It is critical that applicants follow the Research (R) 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

The purpose of this Funding Opportunity Announcement (FOA) is to solicit applications from institutions to participate in the HLA and KIR Region Genomics in Immune-Mediated Diseases Consortium (HLARGC). This cooperative research initiative supports studies to discover and characterize associations between polymorphisms in the human leukocyte antigen (HLA, also known as the Major Histocompatibility Complex or MHC), and natural killer cell immunoglobulin-like receptor (KIR) genomic regions and (1) immune-mediated diseases, including risk and phenotype, and (2) cell, tissue, and organ transplantation outcomes, including rejection, tolerance, and graft-versus-host disease (GVHD).

In addition to supporting HLA and KIR region association studies, a major goal of this program is the assemblage of high-quality, high-resolution genetic data with accompanying disease state and phenotype information. The data generated by the HLARGC will be submitted to the NIAID Bioinformatics Information Support Contract database, the Immunology Database and Analysis Portal (ImmPort). Where appropriate, data from these studies will also be submitted to Database of Genotypes and Phenotypes (dbGaP) and other publicly accessible databases.

The HLA genomic region is the most polymorphic and gene-dense region in the human genome. This four-megabase region on chromosome 6 contains at least 150 protein-coding genes, and includes the HLA Class I, II, and III gene families. The Class I and Class II genes encode molecules responsible for the presentation of endogenously and exogenously derived peptides to T cells. The Class III region contains genes encoding a variety of immune response mediators, including some complement components and cytokines. Many of these genes are implicated in the development of immune-mediated diseases. In addition to their role in peptide presentation, HLA Class I molecules act as ligands for KIR on natural killer (NK) cells. The interaction between HLA and KIR results in either inhibition or, less commonly, activation of NK cell cytotoxic activity. KIRs are encoded by a highly polymorphic region of chromosome 19 and have evolved to enable swift immune responses to a variety of threats. Specific combinations of KIR and HLA haplotypes have been linked to immune-mediated diseases and transplantation outcomes, suggesting that the study of these molecules in tandem may be especially valuable.

The primary goal of this program is to define associations between sequence variations in the HLA and KIR genomic regions with susceptibility or resistance to immune-mediated diseases, including autoimmune diseases, primary immunodeficiencies, and outcomes of cell, tissue, and organ transplantation. Genome-wide association studies (GWAS) of these diseases consistently show the highest level of association within these regions. However, conventional GWAS techniques are inadequate when applied to this dense, highly polymorphic cluster of genes. The HLA region also displays a high degree of linkage disequilibrium, complicating its study. For these reasons, this FOA solicits applications that propose high-resolution approaches specifically targeting the HLA and KIR regions.

The formation of the HLARGC cooperative group has facilitated the exchange of reagents and technologies, fostered collaborations across diseases areas and disciplines, and revealed how common sequence variations within these regions may be linked to multiple diseases. Previous studies carried out by members of the HLARGC have focused on autoimmune diseases (multiple sclerosis, rheumatoid arthritis, juvenile idiopathic arthritis, myasthenia gravis, systemic lupus erythematosus, Crohn’s disease, ulcerative colitis, Behcet’s disease, systemic sclerosis, ankylosing spondylitis, and narcolepsy/hypocretin deficiency), primary immunodeficiencies (IgA deficiency and common variable immune deficiency), and hematopoietic stem cell and cord blood transplantation outcomes.

The goal of this FOA is to continue support of the HLARGC program to further identify, map, and characterize how genetic variants within these regions may influence disease phenotype, progression, and severity; predict health outcomes; and direct treatment strategies, with an emphasis on population diversity. In addition, high quality, high-resolution HLA and KIR region genomic and phenotype data produced from these projects will populate publicly accessible databases such as dbGaP.

This initiative will support prospective and/or retrospective studies investigating the role of the HLA and/or KIR genomic regions in immune-mediated diseases and transplantation outcome. Research projects must be focused on the correlation between sequence variations in the HLA and/or KIR genomic regions with disease clinical phenotype, risk, severity, progression, and/or response to therapy, or transplantation outcomes. Studies investigating associations linked to race or ethnicity are especially encouraged. In addition, as the independent segregation of HLA and KIR genes results in diverse HLA-KIR combinations between individuals, studies of HLA-KIR region gene combinations are especially encouraged. Studies may examine polymorphisms in the protein coding and/or non-coding regions with the HLA and KIR regions, as well as non-classical genes residing in these regions.

Potential areas of research include, but are not limited to, the following:

• The association of HLA and/or KIR region genes, including non-HLA and -KIR genes residing in these regions, or specific combinations of HLA/KIR molecules with susceptibility, resistance, progression, phenotype, and/or response to therapy of immune-mediated diseases, including autoimmune diseases and primary immunodeficiency diseases.
• The association of germline HLA and/or KIR region genes in the susceptibility and prognosis of cancer.
• Associations between transplantation outcomes, including graft rejection, acceptance/tolerance, or GVHD, with varying degrees of donor/recipient mismatch at HLA and/or KIR loci, polymorphisms in the HLA and/or KIR regions, or specific combinations of HLA and KIR molecules in the donor, recipient, or both.
• Mechanistic studies of HLA and KIR interactions, disease associations, and the functional basis of the observed association.
• Association studies of immune-mediated diseases disproportionately affecting specific racial, ethnic, or gender groups, especially minority populations.
• Examples of appropriate immune-mediated diseases include, but are not limited to:
• GVHD
• Allograft rejection (acute and chronic), and survival/tolerance
• Autoimmune diseases, except type 1 diabetes
• Primary immunodeficiency diseases (e.g., common variable immune deficiency and IgA deficiency)

Applications including the following types of studies will be considered non-responsive and will not be reviewed:

• Type 1 diabetes association studies
• Infectious disease and vaccine response association studies
• Interactions between HLA or KIR region genes and genes outside these regions, including but not limited to interactions between HLA molecules and antigen receptors
• Cancer studies focused on somatic (nonheritable) mutation/variation
• Cancer studies examining treatment and/or outcome, unless in the context of transplantation
• Animal studies, including the development or analysis of animal models for HLA- or KIR-related disease studies
• Population diversity studies, unless they are directly linked to immune-mediated disease prevalence or severity studies
• Clinical trials
• Serology-based HLA or KIR typing projects
• HIV/AIDS associated studies

Applicants are strongly encouraged to contact the Scientific Research Contacts well in advance of the application submission deadline to discuss the proposed research program.

Steering Committee

A Steering Committee made up of the Program Directors (PDs)/Principal Investigators (PIs) from U01 and U19 projects funded under this program will serve as the main governing body for the HLARGC. Among other responsibilities, it will identify scientific opportunities, emerging needs and impediments; ensure the timely release of data through publications and/or release of data to public databases; develop guidelines for the publication of collaborative research project results and establish collection standards in collaboration with ImmPort that will facilitate meta-analysis across studies and disease areas.

NIAID Bioinformatics Information Support (ImmPort)

The ImmPort program will provide technical assistance and data submission support for HLARGC awardees. The portal provides online tools that allows users to analyze data and visualize results, integrate data from a variety of laboratories, and supports collaboration between scientists. The data generated by the HLARGC will be submitted to the ImmPort database. ImmPort will be responsible for data receipt, deposition, archive and backup, and subsequent data deposition into dbGAP or other appropriate public databases. ImmPort will communicate with the data liaison of each U01 and U19 project.

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)
• 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) 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.

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).

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are 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 Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise. 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:

Thomas Conway, Ph.D.
Telephone: 240-669-5075
Email: [email protected]

All page limitations 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 an application to this FOA.

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

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

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

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

Include the biosketch of a biostatistician and their qualifications to serve as the project’s statistical expert with direct responsibility for analysis and to act as a data liaison to ImmPort.

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

PD(s)/PI(s) are expected to commit a minimum of 1.8 person months per year to this program. For multi-PD/PI applications, only the contact PD/PI must commit a minimum of 1.8 person months per year.

Include budgets to accommodate travel by the PD(s)/PI(s) and project biostatistician to the annual Steering Committee meeting in Rockville, MD. Assume the meeting will be held over one day.

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

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

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

Specific Aims: List the Specific Aims of the proposed project. Concisely describe the hypothesis or hypotheses to be tested. In addition, state the project’s relationship to the goals of the HLARGC.

Research Strategy: Include the following:

• A description of how the proposed research will contribute to meeting the HLARGC's goals and objectives. Explain the rationale for selecting the methods to accomplish the Specific Aims and address how the project will advance understanding of the role of HLA and/or KIR region genes in immune-mediated diseases, cancer, and/or transplantation. In addition, state the biological significance of the research.
• A section entitled "Timelines and Annual Milestones" containing clearly stated interim and long-term objectives and annual milestones to be achieved during the project, identifying critical decision points, and providing a detailed timeline for the completion of each goal of the proposed research project. Note: timelines for clinical research are requested as part of the PHS Human Subjects and Clinical Trials information and should not be repeated in this section.
• A section entitled "Data and Statistical Plan" containing a detailed description of the statistical considerations used in determining sample size and study power, a justification for the required sample size; details of data collection; and the capture and validation of demographic and phenotypic information.
• A description of how interactions with ImmPort will be conducted.

Note: Specific details for human samples collected from independently-funded clinical trials and studies, and supplied to the PD(s)/PI(s) using patient identifiers will be captured using the PHS Human Subjects and Clinical Trials Information. Do not duplicate information requested under the PHS Human Subjects and Clinical Trials Information.

Letters of Support: If the proposed study includes samples and clinical data that are not currently in the possession of the PD/PI, the application should include a letter of support from the person or institution controlling the samples indicating that the samples and associated clinical/phenotypic data will be made available to the applicant.

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.
• All investigators funded under this FOA will be expected to share their data publicly through ImmPort or other public portals approved by NIH. Therefore, the Data Sharing plan should include a summary of how the applicant will manage data submission and interactions with ImmPort.
• Informed consent forms for all human samples must allow data sharing with ImmPort and other projects within the HLARGC.

Appendix:

Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

For all human samples, provide sample informed consent form(s) that were used to obtain consent for future use. This may be one informed consent document for the entire sample collection, or several different documents, as applicable.

Note: IRB approval of the consent form(s), if applicable, is not required at the time of submission of the application but will be required before the proposed research studies on those samples is begun.

When involving NIH-defined human subjects research, clinical research, and/or clinical trials (and when applicable, clinical trials research experience) 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 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, with the following additional instructions:

Section 2 - Study Population Characteristics

2.7 Study Timeline

If applicable, timelines should address the time needed to acquire samples from independently funded clinical research or clinical trials.

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.

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). 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.

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) 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. See Section III of this FOA for information on registration requirements.

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. 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 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.

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 the prior research that serves as the key support for the proposed project rigorous? 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?

Specific to this FOA:

How will the project significantly advance understanding of the role of HLA and/or KIR region genes in immune-mediated diseases, cancer and/or transplantation?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? 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?

Specific to this FOA:

How appropriate is the experience of the project biostatistician to serve as the project’s statistical expert and to act as the data liaison to ImmPort?

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 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?

Specific to this FOA:

Evaluate the appropriateness of: the proposed timelines and annual milestones, the statistical power of the study, the Data and Statistical Plan and interactions with ImmPort. How appropriate is the description of how phenotypic data will be captured, validated, and linked to later analyses? How adequate is the evidence presented that the human samples from clinical trials or studies were consented to allow for use in the proposed studies, and that the genetic material and phenotypic data necessary for the proposed project will be available within an acceptable timeframe?

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 individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

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?

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 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.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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 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.

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.

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 (GDS).

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 National Institute of Allergy and Infectious Diseases, 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 on the basis of established PHS referral guidelines 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.

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 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

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.

The PD(s)/PI(s) will have the primary responsibility for:

• PDs/PIs will collect and assure the quality of the data; interact with ImmPort staff through the data liaison; submit data to ImmPort, and agree to the subsequent submission of these data to dbGaP by ImmPort in accordance with policies established by NIAID and NCBI and the NIH data sharing policy available at: https://grants.nih.gov/grants/policy/data_sharing/.
• Each PD/PI will serve as a voting member of the Steering Committee (one PD/PI if multiple PDs/PIs); and participate in HLARGC activities.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

• NIH Project Scientist(s) will coordinate NIH staff assistance, including interactions with ImmPort and provide assistance with the design of the Steering Committee technical and management activities.
• The NIH reserves the right to terminate or curtail a study in the event of a substantial shortfall in participant recruitment, follow-up, data reporting, quality control, or other major breach of the approved project. Future year funding may be negotiated downward depending on the progress towards achieving the previously agreed upon research goals, interim objectives and annual milestones.
• Additionally, the NIH Program Officer will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

Steering Committee

A Steering Committee will serve as the governing board of the HLARGC. All consortium investigators will be required to accept and implement common guidelines and procedures approved by the Steering Committee.

• The voting members of the Steering Committee will include one PD/PI from each U01 and two from each U19. Additional PDs/PIs, Project Leaders, and NIH Program Officer(s) will serve as non-voting Steering Committee members.
• NIH may appoint up to two external scientists or additional staff to the Steering Committee as non-voting members. The Steering Committee may appoint additional non-voting members by majority vote.

The Steering Committee will:

• Serve as the main governing board;
• Identify scientific opportunities, emerging needs, and impediments;
• Identify opportunities for and encourage collaborations between consortium members;
• Provide guidance and recommendations to investigators regarding study implementation and conduct;
• Establish policies for joint publication, data handling and interaction with ImmPort and NCBI staff, including protocols and standards for data collection, analysis, and management;
• Ensure the timely release of data through publication and/or release of data to public databases;
• Develop guidelines and policies for publication of collaborative project results;
• Review each project’s progress in achieving set milestones and interim objectives, if requested by the NIH Program Officer(s);
• Prepare reports on cumulative progress of the cooperative group, as requested by the NIH Program Officer(s);
• Establish definitions and data collection standards that will allow pooling of data across studies and disease areas, as needed;
• Establish subcommittees as needed to provide recommendations on shared aspects of the cooperative research group, including but not limited to the activities listed above.

In order to most efficiently utilize research resources and rapidly exchange scientific information to promote HLA and KIR genomics research and NIH objectives, it is anticipated that cooperation or opportunities to collaborate with other NIH funded programs will be initiated in future years and will be coordinated and facilitated by the NIH Program Officer(s).

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 having three members (a designee of the Steering Committee who is not involved in the dispute, one NIH participant, and a third person from within or outside of the consortium who has relevant expertise and who is chosen by the other two) will be convened. 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 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]

Jeffrey Rice, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3552
Email: [email protected]

Danielle Carrick, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6749
Email: [email protected]

Ursula Utz, Ph.D.
National Institute of Neurologic Disorders and Stroke (NINDS)
Telephone: 301-496-1431
Email: [email protected]

Thomas Conway, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5075
Email: [email protected]

Regina Kitsoulis
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-2946
Email: [email protected]

Crystal Wolfrey
National Cancer Institute (NCI)
Telephone: 240-276-6277
Email: [email protected]

Tijuanna DeCoster, Ph.D., MBA
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9231
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.