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
Dementia Care and Caregiver Support Intervention Research (R01 Clinical Trial Required)
Activity Code

R01 Research Project Grant

Announcement Type
Reissue of RFA-AG-18-030
Related Notices

None

Funding Opportunity Announcement (FOA) Number
PAR-21-307
Companion Funding Opportunity
PAR-21-308 , R61/ R33 Phase 1 Exploratory/Developmental Grant/ Exploratory/Developmental Grants Phase II
Assistance Listing Number(s)
93.866
Funding Opportunity Purpose

This Funding Opportunity Announcement (FOA) solicits mechanism-focused dementia care and caregiver support intervention development research at Stages I through V of the NIH Stage Model to address the care needs and promote the health, function, and well-being of persons with Alzheimer’s disease (AD) and Alzheimer’s disease-related dementias (ADRD) and of those providing their care. The NIH Stage Model offers a framework to: (1) support development of efficacious interventions that are defined by their principles; and (2) ensure that these efficacious interventions can be administered in the community or in health systems with fidelity to the intervention’s principles. This includes the development, testing, and validation of scalable training materials and procedures so that these interventions can be delivered with fidelity in community settings or health systems. Settings can include the home, community, or formal care settings, such as nursing homes, assisted living facilities, nursing and rehabilitation centers, hospitals, adult day care, and specialized hospice settings. The overarching purpose of this FOA is to help to lay the groundwork for real-world implementation of AD/ADRD care and caregiving interventions.

The principle-based interventions under development may target behavioral, psychological, interpersonal, social, or institutional processes and may be designed for use at the individual, family, dyad, group, community, or health-systems level. Applications may propose mechanism-focused intervention research for individuals living with dementia or for individuals or systems providing care for people at any stage of AD/ADRD. Applications proposing the development of interventions that address the principles underlying the care needs and challenges for individuals from diverse racial, ethnic, and socioeconomic backgrounds are strongly encouraged. Applications that involve interdisciplinary expertise and translational expertise (e.g., basic behavioral, social, psychological, or neurobiological science expertise relevant to hypothesized intervention mechanisms; expertise in the AD/ADRD service delivery system; and clinical psychological science expertise in areas outside of aging or AD/ADRD, but potentially relevant to AD/ADRD caregiver research, etc.) are also strongly encouraged. Applications may propose to create, modify, and test AD/ADRD care and caregiver support interventions based upon hypothesized mechanisms of action and are encouraged to incorporate a test of essential components or mechanisms of change using an appropriate methodological approach.

Key Dates

Posted Date
August 11, 2021
Open Date (Earliest Submission Date)
September 10, 2021
Letter of Intent Due Date(s)

30 days prior to the application due date

Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS Scientific Merit Review Advisory Council Review Earliest Start Date
October 07, 2021 October 07, 2021 Not Applicable March 2022 May 2022 July 2022
February 10, 2022 February 10, 2022 Not Applicable July 2022 October 2022 December 2022
October 11, 2022 October 11, 2022 Not Applicable March 2023 May 2023 July 2023
February 10, 2023 February 10, 2023 Not Applicable July 2023 October 2023 December 2023
October 10, 2023 October 10, 2023 Not Applicable March 2024 May 2024 July 2024
February 13, 2024 February 13, 2024 Not Applicable July 2024 October 2024 December 2024

All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).

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.

Expiration Date
February 14, 2024
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in 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 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. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.


  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Background

The NIA AD/ADRD Research Implementation Milestones highlight the need for “novel and innovative dissemination and implementation methods to scale up promising practices in dementia care across settings and across disease severity spectrum” (Milestone 13.H). A recent evidence review conducted by the Agency for Healthcare Research and Quality (AHRQ) on “Care Interventions for People Living With Dementia and Their Caregivers” underscored the need for rigorous, well-powered, replicable research addressing issues of intervention fidelity, efficacy, and potential intervention mechanisms, prior to dissemination and implementation on a wide scale. This Funding Opportunity Announcement (FOA) is intended to address challenges highlighted in this evidence review by calling for activities that can lay the groundwork for principle-based Alzheimer's disease (AD) and AD-related dementias (ADRD) care and caregiving interventions that can be delivered with fidelity in the real world. The activities called for in this FOA are designed to facilitate the success of these trials by providing additional stepping stones toward ultimate implementation.

Interventions are described by their essential components, the level of training required, and fidelity. “Simple interventions” are defined in this FOA as single-component interventions that can be administered easily with high fidelity, with minimal or no training required to ensure fidelity (e.g., “nudge” trials, “default” trials, pre-determined text messages etc.). “Complex interventions” are defined in this FOA as single- or multi-component interventions that require training to administer with high fidelity (e.g., interventions administered by clinical personnel, such as palliative care interventions, or interventions to cope with a dementia diagnosis).

Millions of people in the U.S. are afflicted with Alzheimer's disease (AD) and AD-related dementias (ADRD), and this number is increasing. The extensive care needs of individuals with AD/ADRD are variable, and care typically involves great demands on spouses and other family members. Because care also requires coordination with a wide range of community and healthcare providers, it is often associated with high out-of-pocket costs. While many studies have been developed to improve care or support care providers, many factors contribute to the creation of barriers between efficacy and implementation, and few interventions have been implemented at scale. Some of these are systematic barriers that impede implementation and dissemination generally. In addition, some impediments to implementation are specific to the intervention itself, such as deficiencies in (1) knowledge of the underlying mechanism(s) or critical components of the intervention or the implementation strategy for disseminating the intervention, and (2) methods to ensure fidelity of delivery of the intervention in the community, including scalable, tested and validated training materials, that are designed specifically for use by individuals in the community, to deliver complex interventions. This FOA solicits research to address these two major impediments to translation of AD/ADRD interventions into real world settings.

Intervention Principles: The first challenge relates to the lack of knowledge regarding “how and why” interventions work. An insufficient understanding of the underlying principles of interventions, or the mechanisms of action of the interventions, may impede implementation in several ways: 1) simplifying and streamlining an intervention while ensuring that it will retain its potency is not possible when the underlying principles of an intervention are unknown; 2) many interventions need to be modified for a specific population or setting, but modification may interfere with intervention potency if the “active ingredients” necessary for efficacy are inadvertently removed due to adaptation/modification; 3) flexible delivery of interventions is critical to implementation in the community, but interventions cannot be delivered with both flexibility and fidelity if the main underlying principles of an intervention cannot be explained to the person delivering the intervention.

Interventions that are defined by their principles could facilitate implementation by enabling simplification of the intervention and by promoting an understanding of how and when an intervention can or cannot be adapted while still retaining its positive effects. This understanding of principles is required for a scientifically informed understanding of the boundaries in which an intervention can be delivered with flexibility while retaining fidelity, a necessity for successful translation from research to practice.

Training and Fidelity: The second challenge concerns the training and expertise of those who administer intervention trials. Complex interventions conducted in efficacy trials are typically administered by interventionists who are experts or trained by experts, often accompanied by intensive supervision and/or monitoring. Pragmatic clinical trials and real-world implementation realistically cannot involve expert trainers, intensive training, supervision and/or monitoring, but instead may need to rely on training materials provided directly to participants or community representatives. Very few AD/ADRD care and caregiver support interventions, however, include user-friendly, relatively low-cost training materials, geared specifically to the person in the community who will be learning and administering the intervention, and that have been tested and validated for ensuring adequate and sustained fidelity.

This PAR utilizes the NIH Stage Model as its conceptual framework and encourages causal hypothesis testing as described in the Science of Behavior Change (SOBC) experimental medicine approach, wherever appropriate.

The NIH Stage Model for Behavioral Intervention Development: The NIH Stage Model has the goal of creating efficacious, ultimately implementable interventions defined by their principles. It offers a framework for describing where an intervention is in the developmental pipeline and specifies appropriate research activities within different Stages of intervention development. The model facilitates discussion of intervention development research by applicants, reviewers, and funders with a common language. An understanding of the mechanisms of action or the principles underlying an intervention is an inherent goal of the NIH Stage Model.

The NIH Common Fund's Science of Behavior Change (SOBC) Program/Experimental Medicine Approach: The SOBC mechanism-focused, experimental medicine approach is a methodology that is compatible with the NIH Stage Model . It encourages clear a priori specification of the intended mechanistic target(s) of an intervention, and methods that test causal hypotheses about the degree to which an experimental manipulation or intervention engages those targets. Within the experimental medicine approach to behavior change, intervention targets may include mechanisms or processes at any level of analysis (e.g., environmental, social, contextual, interpersonal, behavioral, psychological, and/or neurobiological). The SOBC program established the expectation that behavior change interventions are designed to explicitly test hypotheses about mechanisms of action, and that they incorporate appropriate measures to enable such tests. This includes testing hypotheses about which components of an intervention are responsible for change in a target mechanism or process, as well as hypotheses about whether changes in that mechanism result in a change in the relevant outcome.

This approach, especially when timing is considered within the design (e.g., does the hypothesized mechanism change before the anticipated outcome, or after the anticipated outcome?) and the NIH Stage Model enable each intervention study to contribute to a cumulative science of behavior change, strengthening our understanding of the principles whereby efficacious care and caregiver interventions achieve their effects.

Research Designs

This FOA encourages applications that propose to modify, adapt, and conduct a preliminary test of efficacy and the principles of an existing AD/ADRD care and caregiver support intervention or an intervention originally developed in a non-caregiver population that might be adapted for use in the dementia care and caregiving context. Applicants are expected to articulate their research aims and define the Stage of intervention development proposed using the NIH Stage Model framework. Applicants are required to use an appropriate experimental design to test hypotheses that will identify the essential components of complex interventions, or that will elucidate the mechanism(s) by which an intervention exerts its effects. This FOA also encourages research to develop, test, and validate training materials to ensure fidelity to the principles of an intervention when it is delivered in the real world. The types of behavioral intervention development clinical trials of interest include, but are not limited to, the following:

(1) Mechanism-focused research seeking to develop dementia care and caregiver support interventions defined by their principles. This FOA solicits research to generate, modify, adapt and test interventions while simultaneously testing their hypothesized mechanism of action. Appropriate studies include the following:

  • Stage I mechanism-focused, adequately powered studies to leverage and incorporate Stage 0 (basic science) findings to create and conduct a preliminary test of a dementia care or caregiver support intervention for efficacy and for its principles.
  • Stage I mechanism-focused, adequately powered studies to modify/adapt, in accordance with its principles, and to conduct a preliminary test of an intervention:
    • Adapt and test an evidence-based non-caregiving intervention to a dementia care/caregiving context or population;
    • Modify the form of an existing dementia care/caregiving intervention into a more scalable, streamlined, simplified, and more easily implementable form, and conduct a preliminary test;
    • Modify the form of an existing dementia care/caregiving intervention to improve potency, and conduct a preliminary test.
  • Stage II or III studies testing efficacy using an adequately powered and appropriate experimental design (e.g., experimental medicine approach; factorial or partial factorial design; sequential, multiple assignment, randomized trial (SMART) approach, "MOST," or Multiphase Optimization Strategy) to determine/confirm efficacy and mechanisms of action or essential ingredients.
  • Stage IV studies that test effectiveness of interventions defined by their mechanisms/principles, using an adequately powered and appropriate experimental design. This may include Stage IV Rapid Pragmatic Trials. When Stage IV Rapid Pragmatic Trials are proposed, please note the following:
    • Simple interventions (e.g., "nudge" trials, "default" trials, pre-determined text messages, etc.): must replicate results.
    • Complex interventions: replication is encouraged but not required.
  • Stage V studies aimed at determining the mechanisms of AD/ADRD care and caregiver support intervention implementation strategies.

Two of many possible examples of mechanistic hypotheses and the testing of these hypotheses are provided below for illustrative purposes. Applications proposing mechanisms-focused intervention development work would be designed to test such hypotheses:

  • Example 1: Hypothesizing, based on basic science findings, that changing (increasing or decreasing) a specific target (e.g., a type of empathy such as emotional or cognitive empathy or compassion) will lead to decreased negative affect (e.g., depressive affect or anxiety) in caregivers, and testing whether an intervention designed to change this type of empathy does so (engages the target), and determining if these changes are causally related to the hypothesized changes in caregiver anxiety.
  • Example 2: Hypothesizing, based on basic science findings, that a specific type of music (e.g., music that is known to be liked by the recipient; music of a certain type, like classical music; or music that was played at a critical period during brain development) when played in a specific way, engages a specific target (e.g., emotion, emotion regulation, specific types of memories, etc.) which will lead to the desired outcome (e.g., improved well-being, better emotion regulation, decreased anxiety, improved memory) in persons living with dementia; followed by testing whether a specially-designed music intervention causes the changes in the specified target, and, if so, if these changes are causally related to the hypothesized outcomes.

(2) Research that seeks to enhance fidelity and/or develop, test, and validate training materials to ensure fidelity to the principles of the interventions for those in the community who deliver the interventions. Such projects may include, but are not limited to, the following:

  • Modifying an Intervention to Promote Fidelity: Stage I and Stage III research, guided by the hypothesized mechanisms of change of an intervention, to modify and conduct an adequately-powered preliminary test of this modified intervention, with the goal of maximizing the “real-world” fidelity of delivery to the principles of the intervention while retaining the intervention’s essential “ingredients” (e.g., simplification of the intervention, computerization of intervention modules while retaining intervention potency, etc.).
  • Training Procedure Development and Testing: Within the NIH Stage Model, an efficacious intervention is considered incompletely developed until it can be delivered in the community with fidelity to its principles. Training procedures to ensure optimal fidelity may be developed and preliminarily tested within Stage I studies, and further tested within community-based Stage III trials. Such research is meant to be guided by a focus on determining the mechanisms/principles of an intervention to produce operationalized and validated training materials that result in fidelity to those mechanisms/principles. This FOA supports adequately powered Stage I or Stage III research to create, test, and validate user-friendly, easily deliverable interventions to train care providers in the community to deliver an intervention while maintaining fidelity to the principles of the intervention. Applications proposing to develop training materials for such interventions would aim to ensure that the delivery of the intervention remains true to its principles of action. Examples include, but are not limited to, the following:
    • Modules to train community interventionists (e.g., caregivers, nursing assistants, nurses, occupational therapists, physicians) to deliver specific elements of a complex AD/ADRD care intervention with fidelity in nursing homes or assisted living settings.
    • Modules to train community interventionists to deliver an intervention with fidelity to a family care provider.
    • "Gamified” training materials that community interventionists enjoy, and that increase fidelity of delivery.
    • Training modules, methods, or procedures to improve memory for the essential ingredients/elements or principles underlying an intervention, increasing memory for training materials, and thus increasing fidelity of delivery.
    • Training materials for any intervention that requires training to ensure fidelity to the intervention’s principles when administered in the community.

Specific Areas of Research Interest

AD/ADRD care and caregiver support intervention research can be for ultimate implementation in the home, community, or formal care settings, such as primary care, nursing homes, assisted living facilities, nursing and rehabilitation centers, hospitals, adult day care, and specialized hospice settings. These interventions may target behavioral, psychological, interpersonal, social, or institutional processes and may be designed for use at the individual, family, dyad, group, community, or health systems level. AD/ADRD care and caregiver support interventions may be studied within Stages I, II, III, or IV. Implementation strategies for AD/ADRD care and caregiver support interventions may be studied within Stage V. Applications may propose intervention research for individuals or systems who are providing care for people at early-, mid-, or late-stage AD/ADRD. Applications that address the principles underlying the care needs and challenges for individuals from diverse racial, ethnic, geographic, and socioeconomic backgrounds are strongly encouraged. Applications that involve interdisciplinary and translational expertise, as relevant (e.g., basic science expertise regarding questions about mechanisms; healthcare system expertise when designing interventions to be used in assisted living or nursing home settings) are strongly encouraged. Applications are expected to propose principle-driven intervention development research with an eye toward real-world implementation, involving stakeholders and community participants wherever appropriate. Applications are required to use an appropriate methodology (e.g., the experimental medicine approach) to identify the essential components of interventions, to determine the mechanism(s) responsible for an intervention’s effects, or to demonstrate that intervention can be delivered with fidelity to the principles or mechanisms of action.

Dementia care and caregiver support interventions can focus on a variety of outcomes for the person living with dementia and/or their caregiver, including, but not limited to improvements in sleep, subjective well-being and quality of life, stress coping and stress management, decision-making, care planning, financial planning, adherence to health-promoting behaviors, memory, relationship quality, social engagement, management of behavioral symptoms of dementia, care coordination, care quality, and care delivery.

Intervention approaches may be derived from a variety of fields, including from psychology, neuroscience, behavioral economics, behavioral medicine, health services research, communication science, psychiatry, and geriatric medicine. Digital/mHealth or other technology approaches may be harnessed. Interventions may be at the individual, interpersonal, or systemic level and can include such things as environmental modification, electronic health record (EHR) modification, care coordination modification, etc.

Examples of individual, dyadic, or group level interventions for persons living with dementia and/or their care partners include, but are not limited to, the following:

  • Empathy/compassion-focused interventions to promote emotional well-being for care providers or recipients informed by and incorporating Stage 0 (basic) research on empathy and compassion.
  • Music-based interventions informed by Stage 0 basic research on music, the brain, and human development to inform dosage, type, frequency, etc. of the intervention.
  • Interpersonal interventions (e.g., dyadic caregiver/person with dementia, or interventions with caregivers, care recipients, and providers) leveraging and incorporating Stage 0 research on social, interpersonal, or affective processes.
  • Memory-focused interventions, informed by basic or clinical research on cognition and/or memory, to serve as an adjunct to another health-promoting intervention (e.g., a medication adherence intervention, an intervention to treat insomnia, an intervention to minimize negative affect, etc.) to improve the potency of that intervention.
  • Interventions designed to decrease depression or anxiety levels, adapted for caregivers from interventions designed to decrease anxiety in other populations that are based upon basic principles of behavior change (e.g., behavioral activation, principles of extinction, inhibitory learning, etc.)

Examples of interventions at the organizational or institutional level in Long Term Services and Supports (LTSS) settings, such as in-home health care, assisted living facilities, adult day cares, nursing homes, hospices, hospitals, include, but are not limited to, the following:

  • Care coordination (within a health system or between a health system and a home or community-based system) interventions informed by and incorporating Stage 0 (basic) research on organizational and care team-level processes/mechanisms.
  • Patient or provider decision supportive interventions (e.g., advance care planning, de-prescribing, referral to palliative care services) informed by and incorporating Stage 0 (basic) research on features of incentives, framing, choice architectures, organizational processes/mechanisms, etc.
  • Organizational interventions to promote well-being and quality of life and reduce distress through environmental modification or modification of programs informed by and incorporating Stage 0 (basic) research on environmental affordances, systems processes, and/or processes that impact individual well-being.

Applications Not Responsive to this FOA

The following types of applications will be considered nonresponsive and will not be reviewed. This includes applications that:

  • Do not propose a clinical trial, identified as Stage I, II, III, IV, or V as the primary specific aim.
  • Do not propose a hypothesized mechanism of action or hypothesized essential ingredients based upon quantitative data (hypotheses based solely upon qualitative data will not be reviewed).
  • Do not address issues of power.
  • For Stage IV rapid pragmatic trials only: do not identify as a simple or complex intervention.
  • For Stage IV rapid pragmatic trials only: do not replicate results for simple interventions.
  • For Stage IV and V trials: Do not address generalizability to diverse populations.

Design, Analysis, and Sample Size for Studies to Evaluate Group-Based Interventions: Investigators who wish to evaluate the effect of an intervention on a health-related biomedical or behavioral outcome may propose a study in which (1) groups or clusters are assigned to study arms and individual observations are analyzed to evaluate the effect of the intervention, or (2) participants are assigned individually to study arms but receive at least some of their intervention in a real or virtual group or through a shared facilitator. Such studies may propose a parallel group- or cluster-randomized trial, an individually randomized group-treatment trial, a stepped-wedge design, or a quasi-experimental version of one of these designs. In these studies, special methods may be warranted for analysis and sample size estimation. Applicants should show that their methods are appropriate given their plans for assignment of participants and delivery of interventions. Additional information is available at https://researchmethodsresources.nih.gov/.

The National Institute on Aging (NIA) supports a central resource to NIA staff and extramural investigators to facilitate/support the conduct and management of clinical research. This resource, the Clinical Research Operations Management System (CROMS), is a comprehensive data management system to support the business functions, management, and oversight responsibilities of NIA grants that support the conduct of clinical research with human subjects. It is the expectation by NIA that all successful applicants will interface, integrate, or adapt their information system(s) and processes to interact with existing and future components of the CROMS as necessary.

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
Renewal
Resubmission
Revision

Resubmissions from RFA-AG-18-030 "Dementia Care and Caregiver Support Interventions (R01 - Clinical Trial Required)" are not allowed.

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.

Clinical Trial?

Required: Only accepting applications that propose clinical trial(s).

Need help determining whether you are doing a clinical trial?

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 not limited but need to reflect the actual needs of the proposed project.

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 from 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:

  • 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)

Local 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)

Federal Governments

  • 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) – 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.
  • eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. 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

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace 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 instructions in the Research (R) 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.

Letter of Intent

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

  • Descriptive title of proposed activity
  • Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
  • Names of other key personnel
  • Participating institution(s)
  • Number and title of this funding opportunity

The letter of intent should be sent to:

Lisa Onken, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-496-3136
Email: lisa.onken@nih.gov

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.

Interdisciplinary and translational expertise, as relevant, is strongly encouraged.

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:

The research plan should provide the background and scientific justification for the trial and should address the following.

Significance: The significance of the proposed trial must be stated clearly. A compelling argument must be presented of how the proposed trial will shift caregiver intervention practice or inform health care policy.

Innovation: The application must challenge and seek to shift current behavioral intervention research or clinical dementia care practice paradigms by utilizing the NIH Stage Model.

Approach:The Approach must provide justification for the selected trial elements provided in the Protocol Synopsis, and should include the following:

  • An overview of the proposed study design that must include the following:
    • Stage of Intervention Research (e.g., Stage I, II, III, IV or V of the NIH Stage Model).
    • Rationale for the selected Stage. This includes justification of the evidence from previous basic behavioral/social/affective/cognitive research or from previous relevant clinical trials that the proposed Stage is appropriate.
    • Hypothesized principles or “mechanism of action” of the intervention, including the behavioral, cognitive, affective, or social targets it is hypothesized to engage.
    • Plans for addressing the fidelity of intervention delivery.
    • Rationale for intervention study design (e.g., single case study, multiple baseline, adaptive/SMART design, factorial, partial factorial).
    • Explanation of the hypothesized relevance of process variables (i.e., hypothesized causal targets) and outcome variables (i.e., ultimate behavior to be modified) to the clinical and statistical hypothesis being tested (i.e., the hypothesized role each variable plays in the causal chain; specification of variables as hypothesized moderators, mediators, or outcomes).
    • Discussion of potential biases or challenges in the trial and how they will be addressed and mitigated.
    • Discussion of potential threats to validity and provide clear power calculations that reflect a range of effects sizes of clinical significance.
    • Explanation of how to incorporate trial design with rigorous controls for the Stage of intervention proposed.
    • For Stage I, II, and II studies, explanation of how the design maximizes internal validity of the study.
  • The scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention is appropriate for the Stage of intervention development being proposed (as defined by the NIH Stage Model) and the Stage of the clinical trial proposed is well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of behavioral, social, cognitive, or biological mechanisms.
  • The application provides clear milestones for anticipated next steps through intervention development Stages if the proposed study is successful.
  • For Stage IV and Stage V trials, discussion of how the design maximizes external validity, generalizability, and sustainability of findings across distinct health care settings and diverse staff, caregiver, and patient populations.
  • For Stage IV studies on interventions that require training, real-world training materials have been developed, tested, and validated to ensure the intervention can be delivered in the community with fidelity.
  • For Stage IV studies, the application should include how the intervention applies broadly to diverse AD/ADRD patient population or their caregivers, and how the intervention is suitable for use in real-world settings. The application should also address how the intervention will be well poised to be adopted within a Stage V study (dissemination and implementation).
  • For Stage IV pragmatic trials and Stage V studies, the application describes the partnerships with home health agencies, meal delivery services, adult day centers, respite care centers, assisted living facilities, memory units, nursing homes or other care providers, both nonresidential and residential, and the application documents the commitment of the organization to the project. The application describes how the project will be able to access administrative data (e.g. Medicare or Medicaid claims or Electronic Health Records (EHR)) and implement pilot interventions in various settings (e.g. is there a letter of support if the application proposed to access EHR in a nursing home).

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.

All applications, regardless of the amount of direct costs requested for any one year, should include a Data Sharing Plan.

Appendix:
Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

The NIH announced a policy on allowable appendix materials (NOT-OD-17-098); however, this FOA allows specific materials to be included as appendices that are otherwise disallowed by the general policy. Applications may include as appendices the following materials: focus group guides, structured interview schedules, blank questionnaires or surveys with instructions, observational coding systems, fidelity monitoring checklists and rating tools, and draft or sample intervention manuals. 

PHS Human Subjects and Clinical Trials Information

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

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

The research strategy section of the application should justify the specifics of the trial, such as the proposed intervention and its target(s), stage of intervention research, and characteristics of the study population.

Section 3 - Protection And Monitoring Plans

3.3 Data and Safety Monitoring Plan

The Data and Safety Monitoring Plan (DSMP) should include a description of data monitoring activities, consistent with the NIA Guidance on Clinical Trials. This DSMP should include the following:

  • Plans to ensure that validated systems and controls are in place to assure the integrity of the clinical trial data being collected;
  • Proposed methods and systems for data collection (e.g., Case Report Forms/CRFs), data entry, data verification and data validation. Describe the data query process and frequencies and any planned mitigation strategies in the event of noncompliance;
  • The process for locking the final trial datasets for analysis.

Do not name members of any oversight board in the application. The NIA will appoint members of any oversight committees after consultation with the clinical trial investigator team.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

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 How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. 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 and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

In order to expedite review, applicants are requested to notify the NIA Referral Office by email at ramesh.vemuri@nih.gov when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

Requests of $500,000 or more for direct costs in any year

Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide.

Post Submission Materials

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

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process.  Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

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 the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Specific to this FOA: Is significance of the proposed trial clearly stated? Is there a compelling argument for how the proposed trial will shift care or caregiver intervention practice or inform health care policy?

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

 

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

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?

Specific to this FOA: Does the application challenge and seek to shift current behavioral intervention research or clinical dementia care practice paradigms by utilizing NIH Stage Model?

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed 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?

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 individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Specific to this FOA:

How well does the Approach provide justification for the selected trial elements provided in the Protocol Synopsis? To what extent the overview of the proposed study design include the Stage of Intervention Research (e.g., Stage I, II, III, IV or V of the NIH Stage Model)?

To what degree does the study design include the rationale for the selected Stage, including justification of the evidence from previous basic behavioral/social/affective/ cognitive research or previous relevant clinical trials?

How well does the study design include hypothesized principles or “mechanism of action” of the intervention, including the behavioral, cognitive, affective, or social targets it is hypothesized to engage?

To what extent does the study design include plans for addressing the fidelity of intervention delivery?

To what degree does the study design include rationale for the intervention study design (e.g., single case study, multiple baseline, adaptive/SMART design, factorial, partial factorial)?

How well does the study design include an explanation of the hypothesized relevance of process variables (i.e., hypothesized causal targets) and outcome variables (i.e., ultimate behavior to be modified) to the clinical and statistical hypothesis being tested (i.e., the hypothesized role each variable plays in the causal chain; specification of variables as hypothesized moderators, mediators, or outcomes)?

To what extent does the study design include discussion of potential biases or challenges to the integrity of the trial and how they will be addressed and mitigated?

To what degree does the application address potential threats to validity and present clear power calculations that reflect a range of effect sizes of clinical significance?

To what extent does the application incorporate trial design with rigorous controls for Stage of intervention proposed?

For Stage I, II, and III how well does the design maximize internal validity of the study?

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention appropriate for the Stage of intervention development being proposed (as defined by the NIH Stage Model) and is the Stage of the clinical trial proposed well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of behavioral, social, cognitive or biological mechanisms?

For Stage IV and Stage V trials, how well does the design maximize external validity? How well does this study test generalizability, and sustainability of findings across distinct health care settings and diverse staff, caregiver, and patient populations?

For Stage IV studies on interventions which require training, have real-world training materials been developed, tested, and validated to ensure the intervention can be delivered in the community with fidelity?

For Stage IV studies, how well did the application characterize the intervention? Does the intervention apply broadly to diverse AD/ADRD patient population or their caregivers? Is the intervention suitable for use in real-world settings? If successful, will the intervention be well poised to be adopted within a Stage V study (dissemination and implementation)?

For Stage IV pragmatic trials and Stage V studies, how strong are the partnerships with home health agencies, meal delivery services, adult day centers, respite care centers, assisted living facilities, memory units, nursing homes or other care providers, both nonresidential and residential, and did the application document commitment of the organization to the project? Will the PDs/PIs be able to access administrative data (e.g., Medicare or Medicaid claims or Electronic Health Records) and implement pilot interventions in various settings (e.g., is there a letter of support if the application proposed to access EHR in a nursing home)?

Is the complete Clinical Protocol appropriate for the proposed Stage?

Does the application adequately address the following, if applicable

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

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?

 

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

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.

Specific to this FOA: If this proposed study is successful, does the application provide clear milestones which describe anticipated next steps? That is, what is the anticipated pathway (after the grant period ends) through the Stages of intervention development?

Study Timeline


Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

Protections for Human Subjects

For research that involves human subjects but does not involve one of the 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 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 Individuals Across the Lifespan

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 individuals of all ages (including children and older adults) 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

For Renewals, the committee will consider the progress made in the last funding period.

Revisions

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

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 the National Institute on Aging , 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 will receive a written critique.

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.

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 recipient's business official.

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

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

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain “applicable clinical trials” on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

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, Recipients, 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 laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html.

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.

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.

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 RPPR, 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, application errors and warnings, documenting system problems that threaten submission by the due date, and 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)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

Scientific/Research Contact(s)

Lisa Onken, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-496-3136
Email: lisa.onken@nih.gov

Peer Review Contact(s)

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

Financial/Grants Management Contact(s)

Ryan Blakeney
National Institute on Aging (NIA)
Telephone: 301-451-9802
Email: ryan.blakeney@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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