Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Institute on Aging (NIA) National Cancer Institute (NCI) National Institute on Alcohol Abuse and Alcoholism (NIAAA) National Institute of Allergy and Infectious Diseases (NIAID) Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) National Institute of Environmental Health Sciences (NIEHS) National Center for Complementary and Alternative Medicine (NCCAM) National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Office of Dietary Supplements (ODS) National Heart, Lung, and Blood Institute (NHLBI)
Funding Opportunity Title	Chronic Inflammation and Age-related Disease (R01)
Activity Code	R01 Research Project Grant
Announcement Type	New
Related Notices	June 4, 2014 - Notice NOT-14-074 supersedes instructions in Section III.3 regarding applications that are essentially the same. August 21, 2013: Removed reference to ASSIST in section IV.3, since ASSIST is currently only available for multi-project applications. May 30, 2013 (NOT-OD-13-074) - NIH to Require Use of Updated Electronic Application Forms for Due Dates on or after September 25, 2013. Forms-C applications are required for due dates on or after September 25, 2013.
Funding Opportunity Announcement (FOA) Number	PAR-13-233
Companion Funding Opportunity	None
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.866, 93.393, 93.394, 93.395, 93.396, 93.399, 93.273, 93.855, 93.856, 93.865, 93.113, 93.213, 93.846, 93.837, 93.838, 93.839, 93.233
Funding Opportunity Purpose	The participating NIH Institutes and Centers invite applications to address both the origins and the effects of low level chronic inflammation in the onset and progression of age-related diseases and conditions. Chronic inflammation, as defined by elevated levels of both local and systemic cytokines and other pro-inflammatory factors, is a hallmark of aging in virtually all higher animals including humans and is recognized as a major risk factor for developing age-associated diseases. The spectra of phenotypes capable of generating low-level chronic inflammation and their defining mediators are not clear. Further, a clear understanding of how chronic inflammation compromises the integrity of cells or tissues leading to disease progression is lacking. The role of dietary supplements and/or nutritional status in chronic inflammation in age-related disease is also poorly studied. Thus, there is a critical need to establish the knowledge base that will allow a better understanding of the complex interplay between inflammation and age-related diseases. Applications submitted to this FOA should aim to clarify the molecular and cellular basis for the increase in circulating inflammatory factors with aging, and/or shed light on the cause-effect relationship between inflammation and disease, using pre-clinical (animal or cellular based) models.

Posted Date	May 30, 2013
Open Date (Earliest Submission Date)	September 5, 2013
Letter of Intent Due Date(s)	Not Applicable
Application Due Date(s)	Standard dates apply, by 5:00 PM local time of applicant organization. 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.
AIDS Application Due Date(s)	Standard AIDS dates apply, by 5:00 PM local time of applicant organization.
Scientific Merit Review	Standard dates apply
Advisory Council Review	Standard dates apply
Earliest Start Date	Standard dates apply
Expiration Date	September 8, 2014
Due Dates for E.O. 12372	Not Applicable

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

A central molecular feature of acute inflammation is the production, primarily by innate immune cells, of cytokines, chemokines, and other inflammatory molecules that often expand the response from its tissue of origin to a systemic level. There is considerable epidemiological evidence indicating that aging is associated with a chronic increase in circulating levels of several of these same effectors, including IL-6, TNF-alpha and CRP. The age-related increase in circulating levels of these mediators is generally several orders of magnitude lower than that observed during the classical acute inflammation that occurs in response to injury or infection. In contrast, however, it is significantly longer in duration, often measured in years rather than hours.

Chronic inflammation has been linked to major age-related changes including physical frailty, energy imbalance, homeostatic dysregulation, and changes in body composition which in turn are believed to underlie many of the chronic diseases and conditions affecting the elderly. Indeed, chronic inflammation has been linked to many age-related chronic diseases including neurodegeneration, Alzheimer’s disease, atherosclerosis, cancer, sarcopenia, kidney and lung diseases, metabolic syndrome, diabetes and many others.

Several critical questions remain unanswered, including the cellular origin of the inflammatory mediators and their role in age-related disease, either as causative agents or as a consequence of tissue damage, or whether both are interconnected by a more complex linkage. The role of dietary supplements and/or nutritional status on chronic inflammation is also of interest but poorly studied. It has been proposed that poor immune function, persistent infections (e.g., by CMV or HIV), and breakdown of the intestinal barrier during aging could lead to chronic activation of the innate immune system. In addition, research has shown that pro-inflammatory cytokines can be produced both by senescent cells present in many tissues (and often in higher abundance at sites of injury) and by pre-adipocytes present in fat depots, which also tend to increase with age. At the sub-cellular level, several potential drivers should be examined, including the NF-kB pathway, free radicals, or autophagy. The degree to which each cell type contributes to chronic inflammation at different sites and in relation to different chronic diseases is another open question. Similarly, the role of inflammatory mediators might vary with each specific chronic disease and this also needs to be addressed.

Perhaps the most critical need is to fully understand the potential effects, both positive and negative, of blocking the inflammatory state on different age-related diseases and conditions. While there is epidemiological evidence suggesting a causative role for chronic inflammation in age-associated disease onset and progression, the evidence is still inconclusive. Several clinical trials are currently in progress that will address whether reducing the inflammatory state can affect outcomes (cardiovascular, diabetes and others) in individuals with otherwise comparable classical risk factors for those diseases, yet even the necessary basic understanding of the biology behind these approaches is incomplete.

This FOA aims to clarify the molecular and cellular basis for the increase in circulating inflammatory factors with aging, and to shed light on the cause-effect relationship between inflammation and disease, using pre-clinical (animal or cellular-based) models.

The focus of this FOA is on understanding the basic molecular and cellular mechanisms that link aging with inflammation and chronic diseases. The long term view is to better inform clinical trials and eventually interventions that will directly benefit humankind, but clinical trials are not the focus of this FOA. Experimental approaches might include ablation of relevant aspects of the chronic inflammatory state, comparative biology, expression profiles, or others. Examples of responsive areas of research include, but are not limited to:

• Develop novel technologies and/or approaches that increase the ability to measure low level inflammation in the context of aging organisms.
• Identification of the origin of the pro-inflammatory state associated with aging.
• Further definition of the signature of chronic (as opposed to acute) inflammation in humans or animal models.
• Investigations on the role of chronic inflammation in immune-privileged tissues such as the brain.
• Studies on the role of inflammation on general conditions of aging (frailty, resilience) that predispose to diseases or conditions.
• Studies on the crosstalk between inflammation and tissue metabolic or physiological function.
• Identification of feedback loops and cross-talk between disease and inflammation.
• Possible trade-offs involved in approaches that diminish or eliminate the pro-inflammatory state of aging.
• In animal models, testing the effect of anti-inflammatory interventions on the development of age-related diseases and conditions.

In addition to these common areas of interests, the participating Institutes and Centers (ICs) are interested in the following areas of research:

Office of Dietary Supplements (ODS):

Studies on the role of dietary supplements and/or nutritional status in the chronic inflammation and age related diseases.

National Institute on Alcohol Abuse and Alcoholism (NIAAA):

Many diseases associated with chronic alcohol consumption overlap with those associated with aging, including neurodegeneration, lung infection, muscle wasting, cardiovascular diseases, diabetes, and some cancers. Chronic alcohol consumption leads to chronic elevation of inflammatory markers in circulation. Therefore, NIAAA proposes the following topic areas:

• Characterization of inflammatory mediator profiles associated with aging in the presence and absence of chronic alcohol consumption and expansion of this profile to include more specific and stable markers in the general population. Examination of the relationship between aging and excessive alcohol on chronic inflammatory markers and whether these effects are additive or synergistic would be of interest.
• Investigations on the cellular origin of the inflammatory mediators in age-related inflammation, compared and contrasted with alcohol-related inflammation.
• Comparisons between mechanisms associated with the increased susceptibility to pneumonia due to aging or as a consequence of chronic alcohol intake.

The role of subclinical inflammation and oxidative stress in muscle wasting and comparisons between age-related vs alcohol-related sarcopenia.

National Institute of Allergy and Infectious Diseases (NIAID):

• Studies to understand the links between age-related adiposity, low-level chronic inflammation, and immune system dysfunction in the elderly.
• Mechanisms by which incomplete resolution of an immune response to infection contributes to age-related chronic inflammation.
• Effects of increased levels of reactive oxygen species, declines in anti-oxidant capacity, and/or activation of the innate immune response on age-associated chronic inflammation.
• Determine the mechanisms by which chronic inflammation contributes to immune system dysfunction associated with aging, such as poor immune responses to infections and/or vaccines, and increased incidence of immune-mediated disease.
• Identification of mechanisms or pathways that could be targeted to prevent or reverse chronic immune activation in HIV-infected individuals on suppressive antiretroviral therapy.

National Institute of Environmental Health Science (NIEHS):

• Studies that identify the role of environmental exposures in initiating and/or sustaining a chronic inflammatory state.
• Studies that focus on genetic susceptibility to chronic inflammation and its interaction with environmental exposure in determining risk or protection from age-related diseases or disorders.

National Center for Complementary and Alternative Medicine (NCCAM):

Studies to elucidate molecular targets using non-nutritional natural products that likely modulate the effects of inflammation-induced pain in the elderly. With NCCAM has a special interest in projects that address the following program areas:

• Natural product modulators of inflammation-induced pain that elucidate novel mechanisms of action, including analgesic or noxious stimuli (plant derived analgesics, marine neurotoxins, venoms).
• Anti-inflammatory properties of probiotics in immunosenescence and pain in the elderly.

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS):

The role of chronic inflammation in the pathophysiology, etiology and progression of diseases or conditions in the NIAMS mission area, including (and not limited to) osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, scleroderma, psoriasis, alopecia areata, wound healing. (NIAMS webpage/long range plan: http://www.niams.nih.gov/About_Us/Mission_and_Purpose/long_range.asp)

National Institute of Child Health and Human Development (NICHD):

NICHD is interested in how the inflammatory cytokines generated by adipocytes and by macrophages embedded in the fat mass as a result of childhood obesity can accelerate the appearance of diseases associated with aging, especially T2DM, now commonly seen in adolescence, and atherosclerotic plaques in the third decade.

National Heart, Lung, and Blood Institute (NHLBI):

Investigation into the influence of chronic inflammation associated with aging on the development, etiology and progression of diseases within the NHLBI mission, including (and not limited to) hypertension, aneurysm, lymphatic disease, peripheral vascular disease, atherothrombosis, coronary artery disease, heart failure, idiopathic pulmonary fibrosis (IPF), asthma, chronic obstructive pulmonary disease (COPD), lung vascular disease, anemia, venous thromboembolism (VTE), and chronic inflammatory complications as a function of age that develop in patients following blood transfusion or hematopoietic stem cell transplantation (HSCT), or with hemoglobinopathies.

National Cancer Institute (NCI):

• Studies that define mechanistically how aging-associated inflammation causes cancer initiation, progression, or affects the tumor microenvironment.
• Studies that identify or characterize how etiological factors such as viruses, the microbiota, or chemical exposures influence inflammation-mediated tumorigenesis in aging individuals or models.

Funding Instrument	Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.
Application Types Allowed	New Resubmission The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.
Award Budget	For all participating ICs, with the exception of NHLBI, application budgets are not limited, but need to reflect the actual needs of the proposed project. NHLBI will not accept applications requesting $500,000 or more in direct costs in any year.
Award Project Period	The scope of the proposed project should determine the project period. The maximum project period is 5 years.

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)

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are 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 (PDs/PIs)

All PDs/PIs must have an eRA Commons account and should work with their organizational officials to either create a new account or to affiliate an existing account with the applicant organization’s eRA Commons account. 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.

NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for 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.

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.

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.

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

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

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

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

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.

• 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.

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout 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, NIH. Applications that are incomplete will not be reviewed.

Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact NIH program staff 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.

Note: NHLBI will not accept applications requesting $500,000 or more in direct costs in any year.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.

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? How likely is it that the application will advance our understanding of the relationships between aging, chronic inflammation and chronic disease?

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?

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?

If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

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 Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

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

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.

Renewals

Not Applicable

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

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

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 Center for Scientific Review, 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.

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. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. 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

Not Applicable

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.

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)

Web ticketing system: https://public.era.nih.gov/commonshelp
TTY: 301-451-5939
Email: [email protected]

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 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]

Felipe Sierra, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-496-6402
Email: [email protected]

Alison Deckhut Augustine, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3475
Email: [email protected]

For HIV-related questions:

Peter S. Kim, M.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-451-2761
Fax: 301-402-1505
Email: [email protected]

John Williamson, Ph.D.
National Center for Complementary and Alternative Medicine (NCCAM)
Telephone: 301-496-2583
Email: [email protected]

Bernadette Tyree, Ph.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-5055
Email: [email protected]

Kathy Jung, Ph.D.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-8744
Email: [email protected]

Cindy P. Lawler, Ph.D.
National Institute of Environmental Health Sciences (NIEHS)
Telephone: 919-316-4671
Email: [email protected]

Gilman Grave, M.D.
National Institute of Child Health and Human Development (NICHD)
Telephone: 301-496-5593
Email: [email protected]

Johanna Dwyer, D.Sc., R.D.
Office of Dietary Supplements (NIH/ODS)
Telephone: 301-496-0048
Email [email protected]

Young S. Oh, Ph.D.
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0560
Email: [email protected]

For lung disease-related questions:

Antonello Punturieri, Ph.D.
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0230
Email: [email protected]

For blood disease-related questions:

Andrei Kindzelski, Ph.D.
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-402-0658
Email: [email protected]

Ron Johnson
National Cancer Institute (NCI)
Telephone: 240-276-6228
Email: [email protected]

Maqsood Wani, Ph.D.

Chief, Cell Biology IRG
Center for Scientific Review (CSR)
Telephone: 301-435-2270
Email: [email protected]

Linda Whipp
National Institute on Aging (NIA)
Telephone: 301-496-1472
Email: [email protected]

Donna R. Sullivan
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-594-6361
Email: [email protected]

Shelley M. Carow
National Center for Complementary and Alternative Medicine (NCCAM)
Telephone: 301-594-3788
Email: [email protected]

Melinda B. Nelson
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-435-5278
Email: [email protected]

Judy S. Fox
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-4704
Email: [email protected]

Wanda Boggs
National Institute of Environmental Health Sciences (NIEHS)
Telephone: 919-316-4638
Email: [email protected]

Bryan Clark
National Institute of Child Health and Human Development (NICHD)
Telephone: 301-728-7017
Email: [email protected]

Ann Marie Brasile
National Heart, Blood, and Lung Institute (NHLBI)
Telephone: 301-435-0166
Email: [email protected]

Sean Hine
National Cancer Institute (NCI)
Telephone: 240-276-6291
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.