It is critical that applicants follow the Multi-Project (M) 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

Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to solicit applications for Senator Paul D. Wellstone Muscular Dystrophy Specialized Research Centers (MDSRCs). These Centers promote collaborative basic, translational and clinical research and provide important resources that can be used by the national muscular dystrophy research community. A goal of this Centers program is to support important and innovative research in the muscular dystrophies that is best pursued through this interdisciplinary and collaborative center environment, and projects that may not be as effective if supported by "stand-alone" research project grants. The Centers also provide outstanding environments for the training of new scientists electing to pursue careers conducting research in high priority areas of muscular dystrophy. Finally, Center investigators are expected to engage the patient and advocacy communities in conversations to increase awareness of research, encourage patient participation in research and incorporate the perspectives of these communities in the conduct of patient-centered research.

Background

The Muscular Dystrophy Community Assistance, Research, and Education Amendments of 2001 (the MD-CARE Act, Public Law 107-84) specified provisions for expanding and intensifying research on muscular dystrophy. One provision of the MD-CARE Act was that the NIH establish centers of excellence for research on muscular dystrophy. The Muscular Dystrophy centers program was subsequently developed in honor of Senator Paul D. Wellstone, a champion of muscular dystrophy research. Through open competitions and peer review of applications for awards, the participating NIH institutes established three Centers in 2003, three more in 2005 and have since maintained six active centers.

The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Neurological Disorders and Stroke (NINDS) are committed to continuing and enhancing the tradition of scientific excellence that has been fostered in this centers program.

This Wellstone Centers program was formally evaluated in 2018 by an external Working Group of the NIAMS Advisory Council, facilitated by NIH staff. The report from the Working Group was approved by the Council on February 5, 2019, and the Executive Summary is available at https://www.wellstonemdcenters.nih.gov/sites/wellstone/files/WellstoneCenterEvalRptExecSumm-508.pdf . Recommendations described in the report were incorporated into this funding opportunity announcement and informed other aspects of the program.

Muscular dystrophy refers to a group of hereditary, progressive degenerative disorders causing weakness of the skeletal or voluntary muscles. There are many different forms of muscular dystrophy, which differ in their age of onset, severity, and pattern of muscles affected. Most types of muscular dystrophy are not simply muscle disorders, but rather multi-system disorders with manifestations in a variety of body systems, including the heart, respiratory system, gastrointestinal system, endocrine glands, skin, eyes, brain, and other organ systems. The major forms of muscular dystrophy include congenital, Duchenne/Becker, Emery-Dreifuss, facioscapulohumeral, limb-girdle, myotonic, and oculopharyngeal. Although some forms first become apparent in early childhood, others may not appear until middle age or later, but all have a significant clinical, economic, and psychosocial consequences.

Studies that are responsive to this FOA must be focused on one or more type of muscular dystrophy including those conditions listed above or other inherited condition(s) that directly affect muscle, lead to progressive weakness and muscle degeneration and have pathophysiological mechanisms and clinical manifestations similar to other muscular dystrophies. Potential applicants are strongly encouraged to contact NIH program staff listed under Scientific Contacts in section VII. below prior to developing an application if it is on a disease/condition not listed above, or risk having the application withdrawn as non-responsive.

Different muscular dystrophies are distributed across the progression from disease characterization to therapy development, to conducting clinical trials, to incorporating approved therapies into the standard of care. Currently, therapeutic options to treat any of the muscular dystrophies are limited. For some muscular dystrophies there remains a need for cohort studies to identify genetic mutations and characterize disease progression, as well as studies in cell and animal models to understand disease mechanisms. For other dystrophies there have been significant advances in the development of candidate therapeutics that address specific disease mechanisms, and several candidates are currently being tested in clinical trials. In addition to the development of therapies that address "root" causes, research in optimizing symptomatic treatment such as respiratory support, nutrition and physical therapy are critically important to improve quality of life and decrease associated morbidity. In addition to the need for new disease- or symptom-modifying therapies, there are gaps in understanding how the muscular dystrophies affect the lives of patients and their families and interfere with social interactions, education and workforce integration of those living with muscular dystrophies. There may also be missed opportunities for optimizing health care and improving accesses to care and services.

The Action Plan for the Muscular Dystrophies (https://mdcc.nih.gov/action_plan/2015-action-Plan-to-MDCC-508comp.pdf), updated and approved in November 2015 by the interagency Muscular Dystrophy Coordinating Committee (MDCC) (https://mdcc.nih.gov/index.htm), is a consensus document of high priority research objectives and other strategies to decrease the consequences of these diseases. This document was developed with input from patients, advocacy groups, Federal agencies and basic-, translational- and clinical-scientists to guide the muscular dystrophy research field for years to decades. Applicants to this FOA are encouraged to consider this Action Plan when selecting research projects for their proposed Center.

Cardiomyopathy and respiratory dysfunction in muscular dystrophies are clinically important but understudied. Patients often experience sleep disruptions due to decreased respiratory muscle function or other respiratory complications. High priority research objectives related to cardiomyopathy, respiratory dysfunction and disrupted sleep are included in the Action Plan, and applicants to this FOA are encouraged to consider proposing projects that address these and other objectives.

MDSRC Research Themes

NIAMS, NICHD, NHLBI and NINDS seek to continue this MDSRC program to advance research in the muscular dystrophies leading to improved understanding of these diseases and develop effective treatments and other strategies for reducing disease consequences. Under this FOA, each Center application must propose a clinical research project and at least one other project, which could include basic, preclinical translational or clinical research. The research projects should be related to a common theme, synergistic and should leverage the multidisciplinary and collaborative environment of this Center mechanism. Awards are expected to contribute to the long-term goals of advancing understanding of the causes and natural history of the dystrophies, developing therapies and reducing the impact of one or more form(s) of muscular dystrophy, as well as the training, research resource sharing and patient/community outreach goals described below. Projects should be focused only on muscular dystrophy research and may include studies of the impact of these diseases on skeletal muscle, the heart, respiratory system, sleep, smooth muscle, the central nervous system, gut or other organ systems as well as neuropsychological or neurobehavioral studies. Areas of research can include, but are not limited to the following:

• Characterizing disease natural history or genotype/phenotype correlations
• Characterizing and/or validating molecular, biochemical, physiological, imaging or other types of biomarkers for use in therapy development or clinical trials
• Developing and/or validating clinical outcome assessment measures, including patient-reported outcome (PRO) measures, or clinical scales for use in clinical trials
• Identifying new muscular dystrophy causing genetic mutations
• Identifying, characterizing and validating therapeutic targets
• Identifying and validating genetic or epigenetic modifiers of disease presentation or severity
• Engineering and characterizing new cell or animal models of disease to advance studies of pathophysiology or preclinical translation
• Screening, optimizing and preclinical testing of candidate therapeutics
• Activities leading to investigational new drug (IND) or investigational device exemption (IDE) applications to the FDA
• Epidemiological, behavioral or health outcomes studies to assess patient- and family-centered outcomes with the eventual goal of reducing overall consequences of disease
• Early-stage clinical trials (proof of concept trials, safety/tolerability, dose ranging studies, etc. However, phase 3/registration trials are not permitted.)

MDSRC applicants are encouraged to consider projects that address the high priority areas described in the Action Plan for the Muscular Dystrophies (https://mdcc.nih.gov/action_plan/2015-action-Plan-to-MDCC-508comp.pdf).

The research problems proposed should require substantial collaborative efforts to solve, and thus are best carried out in a center setting. Collectively and in cooperation with the NIH, the MDSRCs form part of a coordinated national program. Applicants are expected to emphasize new ideas, novel approaches, and state-of-the-art technologies to advance understanding of disease and develop effective treatments and other strategies to improve the lives of muscular dystrophy patients. Applications should include multidisciplinary collaborative efforts, especially those involving basic scientists and clinicians with appropriate expertise. Center applications are encouraged to include investigators with significantly different and synergistic expertise such as muscle physiologists, neurologists and bioinformaticians or engineers. MDSRC applicants must also propose resource core facilities, training and outreach activities that will enhance muscular dystrophy research on a national or international level.

Applicants seeking support for projects that are stand-alone, single-component basic, translational, clinical studies or trials in muscular dystrophy should contact the Scientific/Research Contact listed in Section VII. Agency Contacts below for guidance on other, more appropriate funding opportunities.

General Description of MDSRC and Center Components

The organizational structure of the proposed MDSRC should facilitate the flow of new scientific findings and technologies into translational and clinical research. Each center must include clinical research as defined below.

Clinical research is research with human subjects that is:

1. Patient-oriented research. Research conducted with human subjects (or on material of human origin such as tissues, specimens, and cognitive phenomena) for which an investigator (or colleague) directly interacts with human subjects. Excluded from this definition are in vitro studies that utilize human tissues that cannot be linked to a living individual. It includes:

• mechanisms of human disease
• therapeutic interventions
• clinical trials
• development of new technologies

2. Epidemiological and behavioral studies.

3. Outcomes research and health services research.

Although guidance is provided in this FOA for interventional clinical trials in MDSRCs, clinical trials using investigational drugs or biologics are NOT a required element of an MDSRC. Each center may also contain basic and/or translational studies research with an emphasis placed upon moving the research field forward toward novel or improved therapies or other strategies for reducing impact of the muscular dystrophies.

The minimal structural requirements of a Wellstone MDSRC under this FOA are:

• Two or more projects involving collaborations of investigators. At least one of these projects must address clinical research aims and must involve the direct interaction of Center investigators with MD patients;
• A Center Director and Co-Director, responsible for scientific and administrative oversight of the Center;
• An Administrative Core that promotes a Center environment through enhanced communication and collaboration of investigators within and outside the Center. The Administrative Core must also promote conversations with the patient/advocacy community to increase awareness of the research, promote enrollment in clinical studies and incorporate the perspectives of patient/advocates in the research conducted by the Center. The Administrative Core will establish a Center Advisory Committee including external scientific and lay members;
• A Scientific Research Resource Core that is to be shared with the national muscular dystrophy research community and meets the needs of the community. A Center can have other cores that are justified by the level of use within the Center, but are not necessarily shared with researchers outside the Center; and
• A Training Core to promote training and career development of students and fellows associated with the Center, recruit new trainees, promote support through individual fellowships, organize training activities for the students and fellows in other Wellstone Centers and across the entire muscular dystrophy research community.

Projects

Each of the proposed research projects should address problems that require a substantial collaborative research effort to solve, and are best suited for a center environment rather than a stand-alone grant. Collectively, the projects should involve synergistic teams of researchers with complementary expertise such as basic and clinical, skeletal muscle and other organ systems, primary data collection and bioinformatics, etc. Collaborations should be arranged to bring the best expertise to bear on a problem, whether the proposed collaborations are all on-site or utilize consortium agreements with off-site investigators at existing MDSRCs or off-site investigators not affiliated with an MDSRC. Although a clinical project is required, this need not be a clinical intervention trial. See section IV.2 for additional guidance on projects that propose a clinical trial. Epidemiological, behavioral and health outcomes research studies for the muscular dystrophies are also encouraged.

Leadership

The Center Director and Co-Director must develop and maintain a center environment that fosters traditional and novel approaches to multi-disciplinary research collaborations and training. The Center Director and Co-Director cannot serve as the Program Director/Principal Investigator of a project in another active MDSRC award. But, other than this restriction, collaborations among Centers are encouraged.

Administrative Core

The Administrative Core must provide for the integration and management of activities within the MDSRC. The Administrative Core must also promote interactions and communications between the research and patient/advocacy communities on both a national and local level. Funded MDSRCs are expected to utilize the Administrative Core to establish and maintain a website to communicate the Center mission and the availability of training opportunities and specimens/data available through the Shared Scientific Resource Core. Each Center must form an external Center Advisory Committee (CAC) with scientific, clinical and patient advocate representation, composed of at least five members. The CAC should meet in-person or electronically approximately once a year, beginning in the first or second year of the Center award. Applicants are encouraged to form the strongest teams to address the research questions, regardless of geography, and the Administrative Core must be responsible for coordinating communication among the center sites and integrating participating researchers into a cohesive center environment, even if geographically dispersed.

To promote awareness of muscular dystrophy research and the Wellstone Centers program in the patient/advocacy communities, the Administrative Core must develop activities or materials, such as seminars, web-based information, or lab tours involving patients and their families interacting with junior and senior investigators. Participation of patient advocacy groups in the planning and conduct of outreach activities is encouraged.

Shared Resource Core

The shared Scientific Research Resource Core must be designed and managed to support the research of the MDSRC, as well as serving as a resource for the national and perhaps international muscular dystrophy research community. Applicants may wish to consult the recently updated Action Plan for the Muscular Dystrophies (https://mdcc.nih.gov/action_plan/2015-action-Plan-to-MDCC-508comp.pdf) for consensus statements on infrastructure needs of the muscular dystrophy research community. Applicants are encouraged to propose a core that will provide services, specimens or other resources that are rate limiting to the progress of muscular dystrophy research, so that the core will help to accelerate research conducted by users within and outside the MDSRC.

Training Core

As nationally recognized centers of excellence in muscular dystrophy research, the MDSRCs are expected to play a leadership role in training new researchers for the muscular dystrophy field, contributing to the development of future research leaders. Each center must include a Training Core to 1) enhance the training environment and promote career advancement for students and fellows working on projects supported by the Center, 2) recruit trainees new to muscular dystrophy research, 3) promote trainee support through individual fellowships or career development awards from public and private funding organizations, 4) organize research meetings for trainees across the network of Wellstone Centers and 5) organize training activities such as courses or webinars for the overall muscular dystrophy research community. Leveraging existing training programs is encouraged, and support from the MDSRC should add value to existing programs by enhancing the focus on the muscular dystrophies and increasing the number of trainees. Encouraging mentored researchers to apply for individual fellowships or career development awards will help prepare them for independent research careers. This core may propose activities that enhance the training environment through specialized coursework, a seminar program, retreats for presentation of trainee research, journal clubs or other activities that contribute to the preparation of junior investigators for careers in muscular dystrophy research. Training activities must emphasize scientific rigor by providing guidance and assessing the implementation of strategies to ensure unbiased and well-controlled experimental design, methodology, analysis, interpretation and reporting of results. Trainees should learn about the broad range of research conducted by investigators at their own and other centers including preclinical translational research and clinical studies. Exposure to research at other Wellstone Centers is also encouraged through exchange programs, short-term training opportunities or visits to learn new research approaches. Non-clinical students and postdocs should get exposure to clinical research and clinical research projects should involve medical students, clinical fellows and residents.

The Wellstone Network

Recipients of MDSRC awards will become part of a national program in muscular dystrophy and will be expected to participate in network activities, including meetings of the Steering Committee (composed of Center Directors and Co-Directors, and NIH staff) and a biennial centers meeting that rotates among the Wellstone Centers network sites.

For answers to common questions about the Wellstone Centers and this FOA, see: https://www.wellstonemdcenters.nih.gov/addl_links.htm

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

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

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

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

Applicant Organizations

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

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

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

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

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

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

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).

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

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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.

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 the proposed activity
• Name(s), address(es), and telephone number(s) of the 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:

Emily Carifi, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-0665
Email: [email protected]

Available Component Types	Research Strategy/Program Plan Page Limits
Overall	12
Admin Core	6
Training Core	12
Shared Research Resource Core	12
Each Project	12

Additional page limits 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 a multi-component application.

The application should consist of the following components:

• Overall: required
• Administrative Core: required, maximum of one
• Training Core: required, maximum of one
• Shared Research Resource Core: required, one or more
• Projects: required, two or more

When preparing your application, use Component Type Overall .

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

Complete entire form.

Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

Follow standard instructions.

Enter primary site only.

A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this FOA) for the entire application.

Each applicant institution must name an MDSRC Center Director (Program Director/Principal Investigator) who will be the key figure in the administration, management, and coordination of the Center grant.

A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.

A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

Specific Aims: Describe the overall goals of the center for the time frame of the grant. Describe the research objectives of the center for advancing understanding of disease mechanisms, developing therapies, advancing patient care or reducing disease consequences. Also describe the center's objectives for developing and sharing research resources, training junior researchers, educating and listening to the patient/advocacy communities, and promoting enrollment in clinical studies, consistent with achieving the goals of the program.

Research Strategy: The Overall Research Strategy should describe the major theme of the Center, its goals and objectives, background information, the overall importance of the research in developing therapies or reducing the consequences of disease, and the expected near- and long-term influence on the overall field of muscular dystrophy research if the goals and objectives are achieved. Describe the rationale for the total proposed program. Explain the strategy for achieving the goals defined for the overall program and how each research project and core relates to that strategy. A successful Center grant application will include a well-integrated research plan that clearly shows how the proposed projects and cores will foster preclinical and or clinical development of novel therapeutics or other strategies to reduce the impact of the muscular dystrophies. The program should be viewed as interrelated research projects, each of which is not only individually scientifically meritorious but is also complementary to the other projects and related to the overall theme developed for the Center. Provide justification in the application that: (a) the proposed projects are such that they require an intensive collaborative effort to succeed and (b) that key personnel will collaborate effectively.

Describe the organizational structure of the MDSRC including the components of the Center. Also describe any connections between the proposed Center and other organizations such as patient advocacy groups or industry partners. Explain how different components of the organization, including key personnel, will interact, why they are essential to accomplishing the overall goal of the research, and how combined resources create capabilities that are more than the sum of the parts.

For renewal applications, document achievement of the goals of the prior funding period.

Letters of Support: In studies where pharmaceutical/biotechnology companies or patient groups/voluntary health organizations are providing study agents, research materials, data, services or additional funding, written agreements by an official of each company or organization affirming these arrangements must be provided with the application as letters of support.

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, must address a Data Sharing Plan and a Resource Sharing Plan. The Administrative Core section of the application will describe overall plans to coordinate sharing of data and resources (see guidance below) and the Director of the Administrative Core should take responsibility for fulfilling these sharing plans for the overall Center.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Overall)

When involving NIH-defined human subjects research, clinical research, and/or clinical trials 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, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

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.

When preparing your application, use Component Type Administrative Core.

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

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget forms appropriate for the specific component will be included in the application package.

The Center Director and Co-Director must each have a minimum total commitment of 2.4 person months effort to the MDSRC, which should include appropriate effort to the Administrative Core as well as other cores and/or projects.

The Administrative Core of the MDSRC application must include funds for the travel of Center investigators to the biennial meeting of the Wellstone Network, and for visits of Center investigators or trainees to other MDSRCs or other collaborative sites to exchange scientific ideas, to plan multi-Center research projects, or to receive training in specialized techniques.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Specific Aims: Describe the goals of the Administrative Core and how these goals will contribute to a substantial and sustained influence of the center on the overall field of muscular dystrophy research. The specific aims must address plans for communication and coordination of efforts within the center, facilitating interactions with researchers outside the center, seeking advice from an external advisory committee, promoting outreach to the patient/advocacy communities, promoting enrollment in clinical studies, and any other goals at the discretion of the applicants.

Research Strategy: The Administrative Core will be responsible for the management and administration of the overall Center. This section of the application should describe the strategies and processes that will be used to manage the Center and achieve the goals. This Core, led by the Center Director, will provide oversight for the projects and cores, promote coordination and collaboration within the Center and with investigators and organizations outside the Center. A narrative description should be provided that includes the planning and coordination of research activities; the integration of cross-disciplinary research; the oversight of fiscal and resource management; and the maintenance of ongoing communication. Indicate who will be responsible for each of these activities. Applicants must specify appropriate administrative/business management staff and oversight mechanisms by the Center Director, Center Co-Director, and a Center's Executive Committee.

The Administrative Core must propose the development and maintenance of a website for the center. This website must provide information on the research projects conducted by the center, promote patient recruitment for clinical studies and publicize training opportunities and other information of value to the research or patient/advocacy communities or the general public. The website must publicize shared scientific resources (disease models, reagents, biospecimens and/or data) or specialized services that are available through the Shared Scientific Resource Core and through projects of the Center. The website must also describe the process for requesting access to these shared resources, any cost to the requester, the process for reviewing and approving requests received, and the expected time from request to delivery. To promote the reproducibility of research results, detailed research protocols and standard operating procedures for research conducted by the center must be made available through the center website.

The Administrative Core will also be responsible for outreach activities to the patient and advocacy communities. Applicants are encouraged to propose activities such as presentations, lab tours or other face-to-face interactions between researchers and members of the patient and advocacy communities. Applicants are encouraged to educate the patient/advocacy communities about muscular dystrophy research, include the perspectives of patients and their families when making decisions regarding research directions and promote patient enrollment in clinical studies conducted by the center and at other institutions.

When multiple performance sites are planned, the Administrative Core must include leadership and communication plans adequate to manage the multiple sites.

The Administrative Core must establish an Executive Committee, composed of members of the Center, and a Center Advisory Committee (CAC), composed of people outside the Center. Members of the CAC should be identified in renewal applications only; applications for new Centers should not identify candidate CAC members or contact them prior to award. Describe how the CAC will contribute to oversight of the research projects, core facilities, data and resource sharing plans and training environment of the Center, and how recommendations by the CAC will affect decision making by the Center Director and Co-Director. The CAC should meet approximately once a year and brief reports of the proceedings of the meeting and recommendations of the committee must be included in the progress reports of the Center.

In order to assure active collaboration with other Centers, the MDSRC Director, Co-Director, and other staff should attend biennial meetings of the MDSRC Network, contribute to the coordination of effort, and/or help to refine and standardize operating procedures among the Centers.

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:

The Administrative Core must provide oversight of the Data and Resource Sharing plans for each component of the Center. Applications are expected to provide an overall Data Sharing Plan and an overall Resource Sharing Plan for the Center describing the timely sharing of specimens, cells, animal models and redacted data generated with support from this award with other qualified research scientists, both within and outside the MDSRC network, and ensuring that such data are HIPPA compliant. The application sections for the Shared Scientific Resource Core and the Projects (below) must each contain their own, detailed sharing plans for the data and resources available from those components. The Administrative Core must describe how oversight of the individual components will be managed to ensure that data and resources are made available to other researchers in a timely manner to enhance research within and outside the MDSRC. The overall Data/Resource Sharing Plans must describe collective data and resources of the center that will be made available to other researchers and when each will become available. Individual component plans must describe the process for evaluating requests for access to the data and/or biospecimens, and the expected time from when the request is received to when the request if filled. The overall Data/Resource Sharing Plans should describe strategies to ensure that the individual components fulfill the responsibilities of their sharing plans. Tables describing the data and other resources shared by the individual components (see guidance in each of those sections below) must be included in the annual progress reports for those components with a summary of overall data and resource sharing in the Administrative Core progress report.

Appendix:

Only limited items are allowed in the Appendix.Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

When involving NIH-defined human subjects research, clinical research, and/or clinical trials 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 a 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

When preparing your application, use Component Type Training Core

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

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Training Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Training Core)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Application guide states that Project Narrative is required. However it is only required for the Overall component. Specific names provided for Other Attachments must be no more than 50 characters including spaces.

Project /Performance Site Location(s) (Training Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Training Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• The Training Core Lead must request at least 1.2 person months effort per year for this Core
• Training coordinators at other institutions involved in the Center may also request effort, commensurate with their responsibilities for the Core.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Training Core)

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

The budget for the Training Core must include support for activities to enhance the training environment, promote career advance of trainees, recruit trainees new to muscular dystrophy research, support for meetings of the trainees among all of the Wellstone Centers and support for courses or webinars made available to the overall muscular dystrophy research community, commensurate with the aims of the core.

PHS 398 Research Plan (Training Core)

The PHS 398 Research Training Program Plan Form is comprised of the following sections:

• Training Program
• Faculty, Trainees, and Training Record
• Other Training Program Sections
• Appendix

Follow all instructions provided in the SF424 (R&R) Application Guide with the following additional modifications:

Note: Data Tables are not applicable to this FOA.

Specific Aims: Propose specific aims that are aligned with the overall goals of training the next generation of researchers in basic, translational and clinical studies of the muscular dystrophies.

Research Strategy:

Program Administration: Describe the acknowledged strengths, leadership and administrative skills, training experience, scientific expertise, and active research of the Training Core Leader. Relate these strengths to the proposed management of the training core. Describe the planned strategy and administrative structure to be used to oversee and monitor the core.

Program Faculty: The application must include information about the Center faculty who will be available to serve as preceptors/mentors and provide guidance and expertise appropriate to the level of trainees proposed in the application. Describe the complementary expertise and experiences of the proposed Center Faculty, including active research and other scholarly activities in which the faculty are engaged, as well as experience mentoring and training individuals at the proposed career stage(s). For any proposed Center Faculty lacking research training experience, describe a plan to ensure successful trainee guidance by these individuals.

Proposed Training: The Training Core must propose specific activities aimed at achieving the following goals 1) enhance the training environment and promote career advance for students and fellows working on projects supported by the Center, 2) recruit trainees new to muscular dystrophy research, 3) promote trainee support through individual fellowships or career development awards from public and private funding organizations, 4) organize research meetings for trainees across the network of Wellstone Centers and 5) organize training activities such as courses or webinars for the overall muscular dystrophy research community.

1. Enhancing the training environment and promoting career advance: The application must propose activities relevant to trainees in laboratory research and in clinical research, and non-clinical trainees (students and postdoctoral fellows) should be exposed to clinical aspects of muscular dystrophy research. Describe for whom the training program is intended, including the training level(s) of the trainees, the academic and research background needed to pursue the proposed training, and, as appropriate, plans to accommodate differences in preparation among trainees. Include information about planned courses, mentored research experiences, and any activities designed to develop specific technical skills or other skills essential for the proposed research training. Describe how trainees will be educated in the conduct of basic, preclinical translational and/or clinical research for the muscular dystrophies and how the training plan will encourage scientific rigor and transparency in the reporting of results. The Core Director should describe program activities intended to develop the working knowledge needed for trainees to select among and prepare for the next step in varied research career options available in the biomedical workforce. For example, programs should provide all students and fellows with training in data analysis and interpretation, oral and written presentation of research results. All postdoctoral fellows should also be provided with training in laboratory, personnel and project management.

2. Recruiting trainees new to muscular dystrophy research: Activities should be proposed to raise awareness of muscular dystrophy research among undergraduates, medical students and clinical fellows to encourage them to consider careers in this field. Special attention should be given to recruiting trainees from underrepresented groups with respect to race, ethnicity, gender, socio-economic status and disabilities. Short-term research experiences in the labs supported through the Center or in clinics associated with the Center can have a significant influence on the career decisions of trainees. Leveraging existing resources such as institutional training programs is encouraged, and support from the MDSRC must add value to existing programs by enhancing the focus on the muscular dystrophies and increasing the number of trainees.

3. Promoting trainee support through individual fellowships: Activities must be proposed to guide students and fellows in selecting and applying for individual fellowships that are available from public and private funding organizations, including muscular dystrophy advocacy organizations. Guidance should be individualized to increase the likelihood of success in receiving support. Strategies may include a panel of mentors to review and critique draft fellowship applications, and editing assistance for trainees for whom English is a second language. The Director of the Training Core must track these fellowship applications and report on the success rates in annual progress reports.

4. Wellstone Network trainee meetings: Propose activities that give trainees at different Wellstone Centers an opportunity to meet and present their research results. These could be in-person meetings and/or web-based meetings.

5. Training for the overall muscular dystrophy research community: Propose activities, such as courses, workshops or seminars that focus on basic, translational and clinical research for the muscular dystrophies and are open to students and fellows within and outside the Wellstone Centers Network.

Throughout the activities of this core, trainees should receive guidance and be assessed on the implementation of strategies to ensure unbiased and well-controlled experimental design, methodology, analysis, interpretation and reporting of results. The NIH provides training resources on scientific rigor and reproducibility that should be incorporated into the training core (https://grants.nih.gov/policy/reproducibility/training.htm ).

Institutional Environment and Commitment to the Program: The sponsoring institution must assure support for the training environment of the MDSRC as proposed in the Training Core including assurance that sufficient time will be allowed for the Training Core Leader and other Center Faculty to contribute to the proposed training. Institutions with ongoing research training, student development, or career development programs in which the MDSRC faculty are eligible to participate as mentors must explain what distinguishes the proposed Training Core from existing training programs at the same trainee level, how the programs will synergize, if applicable, whether trainees are expected to transition from one support program to another, and how the training faculty, pool of potential trainees, and resources are sufficiently robust to support the proposed training in addition to existing ones.

For all applications, describe the track record of success in training students and fellows in basic, translational and clinical research. Applications for renewal of Centers must also highlight how the training program has evolved in response to changes in relevant scientific and technical knowledge, educational practices, the research job market, etc.

Plan for Instruction in the Responsible Conduct of Research

Individuals are required to comply with the instructions for Plan for Instruction in the Responsible Conduct of Research as provided in the SF424 (R&R) Application Guide.

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 must address a Data Sharing Plan and Resource Sharing Plan. See additional guidance provided above in the "Administrative Core" section.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

When preparing your application, use Component Type Shared Resource Core.

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

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Shared Scientific Resource Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Shared Scientific Resource Core)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Shared Scientific Resource Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Shared Scientific Resource Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Shared Scientific Resource Core)

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Shared Scientific Resource Core)

Specific Aims: Describe the goals of the Shared Scientific Resource Core. The aims must address not only the delivery of services or materials, but also the processes for ensuring the consistent quality of the services or materials, fair access by users and efficient use of the resources in important projects in muscular dystrophy research.

Research Strategy: Describe the function of the core as a resource to the program. This section must clearly present the facilities, techniques, and professional skills that the core will provide. A core is principally designed as a service or resource component; it would be highly unusual to include research in a core (a possible exception would be methodology development).

Describe the role of the core as a resource to the program as a whole. Discuss ways in which these centralized services will produce an economy of effort and/or savings in overall costs compared to their inclusion as part of each project in the program. To aid in the review of the application it is recommended that applicants prepare in tabular form information concerning the research projects that each facility core unit would serve and the proportion of the cost of the facility core unit associated with each research project involved.

Cores are seldom created specifically for the MDSRC and more often already exist in some form prior to the application. When proposing support for an already existing core, describe how the MDSRC award would enhance the resources or services already available through new innovation and technology development, expanded availability, increased throughput, etc.

Each Center must contain a scientific core that provides services and/or resources that are shared with other investigators nationally and perhaps internationally. These resources could be reagents, specimens, services or technical expertise that will help to accelerate progress of multiple projects toward the development of therapies or other strategies for improving the lives of patients with muscular dystrophy. Describe how this shared core will meet the needs of the national/international muscular dystrophy research community. If cores providing similar resources are already available, explain the need for this additional core.

Additional cores may be proposed if they are needed to advance the local research effort and if they fit within the budget limits described elsewhere in this FOA. For each scientific core, the applicant should identify projects that will depend on the services and/or resources proposed. Projects outside the Center that would use the core should be described in general terms and investigators outside the Center should not be contacted, as this would lead to conflicts of interest during peer review.

Letters of Support: If leveraging existing core facilities or services, provide letters of support from those who lead/manage the existing resource (if not part of the Wellstone Center). If biospecimens are collected by the shared scientific resource from investigators outside the center, provide letter(s) of support from the originating investigator(s).

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:

A resource sharing plan is a key element of the description of this core. Describe the resources that will be shared and when these resources will become available to researchers within and outside the MDSRC. Plans must describe the process for evaluating requests for access to the resources, and the expected time from when the request is received to when the request if filled. The Administrative Core will provide oversight for the sharing plans for each component of the center. The application section for this Shared Scientific Resource Core must contain the sharing plan specific for this core. A table of the requests for access to resources must be included in annual progress reports. This table must include the requester's name and institution, nature of the request, date request was received, description of what was shared and the date when data or biospecimens were sent to the requester.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

For renewal applications, include in the Appendix records of the sharing of data/services/resources from the previous term of the grant. Provide a table of requests received and what was provided to address the request. Identify requesters by institution or organization but not by name (to avoid potential review conflicts of interest).

PHS Human Subjects and Clinical Trials Information (Shared Scientific Resource Core )

When involving NIH-defined human subjects research, clinical research, and/or clinical trials 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 a 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

When preparing your application, use Component Type 'Project.

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

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Project)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Project)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Project)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Project)

ASSIST will default to Project Lead . If you would like to use a different category, then replace Project Lead below with a different Category (e.g., Core Lead).

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Project)

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Project)

Specific Aims: Describes the specific goals and objectives of the project

Research Strategy: Clearly state the project's overall objective and explain its relevance to the central theme of the Center. In addition, an explanation should be included describing how the project relates to and both complements and enhances the other research projects and cores of the program. Explain why the project is best suited to be carried out as part of the Center, rather than being a stand-alone project that could be supported through an NIH research project grant or other mechanism. Explain how the project addresses a critical need in progress toward effective therapies for one or more forms of muscular dystrophy or other strategies to reduce disease consequences.

Each MDSRC must contain at least one clinical study, but this study is not required to be an interventional clinical trial. Options for clinical studies include but are not restricted to evaluation of natural history, development and validation of biomarkers and clinical outcome assessment measures including PROs, and other studies contributing to clinical trial readiness. Knowledge from such clinical studies is essential for the design of subsequent clinical trials and can be invaluable for the muscular dystrophy field. Applicants are encouraged to include clinical fellows, residents and other clinicians in the project(s) and other activities of the Center.

If the project includes an interventional clinical trial, the description of the significance should support the potential value and feasibility of successfully completing the study within the term of the grant, including preclinical rationale. The preclinical rationale should provide evidence that the rigor of preclinical efficacy studies and the level of effect of the agent are both sufficient to warrant clinical testing of the agent (for guidance, see https://grants.nih.gov/grants/guide/notice-files/NOT-NS-11-023.html). The approach section should describe evidence that regulatory requirements will be met in a timely manner, evidence of drug/biologic availability for use in a trial, and agreement of all participating clinical/corporate partners. Clinical trials involving the testing of new investigational therapeutics, new indications for FDA-approved drugs, or other medical interventions under a research protocol should be performed under an IND, unless otherwise agreed upon by the FDA. If not exempt, the applicant must provide the NIH with the name and organization of the IND/IDE holder, the date the IND/IDE was filed with the FDA, the FDA IND/IDE number, and any comments from the FDA regarding this protocol. Studies will not be funded unless necessary regulatory approval has first been obtained; regulatory approval at the time of application is preferred. It is strongly encouraged that clinical studies utilize established Common Data Elements (CDEs; see https://www.commondataelements.ninds.nih.gov/#page=Default to ensure comparability with other clinical trials in muscular dystrophy.

Because of the budget limitation of the overall Center and requirements for other components, any interventional clinical trials proposed as part of the MDSRCs are likely to be phase 0/exploratory IND, phase 1, or early stage proof of concept trials. Any clinical trial proposed within MDSRCs should be designed to validate the therapeutic target or candidate therapeutic (phase 0 trial) or to provide specific data that will be necessary to design a subsequent definitive efficacy trial (phase 1 or early stage proof of concept trial). The proposed study must address questions that, when answered, will optimize the design of the eventual definitive clinical trial rather than simply address the clinical question with lower power. Underpowered efficacy trials that are unlikely to advance the development of a candidate therapeutic must be avoided. Examples of relevant clinical research include, but are not limited to, the following:

• Studies to assess whether the candidate therapeutic engages and modulates the presumptive molecular target (i.e., exploratory IND or phase 0 trials);
• Studies to optimize the intervention strategy: for example, studies designed to investigate dose-concentration, dose-response, or concentration-response relationships may contribute to optimal dosage selection for definitive trials;
• Studies to assess the appropriate delivery system or parameter settings of an electronic device or surgical technique;
• Studies to assess the safety and tolerability at various doses or concentrations of a specific intervention;
• Studies designed to evaluate whether an intervention produces sufficient evidence of short-term activity (e.g., biomarker activity) in humans as to justify an efficacy trial;
• Studies designed to select the best of two or more potential interventions or dosing regimens to evaluate in a subsequent definitive trial, based on tolerability or evidence of biological activity;
• Studies to identify inclusion and exclusion criteria to be applied in the phase III clinical trial.

As noted previously, when clinical trials are proposed, there must be strong evidence provided in support of the potential value and feasibility of the study, including clear preclinical rationale, unimpaired regulatory status, evidence of drug/biologic availability for use in a trial, and agreement of all participating clinical/corporate partners.

Protection of Human Subjects: Subjects who participate in MDSRC clinical research projects should be fully informed, using appropriate consent procedures. The consent form for funded projects should specifically address the following: (1) disclosure that biological materials and clinical data will be distributed to other researchers; (2) assurance that such data will be de-identified and stored and maintained without personal identifiers; (3) disclosure that analyses of these data will be conducted by other scientists currently not included within the current research team, potentially including those with commercial interests; (4) that the data collected by the researchers may be used to study their specific disorder as well as other disorders.

Letters of Support: In studies where a pharmaceutical/biotechnology company is providing the study agent, a written agreement by a company official affirming this arrangement must be provided with the application as a letter of support.

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, must address a Data Sharing Plan and a Resource Sharing Plan. Describe the data and resources that will be shared and when these resources will become available to researchers within and outside the MDSRC. Plans must describe the process for evaluating requests for access to the resources, and the expected time from when the request is received to when the request is filled. The Administrative Core will provide oversight for the sharing plans for each component of the center. The application section for each Project must contain the sharing plan specific for that component. A table of the requests for access to resources must be included in annual progress reports. This table must include the requester's name and institution, nature of the request, date request was received, description of what was shared and the date when data or biospecimens were sent to the requester.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

For clinical research projects, the participant consent form must be included in the Appendix.

PHS Human Subjects and Clinical Trials Information (Project)

When involving NIH-defined human subjects research, clinical research, and/or clinical trials 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 a 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

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

For information on how your application will be automatically assembled for review and funding consideration after submission go to: http://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

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) and component Project Leads 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.

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 (SAM). Additional information may be found in the SF424 (R&R) Application Guide.

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

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

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.

In addition, for applications involving clinical trials:

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

For this particular announcement, note the following:

Centers must be designed to include the following components: two or more scientific project(s), an Administrative Core, a Shared Scientific Research Resource Core with national impact, and a Training Core. Applications may include additional core facilities within the overall budget cap. After the review of the individual components, an overall impact score will be assigned to the center application. The overall score will reflect a) the scientific merits of the research project(s), b) the overall effectiveness and adequacy of core resources and facilities, c) the qualifications of the Center Director and Co-Director, d) the quality of the plans for management and oversight of the Center, e) the institutional commitment, and f) the synergy among the components and overall impact of the Center. The overall score for the center application may be higher or lower than the average of the individual components based on the assessment of whether the whole is greater than the sum of its parts.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the Center 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 Center 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 Center that by its nature is not innovative may be essential to advance a field.

Does the Center address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the Center 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?

In addition, for applications involving clinical trials

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

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

In addition, for applications involving clinical trials

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

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?

In addition, for applications involving clinical trials:

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

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

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?

In addition, for applications involving clinical trials:

Does the application adequately address the following, if applicable?

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)?

Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

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?

Is there tangible institutional commitment to the establishment and growth of the MDSRC? Will the institution provide incentives and rewards to promote the mission of team-based research? Is there substantial institutional commitment to tenured faculty positions, dedicated space and other resources, and sufficient time release to allow the investigators to pursue the goals of the MDSRC? Is the physical distribution of Center investigators and core resources conducive to the synergy necessary for a successful MDSRC? Will existing NIH-supported core facilities be shared with the MDSRC? Do the institutional administration and environment provide opportunities for Center growth? If applicable, are there sufficient commitment and support on the part of institutions associated with the MDSRC through consortium agreements?

In addition, for applications involving clinical trials:

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

As applicable for the Center 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.

Center Justification

Is there strong justification that this will be a successful Center, with each of the projects and cores not only individually scientifically meritorious but also complementary to the other components, and related to the overall theme developed for the Center? What is the scientific gain from combining the individual projects/cores into a Center?

Is there justification in the application that: (a) the proposed projects are such that they require an intensive collaborative effort to succeed and (b) that key personnel will collaborate effectively? Are there appropriate plans for the Center to collaborate and otherwise contribute to the national MDSRC program, through participating in the annual meeting, workshops, training, collaborative efforts, or other MDSRC-wide activities?

Scientific Achievement and Leadership

Does the application provide convincing evidence that the Center, if funded, will become a leader/resource in muscular dystrophy research?

What are the past accomplishments of the Center or the demonstrated ability of the projects and core personnel in conducting similar programs? Is there evidence of established leadership in scientific research and demonstrated capabilities in program administration?

How are internal or external advisory committees utilized to assist in making scientific/administrative decisions and evaluating progress and direction? What methods are used to facilitate the interaction of participating investigators and assure a cohesive program (sharing and evaluation of results, new ideas)?

Is there evidence of administrative planning and leadership capability to provide for internal quality control of ongoing research, allocation of funds, enhancement of internal communication and cooperation among the investigators involved in the program and replacement of the PD/PI if required on an interim or permanent basis?

Study Timeline

Specific to applications proposing clinical trials:

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

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.

When the proposed Center 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.

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

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

Not Applicable

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

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 .

Reviewers will comment on the quality of the Data and Resource Sharing Plans. How reasonable are the plans for publicizing data and research resources available from the Center to the broad muscular dystrophy research community? If the sharing plans described in the application are followed will requests for access to data and or research resources be appropriately prioritized and will important data/resources be shared in a timely manner?

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

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

Overall Impact - Individual Scientific Projects

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). 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 especially innovative may be essential to advance a field.

In addition, for applications involving clinical trials:

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

Scored Review Criteria - Individual Scientific Projects

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

Significance

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

Is the proposed project sufficiently novel and meritorious and the research plan feasible, in addressing one or more stages in the development of therapies or other strategies to improve the lives of muscular dystrophy patients? For disease mechanism/therapeutic target identification and validation projects, is a plan provided as to how these efforts help to support the therapeutic development pipeline?

In addition, for applications involving clinical trials

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

Investigator(s)

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

Do the collaborative efforts require substantial, and not token, contributions from the partners for successful completion? For studies aimed at developing therapeutics, are there plans for involving industry partners that would enhance the research, accelerate progress or increase the likelihood of developing a product that improves the lives of dystrophy patients?

For clinical research project(s), does the research team involve trainees at various career stages from medical students to fellows and junior faculty?

In addition, for applications involving clinical trials

Does the project leader and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

Innovation

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

In addition, for applications involving clinical trials

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the Project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?

If the Project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

For preclinical translational research projects, is there a clear step-by-step plan, including adequate milestones, to track and evaluate the therapeutic development effort?

In addition, for applications involving clinical trials

Does the application adequately address the following, if applicable?

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

Environment

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

Do the problems to be addressed require both a center atmosphere and an intensive collaborative effort for successful completion?

In addition, for applications involving clinical trials

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

Additional Review Criteria - Individual Research Projects

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.

Study Timeline

Specific to applications proposing clinical trials

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

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 Animal Section.

Biohazards

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

Review Criteria for the Administrative Core

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

Are the structure and goals of the proposed Administrative Core well described and appropriate to meet the leadership and management needs of the overall center? Are appropriate plans described to engage the patient/advocate community to educate them on the research of the center, promote recruitment for clinical studies and incorporate the views of this community into the design and conduct of research studies? Are the organizational structure and other plans for managing the Center's activities for prioritization of competing needs appropriate and clear? Is the Management Plan for fiscal accountability and communications between organizational components appropriate? Are the approaches, criteria and plans to measure, monitor, track and evaluate the progress and performance of all project activities thoroughly described and adequate to assess progress/performance? Are there appropriate plans for establishing the Center Advisory Committee, and will this Committee contribute to the oversight of Center research projects, the Shared Resource Core, the Training Core and other components?

Do the Director and Co-Director have the leadership and research qualifications to lead a Wellstone Center? Do they have the collective expertise to identify and focus research projects on clinically relevant issues? Are there plans for establishing an Executive Committee and interacting with this committee in a way that will promote the success of the Center?

Is there an appropriate plan for establishing and maintaining effective communications and cooperation among Center investigators and with investigators outside the Center? Are there appropriate plans for establishing and maintaining a website for the Center that provides useful information to the research community about shared resources, research protocols and training opportunities?

Review Criteria for the Training Core

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

Does the proposed Training Core appropriately address all of the following goals:

• Enhancing the training environment of the Center and promoting career advance for trainees
• Recruiting trainees new to muscular dystrophy research
• Promoting trainee support through other fellowship funding opportunities
• Coordinating training meetings with the other Wellstone Centers
• Extending training activities to the broader muscular dystrophy research community

Are the objectives, design and direction of the proposed research training activities likely to prepare trainees for future careers in muscular dystrophy research? Do the courses, where relevant, and research experiences provide opportunities for trainees to acquire state-of-the-art scientific knowledge, methods, and tools that are relevant to the goals of the training program? Does the program provide appropriate inter- or multidisciplinary research training opportunities in the muscular dystrophies? Are there appropriate plans for non-clinical trainees to be exposed in a meaningful way to clinical research?

Is the level of institutional commitment to the training program, including administrative and research training support, sufficient to ensure the success of the program? Is it clear how the proposed training program is distinguished from other externally funded training programs at the institution and does the training core leverage existing training resources and add additional value to existing programs?

Does the PD/PI have the scientific background, expertise, and administrative and training experience to provide strong leadership, direction, management, and administration of the proposed research training program? Do the preceptors/mentors have strong records of training individuals at the level of trainees proposed in the program? How successful are past students/postdoctorates that have been trained in muscular dystrophy research by the preceptors/mentors of this center, considering their research productivity and career stage? Has the training environment in muscular dystrophy research at the applicant institution(s) contributed to the success and productivity of past trainees in terms of research accomplishments, career positions, leadership roles, etc.?

Additional Review Considerations for the Training Core

Training in the Responsible Conduct of Research

All applications for support under this FOA must include a plan to fulfill NIH requirements for instruction in the Responsible Conduct of Research (RCR). Taking into account the specific characteristics of the training program, the level of trainee experience, and the particular circumstances of the trainees, the reviewers will evaluate the adequacy of the proposed RCR training in relation to the following five required components: 1) Format - Does the plan satisfactorily address the format of instruction, e.g. lectures, coursework and/or real-time discussion groups, including face-to-face interaction? (A plan involving only on-line instruction is not acceptable.); 2) Subject Matter Does the plan include a sufficiently broad selection of subject matter, such as conflict of interest, authorship, data management, human subjects and animal use, laboratory safety, research misconduct, research ethics? 3) Faculty Participation - Does the plan adequately describe how faculty will participate in the instruction? For renewal applications, are all training faculty who served as course directors, speakers, lecturers, and/or discussion leaders during the past project period named in the application? 4) Duration of Instruction - Does the plan meet the minimum requirements for RCR, i.e., at least eight contact hours of instruction? 5) Frequency of Instruction Does the plan meet the minimum requirements for RCR, i.e., at least once during each career stage (undergraduate, post-baccalaureate, predoctoral, postdoctoral, and faculty levels) and at a frequency of no less than once every four years?

Review Criteria for Scientific Research Resource Core(s)

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

Are the core activities capable of effectively and efficiently supporting research productivity and collaborations and are they essential to the mission of the Center? If other, similar cores are already available to the research community, is there still a significant need for this core?

Is there strong evidence via the core description that at least one Scientific Research Resource Core will serve as an important national/international resource for the muscular dystrophy research community? Is there sufficient likelihood that this core facility will be used by researchers within and outside the Center, and that the resources provided will significantly accelerate progress on the projects that make use of this core?

Is there a strong commitment to provide services and/or resources to the national muscular dystrophy community and are plans for oversight and prioritization of user requests for core services adequate and fair? Are there appropriate plans and oversight to ensure that requests for shared resources will be addressed in a timely manner?

If the core facility is already established and supported by funding other than an MDSRC, how will the MDSRC award enhance the resources available? If designed as a fee-for-service facility, are the projected fees appropriate for recovery of only the variable costs (supplies, service contracts, etc.) and not the costs of personnel and equipment?

Are the staffing, allocated space, equipment, and other resources that are available to the core sufficient to meet the anticipated demand on its services?

For renewal applications, is there a documented success of providing fair and timely access to important shared resources broadly to the muscular dystrophy research community?

Additional Review Considerations-Individual Research Projects

As applicable for the individual 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.

Select Agent Research

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

Resource Sharing Plans

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

Authentication of Key Biological and/or Chemical Resources

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

Budget and Period of Support

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

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

As part of the scientific peer review, all applications:

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

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

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

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

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

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

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

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

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

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

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

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

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

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

Cooperative Agreement Terms and Conditions of Award

Not Applicable

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

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

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

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

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

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

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

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

Glen Nuckolls, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-5876
Email: [email protected]

Thomas Cheever, Ph.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-5019
Email: [email protected]

Danuta Krotoski, Ph.D.
Eunice Kennedy Shriver National Institute for Child Health and Human Development (NICHD)
Telephone: 301-496-5576
Email: [email protected]

Brian Kit, MD, MPH
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-827-4151
Email: [email protected]

Sherry Dupere, Ph.D.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-451-3415
Email: [email protected]

Tijuanna DeCoster, MPA
National Institutes of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9231
Email: [email protected]

Sheila Simmons
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-9812
Email: [email protected]

Bryan S. Clark, M.B.A.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6975
Email: [email protected]

Anthony Agresti
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0186
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.