kristoff@GENBANK.BIO.NET (Dave Kristofferson) (03/02/90)
REQUEST FOR COOPERATIVE AGREEMENT APPLICATIONS: RFA-90-HD-01 COOPERATIVE MULTICENTER NETWORK OF NEONATAL INTENSIVE CARE UNITS P.T. 34, FF, II; K.W. 0775020, 0775025, 0411005, 0710030, 0785035 National Institute of Child Health and Human Development Application Receipt Date: May 22, 1990 PURPOSE The National Institute of Health and Human Development (NICHD) invites applications from investigators to participate with the NICHD under a Cooperative Agreement in an ongoing multicenter clinical study designed to investigate the safety and efficacy of treatment and management strategies to care for infants in Neonatal Intensive Care Units (NICU). The objective of this study is to facilitate evaluation of these strategies by establishing a network of centers using common protocols to study the requisite number of patients in order to provide answers more rapidly than individual centers acting alone. The NICHD program staff will assist the principal investigators of the selected NICUs and the Advisory Board in identifying research topics of high priority and in designing protocols appropriate to the evaluation of optimal management in these areas. It is anticipated that 8 to 10 clinical centers will be selected for the program. The deadline for receipt of applications is May 22, 1990. Applications received after this date will not be considered. Only institutions in the United States will be eligible for participation. ADMINISTRATIVE BACKGROUND Modern neonatal medicine has introduced a number of principles of management and innovative methodologies without rigorous use of the controlled observation necessary for the objective evaluation of many of these innovations. A major problem has been the balance between assuring prompt implementation of new technologies, procedures, treatments and drugs, and adequate evaluation of their safety and efficacy. Indeed, because of the urgent demands of sick patients, care is often based on limited knowledge of new modalities not subjected to critical studies prior to introduction and use. In a critically ill baby, an innovative idea may be tried which, if the baby's condition improves, can rapidly set a new trend, and become the standard of care. Therefore, their incorporation into the NICUs arsenal of therapies frequently is based on limited experience, and their efficacy and/or safety have not been evaluated scientifically. The cooperative nature of the present approach allows the study of significant clinical problems occurring too infrequently for any one institution to have adequate numbers for a valid clinical study within a reasonable time span. This is an important consideration in view of trends that exist in NICUs, where therapeutic interventions may change within months before adequate studies of safety and efficacy are initiated, much less completed. This approach facilitates the review and approval by Institutional Review Boards (IRB) of protocols that address complex clinical research questions that result from the joint efforts by: NICHD staff; an Advisory Board composed of leading neonatologists, consulting experts, clinical trial experts; and the Network Steering Committee. Protocols will be developed to evaluate therapeutic management of major problems currently at issue in NICUs. In addition, the Newborn Network will address important issues of newborn care through observational studies designed to assess the consequences of disease, procedures, and therapeutic interventions, as well as to generate hypotheses concerning future treatment strategies. In addition to the rigorous follow-up evaluation provided by successful applicants, the Newborn Network may fund specialized follow-up studies designed to elucidate unique physiologic, developmental, and social risks of its study population. In an attempt to respond to the need for well-designed clinical neonatal medicine trials, the NICHD established a cooperative multicenter Network of Neonatal Intensive Care Units in 1986. Seven participating university centers and a Data Center were selected among respondents to a Request for Applications (RFA). This Newborn Network maintains a generic data base on all infants admitted at <1500 grams. Protocols on the prevention of sepsis, intraventricular hemorrhage, pulmonary hypertension, and surfactant administration have been initiated. Centers that join the Network in the next award period (beginning April 1, 1991) would be expected to participate in the protocols ongoing at that time. Future protocols in all major areas of newborn pathophysiology including cerebral function, pulmonary physiology, gastrointestinal function and nutrition, immunology, etc., are of interest. Also of interest are the evaluation of drugs in the newborn and the rapid transfer of new technologies to neonatal medicine. RESEARCH SCOPE NICHD invites applications from both current members of the NICU Network (competitive continuation applications) and prospective members (new applications). The minimum requirements for applicants, investigators, and their NICU research units are as follows: 1. Participants must be based in a level III neonatal intensive care unit that admits both inborn and outborn patients. Professional staffing of the unit should include at least of four full-time board-certified neonatologists. 2. The NICU should be located in an institution with a perinatal program that delivers high-risk pregnancies and has at least one full-time perinatologist on staff. There should be a history of cooperation between neonatology and obstetrics toward excellence in clinical care, maintenance of a data base, and research productivity. An obstetrician who has documented interest and experience with clinical trial research and is willing to participate in the NICU Network should be designated. 3. The applicant NICU should have an established perinatal/neonatal data system, preferably computerized, with experience in defining and quantitating patient populations for clinical studies. All successful applicants must be willing to provide complete, accurate, and timely data to the NICU generic data base. 4. Applicant NICUs should have at least 500 admissions per year including both inborn and outborn infants. No more than 30% of admissions should be outborn. Large perinatal centers will be given preference to combined services composed of a small inborn unit and a transfer/tertiary care service. 5. The applicant NICU should have state-of-the-art facilities and clinical capabilities, including bedside monitors with trend capabilities, noninvasive methods of oxygen and carbon dioxide determination, the current generation of ventilators, etc. A full complement of pediatric subspecialists should also be available including cardiology, gastroenterology, infectious disease and immunology, neurology, nephrology, ophthalmology, pathology, pulmonology, surgery, genetics and development medicine, and nutrition. A full-time respiratory therapy program and pharmacy capable of supporting clinical research must also be available. Appropriate laboratory facilities should include hematology, chemistry, endocrinology, blood bank, blood gas, microbiology, serology, and immunology. A specialized radiology program (CAT scan, portable x-ray, and portable ultrasound for echocardiography and head ultrasound), and portable EEG facilities must be available and freely accessible to the NICU. Magnetic resonance imaging is desirable. 6. The applicant NICU should have an established neonatal follow-up clinic (short and long-term) with several years of experience in following patients from the NICU. The majority (70%) of infants less than 1500 grams who have been discharged from the NICU should be enrolled in the program, as well as other infants at risk for developmental delay. The professional staff should include a developmental pediatrician or neonatologist with developmental expertise. Specialists available to consult should include pediatric neurology, pediatric psychology, occupational and/or physical therapy, and pediatric ophthalmology, as well as social services. A system of ongoing data collection on these infants must be operational. 7. The applicant NICU should clearly express its interest to participate in a cooperative manner with other centers, the NICHD, and the Data Coordinating Center in the definition of research protocols, uniform data forms, and data transfer. 8. There should be a firm departmental and institutional commitment to collaborative neonatal research as demonstrated by a documented history of clinical research productivity (recruitment performance, publications, etc.) in past or present clinical trials. 9. The application must exhibit a preparedness to pursue capitation of operational costs for each protocol in the Network (see Budget section). 10. The NICHD also funds clinical research in a Maternal-Fetal Network whose applications will be due on May 22, 1990. NICHD encourages applications from institutions that propose participation in both the Neonatal and the Maternal-Fetal Networks. DIRECTION AND MANAGEMENT OF THE NETWORK The management of the NICU Network includes three committees as follows: 1. A Steering Committee will be responsible for protocol development, assisted by the Advisory Board and the Data Safety and Monitoring Committee. The Steering Committee will have primary responsibility for the conduct of protocols and the preparation of publications. The Steering Committee will be composed of each principal investigator, one representative from the Data Center, and three NICHD staff. NICHD staff will comprise the Director of the Center for Research for Mothers and Children (CRMC), a neonatologist from the Pregnancy and Perinatology Branch (NICU program officer), and a representative from the Epidemiology and Biometry Research Program. The NICU program officer will be the only voting NICHD staff member of the Steering Committee. An outside chairman, who is not participating as a principal investigator, will be selected by the NICHD. 2. An Advisory Board will advise the Steering Commmittee in the identification and prioritization of topics for network research. The Advisory Board, chosen by the NICHD with the advice of the Steering Committee, will be composed of individuals with expertise in clinical trials, biostatistics, epidemiology, perinatology, and neonatology; the Chairman of the Steering Committee; and the Director of the CRMC and the NICU program officer. Additional members will participate based on the need for specific expertise. 3. A Data Safety and Monitoring Committee will monitor the safety of ongoing clinical trials and advise on their conduct. It will be established by NICHD and will represent expertise in ethics, clinical trial design, neonatology, perinatology, and basic science. CONTENT OF APPLICATION The application should include the following, presented in the following order in the application: 1. NICU Staffing. Provide complete descriptions of the training and qualifications of the principal investigator and neonatal staff who will participate. Specify the past and current involvement in clinical and basic research and their availability to take primary responsibility for research protocols in the NICU Network. Detail the current pattern of research nurse staffing of clinical trials in the unit, including arrangements for recruitment into protocols during evening, nighttime, and weekend hours. Provide specific information on research nurses who would be available for Network assignment. 2. Obstetrical Staffing. Identify an obstetrician who would collaborate actively in protocol development. Provide a description of his/her training, qualifications, basic and clinical research involvement, and availability as above. Document current collaborative relationships between the neonatal and obstetrical services to promote excellence in clinical care, teaching, and research. 3. Perinatal Data System. Describe the data system used by the perinatology/neonatology units and document how it has been and is being used to plan and carry out clinical research. Include the data form as an appendix. 4. Available Population of Clinical Research Subjects. Applicants are encouraged to include females and minorities among study populations. If minorities or females are not included, a clear rationale for their exclusion should be provided. Characterize the patients served by the NICU as follows: a. Number of deliveries and delivery mode. b. Description of the obstetrical population, including percentage of high-risk deliveries, racial mix, payment categories, maternal risk factors (diabetes mellitus, human immunodeficiency virus (HIV), substance abuse, pregnancy induced-hypertension, etc.). c. NICU admissions and survival data by birthweight categories; average length of stay; back-transfer policies. d. Newborn surgical cases (inborn versus outborn), type, survival. e. Referral patterns, transport data (maternal versus infant), and a description of the transport system. f. Complications of NICU care, including nosocomial infection, intracranial hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, bronchopulmonary dysplasia (BPD), rickets, etc. Specify the various subgroups that have been eligible for, and have actually been randomized, in previous or current clinical trials. 5. Clinical strengths and weaknesses of the NICU and Obstetrical Services. Describe in detail the clinical attributes of the NICU (see #4 above) including the following: a. Quality of clinical care (a description of the neonatal training program, fellow/resident/nurse practitioner staffing patterns, nurse/patient ratio. b. A description of the NICU treatment philosophy, including ventilatory management, nutrition, support of the extremely low birth-weight infant, infection surveillance, use of steroids, etc. c. NICU facilities and physical plant (number of beds, level of intensity, monitoring capabilities, office space, computer facilities, etc.). d. Specialized support staff including research nurses, biomedical and computer specialists, Ph.D. research personnel, etc. e. Pediatric subspecialty services. f. Support services and laboratories. Indicate how clinical services have been modified, if necessary, to support clinical research in the past. Finally, discuss any perceived weaknesses in the NICU clinical care system and review planned solutions. Describe the organization, service load, and clinical attributes of the affiliated obstetrical/perinatal service, with special attention to antenatal fetal testing, intrapartum diagnosis, and perinatal pathology. Also describe high-risk management, including the use of steroids, antibiotics, tocolysis, management of hypertension, cesarean rate, chorionic villus sampling, fetal surgery, etc. 6. NICU Follow-up Program. Describe the NICU follow-up program including the following: a. Number and characteristics of infants followed, duration of follow up, dropout rate. b. Report of developmental outcome of NICU graduates from 1984-1989. c. Professional staff. d. A bibliography of publications from the follow-up program. e. Affiliated programs, i.e. BPD clinic, Sudden Infant Death Syndrome program, substance abuse, or HIV clinics, etc. f. An example of forms used (include in appendix). 7. Intent to Participate. Based on your understanding of the NICU Network's structure and function, indicate specific ways in which NICU policies and procedures could be modified to allow effective participation in randomized, multi-center clinical trials. Specifically, indicate your preparedness to participate in network clinical trials according to the terms and conditions of this RFA. 8. Department and Institutional Commitment and Experience. Provide letters of commitment from all involved departments to ensure optimal cooperation for network protocols. Provide evidence of research productivity by the applicant unit in previous or current clinical trials, especially of a collaborative nature. An example of a non-Network clinical protocol which has been completed or is underway should be provided including IRB approval (the protocol and IRB approval should be submitted as an appendix). An accompanying narrative should describe trial preparation (retrospective studies, identification of the study population, funding applications, budget preparation), conduct of the trial (recruitment of patients, integration with other clinical research, assignment of costs to research versus clinical care), resolution of problems encountered, results, and their implications. Applicants who are reapplying as current NICU Network members should provide a separate description of their participation in the NICU Network protocols to date. Include in this description the numbers of patients enrolled and completed, percent enrollment of available patients, and the nature and extent of staff involvement as it affected performance. Also, current NICU Network members should summarize how they have met the terms of award that accompanied the Notice of Award for their initial grant period. 9. Acceptance of Budgetary Mechanism. Provide statements from the department and the institutional sponsored program office assuring cooperation in obtaining the required services and data described above for the NICU Network and assuring cooperation with the proposed plan to capitate operational costs for each protocol. This section should also include a discussion of innovative ideas to make the conduct of clinical trials within the NICU Network more efficient and cost-effective. MECHANISM OF SUPPORT - Terms of the Agreement The funding mechanism to be used to assist the scientific community in undertaking this system of clinical investigation will be a Cooperative Agreement between the participating units and NICHD. The major difference between a Cooperative Agreement and a research grant is that there will be substantial programmatic involvement of NICHD staff above and beyond the levels required for traditional program management of grants. Specifically, the role of the NICHD NICU program officer will be to aid the awardees and the Steering Committee in the following ways: o Assistance in the identification of important areas of study. o Assistance in the development of study protocols. o Assistance in the development and review of capitation-based budgets, including the identification of study costs and special institutional needs. o Assistance in the review and evaluation of each stage of the program before subsequent stages are started, in conjunction with the principal investigators, the Steering Committee, and the Advisory Board. o Assistance in reporting results to the community of investigators and health care recipients. Programmatic responsibility for review and oversight of these Cooperative Agreements will reside with the NICU program officer. This role will include the following: o Assurance of the scientific merit of the trials, including the option to withhold support of a participating center if technical performance requirements such as protocol compliance, enrollment targets, or randomization of subjects are not met. o Assistance in the efficient conduct of the trials, including ongoing review of progress; redirection of activities to improve performance and cooperation if necessary; and frequent communication with other members of the Steering Committee. o Initiation of a decision to modify or terminate a study based on the advice of the Data Center, Data Safety and Monitoring Committee, and Advisory Committee with the mutual consent of the Steering Committee. The responsibilities and authorities of the awardees will be as follows: o Identification of priority issues for research. o Development and implementation of protocols. o Collection and transmission of accurate data in a timely manner. o Analysis of data and publication of results of the NICU trials. All parties will agree to accept the coordinating role of the group and the participatory and cooperative nature of the group process. The support of awards pursuant to this RFA is contingent upon ultimate receipt of appropriated funds for this purpose. The number of awards will be influenced by the overall merit of the applying centers and by the amount of funds available to the Institute. It is anticipated that eight to ten meritorious applications will be funded. The specific terms, conditions, and details of arbitration procedures pertaining to the scope and nature of the interaction between NICHD and the participating NICUs will be incorporated into the Notice of Grant Award. These procedures will be in addition to the customary programmatic and financial negotiations which occur in the administration of grants; they will be invoked only when agreement cannot be reached on issues that may arise after the award between the awardee and the NICU program officer. In that event, an arbitration panel will be formed consisting of one person selected by the principal investigators, one person selected by the Chief of the Pregnancy and Perinatology Branch, and a third person selected by these two members. The decision of the arbitration panel will be binding. The special terms of Award of Cooperative Agreement are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, DHHS grant administration regulations at 45 CFR Part 74, and other DHHS, PHS, and NIH grant administration policies. The NICHD review procedure in no way affects the right of a recipient of a cooperative agreement to appeal an adverse determination under the terms of PHS regulations at 42 CFR Part 50, Subpart D, and DHHS regulations at 45 CFR Part 16. Business management aspects of these awards will be administered by the NICHD Grants Management Section in accordance with DHHS, PHS, and NIH grant administration requirements. Program staff intend that the ongoing Cooperative Agreements will be recompeted every five years, depending on available funds. REVIEW CRITERIA AND PROCEDURES A. Review Procedures Applications that are incomplete or nonresponsive to this RFA will be withdrawn by the Division of Research Grants and NICHD staff upon receipt and returned to the applicants without further consideration. Applications that are complete and responsive may be subjected to a preliminary evaluation by an NICHD peer review group to determine their scientific merit relative to the other applications received in response to this RFA (triage); the NICHD will withdraw from further consideration applications judged to be noncompetitive for award and promptly notify the principal investigator/program director and the official signing for the applicant organization. Those applications judged to be competitive will be further evaluated for scientific/technical merit by a special review committee convened specifically for this purpose by the Scientific Review Program, NICHD. This review will include an evaluation of past performance in the NICU Network for current members followed by a second-level review by the National Advisory Child Health and Human Development Council. Final selection of clinical centers for funding also may be based on the need for diversity in the study population. B. Criteria for Review Applications meeting the minimum requirements will be evaluated on technical merit according to the criteria listed below. 1. Qualifications, Experience, and Commitment of Key Personnel (see Content of Applications items #1, 2). 2. Facilities, Clinical Population, Program (see Content of Applications items #3, 4, 5, 6). 3. Management, Commitment, and Experience (see Content of Applications items #7, 8). 4. Budget - (see Content of Applications item #9 and Budget Guidelines - Appendix I). METHOD OF APPLYING Applications should be submitted on form PHS-398 (revised 10/88). The conventional presentation format for regular research grant applications should be used, with care taken to address the points identified under review criteria and eligibility for participation. The phrase "NICU COOPERATIVE AGREEMENT APPLICATIONS, RFA HD-90-01" should be typed in item 2 of the face page of the application. The RFA label included in the PHS 398 (rev. 10/88) application kit 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 original and four copies of the application should be sent or delivered to: Application Receipt Office Division of Research Grants National Institutes of Health Room 240, Westwood Building Bethesda, Maryland 20892 Also send two copies to: Laurance S. Johnston, Ph.D. Scientific Review Program National Institute of Child Health and Human Development Executive Plaza North, Room 520 Bethesda, MD 20892 Applications including copies must be received by May 22, 1990. Late applications will not be accepted. TIMETABLE Application Receipt Date: May 22, 1990 Initial Review Date: June-July 1990 Review by Advisory Council: January 1991 Anticipated Award Date: April 1, 1991 Inquiries regarding this announcement may be directed to: Linda L. Wright, M.D. Special Assistant to the Director Center for Research for Mothers and Children National Institute of Child Health and Human Development Executive Plaza North, Room 643 Bethesda, MD 20892 Telephone: (301) 496-5575 This program is described in the catalog of Federal Domestic Assistance No. 13.865, Research for Mothers and Children. Awards will be made under the authority of the Public Health Service Act, Section 301 (42 USC241), and administered under PHS grant policies and Federal Regulations 42 CFR Part 52 and 45 CFR Part 74. This program is not subject to review the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency Review. APPENDIX I BUDGET The budget at the time of application will be limited to a BASE BUDGET with maximum allowances as follows: Principal/Co-Investigator component 10% effort Co-ordinator 100% effort Data entry clerk 50% effort Supplies and small equipment (itemized and justified) NTE $4,500 Travel (a total of 10 trips to Bethesda per Network research team) as appropriate Other costs (itemized and individually justified) NTE $2,500 At such time as an application has been approved and is being considered for funding, the applicant will be required to complete protocol budgets for those studies underway within the Network. These budgets will consist of specific protocol-related allowances and will be capitated on the anticipated number of subjects to be enrolled in the study at the applicant NICU. Ongoing annual budgets of NICU Network members will be based on individual protocols that will be funded through a capitation funding. Each NICU Network member will be given base costs (listed above), in addition to a flat fee per patient successfully enrolled and completed. The individual members will be required to project patient enrollment for a specific protocol during a specified time frame; continuation and level of funding will be based on actual recruitment. REQUEST FOR APPLICATIONS RFA NUMBER: 90-CA-12 CLINICAL DIAGNOSTIC STUDIES OF BRAIN TUMOR USING PET AND OTHER IMAGING MODALITIES P.T. 34; K.W. 0715035, 0705010, 0745020, 0706030, 0765020, 0760045 NATIONAL CANCER INSTITUTE APPLICATION RECEIPT DATE: May 18, 1990 LETTER OF INTENT RECEIPT DATE: April 18, 1990 I. INTRODUCTION The Radiation Research Program (RRP), Division of Cancer Treatment (DCT), of the National Cancer Institute (NCI), announces the availability of a Request For Applications (RFA) on the above program. The objective of this RFA is to advance diagnostic clinical research using positron emission tomography (PET) and other modalities such as Magnetic Resonance Spectroscopy (MRS) in evaluating essential features of brain tumor metabolism to improve our knowledge of tumor growth, patient therapy, patient prognosis and management. II. BACKGROUND INFORMATION Advances in the last decade in imaging and imaging-related technology have made possible not only more precise anatomic/pathologic diagnosis but are providing functional information as well. These advances potentially extend the capacity of imaging method from its customary role of anatomic diagnosis with inferred function to observing physiologic and pathophysiologic phenomena directly. This trend in diagnostic imaging of combined information is the direct result of the technological development and clinical use of PET, MRS, and radiolabeled monoclonal antibodies and other imaging modalities. PET has ideal properties for evaluating essential features of tumor metabolism. Such functional imaging may be used to determine many features of malignant state, including unrestrained growth and resistance to anti-neoplastic therapy. In comparison to the tissues from which they arise, tumors have an accelerated intermediary metabolism. This distinction may be used as a basis for characterizing tumor aggressiveness and response to specific anti-neoplastic therapy. It was the consensus of a recent workshop, organized by our program, that the time was ripe to exploit advances in understanding of distinctive tumor metabolism, and the technology of PET, to develop clinically useful analytic methods for assessing regional glucose metabolism, protein synthesis, and DNA synthesis. Based on presentations at the workshop and successful studies at the NIH for brain tumors, it appears that PET studies of the metabolism of other tumors are likely to result in improved knowledge of tumor aggressiveness and patient prognosis. Furthermore, PET is a useful modality for studies on response to radio- and chemo-therapy, on choice of optimal site of tumor biopsy, and on distinguishing between local invasion and the response of normal tissue. These studies may improve surgical treatment planning of cancer patients. Similarly, recent research using MRS in vivo evaluating normal and malignant tissues shows the capability of this modality to provide functional information and identify various metabolites and meaningful metabolic data for patient managements. Features such as PH, the tissue redox state and useful information derived from regional perfusion may be determined by MRS. These and other physiological approaches using MRS can be used to monitor therapeutic response during regional perfusion of malignant tumors in man. Based on successes of PET, MRS, and other modalities in providing significant functional information derived from normal and malignant tissues in vivo, clinical study of brain tumor metabolism becomes not only possible but timely. III. RESEARCH GOALS AND SCOPE The overall objective of this RFA is to advance the use of PET, MRS, radiolabeled monoclonal antibodies and other modalities to evaluate essential features of brain tumor metabolism, to improve our knowledge of tumor growth, to determine effects of therapy, and patient prognosis and management. Stated in other words, the aim of this RFA is to improve our understanding of pathophysiology of brain function in patients with primary brain tumors using PET and other radiographic methods at diagnosis, during and after the course of therapy. Where feasible and appropriate applications for the proposed clinical studies should include a suitable representation of minorities and women. If the applicant cannot comply, a clear rationale for their exclusion must be provided. IV. MECHANISM OF SUPPORT Support of this program will be through the National Institutes of Health (NIH) Grant-in-Aid (RO1) Agreement. 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. This RFA is a one-time solicitation. Generally, future unsolicited competitive continuation applications will compete as research project applications with all other investigator-initiated applications and be reviewed by the Division of Research Grants (DRG). However, should the NCI determine that there is sufficient programatic need, a request for renewal applications will be announced. In that event, only the recipients of awards under the RFA will be eligible to apply. Approximately $900,000 in total costs per year for five years will be committed specifically to fund applications that are submitted in response to this RFA. The funding level 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 the present RFA should not exceed five years. The earliest feasible start date for the initial awards will be September 1990. Although this program is provided for in the financial plans of the NCI, the award of grants pursuant to this RFA is also contingent upon the availability of funds for this purpose. V. ELIGIBILITY REQUIREMENTS Non-profit and for-profit organizations and institutions, governments and their agencies, and foreign institutions are eligible to apply. All applications need to have the personnel, equipment, facilities, and brain tumor patients in order to conduct the research outlined in item IV. In order to participate in this program, applicant institutions must demonstrate, or meet the following requirements: A. Availability of PET facility and personnel capable to conduct PET research on patients with brain tumors. This includes: metabolism, flow permeability and/or receptors, and other investigations as designed by the applicant. B. Other approaches using MRS, radiolabeled antibodies and other radiographic methods need to have the necessary equipment, facilities, personnel to conduct the proposed research on brain tumors. C. Applicants must demonstrate the availability of an anatomic imaging facility. D. A multidisciplinary team such as nuclear medicine, radiology, radiation oncology, neuroradiology, oncology, and pathology is minimally required to conduct this research. E. An adequate number of brain tumor patients needed for this investigation is essential for this project. F. Applicants must document their ability to evaluate precisely the progression and regression of brain tumors. VI. REVIEW PROCEDURES AND CRITERIA A. REVIEW PROCEDURE Upon receipt, applications will be reviewed by applying DRG referral guidelines and 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 an NCI program staff function. Applications that are judged non-responsive will be returned by the NCI, but may be submitted by the applicant as investigator-initiated regular research grants at the next receipt date. In cases where the number of applications is large compared to the number of awards to be made, the NCI may conduct a preliminary scientific peer review to eliminate those which are clearly not competitive. The NCI will remove from competition those applications judged to be noncompetitive for an award 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 the Division of Extramural Activities, 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. B. REVIEW CRITERIA The NCI peer review will consider the following criteria: 1. Significance of the proposed research to the overall goals of the RFA, namely, to utilize imaging modalities to understand better the biology and pathobiology of brain tumor progression in relation to brain function of patients with primary brain tumors in a manner that leads to better patient management. 2. Originality, scientific and technical merit of the proposed research approach. 3. Competence, experience and ability of the principal investigator and the research team to accomplish the objectives of the overall goals of the RFA. 4. Accuracy and adequacy of the methods, procedures and approaches for the use of the PET and other modalities in brain tumors imaging. 5. Appropriateness and adequacy of the facilities, resources, instrumentation and equipment available to the principal investigator and supporting staff. 6. Evidence of the ability to accrue adequate number of patients with primary brain tumors. 7. Reasonableness of the time/effort devoted by the applicant and his staff to the project. The budget shall not be considered as a review criterion and will be determined after the scientific merit evaluation. Based on the actual budgetary needs for the conduct of the approved research, the review group will recommend an appropriate budget and period of support for each approved application. VII. METHOD OF APPLICATION The regular research grant application form PHS-398 (revised 10/88) must be used in applying for this RFA. These forms are available at most institutional business offices and from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, Room 449, Westwood Building, 5333 Westbard Avenue, Bethesda, Maryland 20892, or from the NCI program director named below. 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. In addition, the RFA number and title 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, in one package to DRG 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, MD 20892** At time of submission, send two (2) additional copies of the application to: REFERRAL OFFICER Division of Extramural Activities National Cancer Institute Room 848, Westwood Building 5333 Westbard Avenue Bethesda, MD 20892 Applications must be received by May 18, 1990. If an application is received after that date, it will be returned. Also, the 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 of NIH awarding unit. VIII. LETTER OF INTENT Prospective applicants are asked to submit, by April 18, 1990, 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 institutions, and the number and title of the RFA in response to which the application is being submitted. The letter of intent is of great benefit to the NCI in planning for and implementing the review process although it is not required, is not binding, and does not enter into the review of subsequent applications. The letter of intent should be sent to the NCI program director: Dr. Matti Al-Aish, Acting Chief Diagnostic Imaging Research Branch Radiation Research Program National Cancer Institute National Institutes of Health Executive Plaza North, Suite 800 Bethesda, MD 20892 Telephone: (301) 496-9531 IX. 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. Matti Al-Aish at the above address. The program director welcomes the opportunity to clarify any issues or questions from potential applicants. This program is described in the Catalog of Federal Domestic Assistance No. 13.395, Cancer Treatment Research. Awards are under the authority of Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) 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.