From owner-sci-resources@net.bio.net Tue Jul 02 23:00:00 1996 Path: biosci!biosci!not-for-mail From: BIOSCI Administrator Newsgroups: bionet.sci-resources Subject: NIH GUIDE - RFA CA-96-017 - V25(21) 06/28/96 Date: 3 Jul 1996 12:04:23 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 556 Sender: daemon@net.bio.net Approved: biosci-help@net.bio.net Distribution: world Message-ID: <4reg7n$60f@net.bio.net> NNTP-Posting-Host: net.bio.net $$XID RFA CA96017 CA-96-017 P1O1 *************************************** INVESTIGATOR GRANTS FOR CLINICAL CANCER THERAPY RESEARCH NIH GUIDE, Volume 25, Number 20, June 21, 1996 RFA: CA-96-017 P.T. 34; K.W. 0715035, 0740000, 0745000, 0755015 National Cancer Institute Letter of Intent Receipt Date: August 30, 1996 Application Receipt Date: November 8, 1996 PURPOSE The Cancer Therapy Evaluation Program (CTEP), Division of Cancer Treatment Diagnosis and Centers (DCTDC), National Cancer Institute (NCI) invites research grant applications to conduct therapeutic clinical trials research employing new agents, concepts, or strategies for the treatment of cancer. This initiative is aimed at encouraging new clinical investigators who have not previously had independent grant funding to submit research applications in this area of research. 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), Investigator Grants for Clinical Cancer Therapy Research, is related to the priority area of cancer. 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 202/512-1800). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic non-profit and for-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State or local governments, and eligible agencies of the Federal government. Applications from minority and women investigators are encouraged. Principal investigators should be new to the clinical research field and should not have been awarded a previous R01 or R29 grant. An important principle to remember is that the more extensive the prior independent research experiences, regardless of funding sources, the greater likelihood there will be diminished priority for award. MECHANISM OF SUPPORT This RFA will use the National Institutes of Health (NIH) individual research grant (R01) as its funding mechanism. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. The total project period for an application submitted in response to this RFA may not exceed four years. The direct cost for the four year period may not exceed $500,000. The direct cost in any budget period may not exceed $150,000 (not including indirect costs for collaborating institutions). The anticipated award date is July 1997. Awards and level of support depend on receipt of a sufficient number of applications of high scientific merit. Although this program is provided for in the financial plans of the NCI, the award of grants pursuant to this RFA is contingent upon the continuing availability of funds for this purpose. This RFA is a one-time solicitation for new applications for award in FY 97. NCI encourages investigators who responded to the previous solicitation (RFA CA-95-012) to resubmit. Future unsolicited competing continuation applications will compete with all investigator-initiated applications and be reviewed according to the customary peer review procedures. FUNDS AVAILABLE Approximately $2,000,000 in total costs per year for each of four years will be committed to fund applications submitted in response to this RFA. It is anticipated that ten new individual awards will be made. RESEARCH OBJECTIVES Background In the past year, a number of groups have expressed concern over the declining number of clinical investigators entering and remaining in academic research. Clinical investigators are a critical component in translating new therapeutic agents and modalities from the laboratory into the clinic. They must maintain a broad perspective and knowledge concerning clinical and basic sciences, while developing new cancer therapies that are hypothesis driven. They are highly interactive with basic and clinical researchers in related disciplines. This translational clinician is considered distinct >From the clinician who also has a PhD or equivalent training and concentrates on basic research or the clinician who participates in cancer research solely by entering patients on clinical trials. The Clinical Investigations Task Force of the National Cancer Advisory Board and a sub-committee of the American Association of Clinical Oncology (ASCO) have both been addressing the problem of the decreasing number of academic clinical investigators. One of the problems identified is the lack of suitable mechanisms for the training and funding of clinical oriented investigators involved in translating basic research into new cancer treatments. The traditional grants mechanisms (R01, R29) are under-utilized and often do not fit the needs of young clinical investigators for the support of clinical trials research. The R29 grant mechanism requires the investigator to devote at least 50 percent effort to a five year project and the yearly budget is limited to approximately $70,000. Most clinicians have major clinical and teaching responsibilities and it is impossible to support both the clinical and laboratory components needed within the budget limitations of an R29 grant. New clinical investigators often do not have the publication or research track record to be competitive for R01 grant support. Thus, very few clinical trial research applications are submitted by new clinical investigators. DCT would like to reverse this trend and encourage new clinical investigators, who have not previously received R01 or R29 grant support, to submit grant applications for the conduct of translational clinical trials research. Project Description The Cancer Therapy Evaluations Program encourages qualified clinical investigators to develop R01 grant applications for the conduct of cancer clinical trials research on new therapeutic agents and modalities. Grant applications must include clinical trials involving human subjects and designed to ultimately improve cancer survival. The clinical trials must have a strong rationale and be based upon preclinical data, preferably generated by the applicant or collaborators, that support the underlying hypotheses. New clinical therapeutic trials employing drugs (including differentiating agents), biologics (including cytokines, antibodies), vaccine strategies, radiation, or surgery whether used as a single agent/modality or in combination are appropriate. Laboratory studies to monitor patients or to study the mechanism of antitumor effect and resistance should be included. The laboratory studies should be in support of the clinical trial, such that their conduct leads to a greater understanding of the relationship of the therapy and biological changes in the patient or the mechanism of action of an anti-tumor response. Laboratory studies would include pharmacokinetic studies of cytotoxic, immune-modulating, differentiation-inducing, and/or targeted therapeutic agents or relevant pharmacodynamic correlative studies. Measurement of particular biological responses would also be desirable particularly when this information would be relevant to the interpretation of the success or failure of the therapy in individual patients on the clinical trial. It is expected that a significant level of effort, at least 25 percent, will be committed to the research project by the Principle Investigator. 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 must be included with the application. 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 4928 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 reprinted 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 August 30, 1996, 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 is helpful in planning for the review of applications. It allows NCI staff to estimate the potential review workload and to avoid conflict of interest in the review. The letter of intent is be sent to: Ms. Diane Bronzert Division of Cancer Treatment, Diagnosis, and Centers National Cancer Institute Executive Plaza North, Room 734 6130 Executive Boulevard MSC 7432 Bethesda, MD 20892-7432 Rockville, MD 20852 (for express/courier service) Telephone: (301) 496-8866 FAX: (301) 480-4663 APPLICATION PROCEDURES The research grant application form PHS 398, (rev. 5/95) is to be used in applying for this RFA. These forms are available at most institutional offices of sponsored research and may be obtained from the Office of Extramural Outreach and Information Resources, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone (301) 435-0714, email: asknih@odrockm1.od.nih.gov. The RFA label available in the PHS 398 application form must be affixed to the bottom of the face page. 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, the RFA number and title must be typed on line 2 of the face page of the application form and the YES box must be marked. Submit a signed, typewritten original of the application, including the Checklist, and three signed, exact photocopies, in one package to: DIVISION OF RESEARCH GRANTS NATIONAL INSTITUTES OF HEALTH 6701 ROCKLEDGE DRIVE, ROOM 1040 MSC 7710 BETHESDA, MD 20892-7710 BETHESDA, MD 20817 (for express/courier service) At the time of submission, two additional copies of the application must also be sent to: Ms. Toby Friedberg Division of Extramural Activities National Cancer Institute Executive Plaza North, Room 636 6130 Executive Boulevard Bethesda, MD 20892 Bethesda, MD 20852 (for express mail) Applications must be received by November 8, 1996. If an application is received after that date, it will be returned. The Division of Research Grants (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. B. Special Instructions for the Completion of the PHS 398 Application "Just-in-Time" is an initiative of the National Institutes of Health (NIH) Extramural Reinvention Laboratory under the auspices of the National Performance Review and government-wide efforts to create a government that works better and costs less. JIT postpones the collection of certain information that currently must be included in all competing applications when submitted. The information for the applications with a likelihood of funding is submitted "just-in-time" for awards to be made. This delayed exchange of information significantly relieves the administrative burden for the 75 to 80 percent of applicants who will not receive an award. In addition, the information that is exchanged "just-in-time" for award will be current, rather than several months old as is currently the case (which often necessitates a request for updated information, e.g., for other support). In responding to the RFA, the following are specific instructions for sections of the PHS 398 application form (rev. 9/95) that should be completed differently from usual. Some sections are modified and others in the application do not need to be completed for the submission of the application but WILL be requested if your application receives a priority score in the fundable range. For all other items in the application, follow the usual instructions on pages 5-20 of the PHS 398 booklet. FACE PAGE (Form AA) - The title and number of the RFA must be typed in line 2a. Failure to do so could result in delayed processing of your application such that it may not reach the review committee in time for review. FORM DD - PAGE 4 - DETAILED BUDGET PAGE FOR INITIAL BUDGET PERIOD Enter direct costs only for the following: o Personnel, Patient Care Costs, Alterations-Renovations - Complete these sections as instructed in the PHS 398 booklet. o Consultant Costs - Itemize only if proposed consultant costs exceed $10,000 or if a consultant is identified as key personnel. o Equipment - Itemize only individual equipment items in excess of $10,000. o Supplies - Itemize (a) all animal costs and (b) any individual supply item which costs more than $10,000. If animals are involved, state their unit purchase and care costs. Enter total animal costs and supply costs on separate lines. o Travel and Other Expenses - Itemize any expense category that exceeds $5,000. FORM EE - PAGE 5 - BUDGET FOR ENTIRE PROPOSED PROJECT PERIOD Do not complete the categorical budget table on form page 5 in the PHS 398 (rev. 5/95). Only the requested total direct costs for each year and total direct costs for the entire proposed period of support should be shown. Begin the budget justification in the space provided, using continuation pages as needed. Budget Justification o List the name, role on project and percent effort for all project personnel (salaried or unsalaried) and provide a narrative justification for each person based on his/her role on the project and proposed level of effort. o Identify all consultants by name and organizational affiliation and describe the services to be performed. o Provide a narrative justification for any major budget items, other than personnel, that are requested for the conduct of the project that would be considered unusual for the scope of research. No specific costs for items or categories should be shown. o Indirect costs will be calculated at the time of the award using the institution's actual indirect cost rate. Applicants will be asked to identify the indirect cost exclusions prior to award. o If consortium/contractual costs are requested, provide the percentage of the subcontract total costs (direct and indirect) relative to the total direct costs of the overall project. The subcontract budget justification should be prepared following the instructions provided above. FORM FF - PAGE 6 - BIOGRAPHICAL SKETCH - A biographical sketch is required for all key personnel, following the modified instructions below. Do not exceed the two page limit for each person. o Complete the education block at the top of the form page. o List current position(s) and those previous positions directly relevant to the application. o List selected peer-reviewed publications directly relevant to the proposed project, with full citation. o Provide information on research projects completed and/or research grants participated in during the last 5 years which are relevant to the proposed project. Title, principal investigator, funding source, and role on project must be provided. Please state whether you have previously served as Principal Investigator on a R01 or R29 grant. FORM GG - PAGE 7 - OTHER SUPPORT - Do not complete. Updated information will be requested by NCI staff from only those applicants being considered for funding. SPECIFIC INSTRUCTIONS - RESEARCH PLAN (Booklet Pages 15-19) - Applications in response to this RFA should be concise and shorter than regular grant applications. Items a-d may not exceed 20 pages in total. a. Specific Aims - In one page or less, list in priority order, the broad, long-range objectives. Describe concisely and realistically the hypothesis to be tested and what the specific research described in this application is intended to accomplish. b. Background and Significance - In two to three pages, use this section to describe (a) how the proposed research will contribute to meeting the goals and objectives of the RFA; and, (b) explain the rationale for the selection of the general methods and approaches proposed to accomplish your specific aims. c-d. Progress Report/Preliminary Studies, Research Design and Methods - In seventeen pages or less, complete as instructed on pages 20-21 of the PHS 398 booklet with the modification that the clinical protocol(s) and up to six publications, manuscripts submitted or accepted for publication, patents, or invention reports can be included in the Appendix (see below). Investigator may use this section to address the following: o preliminary studies pertinent to the application; o rationale and hypothesis for the clinical trial and laboratory studies; o general methods that will be utilized; provide specific details for those techniques which are unique or where a significant departure from a generally accepted technique is important for reviewers to know; o outcome measures that will be used to assess the success or failure of each set of experiments (include statistical analyses for laboratory and clinical studies); o plans for the rigorous data management and verification of research data; o potential pitfalls in the experimental design and alternative studies that will be done if the proposed experiments fail. Items e-f - Human Subjects, Vertebrate Animals - Complete as described on pages 17-18. State clearly the plans for early detection of and protection against adverse effects on human subjects. Documentation for the composition of the proposed study population in terms of gender and racial/ethnic group together with a rationale for its choice must be included in the Human Subjects section (see page 30 for format). APPENDIX (Page 19) - Up to 10 publications, manuscripts submitted or accepted for publication, patents, and invention reports may be provided. Clinical protocol(s) must be included in this section. CHECKLIST (Page 19) - Do not submit the checklist page. For amended applications, applicants must complete the block in the upper right corner of the face page to indicate the previous grant number. A completed checklist will be required prior to award. Questions regarding these instructions may be directed to the program staff listed under INQUIRIES. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed by the Division of Research Grants (DRG) for completeness and by the NCI for responsiveness. Incomplete applications will be returned to the applicant without further consideration. If the application is not responsive to the RFA, NCI 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 Request for Applications will be evaluated for scientific and technical merit by an appropriate peer review group convened by the NCI in accordance with the review criteria stated below. As part of the initial merit review, all applications will receive a written critique and may undergo a process in which only those applications deemed to have the highest scientific merit will be discussed, assigned a priority score, and receive a second level review by the National Cancer Advisory Board. The review group will assess the scientific merit of the studies using the following review criteria: 1. Importance, timeliness, and clinical merit of the clinical trials. 2. Quality of data supporting the proposed clinical trial. 3. Scientific and technical merit of the proposed laboratory studies. 4. Relevance of the proposed laboratory studies to the clinical trials. 5. Research training and clinical qualifications of the Principal Investigator and staff in the area of the proposed research. 6. Availability and quality of the resources necessary to perform research. 7. Quality of data verification and management plans and statistical analysis. The initial review group will critically examine the submitted budget and will recommend an appropriate budget and period of support for each approved application. They will also examine the provisions for the protection of human and animal subjects, the safety of the research environment, and conformance with the NIH Guidelines for the Inclusion of Women and Minorities as Subjects in Clinical Research. AWARD CRITERIA Applications considered by the National Cancer Advisory Board will be considered for award based upon (a) scientific and technical merit; (b) availability of funds; and (c) programmatic priorities. Preference will also be given to clinical investigators who are new to this research area. Letter of Intent Receipt Date: August 30, 1996 Application Receipt Date: November 8, 1996 Review by National Cancer Advisory Board: May 1997 Anticipated Award Date: July 1997 INQUIRIES Written and telephone inquiries concerning the objectives and scope of this RFA and inquiries about whether or not specific proposed research would be responsive are strongly encouraged. The program staff welcome the opportunity to clarify any issues or questions from potential applicants. Direct inquiries regarding general programmatic issues and chemotherapy agents to: Ms. Diane Bronzert, Program Director Division of Cancer Treatment, Diagnosis, and Centers National Cancer Institute Executive Plaza North, Room 734 6130 Executive Boulevard MSC 7432 Bethesda, MD 20892-7432 Telephone: (301) 496-8866 FAX: (301) 480-4663 Email: BRONZERD@DCT.NCI.NIH.GOV Direct inquiries regarding fiscal matters to: Ms. Eileen M. Natoli Grants Administration Branch National Cancer Institute Executive Plaza South, Room 243 6120 Executive Boulevard MSC 7150 Bethesda, MD 20892-7150 Telephone: (301) 496-7800, ext. 256 FAX: (301) 496-8601 Email: NATOLIE@GAB.NCI.NIH.GOV AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No 93.395, Cancer Treatment Research. Awards are made under the authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended, Public Law 99-158, 42 USC 241 and 285) and administered under HHS grants policies. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. The PHS strongly encourages all grant and contract recipients to provide a smoke-free workplace and promote the non-use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routing education, library, day care, health care or early childhood development services are provided to children. 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 Tue Jul 02 23:00:00 1996 Path: biosci!biosci!not-for-mail From: BIOSCI Administrator Newsgroups: bionet.sci-resources Subject: NIH GUIDE - RFA CA-96-011 - V25(21) 06/28/96 Date: 3 Jul 1996 12:03:47 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 1023 Sender: daemon@net.bio.net Approved: biosci-help@net.bio.net Distribution: world Message-ID: <4reg6j$5uj@net.bio.net> NNTP-Posting-Host: net.bio.net $$XID RFA CA96011 CA-96-011 P1O1 *************************************** COOPERATIVE FAMILY REGISTRY FOR EPIDEMIOLOGIC STUDIES OF COLON CANCER NIH GUIDE, Volume 25, Number 20, June 21, 1996 RFA: CA-96-011 P.T. 34; K.W. 0715035, 0785055, 0780030 National Cancer Institute Letter of Intent Receipt Date: August 6, 1996 Application Receipt Date: September 20, 1996 PURPOSE The Extramural Programs Branch, Epidemiology and Biostatistics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), and the Early Detection Branch, Division of Cancer Prevention and Control, NCI invite Cooperative Agreement applications from investigators to participate, with the assistance of the NCI, in a network of organizations constituting a Cooperative Family Registry for Colorectal Cancer Studies (CFRCCS). The purpose of the proposed awards is to stimulate a cooperative effort to: 1. Collect pedigree information, epidemiological data and related biological specimens from patients with a family history of colon cancer in order to provide a registry resource for interdisciplinary studies on the etiology of colon cancer, and to encourage translational research in this area. 2. Identify a population at high risk for colon cancer that could benefit from new preventive and therapeutic strategies. 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), Cooperative Family Registry for Colon Cancer Studies, relates to the priority area of cancer. 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 202-512-1800). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign non-profit and for-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. MECHANISM OF SUPPORT Support of this program will be through the cooperative agreement (U01), an assistance mechanism in which substantial NCI scientific and programmatic involvement with the recipients during performance of the planned activity is anticipated. Under the cooperative agreement, the NIH intention is to support and/or stimulate the recipient's activity by involvement in, and otherwise working jointly with, the awardee in a partner role, but is not to assume direction, prime responsibility, or a dominant role in the activity. This mechanism is appropriate because the participant organizations will be responsible for defining their scientific objectives and approaches. Substantial NCI involvement is anticipated in order to facilitate interaction between the groups, to coordinate their efforts with other ongoing initiatives, and to promote the knowledge and use of this resource among the scientific community. Details of the responsibilities, relationship and governance of the study to be funded under cooperative agreements are discussed later in this document under the section "Terms and Conditions of Award." The total project period for applications submitted in response to the present RFA should not exceed four years. The anticipated award date is April 1, 1997. Because the nature and scope of the research proposed in response to this RFA may vary, it is anticipated that the size of an award will vary also. Awards and level of support depend 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 NCI, awards pursuant to this RFA are contingent upon the availability of funds for this purpose. This RFA is a one-time solicitation. At this time, the NCI has not determined whether or how this solicitation will be continued beyond the present RFA. FUNDS AVAILABLE Approximately $3 million in total costs per year for four years will be committed to specifically fund applications which are submitted in response to this RFA. It is anticipated that two to five awards will be made. This funding level is dependent on the receipt of a sufficient number of applications of high scientific merit. RESEARCH OBJECTIVES Background Recommendations from a panel of scientists convened at the first conference on "Genetic Epidemiology of Cancer: an Interdisciplinary Approach", published in 1994, stated that a resource should be created to support the identification of families with increased occurrence of cancer with a recognized genetic component, to initiate the coordinated collection of pertinent clinical and epidemiologic data and biological specimens, and to establish a much needed resource for interdisciplinary and translational studies on the etiology of cancer. As new knowledge about cancer molecular genetics increases at an extremely rapid pace, these family registries would create and preserve a resource that would otherwise be lost, provide the infrastructure for population-based and collaborative studies that cannot easily be supported through traditional investigator-initiated research grants, and provide the opportunity to design appropriate intervention and therapeutic approaches for the high-risk populations so identified, as well as developing appropriate genetic counseling strategies for this at-risk population. This proposed cooperative agreement, responding to the above and to further specific recommendations from a recent workshop on "Genetic Screening for Colorectal Cancer", is intended to complement and expand previous family registry initiatives by creating a Cooperative Family Registry for Colorectal Cancer Studies (CFRCCS). Colorectal cancer is the third most common malignancy in the world. In the U.S. over 157,000 people are diagnosed with colorectal cancer each year, and 60,500 die of this disease annually. Mortality from colorectal cancer has changed very little in the last 50 years, and early detection is one of the most important factors for a good prognosis. It is estimated that approximately 10 to 15 percent of colorectal cancer is familial, and that one person in 200 may carry high-risk alleles of the genes causing inherited colorectal cancer. It is also estimated that the same genes may be involved in as much as 13 percent of sporadic tumors. Currently, germline mutations of several identified genes have been shown to be responsible for hereditary forms of colorectal cancer. Familial adenomatous polyposis (FAP) is a rare inherited condition leading to colorectal cancer. Even though the clinical characteristics of this disease were first described more than one hundred years ago, its molecular bases are only now being elucidated. Germline mutations of the APC gene seem to be responsible for this condition. The APC gene was mapped to the long arm of chromosome 5 in 1991. The APC gene is involved as well in the etiology of Gardner syndrome, a variant of familial polyposis in which desmoid tumors, osteomas, and other neoplasms occur together with multiple adenomas of the colon and rectum. Hereditary non-polyposis colorectal cancer (HNPCC) is one of the most common cancer susceptibility syndromes. It is characterized by dominant transmission and high penetrance. Families with HNPCC are delineated as having at least three relatives in two generations with colorectal cancer, with one diagnosed before age 50. These families also have elevated incidence of cancers of the endometrium, stomach, urinary tract, and other sites. Four different mismatch repair genes have been implicated recently in the etiology of HNPCC. Mutations in hMSH2, mapping to chromosome 2 and to the gene that encodes a human homologue of the E.coli mismatch repair protein mutS, account for the majority of cases of HNPCC. Mutations in hMLH1, homologue of the bacterial repair gene mutL, map to chromosome 3 and are also found in families with HNPCC. Mutations in hPMS1 and hPMS2, encoding homologues of the bacterial MutL and yeast PMS1, are thought to account for a minor fraction of HNPCC. In families with HNPCC a mutation of one gene copy is inherited, and a somatic mutation in the second copy is associated with a particular form of genetic instability termed microsatellite instability or replication error (RER). Microsatellite instability is caused by slippage of one strand relative to the other, and consequent increases of oligonucleotides containing repetitive sequences. Such defects are usually repaired by mismatch repair genes. The implication of this observation is that lack of mismatch repair causes the accumulation of mutations at increased rate in key oncogenes or tumor suppressor genes, thus speeding the development of malignancy. In addition, the observation of microsatellite instability in a variety of sporadic tumors seen in the syndrome suggests that somatic mutations, or low penetrance germline mutations causing mismatch repair defects, may be the cause of a significant portion of many types of cancers seen in the general population. The ongoing identification of additional susceptibility genes for colorectal cancer will soon make it possible to fully characterize hereditary cancer patients and high-risk relatives and provide them with an assessment of their cancer risk using molecular techniques. However, much knowledge needs still to be acquired and a higher grade of technical development achieved, before this strategy becomes applicable to the general population. It is an NCI commitment to reduce morbidity and mortality from malignancies, and a currently pressing issue is how the recent advances in colon cancer genetics and genetic epidemiology can be translated into public health strategies aimed at early detection. An important strategy is predictive testing through the use of molecular genetic assays to detect inherited cancer-predisposing mutations in clinically healthy individuals. Appropriate and timely translation of discoveries in molecular genetics into the reduction of morbidity and mortality for inherited forms of cancer through predictive testing will entail seeking the answer to a series of immediate and specific scientific questions which are beyond the laborious task of gene identification. The CFRCCS will facilitate high-priority multidisciplinary investigations necessary to complete the translational research process that will lead to the application of predictive testing for colorectal cancer susceptibility in high-risk populations, and to the design of effective prevention and therapeutic approaches. Such investigations may include, but are not limited to: mutational analysis to determine the spectrum of significant mutations versus rare polymorphisms; the study of the penetrance of these inherited mutations (age-dependent risk of being affected in mutation carriers), their expressivity (organ and tissue affected) and the clinical consequences (natural history of the disease); the study of gene penetrance, gene-gene interaction, and the interaction with factors influenced by lifestyle, such as dietary, and reproductive and hormonal factors; and the study of the ethical, legal, and social implication of genetic testing for colorectal cancer and associated syndromes. Research Goals and Scope The purpose of this RFA is to stimulate a collaborative effort for the establishment of a cooperative family registry for epidemiologic and interdisciplinary studies of individuals at high risk for colorectal cancer. A population-based approach, utilizing resources such as the SEER registries, or other cancer registries, is strongly encouraged. Limited funding will be available for pilot or feasibility studies using the family registry resources, to provide preliminary data for the subsequent submission of regular research grant applications in epidemiologic, prevention or basic biological research. Many different approaches to colon cancer research will be able to take advantage of family registry resources, as new knowledge and molecular tools become available. The existence of the CFRCCS would enhance the cost-effectiveness of: (1) the identification and follow-up of high-, intermediate-, and low-risk individuals for the purpose of preventive intervention; (2) the evaluation of the effectiveness of optional treatment strategies as they become available; (3) molecular epidemiology studies generating and testing etiologic hypotheses; and (4) the integration of laboratory studies on cancerogenic mechanisms with epidemiologic and genetic data for colorectal cancer. Current epidemiologic studies of familial colorectal cancer are limited by the feasibility and expense of collecting a sufficient number of high- and intermediate-risk families to define the genetic heterogeneity of the familial disorder. Moreover, as new statistical approaches become available to explore the interaction between genetic and environmental factors in the etiology of colorectal cancer, the collection of appropriate epidemiologic data on exposure to potential risk factors in high-risk families becomes extremely important. Other limitations are the lack of archival or fresh-frozen tissue specimens and blood samples, and the difficulty in collecting and validating clinical and epidemiologic data, and the lack of population-based controls. The CFRCCS will enable participant organizations to: identify individuals with a family history of colorectal cancer and various familial syndromes that include colorectal cancer and propose the best sampling design to this end; collect and define the related pedigrees; and collect clinical (tumor type, stage at diagnosis, hormonal evaluation, etc), epidemiologic (age at diagnosis, sociodemographic status, risk factors, etc.), and other relevant baseline and follow-up data (such as treatment history) to correlate with pedigree information. Support for collection of population-based controls may be included. Support for the collection, processing, and storage of related biological specimens, including at a minimum blood samples and paraffin blocks, must be included. Support for molecular genetic analyses of participants may be included. The CFRCCS is intended to assist investigators funded through other sources by providing data and biological specimens to be used for multidisciplinary and translational studies on the etiology of colorectal cancer and associated syndromes, and to identify a population at high-risk that could be prospectively followed for the purpose of prevention and treatment-oriented research. The applicants should demonstrate the capability and willingness to develop common protocols during the first six months of the award, including but not limited to: o ascertainment of colorectal cancer patients and families o epidemiologic, family history, and clinical data collection. validation, and management (statistical support) o collection and banking of biological specimens o follow-up for outcomes, recurrence, and mortality o appropriate genetic counseling of patients and family members The awardees should demonstrate capability and willingness to provide the data so collected to a central NCI coordinating database. The awardees will provide to the research community at large pedigree information, epidemiological data, and biological specimens for high- priority research studies. It is anticipated that prioritization of the research study proposals requesting access to the CFRCCS' resources will be made by an Advisory Committee (AC), and will be based on scientific validity criteria established by the Steering Committee (SC) as described below: The NCI will help to coordinate and promote this process through the Program Coordinator's membership in these committees. SPECIAL REQUIREMENTS A number of issues need to be discussed by the applicants to promote the development of a CFRCCS site. Applicants are encouraged to submit and describe their own ideas on the best scientific approach to meet the goals of this RFA. Applicants must propose detailed plans for how to organize the CFRCCS in the most cost- effective and scientifically sound manner, as well as their plans for establishing collaborations. Advantages and disadvantages of the proposed approaches should be discussed. Plans should describe resources, including the availability of probands and a reasonable estimate of the expected availability and quality of pedigree information and related epidemiological data and biological specimens. Each application must have an Operation Core for statistical and logistic support, capable of providing the necessary coordination for specimen and data collection, and functioning as a central facility at the applicant's institution for management and storage of data and specimens. Appropriate data retrieval and data management procedures and quality control methods for the epidemiological and clinical data. Procedures for quality control for specimen collection and storage and pathology review should be described. Applicants must address coordination of quality control among awardees with regard to collection and storage of data and specimens and state their willingness to cooperate with other awardees in developing policies for quality control and to share data and protocols with other awardees, as well as providing the collected data to a central NCI coordinating database. The Operation Core should be adequately described, including the facilities for data collection and storage and specimen storage, as well as the investigators' experience in this area. The applicants must provide details on appropriate facilities and biohazard precautions and comply with the applicable Federal, State, and Local regulations, laws and finances in the operation of the Registry. Information on the nature of the data collected at baseline and follow-up should be provided. Examples of data forms, epidemiologic questionnaire, medical records and abstracting procedures, and software that may be appropriate for the use of the CFRCCS should be included in the appendix. Methods should be proposed to retrieve and establish an inventory of biological specimens, such as blood, fresh-frozen tissue, tissue blocks and slides. Procedures for quality control of specimens, storage and pathology review should be described. Applicants should discuss their rationale for the selection of families and controls to be included in the CFRCCS site, should document their ability to recruit a sufficient number of participants, must be able and willing to interact effectively with each other, and should state their willingness to follow the common "core" protocols that will be developed and agreed upon during the first six months of the registry. The applicants should demonstrate the capability for developing common protocols including, but not limited to: o ascertainment of colorectal cancer families; o epidemiologic and clinical data collection, validation and management (statistical support); o collection and banking of biological specimens (blood and tissues); o follow-up for cancer treatment, recurrence, mortality, and core epidemiologic data; o counseling of family members on risk and possible preventive or therapeutic interventions. The applicants must state a willingness and should discuss their approach to cooperate with the SC and the AC in evaluating research proposals utilizing the CFRCCS resources, and to abide by the decisions of the AC in prioritizing such proposals, after final approval by the SC based on data and specimen availability. The applicant should provide the name and qualifications for the second investigator from his/her Institution to be designated as a member of the SC. As the principal investigators of the funded applications and one designee will be members of a SC which will meet three times in the first year and twice in each subsequent year, travel funds for these meetings should be set aside as a budget item. As the AC will meet with the SC once a year, funds should also be included to support travel by one member of the AC to one SC meeting once a year, plus any additional travel anticipated for AC members. Study Organization and Function The overall structure of the CFRCCS will consist of two to five funded Institutions (awardees) that are governed and coordinated through the SC. Each awardee unit will be composed of one funded site, an Operation Core at the funded site, and a P.I. providing the scientific and administrative leadership for the unit and serving as the Head of the Operation Core. The overall function of the CFRCCS is to promote multidisciplinary and translational research in the framework of studies in the genetic epidemiology of colorectal cancer, by serving as a national resource to the research community at large. Requests for specimen and data >From the awardees and their collaborators will be reviewed, prioritized by the AC, and approved by the SC along with all other requests from investigators in the research community at-large. The Terms and Conditions of Award, below, will be included in all awards issued as a result of this RFA. It is critical that each applicant include specific plans for responding to these terms. Terms and Conditions of Award These special Terms of Award are in addition to and not in lieu of otherwise applicable OMB administrative guidelines, HHS Grant Administration regulations at 45 CFR part 74 and 92, and other HHS, PHS, and NIH Grant Administration policy statements. The administrative and funding instrument used for this program is a cooperative agreement (UO1), an assistance mechanism (rather than an acquisition mechanism) in which substantial NIH scientific and/or programmatic involvement with the awardee is anticipated during performance of the activity. Under the cooperative agreement, the NIH purpose is to support and/or stimulate the recipient's activity by involvement in and otherwise working jointly with the award recipient in a partner role, but it is not to assume direction, prime responsibility, or a dominant role in the activity. Consistent with this concept, the dominant role and prime responsibility for the activity resides with the awardee(s) for the project as a whole, although specific tasks and activities in carrying out the studies will be shared among the awardees and the NCI Program Coordinator. 1. Awardee Rights and Responsibilities Awardees will have primary rights and responsibilities to define projects and approaches and to plan and conduct the project, including: o The Awardee's PI will participate as a permanent member of the SC and designate a second investigator from his/her institution to be a permanent member of such committee; o The Awardee will work together with the other Awardees through the SC to establish the CFRCCS operating policies, uniform core protocols, and quality control procedures for specimens and data. The Awardee will be required to accept and implement the common policies and procedures approved by the SC; o The Awardee must agree to provide access to both specimens and data to investigators both within and outside the awardee's institutions, based on the prioritization of the research proposals set by the AC and final approval by the SC. The Awardee will abide by the decisions of the SC based on recommendations from the AC; o The Awardee will retain custody of, and have primary rights to, the data developed under this awards, subject to the Government rights of access consistent with current HHS, PHS, and NIH policies; o Each awardee will need to implement and comply with the common study protocols as established by the SC, and in compliance with the agreed upon timetable, but additional elements could be appended by individual institutions to address issues of unique interest or capabilities in each center; o The Awardee must provide a semi-annual progress report to the EPB, DCEG, NCI, and a copy to the chairperson of the SC, in a format that is compatible with the annual progress report of the other awardees. Information on the operation of the CFRCCS site as well as performance and progress on pilot studies are to be included; o Collaboration among awardees in the reporting of findings originated from this initiative is encouraged. Collaborative publications among awardees and NCI are anticipated; Immediately after the notification of award, the successful applicant should also provide the name of one scientist not affiliated with his/her Institution as a potential member of the SC. In addition, each applicant should provide the names and qualifications of two scientists not affiliated with his/her Institutions as potential members of the AC. Letters of commitment and CV's from the potential members of the AC and SC should be attached. 2. National Cancer Institute Staff Responsibilities The NCI Program Coordinator will be designated by the Chief, Extramural Programs Branch, EBP, DCEG, NCI. He/she will have substantial scientific-programmatic involvement during conduct of this activity through participation in the SC and AC activities. The Program Coordinator will provide technical assistance, advice and coordination, assure that the SC and the AC follow the NIH guidelines on conflict of interest issues, and play a critical role in promoting the availability and use of the registry. The role of the Program Coordinator is to assist and facilitate, but not to direct, the activities supported by the CFRCCS. The NCI Program Coordinator will: o Lend his/her expertise and overall knowledge of the NCI- and NIH-sponsored colorectal cancer research to facilitate the selection of scientists non-affiliated with the awardees institutions who are to serve in the AC and SC; o Serve as liaison, helping to coordinate activities among the awardees; act as a liaison to the NCI, and as an information resource about extramural multidisciplinary cancer research activities in the area of genetics and molecular epidemiology of colorectal cancer; o Attend the SC meetings as a voting member, assist in developing operating guidelines, quality control procedures, and consistent policies for dealing with recurrent situations that require coordinated action; o Serve as liaison between the SC and the AC, attending AC meetings in a non-voting liaison member role, and lending a degree of continuity between AC and SC, as the ad-hoc AC composition may change depending on the expertise required to review the submitted research proposals; o Serve on subcommittees of the SC and the AC as required; o Assist in the monitoring of field data collection, helping to ensure standardization in methods across study centers; and assist in the interpretation and reporting of the collected information. This will be necessary because of the complexity of this multisite structure, requiring an high degree of coordination and program involvement to achieve adequate standardization of procedures; o Assist by providing advice in the management and technical performance of the investigation. The Program Coordinator will serve as scientific liaison between the awardees and other program staff at NCI who have previous experience in the establishment of cancer registries and tumor bank; o Assist in promoting the availability of the CFRCCS resources to the scientific community at large, for use in translational and prevention-oriented colorectal cancer research, as stated in this RFA goals. The NCI reserves the right to reduce the budget, to withhold support, and to suspend, terminate or curtail a study or an award in the event of substantial shortfall in specimen accrual, data reporting, inadequate quality control in specimens or clinical data collection, non-adherence to biohazard precautions, refusal to carry out the recommendations of the SC and AC, or substantial failure to comply with the terms of the award. 3. Collaborative Responsibilities a. Steering Committee The SC will serve as the main governing board of the CFRCCS (see "Terms and Conditions of Award"). The SC membership includes the NCI Coordinator, the P.I., one other investigator from each awarded cooperative agreement, and one research scientist with expertise in the field of multidisciplinary and translational colorectal cancer research who is not affiliated with any of the awardees institutions. This last member will be appointed by mutual agreement of the NCI Coordinator and the PI's. Additional members can be added by action of the SC. Other appropriate NCI staff may need to attend the SC meetings if their expertise is required, to participate in specific discussions. The SC will be responsible for reviewing the plans for development of the CFRCCS proposed in the individual applications of the awardees. This Committee will develop uniform procedures for data collection and management, tissue collection, processing and distribution, and quality control. The SC will develop the criteria for review and prioritization of research proposals requiring the use of the CFRCCS's resources. The NCI Program Coordinator will assist the other members of the SC in all these tasks. Furthermore, the NCI Program Coordinator will serve as the scientific liaison between the awardees and the other program staff of NCI who have previous experience in the establishment of family cancer registries. Awardees will be required to accept and implement the common guidelines and procedures approved by the SC. The first meeting of the SC will be called by the NCI Program Coordinator shortly after award of the cooperative agreements. At this initial meeting, the Committee will elect a Chairperson (someone other than the Program Coordinator). The Chair of the SC is responsible for coordinating the Committee's activities, for preparing meeting agendas, and for scheduling and chairing meetings. The Program Coordinator attends and participates in all meetings of the SC, and should be informed of any major interactions. Subsequent meetings will be planned and scheduled at this meeting. Two additional meetings will be held during the first year of operation, and there two meetings a year thereafter, one of which with the AC. The meetings will be held in Bethesda or at another convenient location. Accordingly, respondents must request sufficient funds within the submitted budgets to accommodate travel expenses for the P.I. and his designee. Subcommittees will be established by the SC as it deems appropriate. The SC will be responsible for confirming the availability and accessibility of specimens and data for use by investigators requesting the use of the registry resources for approved research proposals. In no circumstance will the SC overturn the recommendation of the AC, except when specimens and/or data are not available. The SC will select members for the AC. The SC, in the conduct of all business matters, will pay particular attention to conflict of interest issues, and will bring such matters to the attention of the AC and of the NCI Program Coordinator. b. Advisory Committee The AC is responsible for reviewing, evaluating and approving research proposals submitted by investigators from the research community at large, as well as from the awardees, for the use of the registry resources. A recommendation in terms of priority of the proposed research will be provided to the SC after review of each application. The AC will meet with the SC at least once yearly, at one of the two scheduled SC meetings. Accordingly, respondents must request sufficient funds in the submitted budget to accommodate travel expenses of the selected AC members. The AC will be composed of senior scientists with expertise in multidisciplinary and translational research in the field of colorectal cancer, which may include epidemiologists, laboratory researchers, clinicians, or other expertise that the SC deems needed. The membership of the AC may vary, depending on the scientific areas of the proposed research to be reviewed and evaluated, and temporary "ad hoc" members can be selected if additional expertise is required for specific applications. All members will be selected by the SC (two nominee per awarded site). The tenure of the permanent AC members will be of two years. The Program Coordinator will function as a non-voting liaison member between the AC and the SC, and attend the AC meetings. The members of the AC will evaluate all research proposals (those of the awardees as well as from the research community at large) proposing to utilize the CFRCCS resources, according to the evaluation and review criteria provided by the SC. The review of proposals can be conducted either in person, by conference call or by mail at least twice a year. All reviews will be conducted according to rules pertaining to the conduct of reviews for NIH grants, contracts, and cooperative agreements and to the review criteria developed by the SC, paying special attention to issues of conflict of interest, whether real or apparent. The AC will provide a recommendation to the SC as to the priority of the proposed research. The AC Chair will forward the final recommendation to the SC. The AC will provide advice to the SC on scientific matters as appropriate and needed. 4. Arbitration Procedures Any disagreement that may arise on scientific/programmatic matters (within the scope of the award), between the award recipients and the NCI may be brought to arbitration. An arbitration panel will be composed of three members, one selected by the SC (without the vote of the Program Coordinator) or by the individual awardee in the event of an individual disagreement, a second member selected by the NCI, and the third member selected by the two prior selected members. This special arbitration procedure in no way affects the awardee's right to appeal an adverse action that is otherwise appealable in accordance with the PHS regulation at 42 CFR part 50, subpart D and HHS regulation at 45 CFR part 16." 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 subpopulation 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 on the Inclusion of Women and Minorities as Subjects in Clinical Research," which have been published in the Federal Register of March 28, 1994 (59 FR 14508-14513) and reprinted in the NIH GUIDE FOR GRANTS AND CONTRACTS, Volume 23, Number 11, March 18, 1994. Investigators may obtain copies of the policy from these sources or >From the program staff or contact person listed below. Program staff may also provide additional relevant information concerning the policy. LETTER OF INTENT Prospective applicants are asked to submit, by August 6, 1996, 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, the participating institution(s), 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 a subsequent application, the information that it contains allows NCI staff to estimate the potential review workload and avoid conflict of interest in the review. The letter of intent is to be sent to Dr. Daniela Seminara, at the address listed under INQUIRIES. APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 5/95) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research and may be obtained from the Office of Extramural Outreach and Information Resources, National Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 301-435-0714, e-mail: asknih@odrockm1.od.nih.gov. A number of issues need to be discussed by the applicants to promote the development of a CFRCCS site. Applicants are encouraged to submit and describe their own ideas on the best scientific approach to meet the goals of this RFA. Applicants must propose detailed plans for how to organize the CFRCCS in the most cost-effective and scientifically sound manner, as well as their plans for establishing collaborations. Advantages and disadvantages of the proposed approaches should be discussed. Plans should describe resources, including the availability of probands and a reasonable estimate of the expected availability and quality of pedigree information and related epidemiological data and biological specimens. Each application must have an Operation Core for statistical and logistic support, capable of providing the necessary coordination for specimen and data collection, and functioning as a central facility at the applicant's institution for data and specimens management and storage. Appropriate data retrieval and data management procedures and quality control methods for the epidemiological and clinical data. Procedures for quality control for specimen collection and storage and pathology review should be described. Applicants must address coordination of quality control among awardees with regard to collection and storage of data and specimens, state their willingness to cooperate with other awardees in developing policies for quality control and to share data and protocols with other awardees, as well as providing the collected data to a central NCI coordinating database. The Operation Core should be adequately described, including the facilities for data collection and storage and specimen storage, as well as the investigators' experience in this area. The applicants must provide details on appropriate facilities and biohazard precautions and comply with the applicable Federal, State, and Local regulations, laws and finances in the operation of the Registry. Information on the nature of the data collected at baseline and follow-up should be provided. Examples of data forms, epidemiologic questionnaire, medical records and abstracting procedures, and software that may be appropriate for the use of the CFRCCS should be included in the appendix. Methods should be proposed to retrieve and establish an inventory of biological specimens, such as blood, fresh-frozen tissue, tissue blocks and slides. Procedures for quality control of specimens, storage and pathology review should be described. Applicants should discuss their rationale for the selection of families and controls to be included in the CFRCCS site, should document their ability to recruit a sufficient number of participants, must be able and willing to interact effectively with each other, and should state their willingness to follow the common "core" protocols that will be developed and agreed upon during the first six months of the registry. The applicants should demonstrate the capability for developing common protocols including, but not limited to: the ascertainment of colorectal cancer families; the collection of epidemiologic, family history and clinical data and their validation and management; the collection and banking of biological specimens; follow-up of the identified population for cancer treatment, recurrence, mortality, and core epidemiologic data; and the appropriate counseling of family members on risk and possible preventive or therapeutic interventions. The applicants must state a willingness and should discuss their approach to cooperate with the SC and the AC in evaluating research proposals utilizing the CFRCCS resources, and to abide by the decisions of the AC in prioritizing such proposals, after final approval by the SC based on data and specimen availability. The applicant should provide the name and qualifications for the second investigator from his/her Institution to be designated as a member of the SC. As the principal investigators of the funded applications and one designee will be members of a SC which will meet three times in the first year and twice in each subsequent year, travel funds for these meetings should be set aside as a budget item. As the AC will meet with the SC once a year, funds should also be included to support travel by one member of the AC to one SC meeting once a year, plus any additional travel anticipated for AC members. Of the funds provided by this RFA, at least 90% of the total cost proposed in each application must be directed to the basic CFRCCS activities (accrual of families, data and specimen collection, management, and retrieval). Up to 10% of the total cost, or $50,000 per year (whichever is smaller, starting from the second year of the cooperative agreement), can be requested for pilot or feasibility studies utilizing the family registry resources. Applicants seeking these funds for pilot studies utilizing the CFRCCS resources, should document their ability to conduct colorectal cancer research and document any of their ongoing work in this area. The research hypothesis, background and rationale and design of the pilot study should be described as part of the research plan, keeping within the allowed page limits. The SC and the AC will review the pilot studies proposed in the application in response to this RFA even if the studies received approval under peer review. Moneys for pilot studies will be restricted until the AC gives these pilot studies high priority ratings, and the requested specimens and/or data are available and have been released by the SC. The review of these pilot studies will occur along with the review and prioritization of other requests submitted by investigators in the research community at large. The pilot studies will begin no sooner than year two of the cooperative agreement. However, if the AC does not rank the pilot project as a high priority, a new pilot study that is rated as high priority by the AC can be substituted. Pilot/feasibility studies should be designed to obtain sufficient data to form the foundation for future RO1 research grant applications, to help identify new areas where additional investigations are warranted, and to promote interdisciplinary and translational colorectal cancer research. The RFA label available in the application form PHS 398 (rev. 5/95) must be affixed to the bottom of the face page. 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, the number and title of the RFA must be typed on line 2a of the face page of the application and YES must be checked. Submit a signed, typewritten original of the application, including the Checklist, and three signed, exact photocopies in one package to the Division of Research Grants at the address below. The photocopies must be clear and single sided. DIVISION OF RESEARCH GRANTS NATIONAL INSTITUTES OF HEALTH 6701 ROCKLEDGE DRIVE, SUITE 1040 - MSC 7710 BETHESDA, MD 20892-7710 BETHESDA, MD 20817 (for express/courier service) At the time of submission, two additional copies of the application must be sent to: Ms. Toby Friedberg Division of Extramural Activities National Cancer Institute 6130 Executive Boulevard, Room 636 Bethesda, MD 20892 It is important to send these copies at the same time that the original and three copies are sent to DRG; otherwise, the NCI cannot guarantee that the application will be reviewed in competition with other applications received on or before the designated receipt date. Applications must be received by September 20, 1996. If an application is received after that date, it will be returned to the applicant without review. If the application submitted in response to this RFA is substantially similar to a research grant application already submitted to the NIH for review, but has not yet been reviewed, the applicant will be asked to withdraw either the pending application or the new one. Simultaneous submission of identical applications will not be allowed, nor will essentially identical applications be reviewed by different review committees. Therefore, an application cannot be submitted in response to this RFA that is essentially identical to one that has already been 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 General Considerations All applications will be judged on the basis of the scientific merit of the proposed project and the documented ability of the investigators to meet the RESEARCH OBJECTIVES of the RFA. Although the technical merit of the proposed protocol is important, it will not be the sole criterion of evaluation of a study. Other considerations, such as the importance and timeliness of the proposed study, access to patients, and multidisciplinary and translational nature of the studies, will be part of the evaluation criteria. Review Method Upon receipt, applications will be reviewed for completeness by the DRG and responsiveness by the NCI. Incomplete applications will be returned to the applicant without further consideration. If NCI staff find that the application is not responsive to the RFA, it will be returned for further consideration. 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 NCI in accordance to the review criteria stated below. As part of the initial merit review, all applications will receive a written critique and undergo a process in which only those applications deemed to have the highest scientific merit, generally the top half of applications under review, will be discussed, assigned a priority score, and receive a second level review by the National Cancer Advisory Board. Review Criteria Applicants are encouraged to submit and describe their own ideas about how to best meet the goals of the cooperative study and their specific protocols, and are expected to address issues identified under SPECIAL REQUIREMENTS of the RFA. The review group will assess the scientific merit of the protocols and related factors, including: o extent to which the application addresses the goals and objectives of the RFA; o adequacy of the applicant's plans for addressing the special scientific and technical program requirements presented in the RFA; o merit of the proposed activities and organizational plans for implementing the CFRCCS; o qualifications and research experience of the Principal Investigator and staff, particularly, but not exclusively, in the area of the proposed research; o time availability of the PI and staff; o availability of, and access to, a suitable patient population; o adequacy of existing physical facilities and resources of the applicants' Institutions; o demonstrated ability and willingness to carry out common protocol; o adequacy of plans for effective cooperation and coordination among participating awardees and the NCI Program Coordinator, as per Special Requirements of the RFA; o adequacy of proposed number of study subjects to be recruited and plans for inclusion of minorities; o adequacy of proposed data to be collected and procedures for data handling, managing, and preparing for analyses; o evidence that appropriate steps have been taken to insure the rights of human subjects; o adequacy of the proposed plan to provide counseling appropriate for the CFRCCS activities o the scientific and technical significance or originality of the proposed pilot studies in the field of translational colorectal cancer research. It is to be noted that the review of this part of the grant application will be given much less weight relative to the review of the registry facilities, procedures and epidemiological data base, as no more than 10 percent of the total cost, or up to $ 50,000 per year for three years (whichever number is smaller, starting the second year of the Cooperative Agreement) may be requested for these studies. The review group will also examine the proposed budget and will recommend an appropriate budget and period of support for each application that is recommended for further consideration. The second level of review by the National Cancer Advisory Board considers the special needs of the Institute and the priorities of the National Cancer Program. AWARD CRITERIA The earliest anticipated date of award is April 1, 1997. The following will be considered for making funding decisions: o scientific and technical merit of the proposed project as determined by peer review; o adequate effort to represent the minority groups in the population sampled; o availability of funds; o program balance among research areas. INQUIRIES Written and telephone inquiries concerning the RFA and the opportunity to clarify any issues or questions from potential applicants are welcome. Direct inquiries regarding programmatic and scientific issues to: Dr. Daniela Seminara Extramural Programs Branch National Cancer Institute Executive Plaza North, Suite 535 6130 Executive Boulevard MSC 7395 Bethesda, MD 20892-7395 Telephone: (301) 496-9600 Email: seminard@epndce.nci.nih.gov Direct inquiries regarding fiscal matters to: Ms. Catherine Blount Grants Management Branch National Cancer Institute 6120 Executive Boulevard Executive Plaza South, Suite 243 Bethesda, MD 20892 Telephone: (301) 496-7800, ext. 262 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.393, Cancer Cause and Prevention 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 Part 52 and 45 CFR Part 74 and 92. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. Unless otherwise noted all PHS grants policies apply. The PHS strongly encourages all grant recipients to provide a smoke-free workplace and promote the non-use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or, in some cases any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. 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 Tue Jul 02 23:00:00 1996 Path: biosci!biosci!not-for-mail From: BIOSCI Administrator Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 25, no. 21, pt. 1of1, 28 June 1996 Date: 3 Jul 1996 11:24:07 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 459 Sender: daemon@net.bio.net Approved: biosci-help@net.bio.net Distribution: world Message-ID: <4reds7$pfi@net.bio.net> NNTP-Posting-Host: net.bio.net $$XID NIHGUIDE 19960628 V25N21 P1O1 ************************************ X-comment: RFAS described: CA-96-011, CA-96-016, CA-96-017, PAR-96-060, PA-96 X-URL: gopher://gopher.nih.gov:70/11/res/nih-guide/guide-files/96.06.28 NIH GUIDE - Vol. 25, No. 21 - June 28, 1996 $$INDEX BEGIN ******************************************************* NOTICES $$INDEX N1 ********************************************************** NCI POLICY ON SMALL SHORT-TERM GRANTS National Cancer Institute INDEX: CANCER NOTICES OF AVAILABILITY (RFPs/RFAs/PAs) $$INDEX R1 09/20/96 ************************************************ COOPERATIVE FAMILY REGISTRY FOR EPIDEMIOLOGIC STUDIES OF COLON CANCER (RFA CA-96-011) National Cancer Institute INDEX: CANCER $$INDEX R2 09/15/96 ************************************************ MINORITY-BASED COMMUNITY CLINICAL ONCOLOGY PROGRAM (RFA CA-96-016) National Cancer Institute INDEX: CANCER $$INDEX R3 11/08/96 ************************************************* INVESTIGATOR GRANTS FOR CLINICAL CANCER THERAPY RESEARCH (RFA CA-96-017) National Cancer Institute INDEX: CANCER $$INDEX P1 ********************************************************** ACUTE INFECTION AND EARLY DISEASE RESEARCH NETWORK (PAR-96-060) National Institute of Allergy and Infectious Diseases INDEX: ALLERGY, INFECTIOUS DISEASES $$INDEX P2 ********************************************************** MODERN VACCINES FOR MYCOSES AND MEASLES (PA-96-061) National Institute of Allergy and Infectious Diseases INDEX: ALLERGY, INFECTIOUS DISEASES THE NIH GUIDE IS AVAILABLE ELECTRONICALLY VIA BITNET OR INTERNET, BY SUBSCRIPTION, AND IS ALSO ON THE NIH GOPHER (GOPHER.NIH.GOV) AND THE NIH WEBSITE (HTTP://WWW.NIH.GOV). ALTERNATIVE ACCESS IS THROUGH THE NIH GRANT LINE VIA MODEM (DATA LINE 301/402-2221); CONTACT DR. JOHN JAMES AT 301/435-2801 FOR DETAILS ON THE NIH GRANT LINE. THE PHS STRONGLY ENCOURAGES ALL GRANT AND CONTRACT RECIPIENTS TO PROVIDE A SMOKE-FREE WORKPLACE AND PROMOTE THE NON-USE OF ALL TOBACCO PRODUCTS. IN ADDITION, PUBLIC LAW 103-227, THE PRO-CHILDREN ACT OF 1994, PROHIBITS SMOKING IN CERTAIN FACILITIES (OR IN SOME CASES, ANY PORTION OF A FACILITY) IN WHICH REGULAR OR ROUTINE EDUCATION, LIBRARY, DAY CARE, HEALTH CARE OR EARLY CHILDHOOD DEVELOPMENT SERVICES ARE PROVIDED TO CHILDREN. THIS IS CONSISTENT WITH THE PHS MISSION TO PROTECT AND ADVANCE THE PHYSICAL AND MENTAL HEALTH OF THE AMERICAN PEOPLE. ALL COMPETING GRANT APPLICATIONS SUBMITTED TO THE NATIONAL INSTITUTES OF HEALTH MUST BE SENT TO: DIVISION OF RESEARCH GRANTS NATIONAL INSTITUTES OF HEALTH 6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710 BETHESDA, MD 20892-7710 BETHESDA, MD 20817 (for express/courier service) THE GRANTS INFORMATION OFFICE, DRG, HAS BEEN INCORPORATED INTO THE NEW OFFICE OF EXTRAMURAL OUTREACH & INFORMATION RESOURCES, OFFICE OF EXTRAMURAL RESEARCH, OFFICE OF THE DIRECTOR, NIH. REQUESTS FOR APPLICATION FORMS, PUBLICATIONS, AND OTHER INFORMATION MAY BE DIRECTED TO THE FOLLOWING: OFFICE OF EXTRAMURAL OUTREACH & INFORMATION RESOURCES 6701 ROCKLEDGE DRIVE, MSC 7910 BETHESDA, MD 20892-7910 TELEPHONE: (301) 435-0714 EMAIL: ASKNIH@ODROCKM1.OD.NIH.GOV $$INDEX END ********************************************************* NOTICES $$N1 BEGIN ********************************************************** NCI POLICY ON SMALL SHORT-TERM GRANTS NIH Guide, Volume 25, Number 21, June 28, 1996 P.T. 34; K.W. 1014006 National Cancer Institute The National Cancer Institute (NCI) advises potential grant applicants that acceptance by the NCI of small research project grants (R03) will be considered only in response to an NCI announcement specifically inviting such applications. Unsolicited grant applications in areas not covered by the announcements proposing preliminary short-term research projects limited in time and amount of support will not be accepted by the NCI. Currently, three specific program announcements inviting small grant (R03) applications are ongoing annually but as of this date will have newly assigned receipt dates of September 15, January 15, and May 15 annually. o PAR-95-091, Cancer Prevention and Control Research Small Grant Program, NIH Guide, Vol. 24, No. 33, Sept 22, 1995. o PAR-95-077, Small Grants Program for Cancer Epidemiology, NIH Guide, Vol. 24, No. 26, July 21, 1995. o PAR-95-023, Small Grants for Therapeutic Clinical Trials of Malignancies, NIH Guide, Vol. 24, No. 3, January 27, 1995. INQUIRIES Written, telephone and email requests for additional information concerning this notice may be directed to: Vincent T. Oliverio, Ph.D. Division of Extramural Activities National Cancer Institute 6130 Executive Boulevard, Room 600 Bethesda, MD 20892 Telephone: (301) 496-9138 Email: oliveriv@dea.nci.nih.gov $$N1 END ************************************************************ NOTICES OF AVAILABILITY (RFPs/RFAs/PAs) $$R1 BEGIN CA-96-011 FULL-TEXT ************************************** COOPERATIVE FAMILY REGISTRY FOR EPIDEMIOLOGIC STUDIES OF COLON CANCER NIH Guide, Volume 25, Number 21, June 28, 1996 RFA AVAILABLE: CA-96-011 P.T. 34; K.W. 0715035, 0785055, 0780030 National Cancer Institute Letter of Intent Receipt Date: August 6, 1996 Application Receipt Date: September 20, 1996 PURPOSE The Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), and the Division of Cancer Prevention and Control, NCI invite cooperative agreement (U01) applications from investigators to participate, with the assistance of the NCI, in a network of organizations constituting a Cooperative Family Registry for Colorectal Cancer Studies (CFRCCS). Approximately $3 million in total costs per year for four years will be committed to fund between two and five applications submitted in response to this RFA. The purpose of the proposed awards is to stimulate a cooperative effort to: (1) collect pedigree information, epidemiological data and related biological specimens from patients with a family history of colon cancer in order to provide a registry resource for interdisciplinary studies on the etiology of colon cancer, and to encourage translational research in this area; and (2) identify a population at high risk for colon cancer that could benefit from new preventive and therapeutic strategies. 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, Cooperative Family Registry for Epidemiologic Studies of Colon Cancer, relates to the priority area of cancer. 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 202-512-1800). INQUIRIES The RFA, which describes the research objectives, application procedures, review considerations, and award criteria for this solicitation, may be obtained electronically through the NIH Grant Line (data line 301/402-2221), the NIH GOPHER (gopher.nih.gov), and the NIH Website (http://www.nih.gov), and by mail and email from the program contact listed below. Dr. Daniela Seminara Division of Cancer Epidemiology and Genetics National Cancer Institute Executive Plaza North, Suite 535 - MSC 7395 Bethesda, MD 20892-7395 Telephone: (301) 496-9600 Email: seminard@epndce.nci.nih.gov $$R1 END ************************************************************ $$R2 BEGIN CA-96-016 FULL-TEXT ************************************** MINORITY-BASED COMMUNITY CLINICAL ONCOLOGY PROGRAM NIH Guide, Volume 25, Number 21, June 28, 1996 RFA AVAILABLE: CA-96-016 P.T. 34, FF; K.W. 0715015, 0785140, 0745027, 0745070, 0755015 National Cancer Institute Letter of Intent Receipt Date: August 7, 1996 Application Receipt Date: September 25, 1996 PURPOSE The Division of Cancer Prevention and Control (DCPC), National Cancer Institute (NCI), invites applications from domestic institutions for cooperative agreements to the Minority-Based Community Clinical Oncology Program (Minority-Based CCOP). New community and research base applicants and currently funded programs are invited to respond to this Request for Applications (RFA). This issuance of the Minority-Based CCOP RFA seeks to build on the strength and demonstrated success of the program over the past six years by continuing the program to support community participation in cancer treatment and cancer prevention and control clinical trials through research bases (clinical cooperative groups and cancer centers supported by NCI) and utilizing the Minority-Based CCOP network for conducting NCI-assisted cancer prevention and control research. It is anticipated that up to ten Minority-Based CCOP awards will be made. Up to $2.7 million in total costs per year for three years will be set aside to fund applications submitted in response to this RFA. 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, Minority-Based Community Clinical Oncology Program, is related to the priority area of cancer. 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 202-512-1800). INQUIRIES The RFA, which describes the research objectives, application procedures, review considerations, and award criteria for this solicitation, may be obtained electronically through the NIH Grant Line (data line 301/402-2221), the NIH GOPHER (gopher.nih.gov), and the NIH Website (http://www.nih.gov), and by mail and email from the program contact listed below. Otis W. Brawley, M.D. Division of Cancer Prevention and Control National Cancer Institute Executive Plaza North, Room 300-D 6130 Executive Boulevard, MSC-7340, Bethesda, MD 20892-7340 Telephone: (301) 496-8541 FAX: (301) 496-8667 Email: ob6g@nih.gov $$R2 END ************************************************************ $$R3 BEGIN CA-96-017 FULL-TEXT ************************************** INVESTIGATOR GRANTS FOR CLINICAL CANCER THERAPY RESEARCH NIH Guide, Volume 25, Number 21, June 28, 1996 RFA AVAILABLE: CA-96-017 P.T. 34; K.W. 0715035, 0740000, 0745000, 0755015 National Cancer Institute Letter of Intent Receipt Date: August 30, 1996 Application Receipt Date: November 8, 1996 PURPOSE The Division of Cancer Treatment, Diagnosis, and Centers (DCTDC), National Cancer Institute (NCI) invites research project grant (R01) applications to conduct therapeutic clinical trials research employing new agents, concepts, or strategies for the treatment of cancer. This initiative is aimed at encouraging new clinical investigators who have not previously had independent grant funding to submit research applications in this area of research. Approximately $2,000,000 in total costs per year for four years will be committed to fund applications submitted in response to this Request for Applications (RFA). It is anticipated that ten new individual awards will be made. 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, Investigator Grants for Clinical Cancer Therapy Research, is related to the priority area of cancer. 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 202/512-1800). INQUIRIES The RFA, which describes the research objectives, application procedures, review considerations, and award criteria for this solicitation, may be obtained electronically through the NIH Grant Line (data line 301/402-2221), the NIH GOPHER (gopher.nih.gov), and the NIH Website (http://www.nih.gov), and by mail and email from the program contact listed below. Ms. Diane Bronzert Division of Cancer Treatment, Diagnosis, and Centers National Cancer Institute Executive Plaza North, Room 734 - MSC 7432 Bethesda, MD 20892-7432 Telephone: (301) 496-8866 FAX: (301) 480-4663 Email: BRONZERD@DCT.NCI.NIH.GOV $$R3 END ************************************************************ $$P1 BEGIN PAR-96-060 FULL-TEXT ************************************* ACUTE INFECTION AND EARLY DISEASE RESEARCH NETWORK NIH Guide, Volume 25, Number 21, June 28, 1996 PA AVAILABLE: PAR-96-060 P.T. 34; K.W. 0715008, 0765033, 0745000 National Institute of Allergy and Infectious Diseases Letter of Intent Receipt Date: August 1, 1996 Application Receipt Dates: October 11, 1996; September 1, 1997; and September 1, 1998 PURPOSE The National Institute of Allergy and Infectious Diseases (NIAID) gives special consideration for funding to scientifically meritorious application in response to Program Announcements. Program Announcements identify areas of ongoing research emphasis for the NIAID. The Division of AIDS (DAIDS), solicits applications to study the pathogenesis of acute/early HIV-1 infection in adults and to evaluate the impact of therapeutic interventions at this early stage of HIV-1 infection on HIV disease. This initiative will fund, through cooperative agreements (U01), five to six HIV-1 Acute Infection and Early Disease Research Units. Each awarded unit will perform innovative, integrated, investigator- initiated pathogenesis and clinical research on acute and early (up to 12 months post initial infection) HIV-1 infection. Each awarded unit will be part of the Acute Infection Research and Early Disease Research Network. The multi-site format (Network) is required to enroll sufficient numbers of these hard-to-identify patients for study. 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, Acute Infection and Early Disease Research Network, is related to the priority area of HIV infection. 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 202-512-1800). INQUIRIES The RFA, which describes the research objectives, application procedures, review considerations, and award criteria for this solicitation, may be obtained electronically through the NIH Grant Line (data line 301/402-2221), the NIH GOPHER (gopher.nih.gov), and the NIH Website (http://www.nih.gov), and by mail and email from the program contact listed below. Carla B. Pettinelli, M.D., Ph.D. Division of AIDS National Institute of Allergy and Infectious Diseases Solar Building, Room 2C-14 - MSC 7620 Bethesda, MD 20892-7620 Telephone: (301) 496-0700 FAX: (301) 402-3171 Email: cp22n@nih.gov $$P1 END ************************************************************ $$P2 BEGIN PA-96-061 FULL-TEXT ************************************** MODERN VACCINES FOR MYCOSES AND MEASLES NIH Guide, Volume 25, Number 21, June 28, 1996 PA AVAILABLE: PA-96-061 P.T. 34; K.W. 0740075, 0715103, 1002045 National Institute of Allergy and Infectious Diseases PURPOSE The National Institute of Allergy and Infectious Diseases (NIAID) gives special consideration for funding to scientifically meritorious applications in response to Program Announcements. Program Announcements identify areas of ongoing research emphasis for the NIAID. The purpose of this PA is to stimulate research on selected emerging and re-emerging diseases for which new or improved vaccines are needed. For the mycoses, the goal is to identify and characterize antigens that induce a protective immune response for coccidioidomycosis, histoplasmosis, blastomycosis, and cryptococcosis. For measles, the goal is to develop safe, new measles vaccines that are highly efficacious when administered in early infancy and that will aid in the control and eventual eradication of measles. 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, Modern Vaccines for Mycoses and Measles, is related to priority area of immunization-infectious diseases. 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 20402-0325 (telephone 202-512-1800). INQUIRIES The PA, which describes the research objectives, application procedures, review considerations, and award criteria for this solicitation, may be obtained electronically through the NIH Grant Line (data line 301/402-2221), the NIH GOPHER (gopher.nih.gov), and the NIH Website (http://www.nih.gov), and by mail and email from the program contact listed below. Dennis M. Dixon, Ph.D. Division of Microbiology and Infectious Diseases National Institute of Allergy and Infectious Diseases Solar Building, Room 3A-06 6003 Executive Boulevard - MSC 7630 BETHESDA, MD 20892-7630 Telephone: (301) 496-7728 FAX: (301) 402-0508 Email: dd24a@nih.gov $$P2 END ************************************************************ From owner-sci-resources@net.bio.net Tue Jul 02 23:00:00 1996 Path: biosci!biosci!not-for-mail From: BIOSCI Administrator Newsgroups: bionet.sci-resources Subject: NIH GUIDE - PAR-96-060 - V25(21) 06/28/96 Date: 3 Jul 1996 12:04:21 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 739 Sender: daemon@net.bio.net Approved: biosci-help@net.bio.net Distribution: world Message-ID: <4reg7l$612@net.bio.net> NNTP-Posting-Host: net.bio.net $$XID RFA PAR96060 PAR-96-060 P1O1 ************************************* ACUTE INFECTION AND EARLY DISEASE RESEARCH NETWORK NIH GUIDE, Volume 25, Number 20, June 21, 1996 PA NUMBER: PAR-96-060 P.T. 34; K.W. 0715008, 0765033, 0745000 National Institute of Allergy and Infectious Diseases Letter of Intent Receipt Date: August 1, 1996 Application Receipt Dates: October 11, 1996; September 1, 1997; September 1, 1998 PURPOSE The National Institute of Allergy and Infectious Diseases (NIAID) gives special consideration for funding to scientifically meritorious applications in response to Program Announcements (PA). Program Announcements identify areas of ongoing research emphasis for the NIAID. In this PA, The Division of AIDS (DAIDS), National Institute of Allergy and Infectious Diseases (NIAID), solicits applications to study the pathogenesis of acute/early HIV-1 infection in adult humans, and to develop and evaluate the impact of therapeutic interventions at this early stage of HIV-1 infection on HIV disease. The goal of this initiative is to build a network of three to five HIV-1 Acute Infection and Early Disease Research Units through cooperative agreements (U01) during the first year, with additional units funded over the next several years as this emerging area of science matures. Each awarded unit will perform innovative, integrated, investigator-initiated pathogenesis and clinical research on acute (i.e, within one month post initial infection) and early (i.e., up to 12 months post initial infection) HIV-1 infection and will be part of the Acute Infection and Early Disease Research Network (AIEDRN). The multi-unit format (Network) is required to enroll sufficient numbers of these hard-to-identify patients for study. 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, Acute Infection and Early Disease Research Network, is related to the priority area of HIV infection. 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 202-512-1800). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic non-profit and for-profit organizations, public and private organizations, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. While foreign organizations are not eligible to apply, domestic organizations may include foreign components. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as principal investigators. MECHANISM OF SUPPORT The administrative and funding mechanism to be used to undertake this program will be the cooperative agreement (U01), an "assistance" mechanism in which substantial NIH scientific and/or programmatic involvement is anticipated. Under the cooperative agreement, the NIH purpose is to support and/or stimulate the recipient's activity by involvement in and otherwise working jointly with the award recipient in a partner role, but it is not to assume direction, prime responsibility, or a dominant role in the activity. Cooperative agreements may include a combination of academic, non-profit research, and commercial organizations; applications that include collaborations with domestic or international organizations with access to larger numbers of people with acute infection and early HIV disease are strongly encouraged. RESEARCH OBJECTIVES Background Approximately 40,000 individuals are newly infected with HIV in the United States each year. Nonetheless, acute HIV infection is an under-diagnosed entity because it is often asymptomatic and because risk behavior associated with HIV infection is not identified. Acute infection is characterized by high levels of viral replication/dissemination to lymphoid tissues and immunologic activation. Observations from several small cohorts suggest that: (a) the concentration of HIV circulating in the blood (viral load) reaches a peak in the first two to four weeks of HIV infection and subsequently declines, and (b) the CD4+ T cell count of acutely infected individuals declines precipitously during the first days of HIV infection, however this rapid decline reverses itself, with a subsequent rebound in the CD4+ T cell count. Individuals with high levels of plasma HIV-1 RNA within six months from seroconversion experience more than tenfold increase in the risk for AIDS development, suggesting that inadequate suppression of viremia during the acute infection may be a critical factor in disease progression. The identification of both host and viral factors that influence the early establishment of a chronic HIV reservoir will facilitate the development, selection and administration of treatment and prevention modalities. Antiviral and/or immunological interventions during acute/early infection may have a great impact on the rate of disease progression and survival in HIV+ individuals. Preliminary results of a placebo controlled European- Australian study of ZDV are promising as CD4+ lymphocytes counts were higher in individuals receiving ZDV. Because of the difficulties associated with identifying individuals at this stage of infection, there have been few studies to analyze the associated viral and immunological changes as well as the effect of therapeutic interventions. Scope of Research This initiative will support innovative, integrated pathogenesis and clinical research for acute (up to one month post initial infection) and early (up to 12 months post initial infection) HIV-1 infection in adult humans. It will support single-unit and multi-unit clinical research and conduct in-depth studies of HIV pathogenesis and factors that influence response to interventions. The treatment strategies will be based on state-of-the-art concepts of early disease pathogenesis. The goal of this initiative is to build a network of three to five HIV-1 Acute Infection and Early Disease Research Units through cooperative agreements (U01) in the first year. Each unit will comprise basic and clinical scientists coordinated under the direction of a single Principal Investigator, and each unit will be part of the Acute Infection and Early Research Disease Network. Unlike many other major NIH cooperative research projects, the structure of the groups and funding are not linked to a specific experiment or clinical trial. Thus this mechanism has the potential for considerable flexibility in resource allocation which will facilitate the rapid testing of hypotheses about the pathogenesis of HIV-1 infection and early phase clinical trials of promising treatments of acute/early HIV infection. The multi year nature of a program announcement provides additional and necessary flexibility to allow the support for the scientific capability to expand and keep pace, as warranted, with this emerging, rapidly developing and high priority area of HIV-related research. In order to address these scientific needs, each unit should: o identify, accrue and retain acute/early HIV-1 positive individuals for pathogenesis studies and clinical trials. This requires strong linkages with and intense screening from unique referral sources such as Sexually Transmitted Diseases (STD) Clinics, emergency rooms, blood banks, and primary care centers, as well as close collaboration with centers and investigators studying existing natural history cohorts. The projected enrollment in the application should be at least 30 to 50 patients per year. Of the total number of subjects, a minimum of 10 to 15 subjects per year should be acutely infected, i.e., within one month post initial infection. Applicants may include studies on ways to improve detection and recruitment of new infected individuals. o conduct independent and collaborative (both through the Network and with outside investigators) studies of the in vivo pathogenesis of early HIV disease. o evaluate and optimize therapeutic interventions in small, focused clinical studies; perform extensive virologic and immunologic evaluation that will provide new insights into the pathogenesis of acute/early HIV infection and the efficacy of therapeutic approaches. The identification and use of existing resources (such as the Centers For AIDS Research, CFAR) should be maximized. The banking and storage of specimens for later analyses and for use in collaboration with investigators outside the network is encouraged. o have the potential capability of supporting, through participation in the Network activities, multi-unit evaluation (Phase I/II and Phase II clinical studies) of novel therapeutic interventions for acute infection and/or early HIV disease. The Network will include the awarded units' clinical sites and laboratories. In order to facilitate interpretation of data across the network, central quality assurance and data management of the laboratories can be provided by the Division of AIDS as needed. The Network activities will be coordinated by a Steering Committee formed by the Unit Principal Investigators. The Network serves to facilitate information exchange, foster collaboration and coordinate activities to minimize duplication. Additionally, the Network should have the capability and flexibility to conduct multi-unit clinical trials involving a larger number of patients (Phase II studies) as scientific opportunities become available. These studies may also require international collaboration. In summary, the primary objective of this PA is to conduct intense pathogenesis research and single- and multi-unit early phase clinical intervention studies into acute infection and early HIV disease. SPECIAL REQUIREMENTS Terms and Conditions of Award A. Applicability. These special Terms of Award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS Grant Administration Regulations at 45 CFR part 74 and 92, and other HHS, PHS, and NIH Grant Administration policy statements. The administrative and funding instrument used by the NIAID to award research projects involving (1) clinical trials, (2) prevention, education and control studies, and (3) epidemiological studies in excess of $500,000 direct cost per year at a single institution or in the aggregate for studies proposing multi-institution collaborative arrangements submitted either as subcontracts to a single application or as separate applications shall be a cooperative agreement (U01), an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIAID scientific and/or programmatic involvement with the awardee is anticipated during the performance of the activity. For single applications, the dollar limit excludes indirect costs of any subcontracts that are reported as a direct cost on the application budget page summary. Under the cooperative agreement, the NIAID purpose is to support and/or stimulate the recipient's activity by involvement in and otherwise working jointly with the award recipient in a partner role, but it is not to assume direction, prime responsibility, or a dominant role in the activity. Consistent with this concept, the dominant role and prime responsibility for the activity resides with the awardees for the project as a whole, although specific tasks and activities in carrying out the study will be shared among the awardees and the NIAID Program Officer or designee. Under the cooperative agreement, a relationship will exist between the award recipient(s) and the NIAID in which the performers of the activities (1) are responsible for the requirements and conditions described below and (2) agree to accept program assistance from a named NIAID Program Officer in achieving project objectives. Failure of an awardee to meet the performance requirements, including these special terms and conditions of award, or significant changes in the level of performance, may result in a reduction in budget, withholding of support, or suspension and/or termination of the award. B. Awardee Rights and Responsibilities The awardee is responsible for: 1. Research design and protocol development, including definition of objectives and approaches, planning, implementation, participant recruitment and follow-up, data collection, quality control, interim data and safety monitoring, final data analysis and interpretation, and publication of results. 2. Establishing with the other Principal Investigators a mandatory AIEDRN Steering Committee to facilitate information exchange, foster collaboration and coordinate activities to minimize duplication. The Steering Committee should designate a single Protocol Chairperson for each multi-unit clinical trial protocol within the research plan and define core data collection strategies, methods and cross-study analyses. 3. Functioning as the scientific coordinator for protocols (Protocol Chairpersons) and assuming responsibility for developing protocols and monitoring study performance for their protocols. All proposed protocols will be submitted by the Protocol Chair through the Principal Investigator to the NIAID Program Officer for review. Multi-unit clinical studies will be submitted to the NIAID Program Officer for review and approval, subject to negotiation with the awardees. 4. Implementing the core data collection strategy and methods for multi-unit studies and cross-study analyses collectively decided upon by the Steering Committee. For each study involving multiple institutions, it is the responsibility of each awardee/site to ensure that data will be collected and submitted in a timely way following such procedures as agreed to by the Steering Committee. Additionally, individual investigators/sites must demonstrate the ability to implement the strategy specifically designed for their individual study population. 5. Establishing mechanisms for internal quality control and monitoring. Awardees are responsible for ensuring the accurate and timely assessment of the progress of studies, including development of procedures to ensure that data collection and management are: (a) adequate for quality control and analysis; (b) for clinical trials, as simple as appropriate in order to encourage maximum participation of clinicians and other providers and study subjects and to avoid unnecessary expense; and (c) sufficiently staffed across the participating institutions. 6. Preparing and submitting interim progress reports, when requested, to the NIAID Program Officer including, as a minimum, summary data on performance of multi-unit studies. The Steering Committee may require additional information on multi-unit studies >From the individual awardees/sites. Such reports are in addition to the annual awardee noncompeting continuation progress reports. 7. Establishing procedures, where applicable, for all participating institutions in coordinated awards to comply with FDA regulations for studies involving investigational agents or devices and to comply with the requirements of 45 CFR Part 46 for the protection of human subjects. 8. Cooperating in the reporting of the study findings. The NIAID will have access to and may periodically review all data generated under an award. Where warranted by appropriate participation, plans for joint publication with NIAID of pooled data and conclusions, are to be developed by the Principal Investigator or Steering Committee, as applicable. NIH policies governing possible co-authorship of publications with NIAID staff will apply in all cases. C. NIAID Staff Responsibilities It is expected that the dominant role and prime responsibility for the activity will reside with the awardee(s) for the project as a whole. However, specific tasks and activities will be shared among the awardee(s) and the NIAID Program Officer and/or Scientific Coordinator(s). The Scientific Coordinator(s) will be the contact for all facets of the scientific interaction with the awardee(s), while the Program Officer will be the contact for issues such as administration and budget. As required for the coordination of activities and to expedite progress, the NIAID Program Officer may designate additional scientific coordinator(s) to provide advice or assistance to the awardee on specific scientific, technical or management issues. The NIAID Program Officer shall retain overall programmatic responsibility for the award(s) and will clearly specify to the awardee(s) the name(s) and role(s) of any such additional individuals and the lines of reporting authority. NIAID Extramural Program staff responsibilities will include: 1. Interacting with the Principal Investigator(s) on a regular basis to monitor study progress. Monitoring may include: (a) regular communications with the Principal Investigator and staff, (b) periodic site visits for discussions with awardee research teams, (c) observation of field data collection and management techniques, quality control, fiscal review, and other relevant matters, as well as (d) attendance at and participation in Steering Committee and other meetings. The NIAID retains, as an option, periodic external review of progress. 2. For multi-unit protocols, convening the first meeting of and subsequent participation in the Steering Committee that oversees study conduct. The NIAID Program Officer will be a full participant and voting member of the Steering Committee and, if applicable, subcommittees. 3. Serving as a resource with respect to ongoing NIAID activities that may be relevant to the research to facilitate compatibility and avoid unnecessary duplication. 4. Substantial assistance in the design and coordination of research activities for awardees including: a. Assisting by providing advice on the management and technical performance of the investigations. b. Providing access to and use of, when appropriate, reagents and assays, and other resources available through NIAID contractors and awardees. c. Technical advice and assistance with meeting FDA requirements for investigational drugs. d. For multi-unit protocols, through participation on the Steering Committee and with the agreements of the Principal Investigator(s), the NIAID Program Officer may coordinate activities among awardees by assisting in the design, development, and coordination of a common research or clinical protocol and statistical evaluations of data; in the preparation of questionnaires and other data recording forms; and in the publication of results. e. Reviewing and approving multi-unit clinical trial protocols to insure that they are within the scope of peer review and for adequacy of safety, human subjects, and representation of women and minorities, as required by Federal regulations. The NIAID Program Officer will monitor protocol progress, and may request that a protocol be closed to accrual for reasons including: (1) accrual rate insufficient to complete study in a timely fashion; (2) accrual goals met early; (3) poor protocol performance; (4) patient safety, human subjects, and women/minority recruitment concerns; (5) study results that are already conclusive; and (6) emergence of new information that diminishes the scientific importance of the study. The NIAID will not permit further expenditure of NIAID funds for a study after requesting closure (except for patients/subjects on-study and final data analysis and reporting). f. Reviewing and providing advice regarding the establishment of mechanisms for quality control and study monitoring for multi-center clinical trials. 5. Making recommendations for continued funding based on: (a) overall study progress, including study subject and/or data accrual; (b) cooperation in carrying out the research (e.g., attendance at Steering Committee meetings, implementation of group decisions, compliance with terms of award and reporting requirements); and/or (c) maintenance of a high quality of research which will allow pooling of data and comparisons across multiple cooperative agreement awards for common data elements. D. Collaborative Responsibilities In addition to the interactions defined above, awardees and NIAID staff shall share responsibility for the following activities: 1. Steering Committee. A Steering Committee will have primary responsibility to facilitate information exchange, foster collaboration and coordinate activities to minimize duplication. For multi-unit clinical trials the committee will establish scientific priorities, develop (through appropriate designees) common protocols and manuals, questionnaires and other data recording forms, establish and maintain quality control among awardees, review progress, monitor patient/subject accrual, coordinate and standardize data management and cooperate on the publication of results. Major scientific decisions regarding the core data of multi-unit clinical trials will be determined by the Steering Committee. The Steering Committee will document progress in written reports to the NIAID Program Officer and will provide periodic supplementary reports upon NIAID request. The Steering Committee will be composed of all Principal Investigators and, as deemed necessary, co-investigators and the NIAID Program Officer (or designee). An initial meeting of the Steering Committee will be convened early after award by the NIAID Program Officer. The final structure of the Steering Committee will be established at the first meeting. The NIAID Program Officer or designee will have voting membership on the Steering Committee and, as appropriate, its subcommittees. The Steering Committee usually will meet at least twice yearly. A Chairperson, other than the NIAID staff, will be selected by vote of the members. The Chairperson is responsible for coordinating the Committee activities, for preparing meeting agendas, and for scheduling and chairing meetings. E. IND Responsibilities For pilot studies, either the Principal Investigator or a pharmaceutical company may file an Investigational New Drug (IND) application to the United States Food and Drug Administration. The sponsor of the IND has responsibility for the conduct of trials under that IND, which includes adhering to applicable Federal regulations. For larger scale, multi center (Phase II) studies, NIAID will retain the option to cross-file or independently file an IND. Reports of data generated by the Network or any of its members required for inclusion in INDs and Clinical Brochures and for cross-filing purposes will be submitted by the Principal Investigator to the NIAID Program Officer upon request. Such reports will be in final draft form and include background information, methods, results, and conclusions. They will be subject to approval and revision by NIAID and may be augmented with test results from other Government-sponsored projects prior to submission to the appropriate regulatory agency. If NIAID holds the IND for a trial, a DAIDS Program Officer will monitor the safety of the treatment(s) being evaluated. Regulatory responsibilities will be the responsibility of NIAID. Standard procedures (e.g., registration of sites participating in clinical trials) will apply. Interim and final reports on toxicity for all sponsored clinical trials will be routinely provided to the DAIDS Scientific Coordinator. F. Arbitration Any disagreement that may arise on scientific/programmatic matters (within the scope of the award) between award recipients and the NIAID may be brought to arbitration. An arbitration panel will be composed of three members -- one selected by the Steering Committee (with the NIAID member not voting) or by the individual awardee in the event of an individual disagreement, a second member selected by the NIAID, and the third member selected by the two prior members. This special arbitration procedure in no way affects the awardee's rights to appeal an adverse action that is otherwise appealable in accordance with the PHS regulations at 42 CFR part 50, subpart D and HHS regulation at 45 CFR part 16. 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 August 1, 1996, a letter of intent that includes a descriptive title of the overall proposed research, the name, address and telephone number of the Principal Investigator, and the number and title of this PA. 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. Tingley at the address listed under INQUIRIES. APPLICATION PROCEDURES Applicants are strongly encouraged to contact NIAID program staff with any questions regarding the responsiveness of their proposed project to the goals of this PA. Applications are to be submitted on the grant application form PHS 398 (rev. 9/95). Application kits are available at most institutional offices of sponsored research and may be obtained from the Office of Grants Information, National Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 301/435-0714, e-mail: asknih@odrockm1.od.nih.gov. The NIH policy ypdate on acceptance for review of unsolicited applications that requires more than $500,000 direct cost for any one year applies to applications to become part of the Acute Infection and Early Disease Research Network. The policy update was published in the NIH Guide, Vol. 25, No. 14, May 3, 1996, and is effective June 1, 1996. The policy requires the applicant to contact, in writing or by telephone, NIAID program staff (see INQUIRIES) when the application development process begins. If the NIAID is willing to accept assignment of the application for consideration of funding, the staff will notify the Division of Research Grants before the application is submitted. The applicant Principal Investigator must identify, in a cover letter sent with the application, the NIAID program staff member who agreed to accept assignment of the application. An application received without indication of prior staff concurrence and identification of that contact will be returned to the applicant without review. For purposes of identification and processing, mark "YES" in item 2 on the face page of the application and type in the PA number PA-96-060 and the title "Acute Infection And Early Disease Research Network". Applications that are not received as a single package on a receipt date or that do not conform to the instructions contained in PHS 398 (rev 9/95) Application Kit (as modified in, and superseded by, the NIAID BROCHURE ENTITLED "INSTRUCTIONS FOR ABBREVIATED APPLICATIONS FOR MULTI-PROJECT AWARDS"), will be judged not responsive and will be returned to the applicant. 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. Applicants from an institution receiving government funds under Center for AIDS Research (CFAR), Strategic Program For Innovative Research On AIDS Treatment (SPIRAT), AIDS Clinical Trial Unit (ACTU), AIDS Vaccine Evaluation Unit (AVEU), DATRI, and CPCRA programs, should describe how these programs are integrated with the proposed studies, if applicable, and ensure that no scientific and budget overlap exists with the proposed project. Submit a signed, typewritten original of the application, including the checklist, and three signed, exact, single-sided photocopies, in one package to: DIVISION OF RESEARCH GRANTS NATIONAL INSTITUTES OF HEALTH 6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710 BETHESDA, MD 20892-7710 BETHESDA, MD 20817 (for express/courier service) At the time of submission, two additional exact copies of the grant application and all five sets of any appendix material must be sent to Dr. Tingley at the address listed under INQUIRIES. REVIEW CONSIDERATIONS Review Procedures Upon receipt, applications will be reviewed for completeness by the NIH Division of Research Grants (DRG) and for responsiveness by NIAID staff. Incomplete and/or non-responsive applications will be returned to the applicant without further consideration. Applications that are complete and responsive to the PA 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 PA. 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. The second level of review will be provided by the National Advisory Allergy and Infectious Diseases Council. Review Criteria The review criteria for this PA are essentially the same as those for unsolicited research project grant applications, with specific areas of emphasis as noted below: A. Scientific, technical, or clinical significance and originality of the proposed research. B. Appropriateness and adequacy of the experimental approach and the methodology proposed to carry out the research, specifically including the adequacy and feasibility of the applicant's plans, methods, approaches and problem solving strategies to: (1) identify, screen and recruit into research projects individuals with acute or early HIV-1 infection; (2) follow subjects for the long term and retain them in research studies; and (3) perform and quality assure laboratory assays in support of these studies. The applicant should demonstrate the ability to enroll and retain an adequate number of subjects given the size of the unit and the proposed scientific agenda. The Network will be encouraged to develop mechanisms, when appropriate, to assure comparability and standardization of laboratory testing across Units. C. Qualifications and research experience of the Group Leader and key staff in the area of the proposed research, specifically: (1) the scientific ability and track record of the applicants in conducting research on the pathogenesis of HIV; (2) the experience, leadership scientific ability and administrative competence of the applicant for the development, implementation and management of pilot Phase I/II clinical trials; and (3) experience of the applicants in performing virologic, immunologic and pharmacologic assays in support of state-of-the-art pathogenesis research and AIDS clinical trials. D. Availability of necessary resources to conduct the research. E. Adequacy of the proposed means for protecting against adverse effects of the research upon humans, animals or the environment, where such are involved. F. In clinical studies, if there is inadequate representation of women and/or minorities in a study design AND this affects the potential to answer the scientific question(s) addressed, such inadequacy will be considered to be a weakness or deficiency in the study design. This weakness will be reflected in the priority score assigned to the project, unless a convincing justification is provided by the investigator to explain the inadequate representation. AWARD CRITERIA Funding decisions will be based on scientific and technical merit as determined by peer review, the availability of funds and program priority. However, the predominant criteria for funding priorities will be the scientific and technical merit of the applications. Schedule Application Receipt Date: September 1, 1996 Scientific Review Date: November 1996 Earliest Date of Award: February 1997 INQUIRIES Written and telephone inquiries are encouraged. The opportunity to clarify any