November 21, 2018, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity are due on this date. No late applications will be accepted for this Funding Opportunity Announcement.
Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
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.
There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.
This Funding Opportunity Announcement (FOA) is a limited competition FOA inviting cooperative agreement (U01) applications from the nine Program Directors/Principal Investigators (PD/PI) of the Research Projects of the Intestinal Stem Cell Consortium (ISCC), an ongoing effort to support research on stem cell biology of the small intestine epithelium. This FOA will support collaborative projects to characterize the minimal, required niche factors that support intestinal stem cells in health and disease, using an integrated, multidisciplinary team science approach, with the ultimate goal of developing novel therapies targeting intestinal stem cells and supportive niche to regenerate and rebuild the human intestine. Only ISCC current participants are eligible to apply to this FOA. The consortium will include a Coordinating Center that will facilitate activities of the consortium and facilitate communication of research results, data and methods within the consortium and to the community. The Coordinating Center is being considered under FOA RFA-DK18-508 "Limited Competition for the Intestinal Stem Cell Consortium Coordinating Center (U24 Clinical Trial Not Allowed)."
The absorptive and protective functions of the intestine depend in part on the intestinal epithelium. This epithelium is characterized by continual turnover, with cells lost at the surface (large intestine) or villi (small intestine) and replaced from progenitor cells in the crypts. These stem cells, influenced by other cells, extracellular factors and factors in the lumen, produce the multiple cell types necessary for healthy epithelial function and self-renew to continue to replenish the epithelium. However, in diseased or inflamed conditions, the epithelium may not be renewed at the pace needed to maintain a barrier against the potentially harmful contents of the digestive tract. The resulting exacerbation of inflammation is thought to contribute to the development and/or maintenance of inflammation-related conditions and diseases of the intestine. Thus, the ability of resident stem cells to heal and maintain the epithelial barrier, commensurate with the need resulting from epithelial cell loss, is essential to normal function of the intestine.
Intestinal stem cells (ISCs), residing in specialized compartments called the crypts of Lieberkühn, generate progenitor cells known as transit-amplifying cells, which reside above the ISCs within the crypts. These cells undergo several additional cell divisions as they migrate upward along the crypt axis and their progeny terminally differentiate into a variety of cell lineages including enterocytes, goblet, enteroendocrine, tuft and M cells. ISCs can support repopulation of the entire intestinal epithelium and mediate tissue repair upon injury.
The precise localization and identity of ISCs have been intensely debated. Historically, ISCs have been postulated to be either actively cycling crypt-based columnar cells (CBC) or quiescent label-retaining cells (LRC) residing at approximately the "+4" cell position from the crypt base. Recently, several molecular markers have been reported to identify ISCs, including Lgr5 for CBC cells interspersed between Paneth cells and Bmi1 for ISCs localized to the "+4" cell position in the upper region of small intestine crypts above the Paneth cell zone. Seminal studies defined Lgr5 as a molecular marker of CBC-class ISCs that persist long-term, self-renew, and give rise to all mature intestinal epithelial lineages. Bmi1+ cells appear to be quiescent ISCs residing in approximately the +4 cell position. These cells remain quiescent and act as a reserve population that can give rise to all intestinal cell lineages after tissue damage.
Control of proliferation, self-renewal, and lineage specification of the stem cells in the crypt are believed to be directed by an actively regulated process based on cell-cell and cell-stroma interactions. The ISC niche or microenvironment is composed of epithelial and underlying nonepithelial cells within the lamina propia populated by stromal, immune, endothelial, and neural cells that support paracrine and/or autocrine signaling. The ISC niche also comprises the extracellular matrix (ECM), a highly dynamic structure that continuously undergoes controlled remodeling, mediated by metalloproteinases that are responsible for ECM degradation. The ECM interacts with the different cells in the niche to regulate stem cell fate. Overall, the components of the niche tightly modulate Wnt, Notch, epidermal growth factor, bone morphogenic protein/ transforming growth factor beta, and Hedgehog signaling pathways to maintain proliferation/differentiation balance. Intestinal epithelial self-renewal, differentiation, and barrier function reflect orchestration of these diverse signals, which support or antagonize each other in different contexts over relatively short distances. Despite the importance of the subepithelial niche, very little is known about its cellular compartments, the specific sources of crucial signals, or how molecular and cellular components are organized for optimal interactions with the epithelium during homeostatic and injured conditions. Any future intestinal stem cell-based therapy, be it humoral, direct ISC injection, or engineered gut segment transplantation, will require a deeper understanding of niche-ISC interactions. Considerable work needs to be done to more fully understand key niche players and their role in maintaining or healing the epithelium. Further work is needed on how this knowledge can best be used to develop therapies that will enhance epithelial repair, and allow for replacement or regeneration of intestinal segments.
The ISCC is a team-science initiative established by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Institute of Allergy and Infectious Diseases (NIAID) in 2009, and re-competed in 2014. The current ISCC consists of one Coordinating Center (CC) and nine individual research U01 projects, tasked at advancing the understanding of intestinal epithelial stem cell biology during development, homeostasis, regeneration, and disease. The ISCC website can be found at http://iscc.coh.org and describes ongoing studies to isolate and characterize ISC, compare populations, and determine how their activity is controlled. This initiative began as a result of the NIDDK workshop on Local Influences on Health and Repair of Intestinal Epithelium held March 25-26, 2008. In addition, this research underpins multiple goals in the Research Plan of the National Commission on Digestive Diseases (http://www2.niddk.nih.gov/AboutNIDDK/CommitteesAndWorkingGroups/NCDD/FinalResearchPlanPosting.htm). While this announcement emphasizes stem cells of the small intestine, it is anticipated that the methods and research results from the supported ISCC projects will aid similar studies in other areas of the gastrointestinal tract and other organs.
The ISCC has succeeded in establishing an intrinsically collaborative, multidisciplinary consortium with significant physician-scientist representation and expertise in several distinct areas including stem cell biology, human intestinal organoid culture, infectious disease, radiation injury, epigenetics, bioengineering, adenoviral delivery, mouse genetics, gastrointestinal (GI) neoplasms, pediatric GI diseases, GI surgery, and short-gut syndrome. The ISCC not only has made great progress towards achieving the original goals, but is also making substantial progress at developing extensive new collaborations within the consortium that merge common interests from their initially separate project proposals.
Research Objectives and Scope
The overall objective of this solicitation is for the continuation of the efforts by the ISCC to develop and implement a Trans-Consortium Project focused at characterizing the minimal, required niche factors that support ISC in health and disease, using an integrated, multidisciplinary team science approach, with the ultimate goal of developing novel therapies targeting intestinal stem cells and their supportive niche to regenerate and rebuild the human intestine. Thus, basic biology of the human system is to be elucidated through the use of animal models and human cell-derived organoids and enteroids, as a first step toward being able to translate principles to eventually be able to treat disease and enhance healing of the gut. It is anticipated that use of damage models, particularly radiation injury, will be an important part of studies.
Because the ISCC will meld the work of multiple laboratories and approaches, it is expected that the group will continue systematic integration and testing of protocols and resources for release to the community. Methods, reagents, resources, biomaterials (including cells or cell lines), data and models are expected to be made available to the research community. Because the individual projects will be coordinated through this consortium and are intended to generate methods, information and materials that are to be made available to the research community, policies for operation of the consortium; final composition and design of coordinated research projects; validation of models, reagents and data; data standards; and the timeline and processes for sharing within the consortium and with the research community will be established by the ISCC Steering Committee (see below). All participants will be expected to adhere to these policies as a term of the award. Policy documents for the ISCC, as currently established, can be accessed on the ISCC website.
Projects may include study of animal models, particularly mouse models, and/or human-derived cells, organoids and enteroids, and tissues of the small intestine. However, clinical studies in humans, beyond collection of tissues or cells for in vitro use or engraftment into animal models, are beyond the scope of this FOA. All research using human subjects, tissues, and cells is subject to Institutional Research Board and NIH and Office for Human Research Protections (OHRP) policies and approvals.
Research of interest includes the areas described above and the examples listed below. These are examples only, and are not intended to be limiting.
Projects are expected to have sufficient scope and complexity to warrant a multi-team approach, as well as evidence of synergistic interactions among PD/PIs. In addition, evidence of robust collaborations with other members of the ISCC, as attested by joint publications and/or preliminary data is expected.
Organization of the ISCC
The ISCC will continue to consist of the following components: the NIH, research projects, a Coordinating Center (CC), a Steering Committee and its Subcommittees, External Consultants, Working Groups and other committees as needed.
The NIDDK and NIAID will be responsible for organizing and providing support for the ISCC and will be involved substantially with the awardees as a "partner" consistent with the Cooperative Agreement mechanism. Designated NIDDK and NIAID Program Officers will provide programmatic oversight, and will monitor progress and adherence to NIH policies. An NIDDK Project Scientist will also be designated and will have one vote on the Steering Committee. The NIAID Program Officer will be an ex officio member of the Steering Committee. The NIDDK and NIAID will jointly appoint the Chairperson of the Steering Committee, and the External Consultants.
A network of synergistic projects will be established through this program to enable multiple, but coordinated, approaches to advance this area of research. The Consortium will be governed by a Steering Committee to coordinate and facilitate research activities for the overall program and to ensure synergy and efficiency. In addition, the Steering Committee will determine policies and implement processes for quality assurance of any data and information disseminated through public resources or activities of the CC. The Steering Committee will also be responsible for establishing and implementing a process for recommendation of pilot projects for consideration for funding consistent with expectations set forth in this announcement. The Program Directors/Principal Investigators (PDs/PIs) (or only the Contact PD/PI, in the case of Multiple PDs/PIs grants) from all awarded U01 cooperative agreements (research projects and CC) will be members of the Steering Committee. In the case of projects with multiple PDs/PIs, the designation of the member, Contact PD/PI must be a part of the Multiple PDs/PIs Leadership Plan.
ISCC members will cooperate within the Consortium to share resources, materials, models, methods, information and data to facilitate progress. All research groups will share responsibility for program development and resource coordination through the ISCC Steering Committee that will be established upon award of the grants. When appropriate, and in accordance with NIH policies (https://grants.nih.gov/grants/policy/data_sharing and https://grants.nih.gov/grants/intell-property_64FR72090.pdf), U01 awardees will be expected to collaborate; share novel reagents, biomaterials, methods, models and resources; and share both positive and negative results that would help guide the research activities of other ISCC members. The NIDDK and NIAID, in concert with the ISCC Steering Committee, will have the option to redirect research activities within the ISCC grants if it is considered beneficial to the overall program.
During the course of the funding period, knowledge and technologies will likely improve, and the rate of progress and focus of work supported by the cooperative agreement may change. It is expected that the PDs/PIs, in consultation with NIH Program staff and the Steering Committee, will make necessary adjustments to accommodate the changing research environment, to remain focused on appropriate goals, to maintain excellent coordination with the other projects to avoid overlaps and competition within the Consortium, and to incorporate new research advances.
Bi-annual Meetings of the ISCC Steering Committee
Members of the Steering Committee must participate in person in an initial meeting soon after award, as well as meetings to be held at least bi-annually thereafter. Meetings are expected to be 1-2 days long. In addition, Subcommittees of the Steering Committee, and Working Groups for scientific planning may be established and require participation by the members through in-person, electronic, or teleconference meetings as appropriate. Steering Committee meetings will be organized and administered by the CC in order to determine the final coordinated research projects to be conducted by the research grantees; determine the administrative and scientific needs to be fulfilled by the CC in coordination with the final research projects; share both positive and negative results; share materials including reagents and techniques; evaluate progress; and identify new research opportunities. At the initial meeting, and thereafter as needed, the Steering Committee members will develop policies for confidentiality, what information and materials will be shared, when they will be shared, and how they will be shared within the ISCC and with the research community. All participants will be obligated to abide by the policies adopted by majority vote of the Steering Committee. In the application, research project budget requests must include costs for the PD/PI and up to one other member of the individual project to attend the initial meeting and the bi-annual meetings. Note that the CC will support costs of the Steering Committee meetings except for costs for research project investigators to travel and attend the meetings. The CC is also responsible for providing and maintaining a record of minutes of the meetings, which will be approved by the Steering Committee Chair and membership. Any Subcommittee, Working Group and conference call meetings will be similarly documented. The External Consultants will meet approximately yearly with the Steering Committee.
The NIDDK and NIAID will appoint 3-5 External Consultants to meet with the Steering Committee. This group will be updated on progress and give feedback to the Steering Committee and NIH on adjustments and future directions for the ISCC research projects and CC. The CC will support costs for consultants to meet once yearly with the Steering Committee.
Annual continuation of funds for each research project is dependent on demonstrated progress from the previous year’s funding.
Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this FOA.
NIAID intends to commit $0.5M to fund up to 1 award in FY 2019.
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.
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.
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.
Buttons to access the online ASSIST system or to download application forms 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.
For information on Application Submission and Receipt, visit Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.
John F. Connaughton, Ph.D.
Chief, Scientific Review Branch
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
All instructions in the SF424 (R&R) Application Guide must be followed.
Letters of Support: Letters of support from collaborators should include information on past collaborative experience.
The following modifications also apply:
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.
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.
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. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.
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.
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.
Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?
Specific to this FOA: Is the project of sufficient scope and complexity to warrant a team approach? Do the specific aims form a single cohesive project, and if accomplished will these aims advance the stated goals of the ISCC? Will testing of the proposed hypotheses yield definitive outcomes that can be accomplished during the funding period?
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: Is there evidence of robust collaborations with other members of the Consortium? Do the investigators provide plans on how they will continue interacting with other members of the ISCC? Is the planned effort by the PDs/PIs appropriate and sufficient for the work proposed? Are the investigators’ backgrounds and expertise sufficient to address the proposed scientific problem(s)? Is it clear that each investigator is necessary and will contribute to achieving the goals of the project? Is there evidence for synergistic interactions among PD/PIs beyond the additive benefits of additional investigators?
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?
Specific to this FOA: Does the program involve innovative ideas or approaches that would be very difficult to pursue through independently funded individual or multiple PD/PI research project grants? Does the program involve innovative combinations of scientific expertise and/or intellectual viewpoints to address its goals?
Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?
Specific to this FOA: Do the investigators provide plans for standardizing technical protocols across collaborating laboratories and for data sharing among groups? Is the project presented as a coherent and fully integrated set of specific aims or objectives? Are the approaches appropriate for the specific aims proposed? Is the Collaborative Plan well defined with identifiable responsibilities for the different investigative teams? Is a plan for management of the collaboration presented, as well as descriptions of what each participant proposes to provide to the collaborative partnership?
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?
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?
Specific to this FOA: Is there evidence of synergy to be gained from the involvement of multiple investigators/institutions? Do the investigators provide plans on how the project will take advantage of the services provided by Coordinating Center?
Collaborative Research Opportunities
Does the research project present an opportunity for research that would be enhanced by consortium interaction, collaboration and expertise?
For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.
When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.
The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.
Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.
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).
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.
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.
Information regarding the disposition of applications is available 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.
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.
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.
For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.
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 ISCC consists of Research Project sites and a Coordinating Center, cooperating through a Steering Committee as described above.
The PD(s)/PI(s) will have the primary responsibility for:
NIH Project Scientists will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below.
Areas of Joint Responsibility include:
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 arbitration after first attempting to resolve the issue through the Steering Committee or its subcommittees, as appropriate. An Arbitration 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 in no way affects the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.
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.
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