MTOPS PROSTATE SAMPLES ANALYSIS CONSORTIUM (MPSA) Release Date: November 21, 2001 RFA: RFA-DK-02-017 National Institute of Diabetes and Digestive and Kidney Diseases (http://www.niddk.nih.gov) National Institute on Aging (http://www.nia.nih.gov) Letter of Intent Receipt Date: February 20, 2002 Application Receipt Date: March 20, 2002 PURPOSE The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Institute on Aging (NIA) invite cooperative agreement applications to establish a MTOPS Prostate Samples Analysis Consortium (MPSA) that will participate in the discovery and validation of biologic markers or genetic susceptibility tests for the detection, risk assessment, and assessment of disease progression of benign prostatic hyperplasia (BPH). The NIDDK has sponsored a large clinical trial, entitled "Medical Therapy of Prostatic Symptoms" or MTOPS, of two treatments for BPH, finasteride and doxazosin. Serum samples were collected yearly from the participants, one quarter of the participants had prostate biopsies collected in years 0, 1, and 5 of the trial. These samples will allow the evaluation of potential biomarkers or genetic susceptibility tests for BPH, response to pharmacological treatments for BPH, and/or correlation with clinical parameters. The purpose of the MTOPS Prostate Samples Analysis (MPSA) Consortium is to establish a scientific consortium of investigators with resources for basic and translational research on biomarkers for BPH. The existing MTOPS Data Coordinating Center will be an integral member of this new MPSA Consortium. ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic for-profit and non-profit organizations, public and private institutions such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Foreign institutions are not eligible to apply. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as Principal Investigators. MECHANISM OF SUPPORT This RFA will use the NIH Cooperative Research (U01) Award mechanism, an "assistance" mechanism (rather than "acquisition" mechanism) in which substantial NIH scientific and/or programmatic involvement with the awardee is anticipated during the performance of the activity. Under the cooperative agreement, the NIH purpose is to support and 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 research will be shared among the awardees and the NIH Project Scientists. Details of the responsibilities, relationships, and governance of a study funded under a cooperative agreement are discussed later in this document under the section "TERMS AND CONDITIONS OF AWARD FOR THE MPSA CONSORTIUM." This RFA is a one-time solicitation. The total project period for an application submitted in response to this RFA may not exceed 3 years. The anticipated award date is September 30, 2002. FUNDS AVAILABLE The NIDDK intends to commit approximately $3,000,000 in total costs in FY 2002 to fund approximately four to five Biomarker Units and one Pathology Coordination Center. The NIA plans to commit $500,000 in total costs for high quality research pertinent to the NIA mission, subject to the availability of funds. An applicant for a Biomarker Unit may request a project period of up to three years and budget for direct costs of up to $300,000 per year. Should an applicant plan to include subcontracts to other institutions or organizations, only the direct costs of those subcontracts will be used to tally the total costs that apply toward the $300,000 direct cost cap. An applicant for a Pathology Coordinating Center may request a project period of up to three years and budget for direct costs of up to $500,000 per year. For further budget information, see the section "APPLICATION PROCEDURES." Because the nature and scope of research proposed in response to this RFA may vary, we anticipate that the size of awards will vary also. Although this program is provided for in the financial plans of NIDDK and NIA, awards pursuant to this RFA are contingent upon the availability of funds for this purpose and the receipt of a sufficient number of applications of outstanding scientific and technical merit. At this time, NIDDK and NIA have not determined whether or how this solicitation will be continued beyond the present RFA. RESEARCH OBJECTIVES Background Benign prostatic hyperplasia (BPH) affects more than 50% of men past the age of 50. BPH is an expensive disease. BPH treatments cost an estimated $5 billion each year, and as the U.S. population ages, these costs will increase. If left untreated, BPH can lead to urinary tract infections, urinary retention, and in occasional cases, kidney disease. BPH is a heterogeneous disorder, with growth occurring at variable growth rates in different portions of the gland and a variable clinical presentation and response to therapy. Although there is no clear link between BPH and prostate cancer, these two prostate diseases occur in a similar population of aging men. NIDDK has sponsored a large clinical trial entitled "Medical Therapy of Prostatic Symptoms (MTOPS)" of two treatments for BPH, finasteride, and doxazosin. The MTOPS study is nearing completion. This trial included the acquisition and storage of serum samples from 4000 patients, and prostate biopsies from approximately 900 patients. Serum samples were collected at the beginning of the study, and at yearly intervals. Each 3 ml sample was split into 6 aliquots, and frozen. Approximately one-quarter of the participants had prostate biopsies taken at years 0, 1, and 5. Each sample consisted of 6 cores, 4 cores were fixed in formalin and imbedded in paraffin. The remaining two samples were frozen in OCT embedding material and stored at -70?C. Each paraffin and frozen section block has been sectioned at least once to establish a pathological diagnosis. The serum and prostate biopsy samples are stored currently in a repository at the MTOPS Pathology Coordinating Unit. Clinical information for each patient is stored in the MTOPS Data Coordinating Center. The pathological diagnoses of these tissue biopsies are predominantly chronic prostatitis, simple atrophy, or the various forms of hyperplasia (i.e. adenomatous, fibromyoadenomatous, leiomyoma, etc.). The availability of these materials presents an extraordinary opportunity to develop and evaluate biological and genetic markers that will further our understanding of the biological and genetic processes contributing to BPH and prostate cancer, or related to response to therapy of BPH. The importance of prostate biomarkers has been repeatedly emphasized at national and international meetings including the NCI-sponsored Prostate Research Progress Group, April 1997, the International Symposium on Prostate Growth, March 1998, and the Symposium on Prostate Growth and Aging, September 13-15, 2000. In contrast to rapid progress obtained with PSA for the detection of prostate cancer, BPH must be diagnosed clinically by symptoms, clinical exam, and diagnostic imaging. There is a great need for better markers for BPH, and for genetic tests to identify patients at high risk for early BPH, for rapidly progressing BPH, and for prostate cancer. Genetic tests are also needed to determine which patients will respond to various forms of pharmacological therapy. The large number of well-characterized patients in the MTOPS consortium should allow for the development and testing of such markers. Objectives and Scope The intent of this initiative is to assemble a cross-disciplinary, multi- institutional MPSA Consortium with a range of expertise to perform cooperative studies using the MTOPS material to evaluate genetic, immunologic, or biochemical biomarkers relevant to the progression of BPH, response to therapy, and the concurrent development of prostate cancer. For simplicity, the term "biomarker" below will include genetic, immunologic, or biochemical markers of disease or susceptibility to disease. The Consortium will generate and validate the biomarkers for use by the research community for a variety of investigations, including testing early detection, prevention, therapeutics, or imaging strategies, and assure their availability to the research community. The approaches used for generating, characterizing, and validating the biomarkers will reflect the blend of experience and creativity of the Consortium component units and will be originated by these investigators. The consortium may also produce research tools such as serum protein arrays, layered expression arrays, or tissue arrays that can be used by the research community. It is anticipated that one Pathology Coordination Center and four or five Biomarker Units will be awarded. Each Biomarker unit will consist of a cross-disciplinary team that may reside, if appropriate, at several institutions. It is expected that either the Principal Investigator or a co-investigator will have demonstrated, published experience in basic research studies that focus predominantly on BPH utilizing human tissue samples. In addition, either the Principal Investigator or a co-investigator must have demonstrated expertise in multi-center clinical trials focused on BPH treatment. One of the investigators must demonstrate expertise in translational research studies focused on prostate diseases. The MTOPS Data Coordinating Center, funded separately from this RFA, will be a part of the MTOPS PSA consortium and will perform a follow-up study of the MTOPS participants by questionnaires and/or death certificates. The participating NIH Institutes have briefly outlined broad areas of biomedical interest related to the goals of this RFA. The NIDDK"s primary interest is in the production and validation of biologic markers or genetic susceptibility tests for the detection, risk assessment, and assessment of disease progression of BPH. Since age is a major risk factor for BPH and prostate cancer, the NIA is interested in the development of biomarkers associated with the aging process and with age-related changes in the sensitivity and specificity of developed biomarkers. The following example illustrates the functions of the MPSA consortium and the ability it offers for moving basic research findings into clinical practice: An investigator within the Consortium identifies a putative biomarker through original laboratory research. Based on the pilot research findings on locally obtained prostate samples, the putative marker seems to be useful for BPH detection or progression or cancer detection. The investigator can then approach the Steering Committee for additional evaluation of the marker. The Steering Committee then has the responsibility to review the data on the potential marker using its standing formal criteria as a guide, which will likely include requirements for laboratory tests, quality controls, and sample size considerations. If necessary, scientific resources from other Biomarker Centers can be pooled to conduct studies. There will also be flexibility so that investigators outside the Consortium could form a collaboration with one of the existing centers or directly bring their discoveries to the Steering Committee (e.g., by Letter of Intent). The investigator, in turn, will agree to share his research findings and become an associate member of the Consortium. A. Interactions The MPSA Consortium, through its component units, Steering Committee, and subcommittees will do the following: o Define how biomarkers will be validated (pathology, imaging, tissue array, quantitative RT/PCR, SNPs, etc.), o Decide when candidate biomarkers have been sufficiently tested against local (non-MTOPS) BPH tissue or serum samples, and are ready to be tested against MTOPS samples, o Prioritize the testing of candidate biomarkers against the MTOPS serum and prostate biopsy samples, o Define methods to use MTOPS serum and prostate biopsy samples efficiently. For example, the consortium may decide to produce and use tissue arrays, moderate throughput ELISA techniques, or batch testing of biomarkers using multi-analyte methods, o Identify technological impediments to generating and validating biomarkers, and select strategies to surmount them, o Share technological, methodological, and clinical information both between MPSA components and with the broader research community, and o Decide when a candidate biomarker is sufficiently characterized and validated so that the biomarker and all available accompanying data can be distributed to the research community for individual investigator-initiated projects. At each step, input will be sought from experts within the MPSA Consortium, within other NIH-sponsored consortia (for example, NIDDK Biotechnology Centers Consortium [RFA DK-99-002, RFA DK00-009], Prostate and Genitorurinary Development [RFA DK-00-015]0, and from the broader research community. During the course of the funding period, technologies will improve and the rate of progress and scope of research under the cooperative agreement may change. Principal Investigators, in consultation with the NIH will be expected to make necessary adjustments to accommodate the changing research environment, to remain focused on appropriate goals, to maintain excellent coordination with the other projects funded under this RFA, and to incorporate new technological advances. B. Biomarker Units Each Unit will be a self-assembled group of multidisciplinary investigators from one or more institutions who provide a unique mix of complementary research experiences. An applicant team will incorporate an appropriate mix of expertise needed to achieve the Unit"s goals and to contribute substantially to achieving the overall MPSA Consortium goals. It is expected that either the Principal Investigator or a co-investigator will have demonstrated, published experience in basic research studies that focus predominantly on BPH utilizing human tissue samples. In addition, either the Principal Investigator or a co-investigator must have demonstrated expertise in multi-center clinical trials focused on BPH treatment. One of the investigators must demonstrate expertise in translational research studies focused on prostate diseases. To expedite translational research, each team must have expertise in both biomarker, and the clinical properties of human prostate disease that inform the design of early detection strategies, prevention, or therapy. Additional areas of expertise may include, but are not limited to, phenotypic, genotypic, genomic or proteomic analyses of disease, prostate biology, pathology, or pathogenesis, therapy, prevention, early detection, diagnostic, laboratory technology or validation, biometry, or epidemiology. The expertise in laboratory science is expected to include research in the biology of prostate hyperplasia and neoplasia that encompasses the development, characterization and testing of biomarkers, development of relevant technologies for biomarker detection, and analytical tools for the evaluation of biomarkers for detection and risk assessment. The expertise in laboratory validation will also include knowledge and practice of Standard Operating Procedures and experience in the statistical evaluation of accuracy, precision, reproducibility, and performance characteristics of tests in multi-center settings. Computational and informatic needs of the Consortium will be provided by a MTOPS Data Coordinating Center. The approaches used to generate, characterize, and validate biomarkers for BPH and other prostatic disease will reflect the blend of experience and creativity of the component investigators. The following examples are intended only to provide broad direction and should be considered illustrative, but not restrictive. An individual application might include the following: 1. Propose standards for validating biomarkers in BPH and other prostate diseases. 2. Review the literature for existing biomarkers or genetic predispositions, and discuss any candidate biomarkers susceptibility loci they have already generated. 3. Propose to generate biomarkers using local prostate samples. Such methods might include genetic, genomic or proteomic techniques such as SNP analysis, differential display, representative difference experiments, gene expression arrays, 2-D gels, protein chips, MALDI/TOF, phage display, monoclonal antibody production, etc. The application should discuss the clinical relevance of the proposed biomarker. 4. Propose methods to characterize the candidate biomarkers of BPH and other prostate diseases using local samples. This may include physiological, pathological, imaging, and genetic, genomic, or proteomic methods. These studies might establish and compare the sensitivity, specificity and predictive accuracy of biomarkers in a clinical context, including inter-and intra-laboratory reproducibility. A number of putative biomarkers exist that could be tested. Statistical power calculations should be discussed. 5. Refine assays and optimize technology. To develop accurate early detection screening tests, it is crucial to develop high-throughput assays/technologies that are reproducible and cost-effective. The Biomarker Units are expected to plan, design, and conduct analytic validation studies, as directed by the Steering Committee, for assay procedures and protocols, etc. Validation studies might include optimizing the selection of targets, design of internal controls, controls for contamination, reagent and instrument standards, technical reproducibility, precision and sensitivity, and well-characterized panels of reference reagents. 6. Propose methods to extensively validate the candidate biomarker using the MTOPS serum and prostate samples. The amount of sample needed and the statistical power calculations should be discussed. These studies might a) Evaluate the specificity, sensitivity, and diagnostic accuracy of biomarkers in predicting extent or severity of disease, b) Relate biomarker expression to clinical outcome. Correlating these biomarkers with the natural history and clinical outcome may prove valuable for therapeutic and follow-up strategies, c) Evaluate computational methods for combining multiple biomarkers for earlier detection and risk assessment in clinical settings, d) Identify high-risk populations and performing comprehensive studies in targeted high-risk populations for validation and potential integration of novel detection strategies, and e) Evaluate gene-environmental interactions for understanding risk and variations (polymorphisms) in susceptibility in high-risk cohorts. 7. Indicate how the biomarkers could be used to test early detection, therapeutic, prevention, and imaging strategies. In the application, applicants must provide methods to maintain unit records, establish, standardize, document, and distribute protocols, and provide for quality control and budgetary oversight. Each Biomarker Unit will establish a database to store, organize, analyze, or visualize data, and to facilitate dissemination of information and data-sharing within the Consortium. Applicants must also provide methods to oversee the daily operation of their unit that will also establish priorities among local candidate biomarkers. It is anticipated that some of the proposals will be quite speculative and innovative, and that applications may lack preliminary data on biomarkers. However, applications should include sufficient information to indicate that the investigative team has sufficient expertise with proposed techniques and that the proposed projects are feasible. C. Pathology Coordination Center The Pathology Coordination Center will maintain the MTOPS serum and prostate samples. The MTOPS samples are currently housed at the University of Colorado. The application must include plans to move the samples, if necessary to their own site. The Pathology Coordination Center will read the prostate biopsies, and distribute the MTOPS serum and prostate samples to members of the consortium. The Consortium may decide to generate specialized sample sets, including, protein arrays or layered expression arrays containing arrayed serum samples, or tissue arrays. The Center may also propose to produce and distribute cDNA or protein samples obtained by Laser Capture Microdissection. These research resources will be made available to the Biomarker Units and, after discussion by the Steering Committee, to the wider research community. The applicant should discuss in detail how it will generate these specialized reagents and how it will handle multiple requests for the samples. The Pathology Coordination Center should have the ability to scale-up assays to allow testing in large number of samples, under the guidance of the steering committee. Whereas the Biomarker Units will have responsibility for standardizing laboratory assays and developing quality control for reagents and technologies, the Pathology Coordination Center should have knowledge and practical experience with Standard Operating Procedures and in the evaluation of the accuracy, precision, reproducibility, and performance characteristics, for example, sensitivity, specificity, positive and negative predictive values. These characteristics are important when sampling body fluids or mixed cell types where only a very small percentage of cells may exhibit the specific genetic or molecular changes. The Pathology Coordination Center will also provide travel and meeting support for the Steering Committee and other committees of the MPSA Consortium (see the section "SPECIAL REQUIREMENTS"). D. Interactions with the Existing MTOPS Data Coordinating Center. The MTOPS Data Coordinating Center will maintain the database that contains clinical and laboratory data on patients enrolled in the MTOPS study. The MTOPS Data Coordinating Center will also perform a follow-up study of the MTOPS participants by questionnaire and/or death certificates. The MTOPS Data Coordinating Center will establish and maintain the Internet- based mechanism for rapid data and document transmission and electronic communication among participants in the MPSA Consortium and between the MPSA Consortium and the NIH. These databases and websites will serve the needs of all Units established by this initiative and will be an important interface between the MPSA Consortium and the larger research community. E. Data Sharing Each MPSA Consortium member will obtain data from the MTOPS Data Coordinating Center and samples from the Pathology Coordination Center after approval by the Steering Committee. Applicants should request support for data retrieval, sample retrieval, and biomarker assays in their budgets. For collaborative studies and specific data analyses, the Steering Committee will select a Statistical Coordinator from among the member institutions. The results of those analyses will be delivered to the Steering Committee, which will determine (1) if and what further analyses should be performed, (2) how the results are interpreted, (3) whether the results impact ongoing data collection, ongoing studies, or future studies, and (4) how the findings should be disseminated. The awardees will retain custody of, and have primary rights to, all data developed under these awards, subject to Government rights of access consistent with HHS, PHS, and NIH policies. Restricted availability of unique research resources, upon which further studies are dependent, can impede the advancement of research and delivery of medical care. Sharing biomaterials, data, and software in a timely manner has been an essential element in the rapid progress that has been made in the genetic analyses of mammalian genomes. NIH policy requires that investigators make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (NIH Grants Policy Statement [https://grants.nih.gov/grants/policy/nihgps], Principles and Guidelines for Recipients of NIH Research Grants and Contracts on Obtaining and Disseminating Biomedical Research Resources: Final Notice, December 1999 http://www.nih.gov/od/ott/RTguide_final.htm. Biomarkers or genetic tests and other research resources that can be patented (e.g., tissue arrays, genetic and phenotypic data for human samples) and that are produced in projects funded by this RFA are expected to be made available and distributed to the broader scientific community. The NIH is interested in ensuring that research resources developed through this RFA become readily available to the research community for further research, development, and application, with the expectation that sharing will lead to products and knowledge to benefit the public. For this reason, NIH is concerned that patents on biomarkers, genetic tests, tissue arrays, and phenotypic and genetic data and other research resources might have a chilling effect on the future development of products and information that may improve the public health. At the same time, NIH recognizes the rights of grantees to elect and retain title to subject inventions developed with Federal funding under the provisions of the Bayh-Dole Act. F. Steering and Other Committees The Principal Investigator and another senior investigator must be willing to be part of a Steering Committee (See TERMS AND CONDITIONS FOR MPSA CONSORTIUM) that will be the main governing board of the MPSA Consortium. The Steering Committee will meet twice each year, and may form other subcommittees (e.g., subcommittees on diseases [BPH, prostate cancer], biomarker validation, phenotyping, bioinformatics, and technology) that will meet either in person or by telephone conference calls. A major goal of these meetings is to facilitate progress by providing a forum for sharing skills, ideas, technology, data, and biological reagents. Participants will also discuss quality assurance, bioinformatics, coordination, and training. SPECIAL REQUIREMENTS The RFA has two special requirements regarding research resources produced in proposed projects (see APPLICATION PROCEDURES for more information): o Applications are required to include a specific plan describing how they will share with the wider scientific community research resources as well as copies of all Material Transfer Agreements used by all institutions involved in the applications. o A proposed plan addressing if, or how, the PI and grantee institution will exercise their intellectual property rights regarding patentable research resources, such as biomarkers and phenotypic and genetic data, for all human samples produced in projects funded under this RFA. Applicants are encouraged to discuss proposals for addressing these requirements with their institutional offices of technology transfer. TERMS AND CONDITIONS OF AWARD FOR THE MPSA CONSORTIUM The following terms and conditions will be incorporated into the award statement and provided to the Principal Investigator(s) and to the institutional official at the time 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 Parts 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 (U01), 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 awardees for the project as a whole. Specific tasks and activities to carry out the studies will be shared by awardees and NIH Project Scientists as described below. 1. Awardee Rights and Responsibilities Common responsibilities o The PI will have primary authority and responsibility to define objectives and approaches and to plan, conduct, analyze, and publish results, interpretations, and conclusions of studies conducted under the terms and conditions of the cooperative agreement award. o The PI will assume responsibility and accountability to the applicant organization officials and to the NIH Institutes for the performance and proper conduct of the research supported by the project in accordance with the terms and conditions of the award. o The PI and another senior investigator will serve as voting members of the Steering Committee, and they will attend two Steering Committee meetings a year. Each Steering Committee member will be responsible for participating in all other Steering Committee activities, for example, conference calls, special subcommittee meetings as may be necessary. o The PI will be responsible for accepting and implementing the goals, priorities, procedures, protocols, and policies agreed upon by the Steering Committee. Studies will proceed into the implementation stage only with the concurrence of the Steering Committee. o The PI will be responsible for close coordination and cooperation with the other components of the MPSA Consortium and NIH Project Scientists. o The PI will establish an Internal Advisory Committee to provide scientific and administrative oversight. The Internal Advisory Committee will be composed of the lead center personnel, and other technical or research personnel. These individuals are not limited to the Unit faculty. The committee is expected to meet at least every two months. The Internal Advisory Committee is charged with both prioritizing projects and periodically reviewing Unit activities to ensure that the objectives outlined in the application are being met. o Awardees will retain custody of, and have primary rights to, the data developed under these awards, subject to Government rights of access consistent with current PHS and NIH policies. Investigators conducting biomedical research frequently develop unique research resources. However, all awardees must adhere to PHS policy for the distribution of unique research awards produced with PHS funding as described under Special Requirements. The NIH Project Scientists, on behalf of the NIH, will have the same access, privileges, and responsibilities regarding the collaborative data as all other members of the Steering Committee. o Within the first three months of the award period, the PI will have the responsibility for establishing written milestones. o Early publication of major findings is encouraged. Publications and oral presentations of work performed under this agreement will require appropriate acknowledgment of NIH support. Analyses to be performed using the collective data from the MPSA Consortium institutions will be determined and directed by the Steering Committee. Individual components wishing to perform analyses of local data will inform the Steering Committee of any such analyses prior to initiation in order to avoid duplication. Review and approval by the Steering Committee, or a Publications Subcommittee, will be required for all analyses before publication or presentation according to criteria that will be developed by the Steering Committee. o Effective conduct of the MPSA Consortium goals will require considerable electronic communication of data and other information among the MPSA Consortium components and between the components and the NIH. Consortium members will be required to transfer data accurately and effectively. Biomarker Units Biomarker units will generate and validate biomarkers relevant to the progression of BPH, response to therapy, and the concurrent development of prostate cancer. The biomarkers will be generated using local samples, then tested on the MTOPS serum and prostate sample set. Pathology Coordinating Center The Pathology Coordination Center will read the prostate biopsies, and maintain and distribute the MTOPS serum and prostate samples to members of the consortium. Under the direction and guidance of the Steering Committee, the Pathology Coordinating Center may generate specialized sample sets and reagents, and scale-up assays to allow testing in large number of samples. These research resources will be made available to the Biomarker Units and, after discussion by the Steering Committee, to the wider research community. The Pathology Coordination Center will also provide travel and meeting support for the Steering Committee and other committees of the MPSA Consortium. Data Coordinating Center The MTOPS Data Coordinating Center, supported separately from the MPSA Consortium, will maintain the database that contains clinical and laboratory data on patients enrolled in the MTOPS study. The MTOPS Data Coordinating Center will also perform a follow-up study of the MTOPS participants by questionnaire and/or death certificates. The MTOPS Data Coordinating Center will establish and maintain the Internet-based mechanism for rapid data and document transmission and electronic communication among participants in the MPSA Consortium and between the MPSA Consortium and the NIH. These databases and websites will serve the needs of all Units established by this initiative and will be an important interface between the MPSA Consortium and the larger research community. 2. NIH Staff Responsibilities The NIDDK and NIA will each identify one Program Officer and one Project Scientist. NIH Program Officers will provide normal stewardship and administrative oversight. They will review the scientific progress of the individual components and review the components for compliance with operating policies developed by the Steering Committee. NIH Program Officers may withhold support, suspend, or terminate an award for lack of scientific progress or failure to adhere to policies established by the Steering Committee. The NIH Program Officers reserve the right to approve moving from one phase of a project to the next. NIH Project Scientists will have substantial scientific-programmatic involvement during conduct of this activity, through technical assistance, advice, and coordination above and beyond normal program stewardship for grants, as described below. The dominant role and prime responsibility for the project as a whole resides with the awardees, although specific tasks and activities in carrying out the studies will be shared by awardees and the NIH. o NIH Project Scientists will coordinate and facilitate the MPSA Consortium programs and be members of the Steering Committee and its subcommittees. Other NIH Staff with relevant expertise may participate in the Steering Committee and subcommittees as non-voting members. o NIH Project Scientists will help the Steering Committee develop and draft operating policies and policies addressing recurring situations that require coordinated action. o The NIH Project Scientists may contribute, through review, comment, analysis, and/or co-authorship, to reporting results of the studies conducted by the MPSA Consortium to the research community and interested lay organizations. Co-authorship by the NIH Project Scientists will be subject to approval in accordance with NIH policies regarding staff authorship of publications resulting from extramural awards. o NIH will form an MPSA Advisory Panel that comprises outside advisors (non grantees) picked by NIH program staff. The MPSA Advisory Panel will meet regularly to review the progress of the MPSA Consortium and to advise the NIH of scientific developments and opportunities that may enhance the achievement of the MPSA Consortium goals. o If necessary to preserve the samples and data about them and/or to continue the research, the NIH reserves the right to require the transfer to an eligible third party any appropriate serum and prostate samples, related reagents, and pertinent data generated as the result of participation in research supported under these awards. Third parties supported under these awards must be informed of this right. 3. Collaborative Responsibilities Steering Committee o The Steering Committee will be the main governing board of the MPSA Consortium. It will develop collaborative protocols and quality control standards, set priorities for biomarker validation using the MTOPS serum and prostate samples, approve the design and implementation of all collaborative studies, facilitate the conduct and monitoring of all collaborative studies, analyze and interpret collaborative study data, and report collaborative study results. Studies will proceed to the validation stage only with the concurrence of the Steering Committee. It will also identify technological impediments to success and strategies to overcome them, develop shared software tools for disseminating information about the MPSA Consortium, identify opportunities for sharing techniques and tools with a wider research community, and decide when biomarkers should be made available to the research community. o The Steering Committee will be composed two investigators from each Biomarker Unit, the Pathology Coordination Center, the MTOPS Data Coordinating Unit, and the two NIH Project Scientists. The two investigators from each component will share one vote. The NIH Project Scientists will share one vote. The Steering Committee will select a chair who will be someone other than an NIH Program Officer. o The NIH reserves the right to augment the scientific expertise of the Steering Committee when necessary. o There will be two Steering Committee meetings annually, both in the Washington, DC, area, at times agreed upon by the Steering Committee and the NIH. The first meeting of the MPSA Consortium will be a Planning Meeting in the Washington, DC, area soon after grants are awarded. At the Planning Meeting, the Steering Committee will be formed and will select a chairperson from among the members who represent the awardees. At the Planning Meeting, the Steering Committee may: (a) draft a charter to detail policies and procedures, a process for monitoring compliance with the policies and procedures, and a process for recommending that the NIH Program Officer(s) act on evidence of non-compliance of any Consortium component with Steering Committee policies, (b) agree upon the terms of the charter, (c) discuss the approaches for generating and validating biomarkers that were proposed in the project applications and any relevant new information, and set initial priorities for the projects that will be pursued and for new technologies (tissue arrays) to be developed, (d) discuss and set initial genotypic and phenotypic parameters required to characterize the patients, (e) discuss and set initial standards for validating the biomarkers for further biological studies and such uses as testing prevention or early detection strategies, or therapies, or diagnostic imaging technologies, (f) develop a bioinformatics subcommittee whose membership will include the key research scientists responsible for bioinformatics, NIH Project Scientist(s) or program staff with relevant expertise, and outside advisors as needed. An Internet-based electronic communications mechanism will be discussed and will be implemented by the MTOPS Data Coordinating Unit. o At their first meeting each year, the Steering Committee will formulate plans for any workshops or symposia to be held. o At the second and subsequent meetings, the Steering Committee will refine the MPSA Consortium"s scientific objectives and implementation as necessary, consistent with the progress of the individual components and the MPSA Consortium. o At any time during the MPSA Consortium, the Steering Committee may examine the characterization and validation data for biomarkers derived by the MPSA Consortium components and decide when a test is sufficiently validated that it may be distributed to the research community for further investigations or applications. o The Steering Committee will plan workshops to which non-MPSA Consortium participants will also be invited to (a) enable the MPSA Consortium to explore scientific or technologic innovation that occurs during the course of the project, (b) inform the research community of the progress made toward derivation or validation of biomarkers, and (c) inform the research community of any technological advances related to derivation and validation of biomarkers. The NIH Project Scientist(s), the MPSA Advisory Panel, and other NIH staff will provide the Steering Committee with advice on participants for the workshops and symposia. o The Steering Committee may establish subcommittees, as it deems appropriate, NIH Project Scientist(s) and other NIH staff will serve on subcommittees as they deem appropriate. 4. Arbitration Any disagreement that may arise on scientific/programmatic matters (within the scope of the U01 award) between awardees and the NIH may be brought to arbitration. An arbitration panel will be composed of three members: one member selected by the Steering Committee (with the NIH Project Scientist(s) not voting) or by the individual awardee in the event of an individual disagreement, a second member selected by the NIH Project Scientist(s), and the third member selected by the two previously selected members. This special arbitration procedure in no way affects the awardee"s right to appeal an adverse action that is otherwise subject to appeal 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 clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). The inclusion of women and children does not apply. All investigators proposing clinical research should read the AMENDMENT "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research - Amended, October, 2001," published in the NIH Guide for Grants and Contracts on October 9, 2001 (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html), a complete copy of the updated Guidelines are available at https://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research, updated racial and ethnic categories in compliance with the new OMB standards, clarification of language governing NIH-defined Phase III clinical trials consistent with the new PHS Form 398, and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable, and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences. REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS NIH policy requires education on the protection of human subject participants for all investigators submitting NIH proposals for research involving human subjects. This policy announcement is found in the NIH Guide for Grants and Contracts Announcement dated June 5, 2000, at the following website: https://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html. URLS IN NIH GRANT APPLICATIONS OR APPENDICES All applications and proposals for NIH funding must be self-contained within specified page limitations. Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) should not be used to provide information necessary to the review because reviewers are under no obligation to view the Internet sites. Reviewers are cautioned that their anonymity may be compromised when they directly access an Internet site. PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT The Office of Management and Budget (OMB) Circular A-110 has been revised to provide public access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at: https://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this RFA in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award. LETTER OF INTENT Prospective applicants are asked to submit a letter of intent by February 20, 2002. The letter should include 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 a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review. The letter of intent is to be sent to: Chief, Review Branch Division of Extramural Activities National Institute of Diabetes and Digestive and Kidney Diseases 6707 Democracy Boulevard, Rm. 752 MSC 5452 Bethesda, MD 20892-5452 (for express/courier service: Bethesda, MD 20817) Telephone: (301) 594-8897 FAX: (301) 480-3505 E-mail: fc15y@nih.gov APPLICATION PROCEDURES The PHS 398 research grant application instructions and forms (rev. 5/2001) at https://grants.nih.gov/grants/funding/phs398/phs398.html must be used in applying for these grants. This version of the PHS 398 is available in an interactive, searchable format. For further assistance contact GrantsInfo, Telephone 301/710-0267, Email: GrantsInfo@nih.gov. The RFA label available in the PHS 398 (rev. 5/2001) application form must be affixed to the bottom of the face page of the application. Type the RFA number (DK-02-027) on the label. 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 title and number must be typed on line 2 of the face page of the application form and the YES box must be marked. The RFA label is also available at: https://grants.nih.gov/grants/funding/phs398/label-bk.pdf. Submit a signed, typewritten original of the application, including the Checklist, and three signed photocopies in one package to: CENTER FOR SCIENTIFIC REVIEW 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 be sent to: Dr. Francisco O. Calvo Chief, Review Branch Division of Extramural Activities National Institute of Diabetes and Digestive and Kidney Diseases 6707 Democracy Boulevard, Rm. 752 MSC 5452 Bethesda, MD 20892-5452 (for express/courier service: Bethesda, MD 20817) Telephone: (301) 594-8897 E-mail: fc15y@nih.gov Applications must be received by the application receipt date listed in the heading of this RFA. If an application is received after that date, it will be returned to the applicant without review. The Center for Scientific Review (CSR) 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 CSR 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. Applicants may apply for a Biomarker Unit, a Pathology Coordination Center, or both. If an applicant applies for both, separate applications must be submitted 1. General Application Format Instructions Applicants are encouraged to submit and describe their own ideas about how best to meet the goals of the cooperative study and their specific protocols, and they are expected to address issues identified under "TERMS AND CONDITIONS OF AWARD FOR THE MPSA CONSORTIUM" and "SPECIAL REQUIREMENTS" sections of the RFA. 2. Applications for Biomarker Units It is expected that either the Principal Investigator or co-investigator(s) will have demonstrated and published experience in basic research studies that focus predominantly on BPH utilizing human tissue samples. In addition, either the Principal Investigator or co-investigator(s) must have demonstrated expertise in multi-center clinical trials focused on BPH treatment. One of the investigators must demonstrate expertise in translational research studies focused on prostate diseases. Applicants should discuss their rationale for the design and derivation of new biomarkers or for altering and improving existing biomarkers based on their experience with biomarkers and their knowledge of basic, translational, and clinical prostate research. Applicants should describe the extent to which they plan to characterize any biomarkers they derive or refine, the methods that they will use to characterize the biomarkers, the rationale for choices of methods, and how generally applicable the methods are, or will be, for benign and malignant prostate diseases. Applicants are expected to discuss assay optimization, quality control, and assay performance. Applicants are expected to discuss methods for establishing priorities among biomarkers, identify the standards they will apply to validate a proposed biomarker, the rationale for the choices, how generally applicable the validation standards are, or will be, for benign and malignant prostate disease, and the purpose(s) for which they anticipate their biomarkers might be used. The roles and expertise of all key personnel, collaborators, and consultants who are associated with this part of the application should be thoroughly documented. Applicants should define the technologic approaches they will use, or any technology that they propose to develop to achieve the goals of biomarker generation, refinement, characterization, and validation. The roles and expertise of all key personnel, collaborators, and consultants who are associated with this part of the application should be thoroughly documented. 2. Applications for the Pathology Coordination Center Applicants for the Pathology Coordination Center must have published and documented their experience in reading human prostate biopsy samples and basic and clinical research studies related to human BPH tissue. Applicants should discuss methods to store, handle, and retrieve MTOPS serum and prostrate biopsy samples, including both paraffin and OTC-embedded samples. Applicants may also propose to develop specialized serum or prostate protein arrays, layered expression arrays, or tissue arrays that allow rapid testing of biomarkers. Applicants should also indicate their familiarity and capability for performing multiple assays (generally ELISAs or bead-based multi-analyte systems) either sequentially or in parallel on these samples. For example, it would be more efficient to test 10-100 tests at once on a single 0.5 ml sample, than to do a similar number of tests individually. These tests will be funded by the individual Biomarker Units, but might be performed at the Pathology Coordination Center. Applicants should discuss the administrative structure of the coordinating unit and plans for providing administrative support for up to five meetings a year. 3. Interactions / Data sharing (applies to Biomarker and Pathology Coordination Centers) The application should include the description of an internal advisory board consisting of the Principal and co-investigators and other important personnel should oversee the daily operation of the unit. Applicants should describe how the unit will fit into, augment, and be supported by the parent institution and plan for designating an alternate or replacement Principal Investigator should it become necessary. Applicants should describe the Internet-based mechanism for rapid electronic communication among participants and the NIH, the structure of their databases and websites for communication within the MPSA consortium and with the research community. Applicants should describe issues of data validity, security, and confidentiality. Applicants should discuss how they would interact with other MPSA Consortium components and the general research community. In this part of the "Research Plan," applicants must include specific plans for responding to the "Terms and Conditions of Award" section. Applicants should state their willingness to collaborate and share data freely with the other MPSA Consortium components and the wider research community. Applicants must include a data sharing plan and copies of all Material Transfer Agreements used by all institutions involved in the application. Applicants are encouraged to use the NIH Simple Letter of Agreement to transfer materials, available at http://www.nih.gov/od/ott/RTguide_final.htm#guide. Applicants should discuss their willingness to serve on the Steering Committee and other Consortium committees and should state their willingness to follow the common protocols that will be developed by the Steering Committee, particularly those that relate to setting priorities for biomarker validation and the standards for characterization and validation. Applicants must state their willingness to plan and attend workshops and symposia. Applicants should describe how their unique blend of experience could contribute to the collective efforts of the MPSA Consortium. Applicants should also describe how they will comply with the involvement of NIH Project Scientist(s) and fulfill the responsibilities of Consortium components to work together cooperatively. Applicants should describe their experience with, and capability for, Internet-based communication and ideas for facilitating electronic communication and other interactions among the MPSA Consortium components, NIH, and the general research community. The scientific review group will evaluate the adequacy of the proposed plan for sharing and data access. Comments on the plan and any concerns will be presented in an administrative note in the summary statement. The adequacy of the plan will be considered by NIH program staff and will be important in determining whether the grant shall be awarded. The sharing plan(s) as approved, after negotiation with the applicant when necessary, will be a condition of the award. Evaluation of non-competing continuation applications will include assessment of the effectiveness of research resource release. Applicants are reminded that the grantee institution is required to disclose each subject invention to NIH within two months after the inventor discloses it in writing to grantee institutional personnel responsible for patent matters. The awarding Institute reserves the right to monitor awardee activity in this area to ascertain if patents or patent applications on biomarkers or other patentable subject matter are adversely affecting the goals of this RFA. 4. Budget Instructions Common to Biomarker Units and Pathology Coordinating Center o Applicants who have additional funds to support ("leverage") the application should indicate the source of funds (institutional, R01, P01, P30, etc.) that permit them to accomplish the project goals. Subcontract budgets should be a separate page, and the subcontract indirect costs should be calculated and listed in the usual place as part of the direct costs of the budget. o Applicants must budget for travel and per diem expenses for participation in the MPSA Consortium Steering Committee, subcommittees, workshops, and symposia. Applicants should budget for three trips to the Bethesda, MD, area each year. Biomarker units only o Only direct costs associated with each subcontract will count toward the direct costs cap of $300,000 on the budget for the each year. o Funds should be requested for testing and validating new biomarkers on the MTOPS samples at the Pathology Coordinating Center and at other Biomarker Units. Applicants are instructed to make budget requests for funds to travel to Steering Committee meetings Pathology Coordination Center only o Applicants should include funds to move the samples, if necessary, to their own site. o Applicants should include travel support for 15 additional outside consultants to attend Steering and other committee meetings and workshops in the Bethesda, MD, area each year. REVIEW 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 for evaluation of a study. Other factors considered to be important for review include demonstrated expertise in clinical prostate disease as applied to the derivation and validation of biomarkers of human disease, a multi- disciplinary team of collaborators, substantial interactions among collaborating researchers, demonstration of appropriate facilities and resources, willingness to share data and reagents freely. Review Method Upon receipt, applications will be reviewed for completeness by the CSR and responsiveness by the NIH. Incomplete applications will be returned to the applicant without 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 NIH in accordance with 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 the applications under review, will be discussed, assigned a priority score, and receive a second level review by the appropriate National Advisory Council. Review Criteria The peer review group will assess the scientific merit of the applications and related factors using the following criteria: 1. Innovation. Does the project employ novel concepts, approaches, or method? Is the project original and innovative? Does the project challenge existing paradigms or develop new methodologies or technologies? Will the approaches advance the field of prostate biomarkers or prostate pathophysiology? 2. Approach. Are the conceptual framework, design, methods, and analyses adequately developed and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics? Are the parameters chosen to characterize and validate the biomarker(s) sufficient and appropriate? Are the standards chosen to validate the biomarker(s) for testing early detection, prevention, therapy, or imaging appropriate and adequate? Will the assay(s) be sufficiently optimized to use in a multi-analyte assay? Can these approaches be used to derive biomarkers in addition to those proposed? 3. Investigators. Are the principal investigator and his/her collaborators appropriately trained and well suited to carry out this work? Do they have the necessary clinical and research knowledge and experience with human BPH tissue biopsies? To what extent do these investigators have the necessary complementary skills? Do the investigators have skills in both prostate disease and biomarkers? Have collaborations been established or consultants identified to provide the appropriate depth and breadth of scientific expertise required for the project? Will this team of investigators contribute unique skills to the overall Consortium? Do the investigators have demonstrated experience in working in multi-center studies? Will the investigators work effectively with other members of the Consortium? 4. Environment. Are the facilities for biomarker and generation and validation appropriate to support the endeavor? Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed experiments take advantage of unique features of the scientific environment and incorporate the best use of collaborative arrangements? Is there evidence of institutional support? 5. Significance. Do the biomarker(s) proposed for derivation/ characterization/validation address an important need for the prostate research community? What is the immediacy of the research opportunity? Over the project period, is there potential for the group to develop biomarkers other than those specified in the application? Pathology Coordination Center 1. Do the investigators have demonstrated research and clinical expertise in reading human BPH biopsies? Have they published research studies involving human BPH tissue? Are there adequate plans for storing, handling, and distributing serum and prostate samples? Does the Center employ novel concepts, approaches, or methods? Are the principal investigator and collaborators appropriately trained and well suited to provide support for multiple investigative teams? Do the investigators have demonstrated experience in working in multi-center studies? Are they willing to cooperate with other investigators in the consortium? Can the site perform the biomarker assays either one at a time or in a multi-analyte assay? Are there adequate plans for providing meeting support for the MPSA Consortium? Additional Considerations for Biomarker Units and Pathology Coordinating Center 1. Interactions. Are there adequate plans for effective interaction and coordination among Consortium components and the NIH? Are the proposed plans to share assays, tools, data, and tests adequate? Do the investigators state their willingness to collaborate extensively and share information fully? Are the Material Transfer Agreements straightforward? Do the investigators state their willingness to abide by the priorities and policies agreed upon by the Steering Committee? Have the applicants proposed sound strategies for communication among themselves, with the other MPSA components, and with the NIH? 2. Budget. Assess the appropriateness of the proposed budget and duration in relation to the proposed research. Does the budget for fundamental infrastructure, biomarker development, characterization and validation, and technology development indicate that the applicants understand the requirements of managing this sort of enterprise? 3. The scientific review group will evaluate the adequacy of the proposed plan for sharing and data access, with comments on the following elements: have the applicants addressed data sharing policies, confidentiality issues, and security considerations? Are there adequate plans for open access to these databases and websites by the general research community? Comments on the plan and any concerns will be presented in an administrative note in the summary statement. The adequacy of the plan will be considered by NIH program staff and will be important in determining whether the grant shall be awarded. The sharing plan(s) as approved, after negotiation with the applicant when necessary, will be a condition of the award. Evaluation of non-competing continuation applications will include assessment of the effectiveness of research resource release. 4. The adequacy of the proposed protection for humans, animals or the environment, to the extent they may be adversely affected by the project proposed in the application. AWARD CRITERIA The intent of this RFA is to enable the NIH to assemble a Consortium of highly qualified investigators whose complementary scientific skills and expertise will enable them to achieve the goal of deriving and validated biomarkers for prostate disease. The NIH will choose Biomarker Units and a Pathology Coordinating Center for the Consortium that will collectively provide the most creative approaches to biomarker design and validation, and have a range of research focus, experience, technology, and resources to ensure that a range of biomarkers are rapidly derived and validated. Applications recommended by the NIH Advisory Councils will be considered for award based upon (a) scientific and technical merit as determined by peer review, (b) the importance of the proposed biomarkers for detection, prevention, and therapy of prostate diseases, (c) the degree of originality, innovation, and diversity of Biomarker, (d) the creativity of the approaches and technologies, (e) the likelihood for substantial contribution by the applicants to a successful collaborative effort, (f) the evidence for willingness to work cooperatively, (g) the quality and availability of the basic science infrastructure and resources, (h) program balance, including sufficient compatibility of features to make a successful collaborative program a reasonable likelihood, and (i) the availability of funds. Schedule Public Information Meeting: January 2002 Letter of Intent Receipt Date: February 20, 2002 Application Receipt Date: March 20, 2002 Peer Review Date: June-August 2002 Council Review: September 2002 Earliest Anticipated Start Date: September 30, 2002 INQUIRIES A public information meeting will be held by Phone Conference in January 2002. The date and time of this meeting, answers to frequently asked questions, and other updates about this RFA will be posted on the NIDDK website http://www.niddk.nih.gov/fund/crfo/highlights.htm as they are developed. Applicants are highly encouraged to visit this website regularly in the course of preparing applications. Potential applicants are encouraged to subscribe to the MPSA Consortium Discussion List at http://list.nih.gov/archives/mpsa_consortium-l.html. These sites will contain the most current information available. Written and telephone inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues that are not addressed at the website to: Robert A. Star, M.D. Division of Kidney, Urologic, and Hematologic Diseases National Institute of Diabetes and Digestive and Kidney Diseases 6707 Democracy Boulevard, Room 647 MSC 5456 Bethesda, MD 20892-5456 Tel: (301) 594-7717 Fax: (301) 496-3510 E-mail: rs301p@nih.gov Frank Bellino, Ph.D. Biology of Aging Program National Institute on Aging 7201 Wisconsin Avenue, Suite 2C231 MSC 9205 Bethesda, MD 20892-9205 Telephone: (301) 496-6402 FAX: (301) 402-0010 Email: fb12a@nih.gov Direct inquiries regarding fiscal matters to: Teresa Farris Marquette Division of Extramural Activities National Institute of Diabetes and Digestive and Kidney Diseases 6707 Democracy Boulevard, Room 728 MSC 5456 Bethesda, MD 20892-5456 Tel: (301) 594-7682 Fax: (301) 480-3504 E-mail: tf102y@nih.gov Linda Whipp Grants and Contracts Management Office National Institute on Aging 7201 Wisconsin Avenue, Suite 2N212, MSC 9205 Bethesda, MD 20892-9205 Telephone: (301) 496-1472 FAX: (301) 402-3672 Email: lw17m@nih.gov AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.849 and 93.866. 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 NIH grants policies and Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. 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 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.
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