It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Program Objectives
Cystic Fibrosis is one of the most common, life-limiting genetic diseases, and is estimated to affect 30,000 Americans. Individuals with CF have inherited two mutated copies of the gene, cystic fibrosis transmembrane conductance regulator (CFTR), in every tissue of the body. Although lung disease is the primary cause of death in CF, multiple organ systems have altered functions including the lung, liver, pancreas, bone, sweat glands, and gastrointestinal and reproductive systems.

Treatment of the pancreatic complications and the lung infections has extended median survival in the United States to around 40 years of age. All states in the U.S. now screen for CF at birth to enable presymptomatic support for nutrition and preventing infections that may further improve the quality of life for these patients. Children identified at birth avoid the malnutrition that was the common presenting sign for CF. In addition, these patients benefit from many new forms of therapy that are being developed to aggressively eradicate bacterial colonization of the lung, control inflammation and lung damage, treat diabetes and liver disease and provide nutritional support.

In addition to treating the signs, symptoms and complications of CF, researchers are investigating molecular and pharmacologic methods to treat the underlying cause of CF. Screening of small molecules has identified lead molecules that increase either expression, processing, trafficking or function of the CFTR protein. This approach has led to the development of the drug ivacaftor which is approved for patients with the G551D substitution in CFTR as well as other mutations. A combination drug lumacaftor/ivacaftor was then approved for patients with the F508del mutation, the most common of the more than 2000 known CF mutations. Another combination drug, ivacaftor/tezacaftor, has been more recently approved. The success of these drugs is spurring the development of additional drugs with more mutation targets and greater potency. Currently triple drug therapy is undergoing pivotal trial evaluation.

Now that subjects with CF are living longer, there is an increased incidence of CF-related diabetes (CFRD). In fact, about 40% of patients with CF will develop diabetes by the age of 20. How mutated CFTR results in diabetes is still unclear. Recent guidelines developed by the Cystic Fibrosis Foundation and the American Diabetes Association suggest that all patients should be screened for the development of diabetes yearly by an oral glucose tolerance test starting at the age of 10. Insulin treatment of CF-related diabetes has been shown to improve survival and lung disease in patients with CF. How new CF drug treatments affect CFRD is not yet clear.

Another increased CF morbidity in part reflecting the longer CF lifespan is CF associated liver disease (CFLD) which can affect up to 30% of patients. Clinically there is great variability, from having asymptomatic liver enzyme elevations to frank cirrhosis. The mechanism(s) responsible for CF disease found in the liver and bile ducts is incompletely understood. Whether or not new CF drug treatment benefits CFLD is not yet known.

Gene therapy approaches to deliver a normal CFTR gene are also being pursued. New vectors with less toxicity have been developed. The availability of improved animal models such as the pig and ferret, which better mimic the human disease, aid in the testing of these new therapies. These encouraging findings suggest that collaborative efforts between basic and clinical researchers could foster the translation of novel basic research findings into preclinical testing in animal models, and potential clinical applications.

CF research often requires the use of specialized technologies and resources to support a cohesive research effort. The goal of the Center is to make state-of-the-art technologies and resources readily accessible to a broad spectrum of investigators working on CF.

Center Structure and Activities

The NIDDK CF Research and Translation Centers are part of an integrated program of research support designed to enhance multidisciplinary research in pathogenesis and treatment of cystic fibrosis and its complications. The goal of these Cystic Fibrosis Research and Translation Core Centers is to support research to develop and test therapies for CF. These Centers will provide resources for communication and collaboration between basic and clinical researchers. CF Research and Translation Core Centers support three primary research-related activities:(1) Research Core Services that provide shared resources to enhance the efficiency of research and foster collaborations within and among institutions with strong existing bases of research on cystic fibrosis; (2) a Pilot and Feasibility Program designed to foster the development of new investigators and to provide seed-support for innovative high-risk projects; and (3) an Administrative Core with an Enrichment Program to promote interdisciplinary interaction and educational updates for investigators.

Institution and Research Base

A CF Research and Translation Center must be an identifiable unit within a single institution such as a university medical center, or within a consortium of cooperating institutions with complementary research bases. In either case, the Center applications must be associated with an existing program of excellence in basic and clinical CF biomedical research. Program excellence is measured through a consistent and outstanding record of productivity and peer-reviewed research funding in CF and related research areas. To justify Center support, there must be a significant research base of NIDDK-funded investigators pursuing research activities in Center topic areas as well as investigators with other sources of peer-reviewed support. NIDDK mission-related research should represent at least 40% of the research base. A high level of integration and close collaboration among Center personnel from diverse scientific disciplines is an important feature of a successful CF Research and Translation Center. Centers should be established around one or more central themes or focus areas that link Center investigators and their research programs. Major themes should be relevant to NIDDK research interests related to cystic fibrosis which include mechanisms underlying the disease (excluding those associated with the specific development of lung disease), development of therapeutic approaches targeting or applicable to multiple organs, and elucidating pathophysiology and/or therapy directed at diabetes, and/or nutrition, gastrointestinal and liver complications of CF. While additional research themes outside the NIDDK mission (e.g., pulmonary complications of CF) may also be described and these research projects may utilize Center resources, applicant institutions should be pursuing major themes directly related to NIDDK research priorities.

Administrative Core with an Enrichment Program

CF Research and Translational Center applications must include an administrative core that will be responsible for allocation and oversight of Center resources. The Administrative Core must have a process to a) assess the productivity, effectiveness, and appropriateness of Center activities; b) determine criteria and selection process for Center membership; and c) foster collaborations and scientific opportunities among its members through the planning of an enrichment program. CF Research and Translational Centers are encouraged to develop a Center website to communicate available resources to the participating Institution(s). The Center Director will provide oversight for the entire Center and should have appropriate administrative experience. One or more Associate Directors should be named who will be involved in the administrative, scientific, or educational enrichment efforts of the Center and who will serve as Acting Center Director in the absence of the Director. A process must be in place that would be used to recommend a successor to the Director, if needed.

The CF Research and Translation Core Center enrichment program must be designed to advance translational research in CF and promote scientific exchange among investigators with research interests in these topic areas, and to enhance interactions between CF researchers and investigators from other fields with relevant expertise. The enrichment program can support activities such as seminars, guest speakers, visiting scientists, consultants, and workshops.

Enrichment of the postdoctoral experience so as to better conduct research in cystic fibrosis is an associated activity of a CF Research and Translation Core Center. While stipends/salaries for fellows cannot be funded from Center funds, the establishment of a Center should provide an enhanced environment for research educational enrichment. Just as in the case of funding for individual research projects, funding for fellowships should be sought from NIH NRSA, institutional training grants (e.g., T32, T35) and individual fellowships (e.g., F30, F32), and other sources such as private foundations, and commercial companies. No formal training support is provided by a CF Center grant.

Biomedical Research Cores

CF Research and Translation Centers are designed around biomedical research cores that provide shared resources for essential services, techniques, or instrumentation to Center participants enabling them to conduct their funded individual research projects more efficiently and/or more effectively. Cores provide specialized technologies and expertise needed to accomplish the stated goals of the Center toward the development of therapies for CF. Each core should provide services to multiple funded research projects. Centers may propose either Institutional Cores or Expanded Cores. Whereas Institutional Cores support research at a single institution or set of cooperating Institutions, Expanded Cores serve specific scientific communities on a regional, national, or international level and should be based on unique expertise or technology available at the domestic Center. Expanded Cores are physically located within a funded United States Cystic Fibrosis Research and Translation Center and are not located outside of the United States. A new category of research base for Cores that are used as an Expanded Core should be considered the "extended research base." The extended research base for an Expanded Core could include all investigators who might expect to use the core in some way that are not located at the specific domestic Center. This might include investigators who would be expected to fully compensate the core service through a charge-back, and thus would not be obtaining direct financial assistance from the Center. The list could include investigators who use the core services but otherwise have no collaborative interactions with other Center investigators. The extended research base should be defined as an entity separate from the institutional research base. For review purposes, it will be evaluated as part of the Expanded Core, in order to distinguish it from the local institutional research base. Examples of types of biomedical core resources that would be considered responsive to this Funding Opportunity Announcement include:

• Collection, analysis, storage and distribution of data and samples;
• Provision of specialized tools and technologies or access to specialized expertise;
• Development, standardization and distribution of reagents and/or protocols;
• Recruitment of patients and coordination of patient studies;
• Development, beta-testing and dissemination of specialty assays, methods, and services on an Institutional or national level;
• Sharing of specialized tools, technologies and expertise among investigators.

In responding to this FOA, applicants are encouraged to propose cores that address specific objectives based on the unique requirements of investigators at the applicant institution(s). Particular emphasis should be placed on services that support and foster interdisciplinary, integrated and translational approaches to research in the Center topic areas. Preference will be given to core support services that are not readily available or cost-effective when supplied from commercial sources, and techniques or technologies that may be technically challenging or require specialized expertise, equipment or infrastructure. Proposed Cores should not focus on pulmonary aspects of CF.

The need for core support from the CF Research and Translation Center must be well-justified, with a broad user base of NIDDK and other NIH-funded investigators pursuing research activities in Center topic areas, as well as CF investigators with other sources of peer-reviewed support. Participants in the CF Research and Translation Center program are encouraged to become fully integrated into, and synergistic with, other NIDDK- and NIH-funded Centers within their institutional setting. This includes the clinical research homes being established by the Clinical and Translational Science Awards supported by the National Institutes of Health (https://www.ctsacentral.org/) and other related NIH roadmap activities, and any related NIDDK-funded Center programs such as the Nutrition Obesity Research Center (NORC) Program (http://www.norccentral.org/ ), the NIDDK Diabetes Research Center (DRC) Program (https://www.diabetescenters.org/ ), the Centers for Diabetes Translation Research (CDTR) (https://www.diabetes-translation.org ) or the Digestive Diseases Research Centers

(http://www.digestivediseasescenters.com/)

Arrangements for sufficient space for core activities or for access to appropriate established facilities should be made. Centers are strongly encouraged to enter into cooperative arrangements with cores already established within their institution, or with other Centers in close proximity, when existing cores offer the services needed. These arrangements are important whenever greater efficiency or cost savings can be realized by such an agreement. However, it should be clear that the CF Research and Translation Center cores can function independently. It may be advantageous for a CF Research and Translation Center to provide support for appropriate personnel to work specifically with Center members in an existing facility/core (e.g., transgenic animal core) at the institution. In this case, the designated CF Research and Translation Center Core Director should work closely with the parent facility core Director to coordinate services, unless the same individual assumes both roles.

Pilot and Feasibility Program

The CF Research and Translation Core Center Pilot and Feasibility (P&F) program provides seed support for new and innovative research projects directed at basic biomedical, clinical and translational research questions relevant to cystic fibrosis complications in the mission of NIDDK. To be considered a viable P&F program, the Center must support a minimum of two pilot projects annually, up to a maximum of four pilot projects. It is anticipated that up to $75,000 in direct costs per year for up to two years will be provided for the majority of approved P&F projects. Efforts to increase the number of P&F awards and availability of funds for the program through the use of program income or alternative funding sources are particularly encouraged.

The P&F program is particularly directed at new investigators and established investigators new to CF research. Established CF investigators pursuing high impact/high risk projects that are a significant departure from their usual work are also eligible for support under the CF Research and Translation Core Center P&F program. P and F support is also encouraged for Investigators underrepresented in research. This Program should be integrated into the overall research goals of the Center and make use of the resources provided by the Cores. P&F programs may also be structured to provide support for establishing interdisciplinary collaborations and to help forge new partnerships between basic scientists and clinical researchers. In general, NIDDK expects CF Research and Translation Centers to solicit investigators at affiliated hospitals or institutions to participate in the Center P&F program. While the distribution of P&F funds to be used in each award category is ultimately at the discretion of the Center P&F committee, it is expected that the Center P&F program will, where possible, place particular emphasis on funding innovative clinical and translational research projects. The focus of new P and F projects should be within the NIDDK mission. All new P and F projects will require prior approval by NIDDK.

CF Research and Translation Centers Directors Meetings

NIDDK is planning to convene a meeting every other year for Center Directors and Associate Directors. This meeting will allow exchange of information on available Core activities and advances between CF Research and Translation Centers.

See Section VIII. Other Information for award authorities and regulations.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

o Hispanic-serving Institutions

o Historically Black Colleges and Universities (HBCUs)

o Tribally Controlled Colleges and Universities (TCCUs)

o Alaska Native and Native Hawaiian Serving Institutions

o Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are not allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
• o NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons.If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization 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 support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

Because a Cystic Fibrosis Research Center has a large and complex administrative structure, the PD/PI must have strong leadership abilities and demonstrated proficiency in managing large, multi-component programs. In addition, the PD/PI should be a recognized leader and authority in the CF research community. The PD/PI must be willing to participate in meetings of the CF Center Directors which are scheduled in years 1, 3 and 5 of the grant.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Only one application per institution (normally identified by having a unique DUNS number or NIH IPF number) is allowed.

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

Research Base: Successful CF Research and Translation Center applications require an existing program of excellence in biomedical research in Cystic Fibrosis. To justify Center support, the CF Research and Translation Center must serve a large research base of NIDDK and other NIH-funded investigators pursuing research activities in Center topic areas, as well as CF investigators with other sources of peer-reviewed support. NIDDK mission-related research should represent at least 40% of the research base. NIDDK research interests related to cystic fibrosis include mechanisms underlying the disease (excluding those associated with the specific development of lung disease), development of therapeutic approaches targeting or applicable to multiple organs, and elucidating pathophysiology and/or therapy directed at diabetes, and/or nutrition, gastrointestinal and liver complications of CF. While additional research interests outside the NIDDK mission (e.g., pulmonary complications of CF) may also be described and these research projects may utilize Center resources, applicant institutions should be pursuing major efforts directly related to NIDDK research priorities.

The application forms package specific to this opportunity must be accessed through ASSIST or an institutional system-to-system solution. A button to apply using ASSIST is available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

John Connaughton, Ph.D.
Chief, Scientific Review Branch
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-7797
Email: [email protected]

Available Component Types	Research Strategy/Program Plan Page Limits
Overall (Use for Overall)	12
Admin Core (Use for Administrative Core)	12
Core (Use for each Biomedical Research Core)	12
P and F Program (Use for Pilot and Feasibility Program)	12

Additional page limits described in the SF424 Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the SF424 (R&R) Application Guide, and should be used for preparing a multi-component application.

The application should consist of the following components:

• Overall: Required (Minimum: 1, Maximum of 1)
• Administrative Core (with Enrichment Program): Required (Minimum: 1, Maximum of 1)
• Biomedical Research Cores: Required (Minimum: 2, Maximum: 6)
• Pilot and Feasibility Program: Required (Minimum: 2, Maximum: 4)

When preparing your application, use Component Type Overall .

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

Complete entire form.

Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

Follow standard instructions.

Project Summary/Abstract: Describe the scientific theme(s) of the CF Research and Translation Center and the need for a Center to support the investigators in the research base. Include the number of Center members and the overall direct costs present in the research base. Provide a brief overview of the research base as it relates to the theme(s) of the Center, as well as an overview of the biomedical research cores, and the pilot & feasibility and enrichment programs.

Project Narrative: In 1-3 sentences describe the relevance of the research to be supported and facilitated by Center activities (Core services; Pilot and Feasibility, and Enrichment programs) on Cystic Fibrosis and public health.

Facilities and Other Resources: Describe the existing environment and facilities briefly in the context of how the Center will use or change existing access, space, and usage; include space maps as needed (see "Other Attachments") and letters of institutional commitment (see 'Letters of Support'). Scientific personnel and institutional resources capable of supporting the research base must be available.

Equipment: A general listing of major, shared pieces of equipment to be used by Center members should be provided. Note: Specific research core facilities, equipment and special resources should be listed in each proposed biomedical research core component.

Other Attachments: The following "Other Attachments" must be included with the Overall Component in order to aid in the review of applications. The filename provided for each attachment will be the name used for the bookmark in the application image. All attachments need to be in .pdf format.

Grant Support: Please title this attachment "Grant Support" and include all Federal and non-federal grant support for CF Research and Translation Center members. Complete and organize alphabetically by the last name of the Center Investigator who is listed as the Project Director/Principal Investigator (PD/PI) on the grant. Include Supporting Organization/Grant Numbers, Complete Grant Title, Project Period, Annual Direct Costs, and Identify Other NIDDK Centers (if the grant listed is also included in its research base). The attachment should include, in order: Current Grant Support (Table A.1), Other Grant Support (Table A.2) and Pending Grant Support (Table A.3). Examples of how Tables A.1, A.2 and A.3 might be formatted are provided for applicant assistance with this requirement (https://www.niddk.nih.gov/research-funding/process/apply/funding-mechanisms/p30/cystic-fibrosis-research-translation-center-application-resources). The 'Current Grant Support' table should include research project grants relevant to Cystic Fibrosis research, which are considered to be potential or likely users of the core services. 'Other Grant Support' should include infrastructure/services grants (other Centers or CTSA awards), training (such as T- or F-awards) grants, and other such grants that support CF-related research but would not be direct users of the core services.

Biographical Sketches of Center Research Base Investigators: Please title this attachment "Center Member Biographical Sketches." Provide biographical sketches for all Center members, as defined by the Center within the application, and organize them alphabetically by the last name of the Research Base Investigator, including any affiliated hospitals or proposed partners. These biographical sketches should use the NIH format.

Description of Center Research Base Investigators: Please title this attachment Description of Center Research Base Investigators and organize alphabetically by Center Member (last name). Provide a narrative description of no more than one page per research base investigator. These narratives should include: the active grant number(s), title(s), and a few descriptive sentences of the investigator’s research projects, as well as a brief description regarding what aspect of the investigator’s research justifies the use of Center core facilities. In the description of the research base, include ONLY those grants awarded, or subcontracted, to investigators at the applicant institution or consortium, not to investigators at other locations. It is particularly important to provide a few sentences indicating the relatedness of a cited grant to research in cystic fibrosis when this is not readily apparent from the project title of the grant.

Center Collaborations: Please title this attachment Center Collaborations and organize alphabetically by Center Member (last name, first name). List all Center Members. Provide primary Department Affiliation, key words for research interests, names of other Center members who are collaborators (through publications, grants or research projects), and the number of collaborative publications (only those relevant to the CF Center).

Optional: Please title this attachment "Relation to Overall Center". Provide Charts and Tables related to the Institutional Commitment at the applicant institution, such as an organizational chart(s) to illustrate the structure, interactions, and leaders of the institution and CF Research and Translation Center.

Enter primary site only.

A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this FOA) for the entire application.

A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.

A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

Introduction to Application: For Resubmission, an Introduction to Application is required in the Overall component.

Specific Aims: Describe the broad long-term objectives of the proposed CF Research and Translation Center. A strategic vision, theme and set of goals must be developed and described in the application. The plan should outline the existing skills and technologies available in the research base as well as other resources at the Institution(s). Provide a brief overview of the research base as it relates to the theme(s) of the Center, as well as a brief overview of the biomedical research cores, and the pilot & feasibility and enrichment programs. This plan should delineate how the Center will enhance ongoing projects, assist in the development of new projects, respond to future opportunities, and promote collaborations toward developing new treatments for CF.

Research Strategy: The Research Strategy should include the following sections instead of the ones listed in the application instructions.

Research Base:

The Center Core grant provides a mechanism for fostering interdisciplinary cooperation within a group of established investigators conducting high quality research on Cystic Fibrosis. Therefore, existence of a strong, substantial research base in CF is a fundamental requirement for, and the most important aspect of, the establishment of a Center. NIDDK mission-related research should represent at least 40% of the research base.

Applicants should include an overview of current research in CF and related areas being conducted at their institution in sufficient detail to allow reviewers to judge its extent and the interrelationship of ongoing research. The relevance to CF of all research included in the research base should be described. Applicants should indicate how the establishment of a Center will provide added dimensions, such as greater focus and increased cooperation, communication and collaboration that would not likely occur without Center resources.

A high level of integration and close collaboration among Center personnel from diverse scientific disciplines is an important feature of a successful CF Research and Translation Center. Accordingly, the applicant should clearly state considerations for Center membership with specific reference to the potential of members to form interactive, collaborative and synergistic relationships. Criteria for becoming a CF Research and Translation Center member should be clearly defined. Each Center, however, is expected to formulate these definitions based on its own situation. Center membership and affiliation are often open to those individuals who would like to promote the mission of the Center. Specific membership criteria, and any affiliation categories (if applicable), should be clearly defined by the Center Director in order to better organize and facilitate the focus of the Center’s mission. Subsets of members based on their degree of participation or other quantitative measures are acceptable. Applicants should provide clear guidelines for a) how Center membership(s) is (are) defined; b) the application and selection processes for Center membership; and c) the obligations of Center membership. Suitable criteria include, but are not limited to, peer-reviewed independent funding, participation in CF-related research, and the need for the use of core facilities. All research base investigators should be Center members. Designation as a Center member without the need for the use of core facilities must be well justified.

Presentation of the research base in the application should be done in two ways: (1) by completing a Table (see "Other Attachments) and (2) by a full narrative description of the CF and related research activities at the applicant institution and any collaborating institutions. This presentation should be organized into several areas of emphasis that demonstrate the research focus of the Center. The research of each Center participant should be discussed and interrelationships of research being conducted by Center participants should be highlighted. Since most, if not all, of the research base will have undergone separate peer review, the quality of the individual funded projects is already established. The more important aspects are: (a) interactions and interrelationships of the research efforts; (b) uses and benefits of core services; (c) plans to develop productive collaborations among Center investigators; and (d) willingness of Center investigators to contribute to the overall objectives of the CF Research and Translation Center.

Strategic Vision:

Theme Provide the central theme(s) of the CF Research and Translation Center and the likely supported research, resources, and relevance to CF. The theme may be broad or focused, depending upon the goals of the Center. For clearer presentation, it is recommended that Center applicants subdivide the research base into areas of research emphasis or central research themes that link Center members and their research programs. Appropriate presentation of the research base is very important since its assessment is a primary emphasis in the evaluation of an application. Major themes should be relevant to NIDDK research interests related to cystic fibrosis which include mechanisms underlying the disease (excluding those associated with the specific development of lung disease), development of therapeutic approaches targeting or applicable to multiple organs, and elucidating pathophysiology and/or therapy directed at diabetes, and/or nutrition, gastrointestinal and liver complications of CF. While additional research themes outside the NIDDK mission (e.g., pulmonary complications of CF) may also be described and these research projects may utilize Center resources, applicant institutions should be pursuing major themes directly related to NIDDK research priorities.

Goals and Directions Describe the current and future directions for the CF Research and Translation Center in the forthcoming project period. Indicate how the research supported by the Center impacts the understanding of CF and its complications. Describe the short, mid- and long-term goals and measures of success. Describe the likely advances expected in the field of CF. Describe the expected, widely-applicable research tools and scientific advances that will emerge from the Center’s emphasis. Describe any basic science work that has successfully been translated to the bedside or plans to enhance that translation in the next project period. Outline the impact of interdisciplinary studies and collaborations, especially among basic scientists and clinical researchers. Renewal applications must also describe the accomplishments of the Center in the preceding project period and how it intends to build upon its successes. These accomplishments should be presented, as appropriate in the areas of basic science and clinical research. The impact of Center-based science should be discussed in detail. Since one of the objectives of the Center is to extend research relevant to CF, new areas of research and acquisition of new funding should be highlighted in the overview. The progress and accomplishments in the research base, to development of multidisciplinary, collaborative, and cooperative interrelationships, and to alteration in the original Center design in order to meet the evolving needs of the research base should be discussed.

Biomedical Research Cores should be discussed and their role in the Strategic Vision described. Summarize the services and resources provided by the CF Research and Translation Center; describe how the biomedical research cores will address the scientific needs of the research base. Brief examples of ongoing or planned research should be discussed as appropriate with reference to the supporting Core. Proposed Cores should not focus on pulmonary aspects of CF.

Integration of investigators of multiple skills and talents Outline steps the CF Research and Translation Center will take to promote interdisciplinary studies and collaborations, especially among basic scientists and clinical researchers. Describe the types of initiatives that will stimulate the teams and attract high-caliber professionals. Applicants should describe any academic and research partnerships that have been or will be pursued in order to advance the goals and mission of the Center.

Building research capacity Provide details on the special talents and resources that will be drawn to and built upon at the CF Research and Translation Center. Indicate how these talents will be harnessed and used to promote new collaborations and produce multidimensional teams to address more complex questions. Describe academic and research partnerships that will be pursued by the CF Research and Translation Center to advance its goals and missions. Describe how the P and F program will help build research capacity. The focus of new P and F projects should be within the NIDDK mission. All new P and F projects will require prior approval by NIDDK.

Provide a plan to determine the need for services and instrumentation of the Center. Address the steps that will ensure that the CF Research and Translation Center proceeds at the cutting edge of technology and concepts. It is expected that biomedical research cores needs may change with time. Include information on the process of re-evaluation of needs and implementation of changes.

Within this section, describe the research capacity and clearly identifiable major scientific focus in CF research. The CF Research and Translation Center initiative fosters interdisciplinary cooperation among established investigators conducting high-quality research related to CF. Therefore, existence of a strong research capability in CF is fundamental to establishment of a new, or continuation of an existing, CF Research and Translation Center.

Innovation:

Address how the CF Research and Translation Center will not only evolve with the science conducted by the Center Investigators, but also challenge and seek to advance or change current research or clinical practice paradigms by using novel theoretical concepts, approaches or methodologies, instrumentation, or interventions. Explain how the synergy of the Center with the research base will lead to novel services and resources in the Cores and their application to important questions in CF research. Describe the potential for interdisciplinary collaborations among Center Investigators. For a Biomedical Research Core that by its nature is not innovative, describe how it is essential to advance the field.

Summarize the services and resources provided by the Center, and how they are managed and coordinated. Describe how the Center will address the scientific needs of the research base. Indicate if any of the proposed cores will utilize or expand cores already existing at the institution. Describe how the proposed Center will leverage existing resources and fill gaps in the services available. Also, describe how the Center will enhance the research base through enrichment activities.

Leveraging of existing resources is encouraged, particularly when this provides a range of services or efficiency that would not otherwise be available. Furthermore, applicants should demonstrate that support for the existing resource through the CF Research and Translation Center provides added value to the resource beyond that which would be provided by paying for use of the resource through a fee for service. Applicants from institutions that have a Clinical Translational Science Award (CTSA) funded by the NIH may wish to identify the CTSA as a resource for conducting the proposed research, if appropriate. In such cases, appropriate letters of support from the CTSA program director or principal investigator should be included with the application detailing plans for appropriate integration and synergy of the CF Research and Translation Center and CTSA activities (See Letters of Support).

In addition, applicants should address the potential for integration, harmonization, and enhancement of CF Research and Translation Center activities through cooperation with other NIH- supported core facilities at the applicant institution. Applicants are encouraged to suggest coordinated efforts, such as enrichment programs or pilot and feasibility programs. Other NIH-supported Centers and associated Cores at the institution should be identified, and assurances provided that overlap or redundancy in Center activities will be avoided unless expressly required to fulfill the mission of the CF Research and Translation Center.

For new applications: Emphasize the anticipated impact of the establishment of a CF Research and Translation Center on the research base. Include an indication of how the establishment of a CF Research and Translation Center will provide added dimensions and new opportunities for CF and related research, along with increased cooperation, communication, and collaboration among investigators.

For renewal applications: Briefly, describe the progress in the research base during the previous project period including development of multidisciplinary, collaborative, and cooperative interrelationships, and any alterations in the original Center design in order to meet the evolving needs of the research base. These accomplishments should be presented, as appropriate, in the areas of basic science, clinical research, public health, prevention, and translation. Since one of the objectives of the Center is to extend research relevant to CF, new areas of research and acquisition of new funding should be highlighted in the overview.

Progress Report Publications List (renewal applications only): List the titles and complete references to all appropriate publications, manuscripts accepted for publication, patents, and other printed materials that have resulted from the project since it was last reviewed competitively. This should be done by using the Consolidated Publications List (Table G) (see this link ) which assists applicants with documenting the contribution of individual cores to peer-reviewed publications by the research base. Only list publications once. Within individual biomedical research core descriptions, refer to publications associated within the core by number as listed in the table of publications. Use an asterisk to indicate any publication that fails to cite Center grant support.

Letters of Support: Include any letters of support for the proposed Center by appropriate institutional officials. Letters should address the commitment of the parent organization, or any of its partners, to the CF Research and Translation Center and its goals. The parent institution is expected to recognize the CF Research and Translation Center as a formal organizational component and provide documented evidence of space dedicated to the needs of the Center, protected time to devote to Center activities, staff recruitment, dedicated equipment, or other financial support for the proposed Center. The parent institution should provide assurance of its commitment to continuing support of the CF Research and Translation Center in the event of a change in directorship and a well-defined plan for this eventuality should be in place. In addition, it is expected that the Institution will support the goal of providing to Center members priority access to Institution’s and Center’s facilities and services at minimal or reduced cost. Both the institution and pertinent departments must show a strong commitment to supporting the Center.

A letter from the PD/PI of any related NIH-funded T32 at the Center institution should be included that acknowledges and details how the PD/PI of the T32 intends to promote cohesive interactions between the two programs.

If collaborations are being developed between the CF Research and Translation Center and the local CTSA staff and/or research personnel, a letter of agreement from the CTSA PD(s)/PI(s) should be included. For any collaborations between the CTSA and a specific Biomedical Research Core, the letter of support should be included within the specific Biomedical Research Core component of the application.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Overall)

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).

All instructions in the SF424 (R&R) Application Guide must be followed

All instructions in the SF424 (R&R) Application Guide must be followed.

When preparing your application, use Component Type Admin Core.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components

Other Attachments (renewal applications only; optional): Additional information related to the Center-supported Enrichment Program activities, such as agendas/announcements for Cystic Fibrosis Research and Translation Center retreats, symposia, workshops, meetings, specialized courses, seminar series, etc., illustrating the interactions among Center members and other investigators, as well as other educational opportunities may be included in the application. This should be loaded as a file in .pdf format titled "Enrichment Program"..

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Center Director and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• The P30 Center Director PD/PI must be the Administrative Core Director. The Center Director PD/PI should be an experienced and respected scientist with a proven track record for obtaining NIH funding. She/he must be able to coordinate, integrate, and provide guidance in the establishment of new programs in CF research. If there are multiple PD/PIs, then these must be Co-Administrative Core Directors.
• In this component, also provide biographical sketches for any consultants. For renewal applications only, provide biographical sketches for the members of the External Advisory Committee. These biographical sketches should use the NIH format. In the additional Senior/Key Profiles section, list those Senior/Key persons in the Project Role of "Other" with Category of "Consultant" or "Advisory Committee." New applications should NOT contact potential External Advisory Committee (EAC) members nor provide names or biographical sketches for EAC members; overall qualifications and areas of scientific expertise for the EAC members may be included.

Budget forms appropriate for the specific component will be included in the application package.

Personnel: The Center Director must provide an at least 1.2 person month effort on the Administrative Core and a total of 2.4 person months effort distributed among the Administrative and other components of the Center. In a multiple-PD/PI application, the combined effort of the PD/PIs must equal 2.4 person months. Where possible and applicable, CF Research and Translation Centers are encouraged to leverage administrative resources in other NIH funded centers (e.g. Diabetes Research Centers, Centers for Diabetes Translation Research, Nutrition Obesity Research Centers, and Clinical and Translational Science Awards) to maximize efficiency of resources.

Travel: Include the costs of domestic and foreign travel only if the travel is directly related to the activities of the CF Research and Translational Center which should include travel for external advisors and guest speakers. Include travel costs for the Center Director and Associate Director (s) to attend the CF Research and Translation Center Directors meetings in Bethesda, Maryland in years 01 and 03 and 05.

Equipment: If pieces of specialized equipment, or computers, costing more than $5,000 are requested, the application must identify similar equipment already available within the institution and provide a clear justification for purchase based on core service provided to CF Research and Translation Center investigators. Requests for general-purpose equipment should be included only after ascertaining the availability of such items within the institution. Justify the request based on this availability. Equipment may only be requested in the initial budget period.

Supplies: Consumable supplies directly related to the operational aspects of the Administrative Core facilities are an allowable expense.

Consultants: Include costs associated with consultants (consultant fees, per diem, teleconferences and travel) when their services are required by the CF Research and Translation Center, such as the members of the External Advisory Board.

Other Expenses: Funds for supporting a CF Research and Translation Center website may be requested. Include funds to support Enrichment Program activities such as workshops, research fora, symposia, Center retreats and seminar series. Funds for Enrichment Program-associated activities such as the printing and distribution/mailing of brochures, programs, and meeting materials, as well as posters and other advertisement materials, may be requested.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component

Specific Aims: Clearly state how the Administrative Core will set the overall direction for the Center, prioritize Center resources, provide external review of Center functions and organize enrichment activities. In addition, there needs to be an indication of how the Administrative Core interacts with the other Cores and Programs to achieve the goals of the Center and ensure optimal utilization of Center Resources.

Research Strategy: The CF Research and Translation Center must be an identifiable organizational unit within a university medical center or a consortium of cooperating institutions including the university-affiliated Center. Such a Center will involve the interaction of broad and diverse elements; thus, lines of authority and approval by the appropriate institutional officials must be clearly specified. The Administrative Core plays a key role in the coordination and functioning of the Center.

The applicant should describe how the Administrative Core will take a leadership role in setting the overall direction of the Center. In addition, direct lines of communication between the Administrative Core and Biomedical Research Cores as well as with the P&F Program should be delineated, as all of these cores/programs serve critical roles for Center integration. Procedures for reviewing the utilization, quality and necessity of Core services must be described.

Centers should describe policies and procedures for changes in core function over the life of the Center. These will allow Centers to adapt to the development of new technologies, existing technologies may no longer be needed, or economic changes such as commercial services may replace core services. Provide a plan to determine the need for services and instrumentation of the Center.

Each applicant institution specifies one or more Center Director(s) (PD(s)/PI(s)) to be responsible for the scientific and administrative leadership of the Center. If multiple Center Directors are proposed, the application must document their complementary expertise. The Director(s) should be an experienced and respected scientist with a proven track record for obtaining NIH funding. She/he must be able to coordinate, integrate, and provide guidance in the establishment of new programs in CF and related research. One or more Associate Directors should be named who will be involved in the administrative, scientific, or educational enrichment efforts of the Center and will serve as Acting Center Director in the absence of the Director. A process must be described that would be used to recommend a successor to the Director, if needed.

Applicants should describe any educational enrichment opportunities provided by the CF Research and Translation Core Center for Center participants, and document ways the Center may facilitate, enhance or foster the institutional educational enrichment environment. Specifically, Center applicants should provide information on related educational/training programs at the Center institution(s) and describe how the CF Center will help to integrate, facilitate and enhance activities of trainees.

The CF Research and Translation Core Center enrichment program must be designed to advance translational research in CF and promote scientific exchange among investigators with research interests in these topic areas, and to enhance interactions between CF researchers and investigators from other fields with relevant expertise. The enrichment program can support activities such as seminars, guest speakers, visiting scientists, consultants, and workshops. The applicants should describe the enrichment program at the Center.

It is expected that organization of the Administrative Core will provide a supportive structure sufficient to ensure accomplishment of the following:

• Coordination and integration of the CF Research and Translation Center components and activities.
• Assessment of productivity, effectiveness, and appropriateness of the CF Research and Translation Center activities, assessment of scientific opportunities, and areas for collaboration among Center members.
• Develop criteria for Center membership and a process for reviewing and updating membership.
• Organization of CF Research and Translation Center enrichment activities, such as retreats, invitation of consultants, meetings, and seminars.
• Organization of the Internal and External Advisory Committees to coordinate and review Center activities.
• Recordkeeping of meeting minutes and measures of success including: use of Center facilities, publications, pilot and feasibility awards, and new grant applications resulting from preliminary data enabled by the CF Research and Translation Center.
• Interactions with other CF Research and Translation Centers, the NIDDK, and other appropriate individuals, groups, or organizations.
• Maintenance of a Center website, with the administrative core taking primary responsibility for its curation and oversight.

Center Evolution: Centers must document policies and procedures for ensuring continuing evolution of core services in response to changing needs. New technologies or services might appear that should be supported, existing technologies might become less important, or economic changes might obviate the need for core services, such as the availability of cost-effective commercial services or core services provided by the research institution. Cores should address the issue of allocation of resources to development of new technologies versus provision of services with existing technologies. In addition, cores must have well-defined policies to ensure that intellectual property is identified and appropriately protected, but that intellectual property issues do not impede sharing of resources. Include a plan for bringing investigators into the Center from within and outside the area of CF research who might provide new technologies. What expertise will these individuals share with the Center?

The administrative structure must include an Internal Advisory Committee (IAC) and an External Advisory Committee (EAC). New applications should not list members of the EAC but should describe what expertise is needed. Renewal applications must list the members of the Internal and External Advisory Committees and document their functions and effectiveness.

The final administrative structure of the Center will be left largely to the discretion of the applicant institution. However, past experience has demonstrated that the effective development of the Center programs requires close interaction between the Center Director, Core/Program Leaders, appropriate institutional administrative personnel, the staff of the awarding agency, and the members of the community in which the Center is located. Therefore, each Center applicant should establish an administrative structure that will permit the development of such interactions. Within this structure, each applicant institution must also establish a mechanism to oversee the use of funds for the proposed pilot and feasibility program. This mechanism must include the use of appropriate consultants for review from the scientific community outside the Center institution. Consultants who will serve on advisory committees should not be specifically identified in the application but the process by which they will be selected should be described. These same consultants may be utilized, if desired, for review of other activities of the Center.

Enrichment Program: The CF Research and Translation Center enrichment program should be designed to advance translational research in CF and promote scientific exchange among investigators with research interests in these topic areas, and to enhance interactions between CF researchers and investigators from other fields with relevant expertise. The enrichment program can support activities such as seminars, guest speakers, visiting scientists, consultants, and workshops. Applicants should describe any educational opportunities afforded by the CF Center for Center participants, and document ways the Center may facilitate, enhance or foster the institutional educational environment. Specifically, Center applicants should provide information on NIDDK or other NIH Institute T32 or K12 programs at the Center institution(s), and describe how the CF Center will help to integrate, facilitate and enhance activities of T32-supported trainees of K12/KL2-supported scholars.

Training postdoctoral fellows to conduct research in CF is an associated activity of a Center. While stipends for fellows cannot be funded from the Center, the establishment of a Center should provide an enhanced environment for educational and enrichment opportunities. Just as in the case of funding for individual research projects, funding for fellowships should be sought from NIH NRSA institutional training grants (e.g. T32, T35) and individual fellowships (e.g. F30, F32), and other sources such as private foundations, and commercial companies.

Letters of Support: A letter(s) from the PD/PI of any related NIH-funded T32 and/or T35 institutional training grant(s) at the Center institution should be included that acknowledges and details how the PD/PI of the T32 or T35 training grant intends to promote cohesive interactions between the two programs. Such letters should also briefly describe how any short-term (e.g. summer) medical student research programs, supported by NIH-funded T32 or T35 training grants, coordinate with Center activities related to the proposed Enrichment Program. Include any other letters of support for the proposed Core, as appropriate.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

Appendix:

Only limited items are allowed in the Appendix.Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Administrative Core)

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the SF424 (R&R) Application Guide must be followed.

Biomedical Research Core

When preparing your application in ASSIST, use Component Type Core. Separate 'Core' components should be created for each individual Biomedical Research Core proposed including optional Regional/National Shared Resources Cores. All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

A biomedical research core is a shared facility that provides a needed service to Center investigators enabling them to conduct their funded individual research projects more efficiently and/or more effectively. Cores should be designed to furnish a group of investigators with materials, techniques, determinations, instrumentations, and/or quality control to enhance research and contribute to cost effectiveness. A recharge mechanism is acceptable to help defray costs to the Center. If such a cost recovery system is developed, a detailed charge justification must be presented. Participating Center members must also be informed to include such costs with their full budget justifications in their applications for individual grant support. Cores may be proposed to support any research activity of the Center, but usually fall into one of five categories: (1) provision of a technology that lends itself to automation or preparation in large batches; (2) complex instrumentation; (3) animal preparation, care and characterization; (4) clinical resources; and (5) service and user training. Limited developmental research is also an appropriate function of a core facility. Such activities, however, must be directly related to enhancing the function or utility of the Core. Proposed Cores should not focus on pulmonary aspects of CF.

Proposed Center research cores may be an institutional shared research core. In such cases, the research core support provided by the CF Research and Translation Center should be proportional to the use of the institutional research core by Center members.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Biomedical Research Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Biomedical Research Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Biomedical Research Core)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Facilities and Other Resources: The description of the physical arrangements, instrumentation and any other resources for the cores should be given special attention. Arrangements for sufficient space for core activities or for access to appropriate established facilities must be made. Centers are strongly encouraged to enter into cooperative arrangements with cores already established within their institution, or with other Centers in close proximity, when the existing cores offer the services needed. These arrangements are important whenever greater efficiency or cost savings can be realized by such an agreement. When proposing the use of a shared facility, details about access, fee-schedules, and prioritization of Center members' use of the shared facility must be described. It may be advantageous for a CF Research and Translation Center to provide support for appropriate personnel to work specifically for Center members in an existing facility/core (e.g., transgenic animal core) at the institution. In that case, the designated CF Research and Translation Center Core Director must work closely with the parent facility Core Director to coordinate services, unless the same individual assumes both roles.

Other Attachments: The following "Other Attachments" must be included within each Biomedical Research Core in order to aid in the review of applications. The filename provided for each attachment will be the name used for bookmark in the application image. All Attachments should be in a pdf format.

Core Facility Use: Please title this attachment "Core Facility Use" and indicate each Core user, funded project that supports the Core use, period of Core use, services used and estimated use. Table E is provided for applicant assistance with this requirement (https://www.niddk.nih.gov/research-funding/process/apply/funding-mechanisms/p30/cystic-fibrosis-research-translation-center-application-resources).

Project /Performance Site Location(s) (Biomedical Research Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Biomedical Research Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Director and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• Where appropriate, an established expert in the core activities may also be included as a consultant to the core.

Budget (Biomedical Research Core)

Budget forms appropriate for the specific component will be included in the application package.

Personnel: A core Director must devote a minimum of 1.0 person month to the Core to ensure adequate oversight. A co-director or other professional or technical staff may be included. The salary amount charged to the CF Research and Translation Center grant must be commensurate with the time spent on Core activities and is subject to institutional and NIH salary policies. Stipends for graduate students and postdoctoral fellows are not appropriate for Biomedical Research Cores. The PD/PI must devote a total of 2.4 person months effort distributed among the Administrative and other components of the Center. In a multiple-PD/PI application, the combined effort of the PD/PIs must equal 2.4 person months.

Equipment: If specialized equipment costing more than $5,000 is requested, the application must provide a clear justification based on the Core services being provided to CF Research and Translation Center Investigators. Requests for general-purpose equipment should be included only after ascertaining the availability of such items within the institution. Justify the request based on this availability. A shared cost within the Institution may be required for equipment purchased through the Center. Requests for general-purpose equipment should be included only after ascertaining the availability of such items within the institution. Justify the request based on this availability. Equipment may only be requested in the initial year of the project period.

Supplies: Consumable supplies directly related to the Core are an allowable expense. This includes office materials as well as laboratory supplies. The supply budgets of separately funded individual research projects must be appropriately reduced to reflect such support, thus eliminating duplication.

Research Patient Care Costs: Research patient care costs (both in-patient and out-patient) are an allowable expense. Attempts should be made to utilize existing clinical facilities, such as those supported by Clinical and Translational Science Awards (CTSAs) and individually supported beds. If the CTSA is to be used, include a letter of agreement from the PD/PI of the CTSA; such a letter (in .pdf format) may be attached as a 'Letter of support' for the appropriate Biomedical Research Core(s). Request costs relating to the clinical research efforts of CF Research and Translation Center investigators ONLY if there is no overlap with other funding. Costs already budgeted in individual projects should be appropriately reduced if such costs are to be transferred to the Center. The CF Research and Translation Center is not intended to be a facility for health care delivery. Thus, only those patient costs directly related to research activities may be charged to the Center.

Travel: Funds for Center investigators/faculty to attend national or international scientific meetings or workshops may not be requested. If well-justified and related directly to Core activities/functions, limited travel funds for Core professional staff may be requested to support travel to national scientific meetings/workshops.

Consultants: Include costs associated with consultants (e.g. consultant fees, per diem, teleconferences, and travel) when their services are required by the core.

Other Expenses: Funds for equipment maintenance/service contracts may be requested but should reflect an equivalent percentage of the service contract based on the overall use by the Center Investigators. The budget justification for any maintenance/service contracts should document usage of the equipment by Center members. Only in very rare cases should full support for a maintenance/service contract be requested, and strong justification must be provided in such cases.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Biomedical Research Core)

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.

Specific Aims: Clearly state the aims of the Biomedical Core.

Research Strategy: Cores may be based solely at the applicant institution or at multiple institutions through subcontracts. If subcontracts are to be utilized the applicant must clearly demonstrate how a cohesive and integrated operation will be ensured and describe the advantages of this approach to the performance of core functions. The Center may also provide resources for funded projects at collaborating institutions without a subcontractual arrangement with the parent institution. Proposed Center research cores may be an institutional shared research core. In such cases, the research core support provided by the CF Research and Translation Center should be proportional to the use of the institutional research core by Center members. As with other research cores, details about access and prioritization of center members to the shared research core(s) should be provided. Moreover, the applicant should document that the CF Research and Translation Center will be in a position to have some input to, and oversight of, the shared institutional core with respect to its management, planning for future changes and improvements, etc.

Expanded Cores: Centers are encouraged to propose Cores that provide unique expertise or technology to a community outside the Institution. These could be on a regional, national or an international level. An Expanded Core may define its own Center research base which is expanded to include investigators from outside of the Center. It may include investigators that just use this resource or service but do not have a formal collaboration with other Center investigators. If an Expanded Core is proposed, please provide the basis for this justification.

Justification for proposing a core: The establishment and continued support of biomedical research cores within a Center are justified on the basis of use by independently funded Center investigators. The minimum requirement for establishing a core is significant usage by two or more investigators with independently-funded, peer-reviewed projects. While investigators holding awards from the Center pilot and feasibility program are appropriate users of the core facilities, their use does not contribute to justification for establishment or continued support of a core. Additionally, the minimum of two independently funded users does not in itself provide sufficient justification. Core usage should be documented in the "Core Facility Use" attachment in Other Attachments above. Please describe a justification for each proposed Core. Proposed Cores should not focus on pulmonary aspects of CF.

Recharge/program income system: A recharge system may be developed to allow investigators to utilize any core. Recharge fees are allowable budgetary items in the investigators' individual research project grants. A system of payment management/accounting must be established such that it is clear to the individual users, the institutional business office, and the NIDDK what the recharge system covers and how funds recovered are being used. Program income must be re-invested into direct support of Center-related activities and/or expenses and may not generate a profit for the Center. This will enable Center investigators to appropriately adjust the budgets on their own grants and ensure accountability. Please describe any recharge system that is used by the Center.

Management of the core and operational plan: The organization and proposed mode of operation of each core should be presented. Included should be a plan for prioritizing investigator use of the core as well as a definition of qualified users. If use by investigators outside the parent institution is proposed, the mechanism by which such investigators will apply and be evaluated and selected should be detailed. The definition of qualified users should not be too narrow. Some minor core use could serve to entice established investigators in other scientific disciplines into CF research. Any proposed, ongoing or completed developmental efforts should be described. If the core is used to train investigators in special techniques, the mechanism for this training should be included.

Applicants should provide information on other programs supporting related resources at their institution and describe the nature of synergy and integration between the CF Research and Translation Center and these other activities. Applicants must also clearly describe how duplication or redundancies of effort, services and resources will be avoided.

Centers are strongly encouraged to enter into cooperative arrangements with cores already established within their institution, or with other Centers in close proximity, when the existing cores offer the services needed. These arrangements are important whenever greater efficiency or cost savings can be realized by such an agreement. However, it should be clear that the CF Research and Translation Center cores can function independently. It may be advantageous for a CF Center to provide support for appropriate personnel to work specifically for CF Center members in an existing facility/core (e.g., transgenic animal core) at the institution. In this case, the designated CF Center Core Director must work closely with the parent facility Core Director to coordinate services, unless the same individual assumes both roles. These arrangements are important whenever greater efficiency or cost savings can be realized by such an agreement. Therefore, financial justification such as comparative costs of other sources of proposed core services as well as plans for cost recovery from users should be detailed.

Because cooperation between CF Research and Translation Centers is also encouraged, but not required, any plans to work with one or more other established CF Research and Translation Centers may be provided along with a description of the benefit(s) to the Center being proposed. Benefits might include, but are not limited to, cost savings, ability to provide additional or improved services, or enhanced productivity by Center members.

Renewal applications: Information relative to cores in renewal applications should generally cover all of the same points as new applications. In addition, past performance and accomplishments should be described and highlighted. The effect of the service provided by a core on investigator productivity and cost effectiveness should also be addressed. In renewal applications, any changes should be carefully documented.

Progress Report Publication List: Core productivity and accomplishments as demonstrated by peer-reviewed research publications supported by the core should be documented; list the number(s) of the relevant publication(s) from Table G above (Center Overview Progress Report and Publications List).

Letters of Support: For Expanded Cores, include letters of support from outside investigators who would use these Cores. If a Clinical and Translational Science Awards (CTSA) is being used a letter of agreement from the PD/PI of the CTSA is required. This letter in pdf format should be attached as a "Letter of support" for the appropriate Biomedical Research Core. Also, provide letters to address the career potential of, and institutional commitment to junior scientists who serve as core managers/technical directors. In addition, other letters of support for the proposed Core may be included, as appropriate

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

Appendix: Limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Biomedical Research Core)

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study

All instructions in the SF424 (R&R) Application Guide must be followed.

When preparing your application in ASSIST, use Component Type P and F Program.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Pilot and Feasibility Program)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Pilot and Feasibility Program)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Pilot and Feasibility Program)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Other Attachments: The following "Other Attachments" must be included with the Pilot and Feasibility Program component in order to aid in the review of applications. The filename provided for each attachment will be the name used for the bookmark in the application image. All attachments should be in .pdf format.

Pilot Project Outcomes (renewal applications only): Please title this attachment "Pilot Project Outcomes" and list all Pilot Projects supported in full, or in part, by the CF Research and Translation Center. Provide information on the most recent 5 or, if applicable, 10-year period. Include the years funded, awardee, dates and amount of P&F funding, pilot project title, P&F award type (i.e. new investigator; established investigator), number of abstracts and publications derived from pilot support, subsequent grants funded or pending applications (including grant number/funding agency and project period), and whether the P&F awardee is still involved in CF research. Table F is provided for applicant assistance with this requirement (https://www.niddk.nih.gov/research-funding/process/apply/funding-mechanisms/p30/cystic-fibrosis-research-translation-center-application-resources ).

Pilot Project Summary/Abstract (all applications): Please title this attachment "Pilot Project Information" and provide a Project Summary/Abstract for each proposed pilot and feasibility project, as well as the biographical sketch of the investigator for each of the proposed pilot and feasibility projects.

Project /Performance Site Location(s) (Pilot and Feasibility Program)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Pilot and Feasibility Program)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of P and F Program Director and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• The P and F program must have a director who is an established investigator in cystic fibrosis research.

Budget (Pilot and Feasibility Program)

Budget forms appropriate for the specific component will be included in the application package.

Personnel: This category should include salary support for the P&F Program Director who must devote a minimum of 1.0 person month to ensure adequate oversight. The PD/PI must devote a total of 2.4 person months effort distributed among the Administrative and other components of the Center. In a multiple-PD/PI application, the combined effort of the PD/PIs must equal 2.4 person months. The salary amount charged to the CF Research and Translation Center grant must be commensurate with the time spent on P and F Program activities and is subject to institutional and NIH salary policies.

Consultants: Include costs associated with consultants (e.g. consultant fees/honoraria, per diem, and teleconferences) when their services are required by the Pilot and Feasibility Program, such as any external reviewers for P and F applications.

Other Expenses: Include funds to support individual Pilot & Feasibility projects. Each center must support a minimum of 2 P&F and a maximum of 4 projects which can be up to $75,000 per year each. The applicant should provide details on how F&A costs for P&F projects with partnering institutions will be handled.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Pilot and Feasibility Program)

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.

Specific Aims: Clearly state the aims of the Pilot and Feasibility Program.

Research Strategy: A Pilot and Feasibility study provides modest research support for a limited time (one to two years) to enable eligible investigators to explore the feasibility of a concept related to the mission of the Center and generate sufficient data to pursue the project through other funding mechanisms. The pilot and feasibility studies are intended to: (1) provide initial support for new investigators; (2) allow exploration of possible innovative new leads or new directions for established investigators and (3) stimulate established investigators who are new to CF research to apply their expertise to research in this area. Pilot and feasibility study support is not intended for large projects by established investigators which would otherwise be submitted as separate research grant applications. Pilot and feasibility funds are also not intended to support or supplement ongoing funded research of an established investigator.

Requirements: Each Center must contain a pilot and feasibility program with a minimum of 2 projects. A maximum of 4 projects can be requested. The focus of new P and F projects should be within the NIDDK mission. All new P and F projects will require prior approval by NIDDK.

Eligibility and related guidelines: Investigators eligible for pilot and feasibility funding generally fall into three categories: (1) new investigators without current or past NIH research support (R01, P01) as a PD/PI (current or past support from other sources should have been modest); (2) established investigators with no previous work in CF who wish to apply their expertise to a problem in this area; and (3) established investigators who propose testing innovative ideas that represent clear departure from ongoing research interests. It is expected that the majority of the investigators will fall into the first category. All eligible investigators, however, must have faculty appointments and be independent investigators. Postdoctoral fellows or their equivalents are not eligible. Each pilot and feasibility study proposal should state clearly the justification for eligibility of the investigator under one of the above three criteria.

A proposed pilot and feasibility study should present a testable hypothesis and clearly delineate the question being asked, detail the procedures to be followed, and discuss how the data will be analyzed. It must be on a topic related to the objectives of the Core Center. Projects should be focused, since funding for these studies is modest and is limited to two years or less. Any one investigator is eligible only once to receive this support, unless the additional proposed pilot and feasibility study constitutes a real departure from his/her ongoing research.

Pilot and Feasibility projects proposing clinical studies are encouraged. The National Center for Advancing Translational Sciences (NCATS) supports Clinical and Translational Science Awards (CTSA) nationwide, which provide services and resources to enhance clinical research (https://ctsacentral.org). Research Centers supported by the NIDDK and other NIH Institutes and Centers are encouraged to collaborate with CTSAs to avoid duplication of effort and enhance utilization of services and resources.

Initial review and management of the pilot and feasibility program: By the very nature of this program, a significant responsibility for its management will be left to the Center administration during the project periods. The application should clearly describe and justify the pool from which potential pilot and feasibility applications will be solicited. This can be limited to investigators at the parent institution or expanded to include investigators at institutions with well-defined affiliation with the Center. Such an affiliation can occur either through a subcontractual relationship for support of core resources or through inclusion of funded projects at a collaborating institution in the research base utilizing the shared resources of the Center. The mechanisms by which information on the availability of pilot and feasibility awards will be disseminated and by which applicants will apply, undergo review, and be selected for these awards must be described and will be an important element in the review of the pilot and feasibility component of the Center.

Since pilot and feasibility studies can be awarded for any period of time up to two years, studies end at various times. In addition, the studies may also be terminated by the Center administration before their approved time limit for various reasons: e.g., (1) the investigator may receive outside funding for the project; (2) the project was found not to be feasible; (3) the investigator may leave the Center institution; etc. When this occurs, the Center may make new awards for pilot and feasibility studies with the remaining funds.

While a Center's administrative framework for management of the pilot and feasibility program is basically left up to each Center (the framework is subject to NIH peer review), certain minimal requirements must be met. There must also be a committee representing all the aspects of the Center which will assist the director in the management of the program. The major responsibilities of the director and the committee will be to:

• Maintain oversight and review of ongoing pilot and feasibility studies;
• Develop and maintain a mechanism for the oversight and review of ongoing P and F projects; this is especially important as a requirement for a second year of P and F support;
• Make recommendations regarding termination or other actions to the Center Executive Committee (or equivalent);
• Prepare and ensure appropriate distribution of announcements of the availability of pilot and feasibility funding;
• Arrange and preside over the scientific merit review of proposals. At least one reviewer from outside the parent institution must be used for each proposal. All reviewers should assign impact scores in accordance with the NIH system. Copies of all of the proposals with written documentation of their reviews, priority/impact scores, and final action must be retained by the Center;
• Maintain, insofar as is possible, a record of subsequent career events of each pilot and feasibility study recipient. This record must also be made available to reviewers at the time of the renewal application;
• Make recommendations to the Center Executive Committee (or equivalent) for final decisions. A record of actions by this committee must be documented.
• Ensure adequate institutional plans and procedures to assure compliance with applicable federal regulations and NIH policies for the protection of human research participants, including the evaluation of risks and protections in project proposals, appropriate ethical oversight of funded projects, and plans for monitoring data and safety in clinical research projects when human research subjects are involved in pilot and feasibility awards;

All applicants should describe how these requirements will be met and have been met in the case of renewal applications. Also, included should be an assessment of the relevancy of the proposed individual pilot and feasibility studies and of the program as a whole to research on cystic fibrosis and to the specific goals, objectives and uniqueness of the individual Center and of the Center program generally.

Pilot and Feasibility program in new application: Applicants should provide (see "Other Attachments") an abstract for each proposed pilot and feasibility project, and the biographical sketch of the investigator of the proposed pilot and feasibility project; these pilot and feasibility proposals are reviewed for scientific merit and eligibility by the applicant Institution's review group. These initial pilot and feasibility studies must have been reviewed by the Center in the manner proposed for review of future studies so that only those considered to be of the highest quality are included in the grant application. The amount of pilot and feasibility funds provided for the first year will be based on the review of the proposed studies. The budget for future years is recommended by the institutional review group based on the quality of the proposed pilot and feasibility studies, and the proposed method for management and review (as evidenced by this set of projects). Also considered will be the review group's evaluation of the future justification for continued pilot and feasibility support.

Pilot and feasibility program in renewal applications: Applicants should provide (see "Other Attachments") an abstract for each proposed pilot and feasibility project, and the biographical sketch of the investigator of the proposed pilot and feasibility project; these pilot and feasibility proposals are reviewed for scientific merit and eligibility by the applicant Institution's review group or process. These initial pilot and feasibility studies must have been reviewed by the Center in the manner proposed for review of future studies so that only those considered to be of the highest quality are included in the grant application.

After the initial review of pilot and feasibility proposals as described above, responsibility for review during the remainder of the project period will reside within the Center itself. After this internal review process, all new P and F projects will require prior approval by NIDDK. This approach provides each Center with the needed flexibility for effective and efficient management of the program. In renewal applications, the review of this program will be based on the past track record, the management of the program, and an assessment of overall potential needs and opportunities.

The historical overview will cover the pilot and feasibility program since the inception of the Center. This should include a list of all pilot and feasibility projects ever awarded. The pilot and feasibility program director may wish to highlight certain studies or certain aspects of the past studies. Collaborations which resulted in lasting relationships, acquisition of new skills by the study recipient, or other significant outcomes should be identified. The relationship of the scope of the various studies to that of the Center should be emphasized.

The description of Center management of the program will present in detail the current system used to manage the pilot and feasibility program, including its integration with and relationship to the rest of the administrative structure. The use of outside consultants for review should be included in the discussion. Important features of the solicitation process should be provided including the distribution and the number of respondents.

Funding levels for the pilot and feasibility program on renewal applications: The format for renewal of pilot and feasibility programs will depend on whether the applicant is requesting: (1) a number of pilot projects less than or equal to that for the previous project period, or (2) an increase in the number of pilot projects.

If the applicant wishes to maintain the same number of pilot projects in a renewal application, the recommendation of the NIH review group will be based on the overall performance of the center's pilot and feasibility program as documented in the application. This recommendation will be based on: (1) the extent to which awarded funds were fully utilized during the previous project period; (2) awards were made to investigators who fully met the eligibility criteria for pilot and feasibility support as outlined above; (3) Center-relatedness; and (4) success of previously supported pilot and feasibility studies (e.g., publications, subsequent independent R01 or other peer-reviewed support, and/or attraction of new investigator into Center related research).

Conversely, should the applicant institution feel that an increased level of funding for the pilot and feasibility program is justified, new pilot and feasibility studies, over and above the number currently awarded, must be submitted with the renewal applications. These proposals would be reviewed by the NIHreview group in a fashion similar to the review of pilot and feasibility studies during the initial review. The NIH review group would assess the new proposals, along with the overall performance of the program during the previous grant period to arrive at a recommendation for a possible increased pilot and feasibility funding level.

Letters of Support: Include any letters of support for the Pilot and Feasibility Program by the appropriate institutional official at partnering organizations if applicable.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

Appendix: Limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Pilot and Feasibility Program)

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study

All instructions in the SF424 (R&R) Application Guide must be followed.

For applications proposing P and F Programs that will accept projects that include Delayed Onset Human Subjects Research or Delayed Onset Clinical Trials, provide a plan to address the protection of human research participants, including the evaluation of risks and protections in project proposals, appropriate ethical oversight of funded projects, and plans for monitoring data and safety in clinical research projects.

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov.

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies) using ASSIST or other electronic submission systems. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

For information on how your application will be automatically assembled for review and funding consideration after submission go to: http://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) and component Project Leads must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management (SAM). Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Many NIH ICs encourage the use of common data elements (CDEs) in basic, clinical, and applied research, patient registries, and other human subject research to facilitate broader and more effective use of data and advance research across studies. CDEs are data elements that have been identified and defined for use in multiple data sets across different studies. Use of CDEs can facilitate data sharing and standardization to improve data quality and enable data integration from multiple studies and sources, including electronic health records. NIH ICs have identified CDEs for many clinical domains (e.g., neurological disease), types of studies (e.g. genome-wide association studies (GWAS)), types of outcomes (e.g., patient-reported outcomes), and patient registries (e.g., the Global Rare Diseases Patient Registry and Data Repository). NIH has established a Common Data Element (CDE) Resource Portal" (http://cde.nih.gov/) to assist investigators in identifying NIH-supported CDEs when developing protocols, case report forms, and other instruments for data collection. The Portal provides guidance about and access to NIH-supported CDE initiatives and other tools and resources for the appropriate use of CDEs and data standards in NIH-funded research. Investigators are encouraged to consult the Portal and describe in their applications any use they will make of NIH-supported CDEs in their projects.

Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

In addition, for applications involving clinical trials:

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

For this P30 Funding Opportunity Announcement, note the following:

Reviewers will be asked to evaluate the following individual sections. The overall impact score is not the average for these components.

• Research Base, including the focus, quality of research, collaborations among members, relevance to the Center's stated research focus, and, for renewal applications, the growth, re-focusing, or evolution of the research base.
• Each Biomedical Research Core, including: the potential of the core to empower CF research by promoting new research directions and creating CF-specific research opportunities that are not available through commercial or institutional resources; the documented need for and use of the proposed services; number of users; qualifications of personnel; management, including prioritization and responsiveness to the needs of the users; quality control management; and any appropriate developmental work.
• Administrative Core, including committee structure, Center membership criteria, Enrichment Program and lines of communication.
• Pilot and Feasibility Program, including the organization of the overall process of solicitation, review, and monitoring of P and F projects, and for renewal applications the quality, appropriateness and outcomes of supported P and F projects.
• CF Research and Translation Center Director (PD/PI), including leadership and commitment to the stated goals of the CF Research and Translation Center.

Center Pilot and Feasibility Programs have the option to support Clinical Trials.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the Center to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the Center proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a Center that by its nature is not innovative may be essential to advance a field.

Does the Center address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the Center are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

In addition, for applications involving clinical trials

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

Specific to this FOA: Does the research base to be supported by the Center show evidence of a strong and consistent record of productivity and peer-reviewed funding related to the proposed focus of the Center? Does NIDDK mission-related research represent at least 40% of the research base? Do the proposed Cores fill a need in the CF research Community, and will they provide services that would otherwise be unavailable, or be more cost-effective if centralized? Do the focus, relevance, interrelationships, quality, productivity, and, to some extent, quantity of the research base support the stated theme of the Center? Will the research base investigators benefit from the services/programs supported by the Center? Will the Center increase efficiency; promote new research directions and collaborations; and prove cost effective? If collaborations with other CF Research and Translation Centers, or individuals outside of the research base are described, do they enhance the productivity or quality of the research base; enhance the services offered by the Center; strengthen the Enrichment Program; allow for a more efficient use of the Center's available resources; or otherwise benefit the research base?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the Center? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

In addition, for applications involving clinical trials

With regards to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

Specific to this FOA: Do the proposed Center Director and Associate Director(s) have the appropriate administrative and leadership experience necessary as well as available time to direct a multicomponent Center? Are the Core Directors well-qualified and appropriate? Are the Center investigators responsible for the individual components willing to interact with each other and contribute to the overall objectives of the CF Research and Translation Center?

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

In addition, for applications involving clinical trials

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

Specific to this FOA: Do the Cores provide new methods, techniques, and/or resources that are not available through commercial or existing institutional resources? Do the Cores demonstrate the ability to adapt when needed to support investigators in emerging areas of CF, as appropriate to the purpose of the Core and the research supported by the Center? Does the Center appear to encourage high-risk , innovative ideas through their P and F program?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the Center? Have investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the Center involves human subjects and/or NIH-defined clinical research, are the plans to address:

1) the protection of human subjects from research risks, and

2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

If the Center involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (exclusion) of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Are there adequate institutional plans and procedures to assure compliance with applicable federal regulations and NIH policies for the protection of human research participants, including the evaluation of risks and protections in project proposals, appropriate ethical oversight of funded projects, and plans for monitoring data and safety in clinical research projects?

In addition, for applications involving clinical trials

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

Specific to this FOA: Are criteria for membership in the CF Research and Translation Center clear and appropriate? Is the major theme of the Center relevant to NIDDK research interests? Is the administrative structure appropriate to monitor Core usage, prioritization, and quality? Are the proposed Cores appropriate for the focus of the Center? Are the proposed Cores not focused on pulmonary aspects of CF? Do the Cores provide added value to what is available elsewhere and will they stimulate the development of new approaches? Is there an appropriate structure to solicit, evaluate, award and monitor the pilot and feasibility studies?

How appropriate and relevant are the proposed cores and the modes of operation (such as potential utilization, prioritization of requests for services, cost-recovery, and quality control monitoring)? Will the cores provide opportunities not otherwise available to the investigators through other available federally-funded and/or institutional resources; represent appropriate cost savings/cost sharing advantage; and stimulate the development of new approaches? If proposed, is support through an institutional biomedical research core well-justified, and would it provide added value and access to the resource that is beyond that which would be provided for the use of the institutional core through a fee-for-service process? Is there any role for the research cores in supporting either new investigators or established investigators moving into CF research? Is appropriate administrative organization proposed for the following:(a) coordination of ongoing research between the separately funded projects and the Center, including mechanisms for internal monitoring;(b) establishment and maintenance of internal communication and cooperation among the Center investigators;(c) mechanism for selecting and replacing professional or technical personnel within the cores;(d) management capabilities, including fiscal administration, procurement, property and personnel management, planning, budgeting, and other appropriate capabilities? Is there efficient and effective use and/or planned use of the limited enrichment funds, including the contribution of these activities to the stated goals of the Center?

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

In addition, for applications involving clinical trials

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

Specific to this FOA: Is there evidence of institutional commitment to the Center program, including lines of accountability, regarding management of the Center grant and the institution's contribution to the management capabilities of the Center? Is there clear potential for interaction with scientists from other departments and institutions?

As applicable for the Center proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Study Timeline

Specific to applications involving clinical trials:

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

When the proposed Center involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

For resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

For Renewals, the committee will consider the progress made in the last funding period.

Research Base: Does the Center show evidence of a stable or growing research base with strong and consistent record of scientific excellence and achievement reflected in an outstanding level of productivity and continuing success in securing peer-reviewed research funding? Does the Center show evidence of fostering multi-disciplinary collaborations among its Center investigators? Have such collaborations resulted in new research directions?

Biomedical Research Cores: Are the number and impact of research publications that acknowledge the Center sufficient to justify each core? Is there a significant fraction of papers that a) acknowledge the Center and b) do not have core personnel as co-authors? Are the number and listing of Center investigators who have used the core and resultant key advances consistent with the level of core investment? Do the number and listing of investigators who have used the core multiple times indicate satisfaction and continuing need for core services? Are there sufficient numbers of users who are not core personnel or their collaborators? Are the number and listing of users who are not Center personnel or members consistent with the best utilization of the core by the community? Are the numbers of services/tests completed by each core indicative of sufficient utilization ? Is the capacity of each core with current resources sufficient to serve the needs of the Center community? Does the Center provide evidence of ability to evolve cores to meet changing needs of the research community? Does the Center provide evidence of Program Income and/or sufficient institutional support? If applicable, has the national/regional shared resource core been effective as well as beneficial to both the Center members and partnering institution(s)?

Administrative Core (with Enrichment Program): Has the administrative structure proven effective? Has oversight of Center activities, including the P and F and Enrichment programs, been effective? Does the Center website show evidence of continuing maintenance and a high level of quality and usability? Has the Enrichment program fostered multidisciplinary approaches to CF research and to attract new investigators or investigators with relevant expertise to CF research?

Pilot and Feasibility Program: Are the numbers and types of P and F awards well justified and related to the goals of the Center? Was the P and F program fully utilized during the previous project period? Were awards made to investigators who fully met the eligibility criteria (as described in the FOA) for pilot and feasibility support? Are data provided to document the outcome of all P and F projects completed in the last five years, including those that failed to lead to further funding? Has the P and F program led to publications of significant impact, subsequent independent R01 or other peer-reviewed support, and/or attracted new investigators into nutrition/obesity-related research? Are research papers generated under these awards, projects successfully funded with independent grants, and key advances linked to these awards well-documented and consistent with the level of support provided? For those Centers who provided P and F support to investigators new to CF research and/or to experienced CF researchers with innovative ideas, were the P and F awardees successful in their outcomes?

Not applicable

As applicable for the Center proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Not applicable.

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genomic Data Sharing Plan .

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s), convened by the NIDDK in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Diabetes and Digestive and Kidney Diseases Advisory Council . The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain applicable clinical trials on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration of all trials whether required under the law or not. For more information, see http://grants.nih.gov/ClinicalTrials_fdaaa/

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols. Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

Awardee-selected Pilot and Feasibility projects, a complete project application (including biographical sketches, personnel and budget justification, research plan, human and/or animal subject sections and any IACUC, IRB or other required documentation), and the critiques of the proposals by the Advisory Committee must be provided to NIDDK with the Just in Time information or prior to the start of the Pilot and Feasibility projects. Awardee-selected projects that involve clinical trials or studies involving greater than minimal risk to human subjects require prior approval by NIH prior to initiation.

• The awardee institution will provide NIH with written study protocols that address risks and protections for human subjects in accordance with NIH s Instructions for Preparing the Human Subjects Section of the Research Plan.
• The awardee institution will provide NIH with specific plans for data and safety monitoring, and will notify the IRB and NIH of serious adverse events and unanticipated problems, consistent with NIH DSMP policies.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

Thomas L Eggerman, MD, PhD.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK))
Telephone: 301-594-8813
Email: [email protected]

Ryan Morris, PhD
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-480-1296
Email: [email protected]

Mark Langer
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-827-6167
Email: [email protected]

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

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 Part 52 and 45 CFR Part 75.