Path: utzoo!utgpu!watmath!iuvax!genet!bionet!net.bio.net!kristoff From: kristoff@NET.BIO.NET (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide for Grants and Contracts, vol. 18. no. 40, part 2, 10 November 1989 Message-ID: Date: 10 Nov 89 04:13:46 GMT Sender: kristoff@NET.BIO.NET Lines: 1140 Vol. 18, No. 40, November 10, 1989 - Page 10 FULL TEXT OF RFAs FOR ONLINE ACCESS INTERNATIONAL COLLABORATION IN ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS) RESEARCH (ICAR) RFA-NIH-NIAID-89-AI-21 P.T. 34; K.W. 0715008, 0785055, 0710030 NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES (NIAID) Letter of Intent Date: December 15, 1989 Application Receipt Date: March 30, 1990 The NIAID invites applications for the expansion of the ICAR program to link U.S. institutions to research units in foreign countries with significant numbers of persons with HIV infection but which may lack important features of the research infrastructure or expertise necessary to conduct epidemiologic research of HIV infection and disease, including HIV-relevant opportunistic infections. Authority for this international program is provided by Public Law 86- 610, the International Health Research Act of 1960. The program focuses on infectious diseases and the immunology of these diseases. LETTER OF INTENT Prospective applicants are encouraged to submit a letter of intent by December 15, 1989, that includes a brief description of the thrust of the research activities and the names of the principal investigator and other key investigators, if known, the U.S. institution, and the foreign institution. The Institute requests such letters in order to provide an indication of the number and scope of applications to be received, permit early communication between staff and the prospective applicant, and indicate the research areas to be covered to allow early preparations for expedited review. The letter of intent is not binding, will not enter into the review of any application subsequently submitted, and is not a requirement for application. The letter of intent should be sent to: Ms. Amy R. Sheon Epidemiology Branch Division of AIDS National Institute of Allergy and Infectious Diseases 6003 Executive Boulevard, Room 240P Bethesda, MD 20892 Telephone number: (301) 496-6177 Correspondence sent to Ms. Sheon by overnight or courier service should use Rockville, MD 20852 for the city, state, and zip code. I. Background HIV infection is a major health problem in many developing countries. Risk factors of infected persons may be represented in quite different proportions than comparable data suggest for industrialized nations. As much as 80 percent of HIV infection in Africa may be acquired through heterosexual transmission, where risk factors include multiple sex partners, contact with prostitutes, and history of sexually transmitted diseases (Johnson and Laga, 1988). Intravenous drug use, prostitution, and receipt of blood products are major risk factors in Asian countries (Des Jarlais and Friedman, 1988). Given the nearly 1:1 male-to- female ratio of infection, transmission from mothers to infants is particularly common in developing countries (Chin and Mann, 1988). By contrast, 63 percent of adult male AIDS cases reported in the United States in 1988 were in non IV drug-using homosexuals or bisexuals. Of all adult AIDS cases reported to the U.S. Centers for Disease Control (CDC) through the end of 1988, only 9 percent have been in females; children under 13 years account for about 2 percent of cases reported to date in the U.S. (CDC, 1989). Little is known about perinatally-acquired HIV infection. In utero transmission has been documented from the presence of virus in cord blood and from necropsies of aborted fetuses. Intra-partum transmission is plausible due to the newborn's exposure to maternal blood during both vaginal and caesarian deliveries, although confirmation of such transmission has been difficult. Post-natal transmission to infants through breastmilk is probably rare but has been documented (Ryder and Hassig, 1988). AIDS in developing countries exhibits virologic and clinical manifestations infrequently seen in the US. HIV-2 has been reported from nearly a dozen West African and Caribbean countries but is rare elsewhere. This virus, first identified in 1985, has biological and epidemiological characteristics similar to HIV-1, although there are striking differences in its antigenic components and nucleic acid composition (Clavel, 1987). While Kaposi's Sarcoma is extremely rare in children with AIDS in the United States, cases have been reported in African children (Rolfe and Wels, 1987). Pneumocystis carinii pneumonia is among the most common serious opportunistic infections faced by persons with AIDS in the U.S. but is rare in Africa (Lucas, et al, 1989). In 1988, five ICARS were awarded to set up collaborative research centers in countries with significant levels of HIV prevalence but with some limitations in their research infrastructures, including Brazil, Malawi, Mexico, Uganda, and Zaire. The present initiative would locate 1-2 additional ICARS in developing countries not already participating in the ICAR Program where available information suggests that HIV infection is currently or soon will be an important public health problem. II. Research Objectives and Scope The mission of the Division of AIDS (DAIDS) is to find ways to prevent, treat, and cure HIV infection and AIDS. DAIDS has a broad interest in the virology, immunology, pathogenesis, epidemiology, diagnosis, treatment, control and prevention of HIV infection. Of special programmatic interest is perinatal and pediatric infection and heterosexual transmission; variability in HIV isolates in different geographic areas and correlation with clinical and epidemiologic factors; potential role of co-factors in transmission or natural history; and similarities and differences in clinical and epidemiologic presentation of disease in different geographical areas. The ICAR seeks to establish collaborative research initiatives between U.S. and collaborating country (host) investigators to conduct research of recognized relevance to the health of people in both countries. It is intended that the effort give priority to the development of self- direction and self-sufficiency of the collaborating foreign laboratory and clinical investigators. The present initiative will permit a wide range of investigations including, but not limited to the following: A. study of the natural history of HIV infection B. identification of risk groups and risk behaviors associated with transmission C. establishment of seroprevalence and seroincidence rates among selected populations D. evaluation of the immunological parameters that affect either the susceptibility to infection among the uninfected or the infectivity among the infected E. assessment of the efficacy of prevention strategies F. investigation of the routes of transmission in perinatally acquired infection G. identification of early biological or clinical markers of HIV infection and HIV disease in adult and pediatric cases Safeguarding the rights and welfare of individuals who participate as subjects in research activities supported by the U.S. Department of Health and Human Services is of paramount importance. Applicants are urged to pay particular attention to the instructions for compliance with regulations concerning the protection of human subjects contained in the Instructions for PHS 398 (rev. 10/88), including convening an Institutional Review Board (IRB) in the host country and developing appropriate consent forms in compliance with DHHS regulations. MINORITIES AND WOMEN The NIH in general, and the NIAID in particular, place special emphasis on the need for inclusion of individuals belonging to those ethnic groups that are considered to be disenfranchised or underprivileged in studies of diseases which disproportionately affect them. Applicants are urged to give special attention, where feasible and appropriate, to the inclusion of these groups in these studies. It is understood that the majority of the study population in the ICARS will, by definition, be comprised of populations which are in a minority in the U.S., which NIAID considers as supportive of an important objective of the Institute. In addition, NIAID urges the applicants to make a special effort to recruit women into study populations, and to devote ICAR resources to studying gender-related issues in HIV infection and disease. III. Additional Information A. Definition of Program Project Grant A program project grant is a mechanism to support a broadly based multidisciplinary research program that has a well-defined central research focus or objective. A principal investigator (PI) representing a U.S. institution is responsible for leadership of the overall program. The application must document the scientific and administrative competence of the PI and provide evidence that the PI has had professional experience in the host country. The program project grant consists of three or more interrelated sub- projects that contribute to the program objective. Each of these scientifically meritorious sub-projects usually is under the leadership of a co-investigator, referred to as a project leader, who usually will be on site in the host country. B. Site of Research Most of the research should be conducted in the foreign country, and the funds should be allocated between the U.S. and host country accordingly. At least 70 percent of all direct costs should be spent in the host country. Any application with below 50 percent of the funds spent in the host country will be returned to the applicant without further review. Any application with between 51 and 69 percent of funds spent in the host country should include strong justification for the reduced foreign allocation and will be considered for acceptance on a case-by-case basis. The U.S. Grantee institution is responsible for developing a mutually acceptable affiliation with an established university, research institute, federal or state health department, hospital, laboratory, etc., in the host country. For an award to be considered, the domestic applicant institution must include proof of affiliation with a host country institution offering to provide a base for project operations and one or more host country collaborators specified as co-investigators. The grant application will not be reviewed unless proof of an acceptable foreign affiliation is included; a letter of agreement signed by a sanctioned representative of the host country institution shall be accepted as proof of affiliation. In addition, it will be necessary to provide documentation that the government of the host country approves of the affiliation and research plans and will facilitate the duty-free importation of equipment and supplies from the U.S. to the host country. Also, it is essential that a plan for release of research findings generated by the collaboration be included with the application. It is anticipated that publications resulting from such collaborative research efforts will be co-authored by foreign and US scientists and that the data will be available to scientists both in the host country and in the U.S. collaborating institution. The plan should demonstrate that host country researchers will take key roles in preparing, authoring, and presenting scientific findings in national, U.S., and/or international refereed journals and scientific meetings. The investigators should demonstrate awareness of other pertinent bilateral or multilaterally-funded research activities in the host country in order to avoid duplication of effort or to take advantage of biomedically-related research or program interventions already underway. C. Off-Site Facilities The grant can provide support for common resources (e.g. laboratory or clinical facilities) that are utilized by two or more projects within the program when such sharing facilitates the total research effort in a cost-effective manner. Since this program is covered by Public Law 86-610, existing facilities may be renovated but new structures may not be constructed. The most successful international collaborations incorporate a thorough integration of host and U.S.- based researchers. It is expected that a core of scientists from the U.S. institution would spend six months to two years or more at the host institution, collaborating with host country scientists in working toward solutions to local health problems associated with HIV infection. Senior scientists with major institutional responsibilities in the U.S. would be expected to spend shorter periods of time, e.g., one or two months at a time several times during the course of the grant. Also, it is permissible to support the travel of foreign professionals and selected technical staff for short visits to the US institution to obtain additional training. D. Guest Scientists To increase the exchange of scientific ideas and expertise, it may be desirable to include one position in the overall personnel projection for a guest scientist from another domestic institution to spend 6-12 months of a sabbatical leave at a host country institution. The nominated individual must have the joint approval of the applicant organization, the host country organization, the nominee, and the nominee's home institution, and must have prior approval by the NIAID. IV. Administration Limited support for administrative activities and research endeavors at the U.S. institution are permitted as long as at least 70 percent of the grant funds (direct costs) are expended in the host country, as discussed above. Recovery of indirect costs will be based on the percentage effort expended by the grantee personnel. Indirect costs will not be paid on any expense incurred by the host country institutions. Coach class travel, or the equivalent thereof, on U.S. flag carriers must be used for international travel. Travel, salary and fringe benefits, and allowances for housing of U.S. personnel based in the host country will be subject to the applicant organization's rules and regulations. Official approvals must be obtained as follows: A. Staff of U.S.-based institutions who visit the host country in connection with ICAR activities must have the concurrence of the U.S. Embassy in the host country prior to the visit. B. Persons coming from other countries to visit the host country on behalf of the applicant institution also must have the concurrence of the U.S. Embassy in the host country prior to the visit. C. A mechanism for approval by officials of the host country for receiving visitors must be developed and must be described in the proposal. Requests for concurrence by the U.S. Embassy must be requested no later than four (4) weeks prior to commencement of travel. Plans should be made for an orderly rotation of domestic investigators visiting the host country base that would not be disruptive to the ongoing research program. For persons planning a prolonged residence at the host country base, opportunities should be made for periodic return visits to the parent or related domestic institutions for training, program planning, or data analysis and to attend relevant scientific meetings. Consequently, domestic investigators based overseas should have the opportunity to participate in scientific forums inside and outside the host country. A. Support Mechanism Approved grants will be funded for up to five (5) years. Long-term support is considered essential for the development of projects that will fully utilize the international medical experience of the individual scientist and that develop effective linkages between domestic and foreign investigators. However, continued support will be based on the satisfactory performance of the grantee as judged by progress described in annual reports (including copies of abstracts and papers submitted for presentation at scientific meetings or for publication) and by periodic site visits by NIAID program personnel. The total cost per grant should be between $300,000 and $500,000 per year (including direct and indirect costs). One (1) to two (2) awards shall be made contingent upon the availability of funds and receipt of a sufficient number of high quality applications. This grant is anticipated to supply seed money for attracting additional funding from other sources. It is expected that the foreign investigators will be encouraged, and assistance will be provided if requested, in preparing grant applications to request such outside support. Grantee institutions which have demonstrated good progress during the project period will be encouraged to reapply for a competing renewal grant application. V. REVIEW PROCEDURES Before preparing an application, the prospective applicant should carefully read the NIAID Information Brochure on Program Project and Center Grants that accompanies copies of this Request for Applications (RFA). The Information Brochure contains special instructions for preparing multi-project applications, review procedures, review criteria and other important information. It is important to follow the instructions for preparing the application as outlined in the Information Brochure. Failure to do so may result in an application with insufficient information for appropriate scientific review. Applications will be reviewed by NIAID staff to determine administrative and programmatic responsiveness to this RFA; those judged to be non- responsive will be returned to the applicant without review. Those applications that are complete and responsive may be subjected to a triage by an NIAID peer review group to determine their scientific merit relative to the other applications received in response to this RFA. NIH reserves the right to withdraw from competition those applications judged as non- competitive and to so notify the applicants. Those applications judged to be competitive for award will be further reviewed for scientific and technical merit by the AIDS Research Review Committee convened by the Division of Extramural Activities, NIAID, during July, 1990. The final level of review will be provided by the National Advisory Allergy and Infectious Diseases Council. REVIEW CRITERIA The application must be directed towards the attainment of the stated programmatic goals (see Section II, "Research Objectives and Scope"). Review criteria outlined in the NIAID Information Brochure for Program Project and Center Grants will be used by the scientific review group to evaluate proposals. The following ADDITIONAL factors will be considered in the scientific and technical review of the application: A. Relevance of applicant's objectives to objectives of the RFA; B. Documented commitment of collaborating institutions and availability of host country personnel; C. Administrative experience and competence of Principal Investigator in the development, implementation, and management of comprehensive research programs and documented capability of Principal Investigator's institution to coordinate the collaboration; D. Familiarity of the principal investigator with the investigators and facilities of the host country institution, and the study populations; E. Adequacy of existing physical facilities and resources of the domestic and host country institutions; F. Applicant awareness of the NIH desire to include women and minorities in study populations, and sensitivity to the host country's culture and to the protection of human subjects. VI. METHOD OF APPLYING The deadline for receipt of applications is March 30, 1990. Applications received after this date will be considered as not responsive to this RFA and will be returned without review. APPLICATIONS THAT ARE NOT RECEIVED AS A SINGLE PACKAGE FROM THE PRINCIPAL INVESTIGATOR AND THAT DO NOT CONFORM TO THE INSTRUCTIONS CONTAINED IN THE PHS 398 (rev. 10/88) APPLICATION KIT WILL BE JUDGED NON- RESPONSIVE AND WILL BE RETURNED TO THE APPLICANT. The regular research grant application form PHS-398 (rev. 10/88) should be used and is available at most institutional business offices or from: Office of Grants Inquiry Room 449 Westwood Building Division of Research Grants National Institutes of Health 9000 Rockville Pike Bethesda, Maryland 20892 Submit a signed, typewritten original of the application, including the Checklist, and six signed, exact, single-sided photocopies, in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, Maryland 20892** If sending the application by overnight mail or courier service, send the application to the above address, but using 20816 as the Zip Code. The RFA label available in the form PHS-398 (rev. 10/88) must be affixed to the bottom of the face page of the original signed application. Failure to use this label could result in delayed processing of the application such that it may not reach the committee in time for review. TO ASSURE THE IDENTIFICATION OF YOUR APPLICATION WITH THIS RFA: The application form must have "International Collaboration in AIDS Research (ICAR)" (RFA 89- AI-21) typed on item 2 of the face page of the application form; and SUBMIT 17 EXACT COPIES OF YOUR APPLICATION DIRECTLY TO: Dr. Manuel J. Torres-Anjel Executive Secretary Epidemiology and Technology Transfer Sub-Committee AIDS Research Review Committee, AIDS Section Program Project and Review Branch National Institute of Allergy and Infectious Diseases Westwood Building, Room 3A10 Bethesda, MD 20892 (301) 496-0818 If sending the application by overnight mail or courier service, send the application to the above address, but using 20816 as the Zip Code. Inquiries regarding matters pertaining to the review of this application or instructions in the brochure should be directed to Dr. Torres-Anjel. Inquiries regarding fiscal matters may be addressed to Ms. Mary Kirker. Questions regarding responsiveness to the RFA should be directed to Ms. Amy R. Sheon. Ms. Mary Kirker Grants Management Branch International Health Section Westwood Building, Room 710 Division of AIDS, NIAID, NIH Bethesda, Maryland 20892 Telephone: (301) 496-7075 Ms. Amy R. Shoen Epidemiology Branch NIAID, NIH 6003 Executive Boulevard Bethesda, Maryland 20892 Telephone: (301) 496-6177 REFERENCES Centers for Disease Control: AIDS and human immunodeficiency virus infection in the United States: 1988 update. MMWR 1989; 38 (4), May 12. Chin J, Mann JM: The global patterns and prevalence of AIDS and HIV infection. AIDS 1988; 2: S247-252. Clavel F: Editorial review: HIV-2, the west African AIDS virus. AIDS 1987; 1: 135-140. Des Jarlais DC, Friedman SR: HIV and intravenous drug use. AIDS 1988; 2: S65-S69. Johnson AM, Laga M: Heterosexual transmission of HIV. AIDS 1988; 2: S49-S56. Lucas S, Goodgame R, Kocjan G, Serwadda D: Letter: Absence of pneumocystosis in Ugandan AIDS patients. AIDS 1989: 3: 47. Rolfe M, Wels KHG: Letter: Kaposi's sarcoma in Zambian children. AIDS 1987; 1: 259-260. Ryder RW, Hassig SE: The epidemiology of perinatal transmission of HIV. AIDS 1988; 2: S83-S89. SPECIALIZED CENTERS OF RESEARCH FOR CHRONIC DISEASES OF THE AIRWAYS, OCCUPATIONAL AND IMMUNOLOGIC LUNG DISEASES, AND LUNG BIOLOGY AND DISEASE IN INFANTS AND CHILDREN RFA 90-HL-01-L P.T. 04, AA; K.W. 0715165, 0705065, 0785055, 1002004, 1003002, 1002034 NATIONAL HEART, LUNG, AND BLOOD INSTITUTE Application Receipt Date: July 16, 1990 GENERAL INFORMATION The Division of Lung Diseases (DLD) is announcing its Specialized Centers of Research (SCOR) programs for new and renewal applications in the following categories: o Chronic Diseases of the Airways o Occupational and Immunologic Lung Diseases o Lung Biology and Disease in Infants and Children These SCOR programs represent a concerted effort that involves both clinical and basic research relative to the etiology, diagnosis, pathogenesis and treatment of these disorders. The special features of SCOR grants include: o They provide opportunities for investigators with mutual or complementary interests to engage in multidisciplinary research focusing on a specific respiratory disorder. o Inherent in the SCOR program is a special interaction between the SCOR director, the grantee institution and the DLD. Funds specifically allocated in a SCOR grant make it possible for investigators from different SCORs to meet and discuss problems of mutual interest and to participate in workshops addressing common research areas. o The DLD's overall SCOR program and each SCOR grant undergo periodic evaluation. The resulting reports of progress are prepared for the information of the Pulmonary Diseases Advisory Committee, the National Heart, Lung, and Blood Advisory Council, and DLD staff. The requirements of SCOR grants include: o Research efforts of the individual centers must emphasize both basic science and clinical research, to assure that advances in the basic sciences are translated rapidly into clinical applications and that clinical needs will provide a direction for the basic sciences. Therefore, applications must include one or more research projects involving human subjects, human materials, or both. Applications must also include basic research projects which clearly relate to the disease focus and which contribute to elucidation of mechanisms underlying the disease, or to improved diagnosis or management of the disease. o Each SCOR must have a well-delineated organizational structure and administrative mechanism to ensure a productive research effort. Because of the size and complexity of a SCOR, prospective applicants are urged to take advantage of the opportunity to consult with DLD staff early in the preparation of the application (See Method of Applying). To provide opportunity for such interactions, the time frame for implementation of this program includes an ample interval between the release of this announcement (11/89) and the receipt date for applications (07/16/90). BACKGROUND AND HISTORY OF THE SCOR PROGRAM The SCOR program was initiated within the Division of Lung Diseases in 1971 as a "Pulmonary SCOR". Since then, several modifications and changes in program direction have been made based on advice and recommendations from the Pulmonary Diseases Advisory Committee. In the 1975 and 1980 competitions, the DLD SCOR program was announced in four disease categories: chronic airways diseases, fibrotic and immunologic lung diseases, pediatrics, and pulmonary vascular diseases; in the 1985 competition the disease categories were: chronic diseases of the airways, occupational and immunologic lung diseases, respiratory diseases of neonates and children and pulmonary vascular diseases. The program expanded in 1977 with the solicitation for applications for adult respiratory failure SCOR grants. Awards were made in two new SCOR disease categories, cystic fibrosis and cardiopulmonary disorders of sleep, following a national competition in 1988. Therefore, new applications entirely devoted to cystic fibrosis or cardiopulmonary disorders of sleep will not be considered responsive to this solicitation as these two topics are the subject of recent SCOR programs. However, individual projects on these topics, if they fit the theme of the center application, may be included in response to this solicitation. In preparation for the current competition, the DLD conducted a series of workshops which included members of the Pulmonary Diseases Advisory Committee, participants in SCOR programs, and ad hoc advisors. Several recommendations made during the workshops have been incorporated into this announcement. For example, the change in the name of the program "Respiratory Diseases of Neonates and Children" to "Lung Biology and Disease in Infants and Children" was a specific recommendation of the workshop participants. Likewise, the scientific program examples under Objectives, Research Goals and Scope of this announcement were recommendations from these meetings. One of the major recommendations from the workshops was to combine the "Pulmonary Vascular Diseases" and "Adult Respiratory Failure" SCOR programs into a single program. This will not be possible as part of this solicitation as the two programs are not in phase, therefore, the DLD will invite the two current pulmonary vascular diseases centers to submit two year renewal applications in response to this announcement; they will compete for available funds (see Mechanism of Support) with all new and renewal applications that are submitted in the three disease categories included in this announcement. OBJECTIVES, RESEARCH GOALS AND SCOPE Applications must be addressed to only one of the three disease categories identified below to be acceptable for this competition. A SCOR grant is a five-year program, therefore, an applicant should submit a five-year plan for all the projects. If a project can be completed in less than five years, it should not be included in the application. Applications may include longitudinal studies or epidemiologic surveys if they are based on populations already under study. The grant will not provide funds for selection of new populations but will support appropriate expansion of populations already being examined under an existing SCOR or under some other program. The maintenance of an ongoing study population, however, is not in itself justification for funding a center. Women and minority individuals should be included in the study population; otherwise, a clear rationale for their exclusion must be provided in the application. Examples of research topics of interest for each SCOR program under competition are listed below. These research topics are intended to provide a perspective of the scope of research that would meet the objectives of this program. It is not required that all or any of these topics be included; investigators are encouraged to consider other topics that are relevant to the goals of these programs. 1 Chronic Diseases of the Airways Chronic bronchitis, emphysema, and the pulmonary aspects of adult and pediatric asthma are the major diseases included in this program area. Elucidation of the basic molecular, cellular and pathophysiologic mechanisms underlying these diseases, combined with strong clinical studies aimed at prevention, improved diagnosis and treatment of these disorders, remain the major goals of research. The research topics identified below are offered only as examples of areas of interest. Better definition of the cellular, humoral and neural mechanisms underlying airways inflammation and airways obstruction is needed. A combination of biochemical, cellular biology and physiologic approaches should help to elucidate the relationship between inflammatory and repair processes and airway obstruction. Further investigations to examine the cellular and biochemical mechanisms of parenchymal lung destruction in emphysema and the relationship of parenchymal destruction to chronic airflow obstruction are also needed. The factors regulating normal airway tone are still not understood. Also the mechanisms by which airways narrow during bronchoconstriction require further definition. The relationship between airway hyperreactivity and acquired smooth muscle hypercontractility warrants further study. Investigations are also needed to determine the role of the bronchial circulation in airway injury and repair. Studies of the effects of chronic obstructive lung disease on respiratory muscle structure and function and on the pulmonary circulation are encouraged. The production, clearance and regulation of airway secretions in health and airway diseases need to be addressed. An important topic for study is the natural history of acute and chronic airways disease, particularly in their early phases, including the effect of respiratory diseases in childhood on pulmonary health in later life. One approach could be through population based studies with emphasis on the identification of risk factors, host and environmental determinants, disease markers and predictors. The genetic basis of airway disease is also of interest. This topic could be addressed using either animal models or existing cohorts. Critical assessment of therapeutic measures and development of new therapeutic strategies remain important goals of this program. 2 Occupational and Immunologic Lung Diseases The Occupational and Immunologic Lung Diseases Program includes basic and clinical research on diseases resulting from exposure to inhaled organic and inorganic substances that may be found in the ambient air of the home or the workplace. Also included in this program are the fibrotic and granulomatous lung diseases of unknown etiology. To be considered responsive to this request, applications should be directed primarily toward investigations of pulmonary processes. Accordingly, proposed studies of systemic responses to substances, even if delivered by the pulmonary route, will not be considered responsive. The research topics identified below are offered only as examples of areas of interest. Of continued interest to the Occupational and Immunologic Lung Diseases SCOR Program is fundamental research on the pulmonary immune system and the role of basic immunologic mechanisms involved in the onset and progression of human interstitial lung diseases. For pulmonary diseases of unknown cause such as idiopathic pulmonary fibrosis and sarcoidosis, determination of the etiology and mechanisms leading to the development of fibrosis in the lung is of particular interest. The pathogenesis of pulmonary fibrosis associated with the pneumoconioses (silicosis and asbestosis) is not well defined and requires continued clinical and basic research efforts. Little is known about the genetic factors that regulate the host response that contributes to the fibrotic process in the lung. Application of molecular genetic and molecular biologic approaches to the study of interstitial lung diseases constitutes a new and desirable direction for future clinical application. The mechanisms by which the human lung responds to infections, whether bacterial, viral, or other microbial agents, are poorly understood. Investigations are needed to define the effects of infections on cellular responses such as the production of cytokines, the induction of inflammatory mediators and the evocation of immune responses in the lung. These studies should be designed to elucidate the events that take place during the reparative processes which occur in the injured human lung, and ultimately the development of chronic interstitial lung disease. Basic studies of the occupational lung diseases resulting from exposure to a wide variety of industrial and other workplace substances are needed. For example, immunochemical studies designed to better characterize and purify antigens from organic dusts may lead not only to improved understanding of the immunologic mechanisms triggered by antigens but also to development of more sensitive and specific diagnostic tests. Application of molecular biological and immunologic technology should help to develop more effective techniques for screening individuals who are at increased risk for development of occupational lung disease. 3 Lung Biology and Disease in Infants and Children The objective of this SCOR program is to expedite the development and application of new knowledge essential for improving the diagnosis, management and prevention of respiratory disorders in neonates, infants and children. Applications should include multidisciplinary approaches that take advantage of the most current ideas and methods of molecular and cellular biology, neurobiology, immunology, developmental biology and physiology. An important goal of this program is to attract basic scientists with expertise in these disciplines, and clinical investigators with training in areas other than neonatal lung diseases, to work with pediatric pulmonary clinicians on problems that encompass the breadth of pulmonary biology and disease in infants and children. The research topics identified below are offered only as examples of areas of interest. Recent advances in molecular and cellular biology offer new opportunities for significant progress in understanding the factors that control growth and differentiation in the developing lung, and that determine the response of the developing lung to injury and repair. The cell biology of developing airway epithelium and the changes in pulmonary endothelial cell functions during development are areas that need further exploration. Developmental neurobiology, including the neuroanatomy, physiology and pharmacology of the developing respiratory networks, needs further investigation. Genetic expression of putative neuromodulators, peptides and mediators during lung development, and the relation of these events to the control of breathing during the perinatal period is another area requiring investigation. These approaches may provide new insights and a better understanding of infant apnea and apnea of prematurity. Since the newborn period is a time of great vulnerability to pulmonary infections, continued efforts are needed to enhance understanding of lung host defense mechanisms. Little is known about the development of pulmonary immune functions, how prematurity affects lung defense functions or the influence of environmental factors on lung defense functions in neonates, infants and children. These issues are important to the development of new approaches for the prevention and treatment of diseases caused by respiratory infections in pediatric populations. Although surfactant replacement therapy holds great promise for the prevention and amelioration of neonatal respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD), strategies for improving respiratory therapies to reduce or minimize chronic lung disease are needed. Careful followup of survivors of RDS and BPD to determine long-term sequelae remains an important priority. The role of genetic factors in determining susceptibility to RDS or chronic lung disease is not known at this time. The efficacy of lung surfactant in treatment or prevention of acute lung injury syndromes, pneumonia, and perhaps other pediatric respiratory disorders also should be explored. EXCLUSIONS Support will not be provided under SCOR grants for research activities focused exclusively on clinical trials or epidemiologic studies. Similarly, support will not be provided for proposed programs containing only basic or only clinical research. While the development of new instrumentation may be a part of a SCOR, support cannot be provided for instrument development alone. In general, funds will not be made available for the purchase and installation of expensive, new equipment that is not closely linked to proposed research. Institute staff should be consulted if there are questions regarding these exclusions. MECHANISM OF SUPPORT The support mechanism for the SCORs solicited in this Request for Applications (RFA) will be the research grant-in-aid (P50) for a period of five years commencing December 1, 1991 (Fiscal Year 1992). Thus, all policies and requirements which govern the grant programs of the Public Health Service will prevail, including the requirement for cost sharing. However, it will differ from the traditional research grant in the degree of goal orientation and in the degree of direct participation by the National Heart, Lung, and Blood Institute (NHLBI). While it is expected that the investigators of the individual centers will plan, direct and execute their own research program, any substantive modifications in the program must be mutually agreed upon by the center director, the grantee institution and the NHLBI. The DLD will monitor the progress of each center throughout the five-year period of support. To foster cooperation among centers, the DLD may arrange periodic meetings of the SCOR investigators. Applicants should include a statement in the application indicating a willingness to participate in such meetings. The policy for SCOR grants establishes the following limits to the requested budgets: o Applications for new SCOR grants may request up to $1.0 million direct costs in the 01 year with a maximum of 4 percent annual escalation thereafter. o Competing renewal applications for SCOR grants may request up to $1.0 million direct costs or 10 percent increase in direct costs over the last noncompeting year, whichever is greater, in the first year of renewal, with a maximum of 4 percent annual escalation thereafter. Applications which exceed these limits will be returned. Requests for special equipment which cause the applications to exceed these limits, however, will be permitted and considered on an individual basis. Applicants should contact DLD staff if they have questions (see Method of Applying). Although this solicitation is included in the plans for Fiscal Year 1992, support of grants pursuant to this announcement is contingent upon receipt of appropriate funds. It is anticipated that 14-20 SCORs will be funded at a total cost of approximately $24 million. The funding of SCORs will be influenced by the amount of funds available to NHLBI, by the overall scientific merit of applications, and by their relevance to NHLBI program objectives. A variety of approaches could be responsive to this solicitation. Accordingly, it is anticipated that there will be a range of requested costs among individual grant applications submitted. REVIEW PROCEDURES AND CRITERIA Applications for SCOR grants will be reviewed and evaluated for scientific, technical and programmatic merit by an initial review group specifically convened for this purpose by the Division of Extramural Affairs, NHLBI. Applications deemed sufficiently meritorious will be site visited. A second level review will be performed by the National Heart, Lung, and Blood Advisory Council. Applicants should submit the strongest application possible. Revisions of applications (additions and deletions of projects, cores or studies) after submission will no longer be permitted. The NHLBI has established a new policy that a SCOR grant application may not be modified by the applicant during the review process, which begins with the submission of the application to the Division of Research Grants (DRG). All projects reviewed at a site visit will be included when the proposal is evaluated by the parent review committee and also when it is considered by the NHLBI Advisory Council. During the review, individual projects will be disapproved by the reviewers only if they are considered to have no scientific merit and will be deleted only if they do not fit into the overall programmatic theme of the application. The major factors to be considered in the evaluation of applications will be: 1 The scientific merit of each proposed project, including the novelty, originality, feasibility and the adequacy of the experimental design; 2 The justification of any core unit designed to support a major component(s) of a SCOR; 3 The adequacy of resources and facilities to support the proposed clinical and basic research; 4 The integration of the various components into an effective center, and the adequacy of plans for interaction and dissemination of information among investigators; 5 The competence of the investigators to accomplish the proposed research goals, and the adequacy of their time commitments to the SCOR program; 6 The qualifications, experience and commitment of the center director and the director's ability to devote adequate time and effort to provide effective scientific and administrative leadership to the SCOR; and 7 The adequacy of internal and external procedures of monitoring and evaluating the proposed research and for providing ongoing quality control and scientific review. Other factors that will be considered in the evaluation of applications include: 1 The commitment of the grantee institution and any cooperating institutions to the program, and the appropriateness of its resources and policies for the administration of a research program of the type proposed; 2 The appropriateness of the budget; and 3 The willingness to interact with other centers and with the NHLBI. METHOD OF APPLYING Letter of Intent. Prospective applicants are requested to submit a letter of intent by April 16, 1990. The letter should include a descriptive title, investigators who might be involved, and any participants outside the applicant institution. The Institute requests such letters only for the purpose of providing an indication of the number and scope of applications to be received and, therefore, usually does not acknowledge their receipt. A letter of intent is not binding; it will not enter into the review of any application subsequently submitted, nor is it a necessary requirement. The letter of intent should be sent to: Charles L. Turbyfill, Ph.D. Review Branch, Division of Extramural Affairs National Heart, Lung, and Blood Institute, NIH Westwood Building, Room 553 Bethesda, MD 20892 Format for Applications Submit applications on PHS Form 398 (rev. 10/88), the same form used for the traditional research-project grant. This form is available in an applicant institution's office of sponsored research (or business office) or from DRG. Specific instructions for preparing a SCOR application are available and should be requested from DLD. Submission of Application Send or deliver the completed application and four (4) signed exact photocopies of it prior to July 16, 1990 to: Division of Research Grants Westwood Building, Room 240 National Institutes of Health Bethesda, Maryland 20892** In addition, two signed copies of the application should be sent directly to Dr. Charles L. Turbyfill at the address listed under Letter of Intent. Applications not received by July 16, 1990, will be considered ineligible. Timetable RFA Release Date: -November 1989 Letter of Intent: -April 16, 1990 Application Receipt Date: -July 16, 1990 National Heart, Lung, and Blood Advisory Council Review: -May 23-24, 1991 Program Initiation: -December 1, 1991 Inquiries Prospective applicants are strongly advised to discuss their potential programs or to seek clarification of this announcement and the special instructions for preparation of applications. Inquiries about preparation of applications should be addressed to: Suzanne S. Hurd, Ph.D. Director Division of Lung Diseases National Heart, Lung, and Blood Institute Westwood Building, Room 6A16 Bethesda, Maryland 20892 (301) 496-7208 The programs of the Division of Lung Diseases of the National Heart, Lung, and Blood Institute are identified in the Catalog of Federal Domestic Assistance, number 13.839. Awards will be made under the authority of the Public Health Service Act, Section 301 (42 USC 241) and administered under PHS grant policies and Federal regulations, most specifically 42 CFR Part 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372, or to Health Systems Agency Review.