Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute of Neurological Disorders and Stroke (NINDS)

National Institute on Aging (NIA)

Funding Opportunity Title
AD/ADRD, Adverse Childhood Experiences, and Social Determinants of Health Ancillary Studies of Existing Longitudinal Cohorts (R01 - Clinical Trial Not Allowed)
Activity Code

R01 Research Project Grant

Announcement Type
New
Related Notices

NOT-OD-22-190 - Adjustments to NIH and AHRQ Grant Application Due Dates Between September 22 and September 30, 2022

Funding Opportunity Announcement (FOA) Number
PAR-22-221
Companion Funding Opportunity
None
Assistance Listing Number(s)
93.853, 93.866
Funding Opportunity Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to support studies that expand the use of existing data resources to drive new discoveries that can lead to better understanding of the relationship between early life social determinants of health (SDOH), adverse childhood experiences (ACEs), AD/ADRD biomarkers, and the development of cognitive impairment and dementia, especially in populations experiencing health disparities.

Key Dates

Posted Date
August 10, 2022
Open Date (Earliest Submission Date)
September 05, 2022
Letter of Intent Due Date(s)

Not Applicable

The following table includes NIH standard due dates marked with an asterisk.
Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS Scientific Merit Review Advisory Council Review Earliest Start Date
October 05, 2022 * Not Applicable Not Applicable March 2023 May 2023 July 2023

All applications are due by 5:00 PM local time of applicant organization. 

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

Expiration Date
October 06, 2022
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

NINDS aims to accelerate research investigating the relationship between early life social determinants of health (SDOH), adverse childhood experiences (ACEs), AD/ADRD biomarkers, and the development of cognitive impairment and dementia, especially in populations experiencing health disparities. Social, environmental, and biological factors present early in life have been linked to the development of dementia and cognitive impairment. However, much remains to be learned about the relationship between social determinants of health (SDOH), adverse childhood experiences (ACEs), AD/ADRD biomarkers, and the development of dementia.

The National Alzheimer's Project Act (NAPA) was passed in 2011 with a primary research goal aimed at finding a way "to prevent and effectively treat Alzheimer's by 2025." Since then, the National Institute on Aging (NIA) and the National Institute of Neurological Disorders and Stroke (NINDS) have held multiple research summits to assess the needs and opportunities relevant to this goal for Alzheimer's Disease (AD) and Alzheimer's Disease Related Dementias (ADRD). Held triennially, the ADRD Summit addresses research priorities in Alzheimer’s disease-related dementias including frontotemporal dementia (FTD), Lewy body dementia (LBD), multiple etiology dementias (MED), and vascular contributions to cognitive impairment and dementia (VCID), along with broader cross-cutting areas, including health equity. At the Summit, draft research recommendations are presented for public comment; revised recommendations are presented for approval by the NINDS Council and become research milestones in the National Plan to Address Alzheimer’s Disease. The testing of early mechanistic pathways that may account for AD/ADRD health disparities via the measurement of changes in risk factors over the life course, and the establishment of new AD/ADRD cohort studies or the augmentation of existing studies to test the interaction of social, environmental, and biological mechanisms was a recommendation of the 2019 ADRD Summit (See 2019 ADRD Summit Recommendations: Topic 2, Recommendation 3, Priority 2 https://www.ninds.nih.gov/sites/default/files/migrate-documents/2019_adrd_summit_recommendations_508c.pdf). Draft recommendations from the 2022 ADRD Summit reiterate and expand upon this recommendation, calling for both the measurement of risk factors over the life course and their association with AD/ADRD and the harmonization of efforts to augment ongoing cohort studies that evaluate the influence of and interaction between social, environmental, and biological mechanisms in producing AD/ADRD inequities. Please see ADRD Summit 2022 Draft Recommendations, Health Equity in AD/ADRD Recommendation 7, Priority 4 for more details.

Adverse childhood experiences, or ACEs, are potentially traumatic events that occur in childhood. ACEs include physical, emotional, and sexual abuse, physical and emotional neglect, and elements of household dysfunction including domestic violence, mental illness, substance abuse or incarceration of a family member and loss of a parent. According to the Centers for Disease Control and Prevention (CDC), ACEs are quite common, with survey data suggesting that approximately 60% of adults report experiencing at least one type of ACE and 15% reporting experiencing 4 or more types of ACEs. Research suggests that ACEs are associated with later physical and mental illness in an additive fashion with the experience of a greater number of ACEs conferring greater risk. Associations have been demonstrated between ACEs and a number of poor health outcomes in adulthood including depression, health risk behaviors and a variety of physical health conditions, including coronary heart disease and stroke. A 2019 CDC Morbidity and Mortality Weekly Report (MMWR) based on data collected from individuals collected from 25 states, estimated that ACEs prevention could lead to a 15% reduction in stroke and a 13% reduction in coronary heart disease. Associations have also been described between ACEs and later life cognitive impairment and dementia, and more research in this area is needed.

Social determinants of health (SDOH) are the conditions in which people are born, live, learn, work, play, worship, and age that affect a wide range of health, functioning, and quality-of-life outcomes and risks. The U.S. Department of Health and Human Services’ Healthy People 2030 initiative groups SDOH into five domains: economic stability, educational access and quality, health care access and quality, neighborhood and built environment, and social and community context. Specific examples of SDOH include: safe housing, transportation, and neighborhoods; racism, discrimination, and violence; education, job opportunities, and income; access to nutritious foods and physical activity opportunities; polluted air and water; and language and literacy skills. It is thought that SDOH significantly affect people’s health and well-being and are a major driver of health inequities observed both within the U.S. and around the world. Examples of SDOH measurement tools can be found in the PhenX Toolkit, an NIH-funded web-based catalog of recommended measurement protocol. Investigators are highly encouraged to use the PhenX Toolkit to maximize comparisons across datasets or studies and facilitate data integration and collaboration.

The associations between and mechanisms, treatment, and prevention of the impact of ACEs and SDOH on Alzheimer’s Disease Related Dementias remains understudied. The impact of ACEs and SDOH may be particularly relevant to NIH-designated populations that experience health disparities (HDPs) in the United States. The NIH defined HDPs include racial and ethnic minority populations, less privileged socioeconomic status (SES) populations, underserved rural populations, and sexual and gender minorities (SGM). More information regarding minority health and health disparities can be found at: Minority Health and Health Disparities: Definitions and Parameters. Information about the NINDS health equity strategic planning and process may be found on the NINDS Office of Global Health and Health Disparities (OGHHD) website: https://www.ninds.nih.gov/About-NINDS/Office-Global-Health-and-Health-Disparities.

NINDS, as part of NIH, strives for rigor and transparency in all research it funds. For this reason, NINDS explicitly emphasizes and provides supplemental guidance to NIH application instructions related to rigor and transparency (https://grants.nih.gov/policy/reproducibility/guidance.htm). For example, the biological rationale for the proposed experiments must be based on rigorous and robust supporting data, e.g., by minimizing the risk of bias and transparently reporting methods and results as described at https://www.ninds.nih.gov/Funding/grant_policy. As stated in the NIH application guidelines, if previously published or preliminary studies do not meet these rigor standards to an acceptable degree, applicants should address how the current study design addresses the deficiencies, and the proposed study design must likewise demonstrate a rigorous and transparent approach.

Objective

This FOA solicits applications proposing ancillary studies to existing longitudinal cohort projects in order to examine the relationship between early life SDOH and ACEs and later risk for cognitive impairment and dementia in populations that experience health disparities. Successful applications should deepen our understanding of the impact of SDOH experienced in the first 25 years of life and ACEs on cognitive impairment and dementia development and progression through the use of existing longitudinal cohort studies and AD/ADRD or other relevant data resources, to drive new discoveries and novel hypotheses that can lead to better understanding of AD/ADRD disease mechanisms, clinical risk assessment and outcomes.

This initiative seeks applications in areas including, but not limited to:

  • The addition of assessments of cognition and/or AD/ADRD relevant biomarkers to existing longitudinal cohorts and analysis of this data.
  • Assessment of SDOH or ACEs in AD/ADRD cohorts comprised of NIH-designated populations that experience health disparities or evaluation of SDOH/ACEs screening implementation.
  • Novel hypothesis generation for mechanistic understanding, clinical risk assessment, or clinical outcome prediction of AD/ADRD disease progression related to SDOH or ACEs in cohorts comprised of NIH designated populations know to experience health disparities.
  • Evaluate or identify the impact of factors associated with risk for and/or resilience to developing cognitive impairment and/or dementia in adults who experienced ACES during childhood..
  • Examine potential impact of childhood SDOH and/or ACES on genetic factors conferring risk for AD/ADRD.
  • Measure risk factors (both established and novel), over the life-course focusing on appropriate risk periods, and associations of these factors with AD/ADRD including cognitive, pathologic, behavioral, and functional outcomes among populations exposed to ACEs or SDOH in AD/ADRD.
  • Studies involving primary data collection with human participants are strongly encouraged to incorporate SDOH measures from the Core and Specialty collections that are available in the PhenX Toolkit (www.phenxtoolkit.org) SDOH Collection.

Characteristics of Responsive Applications

Applications should:

  1. Propose ancillary studies to existing longitudinal cohort projects (or other existing projects with relevant data) in order to examine the relationship between early life SDOH and ACEs and later risk for cognitive impairment and dementia.
  2. Utilize either a prospective or retrospective approach allowing for the collection and analysis of new data or specimens relevant to AD/ADRD, SDOH, or ACES in active projects OR for the proposed new analyses of data or biosamples collected in the past.
  3. Examine AD/ADRD related health outcomes of persons who have experienced i. ACEs during childhood (ages 0-18 years) as defined by the CDC; or ii. have a history of limited health opportunity impacted by early life SDOH (birth to age 25 years) and aim to improve understanding of the relationship between ADRD and ACEs or SDOH.
  4. Include NIH-designated populations who experience health disparities in the United States, including (but not limited to) racial/ethnic minority and other populations with health disparities (i.e. individuals with limited English proficiency).

Applications Not Responsive to this FOA:

Applications not responsive to this FOA will not be reviewed.

  • Applications that do not focus on AD/ADRD.
  • Applications that do not use existing datasets or established longitudinal cohorts.
  • Applications that do not investigate the relationship between i. social determinants of health (SDOH) and/or adverse childhood experiences (ACEs) and ii. AD/ADRD biomarkers and/or the development or progression of cognitive impairment or dementia and AD/ADRD related health outcomes.
  • Projects without a focus on one or more NIH-designated populations that experience health disparities (HDPs).
  • Clinical trials.

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

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?

Not Allowed: Only accepting applications that do not propose clinical trials.

Funds Available and Anticipated Number of Awards

The NINDS has committed $1,000,000 to fund up to two awards. The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

Award Budget

Application budgets should reflect the actual needs of the proposed project.

Award Project Period

The maximum project period is 5 years.

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

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

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

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

  • Hispanic-serving Institutions
  • Historically Black Colleges and Universities (HBCUs)
  • Tribally Controlled Colleges and Universities (TCCUs)
  • Alaska Native and Native Hawaiian Serving Institutions
  • Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Local Governments

  • State Governments
  • County Governments
  • City or Township Governments
  • Special District Governments
  • Indian/Native American Tribal Governments (Federally Recognized)
  • Indian/Native American Tribal Governments (Other than Federally Recognized)

Federal Government

  • 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.

  • 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.
    • 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.
    • Unique Entity Identifier (UEI)- A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
  • eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their full SAM and Grants.gov registrations; 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 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 diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.

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, per 2.3.7.4 Submission of Resubmission Application. 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 2.3.9.4 Similar, Essentially Identical, or Identical Applications)

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.

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.

The range of interdisciplinary expertise of included key personnel that will ensure success and will poise the team for making strong advances should be clearly indicated in the biosketches. Expertise of key personnel should include, but is not limited to, expertise in the design and conduct of longitudinal cohort studies and the analysis of their data, and the study of AD/ADRD and cognitive impairment, ACEs and SDOH, and health equity/health disparities. The roles, responsibilities and authority of each PD/PI must be specified.

R&R or Modular Budget

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

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Specific Aims: State the aims and hypotheses to be tested in the proposed project.

Research Strategy: Organize the Research Strategy by Significance, Innovation, and Approach.

Significance: Clearly state how the project proposes to examine potential relationships between ACEs and early life SDOH and later cognitive impairment or dementia. Describe the rationale and rigor of the supporting preliminary data for testing the hypotheses proposed in the current project. Describe how the proposed project will either collect new data or specimens from active cohorts or analyze existing data/specimens collected in the past in order to examine potential relationships between SDOH, ACEs and cognitive impairment or dementia that were not a part of the original study aims and may inform the current understanding of the ways in which early life experiences may impact later cognitive outcomes. State how information learned from the proposed project may have the potential to impact clinical outcomes or public health considerations. Identify how the information gained from the proposed project may impact populations are at high risk for experiencing health disparities.

Innovation: Describe the innovative attributes the application brings via both the specific analyses proposed and their potential for future impact. Specify any significant (hypothesized) barriers addressing the potential relationship between early life SDOH, ACES, and cognitive impairment/dementia, and clearly indicate how these barriers will be addressed in the application.

Approach:

The approach must detail the strengths and appropriateness of the proposed study in the targeted population(s). The applicant should demonstrate an understanding of SDOH and ACEs, cognitive impairment and dementia, and of the principles of research involving longitudinal cohorts. Particular attention should be paid to including patient populations defined by the NIH as experiencing or at risk for experiencing health disparities, and efforts to include community engagement should be made when possible.

Include information regarding how the proposed project will engage the population(s) of interest and how data will be collected. Clearly describe the existing longitudinal cohort(s) that will be targeted in the current project and delineate what existing data is available and whether new data and/or biospecimens will be collected. Describe how information regarding ACES, early life SDOH, and cognitive impairment or dementia will be or was ascertained in the past. If newly collected or previously archived biospecimens will be studied, include information regarding collection, storage and analysis of these biospecimens. There should be sufficient information provided to establish that the aims proposed do not interfere with the goals of the original study or significantly increase participant burden. Applicants should note whether or not new consent will be required

The study design should be well justified based on current knowledge regarding the relationships between early life SDOH, ACEs, AD/ADRD biomarkers (if applicable), and the development of cognitive impairment or dementia, in populations experiencing health disparities. Information regarding the quality of the data, specimens or data sets being analyzed or aggregated/harmonized for inclusion and the proposed methods for aggregating and harmonizing existing data sets (if applicable) should be clearly described. Any computational models or tools employed should be effectively designed for use by the intended user base.

Discuss potential biases, pitfalls and challenges with the proposed research and how they will be addressed.

NINDS urges investigators to follow the NIH guidance for rigor and transparency in grant applications (https://grants.nih.gov/policy/reproducibility/guidance.htm) and additionally recommends the research practices described at https://www.ninds.nih.gov/Funding/grant_policy to ensure that robust experiments are designed, potential experimenter biases are minimized, results and analyses are transparently reported, and results are interpreted carefully. These recommended research practices include, where applicable, rationale for the chosen model(s) and primary/secondary endpoints, clear descriptions of tools and parameters, blinding, randomization, ensuring adequate sample size, pre-specified inclusion/exclusion criteria, handling of missing data and outliers, appropriate controls, preplanned analyses, appropriate quantitative techniques, clear indication of exploratory vs. confirmatory components of the study, consideration of limitations, and plans for transparent reporting of all methods, analyses, and results so that other investigators can evaluate the quality of the work and potentially perform replications.

Investigators should indicate whether data presented or cited in the application as key support for the proposed work were collected, analyzed, and reported in a rigorous and transparent manner as indicated above. A plan to address any ambiguity, weaknesses, or limitations in the prior research should be included in the application. Proposed experiments should similarly adhere to these high standards of rigor and transparency.

Letters of Support: If an application plans to utilize the infrastructure or resources of existing projects, whether funded by the NINDS, other governmental, or nongovernmental entities, letters of support detailing the terms of collaboration and data sharing (if allowed) must be included, and must be from the appropriate authority/ies of the parent activity (e.g. institutional/foundation official, funding sponsor, and lead PI). Any conflicts in sharing with any known entities should be revealed and discussed. If the proposed study is ancillary to an ongoing parent project, the letter of support from the parent study PD/PI and business official must confirm that the proposed research does not interfere with the parent study, does not place undue burden on participants, and follows approved procedures and policies from the parent study. Letters of support from relevant stakeholders may also be included as evidence of necessary expertise (e.g. professional organizations or patient groups).

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.

The following modifications also apply:

  • All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. Data sharing is strongly encouraged, when possible.
Appendix:
Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
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.

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 fieldof the Senior/Key Person Profile form. 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 unique entity identifier provided on the application is the same identifier 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 NINDS, NIH. Applications that are incomplete or non-compliant will not be reviewed.

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.

For this particular announcement, note the following: All applications under this announcement are to be assigned to the NINDS as the administrative institute.

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:

To what extent does the project propose to examine the relationship between ACEs or SDOH across the lifespan influence on health opportunity or and later risk for AD/ADRD? How does the project propose to collect new data or specimens from active cohorts or analyze existing data/specimens collected in the past in order to examine potential relationships between SDOH, ACEs and cognitive impairment or dementia that were not a part of the original study aims? How will information learned from the proposed project have the potential to impact clinical outcomes or public health considerations?

How well does the application describe whether prior research that serves as the key support for the proposed project employed rigorous practices such as minimization of potential experimenter biases, robust experimental designs, transparent reporting of results and analyses, and careful interpretation? How does the application address ambiguity, weaknesses, or limitations in rigor of the prior research, if applicable?

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?

Specific to this FOA:

To what extent does the composition of the research team have appropriate breadth and inclusiveness of expertise and disciplines, including expertise in AD/ADRD as well as expertise in assessing and evaluating the effects of ACES and SDOH and working with longitudinal cohort data?

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:

To what extent does the application consider barriers to addressing the potential relationship between early life SDOH, ACES, and cognitive impairment/dementia, and indicate how these barriers will be addressed in the proposed project?

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 proposed research incorporate adequate methodological rigor where applicable, including, but not limited to, rationale for the chosen model(s) and primary/secondary endpoints, clear descriptions of tools and parameters, blinding, randomization, adequate sample size, pre-specified inclusion/exclusion criteria, appropriate handling of missing data and outliers, appropriate controls, preplanned analyses, appropriate quantitative techniques, clear indication of exploratory vs. confirmatory components of the study, consideration of limitations, and plans for transparent reporting of all methods, analyses, and results so that other investigators can evaluate the quality of the work and potentially perform replications?

How well does the application demonstrate an understanding of SDOH and ACEs, cognitive impairment and dementia, and the principles of research involving longitudinal cohorts? How well justified is the study design? To what extent does the application include information regarding how the proposed project will engage the population(s) of interest and how data will be collected? How well does the application describe the existing longitudinal cohort(s) and the quality and characteristics of the data and/or biospecimens already collected? What is the quality of the data, specimens or data sets included in the proposed research? How effective are the proposed methods for aggregating and harmonizing existing data sets (if applicable)?

Environment

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

Additional Review Criteria

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

Protections for Human Subjects

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

Not Applicable.

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:S

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 Center for Scientific Review , in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications 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 submitted in response to this FOA. 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.

Recipients 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.

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

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, including of note, but not limited to:

If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Should the applicant organization successfully compete for an award, 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 (including gender identity, sexual orientation, and pregnancy). This includes ensuring programs are accessible to persons with limited English proficiency and persons with disabilities. 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 https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/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 and 2 CFR Part 200.206 “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, recipients 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. NIH FOAs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All recipients 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: 301-637-3015

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)

Rebecca Hommer, M.D.

National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-827-2257
Email: rebecca.hommer@mail.nih.gov

Peer Review Contact(s)

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Financial/Grants Management Contact(s)

Chief, Grants Management Official

National Institute of Neurological Disorders and Stroke (NINDS)
Email: ChiefGrantsManagementOfficer@ninds.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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