDS); for the screening of high- risk individuals; for determining means of diminishing the risk of infection; and for the development of vaccines and other methods of prevention. Notwithstanding these efforts, the rapidity of the increase in diagnosed cases of AIDS and the morbidity from this disease require the mobilization of the most creative scientific talents -- regardless of their scientific discipline or organizational affiliations -- into groups whose objective is to pursue aggressively a concerted research effort to discover and develop vaccines for preventing AIDS. By February 1989, over 84,000 cases of AIDS had been reported in the United States and more than 48,000 of these patients had died. Recent surveillance studies indicate that the total number of AIDS cases is doubling every 12-14 months, with projections of approximately 140,000 to 200,000 cases by 1991. Recent projections indicate that 1,500,000 persons presently in the United States may already be infected with the Human Immunodeficiency Virus (HIV), the etiologic agent of AIDS. It has been estimated that all infected persons will progress to develop AIDS. The National Cooperative Vaccine Development Groups for the Acquired Immunodeficiency Syndrome (NCVDG) will provide assistance to talented scientists to interact, with NIAID support, as a unit to carry out the research essential to realize project objectives. An NCVDG should be composed of scientists from academic and/or non-profit research institutions, and commercial organizations. The NIAID has already awarded its first eleven NCVDGs and the purpose of this current initiative is to expand the network of NCVDGs aimed at facilitating and accelerating efforts in AIDS vaccine development. A listing of these active NCVDGs is available upon request. II. PURPOSE Many single institutions may not have either the critical mass of all of the talents or the ancillary resources needed to translate leads from basic studies into new entities and strategies for AIDS vaccine research. A funding arrangement that permits the combination of available research expertise from diverse institutions with the facilitating resources of the NIAID is desirable. Units, in which these research talents and resources are combined, are termed "NATIONAL COOPERATIVE VACCINE DEVELOPMENT GROUPS FOR THE ACQUIRED IMMUNODEFICIENCY SYNDROME" (NCVDG). They are envisioned as having the capacity to generate new approaches and strategies for the development of AIDS vaccines and to translate rapidly their concepts into improved candidate vaccines. The NCVDG can be focused in one or more vaccine areas and may pursue studies of HIV-based vaccines or studies of relevant model viruses (e.g., the Simian Immunodeficiency Viruses). The group must possess the expertise necessary to conduct adequate evaluation of the proposed approach(s) in preclinical situations. Further studies required for development of identified new vaccines to clinical trial may be a part of the work proposed by an applicant. Alternatively, an NCVDG may recommend that the NIAID conduct these developmental tasks using contracts now in place. III. MECHANISM OF SUPPORT A. Awards will be made as COOPERATIVE AGREEMENTS. Assistance via Cooperative Agreement differs from the research grant in that the Government component (NIAID) awarding the Cooperative Agreement anticipates substantial involvement during performance of the award. The NIAID will be represented by a Scientific Coordinator, who may provide appropriate assistance, advice, and guidance by: participating in the design of Group activities; advising in the selection of sources or resources; coordinating or participating in collection and\or analysis of data; advising in management and technical performance; or participating in the preparation of publications. However, the role of NIAID will be to facilitate and not to direct the activities. There is no intent, real or implied, for staff to direct Group activities or to limit the freedom of investigators. The interaction of academic and non-profit research institutions with commercial (including industrial) organizations and Government is expected to favor the efficient development of new entities and strategies for AIDS vaccines and will facilitate their subsequent development to clinical trial. B. NIAID has set aside $5 million in total costs for the initial year's funding; it is anticipated that 5 to 7 awards will be made, each averaging $500,000 to $750,000 in direct costs. In rare instances -- and with strong justification -- larger amounts (up to $1.5 million) may be requested. Awards will be made for a 5-year period. The earliest starting date for the initial annual period will be February 1, 1990. NIAID plans to invite applications for competitive renewal of cooperative agreements funded in this initiative. C. Awards will be made to successfully competing Groups, rather than to the individual scientists or institutions comprising the Group. Support of all Group activities will be coordinated through a Central Operations Office located within the applicant organization. Each award will be made only to the Principal Investigator's institution. D. All policies and requirements that govern the grant program of the U.S. Public Health Service (PHS), and the National Institutes of Health (NIH) apply. E. Although this program is provided for in the financial plans of NIAID, the award of Cooperative Agreements pursuant to this RFA is also contingent upon the continuing availability of funds for this purpose. IV. DEFINITIONS COOPERATIVE AGREEMENT - An assistance mechanism in which substantial NIAID programmatic involvement with the recipient organization, during the performance of the planned activity, is anticipated. NATIONAL COOPERATIVE VACCINE DEVELOPMENT GROUP (NCVDG) - In this RFA the terms NATIONAL COOPERATIVE VACCINE DEVELOPMENT GROUP, NCVDG, and "group" are synonymous. Each group may be composed of a relatively large number of investigators from academic and/or non-profit research institutions and scientists from commercial organizations who are performing research on various research projects. RESEARCH PROJECT - A discrete, specified, circumscribed project which must relate to the overall theme of the NCVDG. PROJECT LEADER - The leader of each of the scientific research projects of the NCVDG. PRINCIPAL INVESTIGATOR - The person who assembles the NCVDG, submits the single application in response to this RFA and who is responsible for the performance of the Group as a whole and each of the Project Leaders. The Principal Investigator will coordinate Group activities scientifically and administratively and also may lead one of the Research Projects of the Group. The Principal Investigator's institution establishes and operates the Central Operations Office that funds Group members and is legally and fiscally accountable for the disposition of funds awarded. NIAID SCIENTIFIC COORDINATOR - A member of the extramural staff of the NIAID who functions as a peer with the Principal Investigators and Project Leaders and facilitates the partnership relationship between NIAID and the Groups. INVENTION - A new vaccine that is or may be patentable under Title 35 of the United States Code. ARBITRATION PANEL - A group composed of the Principal Investigator or Project Leader of a particular NCVDG as the "group" designee, one NIAID designee, and a third designee with expertise in the relevant area and chosen by the other two. Such panels may help resolve both scientific and programmatic issues that develop during the course of work and restrict progress. V. COMPOSITION A. The composition of a NCVDG is envisioned as follows: 1. Principal Investigator; 2. Project Leaders, each heading a research project. The research projects will utilize diverse scientific disciplines that are appropriate to the realization of Group objectives (e.g. virology, humoral immunology, cellular immunology, biochemistry, structural chemistry, immunochemistry, veterinary pathology, expertise in good laboratory practices, large scale production processes). Each project should focus on a discrete research area and have sufficient merit to be able to stand on its own during peer review; and 3. A Scientific Coordinator designated from the NIAID extramural staff. B. The Principal Investigator, in addition to providing scientific and administrative leadership, may contribute a Research Project. Research Project Leaders will be directly responsible to the Principal Investigator. The formation of the Group, the application in response to this RFA, the overall management of the Group, and the allocation of funds to the various Research Projects will be the responsibility of the Principal Investigator and the Principal Investigator's institution in accordance with PHS policies. C. The constituency of the Group and its research Projects should depend on the talents required to accomplish its scientific and technical objectives as perceived by the Principal Investigator and Project Leaders. The major consideration in structuring an NCVDG should be the mobilization of maximum intellectual strength and the ability to carry out the proposed research. D. The varied talents and commitment required for an effective research program may not be present in a single institution. It is therefore anticipated that the component research projects and the respective Project Leaders within a Group will be derived from separate institutions, and their work will be coordinated by the parent institution through a consortium arrangement. However, more than one Project and Project Leader of an NCVDG might be derived from a single institution. E. A minimum of two but no maximum number of Research Projects per Group is stipulated. However, the Principal Investigator could experience difficulty in providing the desirable level of guidance and Project Leaders might communicate and collaborate less efficiently if the Group were to contain more than five or six research projects, including the Principal Investigator's project. It is therefore advisable to limit the Group to no more than six carefully selected integrated projects. F. In forming a Group, the potential Principal Investigator should remain cognizant of the need for communication, including regular meetings of the members. G. An NCVDG may consist of scientists (Research Projects) from academia, non-profit institutions, and commercial organizations. The active participation of industry is encouraged because it will allow this segment of the scientific community to contribute its intellectual and material resources. Further, the interaction of academic and non-profit research institutions with industry and Government will facilitate subsequent development and marketing of vaccines, although these latter activities are not within the scope of this RFA. VI. RESEARCH GOALS AND SCOPE A. The principal goal of the NATIONAL COOPERATIVE VACCINE DEVELOPMENT GROUPS FOR THE ACQUIRED IMMUNODEFICIENCY SYNDROME is the conceptualization, development, and evaluation of vaccines designed to effectively prevent the Acquired Immunodeficiency Syndrome. This research can focus on HIV or other retroviruses (e.g., the Simian Immunodeficiency Viruses) that are appropriate models for AIDS vaccine development and that may involve animal model studies of vaccine immunogenicity and efficacy. B. Applications for funding as an NCVDG should stress creative approaches to the development of effective AIDS vaccines and may emphasize one or more of the general approaches outlined below. Since the currently funded NCVDGs are also pursuing research in many of these areas, potential applicants are strongly encouraged to contact program staff to determine if their proposed studies address vaccine strategies not currently being funded. APPLICATIONS FOR RESEARCH ON NOVEL VACCINE VECTORS, IMMUNOGEN PROCESSING AND PRESENTATION, CREATIVE METHODS TO ENHANCE IMMUNOGENICITY, AND PASSIVE IMMUNIZATION ARE ENCOURAGED. 1. live attenuated vaccines; 2. whole inactivated vaccines; 3. recombinant proteins or protein fragments; 4. novel recombinant viruses or other vectors (e.g., yeast Ty elements, hepatitis B virus, bacteria); 5. synthetic peptides; 6. anti-idiotype vaccines; C. Applications should address all aspects of the process from any basic research proposed through the subsequent developmental studies, scale-up and production, evaluation in laboratory animals, protection of appropriate species from infection or disease following virulent challenge, and other considerations that relate to the acceptability and utility of candidate vaccines for clinical trials. VII. PATENT COVERAGE Inasmuch as the development of effective AIDS vaccines is the objective of this effort, and since active involvement by industrial laboratories is facilitated by the existence of adequate patent coverage, it is essential that applicants provide plans to assure such coverage. Since multiple institutions may be involved, the situation could be complicated. Each applicant Group must, therefore, provide a detailed description of the approach to be used for obtaining patent coverage and for licensing where appropriate, in particular where the invention may involve investigators from more than one institution. In addition, each Group must provide a detailed description of the procedures to be followed for the resolution of legal problems that may develop. Your attention is drawn to P.L. 96-517 as amended by P.L. 98-620 and instructions published by the Office of Management and Budget in the Federal Register (OMB Circular A-124), Volume 47, Number 34, Friday, February 19, 1982, pp. 7556-7566. Note that non-profit organizations (including universities) and small business firms retain the rights to any patent resulting from Government contracts, grants or Cooperative Agreements. Also a Presidential memorandum of February 18, 1983 extended to all business concerns, regardless of size, the first option to the ownership of rights to inventions as provided in P.L. 96-517. As a result of this memorandum, the relationships among industrial organizations and other participants are simplified, since all Group members can now be full partners in the research and in any inventions resulting therefrom. The specific patenting arrangements among the institutions may vary, and could include joint patent ownership, exclusive licensing arrangements, etc. Applicants are encouraged to develop an arrangement that is most suitable for their own particular circumstances. The proposed patent plan among the institutions comprising the Group must be subitted with the application. This patent agreement signed and dated by the organizational official authorized to enter into patent arrangements for each group member and member institution must be on file with the NIAID, prior to peer review. (See Section IX, "MINIMUM REQUIREMENTS FOR APPLICATION," Part C.) VIII. TERMS OF AWARD: NATURE OF PARTICIPATION OF NIAID STAFF Assistance via a Cooperative Agreement differs from the traditional research grant in that, in addition to the normal programmatic and administrative stewardship responsibilities, the component awarding the Cooperative Agreement anticipates substantial programmatic involvement during performance of the research program. However, the applying Group must define its objectives in accord with its own interests and perceptions of novel and exploitable approaches and must develop the detail of the research design following the guidance given in this RFA. It is the primary responsibility of the Principal Investigator to clearly state the objectives of the Group, to perform the research stipulated in the proposal and to ensure that the results obtained are published in a timely manner. NIAID shall work with the Group and shall be represented by a Scientific Coordinator. The coordinator shall be a member of the professional staff of the Vaccine Research and Development Branch, Acquired Immunodeficiency Syndrome Program, which is an extramural program of the NIAID. During performance of the award, the NIAID Scientific Coordinator may provide appropriate assistance, advice, and guidance by: participating in the design of Group activities; advising in the selection of sources or resources; coordinating or participating in collection and\or analysis of data; advising in management and technical performance; or participating in the preparation of publications. However, the role of NIAID will be to facilitate and not to direct the activities. It is anticipated that decisions in all activities outlined below will be reached by consensus of the Group and that NIAID staff will be given the opportunity to offer input to this process. The manner of reaching this consensus and the final decision-making authority will rest with the Principal Investigator. A. NIAID Participation in Design of Group Activities, Development of Research Protocols and Evaluation of Results 1. The Principal Investigator, Project Leaders, and NIAID Scientific Coordinator will meet periodically (at least twice per year) to review progress, plan and design research activities, and establish priorities. The Principal Investigator will be responsible for scheduling the time and place (generally at one of the performance sites) and for preparing concise proceedings or minutes which will be delivered to the members of the group within sixty days of the meeting. One meeting of all awardees will be held each year at the NIH (or at a site designated by NIAID) during which the Principal Investigator and Project Leaders will present significant findings in symposium format. (APPLICANTS SHOULD INCLUDE TRAVEL FUNDS SPECIFICALLY FOR THIS MEETING WHEN THEY PREPARE THEIR BUDGETS.) It is expected that the agenda for this meeting will be determined by agreement between the Scientific Coordinator and the Principal Investigators. NIAID staff may not chair Group meetings. A critical determinant of Group success will be the degree of communication among its members. Therefore, additional informal meetings among all participants as well as regular telephone and written communication will be important and are encouraged. 2. The NIAID Scientific Coordinator, like other Group members, may suggest studies within the scope of the Group's objectives and research activities; may present to the Group experimental findings from published sources or from contract projects in support of these suggestions; may participate in the design, but not in the execution, of experiments agreed to by the Group; and may participate in the analysis of results. 3. The NIAID Scientific Coordinator may assist the Group or other individual members in research planning, particularly with respect to: a: reduction of duplication of efforts conducted in other extramural projects; b: provision of needed resources and information that may not be otherwise available to the Group; and c: provision of data from testing conducted in resource contract laboratories. B. NIAID Participation in Collection and Analysis of Data, Procedures for Submission of Results to NIAID, and Preparation of Group Findings for Presentation and Publication In addition to the special reports and stipulations described below, reporting requirements will be identical to those currently in existence for awardees of traditional NIH research project grants. 1. The principal end product of NCVDG activities will be the development of HIV vaccines. Although the support of the final developmental work through private resources is encouraged, the Group may recommend that final development be sponsored by NIAID. In the latter case, it will be necessary for the Principal Investigator, appropriate Project Leaders and NIAID representatives to collaborate in the analysis, summarization, preparation, and presentation of data to the appropriate NIAID staff. 2. NIAID will retain the option to cross-file or independently file an application for investigational clinical trial; i.e., an Investigational New Drug Application (INDA) to the United States Food and Drug Administration of any invention resulting from these NIAID supported Cooperative Agreements. Reports of data generated by the Group or any of its members required for inclusion in INDA's and Clinical Brochures and for cross-filing purposes will be submitted by the Principal Investigator to the Scientific Coordinator upon request. Such reports will be in final draft form and include background information, methods, results, and conclusions. They will be subject to approval and revision by NIAID and may be augmented with test results from other Government sponsored projects prior to submission to the appropriate regulatory agency. 3. The NIAID, via the Scientific Coordinator, will have access to data generated under this Cooperative Agreement. Information obtained from the data may be used by the Scientific Coordinator for the preparation of internal reports on the Group's activities. However, the applicant will retain rights to the data, and timely publication of major findings is encouraged. Publication or oral presentation of work done under this agreement is the responsibility of the Principal Investigator and appropriate Project leaders and will require appropriate acknowledgement of NIAID support. C. Inasmuch as certain activities under "TERMS OF AWARD: NATURE OF PARTICIPATION OF NIAID STAFF" require approval by NIAID staff during performance of this Cooperative Agreement (specifically, reports intended for inclusion in INDA's and Clinical Brochures, redistribution of biological materials received from the Government, and dissemination of research findings resulting from the use of these materials), NIAID will establish an arbitration process to resolve any difference of opinion. An arbitration panel, composed of one Group designee, one NIAID designee, and a third designee with expertise in the relevant area and chosen by the other two, will be formed to review any scientific or programmatic issue that is significantly restricting progress. These special arbitration procedures in no way affect the awardee's right to appeal an adverse action in accordance with PHS regulations at 42 CFR Part 50, Subpart D, and HHS regulations at 45 CFR Part 16. D. The special "TERMS OF AWARD: NATURE OF PARTICIPATION OF NIAID STAFF" described in this section are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administration regulations at 45 CFR Part 74, and other HHS, PHS, and NIH grant administration policies. IX. MINIMUM REQUIREMENTS FOR APPLICATION Applications seeking funding as a NATIONAL COOPERATIVE VACCINE DEVELOPMENT GROUP FOR THE ACQUIRED IMMUNODEFICIENCY SYNDROME must meet the following requirements: The application must be from a Group and must: A. name a single Principal Investigator who is an employee of the applicant institution and who will be responsible for the application, for coordinating Group research activities, and for the support of Group activities through a Central Operations Office; B. identify the single applicant organization (grantee institution) that will provide the Central Operations Office and be legally and financially responsible and be accountable for the use and disposition of funds awarded on the basis of this RFA; show availability of personnel and facilities capable of performing and supporting the administrative functions of NCVDG; C. provide a description of the Group's plan for assuring adequate patent coverage of new inventions that may issue as a re