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
Pragmatic Trials for Dementia Care and Caregiver Support (R61/R33 – Clinical Trial Required)
Activity Code

R61/R33 Exploratory/Developmental  Phased Award

Announcement Type
Reissue of PAR-18-585
Related Notices

None

Funding Opportunity Announcement (FOA) Number
PAR-21-308
Companion Funding Opportunity
PAR-21-307 , R01 Research Project
Assistance Listing Number(s)
93.866
Funding Opportunity Purpose

This Funding Opportunity Announcement (FOA) will support pragmatic trials within Stage IV of the NIH Stage Model to improve dementia care across multiple dementia care settings that will: (1) be designed to address practical comparative questions faced by Alzheimer’s disease (AD) and AD-related dementia (ADRD) patients, clinicians, and caregivers (both paid and unpaid); (2) include broad and diverse populations; and (3) be conducted in real-world settings with adequate sample size. These trials are intended to produce results that can be directly adopted by healthcare providers, patients, or caregivers for rapid dissemination and implementation. Successful applications will: (1) improve quality of care of persons with dementia; (2) improve quality of life for persons with dementia and their informal caregivers; (3) deliver more patient-focused, cost-effective care across multiple settings; and/or (4) reduce disparities in dementia care.

This FOA will support Stage I or Stage III pilot research to test the feasibility of implementing and integrating interventions (R61 phase) that, if successful, can transition to an R33 phase (Stage IV) for implementation of large pragmatic trials.

The transition from the R61 to the R33 phase of the award will be administratively reviewed and determined by successful completion of the go/no-go criteria that are specified for the R61 phase.

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 AD/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 steppingstones toward ultimate implementation.

This FOA will support pragmatic trials within Stage IV of the NIH Stage Model that will: 1) be designed to address practical comparative questions faced by Alzheimer’s disease (AD) and AD-related dementia (ADRD) patients, clinicians, and caregivers (both paid and unpaid); 2) include broad and diverse populations; and 3) be conducted in real-world settings in order to improve dementia care across multiple dementia care settings. Trials of interest to NIA are those which can provide insight leading to improvements in clinical outcomes and lessening of caregiver burden, and which can be directly adopted by healthcare providers, patients, or caregivers. They should be conducted, where possible, in routine clinical or home care settings, with adequate sample sizes to detect clinically significant differences in meaningful outcomes and should, where appropriate, address effectiveness across diverse populations.

This PAR utilizes the NIH Stage Model as its conceptual framework:

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 for complex interventions that are designed specifically for individuals in the community.

The NIH Stage Model for Behavioral Intervention Development is intended to address these impediments. It has the goal of creating efficacious, ultimately implementable interventions defined by their principles and 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 inherent in the NIH Stage Model.

For this FOA, pragmatic trials should assess an intervention in the conditions in which it is intended to be used, rather than in ideal circumstances (see "Introduction to pragmatic clinical trials"; “Rethinking Clinical Trials: A Living Textbook of Pragmatic Trials” and NIA AD/ADRD Health Care Systems Research Collaboratory). Trials of interventions that require training to ensure fidelity of delivery, where the validation of training materials has not yet been conducted, should be submitted to PAR-21-307.

Specific Areas of Research Interest

Appropriate settings for pragmatic trials funded under this FOA are home settings (e.g., interventions provided by home health agencies or meal delivery services), adult day centers, respite care centers, assisted living facilities, memory units, nursing homes, health care clinics, or nonresidential and residential settings. Clinical trial designs with outcomes that use administrative data and/or measurements using technology (e.g., patient or caregiver reported outcomes using smartphone or other technology) to enhance generalizability are required. Interventions can involve changes in services, staffing, and training (validated training materials required from previous studies or training materials need to be modified from previous studies during the R61 Phase), environmental modifications, or service coordination, with quality of care and quality of life for persons with dementia and their informal caregivers assessed as primary outcomes. Additional secondary outcomes can include the quality of work life and staff turnover for service-providing agencies. Proposed applications can also collect and analyze data on the use of acute care, timing and frequency of transitions to acute care and rehabilitation settings, and multi-morbidity. PDs/PIs are encouraged to define outcomes and specify the cost associated with capturing outcomes data.

Potential interventions include, but are not limited to, the following:

  • Behavioral economics interventions, such as interventions to improve: uptake of preventive services or guideline concordant care for persons with dementia; improving care of AD/ADRD patients in Long-term Services and Supports (LTSS) settings; improving nursing home staff morale, etc.
  • Pharmacological and non-pharmacological treatments in managing behavioral disorders in people with AD/ADRD in home and institutional settings.
  • Management strategies (e.g., pharmacological treatment, social/family support, combined pharmacological and social/family support) for dementia in community-dwelling people and their caregivers.
  • Strategies to detect/measure/assess dementia.
  • Models of palliative and hospice care for persons with advanced dementia and their families.
  • Interventions aimed at ameliorating racial and ethnic disparities in the treatment of dementia patients.
  • Interventions to help individuals with AD/ADRD and their families navigate the interface of informal and formal care, determine appropriate care transitions, and secure adequate care coordination.
  • Financial planning interventions aimed at anticipating costs of long-term services, supports, and palliative care to help mitigate the effects of such financial strain on the health and well-being of AD/ADRD caregivers and care recipients.
  • Interventions addressing practices of health and long-term care systems that lead to burdensome transitions for persons with advanced dementia.
  • Arts and music-based interventions to improve the well-being of persons with AD/ADRD.
  • Rapidly scalable technology-based interventions to improve health outcomes of caregivers of individuals with AD/ADRD.
  • Interventions integrating application of machine learning and artificial intelligence to improve health outcome and decisions making (e.g., Part D drug plan choice) of persons with AD/ADRD.
  • Telehealth services intervention within LTSS setting to reduce transition to emergency rooms/hospital from nursing home of patients with AD/ADRD.

The trial outcome measure(s) should be clinically meaningful and provide useful information to medical decision makers, whether patients, care providers, health care systems, payers, or policy makers. Outcome measures such as use of health care services, patient and caregiver reported outcomes and other resources should be included.

Research Design

This FOA seeks applications for two types of interventions, with two options for pathways through the Stages of intervention development.

Two Types of Interventions:

  1. “Simple interventions,” defined here as single-component interventions that can be administered easily with high fidelity, with minimal or no training required to ensure fidelity. (Examples: “Nudge” trials, “default” trials, pre-determined text messages, etc.)
  2. “Complex interventions,” defined here as single- or multi-component interventions that require training to administer with high fidelity. (Examples: Interventions administered by clinical personnel, such as palliative care interventions, or interventions to cope with a dementia diagnosis.)

Two Options through the pathways of intervention development:

  • Option 1: Applications on simple interventions may propose Stage I research in the R61 phase and Stage IV research in the R33 phase:
    • R61 Phase: Stage I research to create and/or adapt, and pilot test an intervention.
    • R33 Phase: Stage IV pragmatic clinical trial
  • Option 2: Applications on complex interventions may propose Stage III research in the R61 phase and Stage IV research in the R33 phase:
    • R61 Phase: Stage III research to test the efficacy of operationalized training procedures with the simultaneous testing of the efficacy of the intervention in a community setting.
    • R33 Phase: Stage IV pragmatic clinical trial

The R61 Phase

  1. Option 1 for R61: Stage I intervention development research for simple interventions. During this phase, Stage I research may be conducted to create and/or adapt, examine feasibility and acceptability, and pilot test an intervention to ensure its readiness for a Stage IV pragmatic trial. During the R61 pilot phase, researchers may also conduct, if necessary, the development of instruments and validations of such instruments within health systems to establish their feasibility. They will conduct Stage I research to create or adapt interventions, tailored as necessary to the targeted populations. Interventions, if feasible, acceptable, and showing preliminary evidence of efficacy, can then transition to the R33 phase for implementation of Stage IV pragmatic trials. The specific activities and milestones appropriate for the R61 phase will depend on the individual application and its stage of development.
  2. Option 2 for R61: Stage III intervention development research for complex interventions. R61 Stage III research is community-based efficacy testing and includes the testing of operationalized and scalable training procedures, along with the simultaneous testing of the efficacy of the intervention.

The applicant must include/address, as appropriate, the following activities and milestones for the R61 phase:

  • Specify hypothesized mechanism of action or the principles underlying an intervention (e.g., behavioral economics principle), and the empirical basis for this hypothesis.
  • Fidelity and acceptability in clinical settings.
  • Plan for refining estimates of requirements based on R61 findings with guidance from NIH staff for sample size, numbers of sites, site-to-site heterogeneity, and the implementation timetable.
  • Operationalize intervention and establish partnership with a care provider (e.g., 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 document commitment of the organization to the project.
  • Obtain access to administrative data and implement pilot interventions.
  • Operationalize definitions and objective measures.
  • Assess and justify adequacy and finalize clinically-relevant outcome measures. Note that no project will be allowed to move to the translation/implementation phase without validation data from instrument testing during the R61 phase for Option 2 studies.
  • Consistent with hypothesized mechanisms/principles of the intervention, adapt, as necessary and appropriate, modify, or refine prior interventions (if applicable) for the particular setting or population.
  • Develop plans for site implementation, including site staff, method of identification, randomization (as applicable), participant recruitment and acquisition.
  • For Option 1: Plan adequately for pilot testing intervention(s) and produce preliminary data for R33 administrative review showing feasibility.
  • For Option 2: Provide the required preliminary data that supports the proposed hypothesis, rationale, and/or development plan.
  • For Option 1 Stage I trials only: Plan for intervention refinement and standardization, as well as further testing of feasibility, safety, and acceptability, with preliminary testing of the association between interventions and clinical outcomes.
  • For Option 1 Stage I trials only: Highlight why traditional Stage III testing (highly-controlled, high internal validity real-world clinical) is not required for Stage I requesting to transition to Stage IV pragmatic trials.
  • For Option 2 Stage III trials only: Develop and test inexpensive and user-friendly procedures to train interventionists to deliver the intervention with fidelity.

The R33 Implementation Phase: Stage IV Pragmatic Trial

During the R33 phase, the PD(s)/PI(s) will test the effectiveness of the intervention in a home/clinical setting. General activities for this phase include the following:

  • Only minor intervention refinement, consistent with the hypothesized mechanisms/principles of the intervention, based on insight from the R61 phase; standardization; and confirmatory testing of feasibility, safety, and acceptability, with preliminary testing of the association between intervention(s), targeted mechanism/principle of the intervention, and clinical outcomes.
  • Plan to refine estimates of requirements based on R61 findings, with guidance from NIH staff on sample size, numbers of sites, site-to-site heterogeneity, and the implementation timetable based on data derived from the healthcare delivery partners.
  • Studies supported by the R33 phase should be adequately powered. It is required that the PD(s)/PI(s) provide power calculations for the R33 phase.
  • Plan for site implementation, including site staff, method of identification, randomization (as applicable), and participant recruitment and acquisition.
  • Plan to address all ethical issues and issues related to human subject safety oversight for the pragmatic trials, including the development of informed consent documents or opt-out consents (if applicable) and finalizing site of IRB review. Applicants must propose a single IRB approach for trial oversight to facilitate both appropriate and timely study implementation.
  • For Option 1 only: For simple intervention studies, replicate findings in another site. Applicants are required to identify additional implementation sites for replication purposes prior to beginning the R33 phase. Replication studies under Option 1 must be adequately powered.

Milestones and R61/R33 Transition

Applications must propose a well-defined set of milestones (see required milestones above) for the planning phase (R61) and annual milestones for the implementation phase (R33). Specifically, the transition from the R61 to the R33 phase of the award will be administratively reviewed for successful completion of the go/no-go criteria that will be clearly specified in the R61 phase. Generally, applications could include the following activities and milestones for the R61 phase:

  1. Establishment of partnerships with healthcare providers and documentation of the commitment of the organization(s) to the project and operationalize the intervention.
  2. Establishment of partnerships with healthcare providers and documentation of the commitment of the organization(s) to the project for replication site/trial for applications submitted under Option 1.
  3. Ability to obtain access to Electronic Health Records (EHRs) and modify and implement pilot interventions.
  4. Operationalization of definitions and objective measures of the intervention (i.e., the hypothesized mechanism of action).
  5. Provision of preliminary evidence that the mechanism of action can be manipulated reliably and validly through administrative data sources (e.g., EHR data), where such data sources are available.
  6. Assessment and justification of adequacy and finalization of clinically-relevant outcome measures.
  7. Results of the pilot test intervention(s) and preliminary data for R33 administrative review showing feasibility of the intervention and completion of pragmatic trial protocol.

At the completion of the R61 phase, the applicant will be required to submit a detailed transition request for the R33 implementation phase. R33 transition requests will undergo an administrative review to determine whether the milestones have been met. Unless the R61 meets go/no-go criteria, the R61 may not transition to the R33 phase.

Prospective applicants should note that funding of the R61 phase of a grant application does not guarantee support of the R33 phase. Transition to the R33 phase of the project will occur only if an administrative review process recommends that the R61 planning activities have been successful, the implementation phase of the project can proceed with confidence of success, and funds are available.

Partnerships with application developers for smartphones and access to EHRs

Partnerships with application developers for collecting patients and caregiver reported outcomes, community partners, healthcare delivery organizations will be critical to implementing this FOA. It is anticipated that interventions will generally be performed with either smartphones, sensors and/or administrative data (e.g., partnership with electronically-supported, integrated healthcare delivery organizations to establish efficiencies). The partnership must facilitate access to all EHR data sources relevant to the project (modifying the system when necessary). Further, we encourage collaborations with retail application developers and EHR vendors to scale the adoption of successful interventions to solo and small-group practices.

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 identify a clinical trial, identifying the Stage from NIH Stage Model.
  • Do not identify Option 1 (R61: Stage I to R33: Stage IV) or Option 2 (R61: Stage III to R33:Stage IV).
  • Do not capture primary clinical outcomes from smartphone, sensors, or administrative data sources such as EHR.
  • Propose direct costs at or above $200,000 for data collection for the full R61 phase or direct cost at or above $200,000 for data collection for the full R33 phase.
  • For Stage IV trials: Do not address generalizability to diverse populations.
  • Do not address issues of power for Stage IV (R33 Phase).
  • For Option 1 trials only: do not propose to replicate Stage IV clinical trials during R33 Phase.
  • For Option 1 trials only: do not identify a control group (i.e., open trials) during R33 Phase.
  • For Option 2 trials only: do not identify control groups (i.e., open trials) for both R61 and R33 Phases.

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
Resubmission
Revision

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

For the R61 planning phase, the combined budget for direct costs for up to two years may not exceed $500,000.

For the R33 phase, budgets are expected to go over $500,000. Applicants requesting $500,000 or more in direct costs during the R33 phase in any year (excluding consortium F&A) must contact a Scientific/Research Contact at least 6 weeks before submitting the application.

Award Project Period

The scope of the proposed project should determine the project period. It is expected that the R61 phase will occur during the first 1- 2 years. Researchers who complete R61 development work are encouraged to apply to R61 transition to the R33 implementation phase in pragmatic trials for the remaining 2-4 years of the grant. The maximum period of the combined R61 and R33 phases 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:

Partha Bhattacharyya, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-496-3136
Email: bhattacharyyap@mail.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 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 should be presented of how the proposed trial will shift caregiver intervention practice or inform health care policy.

The scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention are 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.

For Stage IV studies on interventions which 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 pragmatic trials, the application characterizes the intervention well. The intervention applies to a diverse AD/ADRD patient population or their caregivers and is suitable for use in real-world settings. If the intervention is successful, it will be well poised to be adopted within a Stage V study (dissemination and implementation).

Specific Aims: Separate specific aims should be presented for both the R61 and R33 phases within the designated page limit.

Innovation

The design/research plan includes innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice.

The application challenges and seeks to shift current behavioral intervention research or clinical dementia care practice paradigms by utilizing NIH Stage Model.

Approach

The application provides an overview of the proposed study design which includes the Stage of Intervention Research (e.g., Stage I, III, or IV of the NIH Stage Model). The study design includes the rationale for the selected Stage, including justification of the evidence from previous basic behavioral/social/affective/ cognitive research or previous relevant clinical trials. The study design addresses hypothesized principles or “mechanism of action” of the intervention, including the behavioral, cognitive, affective, or social targets it is hypothesized to engage. The application includes plans for addressing the fidelity of intervention delivery. The study design includes rationale for the intervention study design (e.g., single case study, multiple baseline, adaptive/SMART design, factorial, partial factorial). The application provides 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 play in the causal chain; specification of variables as hypothesized moderators, mediators, or outcomes). The study design addresses potential biases or challenges in the trial and how they will be addressed and mitigated. The application discusses potential threats to validity and presents clear power calculations that reflect a range of effect sizes of clinical significance. The application incorporates trial design with rigorous controls for Stage of intervention proposed.

The application describes a unifying and testable hypothesis that transcends both R61 and R33 phases. The application provides clear milestones for the R61 phase and related scientific goals for the R33 phase. Those milestones are conducive to accomplishing the study aims and the goals of the R33 phase are based, in part, on findings collected during the R61 phase.

The power analysis and replication plan are articulated for the R33 phase (note that power calculations are not required for the R61 phase). The application provides the sample size, analytic plan, and overall design for the planned pragmatic trial. The application assesses and justifies adequacy of, and finalizes, clinically relevant outcome measures.

For R61-Stage I or III, the design maximizes internal validity of the study. For R33-Stage IV trials, the design maximizes external validity. The application summarizes how the study will test generalizability, and sustainability of findings across distinct health care settings and diverse staff, caregiver, and patient populations.

The application provides a description of how the study designs, methods, and assessments are complementary, such that outcomes from the R61 phase will enhance the interpretation of outcomes for the R33 stage.

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) 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).

Research Strategy: The Research Strategy should contain separate sections that describe both the R61 and R33 phases. Separate research design and methods could be presented as needed for the R61 and R33 phases. It is not necessary to repeat information or details in the R33 section that are described in the R61 section.

For applications that propose Option 1, the application should adequately plan for pilot testing intervention(s) and produce preliminary data for R33 administrative review showing feasibility. For applications that propose Option 2, the application should provide the required preliminary data to support the proposed hypothesis, rationale, and/or development plan.

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:

  • 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 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 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 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 pragmatic trials, how well did the application characterize the intervention? Does the intervention apply broadly to a 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)?

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:

To what extent does the overview of the proposed study design include the Stage of Intervention Research (e.g., Stage I, III, or IV 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 in 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?

Is there a unifying and testable hypothesis that transcends both R61 and R33 phases? Does the application provide clear milestones for the R61 phase and related scientific goals for the R33 phase? Do those milestones fit the NIH Stage Model? Are those milestones conducive to accomplishing the study aims? Are the goals of the R33 phase based, in part, on findings collected during the R61 phase? If this proposed study is successful, does the application provide clear milestones which describe anticipated next steps (Stage V) trials?

How appropriate are the power analysis and replication plan for the R33 phase (note that power calculations are not required for the R61 phase)? How appropriate are the sample size, analytic plan, and overall design for the planned pragmatic trial? How well did the applicant assess and justify adequacy of, and finalize, clinically relevant outcome measures?

For R61-Stage I and III, how well does the design maximize internal validity of the study? For R33-Stage IV 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?

To what degree does the application provide a description of how the study designs, methods, and assessments are complementary, such that outcomes from the R61 phase will enhance the interpretation of outcomes for the R33 stage?

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 from the nursing home that they will provide access to dataif the application proposed to access to EHR data)?

Research Strategy:

For applications that propose Option 1, to what degree does the application adequately plan for pilot testing intervention(s) and produce preliminary data for R33 administrative review showing feasibility? For applications that propose Option 2, to what extent does the application provide the required preliminary data? How well does the preliminary data support the proposed hypothesis, rationale, and/or development plan?

Is the complete Clinical Trial 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.

 

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

Not Applicable

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)

Partha Bhattacharyya, Ph. D.
National Institute on Aging (NIA)
Telephone: 301-496-3136
Email: bhattacharyyap@mail.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)

Megan Hancock
National Institute on Aging (NIA)
Telephone: 301-827-6335
Email: megan.hancock@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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