Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Institute on Aging (NIA) Office of Dietary Supplements (ODS)
Funding Opportunity Title	Dose Response and Efficacy Studies on the Effects of Vitamin D Supplementation on Functional Outcomes in Elderly (U01)
Activity Code	U01 Research Project Cooperative Agreements
Announcement Type	New
Related Notices	August 20, 2013 This opportunity was incorrectly posted with a FORMC-C package. An ADOBE-FORMS-B2 application package has been added. Due to this error, we will accept applications using either package.
Funding Opportunity Announcement (FOA) Number	RFA-AG-14-001
Companion Funding Opportunity	NoneNone
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.866
Funding Opportunity Purpose	The National Institute on Aging (NIA) invites applications for a clinical trial on effects of vitamin D supplementation on falls and gait speed in older individuals. During the six-year support period, the awardee will implement a randomized controlled trial with sufficient power to determine the dose response and efficacy of vitamin D supplementation in preventing falls, across a range of doses and baseline vitamin D levels. A measurement of effects of supplementation on gait speed should be proposed as a secondary outcome. Applicants are strongly encouraged to consider advanced, cost-efficient designs that include a dose-ranging phase followed by an efficacy phase for select doses (e.g., adaptive designs). The first nine months of the award will provide funds to conduct pilot studies to test recruitment strategies, determine the proportion of those screened who are both eligible and willing to be randomized, and finalize the study protocol, data collection forms and manual of procedures for the trial.

Posted Date	July 8, 2013
Open Date (Earliest Submission Date)	August 23, 2013
Letter of Intent Due Date(s)	August 23, 2013
Application Due Date(s)	September 23, 2013, by 5:00 PM local time of applicant organization. Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
AIDS Application Due Date(s)	Not Applicable
Scientific Merit Review	November-December, 2013
Advisory Council Review	January 2014
Earliest Start Date	Standard dates apply
Expiration Date	September 24, 2013
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.

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

Background

Vitamin D deficiency is widely spread in older community-dwelling individuals. Estimates show that 40% to 100% of U.S. and European elderly are vitamin D deficient, depending upon the population and definition used. Numerous observational studies strongly suggest favorable effects of higher vitamin D intake and/or blood levels on multiple health outcomes in older individuals including falls, fractures, decline in physical and cognitive performance, various cancers, cardiovascular and infectious diseases, multiple sclerosis, and overall mortality. However, these associations do not prove a causal relationship, and there is a potential for residual confounding due to incomplete measurement and control for the influence of lifestyle factors such as sunlight exposure, body mass index, age, skin color and gender.

A 2010 Institute of Medicine's committee report and meta-analysis (Dietary Reference Intakes for Calcium and Vitamin D, IOM 2010) concluded that evidence on the relationship between vitamin D and falls and physical dysfunction (as well as several other outcomes) was insufficient and cannot be used to establish health benefits with any level of confidence because of an overall lack of causal evidence from intervention studies for the task of identifying health outcome indicators.

The most recent meta-analyses (Cameron 2010, Kalyani 2010, Murad 2011, Gillespie 2012, Scragg 2012) confirm the pattern of divergent findings from different trials on falls and do not provide adequate evidence. Specifically, the reports from trials and meta-analyses do not consistently find efficacy of vitamin D supplementation in preventing falls in older adults. Further, among the reports that do find efficacy, the wide range of doses and heterogeneity of trial populations do not permit identification of an effective and safe dose of vitamin D, or the populations that are likely or unlikely to benefit. These uncertainties are particularly important because vitamin D supplementation can have adverse effects. Unless they are clarified, individuals receiving vitamin D supplementation could be placed at unnecessary risk because dosage recommendations may be higher than needed for efficacy or because supplementation is extended to those unlikely to benefit. Thus, there is a need to determine the appropriate vitamin D dose, target population, confirm efficacy and safety of the potentially effective doses on falls and gait speed in this population.

A number of issues related to the need for clinical trials on effects of vitamin D supplementation in elderly in regard to a variety of types of trials and their designs, outcomes, populations, and interventions was reviewed by the DGCG’s Clinical Trials Advisory Panel (CTAP). The panel recommended dose-ranging or dose-ranging/efficacy studies across a wide range of doses and baseline 25 hydroxy vitamin D (25[OH]D) levels to determine effective dose of vitamin D on falls and gait speed in community-dwelling elderly 70 years of age and older. Since the effects of supplementation are expected to be sustained for a time after the intervention ends, a follow-up period to determine a complete time course of the effect should be considered. Doses of vitamin D should be high enough to raise serum 25[OH]D to the levels of potential benefit yet be safe and well tolerated. Measurement of serum 25[OH]D should include the Standard Reference Materials (SRM).

Objectives and Scope

This FOA seeks applications for a dose-ranging/efficacy trial on effects of vitamin D supplementation on falls in older community dwelling adults. Applicants should propose a research plan for a clinical trial that would establish dose-response between the graded doses of vitamin D and falls as well as time course for the response. The trial should also confirm efficacy of dose or doses preselected from the dose-ranging phase. Gait speed should be included as a secondary outcome. The applicants are strongly encouraged to consider advanced, cost-efficient designs that include a dose-ranging phase followed by an efficacy phase for select doses (e.g., adaptive design).

The trial should focus on community-dwelling adults 70 years of age and older who are at elevated risk for falls. A definition of population at increased risk for falls should be proposed and justified by the applicants.

The trial should be designed to evaluate the relationship of the effects of supplementation on outcomes to participants baseline vitamin D status, by including more than one stratum of baseline vitamin D. Persons whose serum 25[OH]D is at or below a level clearly indicating vitamin D deficiency (e.g., 25 nmol/L) should not be enrolled. The maximum level of the highest stratum (e.g, 75 nmol/L) should be selected and justified by the applicants. An alternative approach could be to enroll participants with a wide range of vitamin D levels at baseline and use the baseline level as a covariate in the analysis.

In view of current recommendations for vitamin D intake, the trial should not include a placebo control group. Rather, a minimum intervention dosage should be selected to provide reasonable assurance that total vitamin D intake (diet plus supplement) is not less than the current Recommended Daily Allowance for the age group (e.g., Institute of Medicine, 2010). The selection of dose proposed by applicants should be justified based on the evidence available at the time of application. There remains significant uncertainty about the differences in half-life and long-term effects of vitamin D2 and D3 on the outcomes, and applicants should include rationale for the selection of either form of vitamin D as the study intervention.

There are few data on safety of high dose vitamin D supplementation in this population and applicants should propose a comprehensive safety protocol with well-defined safety parameters that will be monitored during the study.

Because some studies indicate that the beneficial effects of vitamin D supplementation could last for months after the treatment was discontinued, and because too little is known about safety of the long-term supplementation with high doses of vitamin D, applicants should propose and justify an extended follow-up phase (up to one year) to monitor participants for possible beneficial and deleterious effects of vitamin D supplementation after their completion of the intervention. Applicants should provide a rationale for their proposed duration of such a phase.

To ensure high quality of measurements, any studies of serum 25OHD levels should utilize the Standard Reference Materials for 25 hydroxyvitamin D2 and D3 i.e. SRM 2972 and SRM 972a provided by National Institute of Standards and Technology (NIST), and participation in both the NIST-NIH Vitamin D Metabolites Quality Assurance Program (VitDQAP), and the Vitamin D External Quality Assurance Program (DEQAS). In addition, measurement of total 25(OH)D should include separate determinations for serum 25(OH)D2, 25(OH)D3 and 3-epi-25(OH)D3. Applicants should propose an adequate technique for measuring serum 25[OH]D levels such as liquid chromatography-tandem mass spectrometry, or similar assay. Applicants should consider and justify the need for collection and storage of blood and/or its components as well as other biospecimens collected from the study participants.

Applicants should propose a trial with sufficient power to determine the dose response relationship across the range of tested doses and baseline vitamin D strata, which could then be used as a basis for selecting the appropriate dosage(s) and baseline vitamin D eligibility criteria to use in the efficacy phase. Applicants are strongly encouraged to consider a variety of design strategies, including designs in which interim dose-ranging information could be used as a basis for discontinuing some arms and/or extending others to allow definitive determination of efficacy of specific doses.

The first nine months of the award will provide funds to refine the protocol, recruitment and screening strategies, data collection forms, and manual of procedures. During this period the awardee should conduct a pilot study to test recruitment strategies and determine the proportion of screenees who are both eligible and willing to be randomized.

Applicants are strongly encouraged to include personnel with expertise in the wide range of scientific areas pertinent to this research including endocrinology, vitamin D metabolism, geriatrics, biostatistics, clinical trials design and implementation, data management, central laboratory procedures, functional assessment methodology, and others. Applicants are also encouraged to consider implementing the study in the health care systems environment, if feasible.

Project Organization

Applicants should propose appropriate structural components for the trial that at a minimum include a coordinating center, clinical sites, and central laboratory.

Funding Instrument	Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities.
Application Types Allowed	New The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	NIA and ODS intend to commit $1 million in FY 2014 and $1.72 million in FY 2015-2019 for an estimated total of $9.6 million to make one award
Award Budget	The funds available shown above reflect the total costs allowed.
Award Project Period	Six 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.

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) 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 not 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 and should work with their organizational officials to either create a new account or to affiliate an existing account with the applicant organization’s eRA Commons account. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

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

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

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

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

NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:

• To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
• Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
• Of an application with a changed grant activity code.

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.

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

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:

Judith S. Hannah, Ph.D.
Division of Geriatrics and Clinical Gerontology
National Institute on Aging
7201 Wisconsin Avenue, Suite 525A
Bethesda, MD 20892-9205
(Fed Ex Packages use ZIP 20814)
Telephone: (301) 435-0044
Fax: (301) 402-1784
Email: hannahj@nia.nih.gov

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

The forms package associated with this FOA includes all applicable components, required and optional. Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate optional components.

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

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

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

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

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

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

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

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

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) 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.

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.

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.

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 by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.

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.

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?

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?

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?

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?

If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion 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?

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 Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

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

Not Applicable

Renewals

Not Applicable

Revisions

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.

Applications from Foreign Organizations

Not Applicable

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) Genome Wide Association Studies (GWAS).

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.

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

As part of the scientific peer review, all applications:

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

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

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

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

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

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 the DUNS, SAM Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants 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.

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 Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), 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:

All aspects of their study, including any modification of study design, conduct of the study, quality control, data analysis and interpretation, preparation of publications, dissemination of data, tools, and technologies, and collaboration with other investigators. The awardee agrees to accept close coordination, cooperation, and participation of NIA staff in those aspects of scientific and technical management of the study.

Upon implementation of the protocol, each field center, whether a single institution or a consortium of institutions, will follow the procedures required by the protocol regarding study conduct and monitoring, patient management, and data collection.

NIA Scientific Officer has substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

Have access to data generated under this Cooperative Agreement and will periodically review the data and progress reports. NIA Scientific Officer may use information obtained from the data for the preparation of internal reports on the activities of the study.

Serve as a resource to provide scientific/programmatic support during the accomplishment of the clinical trial by participating in the design of the activities, advising in the selection of sources or resources, advising in management and technical performance, or participating in the preparation of publications.

Participate in the monitoring of issues relating to recruitment, retention and follow-up of study participants, and monitoring of data integrity and quality control through consideration of the annual reports, site visits, patient logs, etc. This review may include, but is not limited to, compliance with the study protocol, meeting patient enrollment targets, adherence to uniform data collection procedures, and the timeliness and quality of data reporting.

Assist in the development and modification of study protocols.

Additionally, an agency program official or IC Program Officer will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

The NIA Program Officer will have the right to initiate termination or suspension of the study in the event of (a) substantial shortfall in participant recruitment, follow-up, data reporting, quality control, or other major breach of the protocol; (b) substantive changes in the protocol to which the NIA does not agree; (c) reaching a major study endpoint substantially before schedule with persuasive statistical significance; or (d) human subject ethical issues that dictate study termination.

The addition, modification or replacement of a component or research objectives of this study will require prior written approval of the NIA Program Officer.

Areas of Joint Responsibility include:

A Steering Committee (SC), composed of the principal investigator, as well as the principal investigators of the various field clinical centers, the Data Coordinating Center and of the specialized core facilities, and NIA Scientific Officer. The NIA Scientific

Officer will have voting membership on the SC and, as appropriate, and its subcommittees. The SC will have primary responsibility for facilitating the conduct and monitoring of studies and reporting study results. Awardees will be required to accept and implement the common protocol and procedures approved by the SC. As the components of the SC may be geographically dispersed, the SC should meet with at least monthly conference calls, supplemented as deemed necessary by face to face meetings. Each full member will have one vote. Awardee members of the Steering Committee will be required to accept and implement all policies governing the study conduct approved by the Steering Committee.

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 annual Non-Competing Progress Report (PHS 2590 or RPPR) 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.

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

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

Web ticketing system: https://public.era.nih.gov/commonshelp
TTY: 301-451-5939
Email: commons@od.nih.gov

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

Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone: 301-710-0267
TTY 301-451-5936
Email: GrantsInfo@nih.gov

Judith S. Hannah, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-435-0044
Email: hannahj@nia.nih.gov

Ramesh Vemuri, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-496-9666
Email: vemuri@nia.nih.gov

Deborah Stauffer
National Institute on Aging (NIA)
Telephone: 301-496-1472
Email: stauffed@nia.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 Parts 74 and 92.