NIH’s new Application Submission System & Interface for Submission Tracking (ASSIST) is available for the electronic preparation and submission of multi-project applications through Grants.gov to NIH. Applications to this FOA must be submitted electronically; paper applications will not be accepted. ASSIST replaces the Grants.gov downloadable forms currently used with most NIH opportunities and provides many features to enable electronic multi-project application submission and improve data quality, including: pre-population of organization and PD/PI data, pre-submission validation of many agency business rules and the generation of data summaries in the application image used for review.

Required Application Instructions

It is critical that applicants follow the 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) and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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

The NIAID invites applications from single institutions, or consortia of institutions, to participate in the Nonhuman Primate Transplantation Tolerance Cooperative Study Group (NHPCSG) program. The overarching goals of the NHPCSG are to: (1) develop novel tolerance induction regimens; (2) evaluate the preclinical safety and efficacy of existing and newly developed candidate immune tolerance induction regimens; (3) develop and validate biomarkers for the induction, maintenance and/or loss of immune tolerance or for the prediction of graft rejection; and (4) elucidate the mechanisms underlying the induction, maintenance, and/or loss of tolerance in NHP allograft models of kidney, pancreatic islet, heart, and lung transplantation. The currently funded cooperative agreement grants in the NHPCSG will expire in FY 2017. This FOA and the companion FOA (RFA-AI-16-007) solicit single project (U01) and multi-project (U19) cooperative agreement grant applications for milestone-based research projects focused on NHP models of kidney, pancreatic islet, heart, and/or lung transplantation tolerance to achieve the goals listed above. Prior funding under this program is not required.

Organ transplantation is the preferred treatment for many end-stage organ diseases when other therapies have failed. However, despite significant advances in immunosuppressive medications over the past 20 years that have led to one-year graft survival rates that approach or exceed 90% for most organs, long-term graft and patient survival remains unsatisfactory. Pancreatic islet transplantation as a therapy for type 1 diabetes mellitus (T1D), an autoimmune disease characterized by the destruction of the insulin-secreting beta cells in pancreatic islets, is an investigational therapy for those T1D patients whose disease cannot be effectively managed with exogenous insulin administration, and like organ transplantation, requires the use of life-long immunosuppressive medications.

The overwhelming leading cause of failure of a transplanted organ or pancreatic islets, both short- and long-term, is immune-mediated graft injury. Life-long, generalized immunosuppressive therapy is necessary to prevent immune-mediated injury, but is associated with substantial morbidity and is not always completely effective at preventing immune-mediated injury. Therefore, a key goal of transplantation research is to develop therapeutic strategies for the induction of durable immunologic tolerance to transplanted organs and cells, thus eliminating the need for long-term immunosuppressive medications. Achieving this goal will increase long-term graft survival and life expectancy, and improve health-related quality of life. NHP transplantation studies are a critical step in attaining these goals by providing key supporting data for the design of scientifically sound and ethically acceptable clinical trials. The value of the NHP transplantation model is due, in part, to the close approximation of the NHP immune system and physiology to those of humans.

NIAID is strongly committed to developing safe and efficacious immune tolerance induction regimens that result in enhanced long-term graft survival and reduced morbidity in clinical transplantation. In 1998, the NIAID convened an Expert Panel for Research on Immune Tolerance that endorsed the conceptual framework, scope and timeliness of NIAID’s plan to accelerate research in this area. Two subsequent panels, the NIAID Expert Panel on Ethical Issues in Clinical Trials of Transplant Tolerance and the Expert Review Panel for NIAID's Extramural Transplantation Research Program, identified NHP tolerance research as an essential step to provide "...critical data on safety, toxicity and potential efficacy that cannot be obtained ethically in human clinical trials . In 1999, in response to these recommendations, NIAID and NIDDK formally established a program in NHP models of allogeneic kidney and islet transplantation and expanded and renewed the program in subsequent years, with the last renewal in 2012 (RFA AI-11-039 (U01), RFA AI-11-040 (U19)). In 2004 the scope of the NHPCSG was expanded to include heart and lung transplantation models. This expansion reflected the need to improve outcomes of human heart and lung transplantation, as well as the view that graft rejection is an immunological disease with underlying mechanisms that may be shared across all organs and tissues, and that different organs and tissues may offer unique insights into various facets of immune tolerance induction and graft rejection. The heart and lung portion of the NHPCSG was most recently renewed in 2010 (RFA AI-09-041). The scope of this current renewal U19 FOA and companion U01 FOA (RFA AI-16-007) includes NHP models of allogenic islet, kidney, heart, and lung transplantation.

NIAID has established breeding colonies of specific pathogen-free (SPF) cynomolgus macaques (Macaca fascicularis) and Indian-origin rhesus macaques (Macaca mulatta) to support the research efforts of the NHPCSG; however, NIAID does not guarantee the availability of these animals to NHPCSG investigators. Over the long-term, in addition to providing a reliable supply of animals, this investment will provide the unique opportunity to have fully pedigreed and major histocompatibility complex (MHC)-defined colonies, and the capacity to optimize the utility of the colonies through directed-breeding. Most significantly, this resource will enable researchers to design more powerful studies and better evaluate experimental outcomes through knowledge of the degrees of relatedness and MHC disparity or identity between donors and recipients. In addition, NIAID supports the NHP Reagent Resource http://www.nhpreagents.org/NHP/default.aspx, which develops, produces, and distributes immunologic reagents optimized for use in NHP research, including antibodies for NHP in vitro immuno-diagnostics, and primatized immuno-modulating or immuno-depleting recombinant antibodies and fusion proteins for in vivo administration. The NHPCSG has collaborated with the NHP Reagent Resource in the evaluation and/or development of numerous reagents that are now in use by the wider researcher community.

The NHPCSG is a key component of the NIH mandate to translate basic discovery research to the clinic. NHPCSG funded investigators have made many advances over the years and provided key supporting data for several clinical trials, some of which are ongoing or currently under development. Four external scientific advisory panels have reviewed the NHPCSG program, including a 2005 NIH Expert Panel on Transplantation and NIDDK convened meetings in 2005, 2009 and 2011: Meeting on the Special Statutory Funding Program for Type 1 Diabetes Research, Ad Hoc Planning and Assessment Meeting on Preclinical Type 1 Diabetes Research, and Workshop on Research Supported by the Special Statutory Funding Program for Type 1 Diabetes Research, respectively. All external scientific panels have concurred that this preclinical research program is a critical and high priority area of transplantation immunology research that merits continued support. Currently, the NHPCSG includes seven U01 and two U19 awards that will expire in FY 2017. Therefore, this FOA and the companion, RFA-AI-16-007, solicit new or renewal applications for NHP islet, kidney, heart and lung models of transplantation tolerance to continue the NHPCSG program.

This FOA calls for the use of NHP species for studies of allogeneic islet, kidney, heart, and/or lung transplantation. The scope of the proposed research must encompass the overarching goals of the NHPCSG, including: (1) development of novel tolerance induction regimens; (2) evaluation of the preclinical safety and efficacy of existing and newly developed candidate immune tolerance induction regimens; (3) development and validation of biomarkers for the induction, maintenance and/or loss of immune tolerance or for the prediction of graft rejection; and (4) elucidation of the mechanisms underlying the induction, maintenance, and/or loss of tolerance in NHP allograft models of islet, kidney, heart, and/or lung transplantation.

While individual approaches may vary significantly, the research scope of the applications is restricted to, and must be clearly relevant to, the following two broad areas:

Tolerogenic Approaches:

• In vivo NHP assessment of novel candidate immune tolerance induction agents or novel refinements or modifications of existing immuno-modulating agents or regimens, including development of these agents if required.

Mechanisms/Biomarkers:

• Definition of the underlying immunologic mechanisms of action of the therapeutic approaches under investigation and/or the mechanisms of induction, maintenance and/or loss of tolerance.

And/or

• Development, evaluation, and validation of biomarkers or other novel means for the assessment of the induction, maintenance and/or loss of immune tolerance and/or for the onset of acute or chronic graft rejection.

All U19 individual research projects must contain at least one tolerogenic approach and must have at least one aim devoted to mechanisms and/or biomarker studies (one of the above) or have mechanistic and/or biomarker studies incorporated as integral parts of the research aims.

Note: Additional objectives related to the immune tolerogenic approach or immunologic mechanistic studies may be addressed, such as alternative transplantation sites for pancreatic islets, as long as the primary focus of the application meets the requirements above.

In addition to the requirements above:

• Applicants are encouraged to include collaborations between NHP transplant model researchers and investigators outside this research community, including basic science transplant biologists and immunologists.
• Use of new technologies, including minimally invasive and non-invasive approaches, is encouraged.

Because the long-range goals of this FOA are to develop and evaluate candidate tolerogenic approaches for transplantation in humans, the NIAID expects that there will be communication between the NHPCSG and NIAID-funded clinical trials programs. In addition, this interaction may result in potential opportunities to develop and participate in preclinical studies of safety and efficacy that are necessary for a particular NIAID-sponsored clinical trial.

Applications proposing the following will be considered non responsive and will not be reviewed.

• Studies in animal models other than NHPs, unless the model is used solely as an in vivo assay for assessment of the NHP immune response.
• Human studies or clinical trials.
• Xenotransplantation.
• Preliminary development of a NHP transplantation model.
• Studies focused on improving the isolation, preservation, or supply of organs, tissues, or cells.
• Hematopoietic stem cell transplantation unless in the context of islet or organ transplantation (e.g. bone marrow chimerism experiments).
• Transplantation studies with any organs or tissues other than pancreatic islet, kidney, heart, or lung, unless in the context of islet, kidney, heart, or lung transplantation (e.g. thymus or thymic tissue transplantation as a means of tolerance induction in an islet, kidney, heart or lung model).
• Studies of non-immunological side effects of an immunomodulatory agent.

Applicants are advised to contact the Scientific/Research Contact with any questions they may have regarding the responsiveness of their application.

Milestones

Each U19 project research plan will encompass a milestone-based approach with explicit, detailed, and quantitative yearly milestones. These milestones will be used by NIAID program staff to assess progress and recommend continued funding on an annual basis.

Infrastructure and Opportunities Fund

To capitalize on emerging opportunities and sharing of resources and expertise consistent with the goals of the NHPCSG, an Infrastructure and Opportunities Fund (IOF) of $350,000 total costs per year for the NHPCSG program will be made available for emerging opportunities, pilot and feasibility research and administrative management of the IOF. One institution will be chosen by NIH after award from the successful applicants to manage the IOF. This institution must agree to take responsibility for managing the IOF for the entire NHPCSG. Management of the IOF will involve establishing an administrative structure, making consortium pilot project awards, tracking funds and reporting the status of funds and progress to NIH and the NHPCSG Steering Committee. Examples of activities supported by the current IOF include development/maintenance of an internal website for NHPCSG activities, and new pilot and feasibility research and research resource development projects. IOF projects are submitted by members of NHPCSG and may include collaborating investigators from outside the NHPCSG.

Steering Committee

The Steering Committee responsibilities include identifying scientific opportunities, emerging needs, and impediments, and establishing and overseeing group collaborations. In addition, the Steering Committee oversees the scientific aspects of the IOF, including advising on the goals, priorities, and evaluation criteria for the use of these funds.

Nonhuman Primate Resources

NIAID owns and maintains specific pathogen-free (SPF) breeding colonies of cynomolgus macaques (Macaca fascicularis) and Indian-origin rhesus macaques (Macaca mulatta) to support the studies funded through the NHPCSG. Provision of NHPs from the NIAID breeding colonies to NHPCSG investigators is determined by availability, scientific priority, and equitability. The NIAID Project Scientist makes final decisions regarding allocation of these resources. The Steering Committee provides scientific advice and recommendations to the NIAID regarding breeding strategies, testing, and other considerations to optimize the long-range value of these resources to the research community.

NIAID does not guarantee availability of animals to NHPCSG investigators, particularly when special NHP requirements of a study are limiting, e.g. full or half sibling pairs that are MHC haplotype matched or specific gender requirements. In addition, two of the NIAID breeding colonies (Indonesian- and Mauritius-origin cynomolgus macaque colonies) are young and may not meet the complete needs of the NHPCG in the initial years following award. The Indian-origin rhesus macaque breeding colony is mature and meeting the rhesus needs of the current NHPCSG. However, future availability will depend on the species and country-origin requirements of the awardees and the number of research-aged animals available each year. At such time as the number of animals from the NIAID colonies are sufficient NIAID requires awardees to use animals from these colonies for their NHPCSG studies. Applicants should also be aware that once a colony is mature both male and female progeny will be provided and investigators will be required to take both sexes. NIAID will work with the awardees to accommodate provision of optimal cohorts.

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 in response to 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:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• 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)
• Eligible Agencies of the Federal Government
• 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 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) (formerly CCR) 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.
• 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 and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. 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.

• An investigator may be a PD/PI, multiple PD/PI or U19 Project Leader on only a single application (either RFA-AI-16-007 or RFA-AI-16-008).
• A PD/PI, multiple PD/PI, U19 Project Leader, or U19 Core Leader may serve as a collaborator on another U01 or U19 Project or Core (see companion FOA: RFA-AI-16-007) provided there is no scientific overlap between the applications.
• A U19 Core leader, if not the PD/PI or multiple PD/PI of the U19 or U01 or Project Leader of a U19, may serve as a Core Leader on another U19 provided there is no scientific overlap between the applications.
• Multiple PDs/PIs are allowable on the overall application, however; only one U19 Project Leader or Core Leader is acceptable on the project or core level of the application.
• Each PD/PI or multiple PD/PI must commit a minimum of 1.8 calendar months per year to ensure success of the program. Each U19 Project Leader must commit a minimum effort of 1.2 calendar months per year.

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

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

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).

Applicants can access the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

Most applicants will use NIH’s ASSIST system to prepare and submit applications through Grants.gov to NIH. Applications prepared and submitted using applicant systems capable of submitting electronic multi-project applications to Grants.gov will also be accepted.

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions 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.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

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:

James T. Snyder, PhD
Telephone: 240-669-5060
Email: [email protected]

Component Types Available in ASSIST	Research Strategy/Program Plan Page Limits
Overall	12
Admin Core	6
Core (Scientific Core and Infrastructure and Opportunities Fund Management Core)	6 each
Project (use for Research Projects)	12 each

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; maximum of 1
• Administrative Core: required; maximum of 1
• Infrastructure and Opportunities Fund Management Core: required; 1
• Scientific Cores: optional
• Research Projects: required; minimum of 2

When preparing your application in ASSIST, 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.

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.

Specific Aims: List in priority order, the broad, long-range objectives and goals of the proposed Program. Concisely and realistically describe the hypothesis or hypotheses to be tested.

Research Strategy: This narrative section summarizes the overall research strategy for the multicomponent application, including the significance, innovation and approach of the program and should highlight the program's conceptual unity. The multi-component application should be viewed as a confederation of interrelated research projects, each capable of standing on its own scientific merit, but complementary to one another and interactive. This is an important section for it provides the group of investigators an opportunity to give conceptual wholeness to the overall program by giving a statement of the general problem area and by laying out a broad strategy for attacking the problem. As the strategy develops, each project and core should be cited briefly as to its place in the overall scheme. Summarize the special features in the environment and/or resources that make this application strong or unique. To highlight program synergy, applicants may describe how the individual components will be coordinated and work together to address the overall goals and aims of the program. Include a schematic overview of the interactions and collaborations among the components, and indicate collaborations among members and relevant publications coauthored by members of the program. Program synergy may also be addressed in other sections of the application, as appropriate. Renewal applications should contain a brief description of progress.

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, with the following modification:

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

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

When preparing your application in ASSIST, 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.

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 Core Lead 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.

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

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.

Specific Aims: List in priority order, the broad, long-range objectives and goals of the proposed Administrative Core. In addition, state the core's relationship to the proposed Program's goals and how it is related to the individual Research Projects and Cores in the application.

Research Strategy: The Core Lead is responsible for the application and collaborative research activities. Explain the plans for organizational and administrative management of the overall program, and for coordination and communication within the program and with the NHPCSG Steering Committee. Explain the methods that will be used for monitoring progress in the projects and effective use of any shared resource or scientific cores (if applicable). Explain the plans for management of day-to-day program activities and contractual agreements (if applicable), and a plan for resolution of disputes. If data and statistical analysis are a component of the Administrative Core include detailed plans for these activities.

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, with the following modification:

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

PHS Inclusion Enrollment Report (Administrative Core)

When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

When preparing your application in ASSIST, use Component Type Core

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

SF424 (R&R) Cover (IOF 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 (IOF Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (IOF 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.

Project /Performance Site Location(s) (IOF 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 (IOF Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead 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.

Budget (IOF Core)

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

Application budgets must include the following costs:

• A maximum of 0.36 calendar months' salary for the IOF Management Core Leader.
• A minimum of 4.0 calendar months' salary for an IOF administrator and a maximum of 3.0 calendar months for Information Technology staff (if required) to be included in the Other Personnel category.
• IT computing supplies, if required.
• Costs for pilot/feasibility project per year should be included in the Other Direct Costs category for the remaining funds.
• IOF travel for either the IOF administrator or IT staff member to attend the annual NHPCSG Steering Committee meeting in Bethesda/Rockville, Maryland area.

Note: The Institution's indirect costs for salary, supplies, IOF travel, and IOF projects is included in the proposed $350,000.

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 (IOF Core)

Specific Aims: List the proposed activities and services of the IOF Management Core. Concisely describe how the IOF will operate to serve the NHPCSG.

Research Strategy:

The IOF management plan must include:

• an administrative structure;
• plans for the logistics for review of pilot projects, including receipt of applications and maintaining a review website;
• proposed procedures to support the Steering Committee in the timely award of consortium agreements, including the time interval for establishment and renewal of consortium agreements;
• tracking and monitoring of timely submission and payment of invoices, and plans for handling consortium agreement administration delays;
• plans for interacting with the institutions that will receive IOF funds;
• reporting on the status of the funds and consortium agreements awarded;
• providing an administrative assistant to coordinate these activities with the NIAID, NHPCSG Steering Committee and the institution s grants and contracts staff;
• providing IT support for the maintenance and/or development of an internal NHPCSG website, if required; and
• plans and procedures to ensure that all projects supported from the IOF comply fully with all applicable Federal regulations, policies, and guidelines for research involving nonhuman primates.

Include a statement from the PD/PI (or contact PD/PI if a multi-PD/PI application) agreeing to take fiscal responsibility for the management of the Infrastructure and Opportunities Funds, if chosen by NIAID to administer the fund. This includes the logistics for review of pilot projects, including receipt of applications and maintaining a review website.

The research strategy section for the IOF Management Core applies only to the management of the IOF and this section should NOT include any IOF proposed research projects or review process.

Letters of Support: Provide a letter from the Institution’s signing official agreeing to take fiscal responsibility for the management of the Infrastructure and Opportunities Funds, if chosen by NIAID to administer the fund. This includes the logistics for review of pilot projects, including receipt of applications and maintaining a review website.

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, with the following modification:

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

PHS Inclusion Enrollment Report (IOF Core)

When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment

Report as described in the SF424 (R&R) Application Guide.

When preparing your application in ASSIST, use Component Type Core.

Scientific or Resource Cores may include, but are not limited to, assays or other procedures, resources, and data management and analyses.

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

SF424 (R&R) Cover (Scientific 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 (Scientific Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Scientific 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.

Project /Performance Site Location(s) (Scientific 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 (Scientific Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead 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.

Budget (Scientific Core)

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

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 (Scientific Core)

Specific Aims: List in priority order the broad, long-range activities and resources of the proposed Core. In addition, state the Core’s relationship to the program’s goals and how the Core relates to two or more individual research projects in the application.

Research Strategy: Use this section to describe how the proposed Core activities will contribute to meeting the Program’s goals and objectives. In addition, this section should indicate the relevance of the Core to the primary theme of the application. The application must indicate the specific projects to be served by the Scientific Core(s). The activities of Scientific/Resource Cores must not overlap with those of a proposed project. Include a clear description of the facilities, skills, and techniques to be provided by the Core and describe the interactions of the Core Lead and each of the Scientific Projects.

Letters of Support: Provide any letters of support from collaborators that are specific to the Scientific or Resource Core.

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, with the following modification:

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

PHS Inclusion Enrollment Report (Scientific Core)

When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

When preparing your application in ASSIST, use Component Type Project.

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

SF424 (R&R) Cover (Research Project)

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 (Research Project)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Research Project)

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: Complete this section for each project as you would for an individual grant application. Note: ASSIST screens will show an asterisk for this attachment indicating it is required.

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

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 (Research Project)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead 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.

Budget (Research Project)

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

Purchase of Animals:

• Costs for purchasing animals through sources other than the NIAID animal colonies should be included in the Budget due to the possibility that NIAID animal resources may be inadequate to meet all of the research needs of the NHPCSG or meet the special requirements of projects. Therefore, document under the budget justification reasonable expectation of availability of animals proposed for studies from sources other than the NIAID breeding colonies.
• When NHPs are provided from the NIAID colonies, costs for all shipping, handling, and special testing fees will be the responsibility of the grantee. In future years NIAID may implement a cost recovery program for provision of the NIAID animals. NIAID may elect to decrease the award by the amount budgeted for purchase of animals when these animals are supplied through the NIAID colonies.
• Note that if animals from the NIAID breeding colonies are available for proposed studies, they may not be available for shipment to non-US sites, depending on the country’s import regulations and cost considerations.

Travel: Proposed budgets should include travel costs for the Project Leader and one additional investigator to attend the annual NHPCSG Steering Committee Meeting in the Bethesda/Rockville, Maryland area.

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 (Research Project)

Specific Aims: List the broad long-range objectives and goals of the proposed project. Concisely and realistically describe the hypothesis or hypotheses to be tested. In addition, state the individual project's relationship to the Program’s goals and how it relates to other projects or cores.

Research Strategy: Use this section to describe how the proposed research will contribute to meeting the Program’s goals and objectives and explain the rationale for selecting the methods to accomplish the specific aims. In addition to stating the biological significance of the research, indicate the project's relevance to the primary theme of the application. In addition to the standard scientific description, the interactions among projects and core facilities should be described within each Project.

Note: All projects must include at least one tolerogenic approach and must have at least one aim devoted to mechanisms and/or biomarker studies or have mechanistic and/or biomarker studies incorporated as integral parts of the research aims.

Treatment Protocols, Objectives and Yearly Milestones

• Include a synopsis and a treatment diagram/timeline detailing the proposed treatment protocol(s) and clearly defined experimental endpoints, and a conceptual framework providing rationale for the proposed approach to tolerance induction and the relevance to human transplantation.
• Include clearly stated interim and long-term objectives to be achieved during the project, with impediments and/or critical decision points that could require a revision in the work plan. Include a detailed timeline with the critical decision points notated for the proposed studies.
• Provide detailed, explicit and, where applicable, quantitative milestones that should be achieved each year of the project.

Vertebrate Animals: In addition to a detailed Vertebrate Animal Care section, provide a description of, and rationale for, the proposed acquisition and preparation of the solid organs, tissues or cells to be used in the studies and the proposed methods, source, and number of NHP samplings/biopsies required.

Provide a justification for the numbers of animals (or for the small numbers of animals, if applicable) used per experiment, with a discussion of statistical considerations and statistical soundness of the proposed experiments within the bounds of limited resources and budgetary constraints. Address the conclusions that can be drawn given the number of animals used.

Letters of Support:

Reagent Resources

• Provide letters of commitment from reagent sources, where appropriate, documenting the availability, quantity, and anticipated timelines for supplying the reagents. These letters should be submitted as an attachment to the application.

Non-NIAID Breeding Colony Animal Source:

• Provide letters of availability of animals from other sources should the NIAID breeding colonies not, or only partially, be able to meet the applicants NHP requirements or needs.

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, with the following modification:

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

PHS Inclusion Enrollment Report (Research Project)

When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

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 Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. 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.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project 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 project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit, and in providing an overall impact score, but will not give a separate score for each.

• Is the program as a whole scientifically compelling?
• Will the coordination and synergy of the individual research projects and cores lead towards the achievement of the central objectives of the U19?
• Will the integration of the individual projects into a single program be more beneficial than pursuing each project independently?
• Do(es) the PD(s)/PI(s) have the leadership and scientific ability to develop an integrated and focused research program?
• For applications designated multiple PDs/PIs, is the Leadership Plan both adequate and appropriate to ensure that there will be sufficient coordination and communication among the PDs/PIs?
• Are the plans for coordination, communications, problem identification and resolution, and the establishment of a strong collaborative environment for the U19 appropriate?

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project 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 project 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 project that by its nature is not innovative may be essential to advance a field.

Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? If the aims of the project 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? What is the likelihood that the results of the proposed studies will be translated into or contribute to new approaches and knowledge that are relevant to future studies in NHPs and/or human transplantation?

Are the project leads, collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or 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-project lead, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? Does the Project Lead commit at least the minimum level of effort to ensure the success of the project? Are the expertise and level of effort of NHP transplantation researchers and basic transplantation investigators and/or immunologists appropriate for the success of the program?

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?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the 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 project 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 children, justified in terms of the scientific goals and research strategy proposed?

If biological variables, such as sex or age of nonhuman primates, for the proposed studies are limiting are these limitations adequately justified?

Will all reagents or therapeutics needed for the study be available in the proposed time-frame? Are the proposed approaches appropriate and ready for NHP research? Are approaches to study underlying mechanisms and/or biomarkers appropriate? Are the yearly milestones and timelines adequate, appropriate, and reasonably attainable?

Is the justification for the numbers of animals (or small numbers of animals, if applicable) reasonable? Are the statistical considerations of the proposed experiments and the proposed conclusions that may be reached appropriate? Are the acquisition and preparation of the solid organs, tissues or cells to be used in the studies and the proposed methods, source, and number of NHP samplings/biopsies appropriate?

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? Are appropriate and sufficient animal housing and care facilities available to the investigators to carry out the proposed work?

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the core to exert a sustained, powerful influence on the research field(s) involved.

Reviewers will consider each of the review criteria below, as appropriate for the individual core, in the determination of scientific merit and provide an overall impact score for each Core, but will not give separate scores for these items.

Administrative Core

• Is the administrative and organizational structure appropriate and adequate to the attainment of the objective(s) of the proposed program?
• Is the management plan for fiscal accountability, contractual agreements, and communication within the program appropriate?
• Are the plans for coordination, problem identification and resolution, and the establishment of a strong collaborative environment for the program appropriate?
• Are the administrative plans for the management of projects, including plans for resolving conflicts, appropriate?
• Are the experience, level of commitment, and availability of the Administrative Core Leader and administrative staff adequate to manage the program?

Scientific Cores (if applicable)

• Is provision of the scientific core for the individual Research Projects critical and justified?
• Is the relationship of a scientific core to the central focus of the overall program strong?
• Are the strategy, methodology, and analyses well-reasoned, feasible, and appropriate to accomplish the specific aims of the core, if applicable? Are potential problems, alternative strategies, and benchmarks for success presented, if applicable?
• Are the quality of the relevant facilities or resources provided and criteria for prioritization and usage appropriate?
• Are the qualifications, competence, and commitment of the Core Leader and key personnel appropriate?

As applicable for the project 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.

For research that involves human subjects but does not involve one of the six 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 six 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 project 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 children 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.

Not Applicable

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

Not Applicable

As applicable for the project 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.

Infrastructure and Opportunities Fund Management Core

Is provision of the proposed services to the program adequate? Are the personnel charged with managing the IOF appropriate?

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 NIAID 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 Advisory Allergy and Infectious Diseases 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.
• Progress under any current NHPCSG award, if applicable.
• Timely availability of critical reagents and resources.

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.

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 http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.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.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

PD(s)/PI(s) Responsibilities

The PD(s)/PI(s) will have the primary responsibilities as follows:

• The PD/PI is responsible for defining the research plan and goals within the guidelines of this FOA; setting project milestones and timelines to achieve the proposed goals; overseeing/performing the scientific activities; ensuring successful completion of yearly milestones within the timeframe and budget proposed; cooperating with NIAID programmatic, technical, and administrative staff; and administratively managing the U19.
• Each U19 will have two votes on the NHPCSG Steering Committee. The voting members are one PD/PI, which shall be the contact PD/PI if multi-PDs/PIs, for each award and one additional individual Project Leader or multi-PD/PI to be named by the U19 contact PD/PI. The U19 Project Leader or multi-PD/PI voting member may be rotated to other U19 Project Leaders annually, at the discretion of the U19 PD/PI. Additional PDs/PIs of a multiple PD/PI award and Project Leaders will be non-voting members. For additional information, see Steering Committee below under Areas of Joint Responsibility. The PDs/PIs will participate in all Steering Committee activities, and will follow the policies and procedures developed by the Steering Committee. Other investigators of awards made under the U01 or U19 solicitations may serve as nonvoting members as determined by the Steering Committee.
• The PD/PI may be required to modify yearly milestones prior to award or post-award, based on review and/or NIH Project Scientist and/or PD/PI assessment of the proposed yearly milestones. At the first annual Steering Committee Meeting following award the PD(s)/PI(s) will present an overview of their program and yearly milestones to the NHPCSG Steering Committee. When yearly milestones are not met, a critical reagent is not available, or results indicate that continuation of a peer-reviewed aim is not warranted, the PD/PI will submit on request by the NIAID Project Scientist, a proposal for revision of milestones and/or aims within the scope of the original peer-reviewed award.
• The PD/PI, upon acceptance of an award, agrees to participate in all collaborative studies, including those that involve collaborations with biotechnology and pharmaceutical companies, as specified by the Steering Committee or that may be requested by NIAID.
• The PD/PI will ensure that all NHPs obtained from the NIAID breeding colonies are used only for the expressed purposes of the individual Cooperative Agreements funded through this FOA or proposals recommended by the Steering Committee and approved by NIAID.
• After grant award, one U01 (companion RFA-AI-16-007) or U19 awardee institution will be selected by the NIAID to manage the Infrastructure and Opportunities Fund for the entire NHPCSG. Projects recommended by the Steering Committee and approved by the NIAID Project Scientist for IOF support will be funded as consortium agreements by the NHPCSG grant institution managing the Infrastructure and Opportunities Fund.
• NHPCSG investigators, including collaborators with effort on the U19 and U01 awards, are eligible to apply for IOF project awards. The PD/PI of each U19 will be responsible for ensuring that all IOF awards adhere to the rules and guidelines of the NHPCSG Steering Committee.
• The PD/PI will be responsible for the timely submission for publication of manuscripts (co)authored by members of the grant and supported in part or in total under this Agreement and for adherence to all aspects of the NHPCSG’s Publications Policy, to be determined by the NHPCSG Steering Committee and NIAID.
• Awardees are expected to make new information and materials, including research samples, tools, methods, reagents, and data developed under the NHPCSG grants known and available to the broader research community and other members of this program in a timely manner through publications, presentations, web announcements, submission to public resources or databases, and reports to the NIAID and/or NHPCSG Steering Committee.

NIH Staff Responsibilities

A NIAID program official will also serve as the Project Scientist and will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below.

• The NIAID Project Scientist will serve as facilitators of NHPCSG activities and scientific endeavors and provide advice, technical assistance, and guidance on technical and management issues, such as reviewing progress and subcommittee requirements. The Project Scientist will serve as a liaison/facilitator in identifying potential sources of reagents or other resources, and identifying potential collaborations to further the goals of the NHPCSG. The Project Scientist will also serve as a resource of scientific and policy information related to the goals of the awardee’s research. However, the roles of the Project Scientist will be to facilitate and not to direct the NHPCSG grant activities.
• The NIAID Project Scientist approves the distribution of NHPs from the NIAID breeding colonies for the individual research projects, based on availability and number of animals proposed in the peer-reviewed studies.
• The NIAID Project Scientist will serve as a non-voting member of the Steering Committee. The NIAID Project Scientist may assist in scheduling the meetings of the NHPCSG Steering Committee and subcommittees by the Steering Committee Chair and Subcommittee Chairs and will actively participate with the Chair(s) in developing the meeting agendas. The Project Scientist will participate and assist in the organization and planning of NHPCSG workshops. The Project Scientist will ensure coordination of Steering Committee activities and implementation of its recommendations, decisions, and policies. It is anticipated that decisions in most Steering Committee activities will be reached by consensus and the NIAID Project Scientist will be given the opportunity to offer input into the process, but the manner of reaching this consensus and the primary decision-making responsibility will rest with the Steering Committee, except where stated in this FOA.
• Awards are milestone-based and the NHPCSG program includes the flexibility for the NIAID Project Scientist to approve redirection of research aims within the scope of the original award during the funding period. The NIAID Project Scientist may ask members of the NHPCSG Steering Committee and/or other experts for recommendations when significant redirection is required. NIAID reserves the right to terminate or curtail a study (or any individual U01/U19 grant or U19 project award) in the event of a substantial shortfall in study milestones or other major breach of the approved project.
• Additionally, a NIAID Program Officer will be responsible for the normal scientific and programmatic stewardship of the awards. The assigned NIH Program Officer may also serve as the Project Scientist. This stewardship role will include monitoring program progress and approving changes. The Government, via the NIAID Program Officers, will have access to data generated under this Cooperative Agreement and may periodically review the data and progress reports. NIAID staff may use information obtained from the data for the preparation of internal reports on the activities of the study; however, awardees will retain custody of and have primary rights to all data developed under these awards.

Areas of Joint Responsibilities: Steering Committee

The NHPCSG Steering Committee will serve as the governing board for awardees of this program. Each U19 will have two votes. One voting member will be the PD/PI (or contact PD/PI if a multi-PD/PI award). Additional PDs/PIs of a multiple PD/PI award will be non-voting members. Selected scientists other than the awardees may serve as voting members when additional expertise is required for committee breadth and balance, to be determined by majority vote of the Steering Committee. A Chairperson will be elected by majority vote from among non-government voting members. In addition, the NIAID Project Scientist may appoint up to two external scientists as an Advisory Working Group (acting in a scientific advisory capacity to NIAID) to the Steering Committee as non-voting members. The NIH Project Scientist will also serve as a non-voting member.

• Infrastructure and Opportunities Fund (IOF): The NHPCSG Steering Committee will oversee the Infrastructure and Opportunities Fund for the consortium, including advising on the procedures, policies, and subcommittees, as needed, for the IOF solicitation, receipt, review, development, evaluation, and recommendation of feasibility, pilot, resource development, or collaborative projects or potential resource sharing opportunities and other collaborative needs. The Steering Committee will also assess website and additional professional and administrative staffing needs beyond the administrative support provided as part of the requirements to manage the IOF budget and activities (e.g. for review activities or IT needs) and provide recommendations to the Project Scientist. In addition, the NHPCSG Steering Committee, or a designated subcommittee, will be responsible for an annual report of progress of projects, status of funds, and other activities funded by the IOF program, including outcomes of all completed projects. This Steering Committee activity may be coordinated through the institution responsible for the IOF management.
• Goals and Action Plan: The Steering Committee shall draft a NHPCSG Goals and Action Plan for the funding period by the end of the first funding year. The organization of the drafting of the Action Plan shall begin within six months of award. This Action Plan shall include the organization of at least one workshop to be held during the funding period. The workshop should include participants from outside the NHPCSG to further its goals in building collaborations and engaging the broader research community.
• Group Progress Report: The NHPCSG Steering Committee or a designated subcommittee will prepare a cumulative group progress report or ad hoc reports, as required, on Consortium activities, when requested by the NIAID Project Scientist. At the completion of the second or third year of funding, a progress report may be required that contains, at a minimum, the following information: project overviews; cumulative progress of ongoing and newly-initiated projects; manuscripts published, in press, and in preparation; a list of presentations at regional, national, and international meetings; IOF program progress and activities; other NHPCSG activities; and future plans. The reports will be submitted to the NIAID Project Scientist no later than four months after the NIAID Project Scientist requests a report, or a time agreed upon by the NIAID Project Scientist and the Steering Committee Chair.
• Collaborations: In order to efficiently utilize research resources and rapidly exchange scientific information to promote the NHPCSG objectives, it is anticipated that cooperation or opportunities to collaborate with other NIH funded programs, including clinical trials programs, will be initiated in future years and will be coordinated and facilitated by the NIH Project Scientist.
• Other Steering Committee responsibilities include the following:
• provide guidance to investigators regarding study implementation and design;
• provide recommendations on approval or discontinuing individual IOF projects;
• provide recommendations to NIAID regarding continuation, or redirection of U01 or U19 aims within the scope of the original award, when and if requested by the NIAID Project Scientist.
• develop a publications policy, including guidelines for publication of collaborative project results;
• develop procedures for and conduct periodic reviews of conflict of interest among grantees; and
• advise the NIAID Project Scientist on maximizing the value of the NIAID NHP breeding colonies.
• advise NIAID on scientific opportunities, emerging needs, and impediments related to success of the NHPCSG program.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

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 progress report, 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.

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 registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
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Contact Center Telephone: 800-518-4726
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Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-710-0267

Kristy Kraemer, Ph.D.
National Institute of Allergies and Infectious Diseases (NIAID)
Telephone: 240-627-3520
Email: kkraemer @mail.nih.gov

James T. Snyder, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5060
Email: [email protected]

Cheryl Wall, M.S.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-2956
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.