Part 1. Overview Information

Key Dates

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

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

No late applications will be accepted for this Funding Opportunity Announcement.

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 NOFO or in a Notice from NIH Guide for Grants and Contracts ).

Conformance to all requirements (both in the Application Guide and the NOFO) 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. Notice of Funding Opportunity Description

Purpose

The Molecular Transducers of Physical Activity Consortium (MoTrPAC) (http://commonfund.nih.gov/MolecularTransducers) is a national research consortium designed to discover and perform preliminary characterization of the range of molecular transducers (the ‘molecular map’) that underlie the effects of physical activity.  MoTrPAC’s overall goal is to understand the biological processes and pathways through which physical activity influences health and disease outcomes.  This understanding would allow the development of targeted exercise interventions, such as intensity, duration, and the type of activity, and more targeted physical activity prescriptions.  MoTrPAC seeks to achieve the following: to create a map of the molecular changes that occur after physical activity, in animal models and in humans; and to place this information into a user-friendly database accessible to the larger research community.

MoTrPAC functions as a large, complex, collaborative undertaking:  Clinical Centers (CC) collect tissues such as blood, muscle, and fat from well-characterized participants engaging in physical activity. Biospecimens are analyzed using multiple technologies by Chemical Analysis Sites (CAS). Preclinical Animal Studies Sites (PASS) provide additional tissues that cannot be obtained from human subjects and allow for further characterization and validation of molecular transducers identified from the chemical analysis of human samples. A Bioinformatics Center (BIC) oversees data standardization, integration, and storage, leads the development of computational tools for the integrated analysis of clinical and molecular data, and implements data sharing and. The Consortium Coordination Center (CCC) provides overall coordination.

The overall design of the MoTrPAC study has been described in a recent publication https://pubmed.ncbi.nlm.nih.gov/32589957/ . Briefly, this study has two study arms, namely, a clinical arm and a rodent animal model arm. In the clinical study, sedentary human participants undergo acute physical activity challenge and then randomization to a 12-week training regimen of either endurance or resistance exercise, before a second physical activity challenge. In humans, there is also an observational study of highly active participants.  Blood, skeletal muscle and adipose tissues from these participants are analyzed to generate a molecular map of physical activity. In children, only blood is collected.  In a parallel arm, the rat model undergoes a similar physical activity regimen.  Nineteen biological tissues were collected, including tissues that cannot otherwise be harvested from humans, and analyzed for omics signatures.

Background and Objectives

The COVID-19 pandemic has had a profound impact on MoTrPAC. Significant delays in recruitment for the clinical study has had cascading effects on other MoTrPAC components.  MoTrPAC clinical center investigators worked closely with their local institutions, and with the study DSMB and sIRB to ensure the safe resumption of recruitment and of clinical activities.  All clinical centers resumed full recruitment and clinical activities in FY22. As COVID restrictions were eased, the consortium completed the animal study arm, tissue specimens were analyzed, and data analysis is currently underway.

The entire MoTrPAC program has been extended to complete the clinical study, data generation, analyses, and data release to the research community.  The program extension was approved to complete recruitment, within the existing infrastructure.  Four Limited Competition NOFOs will facilitate activities to ensure completion of the MoTrPAC clinical study.

Consortium Coordinating Center

The goals of the Consortium Coordinating Center ( CCC) are to provide overall coordination of the Consortium, to monitor study protocol implementation, to coordinate the collection and distribution of data and biological samples from MoTrPAC studies, and to contribute to the creation of a resource for future researchers. The primary purpose of this NOFO is to provide support the existing Consortium Coordinating Center (CCC) during the study’s continuation. RFA-RM-23-010 will support continuation of the MoTrPAC Clinical Centers.

This limited competition funding opportunity announcement (NOFO) is to solicit an application from current CCC awardees to continue clinical coordinating center activities during the completion of the Molecular Transducers of Physical Activity Consortia (MoTrPAC) study.

It is intended that the Consortium Coordinating Center includes (but is not limited to) the following cores and functions:

The Data Management Analysis and Quality Control Center (DMAQC) will be responsible for clinical data acquisition, data management and data analysis related to QC, as well as select presentations and publications; managing safety-related events with assistance from the Exercise Intervention Core (EIC); working with the Biospecimen Repository on sample tracking and QC; and have primary responsibility for preparation od DSMB reports and presentations and Central IRB submissions.

The Biospecimen Repository will oversee the collection, storage, and tracking integration with the clinical data management system, shipping and quality control of the biological samples.

The Exercise Intervention Core (EIC) will help resolve issues that arise related to the delivery of the interventions and in performing clinical assessments; facilitate the operation of QC working groups related to the intervention and clinical assessments; work with programmers and project managers in DMAQC to develop real-time reports for intervention and clinical assessment QC; chair site visits; assist with DSMB reporting; and participate on the DMAQC safety team.

The Administrative Core (ACC) will facilitate communication across the consortium, oversee scheduling of calls and conferences, and prepare minutes for committee and subcommittee meetings.

.Applicants to this NOFO should address how they will lead collaborative MoTrPAC science from the position of the CCC. To achieve success, the NIH expects all MoTrPAC awardees to employ best practices of team science, including mutual respect, cooperation, and collaboration, with all consortium members. The NIH also expects adherence to the currently approved protocol and standards for data analysis set forth and mandated by the DSMB. As the national leader for the NIH MoTrPAC program in cooperation with NIH, the Program Director/Principal Investigator(s) of the CCC is expected to have broad experience in working collaboratively across disciplines ability to communicate clearly with all relevant stakeholders and work to find common ground.

Awardees of this NOFO will work together among themselves and with other components of the consortium in ensuring 1) the analysis of biological specimens from study participants, 2) timely generation and sharing of the data, and 3) generation of the molecular maps that transduce the benefits of physical activity.  It is essential that applicants for this NOFO familiarize themselves with the companion NOFOs for the Clinical Coordinating Center, Bioinformatics Center, and Chemical Analysis sites to understand how they will and should continue to function together as part of the consortium.

It is essential that applicants for this NOFO familiarize themselves with the companion NOFOs to understand how they will and should continue to function together as part of the consortium.   

The CCC will work with NIAMS, NIH OD, individual Clinical Centers, the Chemical Analysis Sites, the Bioinformatics Center and the PASS. The objectives for this limited competition NOFO are to provide overall project coordination, administration, and standardization, while emphasizing participant safety and a commitment to diversity. In particular, this NOFO seeks an application, from the current MoTrPAC CCC, that proposes activities to meet the following broad goals:

• Organization and administration of the MoTrPAC Steering Committee, its subcommittees and working groups, the Data Safety Monitoring Board, and IRB.
• Ensuring the integrity of the study design by ensuring quality control and standardization in executing study protocols and in clinical/animal data acquisition, and in developing policies for presentations and publications, and data sharing.
• Facilitation of study progress at the clinical centers, animal, and chemical analysis sites by monitoring participant recruitment, retention, and safety, adherence to protocols, and biospecimen management; and training, certifying, and monitoring staff on protocols and procedures.
• Biospecimen acquisition, storage, and shipping.
• Data collection, storage, and analysis.
• Reporting, outcomes, and dissemination.

Program Formation and Governance:

MoTrPAC awards are administered as cooperative agreements, with close interactions amongst the awardee, awardees from the companion NOFOs, and NIH staff. The PDs/PIs of awards and NIH program staff form the MoTrPAC Steering Committee, which is responsible for consortium governance, subject to oversight by an NIH MoTrPAC Working Group of the NIH Common Fund. The Steering Committee is responsible for the overall scientific direction of the program; assuring compliance with program policies and procedures; designing study protocols; implementing studies; ensuring data quality and completeness; planning for analysis and interpretation of data; and reporting results in presentations and publications.

The Steering Committee has established subcommittees and working groups: subcommittees have specific scientific jurisdiction of various aspects of the consortium; and subcommittees charge working groups specific tasks as necessary.  Subcommittees make recommendations to the Steering Committee for final approval. This process has been utilized by MoTrPAC to develop policies and documents including the clinical protocol, ancillary studies policy, and data sharing policies (https://motrpac.org). 

External Study Monitoring

Five to seven External Scientific Advisors will provide input based on their individual areas of expertise as needed over the course of the program. They will assist the NIH MoTrPAC Working Group regarding processes and substantive 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.

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 NOFO.

Section III. Eligibility Information

1. Eligible Applicants

This is a limited competition open only to the currently supported Molecular Transducers of Physical Activity Consortium (MoTrPAC) Consortium Coordinating Center, awarded in RFA-RM-15-014.

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.

• System for Award Management (SAM)– Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
  • Unique Entity Identifier (UEI)- A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registration; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov – Applicants must have an active SAM registration in order to complete the Grants.gov registration.

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

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

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 their organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.

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

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see 2.3.9.4 Similar, Essentially Identical, or Identical Applications)

This is a limited competition open only to the currently supported Molecular Transducers of Physical Activity Consortium (MoTrPAC) Consortium Coordinating Center, awarded in RFA-RM-15-014. There will be a single unified application, although NIH intends to make separate awards for parts of the Consortium Coordinating Center (e.g., DMAQC, EIC, Biospecimens Repository, Administrative Core etc.)

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 NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide except where instructed in this notice of funding opportunity 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.

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 NOFO.

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.

A statement of strong commitment and willingness to participate in consortium activities to complete the MoTrPAC program, data analysis and publication of observed results should be provided.

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

Proposed key personnel should reflect the continuity of the expertise and experienced personnel required for the ongoing MoTrPAC program. Personnel should demonstrate strong scientific, administrative, technical, and management expertise in the areas necessary to complete the CCC functions.

R&R Budget

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

A budget is required.  There will be a single CCC award.  However, the application should provide separate budgets for each part of the CCC, as NIH intends to make separate awards for each part of one CCC: DMAQC, EIC, Biospecimen Repository, and ACC.

R&R Subaward 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, with the following additional instructions:

Specific Aims: The overall goal of MoTrPAC is the development of a molecular map of transducers that underlie the effects of physical activity in humans, to provide a database and associated tools for storage and integration of clinical physiological and metabolic data along with multiple types of chemical analysis data derived through metabolomics, proteomics, genomics, transcriptomics, or similar technologies, and to make the map accessible to the research community. The Consortium Coordinating Center (CCC) provides overall coordination of the Consortium, monitors study protocol implementation, coordinates the collection and distribution of data and biological samples from MoTrPAC studies, and contributes to the creation of a resource for future researchers.  Please describe the CCC’s role in achieving the overall objectives of the MoTrPAC.

Research Strategy: A summary of accomplishments to date should indicate that the expertise of the staff and the resources available are appropriate for the project.  Describe plans for the continued functioning of the CCC, including the following:

• Facilitating study progress at the clinical centers, by monitoring participant recruitment, retention, and safety, adherence to protocols; and training, certifying, and monitoring staff on protocols and procedures
• Ensuring accurate biospecimen management and tracking, to provide samples in a timely way to Chemical Analysis Sites, and according to the MoTrPAC-approved tissue analysis plans
• Interacting with the study DSMB and IRB, to provide reports and presentations
• Providing clinical and physiologic data to the Bioinformatics Center, and working with MoTrPAC colleagues on data QA/QC
• Participating in analyses of physiologic and clinical data as required
• Maintaining communications among consortium committees and subcommittees, by organizing and scheduling meetings, agendas and notes of meetings

Progress Report: A progress report to-date summarizing various MoTrPAC consortia activities and specific accomplishments should be included.

Milestones and Timeline: Describe an approximate timeline for the proposed project, along with milestones.

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. 

Other Plan(s):

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

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

• Resources generated by MoTrPAC are expected to be widely shared with the Consortium and with the broader scientific community for research. The MoTrPAC Steering Committee has developed and is implementing Consortium-wide policies, including for data and resources. The Steering Committee has ratified a Consortium Data Sharing Plan, which has also been reviewed and approved by the study DSMB.  Applicants should include a copy of the Consortium Data Sharing Plan. By providing a statement of strong commitment and willingness to participate in consortium activities, applicants agree to abide by the consortium-developed Sharing Plan. Applicants should also complete the template DMSP provided.

Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

• No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

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

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.

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 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 form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this NOFO for information on registration requirements.

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

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by the Office of Strategic Coordination (OSC), 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

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.

Overall Impact

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

Scored Review Criteria

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

Significance

Does the proposed Consortium Coordinating Center address the needs of the research program? Is the scope of activities proposed appropriate to meet those needs? Will successful completion of the aims bring unique advantages or capabilities to the research program?

Specific to this NOFO,

How will the functions of the Coordinating Center contribute to the successful completion of the MoTrPAC study?

Investigator(s)

Are the PD(s)/PI(s) and other personnel well suited to their roles in the Consortium Coordinating Center? Do they have appropriate experience and training, and have they demonstrated experience and an ongoing record of accomplishments? Do the investigators demonstrate significant experience with coordinating collaborative basic and clinical research? If the Center is multi-PD/PI, do the investigators have complementary and integrated expertise and skills; are their leadership approach, governance, plans for conflict resolution, and organizational structure appropriate? Does the applicant have experience overseeing selection and management of subawards, if needed?

Specific to this NOFO,
Do the investigators provide sufficient details to demonstrate their willingness to collaborate with NIH scientists and staff, and with investigators and staff from other elements of the MoTrPAC?

Innovation

Does the application propose novel management strategies in coordinating the research program? Are the strategies novel to one type of research program or applicable in a broad sense? Is a refinement, improvement, or new application of management strategies proposed?

Approach

Are the overall strategy, operational plan, and organizational structure well-reasoned and appropriate to accomplish the goals of the consortium? Will the investigators promote strategies to ensure a robust and unbiased scientific approach across the consortium, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the consortium is in the early stages of operation, does the proposed strategy adequately establish feasibility and manage the risks associated with the activities of the consortium? Are an appropriate plan for work-flow and a well-established timeline proposed? Have the investigators presented adequate plans to ensure consideration of relevant biological variables, such as sex, for studies of vertebrate animals or human subjects?

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

Specific for this NOFO:

How will the plans for quality assurance/quality control maintain the high standards for clinical recruitment?

Environment

Will the institutional environment in which the CCC will operate contribute to the probability of success in facilitating the research? Are the institutional support, equipment and other physical resources available to the investigators adequate? Will the CCC benefit from unique features of the institutional environment, infrastructure, or personnel? Are resources available within the scientific environment to support electronic information handling?

Additional Review Criteria

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

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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

Vertebrate Animals

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

For Renewals, the committee will consider the progress made in the last funding period.

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).

.

Authentication of Key Biological and/or Chemical Resources:

For [programs/projects/networks/consortia/resources] 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 the Center for Scientific Review, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications will receive a written critique.

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

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

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 NOFO. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

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

3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information

1. Award Notices

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

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

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

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

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

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:

• Federal wide Research Terms and Conditions
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

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

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS will be required to complete an HHS Assurance of Compliance form (HHS 690) in which the recipient agrees, as a condition of receiving the grant, to administer programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, age, sex and disability, and agreeing to comply with federal conscience laws, where applicable. This includes ensuring that entities take meaningful steps to provide meaningful access to persons with limited English proficiency; and ensuring effective communication with persons with disabilities. Where applicable, Title XI and Section 1557 prohibit discrimination on the basis of sexual orientation, and gender identity, The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. See https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html .

HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this NOFO.

• For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.htmlandhttps://www.lep.gov.

• For information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including providing program access, reasonable modifications, and to provide effective communication, see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html.

• HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.

• For guidance on administering programs in compliance with applicable federal religious nondiscrimination laws and applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/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.html or call 1-800-368-1019 or TDD 1-800-537-7697.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 and 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.”

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 recipients 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 recipients for the project as a whole, although specific tasks and activities may be shared among the recipients 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. PI(s)/PD(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 recipients 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 recipient(s). As required for the coordination of activities and to expedite progress, NIH may designate additional NIH staff to provide advice to the recipient 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 recipients 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 recipient 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 recipients. 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 recipients 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 collective 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.
• Chairs and co-Chairs of various MoTrPAC committees and subcommittees continue to serve in their current roles.  The Chair and co-Chair of the Steering Committee provide leadership to the consortium by conducting its meetings, representing the Consortium to the External Scientific Advisors, and by interacting closely with the other consortium members.
• 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 recipients, 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 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 recipient. This special dispute resolution procedure does not alter the recipient'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. Data Management and Sharing

Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.

Consistent with the NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

4. Reporting

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

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.

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

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

Enter text here.

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 threaten submission by the due date, and post-submission issues)

Finding Help Online: https://www.era.nih.gov/need-help (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: [email protected] (preferred method of contact)
Telephone: 301-480-7075

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

Stephanie George, Ph.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-4974
Email: [email protected]

Center for Scientific Review (CSR)
Email: [email protected]

Sahar Rais-Danai
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-5032
Email: [email protected]

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 and 2 CFR Part 200.