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

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

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

The purpose of this Funding Opportunity Announcement (FOA) is to seek applications for the Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Centers (IDDRCs). This Funding Opportunity Announcement (FOA) invites applications for research center grants 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 its dissemination, and that support IDD-related projects funded by other sources; and 2) at least one specific research project related to one of several focus themes identified as an area of research need in IDD. Funds for the majority of outside research projects using these core facilities come from independent sources including Federal, State, and private organizations.

For 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 had 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 prior round of IDDRC competition, the goal was to transition the IDDRC program into a functional network of collaborative research centers funded under the U54 Specialized Center--Cooperative Agreement mechanism. This new round of competitions will support IDDRCs through the P50 (Specialized Center) mechanism. This mechanism will allow the research community to continue to respond to emerging needs within the IDD field through a combination of core services and research project(s).

The goals of the IDDRC program 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 priorities 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.

The themes that arose from recent workshops and meetings sponsored by NICHD and other NIH conferences in addition to the priorities of the IDD form the basis for the focus themes that have been identified as areas of research need and that will inform the specific research project(s) proposed in response to this FOA.

NICHD 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 virtual network that may facilitate development of the infrastructure necessary for the conduct of larger research programs or clinical trials. The P50 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 the next 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 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 graduate students, postdoctoral researchers, 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. In addition, for the purposes of this FOA, it is essential that scientific personnel and institutional resources capable of providing a strong research base in the IDD field are available.

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 P50 Center 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, "outside," federally-funded, peer-reviewed research projects in addition to the research project(s) funded directly through this P50 award.
• 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 or cooperative agreement 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 IDDRCs is permitted and encouraged, provided that an appropriate cost-recovery mechanism is developed.
• Use of Core facilities by graduate students or postdoctoral researchers supported by Institutional National Research Service Awards (T32) or other fellowships or career development awards (such as F and K awards) is allowable and encouraged.

Administrative Core

The Administrative Core should provide for the integration and management of activities within the IDDRC. Each Center should form an External Advisory Committee (EAC) composed of at least five members, with scientific, clinical and patient advocate representation. 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 provide the leadership and communication needed to manage the multiple sites. Any educational elements should be organized and coordinated within the Administrative Core.

In addition, the Administrative Core will provide dissemination services in order to promulgate information and promote communication about the research supported by the Center to a diverse audience of other scientists, educators, policy makers, the government, and the public, including those with IDD conditions and their families. The Center should serve as a communication liaison between investigators conducting state-of-the-art research and the public, and where appropriate, the information should be structured so that it can effectively reach diverse populations, including non-English-speaking people and racial and ethnic minorities.

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;
• Provision of clinical navigator services to assist investigators with translational resources available at the Center;
• 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.

Applications must include at least one specific Research Project that has not been previously funded and addresses one or more of the focus themes identified as an area of research need. These are recognized as potentially exploratory, discovery-based, and/or high-risk projects, with the goal of yielding interpretable results that will either prove or disprove the proposed hypothesis.

Each Research Project must utilize at least two cores of the IDDRC, which may include the Administrative Core and/or the Clinical Translational Core. Primary funding must be through this P50 mechanism, but other sources of funding are allowed (federal grant, philanthropic, or foundational support). The project can address a broad array of intellectual disorders, including new, recently characterized, or under-researched areas such as comorbid mental health conditions in IDD. The focus areas are as follows, in no order of priority:

Comprehensive omics Approaches

Comprehensive -omics approaches (e.g., genomic, transcriptomic, epigenomic, proteomic, metabolomic) that will markedly increase our understanding of IDD conditions to improve diagnosis, management, 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, chromatin immunoprecipitation (ChIP), histone modification, or other epigenetic studies on individuals with a shared or related IDD diagnosis but variable manifestations (such as range of cognitive or behavioral 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;
• Single-cell transcriptomics on samples of differentiated human induced pluripotential stem cells (iPSC), brain organoids, or central nervous system tissue.

Development of Biomarkers or Assessment Measures in More than one IDD Condition

Development of a biomarker, assessment measure, or clinical intervention for more than one IDD condition or a group of related IDD conditions that share a common feature or metabolic or molecular pathway. Examples include, but are not limited to:

• Use of a human iPSC or brain organoid model to develop a biomarker or measure for a group of related conditions that demonstrates sensitivity to biologically-relevant perturbations to the system;
• Development of an assessment paradigm for an allelic series in an animal model for an IDD condition that exhibits a range of phenotypes;
• Development of an electrophysiological paradigm for two or more IDD conditions that share a common metabolic or molecular pathway;
• Creation of a clinical trial for a plausible target in two or more IDD conditions that reflects a shared etiology or molecular pathway.

Outcome Measures or Biomarkers 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 or biomarker for an animal model (e.g., mouse, rat, nonhuman primate) of an IDD disorder that reliably detects changes in cognitive function or behavioral response to a drug treatment;
• Development of a measure of cognitive or behavioral function (e.g., depression, psychotic ideation) in individuals with an IDD condition that is sensitive to an intervention;
• Development of a measure or biomarker that can be applied to more than one IDD conditions that share a common feature or metabolic or molecular pathway;
• Demonstration of changes in an existing measure or biomarker in individuals with an IDD condition in response to therapy.

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. A medication can be repurposed from its original indication, but any clinical trial must adhere to NIH Clinical Trial guidelines (https://grants.nih.gov/policy/clinical-trials.htm), with defined milestones and go/no-go decision points. 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 cognitive or behavioral measure;
• Use of a medication and behavioral treatment in combination for individuals with an IDD condition to demonstrate improved or synergistic 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.

Preventing and Mitigating the Impact of Exposures that Can Cause IDD

Exposures of many types medications, substances of abuse, infectious agents, environmental exposures, toxins increase the risk of developing IDD. Therefore, therapeutic agents that can prevent or mitigate the risk of IDD following such exposures have the potential for broad clinical and public health impact. Exposures of interest may occur in the pre-conceptional, prenatal, postnatal or childhood period, and may involve the broader family or community. Examples include, but are not limited to:

• A project that develops a therapy or treatment for an animal model subjected to an exposure associated with an IDD-related cognitive or behavioral phenotype;
• A project that proposes an intervention to reduce the risk of developing an IDD due to preterm birth;
• A project looking at factors that may mitigate the impact of a prenatal exposure, such as alcohol, opioid or other medication, other substance of abuse, cytomegalovirus, Zika virus, etc. on a child’s risk of IDD;
• Studies of a therapeutic intervention that may mitigate the impact of an environmental toxin (such as lead) that can lead to IDD.

Interventions and Management of Co-morbid Mental Health Conditions

Individuals with IDD experience behavioral symptoms and mental health conditions at considerably higher rates than the general population, including behavioral symptoms such as depression, aggression, or suicidal ideation or mental health conditions such as attention deficit hyperactivity disorder (ADHD), bipolar disorder, or psychotic disorders. These can be extremely challenging to manage in individuals with IDD due to the language, cognitive, and sensory impairments that often impede traditional strategies for evaluation and treatment. Many children and adults with IDD are diagnosed with behavioral or mental health conditions in the absence of assessment tools appropriate to IDD populations, and psychotropic medications are often administered to individuals with IDD, without an adequate understanding of their potential interactions and associated safety risks. Studies are encouraged that include individuals with IDD who are on multiple psychotropic medications in the study design. Priority will be given to novel interventions that go beyond traditional behavioral management of symptoms. Examples include, but are not limited to:

• Development of new tools or adaptation of existing tools that can be used in the management of behavioral symptoms or mental health conditions that identify and account for level of cognitive functioning in individuals with IDD;
• Studies of the safety and efficacy of commonly-used psychotropic medications in treating specific behavioral symptoms or mental health conditions in individuals with IDD;
• Studies to delineate variability in pharmacokinetics and pharmacodynamics of psychotropic medications in individuals with IDD;
• Studies that use pharmacogenomic strategies to select the safest and most efficacious psychotropic medications for use in individuals with IDD, which can then be clinically validated.

Innovative Technologies to Improve Assessments, Interventions, and Outcomes for Those with IDD

There has been an explosion of new technologies aimed at assessing and improving health, including wearable devices, communication aids, robotics and e-textiles. There have also been enormous advances in technologies that were not created for health-related purposes, but that have potential applicability to health assessments and interventions, including mobile device applications ( apps ) and social media platforms. Most of these technologies were originally developed for use in adults, particularly those with typical development, so there is a need for valid and reliable technological tools and adaptive devices for those with IDD. Examples include, but are not limited to:

• Development of validated eye tracking technologies to identify and monitor social gaze preferences in children with autism receiving interventions targeting their social interactions;
• Use of actimetry sensors to identify and monitor sleep behaviors or activity levels to measure biological indicators and response to interventions;
• Development of devices that monitor physiologic parameters (such as heart rate monitors, multi-channel EEGs, or instruments that measure metabolite levels) for digital phenotyping or to serve as a proxy measure for other outcomes of interest, such as anxiety;
• Validation of apps, devices, and social media platforms to aid communication in individuals with IDD and language impairments;
• Application of mobile technologies to deliver video- or computer-based interventions to individuals unable to travel to academic centers to participate in research or clinical programs.

The Center Director(s) (PD(s)/PI(s)) are responsible for developing and maintaining a Center environment that fosters traditional and novel approaches to multi-disciplinary research collaborations and educational activities.

As national resources for IDD research, the IDDRCs play leadership roles in the education of new investigators for the IDD research field and in educating the patient and lay communities regarding educational and research activities. Each center should establish and maintain a strong mentoring environment for predoctoral and postdoctoral investigators in IDD research, as well as new and early stage investigators. The center may include, as examples, education on manuscript writing and reviewing, grantsmanship, team science approaches and lab management, as well as the ethical conduct of research. Other features of the environment may include a seminar program, retreats for presentation of research, journal clubs, or other activities that contribute to the preparation and mentorship of new and junior investigators for careers in IDD research. Education and outreach activities for the lay public may include seminar series, newsletters, public presentations, town hall meetings, or other events to disseminate the goals and accomplishments of the center. Educational and dissemination activities should be organized within the Administrative Core.

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. For example, the commitment may take the form of faculty appointments and/or partial salary support for investigators, purchase of research equipment, and/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 outside research projects. However, all activities using IDDRC Center funds must be relevant to the mission of NICHD's IDDRC program.

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. NICHD encourages investigators within the Centers to apply for a variety of other grants, including clinical trials grants (e.g., R34, R01, and U01).

Recipients of IDDRC awards will become part of a national program in IDD research and will be expected to participate in IDDRC network activities, including monthly leadership calls, shared and coordinated activities and projects when appropriate, and an annual meeting of the IDDRC Leadership Committee (composed of IDDRC Directors, NIH program staff, and other relevant parties), that is held in either the Washington, DC area or rotates among the IDDRC sites.

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

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

Higher Education Institutions

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

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

o Hispanic-serving Institutions

o Historically Black Colleges and Universities (HBCUs)

o Tribally Controlled Colleges and Universities (TCCUs)

o Alaska Native and Native Hawaiian Serving Institutions

o Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

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

Other

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

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are not allowed.

Applicant Organizations

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

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

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

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

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

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

The PD(s)/PI(s) (known as the IDDRC Center Director) should be a scientist or science administrator who can provide effective scientific and administrative leadership. The PD(s)/PI(s) of the IDDRC should be a recognized scientific leader(s) experienced in the field of IDD research and must be able to coordinate, integrate, and provide guidance in the establishment of research programs. The Director(s) will be responsible for the organization and operation of the IDDRC and for communication with the NICHD on scientific and operational matters. The Director(s) should be able to integrate and synthesize the proposed research, and, thereby, serve as an example to other investigators. The Center Director(s) should have a minimum total combined commitment of 2.4 person-months to the IDDRC. The Center Director(s) may also serve as the Director(s) on the Research Project component or a Core of the IDDRC. The Center Director(s) cannot serve as a Project PD/PI on another active IDDRC award.

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

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

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

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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

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

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

The letter of intent should be sent to:

Melissa A. Parisi, MD, PhD
Telephone: 301-435-6880
Email: [email protected]

Available Component Types	Research Strategy/Program Plan Page Limits
Overall	12 pages
Admin Core (use for Administrative Core)	12 pages
Clin Transl Core (use for Clinical Translational Core)	12 pages
Project (use for Research Projects)	12 pages
Core (use for Other Cores)	12 pages

Additional page limits described in the SF424 Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the SF424 (R&R) Application Guide, and should be used for preparing a multi-component application.

The application should consist of the following components:

• Overall: required
• Admin Core: required; 1 minimum, 1 maximum
• Clinical Translational Core: required; 1 minimum, 1 maximum
• Research Project(s): required; 1 minimum, 2 maximum
• Other Core(s): required, 1 minimum, 4 maximum

When preparing your application, use Component Type Overall .

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

Complete entire form.

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

Follow standard instructions.

Facilities and Other Resources: Describe the institutional support and commitment to the IDDRC. 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. 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.

Other Attachments: Applicants must provide a section on outside research projects with other sources of funding that are proposed for core usage. Name the attachment "Research Projects.pdf". This will be the name used for the bookmark accessible to reviewers. Projects should be listed in alphabetical order by PD/PI surname. Research Projects must be currently funded or pending award (status = to be paid in eRA Commons or IMPACII).

For each outside funded research project proposed to access the IDDRC Research Center, provide the following information. Do not exceed one page per project; applications exceeding this limit will not be reviewed:

• PD/PI and level of effort (person-months)
• Title of project
• Source of support (including grant number and project designation, 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 the center mission and IDD research
• Brief justification for use of IDDRC core resources.

Enter primary site only.

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

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

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

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

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

Specific Aims: Include Specific Aims for the overall Center.

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 Project relate to that strategy. Explain how the different aspects of the organization, including key personnel, will interact, why they are essential to accomplishing the overall goal of the research, and how combined resources create a Center that is more than the sum of its parts. Include all necessary tables, graphs, figures, diagrams and charts in this section. In addition, provide the following information:

• Purpose and Objectives of the Center: Discuss the philosophy and objectives of the IDDRC and general plans for the proposed grant period. This section 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 authority of the Center Director(s), the dissemination and communication plan, the use of internal user or Executive Committees and External Advisory 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 not previously cited: Describe any other experience the applicants have had 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) Educational activities for graduate students, postdoctoral fellows, junior investigators, or members of the lay public that contributed to the center/program/core environment.

3) Investigators attracted to the field by the center/program and its core facilities, including trainees, new investigators and visiting investigators;

4) Impact of the center/program/core on the institution and community, including documentation of past successes in advancing IDD knowledge and research;

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) Other accomplishments.

Letters of Support: Provide letters of support from institutional officials and letters of assurance/agreement for any collaborative and cooperative endeavors or subcontracts. 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: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modifications:

All applications, regardless of the amount of direct costs requested for any one year, should include a Data Sharing Plan. The Data Sharing Plan will be considered during peer review and by program staff as award decisions are being made as appropriate and consistent with achieving the goals of the program. It is expected that the results of NICHD-funded research will be shared with the wider scientific community in a timely manner.

Awardees are strongly encouraged to deposit large-scale, human genetic data in the database for Genotype and Phenotype dbGaP (https://www.ncbi.nlm.nih.gov/gap) or other NIH-supported Data Commons. For autism-related data, awardees are required to deposit their data in the NIMH Data Archive (https://ndar.nih.gov/). Projects that propose to recruit subjects with Down syndrome are encouraged to promote enrollment of research subjects in the Down syndrome patient registry supported by NIH, DS-Connect (https://DSConnect.nih.gov/). For other data and biospecimens from human genetic or non-genetic studies, awardees are encouraged to use the NICHD Data and Specimen Hub DASH (https://dash.nichd.nih.gov/) or other equivalent broad-sharing data and/or biospecimen repositories.

The following resource describing Common Data Elements may be helpful during the planning phases of a project when considering ways to optimize data collection in order to facilitate broad data sharing: https://www.nlm.nih.gov/cde/.

Appendix:

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

PHS Human Subjects and Clinical Trials Information (Overall)

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

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).

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

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

When preparing your application, use Component Type Admin Core.

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

Complete only the following fields:

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

Enter Human Embryonic Stem Cells in each relevant component.

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

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

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

List all performance sites that apply to the specific component.

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

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

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

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 equipment purchase or alterations and renovations. For additional years of support requested, justify any significant increases in any category over the first 12-month budget period. No recurring annual escalations in costs are allowed.

Allowable costs for the Administrative Core may include:

• Salaries for the Center Director(s) (PD(s)/PI(s)) specifying a minimum total combined commitment of 2.4 person-months (20 percent) effort to the IDDRC;
• Salaries and support for a limited number of administrative and clerical personnel, such as a 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 and communication of research results to investigators, the scientific community and lay public;
• Costs related to seminars or meetings designed to promote interdisciplinary interaction, education, or Center cohesiveness;
• Costs related to External Advisory Committee meetings;
• Costs of minor renovation for Cores may be included within the IDDRC budget; NICHD provides no funds for new construction;
• Travel of Center investigators to other IDDRCs or other collaborative sites to exchange scientific ideas, to plan multi-Center research projects, or to learn specialized techniques; and
• Travel for 2-3 IDDRC staff to annual meeting of the IDDRC Steering Committee (composed of IDDRC Directors, NIH program staff, and other relevant parties), to confer with other NICHD IDDRC Directors and program staff and promote scientific interaction among the Centers. This is held in either the Washington, DC area or rotates among the IDDRC sites.

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

Specific Aims: Include Specific Aims for the Administrative Core.

Research Strategy: The Administrative Core will be responsible for the management and administration of the overall IDDRC. This section of the application should describe the strategies and processes that will be used to manage the Center and achieve its goals. This Core, led by the Center Director(s), 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; the dissemination and communication plan; 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(s) should participate in monthly leadership calls, develop shared and coordinated activities and projects when appropriate, help to refine and standardize operating procedures among the Centers, and attend an annual meeting 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:

• Objectives of the Core
• Organizational Chart
• Staffing: Description of administrative/business management staff and oversight mechanisms by the Center Director (PD/PI), Center Co-Director (if applicable), and a local Executive Committee.
• Services Provided: Description of current and projected services to other Core and Research Projects, as well as the process for prioritizing requests for use of Core facilities by the various research projects. If this Core already exists, include a description of past services provided by the Administrative Core personnel, new technologies developed, changes in protocols or Core administration, dissemination and community activities, and other significant accomplishments. The Administrative Core should establish and maintain a website to communicate the Center's mission and the availability of Core services. When multiple geographic sites are involved in the IDDRC, the Administrative Core should provide the leadership and communication needed to manage the multiple sites.
• Education: Include plans to establish and maintain an educational 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 expected. The educational activities for the center may include, as examples: manuscript writing and reviewing, grantsmanship, team science approaches and lab management, as well as the ethical conduct of research. Other features of the educational environment may include a seminar program, retreats for presentation of research, journal clubs, or other activities that contribute to the preparation and/or mentorship of new faculty members or junior investigators for careers in IDD research.
• Dissemination and communication Plan: Include a plan to promote communication about the research supported by the Center to a diverse audience of other scientists, educators, policy makers, the government, and the public, including those with IDD conditions and their families. The Center should serve as a communication liaison between investigators conducting state-of-the-art research and the public, and where appropriate, the information should be structured so that it can effectively reach diverse populations, including non-English-speaking people and racial and ethnic minorities. Education and outreach activities for the lay public may include websites, seminar series, newsletters, public presentations, town hall meetings, or other events to disseminate the goals and accomplishments of the center.
• Executive Committee and External Advisory Committee: The Administrative Core should establish a local Executive Committee, composed of members of the Center, and an External Advisory Committee, composed of members outside the Center. Describe the general composition of the EAC, but do not name specific individuals in the application unless the EAC has already been constituted. Describe how the External Advisory Committee will contribute to oversight of the Core facilities and specific research project(s), as well as the educational 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.
• IDDRC Steering Committee: The Center Director(s) is expected to participate in a steering committee of the entire IDDRC network composed of IDDRC Directors, NIH program staff, and other relevant parties. This committee will hold monthly conference calls and at least 1 annual IDDRC face-to-face network meeting.
• Cost effectiveness and plans for quality control: Describe any cost structures such as fee-for-service, in-kind, charge-back systems, or other methods used to establish cost effectiveness of the Core services. Describe quality controls systems in place to measure the accuracy, reproducibility, and reliability of equipment, assays or services in order to ensure the quality and value of the Core services broadly and the center as a whole.
• User satisfaction surveys: Describe frequency and content of user satisfaction surveys, evaluation of cost effectiveness, and other means to assess quality and value of services to investigators.

Letters of Support: Include any letters of support or collaboration specific to this Core.

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

All applications, regardless of the amount of direct costs requested for any one year, should include a Data Sharing Plan. The Data Sharing Plan will be considered during peer review and by program staff as award decisions are being made as appropriate and consistent with achieving the goals of the program. It is expected that the results of NICHD-funded research will be shared with the wider scientific community in a timely manner.

Awardees are strongly encouraged to deposit large-scale, human genetic data in the database for Genotype and Phenotype dbGaP (https://www.ncbi.nlm.nih.gov/gap) or other NIH-supported Data Commons. For autism-related data, awardees are required to deposit their data in the NIMH Data Archive (https://ndar.nih.gov/). Projects that propose to recruit subjects with Down syndrome are encouraged to promote enrollment of research subjects in the Down syndrome patient registry supported by NIH, DS-Connect (https://DSConnect.nih.gov/). For other data and biospecimens from human genetic or non-genetic studies, awardees are encouraged to use the NICHD Data and Specimen Hub DASH (https://dash.nichd.nih.gov/) or other equivalent broad-sharing data and/or biospecimen repositories.

The following resource describing Common Data Elements may be helpful during the planning phases of a project when considering ways to optimize data collection in order to facilitate broad data sharing: https://www.nlm.nih.gov/cde/.

Appendix:

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

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

When preparing your application, use Component Type Clin Transl Core .

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

SF424 (R&R) Cover (Clinical Translational Core)

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Clinical Translational Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Clinical Translational Core)

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

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

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

Project /Performance Site Location(s) (Clinical Translational Core)

List all performance sites that apply to the specific component.

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

Research & Related Senior/Key Person Profile (Clinical Translational Core)

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

Budget (Clinical Translational Core)

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

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. No recurring annual escalations in costs are allowed.

Allowable costs for the Clinical Translational Core may include:

• Salaries and support for Core Director(s)/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.

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

PHS 398 Research Plan (Clinical Translational Core)

Specific Aims: Include Specific Aims for the Clinical Translational Core.

Research Strategy: The Clinical Translational Core will be critical for supporting research that allows application of basic science discoveries to the clinical setting, treatment development, and/or clinical trials. This section of the application should describe the strategies and processes that will be used to promote the clinical and translational goals of the Center. This Core, led by the Core Director(s), will provide oversight for translational services provided by the Core. The Research Strategy should describe the planning and coordination of translational research activities; the integration of cross-disciplinary translational research supports; and the maintenance of ongoing communication between Core staff and investigators. The application should provide the following information about the Clinical Translational Core:

• Objective of the Core
• Staffing: Brief description of scientific, technical, and support staff functions.
• Services Provided: Description of current and projected services available to Research Project(s) of the Center and Projects Proposed for Core Use, as applicable, as well as the process for prioritizing requests for use of Core facilities by the various research projects. If this Core already exists, include a description of past services provided, new technologies developed, changes in protocols or Core administration, and other significant accomplishments.
• Administration: Description of overall management of the Core.
• Justification: Description of services provided and their bearing on productivity and quality. Describe how the service(s) provided 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: For Research Projects proposed to utilize the Core, provide a list or table of projected usage of Core services (e.g., assays performed, animals supplied, etc.). Sort the list/table in alphabetical order by last name of PD/PI, and include the grant number for each relevant project. Compile a summary of usage data across all projects for each category of services.
• Cost effectiveness and plans for quality control: Describe any cost structures such as fee-for-service, in-kind, charge-back systems, or other methods used to establish cost effectiveness of the Core services. Describe quality controls systems in place to measure the accuracy, reproducibility, and reliability of equipment, assays or services, including service contracts, maintenance schedules, and technical monitoring of services provided in order to ensure the quality and value of the Core services.
• User satisfaction surveys: Describe frequency and content of user satisfaction surveys, evaluation of cost effectiveness, and other means to assess quality and value of services to investigators.

Letters of Support: Include any letters of support or collaboration specific to this Core.

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

All applications, regardless of the amount of direct costs requested for any one year, should include a Data Sharing Plan. The Data Sharing Plan will be considered during peer review and by program staff as award decisions are being made as appropriate and consistent with achieving the goals of the program. It is expected that the results of NICHD-funded research will be shared with the wider scientific community in a timely manner.

Awardees are strongly encouraged to deposit large-scale, human genetic data in the database for Genotype and Phenotype dbGaP (https://www.ncbi.nlm.nih.gov/gap) or other NIH-supported Data Commons. For autism-related data, awardees are required to deposit their data in the NIMH Data Archive (https://ndar.nih.gov/). Projects that propose to recruit subjects with Down syndrome are encouraged to promote enrollment of research subjects in the Down syndrome patient registry supported by NIH, DS-Connect (https://DSConnect.nih.gov/). For other data and biospecimens from human genetic or non-genetic studies, awardees are encouraged to use the NICHD Data and Specimen Hub DASH (https://dash.nichd.nih.gov/) or other equivalent broad-sharing data and/or biospecimen repositories.

The following resource describing Common Data Elements may be helpful during the planning phases of a project when considering ways to optimize data collection in order to facilitate broad data sharing: https://www.nlm.nih.gov/cde/.

Appendix:

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

PHS Human Subjects and Clinical Trials Information (Clinical Translational Core)

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

When preparing your application, use Component Type Project.

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

SF424 (R&R) Cover (Research Project)

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Research Project)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Research Project)

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

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

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

Project /Performance Site Location(s) (Research Project)

List all performance sites that apply to the specific component.

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

Research & Related Senior/Key Person Profile (Research Project)

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

Budget (Research Project)

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

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

PHS 398 Research Plan (Research Project)

Specific Aims: Include Specific Aims for the Research Project, clearly stating the overall objective of the project and indicate which of the focus themes it addresses, as well as its relevance to the focus theme chosen.

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. NICHD urges applicants to the IDDRC program to consider the rationale for the chosen animal model(s) and endpoints, adequacy of controls, route and timing of therapeutic dosing, justification of sample size, statistical methods, blinding methods, strategies for randomization, and robustness and reproducibility of results when describing preclinical studies and designing the specific Research Project. Examples of the critical elements of a well-designed study are described in this site: https://www.nih.gov/research-training/rigor-reproducibility. The overall NIH policy on enhancing reproducibility through rigor and transparency is described here: http://www.ninds.nih.gov/funding/transparency_in_reporting_guidance.pdf ).

A minimum of two Cores (which may include the Administrative and/or Clinical Translational Core) of the Center must be utilized by each Research Project and should be identified.

Organize the Research Strategy as described in the SF424 Application Guide and using the instructions provided below. Start each section with the appropriate section heading Significance, Innovation, Approach. In the application, 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. Because the focus themes represent difficult, challenging scientific questions that may require overcoming critical barriers in the field, NICHD recognizes that applications may include Research Projects that are exploratory, discovery-based and/or higher risk in nature. For example, if proposing a novel hypothesis, the investigators should be able to prove or disprove that hypothesis by the end of the funding period; if proposing an exceptionally innovative methodology or technology, the investigators should be able to develop it by the end of the funding period or demonstrate conclusively that the approach is not feasible. If external sources of funding are available for the project, these must be clearly stated, including source, amount, and duration of support.

Letters of Support: Include any letters of support or collaboration specific to this Research Project.

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

All applications, regardless of the amount of direct costs requested for any one year, should include a Data Sharing Plan. The Data Sharing Plan will be considered during peer review and by program staff as award decisions are being made as appropriate and consistent with achieving the goals of the program. It is expected that the results of NICHD-funded research will be shared with the wider scientific community in a timely manner.

Awardees are strongly encouraged to deposit large-scale, human genetic data in the database for Genotype and Phenotype dbGaP (https://www.ncbi.nlm.nih.gov/gap) or other NIH-supported Data Commons. For other data and biospecimens from human genetic or non-genetic studies, awardees are encouraged to use the NICHD Data and Specimen Hub DASH (https://dash.nichd.nih.gov/) or other equivalent broad-sharing data and/or biospecimen repositories.

The following resource describing Common Data Elements may be helpful during the planning phases of a project when considering ways to optimize data collection in order to facilitate broad data sharing: https://www.nlm.nih.gov/cde/.

The following modifications apply to any specific Research Project responding to one of the focus themes that addresses autism research:

• The NIMH Data Archive (NDA; formerly the 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.
• All autism-related projects are required to contribute data to NDA, which will function as a data repository. NDA 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 NDA, please visit https://ndar.nih.gov/.

The following modifications apply to any specific Research Project that addresses Down syndrome research:

NIH intends to maximize the availability of publications and the sharing of underlying data and biospecimens for Down syndrome-related projects. Applicants are encouraged to develop a Public Access and Data Sharing and Management Plan that (1) describes their proposed process for making resulting publications and biospecimens, and to the extent possible, the underlying primary data immediately and broadly available to the public; (2) if applicable, provides a justification to NIH if such sharing is not possible. Underlying primary data should be made as widely and freely available as possible while safeguarding the privacy of participants and protecting confidential and proprietary data. In addition, projects that propose to recruit subjects with Down syndrome are encouraged to promote enrollment of research subjects in the Down syndrome patient registry supported by NIH, DS-Connect (https://DSConnect.nih.gov/).

Appendix:

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

PHS Human Subjects and Clinical Trials Information (Research Project)

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

When preparing your application, use Component Type [Name of] Core.

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

SF424 (R&R) Cover (Other Core(s))

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Other Core(s))

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Other Core(s))

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

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

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

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

List all performance sites that apply to the specific component.

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

Research & Related Senior/Key Person Profile (Other Core(s))

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

Budget (Other Core(s))

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

For any Other Cores, 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. No recurring annual escalations in costs are allowed.

Allowable costs for Other Core(s) may include:

• Salaries and support for Core Director(s)/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.

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

PHS 398 Research Plan (Other Core(s))

Specific Aims: Include Specific Aims for the Core.

Research Strategy: Provide the following information:

• Objective of the Core
• Staffing: Brief description of scientific, technical, and support staff functions.
• Services Provided: Description of current and projected services to Research Projects and Projects Proposed for Core Use, as applicable, as well as the process for prioritizing requests for use of Core facilities by the various research projects. If this Core already exists, include a description of past services provided, new technologies developed, changes in protocols or Core administration, and other significant accomplishments.
• Administration: Description of overall management of the Core.
• Justification: Description of services provided and their bearing on productivity and quality. Explain how this Core will advance the diagnosis, prevention, treatment, and amelioration of IDD in individuals with these conditions.
• Utilization of Core: For Research Projects proposed to utilize the Core, provide a list or table of projected usage of Core services (e.g., assays performed, animals supplied, etc.). Sort the list/table in alphabetical order by last name of PD/PI, and include the grant number for each relevant project. Compile a summary of usage data across all projects for each category of services.
• Cost effectiveness and plans for quality control: Describe any cost structures such as fee-for-service, in-kind, charge-back systems, or other methods used to establish cost effectiveness of the Core services. Describe quality controls systems in place to measure the accuracy, reproducibility, and reliability of equipment, assays or services, including service contracts, maintenance schedules, and technical monitoring of services provided in order to ensure the quality and value of the Core services broadly and the center as a whole.
• User satisfaction surveys: Describe frequency and content of user satisfaction surveys, evaluation of cost effectiveness, and other means to assess quality and value of services to investigators.

Letters of Support: Include any letters of support or collaboration specific to this Core.

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

All applications, regardless of the amount of direct costs requested for any one year, should include a Data Sharing Plan. The Data Sharing Plan will be considered during peer review and by program staff as award decisions are being made as appropriate and consistent with achieving the goals of the program. It is expected that the results of NICHD-funded research will be shared with the wider scientific community in a timely manner.

Awardees are strongly encouraged to deposit large-scale, human genetic data in the database for Genotype and Phenotype dbGaP (https://www.ncbi.nlm.nih.gov/gap) or other NIH-supported Data Commons. For autism-related data, awardees are required to deposit their data in the NIMH Data Archive (https://ndar.nih.gov/). Projects that propose to recruit subjects with Down syndrome are encouraged to promote enrollment of research subjects in the Down syndrome patient registry supported by NIH, DS-Connect (https://DSConnect.nih.gov/). For other data and biospecimens from human genetic or non-genetic studies, awardees are encouraged to use the NICHD Data and Specimen Hub DASH (https://dash.nichd.nih.gov/) or other equivalent broad-sharing data and/or biospecimen repositories.

The following resource describing Common Data Elements may be helpful during the planning phases of a project when considering ways to optimize data collection in order to facilitate broad data sharing: https://www.nlm.nih.gov/cde/.

Appendix:

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

PHS Human Subjects and Clinical Trials Information (Other Core(s))

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov.

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

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

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) and component Director(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

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

See more tips for avoiding common errors.

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

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

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

For this particular announcement, the overall score for applications will emphasize the following:

• Overall effectiveness and adequacy of Core resources and facilities;
• Scientific merit and potential to impact the IDD field of the specific Research Project(s) responding to one of the focus themes;
• Scientific merit and relevance to IDD of the research projects proposed for Core usage;
• Ability of the Clinical Translational Core to successfully promote treatment development for IDD;
• Qualifications of the Center Director(s);
• Quality of the plans for management and oversight of the Center;
• Institutional commitment;
• Quality of the plan for dissemination and communication of findings to its many constituents;
• Accomplishments of the Center if it already exists; and
• Synergy among the components of the Center.

The review will evaluate the potential for the Center as a whole to have a significant impact on the field during the terms of the award, weighing the balance of more conventional approaches with highly innovative components or projects in which success is not guaranteed. 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.

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

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

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

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

Specific to this FOA: Does the program, including the Clinical Translational Core, have the potential to advance treatment development for IDD? Does the specific Research Project proposed demonstrate synergy with the Center's goals, utilize the Center's resources appropriately, and have potential to make advances in its area of focus? Do the research projects proposed for Core usage have scientific merit and relevance to IDD and to the Center's mission and goals?

In addition, for applications involving clinical trials

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

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

Specific to this FOA: Does the Center Director(s) 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?

In addition, for applications involving clinical trials

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

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

Specific to this FOA: Are the Core services provided cutting-edge or state-of-the-art? If the Core services are standard but fulfilling a critical need, are the projects accessing those services innovative and/or likely to advance the field?

In addition, for applications involving clinical trials

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

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

If the Center involves human subjects and/or NIH-defined clinical research, are the plans to address:

1) the protection of human subjects from research risks, and

2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Specific to this FOA: 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 centers, is there a track record of success in advancing progress in IDD-related research? Is the Center organized to support activities, projects, or clinical trials across the virtual IDDRC network?

In addition, for applications involving clinical trials

Does the application adequately address the following, if applicable

Study Design

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

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

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

Data Management and Statistical Analysis

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

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

Specific to this FOA: 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 to meet the needs of the Center? Is the institutional commitment to the requirements of the program adequate? Do the research projects proposed for core usage appropriately access core services?

In addition, for applications involving clinical trials

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

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

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

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

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

Integration of the Overall 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 reviewers 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 Cores and specific Research Project reflect a cohesive research program?
• Is value added by having the proposed Cores and specific Research Project comprise a Center that allows the Center to leverage additional resources that would not have been possible without an integrated Center structure?
• Are the projects proposed for Core usage relevant to IDD and well integrated with the Center Overall?
• Is the Center multidisciplinary in scope and do the breadth and overall quality of the Center's program, the Core Components, the specific Research Project, and projects proposed for Core usage have the ability to catalyze significant research advances in IDD?
• Is the dissemination plan integrated with the scientific goals of the Center and likely to fulfill the purpose of facilitating communication among stakeholders, including scientists, educators, the public, policy makers, and those with IDD and their families?

Study Timeline

Specific to applications involving clinical trials

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

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

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

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

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

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

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

Not Applicable

Not Applicable

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.

Not applicable

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

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

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

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

Review Criteria for Core Components

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.

Administrative Core

Reviewers will evaluate the following:

• Core Director’s experience in research administration;
• Appropriateness of administrative structures and day-to-day management of the program;
• Decision-making process within the proposed center for the evaluation of research productivity, allocation of funds, and management of resources;
• Process for prioritizing use of Core facilities by the various research projects;
• Process for evaluating research projects and investigators for membership in the Center and access to the Cores;
• Mechanisms proposed for regular communication and coordination among investigators in the program;
• Plan for program evaluation, including the use of an internal Executive Committee and External Advisory Committee; and
• Plan for dissemination of research findings to a broad spectrum of constituents, and where appropriate, a strategy for communicating the information to reach diverse populations, including non-English-speaking people and racial and ethnic minorities.

Clinical Translational Core

Reviewers will evaluate the following:

• Experience of the Core Director in directing translational science;
• Likelihood that the service(s) provided will support translational science in IDD;
• Promotion of projects that will lead to treatment development and/or clinical trials;
• Responsiveness of the Core to Human Subjects issues that may arise.
• Cost effectiveness and quality control of the Core.

Other Core(s)

Reviewers will evaluate the following:

• Qualifications, experience, and commitment of the Core Director(s) and other Core personnel;
• Quality of the services provided;
• Cost effectiveness and quality control of the Core;
• If Core already exists, the effectiveness and relevance of provided services and development of new technologies or other significant advances;
• Utility of the Core to the program.

Reviewers will assign an impact score based on the likelihood of success for each specific Research Project responding to one of the focus themes. Since the focus themes represent difficult, challenging scientific questions that may require overcoming critical barriers in the field, NICHD recognizes that applications may include Research Projects that are exploratory, discovery-based and/or higher risk in nature. In evaluating higher risk components or exploratory projects with limited preliminary data, the reviewers will weigh the potential to achieve transformative, paradigm-shifting advances against the risks. The reviewers will evaluate the likelihood that interpretable results will be obtained from exploratory or high- risk studies. For example, if proposing a novel hypothesis, the investigators should be able to prove or disprove that hypothesis by the end of the funding period; if proposing an exceptionally innovative methodology or technology, the investigators should be able to develop it by the end of the funding period or demonstrate conclusively that the approach is not feasible.

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

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

Significance

Does the Research Project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the Research Project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? Will the Center structure facilitate the Research Project's ability to make substantive advances in at least one of the focus themes listed in Section I? If high-risk or exploratory, does the Research Project have the potential to achieve transformative, paradigm-shifting advances in the field?

Investigator(s)

Are the Research Project Director(s), collaborators, and other researchers well suited to the Research Project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the Research 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 Project? Have investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the Research Project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Is adequate rigor incorporated into study design, analysis, interpretation, and reporting? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects? If the Research Project is high-risk or exploratory, will interpretable results be obtained?

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

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

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following 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 Research Project, 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) Genomic Data Sharing Plan.

Authentication of Key Biological and/or Chemical Resources

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

Budget and Period of Support

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

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

As part of the scientific peer review, all applications:

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

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

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National 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. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

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

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

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

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

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

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain applicable clinical trials on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

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

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

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

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

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

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

Cooperative Agreement Terms and Conditions of Award

Not Applicable

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

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

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

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

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

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

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

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

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

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

Sherry Dupere, PhD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-496-3415
Email: [email protected]

Bryan Clark, MBA
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 Part 75.