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

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

This FOA seeks to support pragmatic trials for dementia care in Long-term Services and Support (LTSS) settings which will: 1) be designed to address practical comparative questions faced by patients, clinicians, and caregivers (both paid and unpaid); 2) include broad and diverse populations; and 3) be conducted in real-world 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 address effectiveness in diverse populations.

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" https://www.nihcollaboratory.org/Products/Introduction%20to%20pragmatic%20clinical%20trials.pdf and Rethinking Clinical Trials: A Living Textbook of Pragmatic Trials https://www.nihcollaboratory.org/wiki/Pages/Home.aspx).

Appropriate settings for pragmatic trials funded under this FOA will be home health agencies, meal delivery services, adult day centers, respite care centers, assisted living facilities, memory units, nursing homes or other settings, both nonresidential and residential. Designs such as cluster randomization and use of administrative data to enhance generalizability are encouraged. Interventions can involve changes in services, staffing and training, 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 use of acute care, timing and frequency of transitions to acute care and rehabilitation settings, and multimorbidity.

Potential interventions include, but are not limited to:

• Comparing the effectiveness of pharmacological and non-pharmacological treatments in managing behavioral disorders in people with ADRD in home and institutional settings
• Comparing the effectiveness and costs of alternative detection and management strategies (e.g., pharmacological treatment, social/family support, combined pharmacological and social/family support) for dementia in community-dwelling people and their caregivers
• Testing clinical interventions and models of palliative and hospice care for persons with advanced dementia and their families
• Interventions ameliorating racial and ethnic disparities in the treatment of dementia patients among dual eligibles
• Interventions to help individuals with 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 and supports and palliative care to help mitigate the effects of such financial strain on the health and well-being of 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
• Evaluating the benefits and cost-effectiveness of ADRD-friendly communities
• Comparing settings offering arts-based interventions with settings that do not to determine the value of these interventions for the well-being of persons with 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 and other resources can be included.

This FOA encourages preliminary data collection during the R21 phase before proceeding to the R33 implementation phase. PDs/PIs with preliminary data are encouraged to submit their application to RFA-AG-17-064 "Pragmatic Trials for Dementia Care in Long-term Services and Support (LTSS) Settings (R01)".

During the R21 pilot phase, researchers will test the feasibility of implementing interventions in LTSS settings which, if successful, can be transitioned to the R33 phase for implementation of pragmatic trials. The specific activities and milestones appropriate for the R21 phase will depend on the type of intervention under study and its stage of development. Generally, the applicant could include the following activities and milestones for the R21 phase:

• Establish a partnership with a LTSS 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 in LTSS settings.
• Operationalize definitions and objective measures of the LTSS intervention.
• Provide preliminary evidence that the mechanism of action can be manipulated reliably and validly through an intervention.
• Assess and justify adequacy and finalize clinically-relevant outcome measures.
• Plan adequately for pilot testing intervention(s) and produce preliminary data for R33 administrative review showing feasibility.

During the R33 Phase, PDs/PIs should implement the intervention in a LTSS setting. General activities may include:

• 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.
• Plan for refining estimates of requirements based on R21 findings with guidance from NIH staff for sample size, numbers of sites, site-to-site heterogeneity, and the implementation timetable based on data derived from the LTSS partners.
• Studies supported by the R33 phase should be adequately powered. It is recommended that PDs/PIs provide power calculations for the R33 phase.
• Development of plans for site implementation, including site staff, method of identification, randomization (as applicable), participant recruitment and acquisition.
• Replicating findings in another site. Applicants may choose to, but are not required to, identify additional implementation sites in consultation with the NIH staff for replication purposes prior to beginning the R33 phase.
• It is suggested that applicants address all ethical issues and issues related to human subject safety oversight for the pragmatic trails, including developing informed consent documents or opt-out consents (if applicable) and finalizing the site of IRB review in the Human Subjects Protection Plan. Further, applicants should propose a consolidated or centralized IRB approach for trial oversight to facilitate the appropriate and timely implementation of the study.

The project must be supported by a well-defined set of milestones (see suggested milestones above) for the planning phase (R21) and annual milestones for the implementation phase (R33). Specifically, the transition from the R21 to the R33 phase of the award will be administratively reviewed and determined by successful completion of the Go/No-Go Criteria defined for the R21 phase.

At the completion of the R21 planning 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 R21 meets Go/No-Go Criteria, the R21 may not transition to the R33 phase (i.e. it is anticipated that not all funded R21 projects will transition to the R33 phase).

Prospective applicants should note that funding of a R21-phase grant application does not guarantee support of the R33 implementation phase. Transition to the R33 phase of the project will occur only if an administrative review process determines that the R21 planning activities have been successful and the implementation phase of the project can proceed with confidence of success, and if funds are available.

Applications on these topics will not be considered responsive and will not be reviewed:

• Trials on a general nursing home/assisted living patient population without a focus on ADRD
• Trials without a control group identified (i.e. open trials)
• Trials which require complex or expensive implementation or monitoring
• Trials which do not leverage opportunities (e.g. electronic health records) made available by integrated health care systems

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

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Higher Education Institutions

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

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

o Hispanic-serving Institutions

o Historically Black Colleges and Universities (HBCUs)

o Tribally Controlled Colleges and Universities (TCCUs)

o Alaska Native and Native Hawaiian Serving Institutions

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

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

Other

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

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

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

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

Program Directors/Principal Investigators (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.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

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

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

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).

Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

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: [email protected]

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

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.

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

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

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

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

All instructions in the SF424 (R&R) Application Guide must be followed. Applicants should budget for travel to an annual investigators meeting to be held in the Washington, D.C. area.

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

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

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

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

Research Strategy: The Research Strategy should contain separate sections that describe both the R21 and R33 phases. Separate research design and methods could be presented as needed for the R21 and R33 phases. It is not necessary to repeat information or details in the R33 section that are described in the R21 section.

Preliminary data are not required for an R21/R33 application. Any preliminary data that will support or justify the proposed hypothesis, rationale or development plan may be included.

PDs/PIs should propose to follow best practices for the conduct of their randomized trial, and, in particular, clearly state how randomization will be performed. For example, if randomization is performed at the long-term care facility level, the applicant should describe how many effective observations there will be after accounting for intra-cluster correlation. If the randomization is at a lower level than the long-term care facility, the PD/PIs should address potential threats to validity that could occur due to contamination across treatment groups. PDs/PIs should clearly present power calculations that reflect a range of effect sizes of clinical significance. Specifically, it is recommended that PDs/PIs provide beta ranges to assess the sample size/and effect size across multiple sites.

Trial design should incorporate rigorous controls, prospectively identified, preferably by randomization. The design may incorporate novel randomization approaches, such as by cluster or timing of implementation. If another method is used to generate the comparison group, perhaps by staged assignment or staged implementation of the intervention, it should provide comparable rigor. The design should also maximize external validity of the study by testing generalizability, feasibility and sustainability of findings across distinct health care settings and diverse staff, caregiver and patient populations. Proposed analytic plans for applications that propose cluster-randomized trials should address adequacy of sample size and study power and employ analytic strategies relevant for such pragmatic trial designs. Applicants are strongly encouraged to consult the Pragmatic Trial Living Textbook maintained by the NIH Collaboratory https://sites.duke.edu/rethinkingclinicaltrials/.

Applicants should provide a description of how the study designs, methods and assessments are complementary such that outcomes from the planning phase will enhance the interpretation of outcomes at the implementation stage. For example, in the planning phase the PD/PI can propose only one intervention in a LTSS setting and implement it to show feasibility of participation from a LTSS care provider (e.g. long-term care facility partner or home-care agency). In the implementation phase the PD/PI can propose multiple interventions across multiple sites.

Since the intent of this announcement is to leverage findings from planning phase to implementation phase and increase the potential for translation research, the PDs/PIs are encouraged to collaborate with LTSS providers (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) to maximize the possibility of translation.

Milestones and R21/R33 Transition

The application must include milestones applicants expect to achieve by the end of the R21 phase. Milestones should be specific, quantifiable, and scientifically justified; they should not be simply a restatement of the specific aims for the R21 phase. It is recommended that PDs/PIs include a section labeled "milestones" describing milestones to be achieved during the R21 phase to qualify for the transition to the R33 as part of Research Strategy within the approach section.

Applicants can establish Go/No-Go Criteria as they deem fit for their application, but must include the following: (1) establish partnership with LTSS 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, etc.) and document commitment of the organization to the project; (2) obtain access to needed administrative data and modify and implement pilot LTSS intervention(s); and (3) pilot test intervention(s) and produce preliminary data for R33 administrative review showing feasibility of the LTSS intervention(s).

It is understood that the proposed milestones for the R33 phase may be revised based on activities during the R21 planning phase. In the event of an award, the PD/PI and NIH staff will negotiate a list of milestones for each year of support.

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, with the following modification:

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

Appendix:

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

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

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

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.

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

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

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

See more tips for avoiding common errors.

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

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

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

For this particular announcement, note the following:

The R21/R33 phased innovation grant supports interventions in LTSS settings. An R21/R33 grant application need not have preliminary data, extensive background material or preliminary information; however, they may be included if available. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Accordingly, reviewers will focus their evaluation on the conceptual framework, the level of innovation for implementing LTSS intervention, and the potential to significantly advance our knowledge or understanding. Reviewers will assign a single impact score for the entire application, which includes both the R21 and R33 phases.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? How well did the PDs/PIs characterize the pragmatic trial intervention (or combination of several interventions)? Does the intervention apply broadly to the ADRD patient population or their caregivers? Is the intervention suitable for use in real-world settings?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? Does the application provide evidence of how the planned collaboration will work among a team with potentially very different backgrounds?

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?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

Is there a unifying and testable hypothesis that transcends both R21 and R33 phases? Does the application provide clear milestones for the R21 phase and related scientific goals for the R33 phase? Are those milestones conducive to accomplishing the study aims? Are the goals of the R33 phase based, in part, on findings collected during the R21 phase?

How well did the PDs/PIs operationalize definitions and objective measures of the LTSS intervention? What is the quality of the evidence (note that we are not requesting preliminary data) that the mechanism of action can be manipulated reliably and validly in the LTSS setting to carry out the pilot R21 phase? Will the R21 phase produce preliminary data for R33 administrative review showing feasibility (i.e. will the PD/PI show he/she can make changes in the LTSS settings and conduct an intervention)?

How appropriate is the power analysis for the R33 phase? (Note that power calculations are not required for the R21 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?

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 PDs/PIs 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 LTSS settings (e.g. is there a letter of support if the PD/PI proposed to access EHR in a nursing home and show an advanced care planning video)?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

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.

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

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

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

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Not Applicable

Not Applicable

Not Applicable

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

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.

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NIA, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Council on Aging. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. 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.

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

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

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

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

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

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

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

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

Cooperative Agreement Terms and Conditions of Award

Not Applicable

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

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.

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

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

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

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

Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)

Telephone: 301-710-0267

Partha Bhattacharyya, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-496-3136
Email: [email protected]

Ramesh Vemuri, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-402-7700
Email: [email protected]

Richard Proper
National Institute on Aging (NIA)
Telephone: 301-402-7735
Email: [email protected]

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

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