National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
NIDDK utilizes High Impact, Interdisciplinary Science (RC2) grants to support projects that will lay the foundation for new fields of investigation within the mission of NIDDK. The RC2 is envisioned to use an interdisciplinary approach to generate a research resource and/or foster discovery-based or hypothesis-generating science that can have a significant impact on the broader scientific community.
This targeted FOA specifically seeks to generate scientific advancements addressing the role of the autonomic nervous system in the regulation of peripheral metabolism and its role in diabetes, obesity and related metabolic disease. Interdisciplinary teams may propose to develop resources in the form of novel tools or methodologies that when applied to the autonomic nervous system will contribute to elucidating its functional role in metabolism. Alternatively, teams may focus on novel approaches to address specific knowledge gaps or scientific questions that will significantly contribute to our understanding of role of the autonomic nervous system in metabolism with the goal of accelerating scientific progress in the treatment and prevention of metabolic disease.
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.
August 9, 2018 per issuance of NOT-DK-18-022. (Original Expiration Date: June 02, 2021 )
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.
The autonomic nervous system (ANS), composed of the sympathetic and parasympathetic nervous systems, plays a critical role in the regulation of physiological responses to both internal and external stimuli. While systemic physiological and pharmacological studies provide evidence of a neural contribution to key metabolic processes such as gluconeogenesis, glycogen storage and lipolysis, there is still relatively little known about the neuroanatomy, neurophysiology and molecular biology of the sensory, parasympathetic and sympathetic fibers associated with peripheral tissues, such as the liver and pancreas, Importantly, we still do not know the functional neuronal circuits involved in regulating key metabolic processes involved in metabolic homeostasis.
Detailed neuroanatomical mapping of neurons and neural circuits in the pancreas, liver and adipose tissue is not available. Cell-specific molecular characterization of the neurons in individual tissues or functional connectivity of neurons within these tissues has not been investigated. Defining cellular and circuit-level function is dependent on detailed knowledge about the components and structure of the circuit, including anatomical position, neurotransmitter content, dendritic and axonal connects, receptor profile, role of glia and electrical properties. Approaches used to identify cell-specific function in the central nervous system (CNS) are only recently being applied to the ANS. Recent data suggest that the application of optogenetics and Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) to the peripheral nervous system is not straightforward due to the diverse and unique characteristics of the peripheral tissues innervated by the ANS. Other common methodologies used for the CNS, such as the use of tissue slices, may also be applicable to the ANS. Therefore, the development of new or modification of existing, tools and methodologies that can be utilized to elucidate the role of the ANS in peripheral metabolism would significantly advance scientific exploration of this important area.
In addition to the basic neuroanatomy and neurobiology of the ANS, many scientific questions and gaps remain unanswered regarding the functional role of the ANS in metabolism. Little is known about how changes in the individual branches of the ANS contribute to maintaining metabolic homeostasis during the development of obesity, type 2 diabetes or hepatic steatosis. For example, it is still not clear whether parasympathetic nervous system activity is increased or decreased with increased adiposity or how to reconcile the role of the sympathetic nervous system in obesity in the context of both increased lipolysis and fat deposition. Neural feedback loops involving sensory afferents which monitor changes in the metabolic milieu are likely to influence efferent pathways that regulate metabolic function. Therefore, one would predict temporal changes in the neural control and contribution to tissue function and metabolic homeostasis in the progression from normal physiology to the onset of disease to overt pathology. Hypoglycemia-associated autonomic failure, a consequence of repeated iatrogenic hypoglycemic due to insulin therapy, is known to influence the counter-regulatory responses necessary to establish glucose homeostasis. Methodologies that facilitate the measurement of tissue-specific autonomic neural activity and function within the context of chronic animal models of metabolic disease will greatly contribute to our understanding of how the ANS regulates end organ function and is of primary importance in the development of therapeutics to treat disease.
With this FOA, the Division of Diabetes, Endocrinology and Metabolism within the National Institute of Diabetes and Digestive and Kidney Diseases is calling attention to this fundamental, but difficult, area of science as particularly amenable to multidisciplinary teams of outstanding scientists with expertise in neuroscience, metabolism and autonomic nervous system physiology and function. Additional expertise in data analysis and integration would also be recommended. Projects should focus on end organs or tissues that play a significant role in maintaining metabolic homeostasis or are known contributors to metabolic dysregulation. Tissues of interest include: liver, pancreas, adipose tissue and bone. Applications focusing on other tissues are not responsive to this FOA.
Applications should propose to develop and validate novel tools or methodologies to facilitate the detailed analysis of complex circuits and provide insights into cellular interactions that underlie metabolic processes. The new tools and technologies should confer a high degree of cell-type and/or circuit-level specificity. Alternatively, applications may focus on key hypothesis or scientific questions that address the role of the ANS in metabolic diseases. Validation of the utility of the tool/technology within the context of the functional significance of the circuit or metabolic process is considered a required component of all applications.
Applications focusing on neuroanatomical and histological methods or tools should strongly consider investigating human tissue in addition to tissues derived from animal models.
Examples of Potential Projects:
Development of novel or improved methods (genetic or non-genetic) to deliver active agents such as channel markers or light-sensitive markers to targeted peripheral sensory or efferent neurons innervating end-organs contributing to metabolic homeostasis.
Single cell analysis of peripheral autonomic neurons in tissues regulating metabolism including methods of disassociation of neurons to facilitate single cell analysis and the identification of cell-specific markers.
Identification of functional afferent-efferent neuronal circuits that mediate key metabolic processes such as hepatic glucose production, lipolysis or beiging of adipose tissue
In vitro or in situ systems to investigate the signals necessary for development of parasympathetic or sympathetic neurons from induced pluripotent stem (IPS) cells including co-culturing of neurons with islets, hepatocytes, adipocytes or osteocytes
Development of methods to measure specific tissue-targeted peripheral neural activity or specific tissue function in response to neural stimulation, including implanted sensors in chronic models of metabolic disease.
Scope and Specific Requirements
The scope of this FOA includes, but is not limited to, the following:
Groundbreaking, innovative, high impact and cross-cutting research projects that will improve and accelerate biomedical research.
Basic, clinical and translational projects that could fundamentally enhance the research enterprise and that require the participation, interaction, coordination and integration of activities carried out in multiple research laboratories.
Creation of large scale unique resources and/or development of transformative technologies that can benefit a wide range of investigators.
High-impact discovery-based and hypothesis-generating science.
RC2 projects are not intended to support:
Traditional investigator-initiated, hypothesis-driven and highly focused studies (best supported by the R01 or P01 mechanisms).
Research that is a logical extension of ongoing work.
Core (or related) services to supplement the budgets of existing R01-type efforts.
Applications with a major emphasis outside of the mission of the NIDDK.
Prior Consultation with NIDDK
Consultation with NIDDK staff at least 3 months (and preferably 6 months) prior to the application due date (including resubmission applications) is strongly encouraged for submission of the High Impact, Interdisciplinary Science in NIDDK Research (RC2) application. If requested, NIDDK staff will consider whether the proposed RC2 meets the goals and mission of the Institute; whether it addresses one or more high priority research areas; and whether the application is best fit to the RC2 activity code (or could the proposed work be supported efficiently through traditional NIH funding mechanisms such as a large multi-PI R01).
NIDDK staff will not evaluate the technical and scientific merit of the proposed project; technical and scientific merit will be determined during peer review using the review criteria indicated in this FOA. During the consultation phase, if the proposed project does not meet NIDDK's programmatic needs or is not appropriate for this FOA, applicants will be strongly encouraged to consider other Funding Opportunities.
Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.
Renewal: The number of renewals is not fixed as it is anticipated that the underlying science will change over time. However, the maximum total funding period for any RC2 award is 10 years.
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
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The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.
The total annual cost for individual awards is expected to vary, depending on the scope of the project and the number of participating institutions. Application budgets are not limited but need to reflect the actual needs of the proposed project.
The scope of the proposed project should determine the project period. The maximum project period is 5 years.
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
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.
The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:
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.
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:
The letter of intent should be sent to:
John Connaughton, Ph.D.
Chief, Scientific Review Branch
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
1) A description of the collaborative team aspect of the work proposed including the requirements and roles to be played by each member of the team. The justification for drawing investigators from varied disciplines should be well defined. A rationale must be provided explaining how this grant will enhance integration and collaboration amongst those participants, beyond what would normally be expected of a group of investigators with shared interests at the same institution. These activities should significantly enhance the investigators' existing capabilities and introduce new approaches to the research aims of the collaborative team. The role(s) for each member of the team and how this will provide the requisite synergies for answering the complex problem should be clearly articulated.
2) A clear plan of operation should be provided for the administrative structure and proposed interactions among the investigators. Provide a plan to facilitate the interaction of PD/PIs and key personnel at different sites or institutions, including the need for electronic communication and/or travel. Lines of communication and exchange of data should be clearly established, including how data and resources will be easily shared among the collaborating investigators. The plan for development and use of resources should help to promote the interdisciplinary and collaborative research aspect of the project. The allocation of resources to the development of new technologies in comparison to provision of services with existing technologies should be addressed.
All instructions in the SF424 (R&R) Application Guide must be followed.
Key Personnel salaries derived from the grant will depend on the effort provided and institutional salary as well as existing NIH policies. It is recommended that the contact PD/PI devote at least three person months of his/her efforts to the project. The application should include salaries for individual PD/PIs only to the extent that they provide an essential function of the collaborative team. No overlap of time or effort between this award and separately-funded projects is permitted.
It is anticipated that the research environment available to each team member will be sufficient to support the proposed work. However, requests for essential equipment must include a clear justification in terms of need and service to collaborative team investigators. General purpose equipment needs should be included only after surveying the availability of such items within the institution.
Research patient care costs (both in-patient and out-patient expenses) will be considered in the context of other existing institutional clinical resources. Attempts should be made by the applicant institution to utilize existing clinical facilities, such as CTSAs. Costs relating to the clinical research efforts of investigators may be funded through this award, provided there is no overlap of funding. The RC2 is not intended to be a facility for health care delivery; thus, only those patient costs directly related to research activities may be charged to the grant.
Domestic and foreign travel of project personnel directly related to the collaborative team activities of the award as well as travel of collaborative team members for attendance at annual meetings is allowable.
Consultants and any associated costs (consultant fees, per diem, travel) may be included when their services are required within the award.
Research Strategy: In addition to describing the significance of the problem being addressed and the relevance to the mission of the NIDDK, the applicant should specifically address why the problem is best suited for this FOA, as described below. The application must provide an explanation of how the study proposed will fill a gap in the current knowledge in the field, or contribute a significant resource or technology that is currently lacking. Projects are expected to demonstrate the following:
The work cannot be reasonably expected to be carried out successfully without support provided by this FOA.
Specific outcomes of the proposed project promote and advance the mission of the NIDDK to improve health.
Funding will accelerate current and future research across a broad range that comprehensively encompasses the particular scientific area of study.
The proposed project is something that no other entity is likely or able to do, and there is a public health benefit to having the results of the research in the public domain.
The project or generated results and resources can be expected to become integrated into the broader research community.
There is a plan to sustain applicable research efforts and resources beyond funding.
If the applicant plans to create and appoint an External Advisory Committee (optional), the application must describe the expertise and responsibilities of the potential External Advisory Committee members. For a new application, if applicable, do not contact, recruit, or name potential members. For a renewal application, provide the names of current and former members.
Letters of Support: Any resources or expertise outside of the team of investigators, including institutional support through core facilities or resources, should be evidenced by appropriate letters of support from the relevant individual.
The following modifications also apply:
All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan and comply with NIH Genomic Data Sharing Policy http://Policy https://osp.od.nih.gov/scientific-sharing/genomic-data-sharing. Consents should allow broad sharing of anonymized and de-identified data with the scientific community? and comply with NIH Genomic Data Sharing Policy?.
Applicants are expected to register resources supported by this FOA with the NIDDK Information Network (dkNet) at and use Research Resource Identifiers (RRID) assigned through dkNet in any publication supported by this FOA.
A description of the development, sharing and sustainability of resources generated. If the application proposes the generation of a research resource, the application must provide a description of the resource to be generated. A resource could be something tangible such as biosamples, reagents, antibodies, reporters, cell lines, etc.; or could be the types of datasets generated by discovery research (e.g. RNAseq, omic profiles, epigenetic maps, etc). The application is expected to address how the successful completion of this project will provide a research resource useful for the broader research community. In this section, the applicant should also adequately address how the resource will be shared and sustained beyond the funding period of the RC2 as appropriate and consistent with achieving the goals of the program.
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.
Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide.
The following criteria will be used in the administrative staff review of these requests:
A. Relevance to the NIDDK: Importance of the complex problem or resource to the NIDDK mission.
B. Programmatic priority: Will the proposed research significantly advance the mission of NIDDK?
C. Programmatic balance: How does the proposed research relate to currently funded research in the NIDDK and by the investigative team?
D. Activity Code: Is the proposed work appropriate for the RC2 activity code? Can the proposed work be efficiently supported through traditional NIH funding mechanisms, such as a large multi-PI R01?
Important Update: See NOT-OD-18-228 for updated review language for due dates on or after January 25, 2019.
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.
A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.
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?
In addition, for applications involving clinical trials:
Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?
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?
In addition, for applications involving clinical trials:
With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?
Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?
In addition, for applications involving clinical trials:
Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?
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?
In addition, for applications involving clinical trials:
Does the application adequately address the following, if applicable
Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?
Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?
Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?
Data Management and Statistical Analysis
Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?
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?
In addition, for applications involving clinical trial:
If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?
Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?
If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?
If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?
Has a plan been developed to facilitate the interaction of PD/PIs and key personnel at different sites or institutions? Will data and resources be easily shared with the interdisciplinary team within the collaboration to address the application in an integrated, interdisciplinary way as appropriate and consistent with achieving the goals of the program?
Research Resource or Tool
If the application proposes the generation of a research resource or tool, will successful completion of this project generate a research resource or tool that will be highly useful and/or transformative for the broader community? If so, how will it be sustained beyond the funding period?
Specific to applications involving clinical trials
Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?
Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?
For research that involves human subjects but does not involve one of the 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.
For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.
For Renewals, the committee will consider the progress made in the last funding period.
For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.
Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).
Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).
For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.
Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.
Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications. Following initial peer review, recommended applications will receive a second level of review by the National Diabetes and Digestive and Kidney Diseases Advisory Council (NDDKAC). The following will be considered in making funding decisions:
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.
Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.
If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain "applicable clinical trials" on the ClinicalTrials.gov Protocol Registration and Results System Information Website (http://register.clinicaltrials.gov). NIH expects registration of all trials whether required under the law or not. For more information, see http://grants.nih.gov/ClinicalTrials_fdaaa/
Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that the application as well as all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols. Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).
Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).
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 https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see 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 https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.
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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