Part 1. Overview Information

Key Dates

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide,except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts ).

Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

This initiative is funded through the NIH Common Fund, which supports cross-cutting programs that are expected to have exceptionally high impact in science. All Common Fund initiatives invite investigators to address problems that may seem intractable or to seize new opportunities that offer the potential for rapid progress.

Purpose

The purpose of this FOA is to invite applications for Preclinical Animal Study Sites (PASS) as part of the Molecular Transducers of Physical Activity in Humans Consortium (MoTrPAC) (http://commonfund.nih.gov/MolecularTransducers). Awards made through this FOA will support preclinical mechanistic studies on a range of molecular compounds identified in the initial PASS exercise protocol which was designed to complement and substantially expand the data from the human clinical study in MoTrPAC. This FOA is expected to support up to 4-6 additional Preclinical Animal Study Sites (PASS) as part of the MoTrPAC.

The work of the three existing PASS is divided into two phases. In Phase 1, the investigators developed and utilized treadmill running and tissue sampling protocols for Fisher 344 rats that parallel and greatly expand the potential impact of the MoTrPAC clinical protocols for active and sedentary volunteers. The PASS Phase 1 included two separate arms to examine the response of two age groups (6 and 18 months) of male and female animals to either an acute bout of exercise or to an intensive and progressive aerobic (70% VO2max) training protocol ranging from one to eight weeks in length. Harvesting tissues from both acutely- and training-exercised Fisher 344 rats along with appropriate sedentary controls has been completed, and the tissues have been distributed to the Chemical Analysis Sites for analysis according to MoTrPAC guidelines

In Phase 2 the three original PASS study sites are designing and conducting detailed mechanistic studies to identify the sources, signaling pathways, physiological targets, and functions of mobilized and identified molecular transducers of physical activity; recognize feedback and interaction effects among different pathways and tissues; and discover specific roles of the molecules associated with specific health benefits. The original three PASS sites have begun analyses of mechanisms involved in transducing the effects of exercise. Preliminary data from five abundant PASS tissues indicate that molecular signals produced by physical activity are abundant and diverse (MoTrPAC-data.org)

In view of the enormous number of molecules mobilized in the two treadmill exercise arms of the study, this new RFA calls for additional applications to join the consortium for the remainder of the MoTrPAC funding period to explore the mechanistic links between the candidate molecular transducers of physical activity and functional effects of exercise in tissues. Building on existing and future animal and human data, such preclinical studies will extend knowledge of the benefits of molecular transducers of exercise. Overall, data from existing and newly funded PASS studies are anticipated to substantially increase our understanding of how tissues and organs other than muscle, fat and blood adapt to the exercise induced changes. Data from the 19 PASS tissues will extend the analyses of candidate transducers of physical activity from the clinical study (muscle, adipose tissue and plasma) across multiple organs and tissues that are not accessible from human participants. Applicants should propose what they think is the best strategy and approach for investigating how these mobilized compounds synergize to coordinate the overall homeostatic response to exercise in a variety of tissues. Grantees from this RFA will work in conjunction with the MoTrPAC Steering Committee (of which they will be members) to finalize the molecules that will be investigated

The MoTrPAC Bioinformatics Center (BIC) will conduct a data Webinar for interested applicants at a date to be announced on the MoTrPAC Data Hub Website, the MoTrPAC site, and the Common Fund site soon after publication of this FOA.

Background

The goal of the Molecular Transducers of Physical Activity in Humans Consortium (MoTrPAC) is to assemble a comprehensive map of the molecular changes that occur in response to physical activity and, when possible, relate these changes to the benefits of physical activity. This map will contain the many molecular signals that transmit the health effects of physical activity and indicate how these molecules are altered by variables such as age, sex, body composition, fitness level, and chronic exposure to exercise. Information will be housed in a user-friendly public data resource that any researcher can access to develop hypotheses regarding the molecular mechanisms through which physical activity can improve or preserve health

Lack of physical activity is at the root of numerous common chronic health problems. Despite this, we still have a poor understanding of the actual molecular mechanisms by which the benefits of physical activity are realized. The development of a molecular map of circulating and/or tissue specific signals produced in response to physical activity and the molecular changes produced in target tissues is a daunting task. Yet, it is now possible because of recent advances in several powerful high-throughput discovery approaches, including metabolomics, genomics, transcriptomics, and epigenomics

Applicants are expected to take full advantage whenever possible of resources such as databases, catalogues, technologies, protocols, and data standards developed through other national and international efforts, particularly NIH Common Fund programs which are described at http://commonfund.nih.gov/. Examples include Libraries of Integrated Networks of Cellular Signatures (LINCS) (http://commonfund.nih.gov/LINCS/index); Epigenomics (https://commonfund.nih.gov/epigenomics/index); Extracellular RNA Communication (https://commonfund.nih.gov/Exrna/index); Human Microbiome Project (https://commonfund.nih.gov/hmp/index); Genotype-Tissue Expression (GTEx) (https://commonfund.nih.gov/GTEx/index); and Metabolomics (https://commonfund.nih.gov/metabolomics/index).

Preclinical Animal Studies Sites (PASS)

The purpose of this FOA is to provide support for four to six additional Preclinical Animal Study Sites (PASS) as part of the MoTrPAC. The PASS will extend the analyses of candidate transducers of physical activity from the PASS tissue collection across multiple organs and tissues that are not accessible from human participants, as well as to provide comparisons to human data (using muscle, adipose tissue and plasma). As noted in the Chemical Analysis Sites FOAs (RFA-RM-15-010 and RFA-RM-15-011), the PASS element of the MoTrPAC has produced approximately 8,000 samples of various tissues (e.g. blood, muscle, adipose tissue, brain, liver, kidney etc.). Harvested tissues have either been distributed to the Chemical Analysis sites for analyses or are stored at the MoTrPAC Biorepository according to MoTrPAC protocols.?

As part of this FOA and for the remainder of the study, all of the PASS sites will investigate the source and signaling mechanisms responsible for effects of candidate molecules and classes of molecules mobilized in response to acute or chronic physical activity from animal or human (once available) studies on target tissues; decisions regarding which molecules to pursue will be made in consultation with the Steering Committee. Participants are being recruited to the Clinal study, but at this writing human biopsy derived data is not yet available. The goal is that the initial mechanistic studies based on PASS data will begin to elucidate molecular cascades likely contributing to findings in the human studies. In addition, PASS studies are likely to substantially expand the findings in the human studies by identifying previously unexplored tissue interactions not possible in human studies. Data from MoTrPAC is expected to serve as a catalyst for future investigator-initiated studies examining the molecular mechanisms of the benefits of exercise and to facilitate a greater understanding of human physiology

Applicants can propose studies that include but are not limited to assays:

1. designed to identify target tissues of candidate molecular transducers, or classes of transducers, using high throughput screening methods or cell and animal models;

2. focused on the functional or molecular changes and targets associated with the effects of physical activity on specific pathways, systems or tissues;

3. focused on finding the function of specific families of molecules altered by physical activity, such as miRNAs, altered gene expression, modified lipids or amino acids, or a variety of post-translational modifications.

4. focused on elucidating the systems biological relationships whereby exercise molecular transducers might produce broad effects across multiple target tissues to connect with existing mechanistic literature. For example, studies might examine the impact of myokines on innate and adaptive immune signaling

The MoTrPAC Bioinformatics Center (BIC) will conduct a data Webinar for interested applicants at a date to be announced on the MoTrPAC Data Hub Website, the MoTrPAC site, and the Common Fund site

Additional exercise studies and tissue collection for analysis by the MoTrPAC Chemical Analysis Sites are not the focus of this FOA

The entire cadre of MoTrPAC PASS investigators (6-9 teams) will collaborate to design and conduct detailed mechanistic studies to identify the sources, signaling pathways, physiological targets and functions of the molecular transducers of physical activity found in blood and tissues, recognize feedback and interaction effects among different pathways, and discover the specific roles of the molecules associated with specific health benefits. Awards under the second preclinical FOA are expected to begin by the end of FY 2020.

PASS PD/PIs will be expected to:

• Work with the MoTrPAC Steering Committee to harmonize their research plans with the full range of the Consortium's efforts.
• Build on existing consortium data (Data Hub) to design and implement cell or animal model-based assays, focused on initial functional characterization of wide variety of molecular transducers of physical activity. As an example, these could be designed to identify the signaling target tissues or classes of candidate molecules that arise due to physical activity. Experiments could also be designed to look for specific biological effects, such as browning of white fat or remodeling/neurogenesis in brain. In view of the large number of molecules in numerous families of molecules that change in response to a single bout of acute exercise, along with the fact that this list will certainly grow substantially since only five tissues are included in the initial data release suggests the importance that studies conducted in awards from this RFA should consider employing a variety of different approaches to study at least one family of molecules with the goal of identifying novel molecular interactions of different classes of compounds that have promise to greatly enhance the understanding of the overall physiological response to activity and open new avenues of research for future investigator initiated research. Similarly, if an applicant is interested in investigating the exercise response in a single tissue the focus should be on screening at least one class of molecules effects in that tissue rather than one tissue, one molecule
• Contribute all data to the MoTrPAC public data resource in order to share all information that could illuminate the function of the molecules that are altered by physical activity.
• Contribute to data analysis and preparation of publications and/or resources originating in the Network.

Program Formation and Governance

The award funded under this FOA will be a cooperative agreement (see Section VI.2.A. Cooperative Agreement Terms and Conditions of Award). Close interactions amongst the awardee, awardees from the companion FOAs, and NIH is required. The PDs/PIs of these awards will join MoTrPAC and will meet and participate on the MoTrPAC Steering Committee. Each funded element of the consortium has one vote. Consortium governance rests with the Steering Committee and is subject to oversight by an NIH MoTrPAC Program Management Team and the NIH Common Fund.

The NIH appointed a chair of the Steering Committee from among the initial MoTrPAC PDs/PIs. The Steering Committee Chair presides at all Steering Committee meetings and serves on an Executive Committee. Subcommittees facilitate development, implementation, and monitoring of specific MoTrPAC functions as needed, such as participant phenotyping, study monitoring (protocol adherence, participant safety, etc.), disbursement of tissues among the Chemical Analysis Sites, tissue analysis, data handling, and quality control. Key personnel will be expected to serve on subcommittees as appropriate according to their expertise.

The Steering Committee meets in person at least annually. Monthly teleconferences are held for the Steering Committee and its subcommittees meet as needed. The CCC is responsible for arranging and facilitating the meetings and teleconferences.

External Study Monitoring

Five to seven External Scientific Advisors provide input based on their individual areas of expertise as needed over the course of the program. They advise the NIH on issues that arise during the project and will help ensure that the resources to be delivered by the program are as useful as possible for the end users

An independent DSMB has been established to monitor and provide recommendations to the NIH regarding participant recruitment/enrollment, safety, data quality, and other issues, as appropriate. The DSMB reviews the Steering Committee-approved common protocol, informed consent templates, milestones, and monitoring plans prior to the start of recruitment. A single central Institutional Review Board (IRB) has streamlined the protocol approval process and to standardize the monitoring of human subjects protection in the MoTrPAC.

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

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

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) 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 to register in eRA Commons.Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active 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.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

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

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

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guideexcept 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.

Letter of Intent

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:

John P Williams
National Institute on Aging
Telephone: 301-496-6403
Fax: 301-402-0010
Email: williamsj6@mail.nih.gov

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA. All instructions in the SF424 (R&R) Application Guide must be followed. All instructions in the SF424 (R&R) Application Guide must be followed. All instructions in the SF424 (R&R) Application Guide must be followed. All instructions in the SF424 (R&R) Application Guide must be followed.

R&R or Modular Budget

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 as provided in the SF424 (R&R) Application Guide.

The following modifications also apply:

• Generally, Resource Sharing Plans are expected, but they are not applicable for this FOA.

Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide. When involving human subjects research, clinical research, and/or NIH-definedclinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

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

3. Unique Entity Identifier and System for Award Management (SAM)

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

4. Submission Dates and Times

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

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

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

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

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

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

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? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Investigator(s)

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

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? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

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

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?

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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

Vertebrate Animals

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

Biohazards

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

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

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

Awardees of this initiative will be full members of the MoTrPAC consortium, and will agree to abide by the data sharing policies of the consortium. Thus, separate resource sharing plans are not applicable for this FOA.

Authentication of Key Biological and/or Chemical Resources:

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

Budget and Period of Support

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

2. Review and Selection Process

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

As part of the scientific peer review, all applications:

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

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

3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information

1. Award Notices

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

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

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

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, 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 https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.htmlhttps://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.htmlor 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.

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:

• Working together under the auspices of the MoTrPAC Steering Committee to determine research approaches, including definitions of objectives, protocol design, sample size and power calculations, and biospecimen analysis plans, and procedures for participant recruitment and follow-up, data collection, quality control, interim data and safety monitoring, final data analysis and interpretation, and publication of results.
• Setting project milestones and conducting research in collaboration with the MoTrPAC Steering Committee and the NIH MoTrPAC Working Group.
• Participating in group activities, including the Steering Committee and its subcommittees, as needed. This includes participation in planning activities during the first awarded year.
• Refining and implementing the resulting consensus project plan at their sites and Consortium-wide, in collaboration with the Steering Committee, CCC, and Bioinformatics Center.
• Abiding by common definitions, protocols, procedures, as chosen by majority vote of the Steering Committee.
• Providing protocols, reports, and data in a timely fashion as agreed upon by the Steering Committee.
• Submitting periodic progress reports in a standard format, as agreed upon by the Steering Committee and NIH MoTrPAC Working Group.
• Submitting all data to a Consortium-wide database, as agreed upon by the Steering Committee. All data generated by the MoTrPAC will be made public via the Consortium database and publications.
• Publishing or otherwise disseminating results and other products of the study in accordance with study protocols and Steering Committee policies on publications. PD(s)/PI(s) will therefore prepare abstracts, presentations, and publications and collaborate Consortium-wide in making the public aware of the program.
• Adhering to policies regarding data access, publication, and intellectual property established by the NIH and the Steering Committee. The NIH will have access to and may periodically review all data generated under an award. NIH staff may co-author publications of findings with awardees consistent with NIH and study policies.
• Supporting involvement of industry or other third party in the study (e.g., participation by the third party; involvement of study resources or citing the name of the study or NIH support; or special access to study results, primary data/summary information, or resources) when determined to be advantageous and appropriate by the Steering Committee. However, except for licensing of patents or copyrights, support or involvement of any third party is permitted only after concurrence by NIH.
• Maintaining the confidentiality of participant information acquired by the investigators as well as proprietary information of any company collaborating with the study.
• Retaining custody of and having the 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.

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

The Project Scientist(s) will have substantial scientific and programmatic involvement during the conduct of this activity through technical assistance, advice, and coordination. However, the role of NIH staff will be to facilitate and not to direct the activities. It is anticipated that decisions in all activities will be reached by consensus and that NIH staff will be given the opportunity to offer input to this process.

The Project Scientist(s):

• Will serve as the contact point for all facets of the scientific interaction with the awardee(s). As required for the coordination of activities and to expedite progress, NIH may designate additional NIH staff to provide advice to the awardee on specific scientific and/or analytic issues. Such staff may include additional program officials and/or advisory personnel, who will provide direct technical assistance to the awardees to optimize the conduct and/or analysis of the study, or who may assist in the coordination of activities across multiple centers.
• Will participate fully as a voting member of the Steering Committee and, where applicable, its subcommittees. The Project Scientist(s) will assist and facilitate the group process and not direct it. This includes assisting in developing operating guidelines, quality control procedures, and consistent policies for dealing with situations that require coordinated action. The Project Scientist(s) will be responsible for working with the awardee as needed to manage the logistic aspects of the project.
• Will invite five to seven External Scientific Advisors, who do not hold MoTrPAC awards, to work with the Steering Committee as needed and advise the NIH regarding the planning and conduct of the study. The External Scientific Advisors will meet with the Steering Committee for its in-person meetings and teleconferences as needed.
• Will serve as a liaison and help coordinate activities, including acting as a liaison to other NIH Institutes/Centers, and as an information resource for the awardees. The Project Scientist(s) will also help coordinate the efforts of the MoTrPAC with other groups conducting similar efforts.
• Will report periodically on progress to the NIH MoTrPAC Working Group and through it to the NIH Common Fund.
• Will serve as a resource to study investigators with respect to other ongoing NIH activities that may be relevant to the study to facilitate compatibility with the NIH missions and avoid unnecessary duplication of effort.
• Will assist by providing advice in the management and technical performance of the investigations and by coordinating required regulatory clearances for investigational agents used in the study that are held by NIH.
• May coordinate activities among awardees by assisting in the design, development, and coordination of a common research or clinical protocol and statistical evaluations of data; in the preparation of questionnaires and other data recording forms; and in the publication of results.
• May serve as co-authors on study publications. In general, to warrant co-authorship, NIH staff must have contributed to the following areas: (a) design of the concepts or experiments being tested; (b) performance of significant portions of the activity; (c) participation in analysis and interpretation of study results; and (d) preparation and authorship of pertinent manuscripts.
• In addition, a separate NIH Program Official identified in the Notice of Award (NoA) will be responsible for the normal stewardship and monitoring of the award including review and approval of all progress reports and all budgetary decisions. Additional responsibilities for the NIH Program Official include:
• Interacting with the PD(s)/PI(s) on a regular basis to monitor study progress. Monitoring may include regular communications with the PD/PI and staff, periodic site visits, observation of field data collection and management techniques, quality control, fiscal review, and other relevant matters, as well as attendance at Steering Committee, DSMB, and related meetings. The NIH retains, as an option, periodic review of progress by researchers not involved with the study.
• Reviewing and approving protocols prior to implementation to insure they are within the scope of peer review, for safety considerations, as required by Federal regulations.
• Monitoring protocol progress, and may request that a study protocol be closed to accrual for reasons including (a) accrual rate insufficient to complete study in a timely fashion; (b) accrual goals met early; (c) poor protocol performance; (d) patient safety and regulatory concerns; (e) study results that are already conclusive; and (f) emergence of new information that diminishes the scientific importance of the study question. The NIH will not permit further expenditures of NIH funds for a study after requesting closure except as specifically approved by the NIH.
• Making recommendations for continued funding based on (a) overall study progress, including sufficient patient and/or data accrual; (b) cooperation in carrying out the research (e.g., attendance at Steering Committee meetings, implementation of group decisions, compliance with the terms of award and reporting requirements); and/or (c) maintenance of a high quality of research, which will allow pooling of data and comparisons across multiple cooperative agreement awards for common data elements.
• Appointing a DSMB as appropriate. The NIH Program Official or their designee will serve as the Executive Secretary and/or NIH program representative on the DSMB. The DSMB will review interim results periodically and provide guidance to the NIH.

Areas of Joint Responsibility include:

• Close interaction among the participating investigators will be required, as well as significant involvement from the NIH, to develop the overall project. The PDs/PIs, key personnel and the Project Scientist(s) will make up a Steering Committee which will meet in person, along with the External Scientific Advisors, up to three times in the first year and at least annually after that, and monthly or as needed on conference calls to share information on data resources, methodologies, analytical tools, as well as data and preliminary results. PDs/PIs, key co-investigators, other key staff, and pre- and post-doctoral trainees are eligible to attend these meetings. The Steering Committee may invite additional experts as needed, and other government staff may attend the Steering Committee meetings as desired. Each funded element will each have one vote and the NIH Project Scientist(s) will have one vote.
• The Steering Committee may establish subcommittees as needed to address particular issues. Subcommittees will include representatives from the MoTrPAC and the NIH and possibly other experts. The Steering Committee will have the overall responsibility of assessing and prioritizing the progress of the various subcommittees.
• The Chairperson of the Steering Committee will be selected by the NIH. The Chairperson provides leadership to the Steering Committee by conducting its meetings, representing the Consortium to the External Scientific Advisors, and by interacting closely with the other awardees during protocol development and implementation.
• The Steering Committee has primary responsibility to design research activities, establish priorities, develop common protocols and manuals, questionnaires and other data recording forms, establish and maintain quality control among awardees, review progress, monitor patient accrual, coordinate and standardize data management, and cooperate on the publication of results. Major scientific decisions regarding the core data will be determined by the Steering Committee. The Steering Committee will document progress in written reports to the NIH Program Officials and the NIH MoTrPAC Working Group and will provide periodic supplementary reports upon request.
• The External Scientific Advisors will work with the Steering Committee and provide advice as needed. The primary role of the External Scientific Advisors is to advise the NIH with regard to all aspects of the study as needed.

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.

3. Reporting

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement. A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

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 agreementsare required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

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

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants. eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threatensubmission by the due date, and post-submission issues)

Finding Help Online:http://grants.nih.gov/support/(preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

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

Grants.gov Customer Support(Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email:support@grants.gov

John P Williams, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-496-6403
Fax: 301-402-0010
Email: williamsj6@mail.nih.gov

Richard Ingraham, Ph.D.
Center for Scientific Review (CSR)
Telephone: 301-496-8551
Email: richard.ingraham@nih.gov

Mahasin Ingram
Grant Management Specialist
National Institute on Aging (NIA)
Telephone: 301-402-7736
Email: ingrammk@mail.nih.gov

Section VIII. Other Information

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