Department of Health and Human Services
Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute on Aging (NIA)
National Institute of Nursing Research (NINR)

Funding Opportunity Title

Pilot Clinical Trials for the Spectrum of Alzheimer’s Disease and Age-related Cognitive Decline (R01)

Activity Code

R01 Research Project Grant

Announcement Type

Reissue of PAR-14-089

Related Notices
  • NOT-OD-16-004 - NIH & AHRQ Announce Upcoming Changes to Policies, Instructions and Forms for 2016 Grant Applications (November 18, 2015)
  • NOT-OD-16-006 - Simplification of the Vertebrate Animals Section of NIH Grant Applications and Contract Proposals (November 18, 2015)
  • NOT-OD-16-011 - Implementing Rigor and Transparency in NIH & AHRQ Research Grant Applications (November 18, 2015)
Funding Opportunity Announcement (FOA) Number

PAR-16-365

Companion Funding Opportunity

PAR-16-364, R01 Research Project Grant

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

93.866, 93.361

Funding Opportunity Purpose

This Funding Opportunity Announcement (FOA) invites applications that propose to develop and implement Phase I or II clinical trials of promising pharmacological and non-pharmacological interventions in individuals with age-related cognitive decline and in individuals with Alzheimer's disease (AD) across the spectrum from pre-symptomatic to more severe stages of disease, as well as to stimulate studies to enhance trial design and methods.

Key Dates
Posted Date

October 6, 2015

Open Date (Earliest Submission Date)

November 16, 2015

Letter of Intent Due Date(s)

Not Applicable

Application Due Date(s)

December 16, 2015 (New, Resubmission, and Revision applications) followed by Standard dates ), by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on these dates.

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

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review
Advisory Council Review
Earliest Start Date
Expiration Date

September 8, 2018

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

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

There are several options to submit your application to the agency through Grants.gov. You can use the ASSIST system to prepare, submit and track your application online. You can download an application package from Grants.gov, complete the forms offline, submit the completed forms to Grants.gov and track your application in eRA Commons. Or, you can use other institutional system-to-system solutions to prepare and submit your application to Grants.gov and track your application in eRA Commons. Learn more.

Problems accessing or using ASSIST should be directed to the eRA Service Desk.
Problems downloading forms should be directed to Grants.gov Customer Support.
Table of Contents

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

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

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

The biggest risk factor for Alzheimer's disease (AD) is age, and AD is the most common cause of dementia in those aged 65 and older.  Because of the aging of populations worldwide, this disorder will reach epidemic proportions even in best case scenarios, with an enormous human and economic burden.  AD is one of the most persistent and devastating dementing disorders of old age, because it eventually leads to a complete loss of memory and of the ability to function independently. It is estimated that over five million people in the United States have AD in its various stages at an estimated cost to society of over $200 billion per year.  It is projected that 11 to 16 million people and their families could be affected by AD by the middle of this century if no effective therapies are developed to prevent, slow or stop the disease.

The vast majority of older adults will experience some deterioration in cognitive function as they age.  This age-related cognitive decline may presage AD or other neurodegenerative disorders, but even when it does not it can have substantial influence on quality of life, character of personal relationships, and the capacity for making informed decisions about health care, retirement, and other issues faced daily by millions of adults.

Currently there are only a few interventions that have been approved by the Food and Drug Administration for the treatment of AD, and those approved have demonstrated only modest effects in modifying the clinical symptoms for relatively short periods.  None has shown a clear effect on disease progression.  The Alzheimer’s Association’s 2015 trajectory report estimated that a treatment delaying onset by five years and beginning to show its effect in 2025 would decrease the total number of older Americans with Alzheimer’s from 8.2 million to 5.8 million in 2030.  Moreover, a treatment that even slowed disease progression would result in far fewer people with Alzheimer’s disease in the severe stage that requires the highest level of care with the greatest costs.

In response to this looming public health crisis in the United States and worldwide, a growing number of countries are increasing their investment in all aspects of AD research.  On January 4, 2011, President Obama signed into law the National Alzheimer’s Project Act (NAPA).  As part of the Strategic Planning Process for the implementation of the National Alzheimer’s Project Act, (see http://aspe.hhs.gov/daltcp/napa/ for more information) the National Institute on Aging (NIA) at the NIH with support from the Foundation for the NIH (FNIH) organized and hosted two Alzheimer’s Disease Research Summits entitled “Path to Treatment and Prevention,” which was held on the NIH campus in May 2012 and February 2015.  The overarching goal of the summits was to formulate a strategy for a new integrated, multidisciplinary research agenda to enable the development of effective therapies (disease modifying and palliative) across the disease continuum for the cognitive as well as neuropsychiatric symptoms of Alzheimer’s disease and to identify the resources, infrastructure, and public private partnerships necessary to successfully implement this translational agenda. This FOA is consistent with the recommendations of these AD research summits, http://www.nia.nih.gov/newsroom/alzheimers-disease-research-summit-2012-recommendations; https://www.nia.nih.gov/research/recommendations-nih-ad-research-summit-2015.

Maintenance of cognitive health with age is also a growing public health imperative.  The 2010 Cognitive Aging Summit, held by the NIA in conjunction with the McKnight Brain Research Foundation (MBRF) and the Foundation for NIH (FNIH), included recommendations to “increase opportunities at the interface of basic and clinical science to enhance the clinical trial enterprise” and “encourage more integrative models of mechanisms for age-related decline/maintenance/adaptation.” In 2014, the NIA, in collaboration with the MBRF and the FNIH, the National Center for Complementary and Integrative Health (NCCIH) and the NIH Office of Behavioral and Social Research (OBSSR), published an FOA, the purpose of which was to encourage the development of therapeutic approaches that aim to drive beneficial plasticity of the aging brain and remediate age-related cognitive decline.  Recently, the Institute of Medicine completed a study of the public health dimensions of cognitive aging, entitled “Cognitive Aging: Progress in Understanding and Opportunities for Action” (http://iom.nationalacademies.org/Reports/2015/Cognitive-Aging.aspx).  The study report included the recommendation for single- and multi-component clinical trials of promising interventions to promote cognitive health and prevent cognitive decline, testing for both cognitive status and functional outcomes.

Research Objectives

The goal of this FOA is to invite research grant applications that provide clinical testing (Phase I and II) of promising pharmacological and non-pharmacological interventions for cognitive and neuropsychiatric symptoms in individuals with age-related cognitive decline and in individuals with AD across the spectrum from pre-symptomatic to more severe stages of disease, as well as to stimulate studies to enhance trial design and methods.

Examples of interventions for evaluation include but are not limited to: pharmacological interventions that target eradication or progression of deposition of disease neuropathology; repurposed drugs that have promise for AD treatment such as chemotherapeutic agents or drugs for insulin dysregulation/diabetes; novel cognitive training or cognitive engagement approaches; aerobic exercise and/or other movement therapies, such as Tai Chi; sleep enhancement; mindfulness-based stress reduction; nutritional supplementation or adoption of specific dietary programs; and/or combinations of interventions including the mixture of pharmacological with non-pharmacological therapeutics.

This FOA encourages clinical trial applications including but not limited to the following:

  • Studies to refine the intervention strategy.  These studies could include work to determine appropriate dosage of drugs, duration of treatment, and the delivery system.  For non-pharmacological interventions, such work might examine the intensity or duration of therapy required.  For all interventions, the potential synergistic effects of combined interventions could be explored.
  • Studies to evaluate the safety and/or efficacy of the intervention(s). 
  • Studies that elucidate mechanism of action.  In some cases, there may be interventions that have some level of demonstrated efficacy (e.g., exercise for age-related cognitive decline), but lack a real understanding of the mechanism of action. Work in this area could use a variety of approaches appropriate to the intervention to elucidate the mechanism of action and therefore allow both confirmation of engagement of the intervention target and potentially optimize the intervention.
  • Studies to define and refine the target population and ensure adequate enrollment, protocol adherence and subject retention.
  • Studies that address heterogeneity of response.  This would include identification of specific individuals according to genetic profiles, behavioral factors, and/or sociocultural or demographic factors who are more likely or less likely to benefit from the intervention(s).  Mediators of the therapeutic intervention such as continued educational opportunities, continued engagement in driving or financial decision-making may facilitate real-life function and should be considered.
  • Studies to establish/validate trial outcome measures.  These measures may include clinical/neuropsychological/behavioral measures, neuroimaging measures, and other biological measures in blood and cerebrospinal fluid.

The National Institute of Nursing Research (NINR) is particularly interested in pilot clinical trials addressing behavioral (non-pharmacological) interventions.

Section II. Award Information
Funding Instrument

Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

Application Types Allowed

New
Resubmission
Revision

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards

NIH intends to fund an estimate of 10 - 15 awards, corresponding to a total of $10 million for fiscal year 2016. Future year amounts will depend on annual appropriations.

Award Budget

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

Award Project Period

The scope of the proposed project should determine the project period. The maximum project period is 5 years. 

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

Section III. Eligibility Information
1. Eligible Applicants
Eligible Organizations

Higher Education Institutions

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

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

    • 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)

Governments

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

Other

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

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

Required Registrations

Applicant Organizations

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

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

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

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

Eligible Individuals (Program Director/Principal Investigator)

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

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

2. Cost Sharing

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

3. Additional Information on Eligibility
Number of Applications

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

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

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

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the “Apply for Grant Electronically” button in this FOA or following the directions provided at Grants.gov.

2. Content and Form of Application Submission

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

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

Page Limitations

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

Instructions for Application Submission

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

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

SF424(R&R) Senior/Key Person Profile

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

R&R or Modular Budget

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

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Research Strategy:

Pharmacological Interventions

This Funding Opportunity Announcement (FOA) encourages the submission of applications for the clinical testing of novel candidate therapeutics (small molecule and biologics), as well as for repurposed drugs.  Investigators are strongly encouraged to incorporate pharmacodynamic biomarkers in the design. Investigators are also encouraged to collect and store blood and other biosamples for future genomic and other 'omic' analyses aimed at interrogating treatment responsiveness and examining predictors of decline and progression.

Phase I clinical trials:

Applications for therapeutic agents against known target(s) are expected to include information on the mechanism of action for the therapeutic agent, information regarding the target’s role in disease pathogenesis and clinical relevance of the target, and information on the predicted optimal disease stage (pre-symptomatic, Mild Cognitive Impairment, mild, moderate or severe AD) to engage the target from preclinical development studies.  Applicants proposing a multi-target therapeutic should summarize the available information on the pathogenic pathways that the agent engages and provide a strong clinically-relevant rationale for this approach.

If the molecular target of the therapeutic agent is not known, applications should summarize what is known about the agent’s mechanism of action and whether the agent engages a disease-relevant pathophysiological process.

Finally, applications should contain a plan for future clinical development of the therapeutic agent, including details about the clinical indication (disease stage, target population), plan for use of biomarkers in the course of further clinical development (i.e., biomarkers for target engagement, responsiveness to treatment, and/or tracking of disease progression), and a clinical development timeline.

Phase II clinical trials:

Applications for Phase II clinical trials could be designed as proof of mechanism/target engagement/proof of concept studies.  Applicants should also provide evidence of safety from earlier phase clinical trials and should include further evaluation of safety in the trial design.  Finally, applications should contain a plan for future clinical development, i.e., later stage trials, if a positive signal were to be identified.

Non-pharmacological Interventions:

This Funding Opportunity Announcement (FOA) encourages the submission of applications for the testing of novel non-pharmacological/behavioral interventions.  Applications for clinical trials should include information on proof of mechanism for the intervention(s) being tested.  Applications for clinical trials should also contain a plan for future clinical development, i.e., later stage trials, should a positive signal be identified.  Investigators are encouraged to collect and store blood and other biosamples for future genomic and other 'omic' analyses aimed at interrogating treatment responsiveness and examining predictors of decline and progression.

Protection of Human Subjects: NIA has specific requirements for human-intervention studies that need to be addressed in the grant application.  These requirements are directed toward protecting the safety of participants in intervention studies and assuring that trials are soundly conducted and analyzed. As part of the data and safety monitoring plan (DSMP) for high risk interventions or when there are multiple field sites, NIA requires plans for an independent data and safety monitoring board (DSMB).  Applicants are encouraged to discuss the DSMP with program staff. .

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

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

Planned Enrollment Report

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

PHS 398 Cumulative Inclusion Enrollment Report

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

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. Submission Dates and Times

See Part I. Section III.1 for information regarding the requirements for obtaining a Dun and Bradstreet Universal Numbering System (DUNS) Number and for completing and maintaining an active System for Award Management (SAM) registration. Part I. Overview Information contains information about Key Dates. 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.

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.  If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

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.

4. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

5. 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.

6. Other Submission Requirements and Information

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

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

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 our Post Submission Application Materials policy.

Section V. Application Review Information

Important Update: See NOT-OD-16-006 and NOT-OD-16-011 for updated review language for applications for due dates on or after January 25, 2016.

1. Criteria

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

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? 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? Does the therapeutic target/mechanism of action for the intervention engage a disease-relevant pathophysiological process or processes?  Will the trial improve scientific knowledge or technical capability? Will the intervention presented help overcome the critical barriers to progress in Alzheimer’s clinical trials? 

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? Does the investigator(s) have experience in conducting early stage clinical trials? Does the investigator(s) have the experience/knowledge to plan the future clinical development, i.e., later stage trials, if a positive signal were to be identified?

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? Is the intervention novel for a clinical trial in Alzheimer’s disease; age-related cognitive decline?  Is the proposed therapeutic target/mechanism of action novel or is the clinical indication (disease stage, target population) novel?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? 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? Are the mechanisms of action for the intervention included and well presented in regard to the target and the target’s role in disease pathogenesis and clinical relevance of the target?  Is there adequate information on the predicted optimal disease stage (pre-symptomatic, Mild Cognitive Impairments, mild, moderate, or severe AD)?  If there is a multi-target therapeutic approach, is it well justified and clinically-relevant in rationale?  Is the future clinical development of the therapeutic agent adequately reviewed and discussed? Is there evidence of safety?  Are the pharmacodynamic biomarkers well-reasoned and appropriate to evaluate the success of the intervention?  Will the investigator collect biosamples for ‘omic’ analyses aimed at interrogating treatment responsiveness and examining predictors of decline and progression?

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

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements? Are the resources appropriate for conducting an early stage clinical trial?  Are the resources available to the investigators adequate for the project proposed?  Is the proposed trial population readily available and are there adequate resources for recruitment and retention?  Will the project have the resources to collect and store blood and other biosamples?

Additional Review Criteria

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

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Children 

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

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

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

Resubmissions

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

Not Applicable

Revisions

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

Additional Review Considerations

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

Applications from Foreign Organizations

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

Select Agent Research

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

Resource Sharing Plans

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

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:

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

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications. Following initial peer review, recommended applications will receive a second level of review by the 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.
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

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

Section VI. Award Administration Information
1. Award Notices

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

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

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

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

2. Administrative and National Policy Requirements

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

Cooperative Agreement Terms and Conditions of Award

Not Applicable

3. Reporting

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

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

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

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 Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: https://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 CenterTelephone: 800-518-4726
Email: support@grants.gov

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

Scientific/Research Contact(s)

Laurie Ryan
National Institute on Aging (NIA)
Telephone: 301-496-9350
Email: ryanl@mail.nih.gov

Lois Tully
National Institute of Nursing Research (NINR)
Telephone: 301-594-5968
Email: tullyla@mail.nih.gov

Peer Review Contact(s)

Mark Lindner
Center for Scientific Review (CSR)
Telephone: 301-915-6298
Email: lindnermd@mail.nih.gov

Financial/Grants Management Contact(s)

Katie Ellis
National Institute on Aging (NIA)
Telephone: 301-402-7734
Email:  ellisk@mail.nih.gov

Randi Freundlich
National Institute of Nursing Research (NINR)
Telephone: 301-594-5974
Email: freundlichr@mail.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.

NIH Office of Extramural Research Logo
Department of Health and Human Services (HHS) - Home Page
Department of Health
and Human Services (HHS)
USA.gov - Government Made Easy
NIH... Turning Discovery Into Health®


Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.