Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Funding Opportunity Title	Intellectual and Developmental Disabilities Research Centers 2013 (U54)
Activity Code	U54 Specialized Center- Cooperative Agreements
Announcement Type	Reissue of RFA-HD-10-022
Related Notices	March 7, 2014 - This RFA has been reissued as RFA-HD-14-012.
Funding Opportunity Announcement (FOA) Number	RFA-HD-13-002
Companion Funding Opportunity	None
Number of Applications	Only one application per institution is allowed, as defined in Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.865
Funding Opportunity Purpose	The purpose of this Funding Opportunity Announcement (FOA) is to seek applications for the Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Centers (IDDRCs). The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) invites applications for research center cooperative agreements designed to advance the diagnosis, prevention, treatment, and amelioration of intellectual and developmental disabilities (IDD). This FOA seeks applications from institutions that meet the qualifications for a multi-disciplinary program of IDD research that will include: 1) Cores that facilitate interdisciplinary and translational research in IDD, and support IDD-related projects funded by other sources; and 2) at least one specific research project related to one of five focus themes identified as an area of research need in IDD. Funds for the majority of research projects using these core facilities come from independent sources including Federal, State, and private organizations.

Posted Date	January 16, 2013
Letter of Intent Due Date(s)	March 9, 2013
Application Due Date(s)	April 9, 2013
AIDS Application Due Date(s)	Not Applicable
Scientific Merit Review	June/July 2013
Advisory Council Review	August 2013
Earliest Start Date	September 2013
Expiration Date	April 10, 2013
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. NIH will announce plans to transition the remaining programs in the NIH Guide to Grants and Contracts and on NIH’s Applying Electronically website.

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

The purpose of this Funding Opportunity Announcement (FOA) is to seek applications for the Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Centers (IDDRCs). The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) invites applications for research center cooperative agreements designed to advance the diagnosis, prevention, treatment, and amelioration of intellectual and developmental disabilities (IDD). This FOA seeks applications from institutions that meet the qualifications for a multi-disciplinary program of IDD research that will include: 1) Cores that facilitate interdisciplinary and translational research in IDD, and support IDD-related projects funded by other sources; and 2) at least one specific research project related to one of five focus themes identified as an area of research need in IDD. Funds for the majority of research projects using these core facilities come from independent sources including Federal, State, and private organizations.

For almost 50 years, discoveries made by investigators within the IDDRCs have increased the basic understanding of many forms of IDD and moved the field forward appreciably. Historically the IDDRC program has been funded via Center Core (P30) grants that facilitate program coordination and support central research facilities, administration, and a limited number of new development projects. Over the years, core services have evolved to include state-of-the-art infrastructure in areas such as developmental neurobiology, genomics, proteomics, neuroimaging, epidemiology, biostatistics, behavioral science, and clinical translational research. In the new round of IDDRC competition, the goal is to provide an opportunity to transition the IDDRC program into a functional network of integrated and collaborative research centers. This initiative will support IDDRCs through the U54 (Specialized Center-Cooperative Agreement) mechanism. The U54 mechanism will also allow the research community, in collaboration with the NICHD, to respond to emerging needs within the IDD field.

The goals of the IDDRC program will include the promotion of collaborative, multidisciplinary and interdisciplinary research programs that will not only provide core facilities and support for research in IDD, but will also advance the development of therapeutics and interventions for these conditions.

The missions of the IDD Branch at NICHD are broad and include research on the etiology, pathophysiology, epidemiology, diagnosis and evaluation, prevention, and treatment or amelioration of IDD. The research conducted by the IDDRCs in the past has mirrored this breadth and has covered a wide spectrum of scientific approaches ranging from laboratory research on fundamental processes of normal and abnormal development to clinical, biomedical, behavioral, and biobehavioral studies in persons with IDD. During the past 50 years, the IDDRCs have been highly productive, and solutions to some of the major challenges associated with IDD have emerged from multidisciplinary, collaborative, and integrated approaches.

On April 23-24, 2012, the NICHD held a workshop to identify key research areas, resources, and integration strategies needed to make advances in the field of IDD over the next 5 to 15 years. Participants in the meeting included scientific experts from the research, clinical, and pharmaceutical communities, along with representatives from advocacy groups, other relevant federal agencies, and interested NIH Institutes and Centers. The recommendations that arose from that meeting and priorities of the NICHD form the basis for the five focus themes that were identified as areas of research need and that will inform the specific research project proposed in response to this FOA. In addition, there was broad recognition of the need to promote coordination of IDD-related research endeavors and integration of clinical trial efforts.

NICHD now seeks opportunities to advance research in IDD that take advantage of new technologies that have recently evolved and to encourage cooperation among the Centers, including their integration into a network that may facilitate development of the infrastructure necessary for the conduct of larger research programs or clinical trials. The U54 mechanism provides the opportunity for the Centers to be responsive to these emerging needs, and allows them to be strategically placed to promote future clinical and translational efforts including clinical trials. This FOA represents a step in the evolution of the IDDRC program toward more project-focused and translational approaches to IDD research.

A major goal of the NICHD IDDRC Program is to support research that leads to the prevention and/or amelioration of IDD. The intent of the IDDRC Specialized Center-Cooperative Agreement program is to bring together scientists from various disciplines to work within a Center on the most pressing issues related to IDD. Each IDDRC typically supports investigators studying a range of topics in basic and clinical or applied research. This FOA also encourages support of postdoctoral trainees, junior investigators, and investigators new to the IDD field through their access to Core services, as one of the goals of the IDDRC program is to attract scientists to IDD research. NICHD strongly encourages translation of basic research observations into patient-oriented protocols whose ultimate aims are to validate the mechanistic basis of IDD in humans and to develop new approaches for the prevention, diagnosis and treatment of IDD.

To facilitate compliance with the U54 mechanism, it is essential that scientific personnel and institutional resources capable of providing a strong research base in the IDD field are available. There also must be a strong institutional commitment. The commitment may take the form of faculty appointments and/or partial salary support for investigators, purchase of research equipment, or assignment of research space to facilitate collaborative research and interdisciplinary interaction. Scientists may have access to the Center's centralized facilities and participate in its activities while retaining independent control of their respective research projects. However, all activities using NICHD Center funds must be relevant to the mission of NICHD's IDD Center program.

Applications responding to this FOA must propose a multi-disciplinary program of IDD research that includes Core Components and Research Components. Requirements for these components are described in the following sections.

Each U54 can propose a minimum of three and a maximum of six Cores, with a required Administrative Core and a required Clinical Translational Core as two of the required Cores. Core components must facilitate interdisciplinary and translational research in IDD, and support IDD-related projects funded by other sources.

Each Core must fulfill the following requirements:

• Provide essential facilities or services for at least five federally-funded, peer-reviewed research projects, at least one of which is NICHD-funded.
• Have satisfactory quality-control systems documented for its services or facilities.
• Be cost-effective, i.e., the centralization should result in a lower cost than would be incurred if the same facilities or services were supported by the individual research grant budgets.
• Increase the quality and productivity of research projects receiving Core support.
• In general, contract-supported projects may not be counted as qualifying a Core to meet its five research project minimum requirement. In cases where the funding agency primarily uses the contract mechanism to support investigator-initiated projects rather than the grant/assistance mechanism, the aforementioned restriction may not apply. In these cases, NICHD staff should be consulted. Use of Core facilities by projects funded by research and development contracts will be evaluated on an individual basis. Any use of Core facilities by contracts must be paid for in full from contract funds, not from NICHD Center funds.
• Use of Core facilities by projects located at other institutions is allowable with prior NICHD approval. The sharing of unique Core resources among U54 IDDRCs is permitted and encouraged, provided that an appropriate cost-recovery mechanism is developed.
• Use of Core facilities by individual trainees supported by Institutional National Research Service Awards (T32) or other trainee or career development awards (such as F and K awards) is allowable, with NICHD approval.
• The cost-effectiveness of the Core units must be demonstrated in the application. Mechanisms such as fee-for-service, in-kind, or other means are acceptable.

Administrative Core

The Administrative Core should provide for the integration and management of activities within the IDDRC. Applicants should specify appropriate administrative/business management staff and oversight mechanisms by the Center Director (PD/PI), Center Co-Director (if applicable), and a local Executive Committee. Each Center should form an External Advisory Committee (EAC) composed of at least five members, with scientific, clinical and patient advocate representation, as well as NIH program staff. The composition of the EAC will require NIH approval. The EAC should meet in-person or electronically approximately once a year, beginning in the first or second year of the Center award. Funded IDDRCs must utilize the Administrative Core to establish and maintain a website to communicate the Center missions and the availability of Core services. When multiple geographic sites are involved in the IDDRC, the Administrative Core should include leadership and communication plans adequate to manage the multiple sites. Any training elements should be organized and coordinated within the Administrative Core.

Clinical Translational Core

The Clinical Translational Core must have a translational science focus that supports research allowing application of basic science discoveries to the clinical setting, treatment development, and/or clinical trials. Examples of activities that might be considered as part of a clinical translational core include but are not limited to:

• services related to patient recruitment or natural history studies;
• clinical services in subject assessment, phenotyping, evaluation, or treatment;
• development of biomarkers or validated outcome measures;
• bioinformatics/biostatistics expertise to design clinical trials or provide clinical trial information management;
• manufacturing services that incorporate Good Manufacturing Practices (GMP) for chemical or compound formulation for drug development;
• high-throughput screening to enhance identification of compounds for treatment of IDD;
• collection of human samples from individuals with IDD for biobanking purposes.

U54 applications must include at least one specific Research Component that addresses one or more of the five focus themes identified as an area of research need in IDD by leaders in the field at the NICHD-sponsored workshop held in April 2012.

Each new Research Component project must utilize at least two cores of the IDDRC (including the Administrative Core and/or Clinical Translational Core). Primary funding must be through this U54 mechanism, but other sources of funding are allowed (federal grant, philanthropic, or foundational support). Each Research Component project should be considered the equivalent of an R01 research grant. The five focus areas are as follows, in no order of priority:

(1) Comprehensive omic Approaches

Comprehensive -omic approaches (e.g., genomic, transcriptomic, epigenomic, metabolomic) that will markedly increase our understanding of IDD conditions with no known etiology or IDD conditions with complex etiologies to improve diagnosis, and potentially, treatment. Examples include, but are not limited to:

• whole exome or whole genome sequencing of a well-defined cohort of subjects with IDD to identify genetic or genomic variants likely to cause the phenotype;
• methylation or other studies on individuals with a shared IDD diagnosis but variable manifestations (such as range of cognitive function) to identify potential epigenetic contributors;
• tandem mass spectrometry on biological samples such as saliva, blood or urine from a group of individuals with metabolic or other disorders associated with intellectual disability that might define distinctive biomarkers or metabolic signatures that would allow monitoring of outcomes or response to treatment.

(2) Outcome Measures for Interventions or Treatments

Development of preclinical or clinical outcome measures or biomarkers for the cognitive and/or behavioral phenotypes of IDD that have the potential to demonstrate a change in response to intervention or treatment.

Examples include, but are not limited to:

• development of a measure for an animal model (e.g., mouse, rat, nonhuman primate) of an IDD disorder that reliably detects changes in behavior response to a drug treatment;
• development of a measure of cognitive function in individuals with an IDD condition that is sensitive to an intervention;
• demonstration of changes in an existing behavioral measure in individuals with an IDD condition in response to therapy.

(3) Multi-modal Treatment Approaches

Development of bi- or multi-modal treatment approaches for a single IDD condition or a group of IDD conditions or spectrum disorders to demonstrate combinatorial effects to ameliorate a cognitive or behavioral symptom(s) of the condition(s). The interventions may or may not be disease-specific, and the potential to broaden to multiple IDD disorders is encouraged. Examples include, but are not limited to:

• use of a drug and a training paradigm in an animal model of an IDD to demonstrate improvement in a behavioral measure;
• use of a medication and behavioral treatment in combination for individuals with an IDD condition to demonstrate improved efficacy;
• use of one well-established intervention plus 1-2 medications to improve general symptoms of a mood disorder in individuals with different IDD conditions who share that mood disorder.

(4) Shared Resources Across IDDRCs for Treatment or Assessment

Development of an assessment battery or clinical intervention for an IDD condition or group of IDD conditions that links more than one funded IDDRC into a network, with sharing of at least one unique core resource from each IDDRC. Examples include, but are not limited to:

• development of an assessment paradigm for an allelic series of animal models for an IDD condition that uses the genomics core of one IDDRC and the animal behavioral core of another IDDRC;
• development of a testing paradigm for a specific IDD condition that uses the biostatistics core from one IDDRC and the human behavioral assessment core of another IDDRC;
• creation of a clinical trial for an IDD condition that utilizes the patient recruitment core from one IDDRC and the trial design core from another IDDRC.

(5) Public Health Approaches

Public health approaches to IDD that identify potentially preventable, modifiable, or treatable targets that can yield a rich payoff in ameliorating or improving outcomes for large groups of individuals with IDD or that will reduce risk of developing an IDD. These may include preconceptional, prenatal, postnatal or childhood exposures or risk factors, and may involve the broader family or community. Examples include, but are not limited to:

• a project that addresses the risk of developing an IDD due to preterm birth;
• a project that addresses maternal exposures to potential teratogens (alcohol, cocaine, cytomegalovirus, etc.) that predispose to IDD;
• development of a measure that attempts to reduce environmental factors (such as lead) that can contribute to IDD.

The Center Director (PD/PI) should have a minimum commitment of 20% (2.4 person- months) effort to the IDDRC. S/he should develop and maintain a center environment that fosters traditional and novel approaches to multi-disciplinary research collaborations and training. The Center Director may serve as the PD/PI on the Research Component of the IDDRC. The Center Director cannot serve as project PD/PI on another active IDDRC award.

As national resources for IDD research, the IDDRCs play leadership roles in training of new researchers for the IDD research field and educating the patient and lay communities regarding research activities. Each center should include plans for training and education to establish and maintain a training environment for predoctoral and postdoctoral investigators in IDD research, as well as new and early stage investigators, and to engage the patient and lay community in educational and research activities. Utilization and adaptation of existing training programs are encouraged. The training environment for the center may include, as examples, formal training on manuscript writing and reviewing, grantsmanship, team science approaches and lab management, as well as training on the ethical conduct of research. Other features of the training environment may include a seminar program, retreats for presentation of trainee research, journal clubs, or other activities that contribute to the preparation and/or mentorship of junior investigators for careers in IDD research. Training activities should be organized within the Administrative Core. Participation of patient advocacy groups in the planning and conduct of education and outreach activities is encouraged.

Scientific personnel and institutional resources capable of providing a strong research base in the IDD field must be available. A strong institutional commitment is essential. The commitment may include faculty appointments and/or partial salary support for investigators, purchase of research equipment, or assignment of research space to facilitate collaborative research and interdisciplinary interaction. The facilities should require no more than modest alteration and/or renovation. NICHD provides no funds for new construction but minor renovation for Cores may be included within the IDDRC budget. Scientists may have access to the Center's centralized facilities and participate in its activities while retaining independent control of their respective research projects. However, all activities using IDDRC Center funds must be relevant to the mission of NICHD's IDDRC program.

NICHD encourages investigators within the Centers to apply for clinical trials grants (e.g., R34, R01, and U01). Administrative and scientific organization within a Center and across the network of IDDRCs should enhance opportunities for major discoveries and acquisition of scientific knowledge that will help prevent, diagnose, and ameliorate or treat IDD.

Recipients of IDDRC awards will become part of a national program in IDD research and will be expected to participate in IDDRC activities, including an annual meeting in the Washington, DC area of the Steering Committee (composed of IDDRC Directors, NIH program staff, and other relevant advisors), and an annual IDDRC meeting that rotates among the IDDRC sites.

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	NICHD intends to commit a total of $3.9 million in FY 2013.
Award Budget	Application budgets are not limited, but need to reflect the actual needs of the proposed project. Support for the entire IDDRC should not exceed $1.3 million in total costs per year.
Award Project Period	The scope of the proposed Center should determine the project period. The maximum period is 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.

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)
• U.S. Territory or Possession

Other

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

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

Applicant organizations must complete the following registrations as described in the PHS 398 Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

• System for Award Management (SAM) must maintain an active entity registration (formerly CCR registration), to be renewed at least annually. Use the Sam.gov Manage Entity function to manage your entity registrations. See the Grants Registration User Guide at SAM.gov for additional information.
• eRA Commons

All Program Directors/Principal Investigators (PD(s)/PI(s)) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least6 weeks prior to the application due date.

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.

The IDDRC Center Director (PD/PI) should be a scientist or science administrator who can provide effective scientific and administrative leadership. The Director will be responsible for the organization and operation of the IDDRC and for communication with the NICHD on scientific and operational matters. S/he should be able to integrate and synthesize the proposed research, and, thereby, serve as an example to other investigators. The Center Director should have a minimum commitment of 2.4 person-months to the IDDRC.

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

Only one application per institution (normally identified by having a unique DUNS number or NIH IPF number) is allowed.

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:

• To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
• Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
• Of an application with a changed grant activity code.

For the purpose of this FOA, the NICHD will support no more than one IDDRC cooperative agreement (U54) per institution. An institution cannot have simultaneous funding for a P30 and a U54 as part of the IDDRC program.

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

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.

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

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

• Descriptive title of proposed research
• Name, address, and telephone number of the IDDRC PD/PI
• Names of other key personnel, including Core Component Directors and PI of the Research Component Project(s) responding to one of the five focus themes
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Melissa A. Parisi, M.D., Ph.D.
Intellectual and Developmental Disabilities Branch
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
6100 Executive Boulevard
Room 4B09, MSC 7510
Bethesda, MD 20892
Rockville, MD 20852 (for express/courier service; non-USPS service)
Telephone: (301) 435-6880
FAX: (301) 496-3791
Email: [email protected]

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 five copies of the Appendix files on CD-ROM must be sent to:

• Sherry Dupere, Ph.D.
  Director, Scientific Review Branch
  Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  National Institutes of Health (NIH)
  6100 Executive Boulevard, Room 5B01, MSC 7510
  Bethesda, MD 20892-7510
  Rockville, MD 20852 (for express/courier service; non-USPS service)
  Telephone: 301-496-1485
  FAX: 301-402-4104
  Email: [email protected]

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

• Overview of the Center: 12 pages
• Each Core Component: 12 pages
• Each Research Component: 12 pages

Note that the limit for descriptions of funded Research Projects proposed for Core usage is 1 page for each project.

The following section supplements the instructions found in Form PHS 398 for preparing a multi-component grant application. Additional instructions are required because the Form PHS 398 is designed primarily for individual, free-standing research project grant applications, and has no specific instructions for multi-component applications. All applications must be submitted on Form PHS 398.

The multi-component grant application should be assembled and paginated as one complete document in the following order:

• Overview of the Center
• Core Component: minimum of three and a maximum of six Cores
• Administrative Core (required)
• Clinical Translational Core (required)
• Research Component: minimum of one component
• Research Projects proposed for Core usage: Existing funded projects

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

Face Page (Form Page 1)

In the Face Page for the overall application, include the number and title of this FOA in item/line 2 of the PHS 398 face page. 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, and Human Embryonic Stem Cells (Form Page 2)

Follow all instructions in the Application Guide, but note the following additional instructions:

Senior/Key Personnel: List key scientific and key technical personnel participating in the U54 Center. Use continuation pages as necessary, numbering consecutively. The PD/PI of the IDDRC should be a recognized scientific leader experienced in the field of IDD research and must be able to coordinate, integrate, and provide guidance in the establishment of research programs.

Table of Contents (Form Page 3)

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 Component and Research Component and for the Center as a whole.

Detailed Budget for Initial Budget Period and Budget for Entire Proposed Period of Support

This FOA uses non-modular budget formats described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html).

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 Component and the specific Research Component(s) responding to one of the five focus themes. Use the order indicated.

1. Composite Budgets

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 Component 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.

2. Individual Core Component and Research Component Budgets

Use Form Page 4, "DETAILED BUDGET FOR INITIAL BUDGET PERIOD," of the PHS-398 to present the budget for each Core Component and specific Research Component Project(s) for the first year. In the header for each page, indicate which Component the budget represents, e.g., CORE (or RESEARCH) COMPONENT A, B, etc. Consortium Budgets (if applicable) should be presented as described in Item 1 (Composite Budgets). Total Direct and F & A costs of sub-awardees are to be shown under "CONSORTIUM/CONTRACTUAL COSTS" on individual Component budgets, and a detailed Consortium budget is to be inserted following the appropriate Component budget.

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. In the header for each page, indicate which Component the budget represents, e.g., CORE (or RESEARCH) COMPONENT A, B, etc.

Budget Justifications: For each Core and Research Component, 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. In addition, for Competing Continuation applications, justify any significant increases in any category over the current level of support.

Allowable costs for specific components are as follows:

Administrative Core Unit

• Salaries and support for a limited number of administrative and clerical personnel, such as the Center Director, Center Administrator, secretaries, and clerical support staff;
• Administrative support services, including supplies, duplication, telephone, and maintenance contracts for equipment when not covered by institutional F & A charges;
• Costs related to dissemination of research results to the scientific community and lay public;
• Costs related to seminars or meetings designed to promote interdisciplinary interaction, education, or Center cohesiveness;
• Costs related to advisory committee meetings;
• Travel of Center investigators to other IDDRCs or other collaborative sites to exchange scientific ideas, to plan multi-Center research projects, or to receive training in specialized techniques;
• Travel to 2 Center Directors' meetings annually to confer with other NICHD IDDRC Directors and program staff to promote scientific interaction among the Centers: one meeting of the IDDRC Steering Committee (composed of IDDRC Directors, NIH program staff, and other relevant advisors) will be held in the Washington, DC area, and a second annual IDDRC meeting will rotate among the IDDRC sites.

Core Components

• Salaries and support for core staff;
• Supplies (including animals);
• Scientific equipment;
• Computer facilities and services;
• Travel for technical or administrative staff for technical training or to maintain operation of the core unit;
• Minor renovation or alteration of existing facilities;
• Consultant services.

Specific Research Component Project(s)
The budget for this project should be comparable to a budget for an R01 project or equivalent.

Items not fundable under an NICHD U54 Cooperative Agreement

• Direct support of individual research projects (except the specific Research Component Project(s) responding to one of the five focus themes);
• Salary and support for central institutional administrative personnel usually paid from institutional F & A charges, such as budget officers, grant assistants, and building maintenance personnel;
• Salary and support for administrative activities such as public relations, health or educational services unrelated to the research;
• Travel of investigators to scientific meetings, other than travel of the Center Director or designee to IDDRC-related meetings;
• Support of unfunded research projects by Component Cores (with the exception of the Research Component Project) generally is not allowable, except in rare situations requiring approval by NICHD staff.

Biographical Sketches

Biographical sketches are required for all senior/key scientific and key technical personnel participating in the overall Center, the Core Components, and the specific Research Component project(s). Beginning with Center Director, and following in alphabetical order, submit biographical sketches as described in the "Instruction Sheet for Form PHS-398," using the sample format on the Biographical Sketch Format Page.

Resources

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 for the Center 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 Center, its goals and objectives, background information and the overall importance of the research to advancing the diagnosis, prevention, treatment, and amelioration of IDD. Explain the strategy for achieving the goals defined for the overall program and how each Core and Research Component 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. Include all necessary tables, graphs, figures, diagrams and charts in this section. In addition, provide the following information:

• History, Purpose, and Objectives of the Center: Discuss the philosophy and objectives of the IDDRC and general plans for the proposed grant period. For an existing IDDRC, the history information can emphasize information that demonstrates the Center’s past success in realizing its objectives.
• Administration, Organization, and Operation of the Center: Include information on the support and commitment of the parent institution for the Center, the authority and qualifications of the Center Director, the use of advisory or user committees, and the method of determining Core access and space assignment. Describe the organizational framework and provide an organizational chart.
• Cost-Effectiveness and Quality Control: Describe procedures used to lower costs and assure quality of Center administrative and research activities.
• Connections between the proposed Center and other organizations such as patient advocacy groups, industry partners, or other Centers or IDDRCs.
• Accomplishments of Center not previously cited: Describe any other experience with research centers/programs or core resources, which may include:
  1. Use of center/program/core administrative funds for activities such as consultant services, scientific seminars, renovations, or travel;
  2. Training activities that contributed to the center/program/core environment, and documentation of previous trainees, preceptors, present positions; current trainees, preceptors, research topics;
  3. Investigators attracted to the field by the center/program and its core facilities, including new investigators and visiting investigators;
  4. Impact of the center/program/core on the institution and community;
  5. Role of the center/program/core in facilitating IDD research, assisting young investigators, attracting other research funds, and enhancing collaboration and interdisciplinary research;
  6. Role of center/program/core in facilitating IDD research, assisting young investigators, attracting other research funds, and enhancing collaboration and interdisciplinary research;
  7. Other accomplishments.

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 and page numbers for the relevant human subjects sections.

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 and page numbers for the relevant sections.

Letters of Support. Letters of Assurance/Agreement: Any arrangements for collaborative and cooperative endeavors or subcontracts should be highlighted. Include letters of agreement from consultants. 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. 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 modifications:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Resource Sharing Plan. Provide an overview for and describe the oversight of the resource sharing plan of the Center as a whole.
• In keeping with the goals of the IDDRC Program, the applicants should highlight potentially unique core resources and how they plan to share them with other IDDRCs. A cost-sharing plan to allow other IDDRCs access to such unique resources is acceptable and encouraged, if appropriate.

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

Face Page

Do not use the PHS398 Face Page. For the Administrative Core, include a single cover page listing the title of the Core, the name of the Core Director, and names of any other Key Personnel (with titles and affiliations).

Description, Project Performance Sites, Senior/Key Personnel, Other Significant Contributors, and Human Embroyonic Stem Cells

Do not complete this form page for the Administrative Core.

Table of Contents

Do not complete this form page for the Administrative Core.

Detailed Budget for Initial Budget Period and Budget for Entire Proposed Period of Support

Do not complete these pages for the Administrative Core.

Biographical Sketches

Do not complete this form page for the Administrative Core.

Research Plan

Research Strategy: The Administrative Core will be responsible for the management and administration of the overall U54 IDDRC. 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 Cores and research project(s), and will promote coordination and collaboration within the Center and with investigators and organizations outside the Center. The Research Strategy should describe 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. To assure active collaboration with other Centers, the IDDRC Director should attend annual meetings of the IDDRC Network, contribute to the coordination of effort, and/or help to refine and standardize operating procedures among the Centers. The application should provide the following information about the Administrative Core:

• Objective of the Core
• Organizational Chart
• Staffing: Description of key professional and support staff functions.
• Resources: Description of space and physical resources.
• Services Provided: Description of current and projected services to other Core and Research Components, as well as the process for prioritizing requests for use of Core facilities by the various research projects. If a Core already exists, include a description of past services provided, new technologies developed, changes in protocols or Core administration, and other significant developments.
• Training and Education: Include plans to establish and maintain a training environment for predoctoral and postdoctoral investigators in IDD research, as well as new and early stage investigators, and to engage the patient and lay community in educational and research activities. Utilization and adaptation of existing training programs are encouraged. Further details on this function of the Administrative Core are described in Section I.
• Executive Committee and Advisory Committee: The Administrative Core should establish an Executive Committee, composed of members of the Center, and an External Advisory Committee, composed of members outside the Center and relevant NIH program officers. Describe how the External Advisory Committee will contribute to oversight of the Core facilities and specific research projects, as well as training environment of the Center. The External Advisory Committee should meet approximately once a year virtually or in person, and brief reports of the proceedings of the meeting and recommendations of the committee should be included in the annual progress reports of the Center. Describe plans as to how the Center will work with the External Advisory Committee, but do not name the members in the application.
• Cost effectiveness and plans for quality control

Protection of Human Subjects: If the Administrative Core services involve human subjects, (e.g., recruitment; screening, evaluation, biobanking), discuss the Human Subjects protections and inclusion of women, minorities and their subgroups, and children as research subjects, 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 and the proactive plan to recruit women, minorities, and children. Follow PHS 398 Instructions in preparing this section.

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

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. If not covered under the Overview, provide a plan for sharing any resources specific to this Core Component.

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

Face Page

Do not use the PHS398 Face Page. For each other core component, include a single cover page listing the title of the Core, the name of the Core Director, and names of any other Key Personnel (with titles and affiliations). Identify each proposed Core unit by a letter (A, B, C ) and a title (Administrative Core, Clinical Translational Core, Molecular/Cellular Core, etc.).

Description, Project Performance Sites, Senior/Key Personnel, Other Significant Contributors, and Human Embroyonic Sttem Cells

Do not complete this form page for the other Core Components.

Table of Contents

Do not complete this form page for the other Core Components.

Detailed Budget for Initial Budget Period and Budget for Entire Proposed Period of Support

Do not complete these pages for the other Core Components.

Biographical Sketches

Do not complete this form page for the other Core Components.

Research Plan

Research Strategy: For the required Clinical Translational Core and any other Core Components, provide the following information:

• Objective of the Core
• Staffing: Brief description of scientific, technical, and support staff functions.
• Resources: Description of space and physical resources.
• Services Provided: Description of current and projected services to other Core and Research Components, as well as the process for prioritizing requests for use of Core facilities by the various research projects. If a Core already exists, include a description of past services provided, new technologies developed, changes in protocols or Core administration, and other significant developments.
• Administration: Description of overall management of the Core Component.
• Justification: Description of services provided and their bearing on productivity and quality, as well as documentation of cost-effectiveness and plans for quality control. For the Clinical Translational Core, include a description of the service(s) provided and how it will support research that allows application of basic science discoveries to the clinical setting, treatment development, and/or clinical trials. Explain how this Core will advance the diagnosis, prevention, treatment, and amelioration of IDD in individuals with these conditions.
• Utilization of Core: Provide a summary of projected usage of Core services (e.g., assays performed, animals supplied, etc.) by affiliated research projects, including PD/PI, name of grant, and funding source.

Protection of Human Subjects: If Core services involve human subjects, (e.g., recruitment; screening, evaluation, biobanking), discuss the Human Subjects protections and inclusion of women, minorities and their subgroups, and children as research subjects, 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 and the proactive plan to recruit women, minorities, and children. Follow PHS 398 Instructions in preparing this section.

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

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. If not covered under the Overview, provide a plan for sharing any resources specific to this Core Component.

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

Face Page

Do not use the PHS398 Face Page. For each Research Component, 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, and Human Embroyonic Stem Cells

Do not complete this form page for the Administrative Core.

Table of Contents

Do not complete this form page for the Administrative Core.

Detailed Budget for Initial Budget Period and Budget for Entire Proposed Period of Support

Do not complete these pages for the Administrative Core.

Biographical Sketches

Do not complete this form page for the Administrative Core.

Research Plan

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

Research Strategy: For any project that involves preclinical research, adequate rigor is expected with regard to experimental design, minimizing bias, interpretation of results, and transparency of reporting. There is increasing awareness among neurological disease communities that to assess the predictive value of preclinical research, sufficient information must be available about study design, execution, and analysis. Examples of the critical elements of a well-designed study are summarized in this document: (http://www.ninds.nih.gov/funding/transparency_in_reporting_guidance.pdf). NICHD urges applicants to the IDDRC program to consider these elements when describing preclinical studies and designing the specific Research Component project.

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. Each Research Component project should clearly state its overall objective and explain its relevance to the focus theme chosen. A minimum of two Cores (which may include the Administrative and/or Clinical Translational Core) of the Center must be utilized by each Research Component project and should be identified. In addition, an explanation should be included describing how the project relates to and both complements and is enhanced by the research goals and Cores of the Center. Specify the overall biomedical significance of the work proposed and why the project is best suited to be carried out in the Center environment. As part of the Research Strategy, include information on preliminary studies, data, and/or prior experience pertinent to this application. If external sources of funding are available for the project, these must be clearly stated,including source, amount, and duration of support.

Each specific Research Project will be peer reviewed for scientific and technical merit, as well as for the appropriateness of the project's use of Core services and relevance to the identified focus theme chosen and the goals of the Center.

Protection of Human Subjects: If the Research Component involves human subjects, (e.g., recruitment; screening, evaluation, biobanking), discuss the Human Subjects protections and inclusion of women, minorities and their subgroups, and children as research subjects, following relevant policy announcements.

Inclusion of Women, Minorities and Children. If appropriate for this Research Component, describe the composition of the human subjects and the proactive plan to recruit women, minorities, and children. Follow PHS 398 Instructions in preparing this section.

Vertebrate Animals: If the Research Component involves live vertebrate animals, include a description of the use of live vertebrate animals 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.

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. Provide a plan for sharing any resources specific to this Research Component, with the following modifications:

• In keeping with the goals of the IDDRC Program, the applicants should highlight potentially unique resources and how they plan to share them with other IDDRCs. A cost-sharing plan to allow other IDDRCs access to such unique resources is acceptable and encouraged, if appropriate.

The following modifications apply to any specific Research Component project(s) responding to one of the five focus themes that address autism research:

• The NIH National Database for Autism Research (NDAR) houses research data of all types (genetic, imaging, clinical assessment, etc.) from human subjects involved in autism spectrum disorder (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.
• All autism-related projects will be required to contribute data to NDAR, which will function as a data repository. NDAR will be involved to facilitate sharing activities. Central clinical coordination and local data management for data cleaning and entry and bio-statistical consulting will be the responsibility of the autism project. For more information on NDAR, please visit http://ndar.nih.gov/ndarpublicweb/.

Research projects with other sources of funding that are proposed for Core usage will be evaluated with respect to the appropriateness of their use of core services and relevance to IDD. These projects should be listed in numerical order. The following information is to be given for each research project that is currently funded or pending award (status = to be paid in eRA Commons or IMPACII).

For each funded research project proposed for Core usage, provide the following information (do not exceed one page per project):

• Title of project.
• PD/PI and level of effort (person-months).Source of support (including complete designation and grant number, such as 5 P01 HG 12345 (P.I. - Smith), Project III (P.I.- Jones).
• Indication of funding status (funded or pending).
• Period of support.
• Total first year or current 12-month budget.
• Total project period budget.
• Brief description of project.
• Relevance of the project to U54 center mission and IDD research.
• Core(s) to be accessed with brief justification statement.

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. Provide five copies of appendices on CD-ROMs.

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.

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 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.

The NIH will hold a pre-application informational conference call on January 29, 2013, at 3:00 - 4:30 pm EST, to which all interested prospective applicants are invited. Program and review staff will make presentations to explain the goals and objectives of the FOA and will answer questions from call participants.

To obtain the call-in information, please contact Dr. Melissa Parisi ([email protected]) at least 24 hours prior to the call.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.

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: For U54 applications, the overall score will reflect a) the overall effectiveness and adequacy of Core Component resources and facilities; b) the scientific merit of the specific Research Component project(s) responding to one of the five focus themes; c) the scientific merit and relevance to IDD of the research projects proposed for Core usage; d) the ability of the Clinical Translational Core to successfully promote treatment development for IDD; e) the qualifications of the Center Director; f) the quality of the plans for management and oversight of the Center; g) the institutional commitment; and h) 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 IDDRC 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.

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?

Does the program, including the Clinical Translational Core, have the potential to advance treatment development for IDD?

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?

Does the Center Director have leadership ability and scientific stature, an ability to meet the program's demands of time and effort, and an ability to promote the Center mission among participants? Does the program involve the participation of a suitable number of responsible, experienced investigators with adequate time commitment for the Core and Research Components as well as the overall Center to succeed?

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 Center 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 children, justified in terms of the scientific goals and research strategy proposed?

Are the arrangements for internal quality control of ongoing research, allocation of funds, day-to-day management, contractual agreements, internal communication, external review, and cooperation among the investigators in the program well delineated and appropriate?

Is the administrative and organizational structure conducive to attaining the specific aims of the proposed program? For existing IDD Research Centers, is there a track record of success in advancing progress in IDD research?

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?

Is the Center able to provide adequate infrastructure to support novel approaches to IDD research and has it anticipated current and future needs of the research community? Is the academic and physical environment as it bears on research subjects, space, and equipment, and on the potential for interaction with scientists from other departments and institutions sufficient and conducive for the Research Component project and the Center as a whole? Is the institutional commitment to the requirements of the program adequate?

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.

Integration of the Overall U54 Center

A major emphasis in evaluating the IDDRC is the integration or centeredness of the overall program. The IDDRC will be evaluated as an integrated collection of Core and Research Components oriented around an IDD focus. The review will evaluate the following:

• Does the program function as a true Center rather than a collection of unrelated support services and research projects with the sum of the parts being greater than the individual components?
• Do coordination and integration between the proposed Core and Research Components reflect a cohesive research program?
• Is value added by having the proposed Core and Research Components comprise a Center that allows the Center to leverage additional resources that would not have been possible without an integrated Center structure?
• Is the Center multidisciplinary in scope and do the breadth and overall quality of the Center's program, the Core Components, and the Research Component project(s) have the ability to catalyze significant research advances in IDD?

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 Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children

When the proposed Center or one of the Core or Research Components 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 Human Subjects Protection and Inclusion Guidelines.

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

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.

Reviewers will assign an impact score based on the assessment of each Core Component in terms of the following review criteria. Separate criterion scores will not be assigned for Cores.

For each individual Core Component, the review will evaluate the following:

• Qualifications, experience, and commitment of the Core Director and other Core personnel;
• The quality of the services provided;
• The cost effectiveness and quality control of the Core;
• If a Core already exists, the effectiveness and relevance of provided services and development of new technologies or other significant advances;
• The utility of the Core to the program.

For the Administrative Core, the review will also evaluate the following:

• The Core Director’s experience in research administration;
• The appropriateness of administrative structures and day-to-day management of the program;
• The decision-making process within the proposed center for the evaluation of research productivity, allocation of funds, and management of resources;
• The process for prioritizing use of Core facilities by the various research projects;
• The process for evaluating research projects and investigators for membership in the Center and access to the Cores;
• The mechanisms proposed for regular communication and coordination among investigators in the program;
• The plan for program evaluation, including the use of any internal or external advisory committees;

For the Clinical Translational Core, the review will also evaluate the following:

• The experience of the Core Director in directing translational science;
• The likelihood that the service(s) provided will support translational science in IDD;
• The promotion of projects that will lead to treatment development and/or clinical trials;
• The responsiveness of the Core to Human Subjects issues that may arise;
• The ability of the Core to support efforts that will lead to clinical trials in IDD.

Reviewers will assign an impact score based on the likelihood of success for each Research Component Project responding to one of the five focus themes.

Reviewers will also consider each of the five review criteria below in the determination of scientific and technical 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 Research Component address an important problem or a critical barrier to progress in the field? If the aims of the Research Component 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 Research Component project related to one of the five focus themes responsive to the articulated goals of the program, consistent with the focus of the Center, and the IDDRC program as a whole? Will the Center facilitate the Research Component's ability to make substantive advances in IDD research?

Investigator(s)

Are the PD/PIs, collaborators, and other researchers well suited to the Research Component 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 Research Component project?

Innovation

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

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the Research Component project? Are potential problems, alternative strategies, and benchmarks for success presented? If the Research Component project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? If the Research Component 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 children, justified in terms of the scientific goals and research strategy proposed? If the Research Component project involves preclinical studies, are the vertebrate animal sections adequately described, and is adequate rigor incorporated into study design, analysis, interpretation, and reporting?

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 Research Component project proposed? Will the Research Component project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements? Is the Research Component project well integrated into the Center as a whole?

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:

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

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

Applications will be assigned to the appropriate NIH Institute or Center 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 National Advisory Child Health and Human Development (NACHHD) Council. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.
• Cost-effectiveness of the Core facilities.
• Cost of the Center.
• Compliance with resource sharing policies.

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

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

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

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

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

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

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 PD/PI will have the primary responsibility for defining objectives and approaches, and to plan, conduct, analyze, and publish results, interpretations, and conclusions of their studies. The PD/PI will serve as Center Director and will be responsible for the integration and management of activities within the IDDRC.

The Center Director shall be responsible for organizing a local Executive Committee for day-to-day management of the IDDRC, and an External Advisory Committee, with scientific, clinical and patient advocate representation (final membership to be approved by the NIH). The role of these Committees will include the solicitation, review, and selection of specific Research Project(s) responding to one of the five focus themes and collaborative projects, and the selection and prioritization of projects that will use resources and services that are provided for through the IDDRC.

The Center Director of each IDDRC also serves as a member of the IDDRC Steering Committee (see below) and is required to participate in its activities, to include regular conference calls and two annual IDDRC face-to-face meetingw.

Awardees agree to participate in the overall coordination of NIH research efforts in IDD. This participation may include collaboration and consultation with other NIH awardees, the sharing of information, data, and research materials, and participation in NIH efforts to standardize and harmonize pre-clinical and clinical data collection.

Awardees with a clinical trial component in their IDDRC agree to review of associated data, abstracts, and other publications by the DSMB and the NIH prior to their release.

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 HHS, PHS, and NIH policies.

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

Each IDDRC will have the support of Project Scientists, representing the NICHD, and a Program Official from NICHD staff, who are assigned administrative roles for the IDD being studied and have expertise in the implementation of the IDDRC Program.

The NIH Project Scientists will have substantial scientific-programmatic involvement during conduct of this activity, through technical assistance, advice, and coordination above and beyond normal program stewardship for grants. The NIH Project Scientists also will assist in the interaction between the awardee and investigators of other institutions, as well as between the awardee and other Federal agencies and/or potential commercial sponsors. The NIH Project Scientists will be members of the IDDRC Steering Committee. The NIH Project Scientists retain the option to recommend additional research endeavors within the constraints of the approved research and negotiated budget.

An important part of the NIH IDDRC Program is the coordination of research efforts across different funding mechanisms and research structures, and coordination among efforts aimed at different IDD. The NICHD Project Scientists will have the primary responsibility for this overall coordination.

The NIH may appoint an IDDRC Advisory Committee (IAC), consisting of scientific and public members. The IAC may function in an advisory role to the NIH as necessary on issues that arise related to the IDDRC program. IAC members may participate in the annual meeting of the IDDRC Steering Committee and be consulted as necessary.

The NIH Project Scientists representing NICHD will, collectively, have a single NIH vote on the IDDRC Steering Committee (see below). NIH Project Scientists will abstain from voting on any issue where they are unable to reach a consensus.

Additionally, an agency Program Official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

The Program Official assigned to each IDDRC will exercise oversight responsibilities, including assessment of the progress of the projects toward the accomplishment of specified objectives. The NIH Program Official also retains the option of recommending termination of studies if technical performance falls below acceptable standards, or when specific lines of research cannot be effectively pursued in a timely manner.

Areas of Joint Responsibility include:

Overall coordination of the IDDRC Program will be done by a Steering Committee. The IDDRC Steering Committee will make strategic decisions with regard to goals and research implementation, including the establishment and development of collaborations.

The Steering Committee will consist of the Center Directors of each IDDRC, NIH Project Scientists and any relevant external scientific and public members, as designated by NIH. The Steering Committee will be chaired and co-chaired by IDDRC Center Directors, who are elected by vote of the Steering Committee for staggered two-year terms. The Chair and Co-Chair will be responsible for conduct of regular conference calls. The Steering Committee will hold two face-to-face meetings at least annually, one in the Washington, DC area, and one hosted by one of the IDDRC sites. Each IDDRC and the public member will have one vote on the Steering Committee and the NIH Project Scientists, collectively, will have a single NIH vote.

Each full member will have one vote. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.

Dispute Resolution:

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

When multiple years are involved, awardees will be required to submit the 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.

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

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-710-0267
TTY 301-451-5936
Email: [email protected]

eRA Commons Help Desk (Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: [email protected]

Melissa A. Parisi, MD, PhD
Chief, Intellectual and Developmental Disabilities Branch
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6880
Email: [email protected]

Sherry Dupere, PhD
Chief, Scientific Review Branch
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-496-1485
Email: [email protected]

Bryan S. Clark, MBA
Chief, Grants Management Branch
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6975
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 Parts 74 and 92.