Department of Health and Human Services


Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)
 

Components of Participating Organizations

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institute of Mental Health (NIMH)
National Institute of Neurological Disorders and Stroke (NINDS)

Funding Opportunity Title

Centers for Collaborative Research in Fragile X (U54)

Activity Code

U54 Specialized Center- Cooperative Agreements

Announcement Type

New

Related Notices

Funding Opportunity Announcement (FOA) Number

RFA-HD-14-033

Companion Funding Opportunity

None

Number of Applications

See Section III. 3. Additional Information on Eligibility.

Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.865, 93.242, 93.853

Funding Opportunity Purpose

This funding opportunity announcement (FOA) invites applications for the Centers for Collaborative Research in Fragile X. Successful Centers will be composed of transdisciplinary teams of investigators working together to address focused and challenging scientific questions within targeted areas of research.  The targeted areas of research are intended to address research gaps, drive discovery and further develop research relevant to Fragile X syndrome and Fragile X Gene (FMR1)- Related Conditions. 

Targeted areas of research include:

A) Advancing the understanding of the pathophysiology of FMR1 Related Conditions

B) Facilitating the Development of Treatments for FMR1 Related Conditions

C) Advancing the knowledge of clinical phenotypes for FMR1 Related Conditions.

Each Center will consist of 1) at least three distinct but highly integrated scientific projects, 2) an administrative core and 3) no more than two shared resource cores.

This FOA will not support Phase II/III clinical trials proposing to test efficacy or effectiveness of treatment/interventions using pharmacological or behavioral/psychosocial components in human subjects (patient or non-patient populations).

Key Dates
Posted Date

November 21, 2013

Letter of Intent Due Date(s)

December 21, 2013

Application Due Date(s)

January 21, 2014   

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

February/March 2014  

Advisory Council Review

May 2014

Earliest Start Date

July 2014

Expiration Date

January 22, 2014

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the PHS 398 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. While some links are provided, 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.

Looking ahead: NIH is committed to transitioning all grant programs to electronic submission using the SF424 Research and Related (R&R) format and is currently investigating solutions that will accommodate NIH’s multi-project programs. See NOT-OD-13-075 and  NIH’s Applying Electronically website for more information.

Table of Contents

Part 1. Overview Information
Part 2. Full Text of 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

Part 2. Full Text of Announcement


Section I. Funding Opportunity Description


Purpose

The Fragile X Syndrome Research Centers were originally developed in response to the Children's Health Act of 2000 (H. R. 4365) Section 452E which called for the funding of three Centers.  Over the past ten years, the funded Centers have produced numerous findings that have propelled the field of Fragile X research forward at a rapid pace.

This FOA invites applications for Centers for Collaborative Research in Fragile X. Successful Centers will be composed of transdisciplinary teams of investigators working together to address specific scientific questions within targeted areas of research. The targeted scientific questions are intended to address research gaps, drive discovery and further develop research relevant to Fragile X syndrome and Fragile X Gene (FMR1) Related Conditions.

Background

Collectively, Fragile X syndrome (FXS), Fragile X Associated Tremor/Ataxia syndrome (FXTAS), and Fragile X Associated Primary Ovarian Insufficiency (FXPOI), along with other FMR1 Related Conditions, represent a major health concern and have far-reaching implications for individuals, families, and their future generations.

While FXS, FXTAS and FXPOI have very different clinical symptoms, they all result from variations in a region of the FMR1 gene that contains multiple repeats of three nucleotides, cytosine-guanine-guanine (CGG). The specific repeated pattern and differences in the number of CGG repeats in the gene determine the most common abnormal forms of the gene: premutation and full mutation.

Individuals with fewer than ~55 repeats are considered to have a normal FMR1 gene. Individuals with more than 200 repeats have a full mutation and FXS.  Full mutations are generally associated with intellectual and developmental disabilities (IDD) apparent in early childhood. Repeats in the range of ~55 to 200 are called “premutations” and are associated primarily with adult-onset disorders: FXTAS and FXPOI. Collectively, "FMR1 Related Conditions" refer to any of the clinical conditions due to an abnormal FMR1 allele (premutation or full mutation) and include FXS, FXTAS, FXPOI, and others.

Fragile X Syndrome (FXS)

FXS is the most common inherited cause of IDD and has been estimated to occur in males and females across all racial and ethnic groups. IDD in FXS ranges from mild to severe, and females are more mildly affected, on average, than males because of the potential for favorable X inactivation in females. Emotional and behavioral problems, including attention problems, hyperactivity, anxiety, mood instability, tantrums, aggression, and social deficits are common. As many as 30 to 50 percent of individuals with FXS meet the diagnostic criteria for autism or autism spectrum disorders (ASDs). FXS is considered a portal for understanding a variety of neurobehavioral disorders, including autism, attention-deficit hyperactivity disorder (ADHD), and anxiety disorders.

Fragile X-associated Tremor/Ataxia Syndrome (FXTAS)

The core features of FXTAS are intention tremor and/or ataxia, with gradual cognitive decline beginning with memory and executive function deficits. Psychiatric problems including anxiety, dysinhibition, depression, and apathy are also common. Associated clinical features include peripheral neuropathy, dysautonomia, and particularly in women with FXTAS, hypothyroidism and muscle pain/fibromyalgia. Symptoms of FXTAS typically appear after age 50, although the age of onset correlates with the CGG expansion within the premutation range — the higher the number of repeats, the earlier the onset of tremor or ataxia. The penetrance of FXTAS is incomplete, meaning that not all carriers develop symptoms, and men are more commonly affected than women. Preliminary data on life expectancy from age of onset are variable, with a range from five to 25 years. 

Fragile X-associated Primary Ovarian Insufficiency (FXPOI)

Women with the Fragile X premutation are at risk for primary ovarian insufficiency, which is the onset of menopausal symptoms before the age of 40 years, and reflects a continuum of ovarian function. Fragile X premutation carriers, as a group, experience menopause approximately five years earlier than normal women, and women with the premutation who still have regular menstrual cycles show indications of early ovarian aging. Women with FXPOI not only experience loss of normal fertility but are also at increased risk for osteoporosis and cardiac disease and have higher rates of mortality. Thus, women who have a Fragile X premutation face the increased health risks related to FXPOI and FXTAS as well as the risk that their children will inherit the unstable repeat as either the pre- or full mutation. 

Other FMR1 Related Conditions

In addition to carrying a risk for later developing FXTAS and if female, FXPOI, premutation carriers have been reported in the literature to show symptoms as children that may include ADHD, anxiety, shyness, social deficits, and, on occasion, autism spectrum disorders. Boys appear to be affected more often than girls. However, further research is needed to fully understand these findings.

Development of Research Objectives

In the spring of 2008, the NIH, in response to a request from the U.S. Department of Health and Human Services and the Senate Committee on Appropriations, convened working groups charged with developing the NIH Research Plan on Fragile X and Associated Disorders. The plan consisted of comprehensive recommendations for specific, high-priority research objectives for FXS and the associated disorders of FXTAS and FXPOI. The goals were designed to be used by the NIH and FXS, FXTAS, and FXPOI research communities and to be shared with other federal agencies to facilitate coordinated research activities that could lead to timely detection, diagnosis, treatment, and prevention of the targeted disorders.

In spring 2012, the NIH published a Request for Information (RFI) entitled "Research Priorities in Fragile X syndrome, Fragile X Tremor Ataxia syndrome, Premature Ovarian Failure and Other Relevant Conditions Associated with FMR1 Gene Function" (NOT-HD-12-012) requesting comments from the scientific community, health professionals, patient advocates, and industry regarding future research priorities for these disorders. On May 7-8, 2012, the NICHD convened a meeting revisiting the NIH Research Plan on Fragile X and Associated Disorders, with the intent of reevaluating the existing goals of the Research Plan and providing input to determine whether progress was being made in meeting the goals or if it was necessary to modify the goals or add new ones.  Participants in the meeting included scientific experts from the research and clinical communities, along with representatives from advocacy groups for affected individuals and family members, other pertinent federal agencies and invested NIH Institutes and Centers (ICs).

The specific areas of research interest for this FOA are derived from the original NIH Research Plan on Fragile X and Associated Disorders, responses to the RFI, discussions during the meeting reevaluating the research plan, and the priorities and missions of ICs participating in the FOA.

Objectives of the Research Center

For the purposes of this FOA, three "areas of targeted research" have been identified as being of specific interest:

A.  Advancing the understanding of the pathophysiology of FMR1 Related Conditions

B.  Facilitating the development of treatments for FMR1 Related Conditions

C.  Advancing the knowledge of clinical phenotypes for FMR1 Related Conditions

Applicants for each Center for Collaborative Research in Fragile X must identify at least one of the areas of targeted research to be considered responsive.

Research Projects

Each of the proposed research projects should address problems that require a substantial collaborative research effort and synergy across projects to solve, and are best suited for a Center environment rather than a stand-alone grant.  Projects need to address areas of targeted research.  Collaborations should be arranged to bring the best expertise to bear on the area of targeted research, whether the proposed collaborations are all on-site or utilize consortium agreements with off-site investigators.

Each of the scientific projects should:

1) Be relevant to the area of targeted research of the center.

2) Be fully integrated and synergistic with other scientific projects within the Center.

3) Must have goals and aims that will be completed and will significantly benefit the field within the five-year period of the award.

4) Address one or more of the research gaps or needs listed in the targeted topics of research below.

A.  Advance the understanding of the pathophysiology of FMR1 Related Conditions

Targeted topics of research may address one or more of the following:

Fragile X Syndrome

Fragile X Associated Tremor/Ataxia Syndrome

Fragile X Associated Primary Ovarian Insufficiency

Genetic Basis for FMR1 Disruptions

B.  Facilitate the Development of Treatments for FMR1 Associated Disorders

Targeted topics of research may address one or more of the following:

Fragile X Syndrome

Fragile X Associated Tremor/Ataxia

FMR1 Related Conditions

C.  Advance the Knowledge of Clinical Phenotypes for FMR1 Related Conditions

Targeted topics of research may address one or more of the following:

Fragile X Syndrome

Fragile X Associated Tremor/Ataxia Syndrome

Fragile X Associated Primary Ovarian Insufficiency

FMR1 Related Conditions

Administrative Core

The Administrative Core should provide for the integration and management of activities within the Center. Each Center should expect to form an external Center Advisory Committee (CAC) with scientific, clinical and patient advocate representation, composed of at least five members.  The composition of the CAC will require NIH approval. The CAC should meet in-person or electronically approximately once a year, beginning in the first or second year of the Center award.  Funded Centers are expected to utilize the Administrative Core to establish and maintain a website to communicate the Center missions. Applicants are encouraged to form the strongest teams to address the research questions, regardless of the number of sites and geography.

Resource Core(s)

The shared Resource Core(s) should be designed and managed to support the research of the Center.

Section II. Award Information
Funding Instrument

Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH staff will assist, guide, coordinate, or participate in project activities.

Application Types Allowed

New

The OER Glossary and the PHS 398 Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards

The NICHD and partner components of NIH intend to commit the following estimated total amounts in FY 2014 to support approximately 4 center awards:

NICHD, $4 million total costs

NIMH, $2 million total costs

Award Budget

Budgets for each Center may not exceed $1.3 million direct costs per year and need to reflect the actual needs of the proposed project.

Award Project Period

The scope of the proposed project should determine the project period but is limited to a maximum of 5 years.

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

Section III. Eligibility Information


1. Eligible Applicants


Eligible Organizations

Higher Education Institutions

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

Nonprofits Other Than Institutions of Higher Education

For-Profit Organizations

Governments

Other

Foreign Institutions

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

Required Registrations

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the PHS 398 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.

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

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

Eligible Individuals (Program Director/Principal Investigator)

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 PHS 398 Application Guide.

Because the Collaborative Centers for Research in Fragile X program is intended to support projects conducted by multidisciplinary teams, multi-site applications are strongly encouraged.

Center Director:  Each Center for Collaborative Research in Fragile X must designate a PD/PI as the Center Director who will be the key figure in the administration, management, and coordination of the Center grant. The Director should be a recognized scientific leader experienced in the field of Fragile X or associated disorder research and must be able to coordinate, integrate, and provide guidance in the establishment of research programs. A Co-Director should also be named who will be involved in the administrative and scientific efforts of the Center.  

Senior/Key Personnel:  Centers are encouraged to include investigators whose primary field of expertise is outside of Fragile X but whose inclusion provides a significant, relevant contribution to the project.  This is intended to enrich the perspectives and methodologies brought to bear in addressing the targeted areas of research.  In addition, multidisciplinary teams are strongly encouraged to consider having early-stage or new investigators participate in each of the scientific projects. 

2. Cost Sharing

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

3. Additional Information on Eligibility


Number of Applications

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

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

Section IV. Application and Submission Information


1. Address to Request Application Package

Applicants are required to prepare applications according to the current PHS 398 application forms in accordance with the PHS 398 Application Guide.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the PHS 398 Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

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

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

The letter of intent should be sent to:

Tiina K. Urv, PhD
Intellectual and Developmental Disabilities Branch
Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH
6100 Executive Blvd.
Bethesda, MD 20892-7510
Rm 4B09D, MSC 7510
Phone: (301) 402-7015
Email: urvtiin@mail.nih.gov  

Application Submission

Applications must be prepared using the PHS 398 research grant application forms and instructions for preparing a research grant application. Submit a signed, typewritten original of the application, including the checklist, and three signed photocopies in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)

At the time of submission, two additional paper copies of the application and all copies of the Appendix files must be sent to:

Sherry Dupere, Ph.D.
Eunice Kennedy Shriver National Institute of Child Health and Human Development
6100 Executive Blvd.
Room 5B01G
Bethesda, MD 20892-7501
(for Fedex or other express delivery use zip 20852; don’t use -7501 extension)

Page Limitations

All page limitations described in the PHS 398 Application Guide and the Table of Page Limits must be followed, in addition to the following page limitations to the Research Strategy section of each component of the application.

Instructions for the Submission of Multi-Component Applications

The following section supplements the instructions found in the PHS 398 Application Guide, and should be used for preparing a multi-component application.

The application should consist of the following components:

Overall Component

All instructions in the PHS398 Application Guide must be followed, with the following additional instructions, as noted.

Face Page (Overall)

All instructions in the PHS 398 Application Guide must be followed.  Because the first page of the application is the Title Page, begin the next page with the numeral "2".

Description, Project/Performance Sites, Senior/Key Personnel, Other Significant Contributors, Human Embryonic Stem Cells (Overall)

All instructions in the PHS 398 Application Guide must be followed.  

Table of Contents (Overall)

All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions:

Modify PHS 398 Form Page 3 to enable reviewers to find each component of the application easily. The table of contents should be prepared listing all of the major sections described below and numbered consecutively. Include page numbers for Human Subjects and Vertebrate Animals sections for each Core and Research Project Component and for the Center as a whole.

Detailed Budget for Initial Budget Period (Overall)

All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions:

For the U54 Center application, prepare a series of Composite budget tables as requested below. In addition, a separate detailed budget is required for each Core and for each Research Project Component responding to at least one of the three focus themes. Use the order indicated.

Composite Budget

Use Form Page 4, "DETAILED BUDGET FOR INITIAL BUDGET PERIOD," of the PHS-398 to present the total budget, by component, for all requested support for the first year. In the header for each page, indicate that this is a COMPOSITE budget. For each category, such as "PERSONNEL," "EQUIPMENT," etc., itemize by each Core and Research Project and list the total amount requested for the first year of the Center. If consortium arrangements have been made involving other institutions or organizations, include total costs (direct and Facilities and Administrative (F & A)) associated with such third party participation in the "CONSORTIUM/CONTRACTUAL COSTS" category. Costs for purchased services should be itemized under "OTHER EXPENSES."

Use Form Page 5, "BUDGET FOR ENTIRE PROPOSED PROJECT PERIOD," of the PHS 398 to prepare a budget, by component, that provides totals for each year of requested support and the budget for the entire proposed project period. In the header for each page, indicate that this is a COMPOSITE budget. Include totals of Consortium/Contractual Costs by year for the project.

PLEASE NOTE: Consortium budgets (if applicable) should be presented as described in Composite Budget, including budget for the entire proposed project period. Total direct and indirect costs of sub-awardees are to be shown under Consortium/Contractual costs on the individual component budget and a detailed sub-awardee budget is to be placed following the appropriate Research Project or Core budget.

Items not fundable under an NICHD U54 Cooperative Agreement:

Budget for Entire Proposed Period of Support (Overall)

All instructions in the PHS 398 Application Guide must be followed.   

Biographical Sketch (Overall)

All instructions in the PHS 398 Application Guide must be followed.   Biographical sketches are required for all senior/key scientific and key technical personnel participating in the overall Center, the Resource Cores, and the specific Research Projects(s).  Include the biosketch for the Center Director first, followed by the others in alphabetical order.

Resources (Overall)

All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions:

Briefly describe the features of the institutional environment that are or would be relevant to the effective implementation of the proposed program. As appropriate, describe available resources, such as clinical and laboratory facilities, participating and affiliated units, patient populations, geographical distribution of space and personnel, and consultative resources.

Research Plan (Overall)

All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions:

Specific Aims:  Follow the instructions in the PHS398 Application Guide.

Research Strategy: Describe the major themes of the overall Center, its goals and objectives, background information and the overall importance of the research to the theme of this program as outlined in Section I.  Funding Opportunity Description.  Explain the strategy for achieving the goals defined for the overall program and how each Core and Research Project relate to that strategy. Explain how the different aspects 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 a Center that is more than the sum of its parts. Provide justification in the application that: (a) the proposed research projects require an intensive collaborative effort to succeed, and (b) that key personnel will collaborate effectively.  Include all necessary tables, graphs, figures, diagrams and charts in this section.  In addition, provide the following information:

Protection of Human Subjects. Provide an overview of the human subjects considerations for the Center as a whole.  List the components of the application that involve human subjects.

Vertebrate Animals. Provide an overview of the vertebrate animal considerations for the Center as a whole. List the components of the application that involve live vertebrate animals.

Letters of Support: Include letters of support/agreement for  any collaborative/cooperative arrangements, subcontracts, or consultants.  Letters of support for the U54 Center overall should be included with the Overall Component. Letters of support for individual Research Projects or Cores should be included with those components of the application. For projects to be conducted off site, i.e., at an institution other than the applicant institution, a letter of assurance or comparable documentation, signed by the collaborator as well as the off-site institutional officials, must be submitted with the application. 

Resource Sharing Plan:Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the PHS 398 Application Guide, with the following modification:

Administrative Core

All instructions in the PHS398 Application Guide must be followed, with the following additional instructions, as noted.

Face Page (Administrative Core)

Do not use the PHS398 Face Page. For the Administrative Core, include a single cover page listing the title of the Core and the name of the Core Director with titles and affiliations. 

Description, Project/Performance Sites, Senior/Key Personnel, Other Significant Contributors, Human Embryonic Stem Cells (Administrative Core)

All instructions in the PHS 398 Application Guide must be followed.

Table of Contents (Administrative Core)

Do not complete this form page for the Administrative Core.

Detailed Budget for Initial Budget Period (Administrative Core)

All instructions in the PHS 398 Application Guide must be followed , with the following additional instructions:

Use Form Page 4, "DETAILED BUDGET FOR INITIAL BUDGET PERIOD," of the PHS 398 to present the Admin Core budget  for the first year. In the header for each page, indicate which Component the budget represents, i.e., ADMINISTRATIVE CORE. 

The Center Director must commit to at least 1.8 person months (15%) of effort for the duration of the award. 

Budget for Entire Proposed Period of Support (Administrative Core)

All instructions in the PHS 398 Application Guide must be followed. with the following additional instructions:

Use Form Page 5, "BUDGET FOR ENTIRE PROPOSED PROJECT PERIOD," of the PHS-398 to prepare a budget that provides totals for each year of requested support. In the header for each page, indicate which Component the budget represents, i.e., ADMINISTRATIVE CORE.

PLEASE NOTE: Consortium budgets (if applicable) should be presented as described in Composite Budget, including budget for the entire proposed project period. Total direct and indirect costs of sub-awardees are to be shown under Consortium/Contractual costs on the individual component budget and a detailed sub-awardee budget is to be placed following the appropriate Research Project or Core budget.

Budget Justification

For the Administrative Core, describe the specific functions of key scientific and technical personnel, consultants, collaborators and support staff. For all years, explain and justify any unusual items such as major equipment or alterations and renovations. For additional years of support requested, justify any significant increases in any category over the first 12-month budget period. Identify such significant increases with asterisks against the appropriate amounts. No recurring annual escalations in costs are allowed.

Allowable costs for Administrative Core:

Biographical Sketch (Administrative Core)

Do not complete these pages for the Administrative Core.

Resources (Administrative Core)

All instructions in the PHS 398 Application Guide must be followed.

Research Plan (Administrative Core)

All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions:

Specific Aims:  Follow the instructions in the PHS398 Application Guide.

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 should specify appropriate administrative/business management staff and oversight mechanisms by the Center Director, Center Co-Director, and a local Executive Committee.

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

The Administrative Core should establish an Executive Committee, composed of members of the Center and a Center Advisory Committee, composed of people outside the Center.  Describe how the Center Advisory Committee will contribute to oversight of the scientific projects, core facilities and training environment of the Center.  The Center Advisory Committee should meet approximately once a year and brief reports of the proceedings of the meeting and recommendations of the committee should be included in the progress reports of the Center.  Describe plans as to how the leadership of the Center will work with the Center Advisory Committee.  Do not include the names of the Executive Committee members in the application.

In order to assure active collaboration with other awarded Centers, the Center Director, Co-Director, and other staff are expected to attend annual meetings of the Centers for Collaborative Research in Fragile X, contribute to the coordination of effort, and/or help to refine and standardize operating procedures among the Centers.

The application should also provide the following information:

Organizational Chart

Staffing: Description of key professional and support staff functions.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the PHS 398 Application Guide, with the following modification:

Resource Core(s)

All instructions in the PHS398 Application Guide must be followed, with the following additional instructions, as noted.

Face Page (Resource Core)

Do not use the PHS398 Face Page. For each Resource Core, include a single cover page listing the title of the Core and the name of the Core Director. Identify each proposed Core unit by a letter (A, B, C…) and a title.

Description, Project/Performance Sites, Senior/Key Personnel, Other Significant Contributors, Human Embryonic Stem Cells (Resource Core)

Provide the description and other requested information for each Resource Core according to instructions in the PHS 398 Application Guide.

Table of Contents (Resource Core)

Do not complete this form page for the Resource Core(s).

Detailed Budget for Initial Budget Period (Resource Core)

All instructions in the PHS 398 Application Guide must be followed with the following additional instructions:

Use Form Page 4, "DETAILED BUDGET FOR INITIAL BUDGET PERIOD," of the PHS 398 to present the budget for each Core for the first year. In the header for each page, indicate which Component the budget represents.

Budget for Entire Proposed Period of Support (Resource Core)

All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions:

Use Form Page 5, "BUDGET FOR ENTIRE PROPOSED PROJECT PERIOD," of the PHS-398 to prepare a budget for each Resource Core that provides totals for each year of requested support. In the header for each page, indicate which Resource Core the budget represents.

PLEASE NOTE: Consortium budgets (if applicable) should be presented as described in Composite Budget, including budget for the entire proposed project period. Total direct and indirect costs of sub-awardees are to be shown under Consortium/Contractual costs on the individual component budget and a detailed sub-awardee budget is to be placed following the appropriate Research Project or Core budget.

Budget Justifications:

For each Resource Core, describe the specific functions of key scientific and technical personnel, consultants, collaborators and support staff. For all years, explain and justify any unusual items such as major equipment or alterations and renovations. For additional years of support requested, justify any significant increases in any category over the first 12-month budget period. Identify such significant increases with asterisks against the appropriate amounts. No recurring annual escalations in costs are allowed.

Allowable costs for Resource Core(s):

Items not fundable under an NICHD U54 Cooperative Agreement:

Biographical Sketch (Resource Core)

Do not complete these pages for the Resource Core(s).

Research Plan (Resource Core)

Specific Aims:  Follow the instructions in the PHS398 Application Guide.

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

Discuss ways in which 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 your application, it is recommended that you prepare in tabular form information concerning the scientific projects that each facility core unit would serve.

When proposing support for an already existing resource, describe how the Centers for Collaborative Research in Fragile X award would enhance the resources or services already available through new innovation and technology development, expanded availability, increased throughput, etc.

Protection of Human Subjects:  If Core services involve human subjects, discuss the Human Subjects protections following relevant policy announcements. If all of the individual projects accessing the Core have their own Human Subjects sections, this should be clearly stated in this section.

Inclusion of Women, Minorities and Children.  If appropriate for this Core Component, describe the composition of the human subjects population and the proactive plan to recruit women, minorities, and children.

Vertebrate Animals: If Core services involve live vertebrate animals, include a description of the use of live vertebrate animals according to the Application Guide. If all of the individual Research Projects accessing the Core have their own vertebrate animal assurances, this should be clearly stated in this section.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the PHS 398 Application Guide.

Research Projects

Follow all instructions in the PHS398 Application Guide for a single project application, but note the additional instructions provided below.

Face Page (Research Project)

Do not use the PHS 398 Face Page. For each Research Project, include a single cover page listing the title of the Project, the name of the Project Director, and names of any other Key Personnel (with titles and affiliations).

Description, Project/Performance Sites, Senior/Key Personnel, Other Significant Contributors, Human Embryonic Stem Cells (Research Project)

Provide the description and other requested information for each Research Project according to instructions in the PHS 398 Application Guide.

Table of Contents (Research Project)

Do not complete this form for the Research Projects. 

Detailed Budget for Initial Budget Period (Research Project)

All instructions in the PHS 398 Application Guide must be followed with the following additional instructions:

Use Form Page 4, "DETAILED BUDGET FOR INITIAL BUDGET PERIOD," of the PHS 398 to present the budget for each Research Project for the first year. In the header for each page, indicate which Component the budget represents, i.e., RESEARCH PROJECT A, B, etc.

Budget for Entire Proposed Period of Support (Research Project)

All instructions in the PHS 398 Application Guide must be followed with the following additional instructions:

Use Form Page 5, "BUDGET FOR ENTIRE PROPOSED PROJECT PERIOD," of the PHS-398 to prepare a budget for each Research Project that provides totals for each year of requested support. In the header for each page, indicate which Component the budget represents.

PLEASE NOTE: Consortium budgets (if applicable) should be presented as described in Composite Budget, including budget for the entire proposed project period. Total direct and indirect costs of sub-awardees are to be shown under Consortium/Contractual costs on the individual component budget and a detailed sub-awardee budget is to be placed following the appropriate Research Project or Core budget.

Budget Justifications

For each Research Project, describe the specific functions of key scientific and technical personnel, consultants, collaborators and support staff. For all years, explain and justify any unusual items such as major equipment or alterations and renovations. For additional years of support requested, justify any significant increases in any category over the first 12-month budget period. Identify such significant increases with asterisks against the appropriate amounts. No recurring annual escalations in costs are allowed.

Items not fundable under an NICHD U54 Cooperative Agreement:

Biographical Sketch (Research Project)

Do not complete this form page for the Research Projects.

Research Plan (Research Project)

Specific Aims:  Follow the instructions in the PHS398 Application Guide.

Research Strategy:   Organize the Research Strategy as described in the PHS398 Application Guide and using the instructions provided below. Start each section with the appropriate section heading—Significance, Innovation, Approach.  Specify the overall biomedical significance of the work proposed. As part of the Research Strategy, include information on preliminary studies, data, and/or prior experience pertinent to this application.

Clearly state the overall objective of the project and explain its relevance to the central theme of the Center. In addition, an explanation should be included describing how the Research Project relates to and both complements and enhances the other Projects and Cores of the program. Why the Research Project is best suited to be carried out in the Center environment should be highlighted. Specify the niches filled by each Research Project in advancing research in the area of Fragile X and associated disorders.

For each Research Project, provide a description of the potential value and feasibility of successfully completing the study within the term of the grant.

For studies aimed at developing therapeutics, include 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 individuals with Fragile X or Associated Disorders. Applicants proposing early-stage pilot or exploratory clinical trials (e.g., Phase 0 or I) are strongly encouraged to contact participating program staff as early as possible to discuss the suitability of their project for this funding mechanism.  This FOA will not support Phase II/III clinical trials proposing to test efficacy or effectiveness of treatment/interventions using pharmacological or behavioral/psychosocial components in human subjects (patient or non-patient populations).  

Applications involving preclinical studies must address the the scientific rigor of the experimental design, the strategies used to minimize bias (e.g., blinding and randomization), justification for sample size, the quality of the statistical analyses, the robustness and reproducibility of the reported results, and the consideration of alternative interpretations (see: http://www.ninds.nih.gov/funding/transparency_in_reporting_guidance.pdf).  For translational studies involving animals the rationale for the chosen animal model(s) and endpoints, adequacy of controls, the route and timing of therapeutic dosing and the inclusion/exclusion criteria used during the study must be included. 

Protection of Human Subjects:  If the Research Project involves human subjects, discuss the Human Subjects protections following relevant policy announcements.

Inclusion of Women, Minorities and Children.  If appropriate for this Research Project, describe the composition of the human subjects and the proactive plan to recruit women, minorities, and children.

Vertebrate Animals: If the Research Project involves live vertebrate animals, include a description of the use of live vertebrate animals as indicated in the Application Guide.

Resource Sharing Plan.  Applicants are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the PHS 398 Application Guide, with the following modification:

Provide a plan for sharing any resources specific to this Research Project.  Projects relevant to autism research are strongly urged to consider sharing data within the following mechanism: The NIH National Database for Autism Research (NDAR) houses research data of all types (genetic, imaging, clinical assessment, etc.) from human subjects involved in ASD studies, and is currently on track to receive data from tens of thousands of such subjects.  NDAR’s first data release occurred in November 2010, making mostly clinical assessment data from over 10,000 research subjects available to qualified investigators.  It is expected that in the next several years, ASD data from more than 90% of new investigations will be available in or through NDAR. For more information on NDAR, please visithttp://ndar.nih.gov/ndarpublicweb/.Paste Other Components here

Appendix for the Entire Application

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix (please note all format requirements) as described in the PHS 398 Application Guide.

3. Submission Dates and Times

Part I. Overview Information contains information about Key Dates. 

Information on the process of receipt and determining if your application is considered “on-time” is described in detail in the PHS 398 Application Guide.

Applicants may track the status of the application in the eRA Commons, NIH’s electronic system for grants administration.

4. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

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

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

6. Other Submission Requirements and Information

Applications must be received on or before the due dates in Part I. Overview Information. If an application is received after that date, it will not be reviewed.

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

Pre-Application Information Call and Online Information

The NIH will hold a pre-application informational conference call at 3:00 pm EST on December 5, 2013, which all interested prospective applicants are invited to join.  Program and review staff will make presentations to explain the goals and objectives of the FOA and answer questions from call participants.

To obtain the call-in information, please contact Dr. Tiina Urv (urvtiin@mail.nih.gov or 301-402-7015) at least 24 hours prior to the call. 

Post Submission Materials

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

Section V. Application Review Information


1. Criteria

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

Centers should be designed to include the following components: At least three Research Projects, an Administrative Core, and no more than two Resource Cores.  The proposed number and composition of Projects and Cores should reflect the overall theme(s) and requirements of the Center to achieve its goals, and should be appropriate for the requested budget.  After the review of the individual components, an overall impact score will be assigned to the center application. The impact score will reflect a) the scientific merit of the Research project(s), b) the overall effectiveness and adequacy of Core resources and facilities, c) the qualifications of the Overall Center 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.

Since this FOA specifically seeks applications that address difficult, challenging scientific questions and/or have the potential to overcome critical barriers in the field, the participating ICs recognize that applications may include components or projects that are exploratory, discovery-based and/or higher risk in nature.  The review will evaluate the potential for the Center as a whole to have a significant impact on the field during the terms of the award weighing the balance of more conventional approaches with highly innovative components or projects in which success is not guaranteed.  In evaluating higher risk components or exploratory projects with limited preliminary data, the reviewers will weigh the potential to achieve transformative, paradigm-shifting advances against the risks.  The reviewers will evaluate the likelihood that interpretable results will be obtained from exploratory or high risk studies.  For example, if proposing a novel hypothesis, the investigator should be able to prove or disprove that hypothesis by the end of the funding period; if proposing exceptionally innovative methodology or technology, the investigator should be able to develop it by the end of the funding period or demonstrate conclusively that the approach is not feasible.

Overall Impact - Overall

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).

Scored Review Criteria - Overall

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

Investigator(s)

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

Are the qualifications, experience, and commitment of the Director and Co-Director of the Center for Collaborative Research in Fragile X adequate to lead the Center program and are they devoting sufficient time/effort to achieve Center goals? Does the Center Director have sufficient authority and credibility within the institution and broader community as a base for serving a national leadership role in Fragile X related research? Does the Center Co-Director have appropriate complementary and integrated experience/expertise to help lead a multi-disciplinary center effort? Are there adequate plans for interaction among Center personnel and any off-site investigators?   

Innovation

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

Approach

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

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

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?   

Additional Review Criteria

As applicable for the Centert 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 as an Integrated Effort

The overall U54 Center will be evaluated as an integrated research effort focused on one or more research areas listed under Research Scope.  The relationship and contributions of the Research Projects and Cores to the overall objectives will be discussed and evaluated. Reviewers will assign an impact score based on assessment of the scientific and technical merit of the Center overall. The assessment will take into consideration all proposed Research Projects and Cores, including any with poor ratings. The review will assess the level of merit of the Center as an integrated effort, including the following criteria:

Will there be coordination, collaborations, cohesiveness, and synergy among the research projects and core components as they relate to the common theme of the Center?

Are there clear advantages of conducting the proposed research as a program rather than through separate research efforts?  Will the research efforts taken together have more impact on the field than each separate project conducted in isolation?  Will the research proposed in individual projects be enhanced by the Center?

Are mechanisms proposed for regular communication and coordination among investigators in the Center?

Are administrative structures in place for the day-to-day management of the Center, including arrangements for internal quality control of ongoing research?        

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Children 

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

Vertebrate Animals

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

Biohazards

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

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

Additional Review Considerations - Overall

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

Applications from Foreign Organizations

Not Applicable

Select Agent Research

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

Resource Sharing Plans

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

Budget and Period of Support

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

Review Criteria for Research Projects  

Reviewers will  provide an overall impact score to reflect their assessment of the likelihood for each of the Projects 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 each of the Projects proposed). An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a scientific project that by its nature is not especially innovative or one that is highly innovative with little pilot data -- could both be essential to advance a field.

Scored Review Criteria - Research Projects

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each.

Significance

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

Is the proposed project sufficiently novel and meritorious and the research plan feasible, in addressing one or more of the targeted areas of research as outlined in Section I of this FOA?  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? 

Investigator(s)

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

Is there evidence that each collaborator will contribute substantially? 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 individuals with Fragile X or Associated Disorders?

Innovation

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

Approach

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

Rigor and Transparency: The reviewers will judge the scientific rationale/premise of the study and the quality of the study design. Preclinical studies will be evaluated for the scientific rigor of the experimental design, the strategies used to minimize bias (e.g., blinding and randomization), justification for sample size, the quality of the statistical analyses, the robustness and reproducibility of the reported results, and the consideration of alternative interpretations (see: http://www.ninds.nih.gov/funding/transparency_in_reporting_guidance.pdf).  For translational studies involving animals, the reviewers will also evaluate the rationale for the chosen animal model(s) and endpoints, adequacy of controls, the route and timing of therapeutic dosing and the inclusion/exclusion criteria used during the study.

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?

Additional Review Criteria - Research Projects

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.

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Children 

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the 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 five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

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

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

Additional Review Considerations - Research Projects

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

Applications from Foreign Organizations

Not Applicable

Select Agent Research

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

Resource Sharing Plans

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

Budget and Period of Support

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

Review Criteria for Administrative Core

The Administrative Core provides for leadership and management of all Center activities. Reviewers will consider each of the review criteria below in determining the scientific merit of this core.  Each assigned reviewer will provide one score for the Administrative Core.  The scientific merit of the Administrative Core should be considered by reviewers in determining the overall score for the Center.

Purpose

Is the proposed Administrative Core well matched to the needs of the overall center?

Management

Is the management plan appropriate for scientific administration as well as fiscal administration, procurement, property and personnel management, planning, budgeting, etc.? Is the Center scientific and administrative structure sufficient, including its internal and external procedures for monitoring and evaluating the proposed scientific projects and core facilities/resources? Are there appropriate plans for establishing the Center Advisory Committee and will this Committee contribute to the oversight of Center scientific projects?

Leadership

Do the Director and Co-Director have the leadership and research qualifications to lead a Center for Collaoborative Research in Fragile X? Do they have the collective expertise to identify and focus scientific projects on clinically relevant issues?  Are there plans for utilizing an Executive Committee in a way that will promote the success of the Center?

Communication

Is there an appropriate plan for establishing and maintaining effective communications and cooperation among Center investigators and with investigators outside the Center? 

Environment

Is the environment for the Administrative Core adequate and appropriate to support the overall Center as proposed? Is there evidence of institutional support for the management of the Center?

Review Criteria for Resource Cores

Reviewers will consider each of the review criteria below in determining the scientific merit of each Core.  Each assigned reviewer will provide one score for each Scientific Research Resource Core.  The scientific merit of the Scientific Research Resource Core should be considered by reviewers in determining Overall Impact score for the Center.

Purpose

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

Leadership

Does the core provide adequate leadership and technical expertise to ensure that it meets its stated goals?

Cost Effectiveness

If the core facility is already established and supported by funding other than from the Center for Collaborative Research in Fragile X, how will the Fragile X Center 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?

Environment

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s), 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:

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

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center and 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:

3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information


1. Award Notices

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

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

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

Any application awarded in response to this FOA will be subject to the DUNS, SAM Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

2. Administrative and National Policy Requirements

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

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

The overall function of the Center as described under "Specific Research Objectives".  This includes the development of the standard operating procedures, and consistent emphasis on collaborative interactions between all Center investigators, advisory and steering committees, and NIH representatives. Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

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

An NIH Project Scientist will be responsible for: (1) overseeing the activities of the Center, along with the other entities delineated above, to ensure that studies are properly conducted and completed in a timely fashion; (2) providing advice and guidance to ensure that the Center runs in accordance with NIH policies and procedures, and is consistent with the mission of the NIH to improve public health; and (3) serving as a point of contact for investigators with the NIH; (4) disseminating information from the Institute and communicating with Institute leadership to ensure that the Center operates smoothly.

An NIH Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

The NIH will appoint an Advisory Board for the entire Centers for Collaborative Research in Fragile X Program.  It is expected that this Board will include representatives from academia, industry, other government agencies, and non-profit organizations.  The role of this Advisory Board will include discussion of direction of projects, including vision for integration of studies and how they can best serve the overall goals of the project and stakeholders.  

Areas of Joint Responsibility include:

The NICHD Project Scientist and staff will work closely with the Advisory Board, the Steering Committees, and the PD(s)/PI(s) of all Projects and Cores in order to ensure proper conduct of the Center.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

3. Reporting

When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590 or RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

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

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

Section VII. Agency Contacts

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

Application Submission Contacts

eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

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

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone: 301-435-0714
TTY: 301-451-5936
Email: GrantsInfo@nih.gov

Scientific/Research Contact(s)

Tiina K. Urv, PhD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-402-7015
Email: urvtiin@mail.nih.gov  

Lisa Gilotty, PhD
National Institute of Mental Health (NIMH)
Telephone:  301-443-3825
Email: gilottyl@mail.nih.gov  

Peer Review Contact(s)

Sherry Dupere, PhD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-496-3415
Email: duperes@mail.nih.gov

Financial/Grants Management Contact(s)

Bryan Clark, MBA
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6975
Email: clarkb1@mail.nih.gov

Rebecca Claycamp, MS, CRA
National Institute of Mental Health (NIMH)
Telephone: 301-443-2811
Email: rclaycam@mail.nih.gov

Section VIII. Other Information

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

Authority and Regulations

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.


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