From owner-sci-resources@net.bio.net Wed Jan 04 22:00:00 1995 Path: biosci!biosci!not-for-mail From: BIOSCI Administrator Newsgroups: bionet.sci-resources Subject: NSF - Summary of new documents on STIS - 1 January 1995 Date: 4 Jan 1995 14:32:29 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 52 Sender: biohelp@net.bio.net Approved: biosci-moderator@net.bio.net Distribution: world Message-ID: <3ef7lt$6o@net.bio.net> This message contains a summary of the documents added to the NSF STIS system in the previous week. Reference material concerning STIS follows the summary. ------------------------------------------------------------------------ ** UPDATES TO EXISTING STIS DOCUMENTS ** Document Type: Letter Title: Current List of REU Sites File size (bytes): 88039 STIS Filename: reulist ------------------------------------------------------------------------ ** FOR YOUR REFERENCE ** ------------------------------------------------------------------------ HOW TO OBTAIN DOCUMENTS The above files can be retrieved in electronic form using the STIS system. If you don't know how to use STIS, send an E-mail message to stisinfo@nsf.gov (Internet). You will receive a copy of the STIS flyer via E-mail. If you are already using STIS, you can use the information above to retrieve these files: Documents via E-mail: Send a message to stisserve@nsf.gov (Internet). Use the "STIS Filename" shown above in the "get" command. For example, to retrieve reulist, the text of your message should be as follows: get reulist Anonymous FTP: FTP to stis.nsf.gov. Use the "STIS Filename" shown above to retrieve a file. For example, to retrieve reulist, you would enter: ftp> get reulist WAIS or Gopher: Do a word search on the filename as shown in the summary. If you want a *printed* copy of a document: Send your name and postal mailing address, and the document title and number to "pubs@nsf.gov" (Internet). If you have problems with the above procedures: Send a message to "stis@nsf.gov" (Internet). From owner-sci-resources@net.bio.net Thu Jan 05 22:00:00 1995 Path: biosci!biosci!not-for-mail From: Jay Snoddy Newsgroups: bionet.sci-resources Subject: Small Business Innovation Research solicitation is available (fwd) Date: 6 Jan 1995 13:40:31 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 86 Sender: biohelp@net.bio.net Approved: biosci-moderator@net.bio.net Distribution: world Message-ID: Reply-To: snoddy@oerhp01.er.doe.gov NNTP-Posting-Host: net.bio.net Please excuse any cross-postings. RE: SMALL BUSINESS INNOVATION RESEARCH; DEPARTMENT of ENERGY Solicitation for grant applications Topics: Human Genome Computerized Processing of Biological Data Medical Applications Advanced Environmental Monitoring Technologies and other topics DUE DATE: March 1, 1995 ----------------------------------------- The Office of Health and Environmental Research of the Office of Energy Research would like to call your attention to the 1995 solicitation for grant applications to the Department of Energy (DOE) Small Business Innovation Research (SBIR) program. From this solicitation, about 200 Phase I grant applications from small businesses (500 employees or less) for up to $75,000 over a period of about 6 months will be funded for feasibility studies. Some of these will continue into Phase II, which is the principal research and development effort, funded at up to $750,000 over a two-year period. Grant applications are sought in 44 technical topics which are described in Appendix I of the published solicitation. The awards will be made on a competitive basis among all of the topics. Please note the following topics might be of particular interest for individuals on this electronic newsgroup. Topic No 9. Advanced Environmental Monitoring Technologies ** 10. Human Genome ** 11. Computerized Processing of Biological Data 13. Medical Applications Grant applications are invited only for specific subtopics that are further elaborated in the solicitation. That solicitation contains detailed descriptions of the technical topics and what is sought in grant applications; please note that the technical topics described in the solicitation are to be interpreted literally. Following the instructions and text descriptions found in the solicitation is critical in preparing an application. In many cases, a critical impetus in winning an SBIR grant has been the suggestion by a research scientist to a suitable small business of the need for new instrumentation or technology. Very much in line with the philosophy of the SBIR program, this catalytic action on the part of active researchers has helped interested and competent small businesses develop superior grant applications. Copies of the current DOE SBIR solicitation can be obtained by writing to the following address: SBIR Program Manager, ER-16 U.S. Department of Energy Washington, D.C. 20585 You may also call (301) 903-5707 to receive a copy. In addition you may send a request to sbir-sttr@mailgw.er.doe.gov. The due date for the receipt of grant applications is March 1, 1995. Questions about the program should be addressed to Kay Etzler, the SBIR spokesperson, on (301) 903-5867. However, since the solicitation is subject to the procurement regulations of the Federal Government, no further elaborations will be provided by the SBIR office on any of the written descriptions of the 44 technical topics. ---------------------------------------------------------------------- -Jay Snoddy- Internet: snoddy@er.doe.gov -DOE Human Genome Program- Phone: 301-903-2792 FAX: 301-903-8521 ---------------------------------------------------------------------- From owner-sci-resources@net.bio.net Mon Jan 09 22:00:00 1995 Path: biosci!biosci!not-for-mail From: BIOSCI Administrator Newsgroups: bionet.sci-resources Subject: NSF - Summary of new documents on STIS - 8 January 1995 Date: 9 Jan 1995 16:44:24 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 143 Sender: biohelp@net.bio.net Approved: biosci-moderator@net.bio.net Distribution: world Message-ID: <3esl98$hun@net.bio.net> NNTP-Posting-Host: net.bio.net This message contains a summary of the documents added to the NSF STIS system in the previous week. Reference material concerning STIS follows the summary. ------------------------------------------------------------------------ ** NEW DOCUMENTS ON STIS ** Document Type: International Document Title: INT 95-001 -European Science Foundation Debates Future Role File size (bytes): 14032 STIS Filename: int95001.txt Title: INT 95-002 - Current Status of Programs to Support American Researchers in Japan File size (bytes): 4356 STIS Filename: int95002.txt Title: INT 95-003 - NEDO's International Joint Research Grants for Japan FY 1994 File size (bytes): 8727 STIS Filename: int95003.txt Title: INT 95-004 - 1994 Survey of Research and Development in Japan File size (bytes): 6525 STIS Filename: int95004.txt Title: INT 95-005 - White Paper on Science and Technology Japan FY 1994 File size (bytes): 4947 STIS Filename: int95005.txt Document Type: Program Guideline Title: NSF 94-170 - CISE Minority Institutions Infrastructure Program File size (bytes): 22383 STIS Filename: nsf94170.txt Title: NSF 94-171 -- Combined Research-Curriculum Development Program File size (bytes): 19569 STIS Filename: nsf94171.txt Title: NSF 94-173 THE U.S. TROPICAL OCEAN GLOBAL ATMOSPHERE PROGRAM COUPLED OCEAN-ATMOSPHERE RESPONSE EXPERIMENT File size (bytes): 14176 STIS Filename: nsf94173.txt Document Type: Recruit Title: Chemist (Program Director) File size (bytes): 5408 STIS Filename: vex952.txt Title: Mathematician (Program Director) File size (bytes): 4620 STIS Filename: vex955.txt Title: Mathematician (Program Director) File size (bytes): 5708 STIS Filename: vex956.txt Title: Secretary (Office Automation) File size (bytes): 6438 STIS Filename: vgs9544.txt Title: Supervisory Computer Specialist (Section Head) File size (bytes): 7099 STIS Filename: vgs9545.txt Title: Investigative Assistant (Office Automation) File size (bytes): 5047 STIS Filename: vgs9547.txt Title: Clerical and Administrative Support Positions File size (bytes): 7290 STIS Filename: vgs9548.txt Title: Secretary (Office Automation) File size (bytes): 7553 STIS Filename: vgs9549.txt ------------------------------------------------------------------------ ** UPDATES TO EXISTING STIS DOCUMENTS ** Document Type: Form Title: NSF 94-3 - Grant Proposal Guide Forms Kit(Revised) File size (bytes): 1469 STIS Filename: nsf943.txt Also available: nsf943.zip nsf943.tar Document Type: Phone Book Title: NSF Alpha Telephone File size (bytes): 96782 STIS Filename: phnalpha.txt Title: NSF Organizational Directory File size (bytes): 99792 STIS Filename: phnorg.txt ------------------------------------------------------------------------ ** FOR YOUR REFERENCE ** ------------------------------------------------------------------------ HOW TO OBTAIN DOCUMENTS The above files can be retrieved in electronic form using the STIS system. If you don't know how to use STIS, send an E-mail message to stisinfo@nsf.gov (Internet). You will receive a copy of the STIS flyer via E-mail. If you are already using STIS, you can use the information above to retrieve these files: Documents via E-mail: Send a message to stisserve@nsf.gov (Internet). Use the "STIS Filename" shown above in the "get" command. For example, to retrieve phnorg.txt, the text of your message should be as follows: get phnorg.txt Anonymous FTP: FTP to stis.nsf.gov. Use the "STIS Filename" shown above to retrieve a file. For example, to retrieve phnorg.txt, you would enter: ftp> get phnorg.txt WAIS or Gopher: Do a word search on the filename as shown in the summary. If you want a *printed* copy of a document: Send your name and postal mailing address, and the document title and number to "pubs@nsf.gov" (Internet). If you have problems with the above procedures: Send a message to "stis@nsf.gov" (Internet). From owner-sci-resources@net.bio.net Wed Jan 11 22:00:00 1995 Path: biosci!biosci!not-for-mail From: Ray Dobert Newsgroups: bionet.announce,bionet.sci-resources Subject: NIST UPDATE - DNA Diagnostics funding Date: 11 Jan 1995 22:58:55 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 52 Sender: kristoff@net.bio.net Approved: bionews-moderator@net.bio.net Distribution: world Message-ID: Reply-To: baum@micf.nist.gov NNTP-Posting-Host: net.bio.net Xref: biosci bionet.announce:1677 bionet.sci-resources:1215 Please forward requests for additional information to baum@micf.nist.gov or atp@micf.nist.gov R. Dobert Biotech Info. Center/USDA ---------- Forwarded message ---------- From:baum@micf.nist.gov DATE: January 9, 1995 CONTENTS: New `Tools for DNA Diagnostics' Competition Opened --------------------------------------------------------------------- ADVANCED TECHNOLOGY PROGRAM New `Tools for DNA Diagnostics' Competition Opened NIST's Advanced Technology Program has announced the second focused program competition in the area of Tools for DNA Diagnostics. The technical goal of the program is to develop cost-effective methods to determine, analyze and store DNA sequences for a wide variety of diagnostic applications, such as for agricultural, environmental and health care uses. The business goal of the program is to support the development of a new and potentially very large market for DNA diagnostic systems. An estimated $15 million is available for funding under this competition. Proposals are due by 3 p.m. EST, March 29, 1995. Details of the competition were published in the Dec. 21, 1994, issue of Commerce Business Daily and are available (along with proposal kits) from the ATP office by calling (800) ATP-FUND (283-3863) or sending e-mail to atp@micf.nist.gov (via Internet). Media Contact: Michael Baum, (301) 975-2763 baum@micf.nist.gov ------------------------------------------------------------------ This is the e-mail edition of NIST UPDATE. NIST UPDATE is a bi-weekly synopsis for journalists of current activites, research results, and program announcements from the National Institute of Standards and Technology. If you would like to subscribe to this e-mail edition, send an e-mail note to: MAILSERV@nist.gov In the body of the message, put the command: SUBSCRIBE NIST_UPDATE (don't forget the underbar between T and U). That's all there is to it. Send reports of problems to: baum@micf.nist.gov NIST UPDATE also may be found on the NIST gopher service: gopher-server.nist.gov --------------------------------------------------------------------- From owner-sci-resources@net.bio.net Fri Jan 13 22:00:00 1995 Path: biosci!biosci!not-for-mail From: BIOSCI Administrator Newsgroups: bionet.sci-resources Subject: NIH GUIDE - RFA HL-95-013 - V24(01) 01/13/95 Date: 13 Jan 1995 16:50:36 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 470 Sender: biohelp@net.bio.net Approved: biosci-moderator@net.bio.net Distribution: world Message-ID: <3f774s$onj@net.bio.net> NNTP-Posting-Host: net.bio.net $$XID RFA HL95013 HL-95-013 P1O1 *************************************** HIV-ASSOCIATED PATHOGENS OF THE LUNG: LIFE CYCLE REGULATION NIH GUIDE, Volume 24, Number 1, January 13, 1995 RFA: HL-95-013 P.T. 34; K.W. 0715008, 0715165, 1002027 National Heart, Lung, and Blood Institute Letter of Intent Receipt Date: March 3, 1995 Application Receipt Date: April 28, 1995 PURPOSE The purpose of this solicitation is to encourage research on the molecular basis of cell/life cycle regulation of pathogens and opportunistic microorganisms that cause lung disease in HIV-infected hosts. The request for applications (RFA) focuses on ways in which the environment in the host lung, including signals from host lung cells may affect the microbial mechanisms that determine growth and replication of the microbial agents. Examples of microorganisms that would be appropriate for study under this program are Mycobacterium tuberculosis, Pneumocystis carinii, Histoplasma capsulatum, and Coccidioides immitis. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This RFA, HIV-Associated Pathogens of the Lung: Life Cycle Regulation, is related to the priority area of immunization and infectious diseases. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign for-profit and non-profit institutions, public and private, such as universities, colleges, hospitals, laboratories, units of state and local governments and eligible agencies of the Federal government. Foreign institutions are not eligible for the First Independent Research Support and Transition (FIRST) award (R29). Applications from minority individuals women and new investigators are encouraged. All current policies and requirements that govern the research grant programs of the NIH will apply to grants awarded under this RFA. Awards under this RFA to foreign institutions will be made only for research of very unusual merit, need, and promise, and in accordance with PHS policy governing such awards. Among the disciplines and expertise that may be appropriate for this research program are cell biology, microbiology, genetics, immunology, molecular immunology, molecular biology, infectious diseases, pathology, and pulmonary medicine. MECHANISM OF SUPPORT The support mechanism for this program will be the National Institutes of Health (NIH) individual research project grant (R01) and the FIRST award (R29). While multidisciplinary approaches are encouraged, it is not the intent of this RFA to solicit applications for large studies encompassing a variety of individual subprojects, i.e., program projects. If collaborative arrangements through subcontracts with other institutions are planned, consult the program staff listed under INQUIRIES. Upon initiation of the program, the NHLBI will sponsor periodic meetings to encourage exchange of information among investigators who participate in this program. In the budget for the grant application, applicants should request travel funds for a one-day meeting each year, most likely to be held in Bethesda, Maryland. Applicants should also include a statement in their applications indicating their willingness to participate in these meetings. Applicants (who will plan and execute their own research programs) are expected to furnish their own estimates of time required to achieve the objectives of the proposed research project. Up to five years of support may be requested for R01s; five years are required for FIRST awards. Requested budgets for FIRST awards may not exceed those specified in the FIRST award guidelines. Because a variety of approaches would represent valid responses to this RFA, it is anticipated that there will be a range of costs among individual grants awarded. This RFA is a one-time solicitation. Future unsolicited competing continuation applications may be submitted for peer review and competition for support through the regular grant program of the NIH. It is anticipated that support for this program will begin in September 1995. Administrative adjustments in project period and/or amount may be required at the time of the award. The National Institute of Allergy and Infectious Diseases (NIAID) also supports research aimed at a better understanding of the interactions between the HIV-infected host and a variety of pathogenic and opportunistic infectious agents. Therefore, applications that are of mutual interest are likely to be given a secondary assignment to NIAID in accordance with the NIH referral guidelines. FUNDS AVAILABLE Although financial plans for fiscal year 1995 include approximately $2,000,000 for the total cost of the program for the first year, award of grants pursuant to this RFA is contingent upon receipt of funds for this purpose. It is anticipated that no more than eight awards will be issued under this program. The specific number to be funded will, however, depend on the merit and scope of the applications received and the availability of funds. RESEARCH OBJECTIVES Background The lung is the portal of entry for a variety of microorganisms many of which produce disease associated with the HIV epidemic. Furthermore, the lung is the site of the initial host response to these invading agents and as such is involved in both specific and non-specific mechanisms of defense against infection. In HIV- infected individuals and other immunocompromised hosts the ability of invading agents to disseminate systemically appears to be enhanced due to suppressed cellular immunity. Many of the organisms that threaten immunocompromised individuals have complex life/cell cycles that along with host factors may regulate pathogenic processes in the lung. Little is known about the mechanisms by which pathogenic and opportunistic microorganisms, some of which may have been dormant for years, become harmful to the host. For some of these organisms lack of progress in understanding aspects of their life/cell cycle that influence pathogenesis can be ascribed to difficulty of in vitro culture. For example, the pathogenic Mycobacteria grow very slowly and methods to maintain sustained growth of Pneumocystis carinii in vitro are still being sought. Rapid advances are occurring in understanding the molecular regulation of the order and timing of eukaryotic cell growth and division, including signals that limit growth and cause or prevent cell division. For example, cyclins acting through cyclic-AMP dependent protein kinase appear to be an important feature of the mechanism that integrates cell growth with cell division. A more detailed knowledge of the cell cycle indicates that cell replication appears to depend not just on cell size, but also on the rate of growth and it has become apparent that it is possible for one regulatory mechanism to override another, under certain environmental conditions. Although investigators have begun to define the homeostatic mechanisms that integrate cell growth and division in molecular terms, little is yet known about the enzymatic machinery that might control the rate and timing of life/cell cycling in many pulmonary pathogens and opportunistic agents that cause disease in humans. The mechanisms whereby host cells and specific forms of these microorganisms interact in the lung and the extent to which the intracellular environment of lung cells influence the life/cell cycle of these microbes are also poorly understood. Tuberculosis (TB) has reemerged as an urgent health problem in the United States in the 1980s in conjunction with the HIV epidemic as well as with other factors such as increased homelessness and immigration of people from areas where the incidence of TB is high. An estimated 15 million people in the United States are currently infected with Mycobacterium tuberculosis (Mtb). It is expected that in many of these individuals Mtb will remain dormant, yet a number of them will develop active disease at some point, most likely through reactivation of the organisms they harbor. This is particularly important because of the ease with which Mtb is communicated and because of the many individuals who have medical conditions, especially HIV infection, that increase their risk of developing active TB. A variety of host factors, in addition to HIV infection, put patients at increased risk of TB, presumably by compromising their immune responses. However, little is known about the actual mechanisms that control interactions between the host and Mtb and how such factors may alter the life cycle of the organism. Such knowledge might provide the basis for developing new strategies to prevent and treat TB. Pneumoncystis carinii pneumonia (PCP) continues to be an important complication in individuals infected with HIV. While the use of a number of drugs has had an overall suppressive effect on the incidence of PCP, there remain a number of problems associated with therapy for this infection. It is anticipated that a better understanding of the mechanisms involved in the interaction between host lung cells and the infectious forms of P. carinii might provide alternative approaches for treating this opportunistic infection. Objectives and Scope The objective of this program is to elucidate the role of life/cell cycle regulation of a variety of microorganisms that are associated with the pathogenesis of lung disease, particularly but not exclusively, in the setting of HIV infection. These could include various bacteria, fungi, and protozoa which act as opportunists or as well-recognized microbial pathogens either alone or in combination with HIV infection. Areas of interest under this program include the identification of markers of microbial replication and the interaction of host and microbial factors that allow organisms to continue to remain viable in cells or tissues for many months or years without replicating. Of particular interest are the cellular mechanisms responsible for a change in the relationship between the host cells and the microorganism that lead to active disease processes in the lung. Mycobacteria and P. carinii are likely candidates, but studies that propose to investigate other organisms are also encouraged. For example a variety of fungal organisms such as Histoplasma, Candida, Coccidioides and Aspergillus are also of particular interest. A better understanding of the enzymes controlling life/cell cycle processes might provide insight into the phenomena of microbial latency and activation/reactivation as well as provide novel targets for antimicrobial chemotherapy. The cell division machinery of Mycobacteria, especially Mtb, and the regulation of microbial division, especially in lung tissue, offer potential targets for study with respect to pulmonary tuberculosis. It is thought that the DNA synthetic mechanisms and cell division apparatus of Mtb are unique. The genome of Mtb is 70 percent guanine and cytosine, suggesting that its DNA polymerase has adapted to handle its more highly stable form of DNA. The cell division of Mtb is exceptionally slow for a pathogenic bacterium. It is unknown whether this is due to pauses in DNA synthesis, a low constant rate of DNA synthesis, gaps between DNA synthesis and cell division, or factors unrelated to DNA replication. The DNA replication process of Mtb is thought to be highly error prone which would help explain why the spontaneous occurrence of resistance to chemotherapeutic agents is much higher for Mtb than for other microorganisms. This also suggests that the DNA polymerase of Mtb may proofread inefficiently during replication. The signals that regulate DNA synthesis and the growth of Mtb, especially in the lung remain to be uncovered. The extent to which reactivation may be regulated by DNA replication processes and whether host cell factors influence these processes are completely unknown. While the tubercle bacilli can remain "dormant" for decades in host cells little is known about the signals that regulate the transition between active growth and the "dormant" state. Projects that are directed toward gaining mechanistic insights into the processes of reactivation of Mtb, particularly in the immunocompromised host are of interest. Projects dealing with fungal infections associated with immunocompromised hosts would also be responsive. For example these might focus on Coccidioides immitis which is characterized by a sequence which involves inhalation of infectious conidia into the respiratory tract where they undergo conversion to spherules. It has been suggested that leukocytes and carbon dioxide in the lung play a role in regulating this morphologic change. Once formed the spherules undergo a complex series of processes which give rise to endospores before being distributed locally in the lung or being disseminated to other organs of the body. In addition to the morphologic considerations, a number of other factors are thought to contribute to the virulence of these organisms. These include the antiphagocytic properties of the organism's cell wall, the thickness and large size of the spherule form of the organism and the large number of endospores released from each spherule. The way in which such processes are signalled and regulated are appropriate topics for study under this RFA. In vitro experiments, animal studies and innovative studies using human cells or tissues, are encouraged. Research involving humans should be formulated in the context of mechanistic studies and should address specific hypotheses. Large scale clinical studies are beyond the scope of this RFA. SPECIAL REQUIREMENTS Applications that propose descriptive studies and do not contain hypothesis driven research directed at understanding the mechanisms underlying cell/life cycles of microorganisms and how these contribute to the pathogenesis of lung disease will not be acceptable. Studies focused exclusively on microorganisms will not be acceptable; applications must address microbial-host interactions. Studies directed at understanding how lung cell signals from an immunocompromised host interact with microbial signals to direct microbial growth, replication, dormancy and reactivation are of special interest. Applications that focus on issues relevant to the HIV-immunocompromised host and that use molecular approaches are of particular interest. INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of the NIH that women and members of minority groups and their subpopulations must be included in all NIH supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification is provided that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This new policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43) and supersedes and strengthens the previous policies (Concerning the Inclusion of Women in Study Populations, and Concerning the Inclusion of Minorities in Study Populations) which have been in effect since 1990. The new policy contains some new provisions that are substantially different from the 1990 policies. All investigators proposing research involving human subjects should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research", which have been published in the Federal Register of March 28, 1994 (FR 59 14508-14513), and reprinted in the NIH GUIDE FOR GRANTS AND CONTRACTS of March 18, 1994, Volume 23, Number 11. Investigators also may obtain copies of the policy from the program staff listed under INQUIRIES. Program staff may also provide additional relevant information concerning the policy. LETTER OF INTENT Prospective applicants are asked to submit, by March 3, 1995, a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information that it contains allows NIH staff to estimate the potential review workload and to avoid conflict of interest in the review. The letter of intent is to be sent to Dr. C. James Scheirer, at the address listed under INQUIRIES. APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research and from the Office of Grants Information, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone (301) 594-7248. Use the conventional format for research project grant applications and ensure the points identified in the section REVIEW CONSIDERATIONS are fulfilled. To identify the application as a response to this RFA, check "YES" on item 2a of page 1 of the application and enter the title "HIV-Associated Pathogens of the Lung: Life Cycle Regulation" HL-95-013. The RFA label found in form PHS 398 application kit must be affixed to the bottom of the face page of the original completed application form PHS 398. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. Send or deliver the completed application and three signed photocopies in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** Send two additional copies of the application to the Chief, Review Branch, DEA at the address listed under INQUIRIES. It is important to send these two copies at the same time as the original and three copies are sent to the Division of Research Grants. Otherwise the NHLBI cannot guarantee that the application will be reviewed in competition for this RFA. Applications must be received by April 28, 1995. If an application is received after this date, it will be returned to the applicant without review. The DRG will not accept any application in response to this RFA that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. The DRG will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an introduction addressing the previous critique. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by the DRG and responsiveness to this RFA by the NHLBI. Incomplete applications will be returned without further consideration. If the application is not responsive to the RFA, DRG staff may contact the applicant to determine whether to return the application to the applicant or submit it for review in competition with unsolicited applications at the next review cycle. Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by the Division of Extramural Affairs, NHLBI in accordance with the review criteria stated below. As part of the initial merit review, a process (triage) may be used by the initial review group in which applications will be determined to be competitive or non-competitive based on their scientific merit relative to other applications received in response to the RFA. Applications judged to be competitive will be discussed and be assigned a priority score. Applications determined to be non- competitive will be withdrawn from further consideration and the Principal Investigator and the official signing for the applicant organization will be notified. Review Criteria. The factors to be considered in the evaluation of scientific merit of each application will be similar to those used in the review of traditional research project grant applications including the novelty, originality, and feasibility of the approach; the training, experience, and research competence of the investigator(s); the adequacy of the experimental design; the suitability of the facilities; the appropriateness of the requested budget to the work proposed; and the adequacy of plans to include both genders and minorities and their subgroups as appropriate for the scientific goals of the research. Plans for the recruitment and retention of subjects will also be evaluated. The initial review group will also examine the provisions for the protection of human and animal subjects and the safety of the research environment. AWARD CRITERIA The anticipated date of award is September 29, 1995. In addition to the scientific merit of the applications, awards will be based on significance to the subject of the RFA and the availability of resources. INQUIRIES Inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Hannah H. Peavy, M.D. Division of Lung Diseases National Heart, Lung, and Blood Institute Westwood Building, Room 6A09 Bethesda, MD 20892 Telephone: (301) 594-7425 FAX: (301) 594-7487 Email: hpv%nihhwb1.bitnet@cu.nih.gov Direct inquiries regarding review matters and mail the letter of intent to: C. James Scheirer, Ph.D. Division of Extramural Activities National Heart, Lung, and Blood Institute Westwood Building, Room 557 Bethesda, MD 20892 Telephone: (301) 594-7478 FAX: (301) 594-7407 Email: james_scheirer%nihhwb1.bitnet@cu.nih.gov Direct inquiries regarding fiscal matters to: Raymond L. Zimmerman Division of Extramural Affairs National Heart, Lung, and Blood Institute Westwood Building, Room 4A17 Bethesda, MD 20892 Telephone: (301) 594-7420 FAX: (301) 594-7492 Email: raymond_zimmerman%nihhwb1.bitnet@cu.nih.gov AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance, No. 93.838. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or to review by a Health Systems Agency. The Public Health Service (PHS) strongly encourages all grant recipients to provide a smoke-free workplace and promote the non-use of all tobacco products. This is consistent with the PHS mission to protect and advance the physical and mental health of American people. From owner-sci-resources@net.bio.net Fri Jan 13 22:00:00 1995 Path: biosci!biosci!not-for-mail From: BIOSCI Administrator Newsgroups: bionet.sci-resources Subject: NIH GUIDE - PA-95-020 - V24(01) 01/13/95 Date: 13 Jan 1995 16:50:43 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 372 Sender: biohelp@net.bio.net Approved: biosci-moderator@net.bio.net Distribution: world Message-ID: <3f7753$oo0@net.bio.net> NNTP-Posting-Host: net.bio.net $$XID RFA PA95020 PA-95-020 P1O1 *************************************** DECISION MAKING PROCESSES IN WOMEN'S HEALTH NIH GUIDE, Volume 24, Number 1, January 13, 1995 PA NUMBER: PA-95-020 P.T. 34, II; K.W. 0785035, 0730050 National Institute of Nursing Research Office of Research on Women's Health Agency for Health Care Policy and Research PURPOSE The National Institute of Nursing Research (NINR), the Office of Research on Women's Health (ORWH), and the Agency for Health Care Policy and Research (AHCPR) invite submission of research grant applications to study the treatment and intervention decision making processes associated with non-cancerous health problems of women that frequently result in the surgical procedure, hysterectomy. These health problems have symptoms that may lead to a decision for hysterectomy even when the underlying pathology is limited. These problems include dysfunctional uterine bleeding, leiomyota (fibroids), endometriosis, pelvic pain, and uterine prolapse. Cancerous conditions leading to hysterectomy are not included in this Program Announcement (PA). This PA is jointly sponsored by NIH and AHCPR and both agencies are interested in applications in all the areas described under RESEARCH OBJECTIVES. The AHCPR is particularly interested in studies that include an emphasis on the influence of market forces, cost factors, health care payers, practice variation, and access issues. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This PA, Decision-Making Processes In Women's Health, is related to the priority areas of health promotion and clinical preventive services. Potential applications may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0 or Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. The AHCPR, by statute, can award grants to non-profit organizations only. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT This PA will use the NIH/AHCPR individual research project grant (R01). Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. Though the length of individual studies will vary, support will be provided for a period up to five years, based on availability of funds and sufficient scientific progress. Costs of individual projects will vary. RESEARCH OBJECTIVES Women and their health care providers confront an increasingly complex decision making process related to selecting hysterectomy and/or alternatives as treatment/intervention options. Current scientific investigations are focused on evaluating the efficacy of emerging medical and surgical treatments prior to, during and following hysterectomy; but little investigative effort has focused on the complexity of the decision making process itself. The interaction effect of endogenous and exogenous factors on decision making has not been thoroughly examined. Among these factors are the woman's preferences and symptoms, the clinical practitioner's assessment and treatment plan, and the utilization criteria of the health care payers leading to the decision to implement or not implement hysterectomy as a treatment option. The purpose of this program announcement is to encourage exploration of the treatment and intervention decision-making processes of women experiencing non-cancerous health problems that frequently result in a hysterectomy. These problems, including dysfunctional uterine bleeding, leiomyota (fibroids), endometriosis, and uterine prolapse, have symptoms that may lead to a decision for hysterectomy even with limited underlying pathology. The symptomatology associated with such problems include pelvic pain, excessive and/or frequent uterine bleeding, changes in urination, and related symptoms. In examining the decision making process, it is important to consider the varying perspectives of, and influences on, women having the health problems. In addition, the role of their significant others, their clinical practitioners (nurses, physicians, and others), and health care payers on decision outcomes need consideration. These differing viewpoints and interests are usually the major factors leading to decisions for surgical treatment, such as hysterectomy, rather than using alternative, less invasive and costly treatments or interventions when they are available. There is limited scientific information about how women make these decisions, how they are informed about their treatment options, and what influence, if any, clinical practitioners and health care payers have on their decision making. Numerous methodological approaches may be used to address the study of decision making. It is appropriate to propose both quantitative, qualitative and combined approaches. Currently, hysterectomy is the second most commonly performed major surgery for women in the US. Half of the hysterectomies are performed on women 40 years old or younger. There is considerable regional variation. Whether this variation is related to factors other than clinical decisions and recommendations by clinical practitioners is not clear. Although, total hysterectomy for benign disease historically has been justified on several grounds, there is no convincing evidence that hysterectomy conveys a benefit proportional to the risks of the surgery. Recent advances in technology have enabled us to follow more closely the status of many conditions which lead to hysterectomy. New conservative surgical approaches which spare the uterus are growing in use. A variety of conditions can be indications for hysterectomy, the most common of which are benign conditions, such as uterine leiomyomas, endometriosis, dysfunctional uterine bleeding, and uterine prolapse. Conditions such as endometriosis and leiomyoma usually stabilize or regress at the time of natural menopause. When the effects of these problems become more symptomatic, the usual first line of treatment consists of medical therapies or conservative surgical approaches or watchful waiting. Abnormal uterine bleeding may also be treated with drug therapy. Pelvic pain, which must have a differential diagnosis leading to a decision that it is occurring due to a non-cancerous or other less serious condition, needs to be explored to determine the extent to which it may be the important factor in a decision to treat surgically. Conventional treatment of chronic pelvic pain currently consists of oral contraceptives or nonsteroidal anti-inflammatory drugs. Other treatments or interventions for symptom management of pain may be less invasive and less costly in approach. Approaches to uterine prolapse may include exercise to strengthen the pelvic muscles in mild or moderate prolapse, placement of a pessary especially in older women, and surgery for severe prolapse. Family members are frequently important partners for many women when making health-related decisions. The role and influence of family members in treatment/intervention decisions generally remains unexplored, but could be of potential significance, especially for certain cultural/ethnic groups. Cultural beliefs, mores, and values are factors that are seldom addressed in clinical investigations, particularly in the area of health-related decision making. Such factors could be addressed from an individual, family and/or community perspective. The term clinical practitioner for this announcement refers to the health care professional who is the principal source of care for the patient's condition. This provider may be a primary care physician or nurse, an advanced nurse practitioner, a clinical nurse specialist, a certified nurse midwife, a women's health care specialist, a gynecologist, a general surgeon, or other health professionals who fulfills the above role. In situations where more than one provider is involved, the responsibilities of each provider should be clearly defined. Health care practitioners as well as patients are said to be influenced in making decisions by the policies and procedures of employing organizations, referring organizations, health care payers and other market forces. These include hospitals and other organizations providing clinical services, managed care organizations, health insurance plans, and other "third party" payers that can influence choices actually available or valued by practitioners, patients, and their families. Examples of possible research questions include, but are not limited to: What are the sources of information most frequently used/consulted by women in their self care of their uterine/pelvic symptoms, and for treatment/intervention decisions? What is the reliability of these sources? How do women resolve conflicting information, advice or recommendations in these sources? How do the various sources of information about treatment or control of their clinical problems influence women to seek or use one treatment over another? What are the relationships of symptoms and their management to the decision to have a hysterectomy or not? Are there different levels of symptom intensity related to these decisions? What are the methodological considerations in determining symptom influence on treatment decisions? How does the decision-making process vary within and across cultural/ethnic groups or in geographic regions for different practitioners? Are there specific components of the decision-making process that lead to satisfactory/unsatisfactory outcomes for the patient? To what extent is watchful waiting recommended and adhered to, or are other options sought by women with any frequency? What options are considered and used? How are the appropriateness and effectiveness of clinical decisions for hysterectomy best evaluated? What are the cost differentials across treatment/intervention options? Are these influential to women in making their treatment decisions? Does the type of decision made depend more on the different health care practitioners or on the individual characteristics and symptoms of the woman? Does the type of surgical procedure offered for hysterectomy (abdominal versus vaginal hysterectomy, inclusion of the ovaries or not) directly or indirectly influence the decision for surgery when other options are also indicated? What is the influence of clinical guidelines developed by professional societies and groups related to the noncancerous clinical conditions and their treatments, if any? INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of NIH and AHCPR that women and members of minority groups and their subpopulations must be included in all NIH/AHCPR- supported biomedical, behavioral, and health services research projects involving human subjects, unless clear and compelling rationale and justification is provided that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. The new policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43) and supersedes and strengthens the previous policies (Concerning the Inclusion of Women in Study Populations) which have been in effect since 1990. The new policy contains some new provisions that are substantially different from the 1990 policies. All investigators proposing research involving human subjects should read the "NIH Guidelines For Inclusion Of Women And Minorities As Subjects In Clinical Research," which have been published in the Federal Register of March 28, 1994 (FR 59 14508-14513), and reprinted in the NIH GUIDE TO GRANTS AND CONTRACTS of March 18, 1994, Volume 23, Number 11. Investigators may obtain copies from these sources or from the program staff or contact person listed under INQUIRIES. Program staff may also provide additional relevant information concerning the policy. APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used and will be accepted at the standard application deadlines indicated in the application kit. These forms are available at most institutional offices of sponsored research; from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone 301/594-7248. The number and title of this program announcement must be typed in item number 2a on the application face page. The completed application and five signed, legible copies must be sent or delivered to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892-6300** REVIEW CONSIDERATIONS Applications received under this program announcement will be assigned to an appropriate NIH or AHCPR Initial Review group (IRG) in accordance with established PHS referral guidelines. The IRG, consisting primarily of non-Federal scientific and technical experts, will review the application for scientific and technical merit in accordance with standard NIH/AHCPR review procedures. Notification of the review recommendations will be sent to the applicant after the initial review. Applications assigned to the NIH, recommended for further consideration, and receiving sufficiently high priority will receive a second-level review by appropriate National Advisory Council, whose review will be based on policy considerations as well as scientific merit. Applications that are complete and responsive to the program announcement will be evaluated for scientific and technical merit by an appropriate peer review group convened by the NIH/AHCPR in accordance with the review criteria stated below. As part of the initial merit review, a process (triage) may be used by the initial review group in which applications will be determined to be competitive or non-competitive based on their scientific merit relative to other applications received in response to the RFA. Applications judged to be competitive will be discussed and be assigned a priority score. Applications determined to be non- competitive will be withdrawn from further consideration and the Principal Investigator and the official signing for the applicant organization will be notified. AWARD CRITERIA Decisions to make awards are based on the overall scientific merit of the application reflected in the priority score, availability of funds, and research program priorities within the NINR, ORWH, and AHCPR. INQUIRIES Written and telephone inquiries concerning this PA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding scientific or programmatic issues to: Patricia Moritz, Ph.D., R.N. National Institute of Nursing Research Building 45, Room 3AN-12 45 Center Drive MSC 6300 Bethesda, MD 20892-6300 Telephone: (301) 594-5966 FAX: (301) 480-8260 Email: pmoritz@ep.ninr.nih.gov Virginia Cain, Ph.D. Office of Research on Women's Health Building 1, Room 201 Bethesda, MD 20892 Telephone: (301) 402-1770 FAX: (301) 402-1798 Email: virginia_cain@nih.gov Anne Bavier, M.N., R.N. Agency for Health Care Policy and Research 2101 E. Jefferson Drive Rockville, MD 20852-4908 Telephone: (301) 594-1357, ext. 129 FAX: (301) 594-2155 Email: abavier@po3.ahcpr.gov Direct inquiries regarding fiscal matters to: Sally A. Nichols Grants Management Officer National Institute of Nursing Research Building 45, Room 3AN-32 45 Center Drive MSC 6301 Bethesda, MD 20892-6301 Telephone: (301) 594-6869 Email: snichols@ep.ninr.nih.gov Ralph Sloat Grants Management Officer Agency for Health Care Policy and Research 2101 E. Jefferson Drive Rockville, MD 20852-4908 Telephone: (301) 594-1447 FAX: (301) 594-2155 Email: rsloat@po7.ahcpr.gov AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.361, Nursing Research; 93.180, Medical Treatment Effectiveness Research;and 93.226, Health Services Research and Development. Awards are made under authorization of the 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 Federal Regulations 42 CFR 52. AHCPR Awards are made under authority of the PHS Act, Title IX (42 USC 299-299c-6) and Federal Regulations 42 CFR Part 67, Subpart A. Awards are administered under PHS grants policies and 45 CFR Part 74 (Part 92 for State and local governments). This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. From owner-sci-resources@net.bio.net Fri Jan 13 22:00:00 1995 Path: biosci!biosci!not-for-mail From: BIOSCI Administrator Newsgroups: bionet.sci-resources Subject: NIH GUIDE - PA-95-019 - V24(01) 01/13/95 Date: 13 Jan 1995 16:50:22 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 358 Sender: biohelp@net.bio.net Approved: biosci-moderator@net.bio.net Distribution: world Message-ID: <3f774e$omg@net.bio.net> NNTP-Posting-Host: net.bio.net $$XID RFA PA95019 PA-95-019 P1O1 *************************************** H. PYLORI: BASIC, PRE-CLINICAL, AND CLINICAL RESEARCH NIH GUIDE, Volume 24, Number 1, January 13, 1995 PA NUMBER: PA-95-019 P.T. 34; K.W. 1002027, 0715085, 0765012 National Institute of Allergy and Infectious Diseases Application Receipt Dates: June 1, and October 1, 1995 and February 1, 1996 PURPOSE The National Institute of Allergy and Infectious Diseases (NIAID), invites submission of investigator-initiated research applications for support of research on the definition of the natural history of infection, animal models, protective immune responses to infection, virulence determinants, bacterial genetics, and antibiotic resistance to Helicobacter pylori. This bacterium is known to be associated with chronic gastritis, duodenal and gastric ulcer disease, and possibly with certain malignancies of the stomach. The development of vaccines against this organism is also of interest to the NIAID. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This program announcement, H. Pylori: Basic, Pre-Clinical and Clinical Research, is related to the priority area of immunization and infectious diseases. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-0325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign, for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as Principal Investigators. Foreign institutions are not eligible for the First Independent Research Support and Transition (FIRST) award (R29). MECHANISM OF SUPPORT The mechanisms of support will be the individual research project grant (R01) and the FIRST (R29) award. The total project period for an application submitted in response to this RFA may not exceed five years; a foreign application may not request more than three years of support. FUNDS AVAILABLE The estimated NIAID funds available for the total (direct and indirect) first-year costs of all awards made under this PA will $1,000,000. In Fiscal Year 1996, the NIAID plans to fund four to five R01 and/or R29 grants. This level of support is dependent on the receipt of a sufficient number of applications of high scientific merit. Although this program is provided for in the financial plans of the NIAID, awards pursuant to this program announcement are contingent upon the availability of funds for this purpose. Funding beyond the first and subsequent years of the grant will be contingent upon satisfactory progress during the preceding years and availability of funds. New applications submitted for the June 1 and October 1, 1995 and February 1, 1996 receipt dates will be eligible for funding under this program announcement. Competing continuation applications for already funded projects will NOT be eligible for award from NIAID under this program announcement. RESEARCH OBJECTIVES Background In 1983, a spiral shaped, urease producing, Gram negative bacterium, Helicobacter pylori, was identified in the stomachs of some individuals. Since then, there has been increasing evidence for its association with active and chronic gastritis, peptic ulcers, and duodenal ulcers. Effective treatment of the infection with antibiotics eliminates ulcer recurrences in more than 90 percent of cases. An epidemiologic relationship between atrophic gastritis, which develops in a small percentage of those infected with H. pylori, and gastric malignancies has also been noted. H. pylori colonizes the gastric mucosa of greater than 30 percent of persons in the U.S. and more frequently in African American, Hispanic, and socioeconomically disadvantaged populations in this country. In some developing countries, it is found in almost 100% of the population. Non-ulcer dyspepsia (NUD) and gastric and duodenal ulcer disease, are among the most common human ailments of the upper GI tract requiring medical attention. An estimated 10 percent of people in the United States will develop peptic ulcer disease, a chronic inflammatory condition of the stomach and duodenum, sometime in their lifetime. It is estimated that there are 300,000 new cases, 3.2 million recurrences, and 3,000 deaths due to duodenal ulcer disease each year in the U.S. NUD affects even greater numbers of individuals, but a causal relationship between NUD and H. pylori has not been definitively established to date. Defining this relationship, and identifying even a subset of NUD patients, would facilitate the prescription of appropriate antibiotic therapy for those individuals. A recent Consensus Conference sponsored by NIDDK, NIAID, and the NIH Office of Medical Applications of Research recommended that patients presenting with duodenal or gastric ulcers who were also seropositive for H. pylori be treated with antimicrobial triple therapy to eradicate the organism. The Panel recommended that basic research be conducted in order to generate much needed data on the biology of this organism. The development of an effective preventive strategy, including the development of a vaccine should also be pursued when sufficient information on pathogenesis is available. This initiative will focus on these basic issues, including definition of the natural history of infection, animal models, protective immune responses to infection, virulence determinants, bacterial genetics, and antibiotic resistance. It is known that a significant number (approximately 10 percent) of children under the age of 10 are seropositive for H. pylori. The source of infection, modes of transmission, identification of risk factors, and the consequence of this infection on the health of the young are not known, and are of special interest to the NIAID in the context of this Program Announcement. Research Objectives and Experimental Approaches Well-designed basic, pre-clinical and clinical studies are needed to provide a better understanding of H. pylori biology and pathogenesis so that effective intervention strategies can be designed. Topics of interest to the NIAID include, but are not limited to: o development or use of animals that can be infected with human isolates of H. pylori and that serve as models for stages of the human disease and are amenable to evaluation of prophylactic and therapeutic strategies; o identification of virulence factors of the organism, effect of deletion of virulence factor genes on pathogenesis; o biomarkers (antigens or nucleic acids) of strains of H. pylori that may be associated with particular outcomes of infection such as various forms of NUD, ulcer disease, or asymptomatic carriage; o definition of the genetics of the organism including characterization of plasmids, mechanism of gene transfer, etc; o development and mechanism of antibiotic resistance; o vaccine development; and o natural history of infection, particularly in children, including risk factors and modes of transmission. Multidisciplinary studies and collaboration among investigators with expertise in appropriate disciplines are encouraged. When investigators are at different institutions, individual R01 applications may include consortium arrangements. Collaborative arrangements with ongoing studies that provide patient populations, specimens and data are encouraged (a list of possible resources is included in this PA). Such arrangements should be clearly delineated in the application. The methodologies employed and personnel involved in the study, including statistical analyses, should be described in the application and evident in the study design. The hypothesis(es) to be tested should be clearly stated. The measurement of immunological and bacterial markers is highly dependent on the assay system chosen and its execution. Thus, it is very important that applicants clearly define the methodologies to be used, the rationale for choosing that methodology and for validating results as well as methods of collection, processing, and storage of samples. The value of studies of patients or their specimens will be directly related to the care exercised in selection and initial characterization of cases and controls. Therefore, a detailed description of case recruitment procedures, the criteria to be used for case definition and the manner in which the criteria are to be applied should be included. This is particularly true in the case of non-ulcer dyspepsia for which a generally accepted definition does not exist. Similar care should be given to descriptions of enrollment of comparison groups. INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification is provided that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This new policy results >From the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43) and supersedes and strengthens the previous policies (Concerning the Inclusion of Women in Study Populations, and Concerning the Inclusion of Minorities in Study Populations), which have been in effect since 1990. The new policy contains some provisions that are substantially different from the 1990 policies. All investigators proposing research involving human subjects should read the "NIH Guidelines For Inclusion of Women and Minorities as Subjects in Clinical Research," which have been published in the Federal Register of March 28, 1994 (FR 59 14508-14513) and printed in the NIH Guide for Grants and Contracts, Volume 23, Number 11, March 18, 1994. Investigators also may obtain copies of the policy from the program staff listed under INQUIRIES. Program staff may also provide additional relevant information concerning the policy. APPLICATION PROCEDURES Applications are to be submitted on the grant application form PHS 398 (rev. 9/91) and will be accepted on the standard application deadlines as indicated in the application kit. Requests for continued funding of already funded projects (Type 2) will NOT be considered under this program announcement. Applications may be submitted for the following receipt dates only: June 1, and October 1, 1995 and February 1, 1996. Awards resulting from this program announcement will be made on or about April 1, July 1, and December 1, 1996. Application kits are available at most institutional offices of sponsored research and may be obtained from the Office of Grants Information, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone (301) 594-7248. Each application must be identified by checking "YES" on line 2a of the PHS face page, and the number and title of this program announcement must be typed in section 2a. The completed original and five legible, single-sided copies of the application must be sent or delivered to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** FIRST (R29) applications must include at least three sealed letters of reference attached to the face page of the original application. FIRST applications submitted without the required number of reference letters will be considered incomplete and will be returned without review. Applicants from institutions that have a General Clinical Research Center (GCRC) funded by the NIH National Center for Research Resources may wish to identify the Center as a resource for conducting the proposed research. If so, a letter of agreement from the GCRC Program Director must be included in the application material. REVIEW CONSIDERATIONS Applications will be assigned on the basis of established PHS referral guidelines. Applications will be reviewed for scientific and technical merit by study sections of the Division of Research Grants, NIH, in accordance with the standard NIH peer review procedures. Following scientific/technical review, the applications will receive secondary review by the appropriate national advisory council. As part of the initial merit review, a process (triage) may be used by the initial review group in which applications will be determined to be competitive or non-competitive based on their scientific merit relative to other applications received in response to the RFA. Applications judged to be competitive will be discussed and be assigned a priority score. Applications determined to be non- competitive will be withdrawn from further consideration and the Principal Investigator and the official signing for the applicant organization will be notified. Review Criteria o scientific, technical, or medical significance and originality of proposed research; o appropriateness and adequacy of the experimental approach and methodology proposed to carry out the research; o qualifications and research experience of the Principal Investigator and staff, particularly, but not exclusively, in the area of the proposed research; o availability of the resources necessary to perform the research; o appropriateness of the proposed budget and duration in relation to the proposed research; o adequacy of plans to include both genders and minorities and their subgroups as appropriate for the scientific goals of the research. Plans for the recruitment and retention of subjects will also be evaluated. The initial review group will also examine the provisions for the protection of human and animal subjects and the safety of the research environment. AWARD CRITERIA Applications assigned to the NIAID will compete for available set- aside funds. The following will be considered when making funding decisions: quality of the proposed project as determined by peer review, program balance among research areas of the announcement, availability of funds. INQUIRIES Written and telephone inquiries are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Dennis R. Lang, Ph.D. Division of Microbiology and Infectious Diseases National Institute of Allergy and Infectious Diseases Solar Building, Room 3A21 6003 Executive Boulevard MSC 7630 Bethesda, MD 20892-7630 Telephone: (301) 496-7051 FAX: (301) 402-1456 Email: dl73v@nih.gov Direct inquiries regarding fiscal matters to: Ms. Louise Kreh Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4B35 6003 Executive Boulevard MSC 7610 Bethesda, MD 20892-7610 Telephone: (301) 496-7075 FAX: (301) 480-3780 Email: louise_kreh@exec.niaid.pc.niaid.nih.gov AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.856, Microbiology and Infectious Disease Research. Awards are made under authorization of the 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 grants policies and Federal Regulations 42 CFR 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. The Public Health Service (PHS) strongly encourages all grant recipients to provide a smoke-free work place and promote the non-use of all tobacco products. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people. From owner-sci-resources@net.bio.net Fri Jan 13 22:00:00 1995 Path: biosci!biosci!not-for-mail From: BIOSCI Administrator Newsgroups: bionet.sci-resources Subject: NIH GUIDE - RFA AI-95-005 - V24(01) 01/13/95 Date: 13 Jan 1995 16:50:15 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 450 Sender: biohelp@net.bio.net Approved: biosci-moderator@net.bio.net Distribution: world Message-ID: <3f7747$om4@net.bio.net> NNTP-Posting-Host: net.bio.net $$XID RFA AI95005 AI-95-005 P1O1 *************************************** INTERDISCIPLINARY PROGRAMS IN AUTOIMMUNE DISEASE NIH GUIDE, Volume 24, Number 1, January 13, 1995 RFA: AI-95-005 P.T. 34; K.W. 0715015, 0710030 National Institute of Allergy and Infectious Diseases National Institute of Diabetes and Digestive and Kidney Diseases Juvenile Diabetes Foundation International Letter of Intent Receipt Date: March 15, 1995 Application Receipt Date: June 15, 1995 PURPOSE The National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) of the National Institutes of Health (NIH) and the Juvenile Diabetes Foundation International (JDFI) invite applications for program project grants to support interdisciplinary programs in autoimmune disease. This Request for Applications (RFA) will support programs combining investigations of basic, molecular, immunologic, and genetic mechanisms in the pathogenesis of autoimmunity and the development of innovative therapies for human autoimmune disease. These programs may incorporate investigation into any autoimmune disease, including, but not limited to, Insulin Dependent Diabetes Mellitus (IDDM), or any field of science with relevance to the mechanisms and treatment of autoimmunity. Programs utilizing investigators from different scientific disciplines are particularly desirable, so as to utilize expertise in several areas simultaneously. Applications should be submitted to and will be reviewed by the NIH according to the usual NIH peer review procedures. Funds for each Program Project to be awarded under this RFA will be provided by the NIAID and the JDFI. One or more program projects will be cofunded by NIDDK. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This RFA, Interdisciplinary Programs in Autoimmune Disease, is related to the priority area of diabetes and chronic disabling diseases. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-782-3238). ELIGIBILITY REQUIREMENTS Research grant applications may be submitted by domestic for-profit and non-profit organizations, public and private institutions, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Foreign organizations are not eligible to apply. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as Principal Investigators. MECHANISM OF SUPPORT The mechanism of support will be the program project (P01) grant. This mechanism supports broadly based multi-disciplinary research programs that have a well-defined central research focus, theme, or objective. An important feature of the program project is that the interrelationships of the individual scientifically meritorious projects will result in a greater contribution to the overall program goals than if each project were pursued individually. The program project grant consists of a minimum of three interrelated individual research projects that contribute to the program objective. The program project grant also can provide support for certain common resources termed cores. Such resources should be utilized by two or more projects within the program project. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. The total project period may not exceed five years. At this time, the NIAID is administratively limiting the duration of P01 grants to four years. The earliest anticipated award date is March 1996. FUNDS AVAILABLE The estimated total funds (direct and indirect costs) available for the first year of support for this RFA will be $2.75 million: $1.5 million from NIAID; $1.0 million from JDFI; and $250,000 from NIDDK. In Fiscal Year 1996, the NIAID and the JDFI anticipate jointly funding approximately three or four program projects related to this RFA. Approximately 60 percent of the total costs of each grant will be funded by the NIAID and approximately 40 percent by the JDFI. One or more of these applications will be cofunded by the NIDDK. This level of support is dependent on the receipt of a sufficient number of applications of high scientific merit. Applications may not request budgets in excess of $750,000 total (direct and indirect) costs in the first year. The NIH is currently limiting annual inflationary increases to no more than four percent for future years. Funding rules and policies, including the determination of allowable indirect costs, of each funding organization will be applicable. Post award administration will conform to current policies and requirements that govern the research grant programs of the NIH and the JDFI as appropriate. Although this program is provided for in the financial plans of the NIAID, the JDFI, and the NIDDK, awards pursuant to this RFA are contingent upon the availability of funds for this purpose. Funding beyond the first and subsequent years of the grant will be contingent upon satisfactory progress during the preceding years and availability of funds. At this time, it has not been determined whether or how this solicitation will be continued beyond the period stated in the present RFA. The National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS) is interested in research on the immune mechanisms involved in rheumatic diseases and the development of new therapies for these diseases based on manipulation of the immune system. Applications that are of mutual interest are likely to be given dual secondary assignment to the NIAMS in accordance with NIH Division of Research Grants (DRG) referral guidelines. RESEARCH OBJECTIVES Background Autoimmune diseases affect five to seven percent of the population, resulting in significant morbidity and mortality, and cost billions of dollars annually for health care and loss of productivity. Insulin Dependent Diabetes Mellitus (IDDM) disproportionately affects children and young adults. In addition to IDDM, other diseases included in this category are rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and inflammatory bowel disease. There is no known cure or prevention for these diseases. However, recent developments, including new animal models, the ability to generate transgenic animals, recent new paradigms for the stimulation of T and B cells, the finding of new co-factors for stimulation, and the development of new methods for detecting self-antigens, have revolutionized our thinking about the development of tolerance, both central and peripheral. These new developments in basic immunology may lead to important insights into the pathogenesis and therapy of autoimmune disease. Research Objectives and Scope Application of recent advances in basic immunology to the understanding of the pathogenesis of autoimmune diseases, including the development of novel therapies and possible preventive strategies, is a major goal of this RFA. The specific objectives of this program are to: facilitate the application of new advances in immunology and immunogenetics to the understanding and treatment of autoimmune diseases, including IDDM; increase the understanding of the etiology and pathogenic mechanisms involved in development and progression of autoimmune diseases; enable investigators working on various different autoimmune diseases to come together to work in a collaborative and synergistic way; and promote the collaboration between investigators working in disease-specific models and investigators focusing on basic studies of self tolerance and the defects in this process in several experimental systems. In addition to investigation of the initiation of the autoimmune process, the mechanism of the target organ damage in autoimmune disease is unclear. The elucidation of the destructive pathways resulting from the autoimmune process in these diseases could be useful for the development of therapeutic strategies and is a relevant topic for this RFA. The inclusion of clinical investigators may allow earlier transfer of new information to the clinical setting. SPECIAL REQUIREMENTS The NIAID, the NIDDK, and the JDFI plan to sponsor an annual meeting to encourage the exchange of information among investigators supported under this RFA, foster collaborative efforts, and identify resources that would enhance the productivity of this research program. Applications should include a statement indicating the willingness of the applicant institution to participate in such annual meetings. For this purpose, travel funds for an annual two- day meeting, to be held in the Washington, DC area, should be included in the budget request. Letter of Authorization This RFA is co-sponsored by the JDFI. In order for an application to be considered for funding by the JDFI, applicants must submit a brief letter of authorization co-signed by the Principal Investigator and the official signing for the applicant institution, authorizing release of the application and all related materials to the JDFI. This letter of authorization may be combined with the letter of intent or may be submitted directly to Dr. Elaine Collier at the address listed under INQUIRIES. The summary statement for such applications will be shared with the JDFI at the time of their availability. Applications without such authorization will not be considered for funding by the JDFI. INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification is provided that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This new policy results >From the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43) and supersedes and strengthens the previous policies (Concerning the Inclusion of Women in Study Populations, and Concerning the Inclusion of Minorities in Study Populations), which have been in effect since 1990. The new policy contains some provisions that are substantially different from the 1990 policies. All investigators proposing research involving human subjects should read the "NIH Guidelines For Inclusion of Women and Minorities as Subjects in Clinical Research," which have been published in the Federal Register of March 28, 1994 (FR 59 14508-14513) and printed in the NIH Guide for Grants and Contracts, Volume 23, Number 11, March 18, 1994. Investigators also may obtain copies of the policy from the program staff listed under INQUIRIES. Program staff may also provide additional relevant information concerning the policy. LETTER OF INTENT Prospective applicants are asked to submit, by March 15, 1995, a letter of intent that includes a descriptive title of the overall proposed research, the name, address, and telephone number of the Principal Investigator, a list of the key investigators and their institution(s), and the number and title of this RFA. Although the letter of intent is not required, is not binding, does not commit the sender to submit an application, and does not enter into the review of subsequent applications, the information that it contains allows NIAID staff to estimate the potential review workload and to avoid conflict of interest in the review. The letter of intent is to be sent to Dr. Mark Rohrbaugh at the address listed under INQUIRIES. APPLICATION PROCEDURES Applications are to be submitted on form PHS 398 (rev. 9/91), the standard application form for research grants. Application kits are available at most institutional offices of sponsored research and may be obtained from the Office of Grants Information, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone 301/594-7248. Applicants must adhere to the format and requirements specified in the PHS 398 application kit. In addition, applicants for multicomponent grants are strongly advised to read the information brochure "NIAID Program Project Grants and Multiproject Cooperative Agreements", available >From Dr. Elaine Collier at the address listed under INQUIRIES. Applicants from institutions that have a General Clinical Research Center (GCRC) funded by the NIH National Center for Research Resources may wish to identify the GCRC as a resource for conducting the proposed research. If so, a letter of agreement from either the GCRC program director or principal investigator could be included with the application. For purposes of identification and processing, mark "YES" in item 2a on the face page of the application and type in the RFA number, AI-95-005, and the title "INTERDISCIPLINARY PROGRAMS IN AUTOIMMUNE DISEASE." The RFA label available in the form PHS 398 must be affixed to the bottom of the face page of the original application. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. The signed, typewritten original of the application, including the Checklist, and three exact single-sided copies must be sent to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** At the time of submission, two additional copies and all five sets of appendices must also be sent to Dr. Mark Rohrbaugh at the address listed under INQUIRIES. To ensure their review, applications must be received by both the Division of Research Grants and Dr. Mark Rohrbaugh by June 15, 1995. Applications not received by June 15, 1995 will be considered non-responsive and will be returned to the applicant without review. Concurrent submission of an R01 and a Component Project of a Multi- project Application: Current NIH policy permits a component research project of a multi- project grant application to be concurrently submitted as a traditional individual research project (R01) application. If, following review, both the multi-project application and the R01 application are found to be in the fundable range, the investigator must relinquish the R01 and will not have the option to withdraw from the multi-project grant. This is an NIH policy intended to preserve the scientific integrity of a multi-project grant, which may be seriously compromised if a strong component project(s) is removed >From the program. Investigators wishing to participate in a multi- project grant must be aware of this policy before making a commitment to the Principal Investigator and awarding institution. REVIEW CONSIDERATIONS Review Procedures Upon receipt, applications will be reviewed for completeness by the Division of Research Grants (DRG) and for responsiveness by the NIAID. Incomplete and/or non-responsive applications will be returned to the applicant without further consideration. Complete and responsive applications will be evaluated for scientific and technical merit by an appropriate peer review group convened by the NIAID in accordance with the review criteria stated below. As part of the initial merit review, a process (triage) may be used by the initial review group in which applications will be determined to be competitive or non-competitive based on their scientific merit relative to other applications received in response to the RFA. Applications judged to be competitive will be discussed and will be assigned a priority score. Applications determined to be non- competitive will be withdrawn from further consideration and the Principal Investigator and the official signing for the applicant organization will be notified. The second level of review will be provided by the National Advisory Allergy and Infectious Diseases Council and the National Institute of Diabetes and Digestive and Kidney Diseases Advisory Council. Review Criteria The review criteria for P01 grant applications are the review criteria for large, multicomponent, interdisciplinary program projects as outlined in the NIAID brochure entitled "NIAID Guidelines for Multiproject Research Awards." The program project grant application should include a justification for the appropriateness of that granting mechanism for the proposed project. The distinguishing features of a program project grant include: o A well-defined, unifying goal or problem area of research to which each project relates and contributes, thereby producing a research environment that allows each research effort to share the creative strengths of others. o A program director who possesses recognized scientific and administrative competence. He/she must demonstrate a substantial commitment to the program in time and effort thereby exercising leadership in providing overall direction and in upholding rigorous scientific conduct. o Each research project must, as assessed by peer review, stand on its own independent scientific merit, as well as complement other projects whenever feasible. o The projects require the participation of established investigators in several disciplines or investigators with special expertise in several areas of one discipline. All investigators must contribute to and share the responsibilities of fulfilling the program objective. o Ability of the proposed research to provide knowledge of basic, molecular and genetic mechanisms in the pathogenesis of autoimmunity and the development of innovative therapies for human autoimmune disease. The appropriateness of the proposed experimental plan to validate the utility of the chosen strategy will be considered in this regard. o Adequacy of plans to include both genders and minorities and their subgroups as appropriate for the scientific goals of the research. Plans for the recruitment and retention of subjects will also be evaluated. AWARD CRITERIA Funding decisions will be made on the basis of scientific and technical merit as determined by peer review, program priorities, and the availability of funds. INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Requests for the brochure "NIAID Application Guidelines for Multiproject Research Awards," as well as inquiries regarding programmatic issues may be directed to: Elaine Collier, M.D. Division of Allergy, Immunology, and Transplantation National Institute of Allergy and Infectious Disease Solar Building, Room 4A20 6003 Executive Boulevard Bethesda, MD 20892-7640 Telephone: (301) 496-7104 FAX: (301) 402-2571 Email: EC5X@NIH.GOV Joan Harmon, Ph.D. Division of Diabetes, Endocrinology, and Metabolic Diseases National Institute of Diabetes and Digestive and Kidney Diseases Natcher Building, Room 5AN-18G Bethesda, MD 20892 Telephone: (301) 594-8808 FAX: (301) 480-3503 Email: joanh@dvsgate.niddk.nih.gov Direct inquiries regarding review issues, mail two copies of the application and all five sets of appendices, and mail the letter of intent to: Mark L. Rohrbaugh, Ph.D. Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4C20 6003 Executive Boulevard Bethesda, MD 20892-7610 Telephone: (301) 496-8424 FAX: (301) 402-2638 Email: MR28K@NIH.GOV Direct inquiries regarding fiscal matters to: Ms. Jacqueline Johnson Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4B26 6003 Executive Boulevard Bethesda, MD 20892-7610 Telephone: (301) 496-7075 Email: JJ19E@NIH.GOV Schedule Letter of Intent Receipt Date: March 15, 1995 Application Receipt Date: June 15, 1995 Scientific Review Date: October 1995 Advisory Council Date: January 1996 Earliest Award Date: March 1996 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance, No. 93.855 and No. 93.847. Awards will be made under the authority of the 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 grants policies and Federal Regulations 42 CFR 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. The Public Health Service (PHS) strongly encourages all grant recipients to provide a smoke-free work place and promote the nonuse of all tobacco products. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people. From owner-sci-resources@net.bio.net Fri Jan 13 22:00:00 1995 Path: biosci!biosci!not-for-mail From: BIOSCI Administrator Newsgroups: bionet.sci-resources Subject: NIH GUIDE - RFA HS-96-001 - V24(01) 01/13/95 Date: 13 Jan 1995 16:50:08 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 444 Sender: biohelp@net.bio.net Approved: biosci-moderator@net.bio.net Distribution: world Message-ID: <3f7740$olh@net.bio.net> NNTP-Posting-Host: net.bio.net $$XID RFA HS96001 HS-96-001 P1O1 *************************************** RESEARCH ON THE OUTCOMES OF PHARMACEUTICAL THERAPY NIH GUIDE, Volume 24, Number 1, January 13, 1995 RFA: HS-96-001 P.T. 34; K.W. 0745005, 0730021 Agency for Health Care Policy and Research Letter of Intent Receipt Date: March 1, 1995 Application Receipt Date: April 12, 1995 PURPOSE The Agency for Health Care Policy and Research (AHCPR) invites applications to conduct research on the outcomes of pharmaceutical therapy. This request for applications (RFA) focuses on the effects on patient outcomes of various proposed or existing mechanisms for managing selection, utilization, and cost of pharmaceutical therapies and services. Current restructuring within the health care system provides an important opportunity to enhance understanding of the interrelationships of pharmaceutical treatments and services with patient outcomes. Of particular interest are studies involving the comparative effectiveness and/or cost effectiveness of pharmaceutical therapies within the changing health care system. This is an activity of the research component of AHCPR's Medical Treatment Effectiveness Program (MEDTEP). Section 1142 of the Social Security Act, a part of AHCPR's authorizing legislation, refers specifically to the need to study the outcomes of prescription drug therapy. Awards are a part of the Outcomes of Pharmaceutical Therapy (OPT) program, as introduced in RFA HS-92-03. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. AHCPR urges applicants to submit grant applications with relevance to the specific objectives of this initiative. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0 or Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign non-profit organizations, public and private, including universities, clinics, units of State and local governments, non-profit firms, and non- profit foundations. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as Principal Investigators. MECHANISM OF SUPPORT This request for applications will use the research project grant (R01) mechanism. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. This is a one-time solicitation. The total requested project period may not exceed five years. Annual progress reviews by AHCPR and the availability of funds will determine the continuation of grants up to the five year limit. FUNDS AVAILABLE The AHCPR expects to award up to $2 million for first year support of four to six awards. RESEARCH OBJECTIVES Background The enabling legislation for AHCPR authorizes studies of the effectiveness and appropriateness of health care services and procedures. Section 1142 of the Social Security Act recognizes drug therapy as an important form of treatment and refers to the need to study effectiveness and appropriateness. As a component of MEDTEP, a program was established in March 1992 with RFA HS-92-03, focusing on the patient outcomes of pharmaceutical therapy. As a result of that RFA, AHCPR has awarded sixteen grants focusing on outcomes of pharmaceutical therapy in ambulatory care settings. This RFA initiates an extension of that work, but is not limited to studies in any particular care setting. It focuses on the effects on patient outcomes of various programs, proposed or existing, for managing selection, utilization, and cost of pharmaceutical therapies and services within the changing health care environment. MEDTEP Research Themes This RFA incorporates the themes and concepts common to all MEDTEP research (MEDTEP-Summary PA-94-074). "Effectiveness" refers to outcomes experienced by, or observed in, patients in routine clinical practice. This is distinct from "efficacy" which refers to the potential benefit of clinical interventions provided under ideal circumstances to patients who meet specific criteria. Cost effectiveness summarizes the cost and effect of treatment in terms of specified outcomes measured in nonmonetary units; it indicates value obtained for resources expended. MEDTEP studies focus on clinical conditions that affect large numbers of people (or a large proportion of a major subpopulation); that result in substantial expense; that are significant in Medicaid or Medicare programs; and for which there are large, unexplained variations in treatment. The outcomes to be studied, in addition to traditional measures such as survival and morbidity, include patient- reported outcomes such as perceived health status, functioning, and quality of life. MEDTEP studies typically involve a multidisciplinary team of researchers with clinical and methodological expertise, plus understanding of the perspectives of patients, providers, and policymakers. Methods MEDTEP studies draw on a wide range of research methods that include, but are not limited to: experimental and quasi-experimental designs, case-control and cohort studies, effectiveness trials, meta-analysis, cost effectiveness analysis, decision modeling, and combinations of these methods. Primary data will generally be required; however, these may be combined with, and occasionally replaced by, secondary data when the latter will provide adequate information and efficient means to address the research question(s). Data sources should allow for the detection, measurement, and/or control of: drug exposure, indication for drug use, severity of illness, comorbidities, relevant confounders, and costs of care when appropriate. Measures of short- and long-term outcomes, as well as pre-treatment health status information, are critical data elements. Applications must be explicit and detailed in describing data, methods, and tools for data collection and analysis. The research plan must be justified in terms of potential for answering the proposed research question(s). Applicants who propose to use Medicare or Medicaid data must specify the required data files and explore the availability and cost of obtaining these data with the Health Care Financing Administration (HCFA). The estimated cost must be presented, along with documentation from HCFA, as part of the grant application. This cost should not be included in the total budget request for the project. For more information about data budgets, contact Mr. Ralph L. Sloat, AHCPR Grants Management Officer (see INQUIRIES). Topic Selection Current restructuring within the health care system provides an opportunity to enhance understanding of the interrelationships of pharmaceutical treatments and services, with patient outcomes. The changing mix of payment mechanisms, benefit plans, and cost- containment strategies has widespread implications for patient care. Of particular interest are studies involving the comparative effectiveness and/or cost effectiveness of pharmaceutical therapies within the changing health care system. Studies are expected to compare different clinical approaches to the prevention, diagnosis, treatment, and/or management of common clinical conditions. While most of these studies will involve comparisons among drug therapies and/or related services, studies of drug versus non-drug treatment options also are responsive to the RFA. If it is not feasible to address all important treatment options in a single study, applicants must identify the specific interventions the study will address and justify selections and exclusions. Studies should focus on one or both of the following topic areas: 1. Pharmaceutical Economic Analyses Evaluations of the economic impact of drug therapy are of particular policy relevance in the changing health care environment. Economic information is needed by large-volume purchasers such as managed care organizations to guide formulary decisions, price negotiations, and clinical decision making. Cost-effectiveness, cost-benefit, and cost-utility analyses are responsive to this RFA provided patient outcomes are the central focus. Studies that evaluate monetary cost alone are not responsive. Of special interest are studies that develop tools or analytic models that will be useful in other research. Examples of suitable topics include the following: o Comparative cost effectiveness of alternative drug therapies for treatment of a selected common condition. Choice of condition and treatment options should be justified in terms of clinical and policy relevance. o Cost-utility studies that include user-friendly (to patients and providers) methods or measures for assessing patient preferences, values, and utilities. 2. Effects of Changes in the Health Care Environment There is a trend in health care toward systems of managed care, including health maintenance organizations, individual practice organizations, preferred provider organizations, and coordinated care networks. Often, these systems include some form of case management or pharmaceutical benefit management, for coordination of services and patient monitoring. They also include mechanisms for managing selection, utilization, and cost for pharmaceutical therapies and services. Previous studies have explored the effects of policy and educational interventions on the appropriateness of drug prescribing and use. Many questions remain, however, about the long-term effects of programs that monitor and intervene in the drug management process. Innovations that affect patient outcomes and cost, and that warrant evaluation include: o Interventions designed to change prescribing practices. These range from face-to-face academic detailing, to computer-generated reminders, to adoption of clinical practice guidelines and treatment algorithms that address drug selection and use. o Interventions such as those implemented by large-volume drug purchasers including HMOs, Medicaid programs, and pharmaceutical benefit managers, to optimize the clinical and/or cost effectiveness of drug utilization review (DUR). o Interventions designed to encourage the provision or alter the content of pharmaceutical care. These include reimbursement programs for pharmacist cognitive services within managed care organizations. INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of AHCPR that women and members of minority groups must be included in all AHCPR supported health services research projects involving human subjects, unless a clear and compelling rationale and justification are provided that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. A new NIH policy resulting from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43) supersedes and strengthens NIH's previous policies (Concerning the Inclusion of Women in Study Populations, and Concerning the Inclusion of Minorities in Study Populations), which were in effect since 1990 and which AHCPR had adopted. The new NIH policy contains some provisions that are substantially different from the 1990 policies. AHCPR plans to publish guidelines specific to AHCPR. In the interim, AHCPR will follow the NIH guidelines, as applicable. All investigators proposing research involving human subjects should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research," published in the Federal Register of March 28, 1994 (FR 59 14508-14513) and reprinted in the NIH Guide for Grants and Contracts, Volume 23, Number 11, March 18, 1994. Investigators also may obtain copies of the NIH policy from the AHCPR program staff listed under INQUIRIES. AHCPR program staff may also provide additional relevant information concerning this policy. LETTER OF INTENT Prospective applicants are asked to submit, by March 1, 1995, a letter of intent that includes a descriptive title of the proposed research; the name, address, and telephone number of the Principal Investigator, co-investigators and other key personnel; the applicant institution and other participating organizations or institutions; and the number and title of this RFA. Although a letter of intent is not required, is not binding, and does not enter into the consideration of any subsequent application, the information allows AHCPR staff to estimate the potential review workload and avoid conflicts of interest in the review. The letter of intent is to be sent to: Joanne S. Book Center for Medical Effectiveness Research Agency for Health Care Policy and Research East Jefferson Street, Suite 605 Rockville, MD 20852-4908 APPLICATION PROCEDURES Applications are to be submitted on the research grant application form PHS 398 (rev. 9/91). State and local government agencies may use form PHS 5161 and follow those requirements for copy submission. These forms are available at most institutional offices of sponsored research; the Office of Grants Information, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone (301) 594-7248; and, for AHCPR applications, from Global Exchange Inc., 7910 Woodmont Avenue, Suite 400, Bethesda, MD 20814-3015, telephone (301) 656-3100 (FAX 301 652-5264). The RFA label available in the form PHS 398 (rev. 9/91) form must be affixed to the bottom of the face page of the original application. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, type "RFA HS-96-001" in Section 2a on the face page of the application form and mark the "YES" box. Submit a signed, typewritten original of the application, including the Checklist, and three signed, photocopies, in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** At the time of submission, two additional copies of the application must be sent to: Center for Medical Effectiveness Research Agency for Health Care Policy and Research 2101 East Jefferson Street, Suite 605 Rockville, MD 20852-4908 Applications submitted under this RFA must be received in the Division of Research Grants, NIH, by April 12, 1995. If an application is received after that date, it will be returned to the applicant without review. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed by the Referral Office, Division of Research Grants, NIH, for completeness, and by AHCPR staff for responsiveness to the RFA. Incomplete applications will be returned to the applicant without further consideration. Nonresponsive applications will be transferred to a standing AHCPR or other appropriate scientific review group for review through routine mechanisms. The determination of any application as nonresponsive will be the sole responsibility of AHCPR. Applications may undergo triage by the peer review group on the basis of relative scientific and technical competitiveness. The AHCPR will withdraw from further consideration those applications judged to be non-competitive for award and notify the applicant Principal Investigator and institutional official. When an application is reviewed, the peer review committee may recommend further consideration or no further consideration. The committee also assigns priority scores to the applications for which further consideration is recommended. Recommendations of the peer review committee may be reviewed subsequently by AHCPR's National Advisory Council for Health Care Policy, Research, and Evaluation. The peer review process is rigorous, and only those applications judged to be of greatest merit will be recommended for further consideration. Review Criteria The general review criteria for AHCPR grant applications are: o significance and originality from a scientific and technical viewpoint; o adequacy of the proposed method(s); o availability of data or proposed plan to collect data required for the project; o adequacy of the plan for organizing and carrying out the project; o qualifications and experience of the Principal Investigator and proposed staff; o reasonableness of the proposed budget; o adequacy of the facilities and resources available to the applicant; and o adequacy of plans to include both genders and minorities and their subgroups, as appropriate for the scientific goals of the research. Plans for the recruitment and retention of subjects will also be evaluated. The initial review group will also examine the provisions for the protection of experimental subjects, and the safety of the research environments. Special Review Criteria In addition to the general review criteria noted above, the following special scientific and technical review criteria will apply to this RFA: o scientific importance and policy relevance of the topic; o generalizability of results; o feasibility of answering proposed research question(s) within the project period; o attention to technical issues in case definition, case finding, data collection, and analysis; o quality and adequacy of proposed data; o justification for focus on outcome(s) specified; o adequacy of outcome measure(s); o sensitivity to patient heterogeneity and individual preference; o specification of useful findings or products, and identification of constituency(ies) for these; and o efficiency of the research plan. AWARD CRITERIA Applications will compete for available funds with all other applications for this RFA. In making funding decisions, AHCPR will consider: quality of the proposed project as determined by peer review, availability of funds, and program balance. INQUIRIES The AHCPR welcomes the opportunity to clarify any issues or questions >From potential applicants. Direct inquiries regarding program matters to: Richard J. Greene, M.D., Ph.D. Center for Medical Effectiveness Research Agency for Health Care Policy and Research East Jefferson Street, Suite 605 Rockville, MD 20852-4908 Telephone: (301) 594-1485 Email: JBook@po4.ahcpr.gov Direct inquiries regarding fiscal matters to: Ralph Sloat, Grants Management Officer Agency for Health Care Policy and Research 2101 East Jefferson Street, Suite 601 Rockville, MD 20852-4908 Telephone: (301) 594-1447 Email: RSloat@po7.ahcpr.gov AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance, No. 93.180. Awards are made under authorization of the Public Health Service Act, Title IX, and Section 1142 of the Social Security Act. Awards are administered under the PHS Grants Policy Statement and Federal Regulations 42 CFR Part 67, Subpart A, and 45 CFR Part 74 (45 CFR Part 92 for State and local governments). This program is not subject to the intergovernmental review requirements of Executive Order 12372. The Public Health Service strongly encourages all grant recipients to provide a smoke-free workplace and promote the non-use of all tobacco products. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people. From owner-sci-resources@net.bio.net Fri Jan 13 22:00:00 1995 Path: biosci!biosci!not-for-mail From: BIOSCI Administrator Newsgroups: bionet.sci-resources Subject: NIH GUIDE - RFA HL-95-012 - V24(01) 01/13/95 Date: 13 Jan 1995 16:50:30 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 467 Sender: biohelp@net.bio.net Approved: biosci-moderator@net.bio.net Distribution: world Message-ID: <3f774m$on7@net.bio.net> NNTP-Posting-Host: net.bio.net $$XID RFA HL95012 HL-95-012 P1O1 *************************************** LUNG SPECIFIC DRUG DELIVERY SYSTEMS FOR TUBERCULOSIS TREATMENT NIH GUIDE, Volume 24, Number 1, January 13, 1995 RFA: HL-95-012 P.T. 34; K.W. 0715165, 0740022, 1002027 National Heart, Lung, and Blood Institute Letter of Intent Receipt Date: February 24, 1995 Application Receipt Date: April 7, 1995 PURPOSE The National Heart, Lung, and Blood Institute (NHLBI) invites grant applications to encourage research on novel approaches to therapy, adjuvants to therapy, and prophylaxis of tuberculosis (TB), using the lung as the site of drug delivery. The primary objective of this special grant program is to develop new modalities of treatment for pulmonary TB based on delivery of the therapeutic agent(s) directly to the lung. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This Request for Applications (RFA), Lung Specific Drug Delivery Systems for Enhanced TB Treatment, is related to the priority area of immunization and infectious diseases. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign for-profit and non-profit institutions, public and private, such as universities, colleges, hospitals, laboratories, units of state and local governments and eligible agencies of the Federal government. Foreign institutions are not eligible for the First Independent Research Support and Transition (FIRST) award (R29). Applications from minority individuals women and new investigators are encouraged. All current policies and requirements that govern the research grant programs of the NIH will apply to grants awarded under this RFA. Awards under this announcement to foreign institutions will be made only for research of very unusual merit, need, and promise, and in accordance with Public Health Service policy governing such awards. Among the disciplines and expertise that may be appropriate for this research program are molecular pharmacology, physical chemistry, cell biology, biochemistry, virology, molecular biology, molecular immunology, infectious diseases, pathology, and pulmonary medicine. MECHANISM OF SUPPORT The support mechanism for this program will be the National Institutes of Health (NIH), individual research grant (R01) and the FIRST award (R29). While multidisciplinary approaches are encouraged, it is not the intent of this announcement to solicit applications for large studies encompassing a variety of individual subprojects, i.e., program projects. If collaborative arrangements through subcontracts with other institutions are planned, consult the program staff listed under INQUIRIES. Upon initiation of the program, the NHLBI will sponsor periodic meetings to encourage exchange of information among investigators who participate in this program. In the budget for the grant application, applicants should request travel funds for a one-day meeting each year, most likely to be held in Bethesda, Maryland. Applicants should also include a statement in their applications indicating their willingness to participate in these meetings. Applicants (who will plan and execute their own research programs) are expected to furnish their own estimates of time required to achieve the objectives of the proposed research project. Up to five years of support may be requested for R01s; five years are required for FIRST awards. Requested budgets for FIRST awards may not exceed those specified in the FIRST award guidelines. Because a variety of approaches would represent valid responses to this RFA, it is anticipated that there will be a range of costs among individual grants awarded. This RFA is a one-time solicitation. Future unsolicited competing continuation applications may be submitted for peer review and competition for support through the regular grant program of the NIH. It is anticipated that support for this program will begin in September 1995. Administrative adjustments in project period and/or amount may be required at the time of the award. Applicants from institutions that have a General Clinical Research Center (GCRC) funded by the NIH National Center for Research Resources may wish to identify the GCRC as a resource for conducting the proposed research. If so, a letter of agreement from the GCRC program director and principal investigator should be included with the application. The National Institute of Allergy and Infectious Diseases (NIAID) also has interest in developing new delivery systems and new therapeutic agents for the treatment of tuberculosis. Therefore, applications that are of mutual interest are likely to be given a secondary assignment to NIAID in accordance with the NIH referral guidelines. FUNDS AVAILABLE Although financial plans for fiscal year 1995 include approximately $2,500,000 for the total cost of the program for the first year, award of grants pursuant to this RFA is contingent upon receipt of funds for this purpose. It is anticipated that no more than 10 awards will be issued under this program. The specific number to be funded will, however, depend on the merit and scope of the applications received and the availability of funds. RESEARCH OBJECTIVES Background The spread of tuberculosis (TB) has reemerged as an urgent health problem. Rates for this disease have been increasing since the mid 1980s in association with the HIV epidemic. Recent projections of TB rates made by the Centers for Disease Control suggest that, worldwide, the current high rate of new TB cases in the population is likely to increase over the next 10 years. For industrialized countries, including the United States TB case rates are expected to remain stable or perhaps increase slightly over the next decade. The number of new active cases of TB reported annually in the U.S. population is now approximately 10/100,000 (new cases/100,000 people in the general population), with extremely high rates in HIV infected study populations, about 800/100,000. Current methods of treatment are far from optimal and better ones are being sought to overcome the increasing spread of TB and the problem of incompletely treated TB that contributes to the emergence of drug resistant strains. Since many patients with TB may have significant social problems, compliance with drug therapy is frequently difficult. The development of targeted drug delivery to the lungs as a means of treating TB is desirable for several reasons. Although TB is a systemic disease that can potentially affect any organ system, the lung is the major portal of entry for Mycobacterium tuberculosis (Mtb) and thereby the site of the initial immune response as well as an important site of reactivation disease. Technology for lung specific drug delivery systems is now at a point where aerosols and aerosols combined with liposomes and possibly timed-release methodology may offer advantages for more effective treatment and prevention of TB. Conventional antituberculous medications frequently have serious side effects. Although single drugs can be effective for prophylactic treatment of skin test converters, active disease must be treated using combinations of three or four drugs over a period of at least six to nine months to insure that disease will not recur after treatment is discontinued and to prevent the emergence of resistant strains. Targeted delivery of new formulations, directly to the lungs, could result in high pulmonary levels relative to systemic levels. Thus, increasing effectiveness and decreasing toxicity. Supplementing the dose of agent delivered to the diseased lung, when it is the only clinically involved organ, could make it possible to decrease the duration of treatment in these cases. Because the systemic dose will not be increased, undesirable toxicities would be avoided. Another advantage is that this mode of delivery might make it easier to provide prolonged treatment. It should be possible to design biopolymers or nanoparticles which slowly dissolve and therefore slowly release their drugs to the pulmonary environment. Improved targeted delivery approaches combined with development of new antituberculous drugs or with timed release formulations may reduce the frequency of dose delivery. This would be a major benefit in treating patients in whom it is hard to maintain effective compliance with treatment regimens. For example, longer intervals between treatment would make it easier to deliver directly observed therapy, which is an effective means of getting patients to complete a full course of treatment. Targeted drug delivery may be essential in carrying out future modes of TB therapy such as gene therapy resulting in increased cytokine expression or antisense oligonucleotide therapy blocking protein synthesis. Objectives and Scope The objective of this initiative is to encourage basic research aimed at developing new modalities of treatment for TB, using the lung as the site of drug delivery. Delivery of antituberculous agents to the lung might be used as a means of increasing local concentrations of drug to augment existing, conventional therapy or perhaps the lung could be used as the route of delivery for agents that are intended to work both locally and systemically. It is thought that lowered systemic toxicity provided by this approach would permit much more flexibility for treatment regimens such that smaller, more effective doses may be employed. Conversely, if a lung delivery system is intended as the only route for drug delivery, it would be essential to demonstrate that systemic levels of drug are adequate to treat TB elsewhere in the body. Drugs could be targeted to the lung as opposed to other organs, to airways of a specific size within the lungs, or perhaps to injured or diseased areas as compared to normal ones. Specific cells such as macrophages, endothelial cells, or epithelial cells might be targeted and it should even be possible to deliver drugs to specific organelles within a cell. Potential drug delivery sites could include the alveolar surface itself, or cells on the surface such as macrophages, lymphocytes, or neutrophils. Other targets might include cells and extracellular matrix beneath the epithelium. The nature of the material will affect its fate. For example, insoluble particulate material will largely be taken up by resident alveolar macrophages. Some surfactant phospholipids will be recycled into Type II epithelial cells. Soluble molecules will enter and pass through or between epithelial cells into the extracellular matrix. Some proteins will be found in phagocytic cells in the connective tissue and lymph nodes. Aerosol delivery of therapeutic agents to the lung has been used for many years in the treatment of airways obstructive diseases. Since the 1980s the aerosol application of interferon-alpha (INF-`) has been examined by several groups of investigators for the treatment of various types of lung cancer. Interferon-gamma has also been given to human subjects to activate alveolar macrophages. In general, it seems possible to deliver fairly high concentrations of these agents to the epithelial lung surface and minimize the systemic dose and toxicity. Drugs used in the treatment of TB including rifampin and streptomycin can be encapsulated in liposomes. Drugs such as these could be delivered to the lung in conjunction with antituberculous therapy (administered by mouth or parenterally) to augment therapy or given to replace conventional therapy, if adequate levels can be achieved in all parts of the body. Liposomal preparations of drugs or agents capable of potentiating immune responses may have enhanced uptake by lung cells. Furthermore, it appears to be possible to deliver liposomes by the aerosol route. Surfactant which may be useful as a vehicle for the delivery of other agents can be aerosolized and delivered to the lung. Research topics that could be applicable to the goals of this RFA might include, but are not limited to, the following areas: mechanisms of treatment, drug formulation issues, delivery strategies to get agents to the respiratory tract, targeting strategies to reach particular sites, evaluation of drug delivery and especially, evaluation of effectiveness of lung targeted drug delivery. These issues could be studied at a variety of levels including laboratory modeling animal testing, and human studies. Both animal studies and innovative studies involving human subjects or using human cells or tissues are encouraged. Research involving humans should be formulated in the context of mechanistic studies and should address specific hypotheses. Large scale clinical studies are beyond the scope of this RFA. Pharmacologic agents currently used in antituberculous regimens and agents that appear to show promise for future use are of interest. SPECIAL REQUIREMENTS Applications that propose descriptive studies and do not contain hypothesis driven studies directed at developing lung specific drug delivery systems to aid in the treatment of tuberculosis will not be acceptable. Treatment strategies must be clearly linked to the lung and to specific mechanisms of mycobacterial disease. This program will not support studies directed at development of animal models alone, therefore the models must be applied to the study of lung specific drug delivery strategies for use in the treatment of mycobacterial disease. This RFA is not intended to support in vitro studies of drug screening. Studies to verify that drug in an active state reaches the site intended for deposition should be included. Applications that focus on molecular pharmacologic approaches are of particular interest. INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of the NIH that women and members of minority groups and their subpopulations must be included in all NIH supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification is provided that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This new policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43) and supersedes and strengthens the previous policies (Concerning the Inclusion of Women in Study Populations, and Concerning the Inclusion of Minorities in Study Populations) which have been in effect since 1990. The new policy contains some new provisions that are substantially different from the 1990 policies. All investigators proposing research involving human subjects should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research", which have been published in the Federal Register of March 28, 1994 (FR 59 14508-14513), and reprinted in the NIH GUIDE FOR GRANTS AND CONTRACTS of March 18, 1994, Volume 23, Number 11. Investigators also may obtain copies of the policy from the program staff listed under INQUIRIES. Program staff may also provide additional relevant information concerning the policy. LETTER OF IN