Required Application Instructions

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

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

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

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

The purpose of this FOA is to invite applications for Clinical Centers, which will conduct the clinical studies for the Molecular Transducers of Physical Activity Consortium (MoTrPAC) (http://commonfund.nih.gov/MolecularTransducers). The MoTrPAC 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 in humans. The Clinical Centers are expected to conduct a multi-center study that will recruit participants for physical activity protocols, characterize them with respect to age, sex, and objective physiologic, morphometric, and metabolic fitness measures, and collect biospecimens for analysis using genomics, epigenomics, transcriptomics, metabolomics, and proteomics. The focus is on those molecules that are most likely to facilitate communication among cells, tissues, and organs, and therefore transduce the health benefits of physical activity. This 'molecular map' will enhance and accelerate subsequent mechanistic research for a variety of conditions and diseases affected by physical activity.

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 signals are altered by variables such as age, sex, body composition, fitness level, and 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 plaguing many individuals around the world. Despite this, we have a poor understanding of the actual molecular mechanisms by which the benefits of physical activity are realized. Molecular signals produced by physical activity are likely to be numerous and diverse, with impacts on many target tissues. The development of a molecular map of circulating signals produced by physical activity and the molecular changes that result 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, proteomics, genomics, transcriptomics, and epigenomics.

The MoTrPAC will be funded via cooperative agreements as a consortium, through six interrelated FOAs. Clinical Centers (RFA-RM-15-015) are central to the overall success of the project. The clinical cohort will consist of healthy males and females of all ages and of different races/ethnicities; some volunteers will be highly active at the beginning of the study, while others will have sedentary lifestyles. Investigators will characterize all participants at baseline with respect to age, sex, and objective physiologic, morphometric, and metabolic fitness measures, as well as collect biospecimens (e.g., blood; skeletal muscle and subcutaneous adipose tissue) before and at several times after a single episode of endurance or resistance exercise. Sedentary participants will participate in a multi-week endurance or resistance training program, after which the investigators will again assess appropriate objective physiologic, morphometric, and metabolic fitness measures before and sample blood and tissues before and after an acute bout of exercise. Samples will be extensively analyzed using high-throughput technologies that allow rapid identification of many different biological molecules from large numbers of samples. This service will be provided by the Metabolomics and Proteomics Chemical Analysis Sites (RFA-RM-15-011) and the Genomics, Epigenomics, and Transcriptomics Chemical Analysis Sites (RFA-RM-15-010). Thorough analysis will enable characterization of a variety of molecules that are altered following physical activity and may thereby contribute to mediating the effects of physical activity. Additional awards will allow Preclinical Animal Study Sites (PASS, RFA-RM-15-013) to conduct experiments in animals that will provide tissues to the Chemical Analysis Sites for the identification of molecular transducers induced by physical activity in tissues that cannot be obtained from humans (e.g., lung, liver, brain, and heart), as well as conduct studies focused on preliminary characterization of novel transducers. Molecular data from the Chemical Analysis Sites and physiologic, morphometric, and metabolic data from the Clinical Centers and PASS will be integrated, stored, and shared by the Bioinformatics Center (RFA-RM-15-012). A Consortium Coordinating Center (CCC, RFA-RM-15-014) will coordinate the entire project including PD/PI meeting organization, training, biospecimen storage and shipping, and workshops. A Steering Committee will design and oversee the entire study to ensure that all aspects of the clinical and animal protocols and the analysis plans will contribute to the mapping of molecular changes that occur in response to physical activity and to prioritize which molecules merit additional characterization by the PASS. An institution can apply to more than one of these FOAs.

Study timeline: The first year will be set aside to assemble the Steering Committee and plan the study, during which time only limited funds will be awarded. It will be followed by five additional funded years during which the study will be implemented. PASS are expected to begin to generate tissues at the end of the first year, and so Chemical Analysis Sites will likely begin to analyze animal plasma and tissues early during the second awarded year, while clinical studies get underway. Molecular data should be continually and sequentially available to Consortium members as it is acquired in order to best inform all aspects of the study. Human tissue samples will be analyzed on a rolling basis as they are made available, which is expected to be late in year 2. Clinical Centers are expected to complete their studies by the end of year 5. Analysis of tissues will continue through year 6, and all data are expected to be deposited in a public data resource by the end of year 6. Molecular fingerprints will be gleaned from the data as they are collected, and it is expected that substantial data analyses will take place in year 6. Staff from all MoTrPAC elements are encouraged to participate in analysis of this highly complex and rich dataset. The Bioinformatics Center personnel will facilitate these data analyses and data dissemination.

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 Big Data to Knowledge (https://commonfund.nih.gov/bd2k/index); Bioinformatics and Computational Biology (https://commonfund.nih.gov/bioinformatics/index); 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).

Prospective applicants are invited to an informational webinar with NIH staff on 10/22/2015 at 2:00 pm EDT. Details will be posted at http://commonfund.nih.gov/MolecularTransducers.

The objective of the Clinical Centers is to support a randomized multi-center clinical study to evaluate the molecular transducers underlying the physiological effects of physical activity in 2700 to 3000 participants, including children and adolescents (<18 years) and adults. Clinical Centers recruiting adults are expected to randomize well-characterized healthy participants to an acute bout of physical activity with biospecimen collection before and post-exercise at appropriate time points. Applicants should also propose a short-term (e.g., 12-week) endurance or resistance exercise training program for the adult participants followed by another acute physical activity bout with biospecimen collection. The pediatric center is expected to recruit children and adolescents to assess molecular transducers in response to acute bouts of physical activity; applicants may also propose a short-term (e.g., 12-week) exercise training program designed to improve fitness in a subsample of participants. All participants must be characterized with respect to objective physiologic, morphometric, and metabolic assessments before the acute bout of physical activity and for those in the training program after the training. In proposing characteristics to be assessed, applicants should consider those likely to change with physical activity training. It is expected that the biospecimens (including a minimum of blood, muscle, and adipose tissue from the adults and a minimum of blood from the children/adolescents) will undergo genomic, transcriptomic, metabolomic, proteomic, and epigenetic assessment at separately funded Chemical Analysis Sites.

Adult Clinical Centers

The adult component will be composed of up to six Clinical Centers that together will be expected to enroll between 2400 and 2700 healthy participants >18 years of age. Thus, it is anticipated that each Clinical Center will have the capacity to enroll approximately 450 participants during a four year period. Applicants should propose to expose participants to an acute bout of exercise with biospecimen collection (e.g., blood; skeletal muscle and subcutaneous adipose tissue) before and post-exercise at appropriate time points, up to several hours afterwards. In addition, it is expected that the participants will also be randomized to a 12-week short-term (either an endurance or a resistance) exercise training program. Since the molecular transducers of physical activity likely will be influenced by fitness level as well as chronic exposure to physical activity, the experimental design should include a comparison group of highly fit, athletic participants as well as non-exercised sedentary controls; these groups should not be subjected to exercise training. The comparator groups (sedentary controls and highly fit/athletes) should be smaller in number than the exercise training groups. All study participants must be healthy and capable of participating in physical activity interventions, but should include both sexes and a wide range of ages, race/ethnicities, and other relevant characteristics that adequately reflect the variability of the general population.

Appropriate study designs will allow a complete description of molecular responses to acute physical activity and how those molecular responses are altered by chronic physical activity exposure designed to induce changes in applicable physiologic indicators. Adult Clinical Centers are expected to randomize well-characterized healthy participants to a 12-week endurance or resistance/strength exercise training program. After randomization to treatment group and again at the conclusion of the training program, it is anticipated that this group of enrolled participants will be assessed again for changes in objective physiologic, morphometric, and metabolic fitness measures and undergo an acute physical activity challenge sufficient to produce changes in a variety of purported molecular transducers. Biospecimen collection should be performed at appropriate intervals up to several hours following the acute bout of physical activity, both at baseline and at the conclusion of the training program. In addition to age, sex, BMI, and exposure to chronic physical activity, fitness indicators will be key factors in developing a molecular map. Long-term training programs, studies focused on health outcome assessments (e.g., cardiovascular disease, diabetes, or body weight-related outcomes such as weight loss) associated with physical activity are not appropriate for this FOA.

It is expected that biospecimens (including a minimum of blood, muscle, and adipose tissue) will be collected from all adult participants at time points that will facilitate thorough assessment of molecular/biological responses to physical activity in line with the goals of this project. Serial measurements for the molecular transducers must be conducted at a minimum of baseline/pre-exposure, post-acute exercise, and post-chronic exercise, as well as at specified relevant, well-justified time points. Applicants may propose to collect additional types of biospecimens/samples at additional time points with appropriate justification. Each of these outcomes and time points should be well-justified in the application. These physiologic, morphometric, metabolic, and other health-related fitness evaluations will be used to characterize all participants, to adequately capture covariates that will be used in the analyses, to relate these physiologic outcomes to the molecular transducers, and to relate these physiologic outcomes to the existing literature. Assessment of other domains, such as psychological, emotional, psychosocial, cognitive, or other behavioral factors may also be proposed, but would need to be very well justified. It is important to note that the final clinical study design and sample size will be developed by the Consortium during the study design and planning phase.

Pediatric Clinical Center

Scientists and clinicians increasingly recognize that physical activity in children is an essential component of health, growth, and development and that there are critical periods during which the effect of exercise on growth mediators can impact the developmental trajectory and have long-term health effects. Because it is not known whether molecular transducers differ in children and in adults and during different stages of development, this initiative anticipates supporting an additional Clinical Center to enroll children and adolescents <18 years of age.

The pediatric center component of MoTrPAC should have the capacity to enroll a minimum of 300 healthy children and adolescents of different ages/stages of development. Because of the inherent variability due to developmental stages and the large changes that occur during puberty, children and adolescents should be staged using the Tanner Scale to establish baseline pubertal status.

The proposed pediatric study should seek to assess molecular transducers in response to acute bouts of physical activity. With appropriate justification, applicants may propose to conduct a short-term (e.g., 12-week) training program in a sub-sample of participants to assess molecular transducers of physical activity. The design of the proposed physical activity intervention(s) should be age/developmentally-appropriate and well-justified. Biospecimen collection must include blood at a minimum, and where possible and age-appropriate, muscle and adipose tissues may be collected. Additional types of biospecimens/samples at additional time points could be proposed with appropriate justification. In addition, objective physiologic, morphometric, and metabolic fitness-related assessments should be conducted at baseline in all participants and following any proposed short-term training program, if applicable. The pediatric Clinical Center will collaborate and harmonize with the adult Clinical Centers throughout the duration of the project.

Design and Collaboration of Clinical Centers

It is expected that the six or seven Clinical Centers (including one pediatric center) will together enroll 2700-3000 participants, depending on the final clinical study design(s). Each applicant should propose and justify the study he/she believes will best address the objectives of this funding opportunity and is most appropriate for their participant population. However, all of the Clinical Centers are expected to agree to collaborate with other members of the Consortium; each Clinical Center will conduct a randomized clinical study using a common protocol (determined by the Steering Committee), collect common data elements, use standardized procedures (including standard tissue acquisition and sample storage), submit all data to the data repositories, and complete other activities as determined by the Consortium. Applicants will also need to collaborate with other members of the Consortium and/or external applicants proposing to conduct ancillary or other sub-studies. Thus, applicants should expect to adapt their protocols, sample size, and budgets to accommodate the final common clinical study protocol.

Phases

Phase 1 (Planning phase, approximately 12 months): This phase will involve determination of the final sample sizes for physical activity and comparator groups, collaborative refinement of participant eligibility criteria for each group, definition of fitness indicators and other physical measures to be assessed, determination of the common data elements, development of biospecimen collection procedures, development of the common intervention protocol, development of study milestones (including recruitment expectations overall and at each Clinical Center), development of safety monitoring procedures, generation of data and sample sharing and publication policies, and development of the Manual of Operations. Once these documents have been completed, the clinical study will move into the operational phase, but only following the recommendation of the Data and Safety Monitoring Board (DSMB) and the final approval of the NIH. Staff training in common procedures will also occur during this period.

Phase 2 (Recruitment and testing phase, 48 months): The protocol for the study will be implemented in Phase 2. Clinical Centers will recruit and randomize the appropriate number of participants based on the final study(s) design as determined by the Steering Committee, implement the protocol according to the manual of operations, collect the outcome data specified in the protocol, and provide study data to the CCC. Clinical Centers must have access to personnel and facilities necessary for collection, short-term storage, and shipment of biospecimens for evaluation.

Phase 3 (Close-out phase, 12 months): The final phase of the clinical study will be for close-out of Clinical Center activities and data collection/cleaning activities. Through the final phase, Clinical Centers will remain involved in biospecimen analysis, manuscript writing, and dissemination of results that will be coordinated through the Consortium Steering Committee.

Clinical Study Expectations and Management

All Clinical Centers must agree to implement the common protocol and Manual of Operations that will be developed cooperatively by the Steering Committee during Phase 1. Expectations for the Clinical Centers include participating in the MoTrPAC Steering Committee, developing protocols, determining common data elements, developing common milestones, recruiting and enrolling the appropriate number of participants into one or more physical activity interventions, implementing the intervention(s), performing participant assessments, and collecting/processing appropriate data and biospecimens. The Clinical Centers will collect data and biospecimens in accordance with established study procedures and submit all samples and submit all data to the CCC, central laboratory, and/or Chemical Analysis Sites, as appropriate and required by the Steering Committee. Clinical Centers must have the appropriate expertise for recruitment, implementation of the final protocol, and collection/processing of data and applicable biospecimens. Clinical Centers are also expected to participate and contribute to analyses of data and preparation of publications and/or resources emanating from the Consortium.

Consortium Coordinating Center (CCC)

The CCC will provide the organizational framework for the management, direction, and overall coordination of the national MoTrPAC. It will coordinate the interactions of the individual Clinical Centers and the Chemical Analysis Sites. The CCC will also be responsible for the standardization of protocols, training of staff, and testing of reliability and reproducibility of the core clinical, physiological and other phenotypic assessments to ensure the administration of these measures is consistent across Clinical Centers and research sites. The CCC will work with other MoTrPAC components to insure standardization of data acquisition, protocols, and data analysis pipelines.

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 will be required. Shortly after the award, the PDs/PIs and NIH program staff will form the MoTrPAC Steering Committee. Each funded element will have one vote and the NIH Project Scientist(s) will have one vote. Consortium governance rests with the Steering Committee and is subject to oversight by an NIH MoTrPAC Working Group of the NIH Common Fund.

The NIH will appoint a chair of the Steering Committee from among the MoTrPAC PDs/PIs. The Steering Committee Chair will preside at all Steering Committee meetings and serve on an Executive Committee. The Executive Committee will invite expert consultants as needed, assist as necessary with annual progress reports, and appoint and charge members of subcommittees. These subcommittees will 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 will meet in person three times during the first year and at least annually thereafter. Monthly teleconferences will be held for the Steering Committee and its subcommittees, and these may be more frequent at times to facilitate planning, etc. The CCC will be responsible for arranging and facilitating the meeting and teleconferences. Applicants should plan to attend an initial planning meeting of the Steering Committee in Bethesda, Maryland, on October 13-14, 2016.

The Steering Committee will have responsibility for developing 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 must work cooperatively and interactively during the first year to develop the final protocols and all of the materials necessary to begin the human studies twelve months after award. The final plan, with a study timeline and milestones, will be submitted for consideration by the NIH MoTrPAC Working Group and the NIH Division of Program Coordination, Planning, and Strategic Initiatives (DPCPSI) before the second year of funds will be awarded.

First year planning activities include, but are not limited to:

• Developing physical activity protocols and plans for physiologic, morphometric, metabolic, and other phenotyping of participants;
• Standardizing measures of fitness and physical activity;
• Selecting inclusion/exclusion criteria and sample size;
• Determining the kind of tissues to be sampled, and the number and timing of biospecimen collection from participants;
• Overseeing plans to address the various bio-ethical issues and concerns (e.g., handling of sensitive data, participatory risk, involvement of vulnerable populations, incidental findings) that are likely to arise during the conduct of the research;
• Obtaining approvals as needed at the Consortium Site institutions, such as IRB and IACUC approvals;
• Preparing a Manual of Operations with primary responsibility residing with the CCC;
• Planning the animal studies that will augment/complement the clinical protocol by providing tissues for analysis from exercised animal models that cannot be obtained from people;
• Developing a detailed plan for storage and shipping of all biospecimens;
• Developing detailed plans for the thorough analysis of sampled tissues in the Chemical Analysis Sites, using genetics, transcriptomics, epigenomics, metabolomics, and proteomics. This includes deciding which tissues will be analyzed by each method and adjusting these decisions as results and technologies become available;
• Planning for repositing tissue samples and establishing protocols for access to those samples;
• Planning for data standards, anonymization, assembly, curation, access, analysis, and storage, with primary responsibility residing with the Bioinformatics Center;
• Agreeing to abide by a common data sharing plan as appropriate and consistent with achieving the goals of the program; and
• Developing a detailed timeline with concrete milestones for the entire study.

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.

An independent DSMB will be established to monitor and provide recommendations to the NIH regarding participant recruitment/enrollment, safety, data quality, and other issues, as appropriate. The DSMB will also review 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) may be used if it serves to streamline the protocol approval process and to standardize the monitoring of human subjects protection in the MoTrPAC.

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

Higher Education Institutions

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

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

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

1. State Governments
2. County Governments
3. City or Township Governments
4. Special District Governments
5. Indian/Native American Tribal Governments (Federally Recognized)
6. Indian/Native American Tribal Governments (Other than Federally Recognized)
7. Eligible Agencies of the Federal Government -- NIH Intramural Program
8. 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 allowed.

Applicant Organizations

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

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

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

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

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

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

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

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).

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

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

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

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

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

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

The letter of intent should be sent to:

Richard Ingraham, Ph.D.
Telephone: 301-496-8551
Email: [email protected]

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.

Facilities & Other Resources. Provide detailed information about the proposed Center's resources relative to the current state-of-the-art of the field. Provide sufficient detail to allow reviewers to judge the contributions and interrelationships of relevant ongoing research. Briefly describe the features of the institutional environment that are relevant to the effective implementation of the proposed Center. Describe how these resources will contribute to the Consortium's success.

Other Attachments. The following items should be included as attachments under Other Attachments :

1. Clinical Protocol Synopsis

The file name Clinical Protocol Synopsis.pdf should be used and will be reflected in the final image bookmarking for easy access for reviewers. Applications that lack the Clinical Protocol Synopsis will be deemed incomplete and will not be peer reviewed. The clinical protocol synopsis must include the following information:

• Description of study objectives, scientific rationale, and overall study design;
• Detailed description of the intervention(s), including implementation and monitoring procedures;
• Description of participant eligibility and inclusion/exclusion criteria;
• Participant recruitment, enrollment, randomization, and retention plans, including a discussion of the availability of participants for the proposed study and the ability of the Clinical Center to enroll and retain the proposed number of participants;
• Alternative plan(s) for increasing recruitment in the event that enrollment goals are not being met;
• Strategies to limit participant drop-out, maximize retention, and maximize complete data collection;
• Methods to monitor and improve participant adherence to the intervention;
• Details on the collection of proposed data that will serve to characterize the participants, such as socio-demographic, body habitus/size/composition, and other clinical data;
• Details on the collection of proposed laboratory, physiological, and other data to enable the primary research questions to be addressed;
• Details on the procedures, particularly timing of biospecimen (including blood, muscle and/or adipose tissue samples) collections, as well as a description of the availability and expertise of personnel and facilities required for collection, processing, and shipment of biospecimens;
• Description of safety assessments (monitoring timeline and procedures), including reporting of and follow-up for adverse events and serious adverse events; and
• Description of the data management and quality control plan, including methods for monitoring the quality and consistency of the intervention(s), data collection, and data entry; policies and methods for ensuring blinding of participants, investigators, and study results.

2. Statistical Analysis Plan

The file name Statistical Analysis Plan.pdf should be used and will be reflected in the final image bookmarking for reviewers' easy access. Applications that lack the Statistical Analysis Plan(s) will be deemed incomplete and will not be peer reviewed.

The applicant(s) should describe the statistical methods planned for each specific aim, including the sample size and power calculations and plans for the primary and secondary analyses. The applicant should also describe the treatment assignment procedures, including the randomization and blinding methods for all outcomes and physiological assessments. This plan is critical for judging whether applicants have selected the correct cohort size based on suitable power calculations and/or are using the most appropriate methods to analyze the resulting data, have made appropriate statistical assumptions for the chosen analyses, and will make correct conclusions at the end of the study. Applications should include plans to account for participant drop-out and missing data.

3. Data and Safety Monitoring Plan (DSMP)

The filename Data and Safety Monitoring Plan.pdf should be used and will be reflected in the final image bookmarking for reviewers easy access. Applications that lack the Data and Safety Monitoring Plan will be deemed incomplete and will not be peer reviewed.

The DSMP should be commensurate with the risk level of the proposed clinical research and must be included for all clinical studies (see: http://grants.nih.gov/grants/guide/notice-files/not98-084.html). All applications or study protocols must include a general description of the monitoring plan, policies, procedures, responsible entities, and approaches to identifying, managing, and reporting reportable events (adverse events and unanticipated problems, as applicable) to the applicable regulatory agencies (e.g., the Institutional Review Board (IRB), Office of Human Research Protections, DSMB, NIH).

The DSMP should be study-specific and must address the following areas:

• Who will manage and conduct the monitoring;
• What will be monitored;
• Which time points will be monitored;
• Where the monitoring will occur;
• How the reportable events will be managed and reported; and
• How participant privacy and confidentiality will be managed.

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

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

The budget for the first year will be for participation with the Steering Committee, in study planning activities, and preparation for the clinical study only. This should include minimal personnel costs and travel to three Steering Committee Meetings.

Budgets for the second year and after of the award may be adjusted after the study has been completely planned in year 1.

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:

It is recognized that applicants will NOT know in advance with whom they will be collaborating because the members of the MoTrPAC will not be known before award; therefore applicants should make reasonable assumptions as to the types of collaborations that will be available and build flexibility into their research plans.

Specific Aims: The overall goal is to contribute to the development of a molecular map of transducers that underlie the effects of physical activity in humans by conducting a multi-center study that will provide data and biospecimens for the discovery of the entire range of molecular transducers that underlie the effects of physical activity in humans. Please describe the specific aims for the proposed Clinical Center and the Center's role in achieving the overall objectives of the MoTrPAC.

Research Strategy: Each application must contain a Research Strategy that clearly describes the proposed clinical trial. The research strategy section should include:

• A concise description of the overall strategy, methodology, and analyses to be used to accomplish the goals and specific aims of the study;
• A description of and rationale for the proposed acute and chronic physical activity intervention(s), including the type, duration, frequency, and intensity;
• A description of the types of tissues and timing of biospecimens that could be collected at each time point and the specific methods for biopsy collection and tissue handling;
• A description of and rationale for the physiologic, morphometric, metabolic, and other health-related/fitness evaluations that will be important to characterize participants at baseline and after training, to develop and interpret a molecular map of response to physical activity. For example, these assessments may include body composition (e.g., whole-body air displacement plethysmography), blood chemistry panels, basal metabolic rate (e.g., indirect calorimetry), and pulmonary function (e.g., spirometry). Applicants should specify and provide justification for physiologic indicators of fitness, such as VO2max and strength assessment;
• A discussion of studies that led to the proposed clinical study and information or data from preliminary studies that address the need for the trial;
• A description of the population, including socio-demographic characteristics, in the local catchment area from which participants would be recruited;
• A discussion of the feasibility of conducting the proposed trial, including the track record of investigators in participant recruitment and retention;
• A description of the statistical methods, as outlined above, that are appropriate for the study design;
• Documentation of specific competence and previous experience of the technical and administrative staff who will be integral to the operation of the proposed project, including conductance of studies that employ physical activity and biopsy collection;
• Describe how the proposed team contributes to the development of a molecular map of transducers that underlie the effects of physical activity in humans; and
• A brief acknowledgement of responsibilities and previous experience as part of a multi-center, collaborative project.

In this section, there should be sufficient description of the items listed above to permit thorough evaluation of the proposed study. Technical details contained in the Clinical Protocol Synopsis, Statistical Analysis Plan, and Data and Safety Monitoring Plan can be referenced from within the Research Strategy section, in order to avoid duplicating text.

Preliminary Data: Preliminary data should indicate that the expertise of the staff and the resources available in terms of equipment, infrastructure, and potential subjects are appropriate for the clinical study, and that all elements of the proposed study are feasible, including the proposed physical activity exposures (both acute and training) and relevant participant assessments.

Milestones and Timeline: Because this Consortium will require specific achievable goals, milestones should be proposed by the applicant. Describe an approximate timeline for the proposed project, along with milestones. These will include goals for recruitment, retention, and collection/submission of biospecimens.

Collaboration: Describe how this Clinical Center will work together other Clinical Centers and with the other components of the Consortium to plan and conduct the study using common protocols.

Letters of Support: Institutional commitments made to the Clinical Center should be clearly documented.

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

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. Data from the MoTrPAC are expected to be handled so as to increase the value of the significant public investment in the creation and operation of the Consortium. Consistent with achieving the goals of the program, NIH expects that all project datasets will be widely shared with the scientific community via existing databases such as dbGaP and/or via the Bioinformatics Center for the promotion of additional research, while carefully observing standards of participant privacy, confidentiality, and secure management of health information. Information such as new analytical methods and metabolic, proteomic, and transcriptomic data are expected to be made available through the Bioinformatics Center or via an open access section of a database [such as the Human Metabolome Database (HMDB) or the Scripps Metabolite and Tandem MS Database (METLIN)], other public web sites, and publication in the scientific literature. Cloud-based access to the data and associated informatics components will be expected to be made widely available, first within the Consortium, and subsequently within the general scientific community. All funded elements are expected to participate in achieving high data quality, making the data available publicly in a timely and accessible manner, and analyzing this rich and valuable dataset. All applicants should name a responsible individual as contact for data sharing both within and outside the Consortium, and clearly identify support requested for data sharing.
• Resources generated by the MoTrPAC are also expected to be widely shared with the Consortium and the broader scientific community for research. The Steering Committee will develop and implement Consortium-wide approaches for resource deposition and use, including submission to national repositories as appropriate. Resources include human and animal biospecimens, instrumentation and assays, special standards, protocols, bioinformatics tools, and animal models.

Specific Plan for Sharing Software: A software dissemination plan, with appropriate timelines, is expected in the application. There is no prescribed single license for software produced in this project; however, reviewers will be asked to evaluate the software sharing and dissemination plan based on its likely impact. A dissemination plan guided by the following principles is thought to promote the largest impact:

1. The software should be freely available to biomedical researchers and educators in the non-profit sector, such as institutions of education, research institutions, and government laboratories.

2. The terms should also permit the dissemination and commercialization of enhanced or customized versions of the software, or incorporation of the software or pieces of it into other software packages.

3. To preserve utility to the community, the software should be transferable such that another individual or team can continue development in the event that the original investigators are unwilling or unable to do so.

4. The terms of software availability should include the ability of researchers outside the Center and its collaborating projects to modify the source code and to share modifications with other colleagues as well as with the Center. An applicant should take responsibility for creating the original and subsequent official versions of a piece of software.

5. Given the long-term goals of this initiative to create software and tools for MoTrPAC research that will serve as a resource to biomedical researchers across the nation, applicants are asked to propose a plan to manage and disseminate the improvements or customizations of their tools and resources by others. This proposal may include a plan to incorporate the enhancements into the official core software, may involve the creation of an infrastructure for plug-ins, or may describe some other solution.

6. Any software dissemination plans represent a commitment by the institution (and its subcontractors as applicable) to support and abide by the plan.

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

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

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

See Part I. Section III.1 for information regarding the requirements for obtaining a Dun and Bradstreet Universal Numbering System (DUNS) Number and for completing and maintaining an active System for Award Management (SAM) registration. Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission.

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

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

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 the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

In order to expedite review, applicants are requested to notify the CSR by email at [email protected] when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

The requests by NIH intramural scientists will be limited to the incremental costs required for participation. As such, these requests will not include any salary and related fringe benefits for career, career conditional or other Federal employees (civilian or uniformed service) with permanent appointments under existing position ceilings or any costs related to administrative or facilities support (equivalent to Facilities and Administrative or F&A costs). These costs may include salary for staff to be specifically hired under a temporary appointment for the project, consultant costs, equipment, supplies, travel, and other items typically listed under Other Expenses. Applicants should indicate the number of person-months devoted to the project, even if no funds are requested for salary and fringe benefits.

If selected, appropriate funding will be provided by the NIH Intramural Program. NIH intramural scientists will participate in this program as PD/PIs in accord with the Terms and Conditions provided in this FOA. Intellectual property will be managed in accord with established policy of the NIH in compliance with Executive Order 10096, as amended, 45 CFR Part 7; patent rights for inventions developed in NIH facilities are NIH property unless NIH waives its rights.

Should an extramural application include the collaboration with an intramural scientist, no funds for the support of the intramural scientist may be requested in the application. The intramural scientist may submit a separate request for intramural funding as described above.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

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

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

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

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

Does the project address an important problem or a critical barrier to progress in the field? 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?

Will the study as proposed illuminate understanding of the impact of physical activity on diverse human organs, tissues, and physiological systems?

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

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

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?

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

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

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

Consortium Activities

Have the investigators stated their willingness to collaborate with NIH scientists and staff, and with investigators and staff from other components of the MoTrPAC? Have the investigators stated a willingness to participate in planning the study and to use common protocols? Have the investigators stated a willingness to share all data, biospecimens, and protocols in a timely manner with MoTrPAC members during the project period, and with the broader research community after the completion of the MoTrPAC project consistent with achieving the goals of the program?

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

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

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

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

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

Not Applicable

Not Applicable

Not Applicable

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

Not Applicable

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

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genomic Data Sharing Plan; and 4) Software Sharing Plan.

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

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

As part of the scientific peer review, all applications:

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

Will receive a written critique.

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

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

Scientific and technical merit of the proposed project as determined by scientific peer review.

Availability of funds.

Relevance of the proposed project to program priorities.

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

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

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

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

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

Any application awarded in response to this FOA will be subject to 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.

Milestones are goals that are quantifiable for measuring success, and include associated annual or semi-annual quantitative criteria. Final milestones will be designed by the Steering Committee in collaboration with NIH staff during the first year in the planning phase before initiation of data collection. These will include goals for recruitment, retention, and collection/submission of biospecimens. Recruitment milestones will include calendar time and participant numbers based upon a recruitment period initiation date, projected recruitment duration, projected recruitment rate per month, and final recruitment target. After consideration by the NIH MoTrPAC Working Group, the final set of approved milestones will be specified in the Notice of Award. NIH staff and the study DSMB will formally review study participant accrual during the study according to an agreed-upon schedule. In addition, completion of and adherence to the physical activity training program will be monitored. If justified, future year milestones may be revised based on data and information obtained during the previous year. If, based on the progress report, the project does not meet the milestones, funding for the project may be either restricted or discontinued.

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

Cooperative Agreement Terms and Conditions of Award

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

Additional areas of primary responsibility for PD(s)/PI(s) of Clinical Centers:

• Designating Protocol Chairs. The Program Directors/Principal Investigators (for studies involving multiple coordinated awards) shall designate a single Protocol Chairperson (if the Program Director/Principal Investigator does not assume this role) for each protocol to be carried out by the study group. The Protocol Chairperson shall function as the scientific coordinator for the protocol and shall assume responsibility for obtaining approval to implement the protocol from the Steering Committee and for developing and monitoring the protocol. Significant modifications to approved protocols must be approved by the Steering Committee.
• Implementing collection of data specified by the study protocol as determined by the Steering Committee. For a multi-center study, each awardee/center is required to ensure that data will be submitted expeditiously to the CCC. Additionally, individual investigators/centers must demonstrate the ability to implement the strategy specifically designed for their individual study population.
• Establishing procedures for data quality and completeness. Awardees are responsible for ensuring accurate and timely assessment of the progress of each study, including development of procedures to ensure that data collection and management are: (1) adequate for quality control and analysis; (2) for clinical trials, as simple as appropriate in order to facilitate cooperation/referral of study participants by physicians to avoid unnecessary expense; and (3) sufficiently staffed across the participating institutions. For research involving multiple awards, a plan for analysis of pooled data will be developed by the Steering Committee.
• Submitting interim progress reports, when requested, to the NIH Program Director, including as a minimum, summary data on protocol performance. For coordinated multiple awards or a multi-site single award, the NIH Program Director may require additional information from individual awardees/centers. Such reports are in addition to the required annual noncompeting continuation progress report.
• Establishing procedures, where applicable, for all participating institutions in coordinated awards to comply with FDA regulations for studies involving investigational agents or devices and to comply with the requirements of 45 CFR Part 46 for the protection of human subjects, and the NIH policy requirements for the inclusion of women, minorities and children.
• The Food and Drug Administration Amendments Act of 2007 (FDAAA or US Public Law 110-85) was passed on September 27, 2007. The law requires mandatory registration and results reporting for certain clinical trials of drugs, biologics, and devices. If applicable, the PI or his/her designee will perform the mandatory study registration and reporting of study results to ClinicalTrials.gov. For more information about this law and requirements for sponsors and/or investigators, visit the PRS and U.S. Public Law 110-85 Information Page at http://prsinfo.clinicaltrials.gov.

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.

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

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

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

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

eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-710-0267

D. Lee Alekel, Ph.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-5055
Email: [email protected]

Richard Ingraham, Ph.D.
Center for Scientific Reearch (CSR)
Telephone: 301-496-8551
Email: [email protected]

Ms. Katie Joffee
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-5891
Email: [email protected]

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.