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

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

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

Dementia is one of the most persistent and devastating 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 Alzheimer's and/or another dementia with an estimated cost to society of over $200 billion per year. Because of the aging of populations worldwide, the number of individuals with dementia will reach epidemic proportions even in the best-case scenarios, with an enormous human and economic burden. It is projected that 11 to 16 million people and their families could be affected by dementia by the middle of this century if no effective therapies are developed to prevent, slow or stop it.

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 therapeutic effect on disease progression. The Alzheimer’s Association’s 2015 trajectory report estimates 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 AD in the severe stage that requires the highest level of care with the greatest costs.

While there have been no newly approved treatments for dementia since 2003, there are multiple therapeutics currently in development at various stages. In particular, there are a number of therapies focused on prevention and those trials require screening of thousands of participants to identify eligible individuals. Reliable and efficient trial infrastructure is needed to meet this trial demand. A large proportion of clinical trials across diseases experience delayed recruitment and under-enrollment. There are a number of factors likely contributing to the delay, including the fact that large trials require numerous sites, which can vary in their quality (training, raters, data management, etc.), and lack of ongoing infrastructure support to maintain trial site quality standards (raters, data management, etc.) between trials.

Clinical trial networks can increase the efficiency of research by providing infrastructure, centralized resources, and access to well-characterized participants.

Overall Objectives of this FOA:

• Create infrastructure with expert leadership to streamline implementation of NIH funded AD and other age related dementia clinical trials;
• Develop innovative trial design methods, outcomes and analysis strategies;
• Maintain trial site quality standards (raters, data management, etc.) between trials;
• Develop and implement cutting-edge participant recruitment and retention strategies, especially in diverse populations

The ACTC will coordinate data and administrative functions, including:

• utilize a centralized Institutional Review Board (IRB) for ACTC trials
• create and support data capture system for data pertinent to the ACTC
• secure centralized tissue banking for specimens for ACTC trials
• provide centralized imaging, biostatistics, bioinformatics and data management and analysis support
• manage any relevant public private partnerships

The ACTC should consist of the following units:

• Administration: will be responsible for the management and coordination of ACTC trials and other activities including regulatory and centralized IRB functions.
• Bioinformatics/Data Management: will be responsible for the acquisition, integration and analyses of ACTC data
• Biospecimens: will be responsible for centralized tissue banking for specimens
• Imaging: will be responsible for centralized image storage and analyses
• Recruitment Strategies: will be responsible for developing and implementing cutting-edge participant recruitment and retention strategies, in particular, strategies focused on improving participation of diverse populations
• Clinical Trial Sites: Network of sites participating in the ACTC

Steering Committee:  The Steering Committee will serve as the operational governing board and should include: the PD(s)/PI(s), unit leaders, the NIH and Clinical Site PD/PIs, Project Scientist (voting), the NIH Program Official (ex officio). Among other functions, the Steering Committee will have primary responsibility for finalizing standard procedures and protocols and holding regular meetings and teleconferences. The Steering Committee will also be responsible for reviewing and selecting project proposals from the extramural community (academia/biotech/industry) that will be solicited by grants funded under future funding opportunities to use the infrastructure supported by these U24 awards. .

Additional committees should include, but are not limited to:

• Ethics, to review potential conflicts of interest within the ACTC.
• Publications, to develop policies for presentations and manuscripts of ACTC data and to assure compliance with those policies.
• Biospecimen Allocation Review Committee, to review and make recommendations regarding biospecimen allocation requests.

External Advisory Board: The ACTC should have an external advisory board organized from non-conflicted experts outside of the network as well as a representative from the Food and Drug Administration, and a bioethicist, to guide the leadership in assessing the progress, assessing new scientific opportunities and evaluating the effectiveness of interaction among Units and Clinical Sites. The external advisory board will advise the steering committee on different aspects of the network’s function including prioritization of projects, changes in direction or approach, sharing of data, problem identification and resolution.

Consortium Trials: Trials will be selected from project proposals from industry and academic investigators submitted in response to a future FOA that will solicit applications for clinical trials to be implemented through the ACTC. Other clinical trials may be run through the ACTC, but those received in response to the solicitation will take priority.

Once approved for NIH funding through other FOAs, final protocols will be developed in conjunction with the ACTC. All sites will then have the option to request participation and will be selected based on their capabilities specific to the individual protocols. It is also possible that non-network sites may be added ad hoc for a specific trial, based on their expertise and capacity for a specific trial to complement consortium sites.

Funds for specific trials will be distributed to the Clinical Sites on a per patient basis, according to protocol budgets approved by the ACTC Steering Committee (SC) and via master trial agreements with the Clinical Sites.

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

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

Higher Education Institutions

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

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

• 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

The ACTC may include multiple sites for units and leadership, but there must be a single applicant institution.

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

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

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

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

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

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

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

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

Only one application per institution (normally identified by having a unique DUNS number or NIH IPF number) is allowed.

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

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

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

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

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

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

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

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

The letter of intent should be sent to:

Laurie Ryan, Ph.D.
Telephone: 301-496-9350
Fax: 301-496-1494
Email: ryanl@mail.nih.gov

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed, with the following exceptions of additional requirements:

• For this specific FOA, the Research Strategy section is limited to 30 pages.

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

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

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

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

Facilities & Other Resources: Describe how local clinical research resources such as space and research staff will relate to the activities, and, if applicable, how the network will integrate Clinical and Translational Science Award (CTSA) and/or additional clinical trial resources.

Describe how the administrative offices of the institution (University administration (Regent or Presidential Office), Dean of College (PD/PI primary appointment), Department Head (PD/PI primary department), Office of Sponsored Programs, Office of Contracting and Sub-Awards (if separate from Sponsored Program office) will support the application with administrative space and staff related to the activities.

Demonstrate institution commitment to the PD/PI by providing departmental and institutional support letters and by other means (e.g., additional protected time, departmental research leadership position, facilities, space, or resources for the PD/PI).

Describe proposed data management/software systems.

Other Attachments: Provide evidence that the institution has prior successful experience and on-time performance in management of large multi-site clinical trials. Document timelines in project management of these trials, such as, e.g., subcontract execution, IRB approval, patients screened and randomized, and database lock and primary analysis and publication. Also describe the collaborative leadership structure used in recent/ongoing multi-center trials coordinated.

Include sample standard operating procedures used in the implementation of multi-center clinical trials, including, but not limited to SOPs describing database access, data quality control, data queries with audit trails, etc.

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

Name an experienced research team that will support the project management and implementation of the ACTC trials.

The administrative requirements of the ACTC will necessitate the assistance of an administrator with business management expertise. It is important that such an individual be identified and be directly involved with the fiscal and administrative aspects of the application and grant. The administrator should be able to provide consultation in matters of fiscal administration and be familiar with NIH grant-related compliance policies.

Name an experienced statistician and clinical trial data management expert, with a track record in successfully implementing the statistical and data aspects of multicenter clinical trials.

The biographical sketches should reflect the clinical trial expertise and track record of the proposed research staff.

One of the PDs/PIs should be named as Associate Director who will be involved in both the administrative and scientific efforts of the ACTC.

The PD/PI(s) of the ACTC should have:

• Expertise in AD and/or other neurodegenerative disease clinical trials;
• Demonstrated leadership in the design and conduct of clinical trials, as well as a track record in successfully coordinating and implementing complex, multi-site clinical trials, working with academic, foundation and/or industry partners;
• Demonstrated administrative skills, specifically, the PD(s)/PI(s) should be able to organize and administer the resources created by the ACTC in such a way that they may be shared within the ACTC as well as with other qualified scientists;

Eligible ACTC clinical trial sites should:

• Have at least one experienced Alzheimer’s and/or related disorders clinical trial expert and a full time experienced clinical trial coordinator dedicated to the ACTC.
• Have experience in conducting clinical trials (pharmacological and/or non-pharmacological) in Alzheimer’s and/or related disorders.

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

ACTC should provide sufficient resources for each Clinical Site to include, but not be limited to, at least one full time clinical trial coordinator dedicated to the ACTC as well as sufficient funds to support ongoing recruitment activities at each site.

The PD/PI should commit and maintain throughout the life of the award a minimum of 2.4 person-months of effort per year. For applications with multiple PD(s)/PI(s), a minimum of 1.2 person-months of effort per year is required.

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

ACTC should provide sufficient resources for each Clinical Site to include, but not limited to, at least one full time clinical trial coordinator dedicated to the ACTC as well as sufficient funds to support ongoing recruitment activities at each site.

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

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

Specific Aims: Describe the aims of the overall consortium and outline how the planned infrastructure will contribute to these aims.

Research Strategy: Describe how the ACTC will provide infrastructure to implement at least 5-7 complex, multi-center clinical projects over the funding period, including, but not limited to, the following:

Demonstrate capabilities/expertise across the consortium, but not necessarily at all sites, regarding:

• Treatment trials
• Prevention trials
• Neuropsychiatric trials
• Diversity recruitment
• Spanish language assessment
• Care partner recruitment for research participation
• Capacity to incorporate novel approaches to recruitment and assessment, including innovations in technology

Describe plans to streamline the implementation of trials from start-up to publication, e.g., use of master trial agreements, efficient contracting and centralized IRB;

Outline efforts to develop and share novel and innovative trial design methods, outcomes and analysis strategies;

Clearly articulate how the consortium will create/modify, support and share electronic data capture systems for data pertinent to the ACTC;

Demonstrate the ability to track site performance as it relates to ongoing ACTC trials;

Describe how protocol adherence and data quality will be maximized in collaboration with the Clinical Sites;

Illustrate how ACTC will secure centralized tissue banking for specimens submitted by the members of the ACTC and a biospecimen database that would include all tissue resources of the ACTC with appropriate consent to allow full sharing with qualified investigators;

Describe plans to provide centralized biostatistics, bioinformatics and data management analysis support;

Delineate a clear plan for innovative participant recruitment strategies, with strong emphasis on diverse populations;

Illustrate how the consortium will support meeting and communication coordination among clinical sites of ACTC;

Specify how the ACTC will assure the availability of the data and biospecimens to all qualified investigators in a timely and appropriate manner.

Describe any special expertise or unique strengths offered to the collaborative effort (e.g., experience in clinical trial collaborations with various stakeholders (e.g., industry, foundations, etc.), database tools, hardware, software, quality control tools, monitoring expertise, team leadership and training, communications platforms, website design and management).

Show how the ACTC will provide guidance to investigators developing interventions for AD and related dementias;

Outline how an ACTC website will be developed and maintained to accommodate both the public and investigators.

If there are multiple sites for units and/or leadership of the ACTC, organizational structure and communication must be clearly described.

Letters of Support: General statements of support of collaborative research and the willingness to participate in a collaborative and interactive manner with the Clinical Sites, NIA and its partners (both academic and industry partners) in all aspects of the consortium program should be gathered from the following entities (or their equivalent): 1) University administration (Regent or Presidential Office), 2) Dean of College (PD/PI primary appointment), 3) Department Head (PD/PI primary department), 3) Office of Sponsored Programs, 4) Office of Contracting and Sub-Awards (if separate from Sponsored Program office)

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

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. The plan should include how ACTC resources such as the Electronic Data Capture Systems and any other tools, outcome measures, trial designs, or analysis methods developed by the ACTC will be shared.

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

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

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

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

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

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

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

Applicants are required to follow our Post Submission Application Materials policy.

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

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

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

Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

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

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

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

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

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

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

Communication

Are the proposed interactions/communications between the ACTC leadership, clinical sites and the community (e.g., referring physicians and participant populations) clearly described and optimized?

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

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

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

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

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

Not Applicable

Not Applicable

Not Applicable

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

Not Applicable

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

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).Describe plans and procedures for data sharing both within the consortium and with the broader research community.

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

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

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

As part of the scientific peer review, all applications:

• Will receive a written critique.

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

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

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

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

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

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

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

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

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

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

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

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

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

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

• Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.
• Overall management of the study through the coordinating center and should agree to work cooperatively with the functions and clinical sites
• Developing and implementing systems necessary for communications among the various study organizational components. The coordinating center will facilitate the design and refinement of all protocols, manuals of operations, and forms.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

• The designated NIA Project Scientist will serve as a member of the Steering Committee and have substantial scientific/programmatic involvement during conduct of the cooperative agreement, through technical assistance, advice, and coordination above and beyond normal program stewardship of grants. The awardee agrees to accept assistance from the designated NIA Project Scientist. This person will participate, through the Steering Committee, in the monitoring of issues relating to recruitment, follow up, and adherence to protocols and will assist in the development and/or adjustment of study protocols.
• Additionally, an agency program official or NIA program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

• The Steering Committee, comprised of the PD/PI of the cooperative agreement, the leader of the units and each of the clinical sites, and the NIA Project Scientist will have primary responsibility for finalizing standard definitions, procedures, and measures common for all the protocols. The steering committee will meet every three to six months, or as dictated by the needs of the study. Each full member of the Steering Committee will have one vote, and all major scientific decisions will be determined by majority vote of the Steering Committee. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee. Subcommittees appointed by the Steering Committee, comprised of appropriate staff from the functions and clinical sites, will be involved in the design of protocols and manuals of operations, and in ongoing functions of the study such as preparation of publications.
• To oversee the allocation and distribution of biological specimens generated from the study, the Steering Committee will nominate members for a Biospecimen Allocation Review Committee (BARC). This group will review applications for use of the biological specimens. The format of the application and criteria for the use of repository biological specimens will be developed by the BARC with advice and approval from the Steering Committee and made available to all potential users. Membership on this committee will rotate periodically according to a procedure developed by the BARC. Final approval of member of the BARC and final approval for disposition of samples to investigators following BARC review will be made by NIA staff. The primary governing body of the study will be the Steering Committee, which will have responsibility for the final details of study design and policy decisions and will define the rules regarding access to data and samples.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

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

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

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

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

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: 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 Center Telephone: 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

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

Nina Silverberg, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-496-9350
Email: silverbergn@mail.nih.gov

Ramesh Vemuri, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-496-9350
Email: vemurir@mail.nih.gov

John Bladen
National Institute on Aging (NIA)
Telephone: 301-402-7730
Email: jbladen@mail.nih.gov

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

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