BETA CELL BIOLOGY CONSORTIUM (U01) RELEASE DATE: June 21, 2004 RFA Number: RFA-DK-04-018 (Reissued as RFA-DK-09-011) (see addendum NOT-DK-04-016) EXPIRATION DATE: November 20, 2004 Department of Health and Human Services (DHHS) PARTICIPATING ORGANIZATION: National Institutes of Health (NIH) (http://www.nih.gov) COMPONENT OF PARTICIPATING ORGANIZATION: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (http://www.niddk.nih.gov) CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S) 93.847 LETTER OF INTENT RECEIPT DATE: October 19, 2004 APPLICATION RECEIPT DATE: November 19, 2004 THIS RFA CONTAINS THE FOLLOWING INFORMATION o Purpose of this RFA o Research Objectives o Mechanism(s) of Support o Funds Available o Eligible Institutions o Individuals Eligible to Become Principal Investigators o Special Requirements o Where to Send Inquiries o Letter of Intent o Submitting an Application o Supplementary Instructions o Peer Review Process o Review Criteria o Receipt and Review Schedule o Award Criteria o Required Federal Citations PURPOSE OF THIS RFA The National Institute of Diabetes and Digestive and Kidney Diseases invite new U01 applications to participate in a consortium of investigators and institutions, the Beta Cell Biology Consortium (BCBC); http://www.betacell.org. The BCBC will work collaboratively to generate resources that will facilitate research to 1) understand how endogenous beta cells are made by studying pancreatic development, with the hope of making pancreatic islets in culture 2) explore the potential of animal and/or human stem cells (embryonic or adult; if human embryonic, only NIH approved hES cell lines may be used) as a source for making pancreatic islets, and 3) determine the basic mechanisms underlying beta cell regeneration in the adult as a basis for producing new cellular therapies for diabetes. The BCBC will be responsible for collaboratively generating necessary reagents, mouse strains, antibodies, assays, protocols, and technologies that are beyond the scope of any single research effort. RESEARCH OBJECTIVES Background Type 1 and type 2 diabetes result from the anatomical or functional loss of insulin-producing beta cells of the pancreas. Replacement of these cells through transplantation could offer lifelong treatment for diabetes. A major obstacle in implementing treatment is the lack of sufficient islet cell tissue for transplantation. The generation of an alternative source of pancreatic islet cells derived from human stem/progenitor cells (adult or embryonic) could provide a limitless source of islet cells for transplantation therapies. The Beta Cell Biology Consortium (BCBC), is a basic science consortium of cooperative agreements that originated in 2001 through an RFA DK-01-014 http://grants.nih.gov/grants/guide/rfa-files/RFA-DK-01-014.html In addition to investigator initiated research projects, consisting of 5 U19s and 1 U01, the BCBC supports an administrative infrastructure located at Vanderbilt University that oversees collaborative research cores designed to coordinate efforts in creating key research tools that will support studies in pancreatic development and function (http://www.betacell.org). These resources were created to substantially accelerate efforts to efficiently differentiate animal and human embryonic and adult stem cells into pancreatic progenitor/islet tissue appropriate for transplantation. The BCBC was created in 2001 by RFA DK-01-014 as a direct response to recommendations of the Congressionally-established Diabetes Research Working Group http://www.niddk.nih.gov/federal/dwg/dwgsummary.htm that developed a strategic plan for research in diabetes. Two of the extraordinary research opportunities recommended by the plan were “to increase basic research opportunities on the control and regulation of islet cell differentiation, growth and development” and “to create interdisciplinary centers for Beta Cell Biology to expand current efforts and bring new investigators into the field”. At a May 2002 NIH advisory committee meeting on the Use of Special Congressional Funds for Type 1 Diabetes Research, the advisory panel emphasized “continued investment in cellular therapy as a high priority” http://www.niddk.nih.gov/federal/planning/type1_specialfund/ A companion RFA, RFA-DK-04-017, will request new and competing U19 grants. The BCBC will be comprised of awardees from RFA-DK-04-017 and RFA-DK-04-018, as well as the existing BCBC Coordinating Center located at Vanderbilt University and an existing U01 at the University of Pennsylvania (U01 DK056947). A U01 is a single project similar to an R01, and can have multiple collaborators. A U19 is composed of at least 3 subprojects and 1 or more cores similar to a P01. Research objectives This RFA is intended to provide support for new U01 projects for the BCBC, focusing on research to understand the control and regulation of pancreatic development, as well as islet cell growth and regeneration through the generation of necessary resources and approaches. Major scientific advances and technological breakthroughs in basic disciplines such as developmental biology, stem cell biology, mouse genetics, and bioinformatics demand that a multifaceted, interdisciplinary, coordinated and collaborative approach on several fronts be utilized to generate key reagents, assays and new strategies for the development of novel cellular therapies in diabetes. Therefore, at least 50% of the application should be directly related to the generation of these novel resources and approaches, which could include development of new assays or protocols, development of new animal models, and/or application of a new technology. Research objectives should be focused on at least one of the three targeted scientific goals described below: Beta Cell Development, Beta Cell Regeneration, and/or Stem Cell Biology. Beta Cell Development A goal of this RFA and the BCBC is to understand the developmental pathways required to produce a fully functioning pancreatic islet. Areas of emphasis may include but are not restricted to: o Characterizing sets of specific mouse strains for genes that would mark specific cell lineages in the pancreas and/or regulate fate decisions within the organ. New mouse strains should be created through coordination with the BCBC Mouse ES and Transgenic Core (http://www.betacell.org/php/cc.php); o Characterizing poly- and monoclonal antibodies to cell surface antigens to define critical stages of pancreas development, including cell-specific antibodies that would delineate stem/progenitor cells of the pancreas and be useful for purification of these cells. New antibodies should be developed through coordination with the BCBC Antibody Core (http://www.betacell.org/php/cc.php); o Discovering mechanisms that control pancreatic cell fate decisions using classical vertebrate embryology; o Identifying mesenchymal signals that promote pancreatic growth; o Identifying the signals that regulate the temporal differentiation of islet cells during normal endocrine development; o Identifying the signals that support islet cell morphogenesis, growth, function and survival; o Combining molecular and computational approaches to identify the transcriptional networks that regulate pancreatic development. Beta Cell Regeneration A goal of this RFA and the BCBC is to understand the mechanisms of beta cell regeneration in the adult animal and human islet. Areas of emphasis may include but are not restricted to: o Determining the factors important for beta cell regeneration and designing strategies to foster regeneration; o Developing new animal models, such as non-human primates transplanted with human islets that can be used to identify exogenous or endogenous factors that might promote beta cell regeneration or neogenesis; o Characterizing the lineage of cells that may contribute or participate in beta cell regeneration by genetic marking; o Developing assays to screen chemical libraries for modifiers of beta cell regeneration, differentiation, and/or expansion. Stem Cell Biology A goal of this RFA and the BCBC is to understand the nature of stem/progenitor cells during normal pancreatic development and in the adult pancreatic islet. Areas of emphasis may include but are not restricted to: o Characterizing pancreatic stem/progenitor cells during normal development; o Providing genetic evidence for stem/progenitor cells in the adult pancreas; o If pancreatic stem cells exist in the adult, designing strategies to foster development into new endocrine cells in vivo; o Comparing different sources of human pancreatic progenitor cells at the molecular level; o Using existing NIH-approved human ES cell lines or mouse embryonic cells to efficiently generate endoderm, pancreatic progenitor cells, or differentiated beta cells in culture; o Developing clonogenic assays for quantitatively assessing the efficacy of new cellular replacement therapies. MECHANISM OF SUPPORT This RFA will use the NIH U01 award mechanism. As an applicant you will be solely responsible for planning, directing, and executing the proposed project. This RFA is a one-time solicitation. The anticipated award date is July 31, 2005. Follow the instructions for non-modular budget research grant applications. This program does not require cost sharing as defined in the current NIH Grants Policy Statement at http://grants.nih.gov/archive/grants/policy/nihgps_2001/part_i_1.htm. The NIH U01 is a cooperative agreement award mechanism. In the cooperative agreement mechanism, the Principal Investigator retains the primary responsibility and dominant role for planning, directing, and executing the proposed project, with NIH staff being substantially involved as a partner with the Principal Investigator, as described under the section "Cooperative Agreement Terms and Conditions of Award". Continuation of the cooperative agreement project beyond the initially award period of performance will require an RFA or other announcement. FUNDS AVAILABLE The NIDDK intends to commit approximately $2.5 million in FY 2005 to fund 3-5 grants in response to this RFA. An applicant may request a project period of up to 5 years and a budget for direct costs of up to $500,000 per year. Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of the NIDDK provide support for this program, awards pursuant to this RFA are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications. ELIGIBLE INSTITUTIONS You may submit (an) application(s) if your institution has any of the following characteristics: o For-profit or non-profit organizations o Public or private institutions, such as universities, colleges, hospitals, and laboratories o Units of State and local governments o Eligible agencies of the Federal government o Domestic or foreign institutions/organizations INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with their institution to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH programs. A Principal Investigator may apply for either a U01 or a U19 (RFA-DK-04-017), but not both. SPECIAL REQUIREMENTS To promote the development of a collaborative program among the award recipients, the Principal Investigator is expected to attend BCBC Steering Committee meetings twice a year. A major goal of these meetings is to facilitate progress by providing a forum that will lead to sharing skills, ideas, technology, data, and biological reagents. At the meetings, participants will discuss quality assurance, bioinformatics, coordination, sharing, and a means of informing the community about progress made by the Consortium. Funds should be requested to attend Steering Committee meetings as well as other collaborative meetings of the BCBC. During the course of the funding period, technologies will improve and the rate of progress and scope of the research may change. It is expected that the Principal Investigators, in consultation with NIDDK program staff, will 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 the RFA-01-017, and to incorporate new technological advances. HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (see http://escr.nih.gov). Data and Reagent Sharing: All applications submitted through this announcement and the companion RFA (RFA-DK-04-017) must include technology transfer and sharing plans for both data and unique research resources that are generated by the projects in concordance with the BCBC policies http://www.betacell.org/php/about.php#policies. It is expected that resources developed by the BCBC will be made available to the broader scientific community, after a propriety period agreed upon by the Steering Committee, at no charge other than the cost of reproduction and distribution. Applicants must indicate their willingness to distribute research tools to the wider community including antibodies, transgenic mouse strains, mouse ES cell lines, and other reagents. A distribution plan should be included. Likewise the applicants must describe their willingness to submit microarray data generated through this project, if applicable, to EPConDB http://www.betacell.org/php/epcondb.php and other pertinent information about research resources generated through this U01 to the BCBC Coordinating Center (http://www.betacell.org). COOPERATIVE AGREEMENT TERMS AND CONDITIONS OF THE 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 Parts 74 and 92, and other HHS 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 awardee for the project as a whole, although specific tasks and activities in carrying out the studies will be shared among the awardees and the NIDDK Project Scientist or designee. Under the cooperative agreement, a relationship will exist between the recipient of these awards and the NIDDK, in which the performers of the activities are responsible for the requirements and conditions described below, and agree to accept program technical assistance, advice and/or other coordination above and beyond normal program stewardship from a named NIDDK Project Scientist in achieving the 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 of budget, withholding of support, suspension and/or termination of the award. B. Awardee Rights and Responsibilities The Awardee is a member of the Beta Cell Biology Consortium (BCBC) and is responsible for: o Defining objectives and approaches, and planning, conducting, analyzing, and publishing results, interpretations, and conclusions of studies conducted under the terms and conditions of the cooperative agreement award; o Conducting the research supported by the project in accordance with the terms and conditions of the award; o Participating as a permanent, voting member(s) of the Steering Committee as described below; o Contributing to and implementing the goals, priorities, procedures, and policies agreed upon by the Steering Committee; o Coordinating and cooperating with the other components of the BCBC and with the NIDDK staff; o Contributing to BCBC Core resources and serving on BCBC subcommittees as needed; o Sharing both data and unique research resources that are generated by the projects in concordance with the BCBC policies; 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 HHS and NIH policies. C. NIDDK Staff Responsibilities An NIDDK Program Director identified in the Notice of Grant Award will be responsible for the normal stewardship and monitoring of the award and will serve as the NIDDK Project Scientist. The NIDDK Project Scientist will have substantial scientific-programmatic involvement during conduct of this activity, through technical assistance, advice and coordination. The dominant role and primary responsibility for the activity resides with the awardees for the project as a whole, although specific tasks and activities in carrying out the studies will be shared among the awardees and the NIDDK Project Scientist. An NIDDK Project Scientist will have substantial involvement in the project above and beyond normal stewardship and monitoring of the award, as described below: o Being a voting member of the Steering Committee and, as determined by that committee, its subcommittees; o Being the contact point for all facets of the scientific interaction with awardee(s). As required for the coordination of activities and to expedite progress, NIDDK may designate additional NIDDK staff to provide advice to the awardee on specific scientific issues; o Serving as a resource with respect to other ongoing NIDDK activities that may be relevant to the research of the BCBC in order to facilitate compatibility and avoid unnecessary duplication of effort. Responsibilities as NIDDK Program Director: o Retaining overall programmatic responsibility for the award, and will clearly specify to the awardee the name(s) and role(s) of any additional individuals with substantial involvement in the project and the lines of reporting authority; o Interacting with the Principal Investigator (s) on a regular basis to monitor research progress. Monitoring may include: regular communications with the Principal Investigator and staff, periodic conference calls for discussions with awardee research teams, quality control, fiscal review, and other relevant matters; as well as attendance at Steering Committee meetings, External Advisory Board Meetings, and related meetings. The NIDDK retains, as an option, periodic external review of progress; o Reviewing and approving applications of the Pilot and Feasibility Program to insure that they are within the scope of peer review and NIH guidelines; o Making recommendations for continued funding based on: a) overall research progress, b) cooperation in carrying out the research (e.g. attendance at Steering Committee meetings, implementation of group decisions, compliance with the terms of award, and 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. Joint Responsibilities BCBC Steering Committee o The Steering Committee will be composed of the Principal Investigator from each U01 project, 2 members from each U19 project (the Principal Investigator and co-Investigator), and the NIDDK Project Scientist. Each member of the Steering Committee will have one Steering Committee vote. The chairperson will be someone other that the NIDDK Project Scientist, and will be selected by NIDDK. o The Steering Committee has primary responsibility to establish priorities, develop common protocols, and review progress. The Steering Committee will refine the BCBC scientific objectives consistent with progress in the BCBC components and other laboratories. Major scientific decisions regarding BCBC core data and resources, as well as setting scientific priorities for special programs such as the Pilot and Feasibility Program (http://www.betacell.org/php/cc.php) will be determined by the Steering Committee. The Steering Committee will document progress in written reports to the NIDDK Program Director, and will provide supplementary reports upon request. o There will be two Steering Committee meetings annually, one in the Spring and the other in the Fall. o The Steering Committee may, when necessary, invite additional, non-voting scientific advisors to the meetings at which research priorities and opportunities are discussed. The NIDDK reserves the right to augment the scientific expertise of the BCBC when necessary. o At the Fall meeting each year, the Steering Committee will formulate plans for the Fall Investigator’s retreat or any symposia to be held (http://www.betacell.org/php/cc.php). o The BCBC members will serve on subcommittees, scientifically review applications for special programs such as the Pilot and Feasibility Program, as it is deemed appropriate; the NIDDK Project Officer will serve on subcommittees as appropriate. NIDDK staff with special expertise may serve on subcommittees at the request of the Steering Committee. Subcommittee chairs will be selected from the Steering Committee and will report progress at Steering Committee Meetings and lead discussions at the Annual Investigator’s Retreat. External Advisory Board An independent External Advisory Board has been established by the NIDDK. The External Advisory Board will review periodically interim progress of the U01s, U19s, and BCBC Coordinating Center and report to NIDDK. The External Advisory Board will continue to meet annually. An NIDDK staff person other than the NIDDK Project Scientist/Program Director will serve on the External Advisory Board and organize these meetings. E. Arbitration Any disagreement that may arise on scientific/programmatic matters (within the scope of a U01 or U19 award) may be brought to arbitration. An arbitration panel will be composed of three members--one selected by the awardee (or Steering Committee, with the NIDDK Project Scientist not voting), a second member selected by the NIDDK; 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 regulations at 42 CFR Part 50, Subpart D and HHS regulation at 45 CFR Part 16. WHERE TO SEND INQUIRIES We encourage inquiries concerning this RFA and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research, peer review, and financial or grants management issues: o Direct your questions about scientific/research issues to: Sheryl Sato, Ph.D. Division of Diabetes, Endocrinology and Metabolic Diseases National Institute of Diabetes and Digestive and Kidney Diseases 6707 Democracy Boulevard, Room 6105 Bethesda, MD 20892-5460 Telephone: (301) 594-8811 FAX: (301) 480-3503 Email: firstname.lastname@example.org o Direct your questions about peer review issues to: Francisco O. Calvo, Ph.D. Review Branch National Institute of Diabetes and Digestive and Kidney Diseases 6707 Democracy Boulevard, Room 752 Bethesda, MD 20892-5452 Telephone: (301) 594-8897 FAX: (301) 480-3505 Email: email@example.com o Direct your questions about financial or grants management matters to: Mary K. Rosenberg Grants Management Branch National Institute of Diabetes and Digestive and Kidney Diseases 6707 Democracy Boulevard, Room 708 Bethesda, MD 20892-5452 Telephone: (301) 594-8891 FAX: (301) 594-9532 Email: firstname.lastname@example.org LETTER OF INTENT Prospective applicants are asked to submit a letter of intent that includes the following information: o Descriptive title of the proposed research o Name, address, and telephone number of the Principal Investigator o Names of other key personnel o Participating institutions o Number and title of this RFA 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 by the date listed at the beginning of this document. The letter of intent should be sent to: Chief, Review Branch National Institute of Diabetes and Digestive and Kidney Diseases 6707 Democracy Boulevard, Room 752 Bethesda, MD 20892-5452 (for express/courier service: Bethesda, MD 20817) Telephone: (301) 594-8897 FAX: (301) 480-3505 SUBMITTING AN APPLICATION Applications must be prepared using the PHS 398 research grant application instructions and forms (rev. 5/2001). Applications must have a DUN and Bradstreet (D&B) Data Universal Numbering System (DUNS) number as the Universal Identifier when applying for Federal grants or cooperative agreements. The DUNS number can be obtained by calling (866) 705-5711 or through the web site at http://www.dunandbradstreet.com/. The DUNS number should be entered on line 11 of the face page of the PHS 398 form. The PHS 398 document is available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. For further assistance contact GrantsInfo, Telephone (301) 435-0714, Email: GrantsInfo@nih.gov. SUPPLEMENTARY INSTRUCTIONS Applicants must budget for travel and per diem that will allow the Principal Investigator of the U01 to participate in 2 steering committee meeting, as well as Subcommittee meetings throughout the year. In addition, applicants should plan for at least 3 investigators per U01 grant to attend the Annual Investigator’s Retreat and Subcommittee meetings, when needed. There will be at least one interim review meeting conducted by the External Scientific Board and NIDDK in which the Principal Investigator and collaborating investigators are required to attend, and applicants will be expected to include funds for all required meetings in their travel budget. Additional materials The “Research Plan” should have a section entitled “Collaboration within the BCBC.” In this section: o The applicant should describe how they believe their unique expertise can contribute to the collective efforts of the BCBC. o The applicant should provide evidence of their intention to work together with other members of the BCBC to share ideas, and develop common tools and reagents. o In generating unique research tools, applicants should describe their willingness to cooperate and coordinate with the research activities and priorities of the BCBC Antibody Core/Database http://www.betacell.org/php/cc.php, the BCBC Mouse/ES Core http://www.betacell.org/php/cc.php and the Endocrine Pancreas Consortium Database (http://www.cbil.upenn.edu/EPConDB). All protocols, antibodies, vectors, cells, animals and data generated through the BCBC will be made freely available to the general scientific community. In working with the BCBC Coordinating Center at Vanderbilt University, and Steering Committee, applicants must agree to distribute unique resources developed through the BCBC. o The application must reflect adequate time commitment of personnel. Levels of effort that are awarded will vary depending on the requirements of the research to be performed and the anticipated contributions to the BCBC. o The BCBC is a collaborative effort that requires frequent interactions of awardees among themselves and with the NIH. Applicants must explicitly indicate their willingness to: participate in Steering Committee Meetings (2 times per year), regular telephone conference calls; cooperate with other awardees in the development and design of research priorities, especially regarding resources, and accept the Cooperative Agreement Terms and Conditions of Award given above. o Budget Information: The actual award will vary yearly, depending upon the work scope of the BCBC scientific cores, and other special BCBC programs. USING THE RFA LABEL: 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 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: http://grants.nih.gov/grants/funding/phs398/labels.pdf. SENDING AN APPLICATION TO THE NIH: 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 Bethesda, MD 20892-7710 Bethesda, MD 20817 (for express/courier service) At the time of submission, two additional copies of the application and all copies of the appendix material must be sent to: Chief, Review Branch National Institute of Diabetes and Digestive and Kidney Diseases 6707 Democracy Boulevard, Room 752 Bethesda, MD 20892-5452 (for express/courier service: Bethesda, MD 20817) APPLICATION PROCESSING: Applications must be received on or before 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. Although there is no immediate acknowledgement of the receipt of an application, applicants are generally notified of the review and funding assignment within 8 weeks. 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. However, when a previously unfunded application, originally submitted as an investigator-initiated application, is to be submitted in response to an RFA, it is to be prepared as a NEW application. That is, the application for the RFA must not include an Introduction describing the changes and improvements made, and the text must not be marked to indicate the changes from the previous unfunded version of the application. PEER REVIEW PROCESS Upon receipt, applications will be reviewed for completeness by the CSR. NIDDK will conduct the review. The Chief of the Review Branch, assigned SRA, and NIDDK Program Staff will conduct an administrative review to determine if the application is responsive to the RFA, or missing any information. Incomplete applications will not be reviewed and will returned to the applicant. 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 NIDDK in accordance with the review criteria stated below. As part of the initial merit review, all applications will: o 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 and assigned a priority score o Receive a written critique o Receive a second level review by the National Diabetes and Digestive and Kidney Diseases Advisory Council. REVIEW CRITERIA The goals of NIH-supported research are to advance our understanding of biological systems, improve the control of disease, and enhance health. In the written comments, reviewers will be asked to evaluate the application in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. The scientific review group will address and consider each of the following criteria in assigning the application’s overall score, weighting them as appropriate for each application. o Significance o Approach o Innovation o Investigator o Environment The application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high priority score. For example, an investigator may propose to generate important reagents or tools that by its nature are not innovative but are essential to move the field forward. The BCBC will focus on generating important reagents and tools and conducting challenging research in a cooperative spirit that might be considered too descriptive, ambitious, risky, or less likely to succeed as an individual R01 research project. SIGNIFICANCE: Does this study address an important problem in beta cell biology? If the aims of the application are achieved, how will scientific knowledge be advanced? What will be the effect of these studies on the concepts or methods that drive this field? Will the resources or technology to be developed be useful to investigators working in pancreatic development and stem cell biology and furthermore, benefit the larger beta cell biology/diabetes community? APPROACH: Are the conceptual framework, design, methods, and analyses adequately developed, well-integrated, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics? INNOVATION: Does the project employ novel concepts, approaches or methods? Are the aims original and innovative? Does the project challenge existing paradigms or develop new methodologies or technologies? INVESTIGATOR: Is the investigator appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers (if any)? ENVIRONMENT: 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 or employ useful collaborative arrangements? Is there evidence of institutional support? COLLABORATION: Does the applicant provide evidence of sharing and developing reagents? Does the applicant state their intention to cooperate with other BCBC members? PROTECTION OF HUMAN SUBJECTS FROM RESEARCH RISK: The involvement of human subjects and protections from research risk relating to their participation in the proposed research will be assessed. (See criteria included in the section on Federal Citations, below). INCLUSION OF WOMEN, MINORITIES AND CHILDREN IN RESEARCH: The adequacy of plans to include subjects from both genders, all racial and ethnic groups (and subgroups), and children as appropriate for the scientific goals of the research. Plans for the recruitment and retention of subjects will also be evaluated. (See Inclusion Criteria in the sections on Federal Citations, below). CARE AND USE OF VERTEBRATE ANIMALS IN RESEARCH: If vertebrate animals are to be used in the project, the five items described under Section f of the PHS 398 research grant application instructions (rev. 5/2001) will be assessed. ADDITIONAL REVIEW CONSIDERATIONS BUDGET: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research. The reviewers will also consider the willingness of the applicant to work with other members of the Consortium to provide research resources. RECEIPT AND REVIEW SCHEDULE Letter of Intent Receipt Date: October 19, 2004 Application Receipt Date: November 19, 2004 Peer Review Date: March-April 2005 Council Review: May 2005 Council Earliest Anticipated Start Date: July 31, 2005 AWARD CRITERIA Award criteria that will be used to make award decisions include: o Scientific merit (as determined by peer review) o Availability of funds o Programmatic priorities. REQUIRED FEDERAL CITATIONS ANIMAL WELFARE PROTECTION: Recipients of PHS support for activities involving live, vertebrate animals must comply with PHS Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf), as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm), as applicable. HUMAN SUBJECTS PROTECTION: Federal regulations (45CFR46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained. http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm DATA AND SAFETY MONITORING PLAN: Data and safety monitoring is required for all types of clinical trials, including physiologic, toxicity, and dose- finding studies (phase I); efficacy studies (phase II); efficacy, effectiveness and comparative trials (phase III). The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risk to the participants. (NIH Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, June 12, 1998: http://grants.nih.gov/grants/guide/notice-files/not98-084.html). INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: 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). All investigators proposing clinical research should read the "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 (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines are available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm 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. INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS: The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all human subjects research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them. All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the inclusion of children as participants in research involving human subjects that is available at http://grants.nih.gov/grants/funding/children/children.htm 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. You will find this policy announcement in the NIH Guide for Grants and Contracts Announcement, dated June 5, 2000, at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html. HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (see http://escr.nih.gov). It is the responsibility of the applicant to provide, in the project description and elsewhere in the application as appropriate, the official NIH identifier(s) for the hESC line(s)to be used in the proposed research. Applications that do not provide this information will be returned without review. 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 http://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. STANDARDS FOR PRIVACY OF INDIVIDUALLY IDENTIFIABLE HEALTH INFORMATION: The Department of Health and Human Services (DHHS) issued final modification to the “Standards for Privacy of Individually Identifiable Health Information”, the “Privacy Rule,” on August 14, 2002. The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the DHHS Office for Civil Rights (OCR). Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR website (http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on “Am I a covered entity?” Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.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. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site. HEALTHY PEOPLE 2010: The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This RFA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.healthypeople.gov/. AUTHORITY AND REGULATIONS: This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ in the following citations: No. 93.847, Diabetes Research, No. 93.855. Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under 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 123472 or Health Systems Agency review. The NIH Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm. The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the 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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