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). 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

This Funding Opportunity Announcement (FOA) solicits applications from institutions to participate in the HLA and KIR Region Genomics in Immune-Mediated Diseases Consortium (HLAGC), formerly the HLA Region Genomics in Immune-Mediated Diseases Consortium. This cooperative research group 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, or 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 HLAGC will be submitted to the NIAID Bioinformatics Information Support Contract (BISC) database, ImmPort (Immunology Database and Analysis Portal, https://immport.niaid.nih.gov). Data from these studies will also be submitted to and maintained by dbMHC (http://www.ncbi.nlm.nih.gov/projects/gv/mhc) and dbGaP (http://www.ncbi.nlm.nih.gov/gap), publicly accessible databases of MHC genetics and phenotypes maintained by the National Center for Biomedical Information (NCBI), part of the National Institutes of Health National Library of Medicine (NLM).

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 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. 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 gene cluster on chromosome 19, and have evolved to catalyze 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.

In 2005, the HLAGC was formed by NIAID, with co-sponsorship from NINDS. The primary goal of this program is to define associations between sequence variations in 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 with similar functions. The HLA region also displays a high degree of linkage disequilibrium, complicating its study. For these reasons, it has been determined that a high-resolution approach specifically targeting the HLA and KIR regions is critical.

Previous studies carried out by members of the HLAGC 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 formation of this cooperative group has facilitated the exchange of reagents and technologies, fostered collaborations across diseases and disciplines, and revealed how common sequence variations within these regions may be linked to multiple diseases.

The goal of this FOA is to continue support of the HLAGC 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 dbMHC and 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 risk, severity, progression, and response to therapy, or transplantation outcome. Studies investigating associations within these regions and disease susceptibility or transplantation outcome 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 also encouraged. Studies may examine polymorphisms in the 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.
• 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
• 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: however, applicants may request support for procedures to obtain subject samples provided these procedures and associated costs are strongly justified and would not duplicate clinical cost reimbursements or funding provided from another source.
• Serology-based HLA or KIR typing projects.

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

Steering Committee:

Program Directors (PDs)/Principal Investigators (PIs) from U01 and U19 projects funded under this program will form a Steering Committee after award. The Steering Committee will serve as the main governing body for the cooperative group. 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, prepare cumulative progress reports as requested by the NIAID Program Officer; and establish collection standards in collaboration with BISC that will facilitate meta-analysis across studies and disease areas.

NIAID Bioinformatics Information Support (BISC):

The BISC program (http://www.niaid.nih.gov/about/organization/dait/Pages/bisc.aspx) will provide technical assistance, software development, and data submission support for HLAGC awardees. The primary goal of BISC is to advance the discovery and generation of new hypotheses for immune-mediated diseases by providing an integrated data repository, providing advanced computer support for handling scientific data, disseminating best practices in scientific data analysis, and building and supporting a platform for integrated research and data sharing, via the BISC Immunology Database and Analysis Portal (ImmPort, https://immport.niaid.nih.gov).

The data generated by the HLAGC will be submitted to the BISC database, ImmPort. ImmPort is designed to manage data integration and statistical analysis, and will serve as a central data repository for NIAID-supported research in immune-mediated diseases, including linkages with high resolution HLA genomic information. Each awardee will collect and ensure the consistency and quality of their data, with assistance from BISC, as needed. BISC will be responsible for data receipt, deposition, curation, archive and backup, recovery (as necessary), and subsequent data deposition into and interface with dbMHC or other appropriate public databases (e.g., dbSNP, GenBank). BISC will develop and disseminate software for all data submission and analysis, and establish customized graphical interfaces for frequent and interactive communication with project investigators. BISC will also provide statistical software tools for local interim analysis (as needed), and assist with technical support in the collection, submission, and exchange of data primarily through the statistical liaison of each U01 and U19 project. BISC will provide feedback to the statistical liaison regarding the quality of data submitted, and will accept data from the project(s) in a variety of formats (such as XML or tab-delimited text files), which will be determined in consultation with the Steering Committee and project statistical liaisons.

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.

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).

In addition, the NIH will not accept a resubmission (A1) application that is submitted later than 37 months after submission of the new (A0) application that it follows. The NIH will accept submission:

• To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
• Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
• Of an application with a changed grant activity code.

Applicants must download 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.

It is critical that applicants follow the 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.

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:

Andrea Wurster, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases (NIAID)
Room 3259, MSC-7616
6700B Rockledge Drive
Bethesda, MD 20892-7616 (U.S. Postal Service or regular mail)
Bethesda, MD 20817-7616 (for express/courier service; non-USPS service)
Telephone: 301-451-2660
Email: [email protected]

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

The forms package associated with this FOA includes all applicable components, required and optional. Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate optional components.

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 instruction.

Include the name and biosketch of a biostatistician who will serve as the project’s statistical expert with direct responsibility for analysis and to act as a liaison to BISC.

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

PD(s)/PI(s) are expected to commit substantial time and effort to ensure success of the program and must commit, at a minimum, 1.8 calendar months.

Applicants should include appropriate travel budgets to accommodate travel by the PD(s)/PI(s) and project biostatistician to the annual Steering Committee meeting in Bethesda, MD.

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, in priority order, the Specific Aims of the proposed project. Concisely describe the hypothesis or hypotheses to be tested.

Research Strategy: Within the research strategy, applicants must include the following:

• A section entitled Timelines and Annual Milestones with clearly stated interim and long-term objectives and annual milestones (e.g., subject recruitment and data deposition into ImmPort) to be achieved during the project, identify critical decision points, and provide a detailed timeline for the completion of each goal of the proposed research project.
• A section entitled Data and Statistical Plan, with a detailed description of the statistical considerations used in determining sample size and study power, a justification for the required sample size, and details of data collection, especially the capture of sufficient phenotypic information. Applicants are encouraged to contact the Scientific /Research Contact(s) listed in Section VII to discuss BISC interactions prior to submission.
• A section entitled Study Populations with a description and justification for the selection of study population(s), and (for prospective studies) demonstrated capability to recruit human subjects. Human samples may be derived from ongoing, completed, or prospective clinical trials or studies in which samples were retained for the express purpose of future research or in which individuals are re-consented to allow for this use. Support for clinical procedures to obtain samples that are not part of an associated clinical trial or study (e.g., additional biopsies) should be clearly described and strongly justified. Applications should address ability to acquire human samples and clinical data for the proposed studies in an appropriate timeframe
• If applicable, describe progress made under any current HLA Region Genomics in Immune-Mediated Diseases award.

Letters of Support: If the proposed study includes samples and clinical data from an ongoing clinical trial or 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 (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) 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.

Include in the Appendix an informed consent document compatible with data sharing:

• If previously collected samples will be used during the study, proof of appropriate informed consent and/or IRB approval for the use of previously collected samples, and for the sharing of resulting data is required at the time of submission of the application.
• If samples are to be collected during the study, drafts of all consent forms to be used for the studies, as well as the consent form(s) for any associated clinical trial or study must be included with the application. The consent form for samples collected during the study must be compatible with data sharing with BISC and other projects within the consortium. IRB approval of the consent form(s), if applicable, is not required at the time of submission of the application.

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

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

Part I. Overview Information contains information about Key Dates. 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.

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. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

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 Applying Electronically.

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 by the Center for Scientific Review and responsiveness by the NIAID, NIH. Applications that are incomplete 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 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.

Significance

Does the project address an important problem or a critical barrier to progress in the field? 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?

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

Investigator(s)

Are the PD(s)/PI(s), 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-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Does the project biostatistician have the appropriate experience to serve as the project’s statistical expert and to act as the liaison to BISC?

Innovation

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?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? 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?

Are there sufficient preliminary data to support the proposed research projects?

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?

Are milestones and timelines reasonable and appropriate? If applicable, is the study sufficiently powered? Are the statistical plan and interactions with BISC adequately described and appropriate? Does the applicant describe how phenotypic data will be captured, validated, and linked to later analyses? Is the selected study population(s) well described and justified? For prospective studies, does the applicant demonstrate the capability to recruit human subjects? Is there adequate evidence that the human samples from ongoing, completed, or prospective clinical trials or studies were appropriately retained for future use or that individuals are re-consented to allow for this use? Is support for clinical procedures to obtain samples that are not part of an associated clinical trial or study clearly described and strongly justified? Does the applicant provide compelling evidence that the genetic material and clinical data necessary for the proposed project will be available within an acceptable timeframe?

Environment

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.

Protections for Human Subjects

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.

Inclusion of Women, Minorities, and Children

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.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

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.

Resubmissions

Not Applicable

Renewals

For Renewals, the committee will consider the progress made in the last funding period. Was progress under any current HLA Region Genomics in Immune Mediated Diseases award satisfactory?

Revisions

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.

Applications from Foreign Organizations

Not Applicable

Select Agent Research

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).

Resource Sharing Plans

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) Genome Wide Association Studies (GWAS).

Budget and Period of Support

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 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 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 l. 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.

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 the DUNS, SAM Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants 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.

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 determine and coordinate the scientific and administrative activities of the approved projects; set project goals and timelines; accept and implement common guidelines approved by the Steering Committee.
  
  
• PDs/PIs will collect, validate and assure the quality of the data; interact with BISC staff through the statistical liaison; submit data to ImmPort, BISC’s Immunology Database and Analysis Portal, and agree to the subsequent submission of these data to dbMHC and dbGaP by BISC in accordance with policies established by NIAID and NCBI and the NIH data sharing policy available at: http://grants.nih.gov/grants/policy/data_sharing/.
  
  
• Each PD/PI will attend Steering Committee meetings, serve as a voting member of the Steering Committee (one PD/PI if multiple PDs/PIs); and participate in HLAGC activities.
  
  
• NIAID intends to support the peer-reviewed studies proposed in the awarded grant applications. However, under special circumstances (e.g., duplicative or overlapping specific aims among awardees), the Steering Committee will establish guidelines and review procedures, and will evaluate and recommend to the NIAID opportunities for collaboration, redirection or modification of the peer-reviewed or new projects when applicable and necessary. This policy is in keeping with the terms and conditions of the cooperative agreement mechanism. Any recommendations that result in a change in the research projects must be approved by the NIH Program Officer(s).
  
  
• PD/PI agrees to abide by the HLAGC publication policy, to be drafted with NIH assistance and adopted by the Steering Committee after award.
  
  
• Prior to award, the PD/PI (multiple PDs/PIs) agrees to document their commitment to participation in the collaborative group, signed by the PD/PI (multiple PDs/PIs) and the applicant institution, including serving on the Steering Committee, adhering to Steering Committee polices and decisions, and accepting the participation and assistance of NIH staff.
  
  
• Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

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 support the HLAGC activities through technical assistance, advice and coordination, including providing assistance with the design of the Steering Committee technical and management activities; serve as facilitator of activities, such as the selection of resources and identification of potential collaborations to further the goals of the Program. In addition, the NIH Project Scientist(s) will coordinate NIH staff assistance, including interactions with BISC.
  
  
• NIH Project Scientist(s) will serve as a non-voting member of the Steering Committee, provide assistance to the Steering Committee in the development of procedures for evaluating the performance of research studies, and ensure coordination of Steering Committee activities and implementation of its recommendations, decisions, and policies. It is anticipated that the majority of steering committee decisions will be reached by consensus and the NIH staff will be given the opportunity to offer input into this 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.
  
  
• The Government, via the Project Scientist(s), will have access to data generated under this Cooperative Agreement and may periodically review the data and progress reports. NIH staff may use information obtained from the data for the preparation of internal reports on the activities of the program.
  
  
• The NIH reserves the right to terminate or curtail a study (or any individual award) 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 HLAGC. 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.
  
  
• Each Steering Committee and subcommittee member will participate in all meetings, teleconferences, and activities of those committees. Statistical liaisons are required to attend Steering Committee meetings if statistical issues are to be discussed.

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 data handling and interaction with BISC 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 dbMHC and/or other 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 cumulative progress reports, 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.

Additional details and responsibilities of the Steering Committee will be negotiated at the time of award or post-award.

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 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 annual Non-Competing Progress Report (PHS 2590 or RPPR) 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.

The awardee is solely responsible for the timely acquisition of all appropriate propriety rights, including intellectual property rights, and all materials needed for the awardee to perform the project. Before, during, and subsequent to the award, the U.S. Government is not required to obtain for the awardee any propriety rights, including intellectual property rights, or any materials needed by the awardee to perform the project.

The awardee is required to report to the U.S. Government all inventions made in the performance of the project, as specified by 35 U.S.C. Sect. 202 (Bayh-Dole Act).

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

eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
Finding Help Online: http://grants.nih.gov/support/index.html
TTY: 301-451-5939
Email: [email protected]

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone: 301-710-0267
TTY: 301-451-5936
Email: [email protected]

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

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

Andrea Wurster, PhD
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-451-2660
Email: [email protected]

Jay Colbert
National Institute of Allergy and Infectious Disease (NIAID)
Telephone: 240-669-2980
Email: [email protected]

Tijuanna Decoster
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 Parts 74 and 92.