Department of Health and Human Services
Part 1. Overview Information

 

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute on Aging (NIA)

Funding Opportunity Title

Clarifying the Relationship between Delirium and Alzheimer’s Disease and Related Dementias (R21/R33)

Activity Code

R21/R33 Phased Innovation Award

Announcement Type

New

Related Notices
  • May 10, 2017 - New NIH "FORMS-E" Grant Application Forms and Instructions Coming for Due Dates On or After January 25, 2018. See NOT-OD-17-062.
Funding Opportunity Announcement (FOA) Number

PAR-17-037

Companion Funding Opportunity

PAR-17-038, R01 Research Project Grant

Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.866 

Funding Opportunity Purpose

This Funding Opportunity Announcement (FOA) invites applications that focus on clarifying the relationship between delirium and Alzheimer's disease and related dementias (ADRD). Specifically sought is research focusing on understanding why persons with ADRD are at increased risk to develop delirium, often with a worse prognosis compared to those without antecedent ADRD, and why patients who experience delirium are at higher risk to develop subsequent short- and/or long-term mild cognitive impairment or ADRD, often with an accelerated rate of cognitive decline compared to those without preceding delirium. Relevant research projects may focus on, but are not limited to, those that A) provide insight into possible common, sequential, causative, contributory and/or synergistic pathways underlying both ADRD and delirium, B) elucidate mechanisms that lead to the development of delirium against the background of aging and/or neurodegeneration, with particular emphasis on use of appropriate animal models, C) identify risk factors for the onset and/or progression of delirium in those with ADRD and vice versa, D) diagnose and assess one condition in the setting of the other, E) identify putative phenotypes of patients with co-existing ADRD and delirium, or F) test pharmacologic and/or non-pharmacologic strategies to prevent, treat, or reduce the impact of delirium in patients with ADRD and vice versa. Research supported by this FOA is intended to provide mechanistic insight to improve risk assessment, diagnosis, phenotyping, prevention, and management approaches for both delirium and ADRD.

This FOA will use the R21/R33 phased innovation mechanism to conduct exploratory/developmental studies focused on feasibility or proof-of-concept that may then transition to an implementation phase following successful achievement of pre-defined investigator-proposed milestones. 

Key Dates

 

Posted Date

October 27, 2016

Open Date (Earliest Submission Date)

January 16, 2017

Letter of Intent Due Date(s)

Not Applicable

Application Due Date(s)

Standard dates apply, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on these dates.

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)

Not Applicable

Scientific Merit Review
Advisory Council Review
Earliest Start Date
Expiration Date

January 8, 2020

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.


There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

  1. Use the NIH ASSIST system to prepare, submit and track your application online.
  2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.

  3. Go to Grants.gov to download an application package to complete the application forms offline or create a Workspace to complete the forms online; submit your application to Grants.gov; and track your application in eRA Commons.
Learn more about the various submission options.

Table of Contents

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


Part 2. Full Text of Announcement
Section I. Funding Opportunity Description
Background/Need

Delirium, defined as an acute decline in cognition and attention, is a common complication of illness, acute trauma, and surgery in older adults, and is associated with multiple adverse outcomes including increased morbidity and mortality, falls, and loss of cognitive and physical function and independence. Accordingly, delirium results in longer lengths of hospital stays and is costly to patients, family/caregivers, and the healthcare system. The actual impact of delirium on these issues is markedly underestimated, as delirium is underdiagnosed and inadequately understood, and yet is potentially preventable. More than 7 million hospitalized Americans suffer from delirium each year, a number which is rapidly growing as seniors live longer, have more polypharmacy, undergo more surgeries, and are more likely to be hospitalized in critical care settings. Previous research has led to development of assessment tools for the diagnosis of delirium, identification of its risk factors, prediction of outcomes, and development of strategies to prevent and/or attenuate the course of delirium. However, elucidation of underlying pathophysiology, distinguishing differing phenotypes, and improving diagnosis and prevention strategies for delirium remain key areas for further research.

Alzheimer’s disease and related dementias (ADRD), like delirium, occur most frequently in the older adult. Moreover, these entities may be related, because patients with underlying dementia are 2.5-4.7 times more likely to develop delirium, and patients with delirium have a 12.5-fold increased incidence of newly diagnosed ADRD, either in the short term or long term after their delirium episode has subsided. Although delirium occurs in 66-89% of persons with Alzheimer's disease (AD) during acute illness and hospitalization, it is often dismissed as an inevitable, but transient, condition in AD patients during hospitalization. Compared to those without preexisting ADRD, those with ADRD who develop delirium have a markedly increased rate of rate of cognitive decline, institutionalization, death and overall increase in adverse outcomes following an episode of delirium. Of those without preexisting ADRD who develop delirium in the ICU, over 30% have cognitive impairment in more than one domain over a year after discharge.

Despite this strong association between ADRD and delirium, the mechanisms underlying this association are poorly understood. Greater insights into the relationship between delirium and ADRD may lead to novel approaches for diagnosis, treatment, and prevention of either or both conditions. Thus, the overall goals of this FOA are to A) provide insight into possible common, sequential, causative, contributory and/or synergistic pathways underlying both ADRD and delirium, B) identify risk factors for the onset and/or progression of delirium in those with ADRD and vice versa, C) diagnose and assess one condition in the setting of the other, D) identify putative phenotypes of patients with co-existing ADRD and delirium, and E) test pharmacologic and/or non-pharmacologic strategies to prevent, treat, or reduce the impact of delirium in patients with ADRD and vice versa.

The relationship between ADRD and delirium was highlighted in a transdisciplinary conference co-sponsored by the NIA and the American Geriatrics Society entitled “Delirium in Older Adults: Finding Order in the Disorder” in February 2014 in Bethesda, Maryland. A summary of this conference was published in the Journal of the American Geriatrics Society in 2015. Subsequently, NIA released RFA-AG-16-009, “Collaborative Network to Advance Delirium Research” to facilitate research addressing these exemplary knowledge gaps. Research supported by the current FOA is intended to provide mechanistic insight to improve risk assessment, diagnosis, phenotyping, prevention, and management approaches for both delirium and ADRD.

Scope of the Research

This FOA invites applications that focus on clarifying the relationship between delirium and ADRD through mechanistic and/or clinical studies in animal models or humans. Research approaches may address underlying etiologies, pathophysiology, risk factors, biomarkers, phenotypic variation, diagnosis, prevention, treatment, or outcomes, and racial/ethnic disparities in any of these domains. Types of studies may include empirical, observational, quasi-experimental, or interventional studies using primary data collection and/or secondary analyses. Leveraging ongoing cohorts, intervention studies, networks, data and specimen repositories, and other existing resources and infrastructure is encouraged, as well as the use of multidisciplinary approaches. Applicants are strongly encouraged to consider the use of measures for behavioral and neurological function from the NIH Toolbox®, particularly the cognitive and emotion batteries or subsets of these, and for self-reported outcomes from the Patient Reported Outcomes Measurement Information System (PROMIS®) (both may be accessed through http://www.healthmeasures.net). Developed under the aegis of the NIH Blueprint for Neuroscience Research, the NIH Toolbox offers a set of brief, comprehensive, well-validated and normed assessment tools that are now available for use on the iPad (https://nihrecord.nih.gov/newsletters/2016/02_12_2016/story4.htm). PROMIS, which provides assessment of meaningful patient-centered outcomes, including quality of life, was developed through support from the NIH Common Fund. These instrument systems may be considered for use as the primary data collection measures or in conjunction with measures commonly used by the investigator(s). Use of these measures helps to build data collection with common measures across diverse study designs and populations, furthering the important goals of efforts such as the Precision Medicine Initiative® (https://www.whitehouse.gov/precision-medicine; http://www.nih.gov/precision-medicine-initiative-cohort-program) and Big Data to Knowledge (https://datascience.nih.gov/bd2k/about) by allowing comparison of results and pooling of data across studies.

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

Elucidating Mechanistic Underpinnings of ADRD and Delirium:

Studies may focus on mechanisms underlying common pathways, causal influences of one condition on the other, shared mechanisms that may increase vulnerability to either condition additively or synergistically. Research on factors including, but not limited to the following, is encouraged:

  • Neurotransmitters
  • Neuroinflammation
  • Neuroimmune factors
  • Systemic inflammatory factors
  • Presence of AD pathology, including amyloid deposition and tau pathology
  • Genetic factors

Identification of Risk Factors for Delirium in ADRD Patients and Vice Versa

Studies may focus on identifying risk factors for ADRD patients at risk for delirium, as well as those that predict the onset of ADRD in patients experiencing delirium without underlying dementia. Risk factors that aid in prognosis are also relevant to this FOA. Risk factors may be unique, or part of a risk assessment tool or panel, and may include, but are not limited to:

  • Biological factors: biomarkers, genetic/metabolomic/proteomic, serum/blood levels of biologic   function, neurotransmitters, surrogate markers
  • Environmental and/or hospital factors: environmental substances or conditions (lighting, noise, day/night cycling, sleep deprivation, immobility)
  • Assessment of physiologic and environment stress
  • Comorbidities including traditional diseases as well as geriatric syndromes (frailty, urinary incontinence, arterial stiffness)
  • Iatrogenic factors: pharmacologic, anesthetics and anesthesia variables (e.g., time and depth of sedation)
  • Imaging: structural, functional and/or immune based, neuroimaging, neuroinflammation

Tools for Diagnosis and/or Assessment of Delirium in ADRD Patients and Vice Versa

Studies may focus on tools to accurately facilitate the assessment and/or diagnosis of delirium in patients with underlying ADRD, as well as tools to provide early diagnosis or assess progression of ADRD in patients with delirium. These assessment instruments may focus on a particular factor or consist of an amalgam of several specific measures from a single source (e.g., biomarker panel) or multiple sources (e.g., biologic + imaging). Diagnostic and assessment tools may include measures from single or numerous sources including, but not limited to:

  • Biological: Biomarkers (existing and novel), genetic/metabolomic/proteomic, serum/blood /urine/cerebrospinal fluid levels of biologic function, neurotransmitters
  • Clinical signs and behaviors, including cognition and affect
  • Tools that employ surrogate response for valid and accurate assessment of prehospitalization cognitive status
  • Imaging: structural, functional and/or immune based; neuroimaging, neuroinflammation
  • Functional brain assessment: electroencephalogram, polysomnography
  • Risk factor assessment as described above

Identification of Specific Phenotypes of Delirium in ADRD Patients and vice versa

Research that provides a better understanding of, and ability to distinguish, differing manifestations of delirium (e.g., hypoactive, hyperactive, superimposed on dementia) is valuable for disentangling

the relationship between delirium, dementia, and other neurological conditions. Thus, applications that promote identification of delirium phenotypes, especially in the setting of existing and/or incident ADRD, are encouraged.

Development and/or Testing of Strategies to Prevent, Treat or Improve the Course and/or Outcome of Delirium in ADRD Patients and Vice Versa

Studies may focus on development of novel or existing pharmacologic or non-pharmacologic strategies, or a combination of these strategies, that can prevent, treat, reduce the severity and/or improve the outcome of delirium in ADRD patients and vice versa, targeting the abovementioned risk factors or newly identified targets. Pharmacologic therapy may span any route of administration including intravenous, oral, spinal, cutaneous or other routes. Psychologic, psychiatric and/or cognitive behavioral therapy may be considered. Outcomes that focus on patient preferences and goals and reflect measures of independence, physical function and quality of life should be considered along with traditional medical outcomes. Surrogate and/or caregiver assessment of the patient's cognitive function and behavior should be considered when appropriate.

Phased Innovation Award

This FOA uses the R21/R33 Phased Innovation Award mechanism. Proposed projects should include both an R21 phase, with milestone-driven developmental activities, and an R33 phase with expanded activities that will build on the initial developmental phase to achieve the aims of the entire award. Applications proposing only R21 or R33 activities alone will not be accepted.

Preliminary data are not required for this FOA, but may be included if available.

Prior to funding an application, program staff will contact the applicant to discuss the proposed milestones. The Program Official and the applicant will negotiate and agree on a final set of milestones. These will be incorporated into the terms and conditions of the award and will be the basis for judging the success of the R21 work.

Prior to the end of the R21 phase, awardees will submit a package that requests transition to the R33 phase. This package will include a progress report that describes progress towards each of the initial milestones, and a clear description of how research during the R33 phase will be impacted by attainment of the R21 milestones. These materials will be reviewed by the NIA Program staff and then, if selected, will be transitioned to an R33 award without the need to submit a new grant application. Decisions on transitioning to the R33 phase will be based on the original R21/R33 peer review recommendations, successful completion of the originally described milestones, program priorities, and availability of funds. If R21 awardees are not ready to submit an R33 transition package prior to the end of the R21 award, a no-cost extension for up to one year may be requested, during which time awardees may submit an R33 transition package. This one-year no cost extension period will not count against the 5-year limit for the entire R21/R33 award.

See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information
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

Application budgets are limited to $275,000 in direct costs over the 2-year R21 phase, with no more than $200,000 allowed in any year Budgets are limited to less than $500,000 annual direct costs in the R33 phase.

Award Project Period

The maximum project period is 2 years for the R21 phase and 3 years for the R33 phase.

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.

Section III. Eligibility Information
1. Eligible Applicants
Eligible Organizations

Higher Education Institutions

  • Public/State Controlled Institutions of Higher Education
  • Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

o   Hispanic-serving Institutions

o   Historically Black Colleges and Universities (HBCUs)

o   Tribally Controlled Colleges and Universities (TCCUs)

o   Alaska Native and Native Hawaiian Serving Institutions

o   Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

  • Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
  • Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

  • Small Businesses
  • For-Profit Organizations (Other than Small Businesses)

Governments

  • State Governments
  • County Governments
  • City or Township Governments
  • Special District Governments
  • Indian/Native American Tribal Governments (Federally Recognized)
  • Indian/Native American Tribal Governments (Other than Federally Recognized)
  • Eligible Agencies of the Federal Government
  • U.S. Territory or Possession

Other

  • Independent School Districts
  • Public Housing Authorities/Indian Housing Authorities
  • Native American Tribal Organizations (other than Federally recognized tribal governments)
  • Faith-based or Community-based Organizations
  • Regional Organizations
  • Non-domestic (non-U.S.) Entities (Foreign Institutions)
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.

Required Registrations

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

  • Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
  • System for Award Management (SAM) (formerly CCR) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM. 
  • eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
  • Grants.gov – Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account.  PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal Investigator)

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.

2. Cost Sharing

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

3. Additional Information on Eligibility
Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time.  This means that the NIH will not accept:

  • A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
  • A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
  • An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).
Section IV. Application and Submission Information
1. Requesting an Application Package

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.

2. Content and Form of Application Submission

It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions 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.

Page Limitations

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

Instructions for Application Submission

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

SF424(R&R) Senior/Key Person Profile

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

R&R or Modular Budget

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

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Specific Aims: Separate specific aims must be presented within the designated page limit for both the R21 and R33 phases.

Research Strategy: The Research Strategy should contain separate sections for both the R21 and R33 phases. It is not necessary to repeat information or details in the R33 section that are described in the R21 section.

Milestones and R21/R33 Transition

Applicants must propose a well-defined set of go/no-go milestones they expect to achieve by the end of the planning phase (R21), as well as milestones for the implementation phase (R33) that build on the initial developmental phase to achieve the aims of the entire award. Milestones should be specific, quantifiable, and scientifically justified; they should not be simply a restatement of the specific aims. The transition from the R21 to the R33 phase of the award will be administratively reviewed and determined by successful completion of the go/no-go criteria that were specified for the R21 phase.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

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.

PHS Inclusion Enrollment Report

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

PHS Assignment Request Form

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

Foreign Institutions

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.

3. Unique Entity Identifier and System for Award Management (SAM)

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

4. Submission Dates and Times

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.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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.

7. Other Submission Requirements and Information

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.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review, NIH. Applications that are incomplete or non-compliant will not be reviewed.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in the policy.

Section V. Application Review Information
1. Criteria

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.

For this particular announcement, note the following:

The R21/R33 phased innovation grant supports investigation of novel scientific ideas or new interventions, model systems, tools, or technologies that have the potential for significant impact on biomedical or behavioral and social sciences research. An R21/R33 grant application need not have preliminary data, extensive background material or preliminary information; however, they may be included if available. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data.  Accordingly, reviewers will focus their evaluation on the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding.  Reviewers will assign a single impact score for the entire application, which includes both the R21 and R33 phases.

 
Overall Impact

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).

Scored Review Criteria

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? 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?  

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? 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? 

Are appropriate separate specific aims presented for both the R21 and R33 phrases? Does the application provide clear go/no-go milestones for the R21 phase and related scientific goals for the R33 phase? Are those milestones conducive to accomplishing the study aims? Are the goals of the R33 phase based, in part, on findings collected during the R21 phase?

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?  

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?   

Additional Review Criteria

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Protections for Human Subjects

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Children 

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following 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.

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

Additional Review Considerations

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)  Genomic Data Sharing Plan (GDS).

Authentication of Key Biological and/or Chemical Resources:

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.

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.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NIA, 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.
3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

Section VI. Award Administration Information
1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website.  This includes any recent legislation and policy applicable to awards that is highlighted on this website.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General  and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency.  HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements.  FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award.  An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS.  The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 “Federal awarding agency review of risk posed by applicants.”  This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

3. Reporting

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final 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.

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.

Section VII. Agency Contacts

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

Application Submission Contacts

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)

Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726

Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)

Telephone: 301-945-7573

Scientific/Research Contact(s)

Susan Zieman, M.D., Ph.D.
National Institute on Aging (NIA)
Telephone: 301-496-6761
Email: susan.zieman@nih.gov

Luci Roberts, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-480-5129
Email: luci.roberts@nih.gov

Peer Review Contact(s)

Ramesh Vemuri, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-496-9666
Email: vemurir@nia.nih.gov

Financial/Grants Management Contact(s)

John Bladen
National Institute on Aging (NIA)
Telephone: 301-402-7730
Email: bladenj@nia.nih.gov

Section VIII. Other Information

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.

Authority and Regulations

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.

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