Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Institute of Mental Health (NIMH)
Funding Opportunity Title	National Cooperative Reprogrammed Cell Research Groups (NCRCRG) to Study Mental Illness (U19)
Activity Code	U19 Research Program Cooperative Agreements
Announcement Type	New
Related Notices	June 3, 2014 - Notice NOT-14-074 supersedes instructions in Section III.3 regarding applications that are essentially the same. May 30, 2013 (NOT-OD-13-074) - NIH to Require Use of Updated Electronic Application Forms for Due Dates on or after September 25, 2013. Forms-C applications are required for due dates on or after September 25, 2013.
Funding Opportunity Announcement (FOA) Number	PAR-13-225
Companion Funding Opportunity	Not Applicable
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.242
Funding Opportunity Purpose	The purpose of the National Cooperative Reprogrammed Cell Research Groups (NCRCRG) program is to create multidisciplinary research groups, in partnership with academia and industry, to use patient-derived reprogrammed cells to develop validated platforms for identifying novel targets and developing new therapeutics or diagnostic tools to reduce the burden of mental illness. The collaborations will be pre-competitive, meaning that they lie at the interface between basic academic research and proprietary industrial research and involve cooperation between groups that might otherwise be competitors, with a focus on optimizing tools and measures needed for successful translational research. The Funding Opportunity Announcement (FOA) encourages applications to further develop promising cellular differentiation/characterization protocols and/or disease-relevant assays using patient-derived reprogrammed cells (e.g., induced pluripotent stem cells or iPSCs, induced neuronal cells or iNCs). Critical features of these applications should be (1) a strong emphasis on developing methodology that is robust and replicable across several performance sites, and (2) cross-paradigm validation to yield predictive value for pathophysiology.

Posted Date	May 8, 2013
Open Date (Earliest Submission Date)	August 25, 2013
Letter of Intent Due Date(s)	30 days before the application due date.
Application Due Date(s)	Standard dates apply, by 5:00 PM local time of applicant organization.
AIDS Application Due Date(s)	Not Applicable
Scientific Merit Review	Standard dates apply
Advisory Council Review	Standard dates apply
Earliest Start Date	Standard dates apply
Expiration Date	January 8, 2016
Due Dates for E.O. 12372	Not Applicable

NIH’s new Application Submission System & Interface for Submission Tracking (ASSIST) is available for the electronic preparation and submission of multi-project applications through Grants.gov to NIH. Applications to this FOA must be submitted electronically; paper applications will not be accepted. ASSIST replaces the Grants.gov downloadable forms currently used with most NIH opportunities and provides many features to enable electronic multi-project application submission and improve data quality, including: pre-population of organization and PD/PI data, pre-submission validation of many agency business rules and the generation of data summaries in the application image used for review.

Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts) and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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 National Institute of Mental Health (NIMH) seeks to facilitate the use of patient-derived reprogrammed cells (e.g., induced pluripotent stem cells or iPSCs, induced neuronal cells or iNCs) to study the molecular and cellular basis of mental illness, to identify potential targets for therapeutic intervention and to develop new diagnostic tools or treatments to reduce the burden of mental illness among the public.

Increasing efforts are being directed toward using iPSCs and iNCs to study molecular and cellular abnormalities underlying mental illness, including schizophrenia, mood disorders, autism spectrum disorders, attention deficit hyperactivity disorder and anxiety disorders. These technologies utilize (epi)genetic manipulation of adult somatic cells that reprograms them to stem cell or alternative cell fates, thereby generating an individualized experimental paradigm to study a patient’s disorder. While the strategic goal is to use these cells for basic biological discovery, target identification and screening for new candidate drugs, these studies are subject to similar needs and pitfalls as genetic or clinical studies. These include the need for sufficiently powered sample sizes, cost reduction, quality control, standardization, transparent study design and greater experimental rigor to facilitate replication, and a fast-fail process to eliminate unproductive leads. These and other issues received in-depth attention at an April 2012 reprogrammed cell workshop convened by NIMH and the Foundation for the National Institutes of Health (FNIH) [Using Stem Cells for Biological and Therapeutics Discovery in Mental Illness; Panchision, D.M. (2013) Stem Cells Translational Medicine, 2(3):217-22]

To address research needs identified from the workshop and a recent Request for Information (NOT-MH-12-034), NIMH is establishing a consortium of National Cooperative Reprogrammed Cell Research Groups (NCRCRG) to bridge the gap between basic science and drug development, combining the unique skills of academic and industry researchers to devise and validate cell reprogramming-based assays that are highly replicable and predictive of mental illness pathophysiology.

This Funding Opportunity Announcement (FOA) encourages applications for pre-competitive collaborations between academic and industry partners to utilize promising proof-of-concept cellular differentiation/characterization protocols and/or disease-relevant assays using patient-derived reprogrammed cells (e.g., iPSCs or iNCs) and further develop/validate these for the study of mental illness. The collaborations will be pre-competitive, meaning that they lie at the interface between basic academic research and proprietary industrial research and involve cooperation between groups that might otherwise be competitors, with a focus on optimizing tools and measures needed for successful translational research [e.g., see discussions by Woodcock (2010) Clin Pharmacol & Ther, 87(5):521 3; and Vargas et al., (2010) Clin Pharmacol & Ther, 87(5):527 9]. Critical features of these applications should be (1) a strong emphasis on developing methodology that is robust and replicable across several performance sites, and (2) cross-paradigm validation to yield predictive value for pathophysiology. These features should address the need for rapid dissemination of new techniques/data, sufficiently powered sample sizes, unit cost reduction of cellular reagents/assays, standardization to improve replication and/or a fast-fail process to eliminate false leads. Since the design and conduct of such studies will necessitate several areas of expertise, applicants are encouraged to include multiple Project Director/Principal Investigators (PDs/PIs) on the application.

Note that this FOA is designed for academic-industry collaborations using multi-pronged, validation- and replication-intensive designs to expand upon promising basic reprogrammed cell research. Applications from strictly academic groups to use cell reprogramming for foundational studies of patient-derived cells should instead be submitted to PAR-11-299 or PAR-11-300. Applications with a narrowly defined focus on developing novel, robust and scalable in vitro analytical platforms for high-throughput or high content analysis of neuronal and/or glial function should be submitted to PAR-11-319. Applications to use well-validated platforms for drug discovery, transitioning to clinical trial, should be submitted to PAR-13-086 or PAR-13-087. This FOA does not support commercial production.

Academic-Industrial Partnership:

• Co-participation of academic and industrial scientists is expected from year one of an NCRCRG (herein referred to as a "Group"). Each application must include an Overall Plan along with individual Research Project Plans that reflect an academic-industrial partnership that is either already ongoing or will be active at the time of award. Partnerships must include at least two academic and two industrial organizations large or small among their numbers, although greater numbers of academic and industrial partners can be included and are encouraged. All the partnering organizations are expected to collaborate on the proposed goals in a manner that would enable the entire joint effort to be administered in a unified manner. Each partner organization should have sufficient scientific involvement, and at least one participating investigator with qualifications to lead and/or share authority and responsibility for the overall effort. Groups should exploit the unique advantages and capabilities that public-private collaborations provide, such as tailoring experimental design to the availability of uncommon/valuable resources or translational expertise.
• While there is no cost sharing requirement included in this FOA, the NCRCRG program strongly encourages applicant and collaborating organizations, including private partners (e.g., biotechnology, pharmaceutical, or other private organizations), to contribute resources to this effort. An indication of institutional support from the applicant and its collaborators indicates a greater potential for success and sustainability of the Group. Examples of such support would include (but are not limited to): institution-funded staff time and effort, donated equipment and space, providing free and open access to tools, assays, reagents, databases, workflow processes, or other resource investments. Specific and detailed descriptions of these contributions, as well as assurances that their organization and any collaborators are committed to providing these resources to the Group effort, should be included in the Letters of Support section of each respective Project or Core component. Pharmaceutical, biotechnology or other private partners should include and describe essential personnel who have authority within the organization to allocate resources to ensure successful completion of the proposed research discovery and development efforts.

NCRCRG Governance:

• The outlines of the governance structure are described in the Cooperative Agreement Terms and Conditions of Award. Each NCRCRG ("Group") will be encompassed in one application. If two or more NCRCRG applications are funded, the Groups will be federated into a "Consortium". The application Research Strategy (Overall) should include a section on Governance and Organizational Structure that describes the overall organization, major tasks each partner will complete, and benefits each brings to this alliance to enhance prospects for completing specific aims. This section will also describe shared leadership, conflict resolution, technical, scientific and preclinical or clinical responsibilities where appropriate.
• Each NCRCRG will include an Administrative Core component to assist in these responsibilities.

Project Features:

• The organizing conceptual principle for the NCRCRG should be a strong rationale for the design of patient/sample selection through gene association (e.g., 22q11.2 deletion, 22q13 deletion, CACNA1C and CACNB2 polymorphisms), drug response and/or other objective biological criteria; DSM diagnosis alone is insufficient. The use of the Research Domain Criteria (RDoC) framework is encouraged for classifying psychopathology based on dimensions of observable behavior and neurobiological measures. Multiple comparison groups may be included in an effort to identify common pathways underlying pathophysiology. All cell lines should be linked to detailed genetic and clinical assessment/(endo)phenotyping data, either completed or as part of the proposed research design. Recruitment and clinical/genetic characterization of new subjects is permitted for these applications; however, the central focus of the NCRCRG should be on cell-based research, with other assessments in support.
• An NCRCRG will have two or more Research Projects, each of which should involve academic-industry collaboration and may involve multiple sites, teams and disciplines. The projects should be based on solid preliminary data supporting the utility of one or more cell differentiation, purification or reporting protocol(s), functional assay(s), and/or a promising biological difference between patient and control-derived cells. However, within these constraints there can be a significant component of discovery-based research and methods development or optimization, along with comparison against non-cell-based paradigms. The study design should be directed toward the goal of experimental rigor, replication and transparency of reporting (see Section IV - PHS398 Research Plan), consistent with recommendations for optimizing pre-clinical studies [also see Landis et al., 2012 Nature 490:187-191]. The plan should anticipate that regulatory scientists may rely on data generated using the tools/assays developed from these Projects. Multiple performance sites will be engaged to accomplish these goals. It is understood that cost and technical constraints preclude having sample sizes approaching those of genetic studies, but efforts should be made to account for the statistical power of tests.
• Measurable milestones and a time line of the research activities should be proposed to guide progress over the life of the NCRCRG. Milestones should be well described, quantifiable, and scientifically justified. The milestones should be regarded as criteria for evaluating the progress and direction of the NCRCRG.
• One or more Scientific Core components are permitted when necessary for resource or analytical support. Applications that propose derivation or characterization of large numbers of cell lines should describe technologies or efficiencies to minimize costs. Since this FOA is not designed as a large scale banking initiative, applicants should determine whether centrally-banked (e.g., NIMH Repository or other locations) or shared resources are already available to deliver sufficiently powered sample sizes. Applications that propose the generation of large datasets should describe technologies to maximize efficiencies and coordination in bioinformatics or statistical infrastructure.

Sharing, Collaboration, Dissemination:

• All source cells (e.g., blood, fibroblasts) and expandable derived lines (e.g., iPSCs) used in these studies, along with associated clinical and genotypic data, are expected to be deposited with the NIMH Center for Collaborative Genomic Studies on Mental Disorders, Stem Cell Center, per policy statement NOT-MH-13-002, unless the applicant can provide a compelling justification for an alternative central banking facility. Additional data sharing expectations may apply (see Section IV - Resource Sharing Plan).
• The NCRCRG will coordinate to standardize methodologies and include arrangements for full, transparent and rapid dissemination of raw and processed data, along with new/improved protocols and assay systems, among NCRCRG collaborators (for purposes of replicating results), with dissemination of detailed protocols and assay systems to the broader community by the end of the project period. Sharing should be designed so that all NCRCRG members can participate in troubleshooting failed methodologies or interpreting outlier results. Collaborators within the NCRCRG will interact informally on a regular frequent schedule and meet formally twice yearly, with substantial involvement by NIMH Program staff. A workshop of the entire Consortium of NCRCRGs will be held every year (as applicable), with substantial involvement by NIMH Program staff.
• Applicants are encouraged to include sabbatical arrangements among NCRCRG scientists to facilitate the sharing of novel techniques/protocols. Collaborators are also encouraged to include plans for partnered academic & industry cross-training to bridge expertise in basic science and drug development.
• In the spirit of strategic alliances to meet the objectives of the program, investigators may include plans to cooperate with one or more relevant research projects, centers, networks or consortia, e.g., with NIH R01, P50, U01, U19, U54, U24 awardees, to gain the advantages of broader consensus on research methods for validation, qualification, or creation of public research resources for translational research.

Studies can focus on varying and multiple elements of the preclinical research process, including, but not limited to:

• Using optimized cell line derivation technologies to improve and further validate patient versus control comparisons, such as making isogenic controls of patient-derived iPSCs (e.g., using small molecules or transcription activator-like effector nuclease [TALEN]-based approaches), or directed mutagenesis of non-patient control iPSC lines to mimic disease-associated human alleles. Efforts should include validating iPSCs from multiple clonally defined source cells from the same subject to determine the extent of somatic mosaicism. Footprint-free non-integrating reprogramming methods are preferable.
• Optimizing highly efficient neural differentiation protocols with emphasis on validating regional specification and subtype identity of neural progenitor and/or differentiated cells, which may involve the development and use of appropriate reporter technologies.
• High content or multi-parameter phenomic analysis of well-defined cell subtypes, with obligate validation of regional specification and subtype identity of cells of interest. Application of single cell technologies to genomic/phenomic analysis.
• Optimizing reprogrammed cell-based functional assays for outcome measures relevant to disease pathophysiology. These may include monolayer assays, microfluidic assays such as engineered microphysiological systems (e.g., tissue chips), self-organizing organotypic assays or in vivo engraftment/chimera assays.
• Cross-paradigm validation: comparison of iPSC-based cell phenotypes against other independent measures with respect to pathophysiological relevance to complex brain disorders (e.g., mice with disease-associated human alleles, human phenotypic measures, patient drug response, post-mortem analysis). This can include re-contacting subjects who participated in prior cell-based studies, in order to enrich further analysis (e.g., additional clinical phenotyping, drawing blood for lymphoblastoid cell line production and genetic analysis).
• Standardizing industrial workflow and quality control, including sample preservation/handling, assay miniaturization and/or stabilization, lab to industrial scaling.
• Using validated cellular assays for characterizing candidate molecular targets or therapeutic/toxic effects of compounds on these targets.

Program Technical Assistance Note: Approximately two months in advance of each Letter of Intent due date, an interactive technical assistance webinar will be held for investigators who are interested in information about the structure of collaborations, topics of interest or programmatic requirements of the FOA. Potential applicants are strongly advised to solicit Program feedback from the NIMH Scientific/Research Contact well in advance of the application due date to determine whether their proposed studies align with NIMH priorities and the FOA purpose.

Funding Instrument	Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or Program staff will assist, guide, coordinate, or participate in project activities. .
Application Types Allowed	New Renewal Resubmission Revision The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	The number of awards is contingent upon NIMH appropriations and the submission of a sufficient number of meritorious applications.
Award Budget	Application budgets are not limited, but need to reflect the actual needs of the proposed project.
Award Project Period	The scope of the proposed project should determine the project period. The maximum project period is 5 years.

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

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• 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)

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant organizations must complete the following registrations as described in the SF424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

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

All Program Directors/Principal Investigators (PD(s)/PI(s)) and component Project Leads that are not yet registered in eRA Commons must work with their institutional officials to register. Also, institutional officials at the applicant organization should ensure that the eRA Commons account for the contact PD/PI is affiliated with their organization.

eRA Commons accounts are necessary to use ASSIST to prepare and submit applications.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least 6 weeks prior to the application due date.

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

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

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

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

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

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

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

Most applicants will use NIH’s ASSIST system to prepare and submit applications through Grants.gov to NIH. Applications prepared and submitted using applicant systems capable of submitting electronic multi-project applications to Grants.gov will also be accepted.

It is critical that applicants follow the 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.

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

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

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

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

The letter of intent should be sent to:

David M. Panchision, Ph.D.
Division of Neuroscience and Basic Behavioral Science
National Institute of Mental Health (NIMH)
6001 Executive Boulevard, Room 7189, MSC 9641
Bethesda, MD 20892-9641
Rockville, MD 20852 (for express/courier service)
Telephone: 301-443-5288
FAX: 301-451-5615
Email: [email protected]

Component Types Available in ASSIST	Research Strategy/Program Plan Page Limits
Overall	12
Admin Core	6
Core (use for Scientific Cores)	6
Project	12

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

The following section supplements the instructions found in the SF 424 Application Guide, and should be used for preparing a multi-component application.

The application should consist of the following components:

• Overall
• Admin Core: one, required
• Scientific Cores: optional
• Projects: minimum of two required

When preparing your application in ASSIST, use Component Type Overall .

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

SF424 (R&R) Cover (Overall)

Complete entire form.

PHS 398 Cover Page Supplement (Overall)

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

Research & Related Other Project Information (Overall)

Follow standard instructions.

Other Attachments:

Project/Performance Site Location(s) (Overall)

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.

Research & Related Senior/Key Person Profile (Overall)

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

It is anticipated that the NCRCRG Groups will include outstanding scientists from diverse scientific disciplines within stem cell biology, developmental biology, molecular biology, biochemistry, pharmacology, genetics, basic and clinical neuroscience, and/or mental disorders research into synergistic research teams without regard to institutional affiliation.

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.

Budget (Overall)

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

The contact PD/PI will be expected to devote at least 1.8 person months of effort to the NCRCRG program; any additional multi-PD/PIs will be expected to devote at least 1.2 person month of effort to the NCRCRG program.

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.

PHS 398 Research Plan (Overall)

Introduction to Application: For Resubmission and Revision applications, an Introduction to Application is required in the Overall component. This should detail how the application has changed from the previous version. Resubmissions must include responses to criticisms and issues raised in the Summary Statement of the first submission.

Specific Aims: Provide a concise description of overall NCRCRG aims. Outline how the Projects and Core(s) will contribute to attaining objectives. The renewal should state how, or if, specific aims have changed from the previous funding period. Resubmissions and revisions should state how, or if, specific aims have changed from the earlier application.

Research Strategy: A synthesis of objectives, coordination and governance that addresses logistical challenges for successful pre-competitive partnerships [e.g., see discussions by Woodcock (2010) Clin Pharmacol & Ther, 87(5):521 3; and Vargas et al., (2010) Clin Pharmacol & Ther, 87(5):527 9]. This will include:

Significance: An overview of the proposed NCRCRG ("Group"), describing the central theme and general objectives of the Group, the importance of the problem(s) to be studied and how these will affect pre-clinical research and/or public health. The Group objectives should be relevant to and compatible with the NIMH priorities in Section I - Funding Opportunity Description. Applicants should describe their plans to accommodate the stated NCRCRG program requirements, criteria, and NIMH involvement.

Innovation: Highlighting how the Group seeks to change current paradigms for cell-based research for studying mental illness, including novel concepts, approaches, methodologies, instrumentation, or collaborative structures, and any advantages they provide over current practices. Applications should describe the unique advantages and capabilities that the public-private collaboration will provide, such as tailoring experimental design to the availability of uncommon/valuable resources or translational expertise, and how this synergizes beyond what could be achieved through a traditional research project. This should particularly relate to the NCRCRG program focus on (1) a strong emphasis on developing methodology that is replicable across several performance sites, and (2) cross-paradigm validation to yield predictive value for pathophysiology.

Approach: A clear description of how each component Research Project, Scientific Core (as applicable) and Administrative Core is necessary for the attainment of the NCRCRG program's objectives, including available professional and technical personnel to permit efficient and successful conduct of the proposed research. This should describe major tasks each partner organization will complete, and the benefits each brings to this alliance to enhance prospects for completing specific aims. This should also include evidence that each component Research Project, Core(s) and the Group as a whole has available facilities necessary for conduct of the proposed research;

Evidence that an academic-industrial partnership is either already ongoing or will be active at the time of award, involving at least one lead academic and one lead industrial organization large or small among their numbers (multiple academic and industrial partners are encouraged). All the partnering organizations are expected to collaborate on the proposed goals in a manner that would enable the entire joint effort to be administered in a unified manner. Each partner organization should have sufficient scientific involvement, and at least one participating investigator with qualifications to lead and/or share authority and responsibility for the overall effort, including authority to allocate resources to ensure successful completion of the proposed research discovery and development efforts;

A broad description of resource contributions by the partners within the NCRCRG (e.g., biotechnology, pharmaceutical, or other private organizations) to enhance the overall goals of the effort. Note that more detailed information is to be included in the Letters of Support section of the respective Core or Project components of the application;

A flow chart of organizational governance, including the Group Steering Committee with External Consultation Panel. The qualities and expertise of External Consultation Panel members should be described; however, they should not be named in the application, contacted or appointed prior to review (Note: they will be named at the time of award);

A plan for decision-making regarding identification and evaluation of promising cell-based paradigms for development. The plan should anticipate that regulatory scientists may rely on data generated using the tools/assays developed from these Projects. The plan should account for experimental rigor and control of bias (e.g., with randomization, blinding, sample size estimation, data handling) as appropriate to the specific plans for validated protocols or assays. The plan should also ensure replication, comprehensive transparency of data reporting/sharing and rapid access among the NCRCRG performance sites. Note: Sharing and dissemination beyond the Group, to other NCRCRG program Groups and the broader research community, should be described in the Resource Sharing Plan (below);

A plan to foster and assure the maintenance of close collaboration and effective communication among members of the group. Include plans for scheduling group meetings, notifying group members (including NIMH), and documenting and disseminating group meeting proceedings. Include plans for acknowledging and respecting Group member contributions, including in publications;

A statement that awardees will agree to the "Cooperative Agreement Terms and Conditions of Award" in Section VI.2.A "Award Administration Information";

A description of the steps that will be taken to ensure successful completion of the NCRCRG research should a key member leave the Group, including plans to replace the PD/PI if needed;

A Timeline and Milestones section must be included in the Overall Research Strategy section for the NCRCRG. The timeline should describe the expected progression of the research activities for the overall NCRCRG to the extent that they integrate more than one Research Project and Scientific Core (if any) over the life of the project (Note: activities that are specific to a single Core or Project should instead be described in the Timeline for that particular Research Strategy). Overall milestones should be identified along the timeline. Milestones should be well described, quantifiable, and scientifically justified benchmarks. The milestones should be regarded as criteria for evaluating the progress and direction of the Research Project(s) and should not be just a restatement of the specific aims. During the project period, the applicant will be expected to refer to these milestones in annual progress reports. The funding institute will use the milestones, the annual progress reports, and other measures of productivity and success to judge the progress, impact, and value of the program.

Letters of Support: Include individual letters of commitment to the collaboration and agreement to the stated communication plan (described in the Research Strategy) by all Research Project Leaders. Note that letters detailing resource contributions are to be placed in their respective individual Project and Core components..

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modifications:

• Biomaterial Sharing Section: Per NIMH policy (NOT-MH-13-002), grantees who generate or use human subject-derived reprogrammed cells in their NIMH-funded research are expected to submit relevant source cells (e.g., fibroblasts, olfactory epithelial cells, blood) and reprogrammed derivatives (e.g., induced pluripotent stem cells/iPSCs or other renewable cell lines) to the NIMH Center for Collaborative Genomic Studies on Mental Disorders, Stem Cell Center (http://nimhgenetics.org). The Resource Sharing Plan of applications for NIMH funding should include arrangements and a timeline for submitting relevant biomaterials to the Center, or else provide a clear rationale for why such submission cannot be provided, along with alternative sharing arrangements.
• Data Sharing Section: All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. Clinical and genotypic data that accompany the patient-derived cells are expected to be submitted to the Center for Collaborative Genomic Studies on Mental Disorders. Studies that generate genotype-phenotype data are also expected to deposit these in the database of Genotypes and Phenotypes (dbGaP). Additionally, applications that involve human subject recruitment with a focus on autism spectrum disorders are expected to submit clinical and associated genotype and phenotype data to the National Database for Autism Research (NDAR). Central clinical coordination and local data management for data cleaning and entry and bio-statistical consulting will be the responsibility of the awardee. NCRCRG applications should budget appropriately to comply with these data sharing expectations. As appropriate, the application may propose an NCRCRG-specific data sharing infrastructure, provided it comports with the data sharing expectations described above.
• Human subject consent language associated with such biomaterials and data collection should be consistent with banking and wide sharing through a centralized repository.
• Protocol Dissemination Section: Since a major goal of the NCRCRG Program is methodological and data reproducibility and standardization throughout the research field, each NCRCRG should include a clear and detailed plan and timeline for fully and transparently disseminating new and optimized protocols/assays to other NCRCRG Program Groups and the broader research community, beyond peer-reviewed publications (e.g., web-based resources, training courses, etc.) consistent with achieving the goals of this program, or provide a clear rationale for when/why such open dissemination cannot be provided, along with alternative arrangements.
• Applicants are strongly encouraged to consult with NIMH Program staff when preparing this Sharing Plan. Consideration will be given to investigator adherence to this standard of sharing consistent with achieving the goals of this program when determining funding priorities; the final terms of sharing will be negotiated with NIMH Program staff and will be included in the Terms and Conditions of the Notice of Award.

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

When preparing your application in ASSIST, use Component Type Admin Core.

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

SF424 (R&R) Cover (Admin Core)

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Admin Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Admin 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.

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

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

Budget (Admin Core)

• Budget forms appropriate for the specific component will be included in the application package.
• The NCRCRG funded through this FOA will have a Steering Committee to provide governance (see Cooperative Agreement Terms and Conditions of Award). This budget section should include requests for travel funds (if not covered by private sources) for External Consultation Panel and Steering Committee members to attend one of the two annual meetings onsite; the other meeting can be a web-based meeting. Additionally, if not covered by private funds, this budget section should include requests for administrative funds for organizing a two-day annual workshop involving Consortium Committee members from multiple NCRCRGs (the Consortium) for two of the project years, as the PD/PI will be responsible for organizing the Consortium workshop for those two years.
• Applicants should budget appropriately to comply with data sharing described in the Resource Sharing Plan instructions.
• While the NCRCRG program strongly encourages applicant and collaborating organizations, including private partners (e.g., biotechnology, pharmaceutical, or other private organizations), to contribute resources to this effort, such resources for the Admin Core should be detailed in the Letters of Support section for this component and not be part of the Budget or Budget Justification.

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 (Admin Core)

Introduction to Application: For Resubmission and Revision applications, an Introduction to Application is allowed for each component. This should detail how the application has changed from the previous version. Resubmissions must include responses to criticisms and issues raised in the Summary Statement of the first submission.

Specific Aims: Provide a concise description of Core aims.

Research Strategy:

Significance: Describe how the Administrative Core will contribute to the goals of the overall Group.

Innovation: Highlight any novel features of the Administrative Core that enhance the collaborative effort, including optimizing communication, decision-making and sharing between the Project and/or Scientific Core teams.

Approach: Describe how each Project or Scientific Core (as applicable) will draw upon the Administrative Core and how it in turn will respond to Project or Scientific Core needs. The description of the Core should clearly indicate the facilities, resources, services and professional skills that the Core will provide. Moreover, information must be provided about how the collective operation of the Core will be effected in a coherent manner.

Where applicable, illustrate how Core activities address the needs for rapid dissemination of new techniques/data, sufficiently powered sample sizes, unit cost reduction of cellular reagents/assays, standardization to improve replication and/or a fast-fail process to eliminate false leads. Core activities should facilitate experimental rigor, replication and transparency of reporting, consistent with recommendations for optimizing pre-clinical studies [also see Landis et al., 2012 Nature 490:187-191];

A Timeline and Milestones section must be included in the Research Strategy section for the Core. The timeline should describe the expected progression of the activities specific to the Core (Note: activities that integrate multiple Cores/Projects should instead be described in the Overall Research Strategy). Milestones should be identified along the timeline. Milestones should be well described, quantifiable, and scientifically justified benchmarks. The milestones should be regarded as criteria for evaluating the progress and direction of the Core and should not be just a restatement of the specific aims. During the project period, the applicant will be expected to refer to these milestones in annual progress reports. The funding institute will use the milestones, the annual progress reports, and other measures of productivity and success to judge the progress, impact, and value of the program.

Letters of Support: Include a detailed description of any resource support, specific to the individual Administrative Core, that is provided by the applicant institution and its collaborators (e.g., biotechnology, pharmaceutical, or other private organizations) and which will enhance the potential for success and sustainability of the NCRCRG. Examples of such support would include (but are not limited to): institution-funded staff time and effort, donated equipment and space, providing free and open access to tools, databases, workflow processes, logistical resources or other resource investments. Specific and detailed descriptions of these contributions, as well as assurances that their organization and any collaborators are committed to providing these resources to the Group effort, should be included in this section. Pharmaceutical, biotechnology or other private partners should include and describe essential personnel who have authority within the organization to allocate resources to ensure successful completion of the proposed research discovery and development efforts. Also include individual letters of commitment to the collaboration specific to the individual Core (described in the Research Strategy) by all other collaborators and consultants.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide. These plans should be integrated together into the Overall Research Strategy Section, following the modified instructions for that Section, and not included as part of the individual Core(s).

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

When preparing your application in ASSIST, use Component Type Core.

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

SF424 (R&R) Cover (Scientific Core)

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Scientific Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Scientific 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.

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

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

Budget (Scientific Core)

• Budget forms appropriate for the specific component will be included in the application package.
• Applicants should budget appropriately to comply with data sharing described in the Resource Sharing Plan instructions.
• While the NCRCRG program strongly encourages applicant and collaborating organizations, including private partners (e.g., biotechnology, pharmaceutical, or other private organizations), to contribute resources to this effort, such resources for each individual Scientific Core should be detailed in the Letters of Support section for this component and not be part of the Budget or Budget Justification.

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 (Scientific Core)

Introduction to Application: For Resubmission and Revision applications, an Introduction to Application is allowed for each component. This should detail how the application has changed from the previous version. Resubmissions must include responses to criticisms and issues raised in the Summary Statement of the first submission.

Specific Aims: Provide a concise description of Core aims.

Research Strategy:

Significance: Describe how the Scientific Core will contribute to the goals of the overall Group.

Innovation: Highlight any novel features of the Scientific Core that enhance the collaborative effort, including the coordination of resources and activities between the Project teams.

Approach: Describe how each Project will draw upon the Core and how it in turn will respond to Project needs. The description of the Core should clearly indicate the facilities, resources, services and professional skills that it will provide. Moreover, information must be provided about how the collective operation of the Core will be effected in a coherent manner;

Where applicable, illustrate how Core activities address the needs for rapid dissemination of new techniques/data, sufficiently powered sample sizes, unit cost reduction of cellular reagents/assays, standardization to improve replication and/or a fast-fail process to eliminate false leads. Core activities should facilitate experimental rigor, replication and transparency of reporting, consistent with recommendations for optimizing pre-clinical studies [also see Landis et al., 2012 Nature 490:187-191];

Core components that propose derivation or characterization of large numbers of cell lines should describe technologies or efficiencies to minimize costs. Since this FOA is not designed as a large scale banking initiative, applicants should determine whether centrally-banked (e.g., NIMH Repository or other locations) or shared resources are already available to deliver sufficiently powered sample sizes. Core components that propose the management or analysis of large datasets should describe technologies to maximize efficiencies and coordination in bioinformatics or statistical infrastructure;

A Timeline and Milestones section must be included in the Research Strategy section for the Core. The timeline should describe the expected progression of the activities specific to the Core (Note: Activities that integrate multiple Cores/Projects should instead be described in the Overall Research Strategy). Milestones should be identified along the timeline. Milestones should be well described, quantifiable, and scientifically justified benchmarks. The milestones should be regarded as criteria for evaluating the progress and direction of the Core and should not be just a restatement of the specific aims. During the project period, the applicant will be expected to refer to these milestones in annual progress reports. The funding institute will use the milestones, the annual progress reports, and other measures of productivity and success to judge the progress, impact, and value of the program.

Letters of Support: Include a detailed description of any resource support, specific to the individual Scientific Core, that is provided by the applicant institution and its collaborators (e.g., biotechnology, pharmaceutical, or other private organizations) and which will enhance the potential for success and sustainability of the NCRCRG. Examples of such support would include (but are not limited to): institution-funded staff time and effort, donated equipment and space, providing free and open access to tools, assays, reagents, databases, workflow processes, or other resource investments. Specific and detailed descriptions of these contributions, as well as assurances that their organization and any collaborators are committed to providing these resources to the Group effort, should be included in this section. Pharmaceutical, biotechnology or other private partners should include and describe essential personnel who have authority within the organization to allocate resources to ensure successful completion of the proposed research discovery and development efforts. Also include individual letters of commitment to the collaboration specific to the individual Core (described in the Research Strategy) by all other collaborators and consultants.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide. These plans should be integrated together into the Overall Research Strategy Section, following the modified instructions for that Section, and not included as part of the individual Core(s).

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

When preparing your application in ASSIST, use Component Type Project.

A minimum of 2 projects are required.

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

SF424 (R&R) Cover (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 (Project)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Project)

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

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

Project Narrative: Do not complete.

Project /Performance Site Location(s) (Project)

List all performance sites that apply to the specific component.

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

Research & Related Senior/Key Person Profile (Project)

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

Budget (Project)

• Budget forms appropriate for the specific component will be included in the application package.
• Applicants should budget appropriately to comply with data sharing described in the Resource Sharing Plan instructions.
• While the NCRCRG program strongly encourages applicant and collaborating organizations, including private partners (e.g., biotechnology, pharmaceutical, or other private organizations), to contribute resources to this effort, such resources for each individual Project should be detailed in the Letters of Support section for this component and not be part of the Budget or Budget Justification.

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

PHS 398 Research Plan (Project)

Introduction to Application: For Resubmission and Revision applications, an Introduction to Application is allowed for each component. This should detail how the application has changed from the previous version. Resubmissions must include responses to criticisms and issues raised in the Summary Statement of the first submission.

Specific Aims: Provide a concise description of each Project aims.

Research Strategy:

Significance: Describe the status of current research efforts, the limitations of existing approaches, and how the research questions posed relate to the objectives of the particular project and the NCRCRG as a whole.

Innovation: Highlight any novel features of the Project that relate to the NCRCRG program goals of (1) a strong emphasis on developing methodology that is replicable across several performance sites, and (2) cross-paradigm validation to yield predictive value for pathophysiology. Describe the unique advantages and capabilities that the public-private collaboration will provide, such as tailoring experimental design to the availability of uncommon/valuable resources or translational expertise, and how this synergizes beyond what could be achieved through a traditional research project.

Approach: Describe the feasibility of the proposed experiments, the advantages of any new methodologies, the potential pitfalls, alternative approaches, the means of assessing success of the research to meet the objectives of the Project and the NCRCRG as a whole;

Where applicable, illustrate how Project activities address the needs for rapid dissemination of new techniques/data, unit cost reduction of cellular reagents/assays, standardization and/or a fast-fail process to eliminate false leads. Describe any features of the study design that will allow regulatory scientists to rely on data generated using the tools/assays developed from these Projects;

Experimental rigor, control of bias, and transparency of reporting are all critical determinants of experimental replicability. Consistent with recommendations for optimizing pre-clinical studies [also see Landis et al., 2012 Nature 490:187-191], applicants should consider the following points in their study design, and address those that are appropriate, when describing preliminary data and proposed studies or core activities:

• Experimental design:
  
  • Rationale for the sample selection, assays and/or endpoints
  • Adequacy of the controls
  • Justification of sample size, including power calculation
  • Statistical methods used in analysis and interpretation of results
  • Manner & timing of rescue or intervention
• Minimizing bias:
  • Methods of blinding (allocation concealment and blinded assessment of outcome)
  • Strategies for randomization and/or stratification
  • Reporting of data missing due to attrition or exclusion
  • Reporting of all results (negative and positive)
• Results:
  • Independent validation/replication, if available
  • Robustness and reproducibility of the observed results
  • Dose-response results
  • Verification that interventional drug or biologic reached and engaged the target
• Interpretation of results:
  • Alternative interpretations of the experimental data
  • Relevant literature in support or in disagreement with the results
  • Discussion of effect size in relation to potential impact
  • Potential conflicts of interest

A Timeline and Milestones section must be included in the Research Strategy section for the Project. The timeline should describe the expected progression of the activities specific to the Project (Note: activities that integrate multiple Projects/Cores should instead be described in the Overall Research Strategy). Milestones should be identified along the timeline. Milestones should be well described, quantifiable, and scientifically justified benchmarks. The milestones should be regarded as criteria for evaluating the progress and direction of the research Project and should not be just a restatement of the specific aims. During the project period, the applicant will be expected to refer to these milestones in annual progress reports. The funding institute will use the milestones, the annual progress reports, and other measures of productivity and success to judge the progress, impact, and value of the program.

Letters of Support: Include a detailed description of any resource support, specific to the individual Project, that is provided by the applicant institution and its collaborators (e.g., biotechnology, pharmaceutical, or other private organizations) and which will enhance the potential for success and sustainability of the NCRCRG. Examples of such support would include (but are not limited to): institution-funded staff time and effort, donated equipment and space, providing free and open access to tools, assays, reagents, databases, workflow processes, or other resource investments. Specific and detailed descriptions of these contributions, as well as assurances that their organization and any collaborators are committed to providing these resources to the Group effort, should be included in this section. Pharmaceutical, biotechnology or other private partners should include and describe essential personnel who have authority within the organization to allocate resources to ensure successful completion of the proposed research discovery and development efforts. Also include individual letters of commitment to the collaboration specific to the individual Project (described in the Research Strategy) by all other collaborators and consultants.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide. These plans should be integrated together into the Overall Research Strategy Section, following the modified instructions for that Section, and not included as part of the individual Research Projects.

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

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies) 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.

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 Applying Electronically.

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

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

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review, NIH. Applications that are incomplete will not be reviewed.

Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact NIH Program staff at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide.

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

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

Note that each component of the application has separate instructions for scored 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 NCRCRG that by its nature is not innovative may be essential to advance a field.

Significance

Does the NCRCRG address an important problem or a critical barrier to progress in the field? If the aims of the NCRCRG 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? To what degree does the proposed plan for optimization of cellular tools/protocols/assays support the needs for the targeted disorder? What is the likelihood that it will produce optimized, robust, reproducible assay(s) that will be relevant to the pathophysiology of, diagnostics and/or therapeutics discovery for mental illness?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the overall NCRCRG program? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? To what extent have collaborations been established or consultants identified to provide the appropriate depth and breadth of expertise necessary for the project? Has the PD/PI demonstrated leadership in development, implementation, and management of comprehensive research programs? How adequate are the plans for ensuring effective intra-Group communication, interaction, cohesiveness, and coordination among the PD/PI, Research Project Leaders, and NIH Project Scientists? How well have the investigators demonstrated a commitment to collaborate extensively and provide transparency in detailed reporting, sharing and replicating results within the NCRCRG?

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? How well does the NCRCRG exploit unique advantages and capabilities that a public-private partnership can provide, such as tailoring experimental design to the availability of uncommon/valuable resources or translational expertise? How well do the components synergize beyond what could be achieved through a traditional research project?

Approach

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

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

How sound is the scientific rationale for patient/sample selection that forms the organizing principle of the overall NCRCRG objectives? Are the scientific disciplines represented in the overall plan adequate to achieving the NCRCRG Program objectives? Are adequate plans in place for developing cell-based methodology that is replicable across several performance sites, transparency of data reporting/sharing among the NCRCRG performance sites and cross-paradigm validation to yield predictive value for pathophysiology? Are the timeline and milestones clear and feasible? Are the plans for transparent protocol/methods dissemination to the greater research community appropriate to the goals of the NCRCRG program?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements? How well do the contributions of private partner(s) enhance the NCRCRG scope or goals? Do the collaborating institutions demonstrate a commitment to and plan for transparency in detailed reporting, sharing and replicating results within the NCRCRG? Are plans for any sabbaticals or academic-industry "cross-training" (if applicable) well-conceived and appropriately integrated within the scope or goals of the NCRCRG?

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

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Children

When the proposed NCRCRG involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

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

Biohazards

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

Resubmissions

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

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

Revisions

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

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

Applications from Foreign Organizations

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

Select Agent Research

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

Resource Sharing Plans

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genome Wide Association Studies (GWAS). In particular, reviewers should comment on whether plans sufficiently comport with NIMH policy on source cell and reprogrammed cell sharing (NOT-MH-13-002), including arrangements and a timeline for submitting relevant biomaterials to the NIMH Center for Collaborative Genomic Studies on Mental Disorders, Stem Cell Center (http://nimhgenetics.org), or else provide a clear rationale for why such submission cannot be provided, along with alternative sharing arrangements. Additionally, reviewers should comment on the appropriateness of plans for sharing clinical and genotypic data with the NIMH Center for Collaborative Genomic Studies, genotype-phenotype data with the database of Genotypes and Phenotypes (dbGaP), and/or clinical and associated genotype and phenotype data associated with autism spectrum disorders to the National Database for Autism Research (NDAR).

Budget and Period of Support

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

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

Significance

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

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the Administrative Core? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? To what extent have collaborations been established or consultants identified to provide the appropriate depth and breadth of expertise necessary for the Core activities? Has the Core Leader demonstrated leadership in development, implementation, and management of Core activities? How adequate are the plans for ensuring effective intra-Group communication, interaction, cohesiveness, and coordination with other Group members? How well have the investigators demonstrated a commitment to collaborate extensively and provide transparency in detailed reporting, sharing data/resources and replicating results within the NCRCRG?

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? How well does the Administrative Core exploit unique advantages and capabilities that a public-private partnership can provide, particularly with respect to providing uncommon/valuable resources or services to multiple end users? What novel features of the Administrative Core enhance the collaborative effort, including the coordination of resources and activities between the Project and Scientific Core teams?

Approach

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

If the Administrative Core involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

Is there an adequate description of the facilities, resources, services and professional skills that the Core will provide? Does the plan provide evidence that the collective operation of the Core will be coherent? How well will any private (e.g., industry, organization) partners facilitate the activities of the Core? How effectively does each Project and Scientific Core draw upon the Administrative Core and how effective is the plan to respond to Project and Scientific Core needs? Are adequate plans in place for the Core to facilitate transparency of data reporting/sharing among the NCRCRG performance sites? Are the milestones and timeline of Core activities adequate to judge progress?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment or collaborative arrangements? Is there evidence of institutional support and competence of the applying Institution to serve as the Administrative Core for the Group? How well do the contributions of private partner(s) enhance the Administrative Core scope or goals?

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

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Children

When the proposed Core involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

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

Biohazards

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

Resubmissions

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

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

Revisions

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

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

Select Agent Research

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

Resource Sharing Plans

Reviewers will comment on the Resource Sharing Plans, which are included only in the Overall Component of the application.

Budget and Period of Support

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

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

Significance

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

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the Scientific Core? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? To what extent have collaborations been established or consultants identified to provide the appropriate depth and breadth of expertise necessary for the Core activities? Has the Core Leader demonstrated leadership in development, implementation, and management of Core activities? How adequate are the plans for ensuring effective intra-Group communication, interaction, cohesiveness, and coordination with other Group members? How well have the investigators demonstrated a commitment to collaborate extensively and provide transparency in detailed reporting, sharing data/resources and replicating results within the NCRCRG?

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? How well does the Scientific Core exploit unique advantages and capabilities that a public-private partnership can provide, particularly with respect to providing uncommon/valuable resources or services to multiple end users? What novel features of the Scientific Core enhance the collaborative effort, including the coordination of resources and activities between the Project teams?

Approach

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

If the Scientific Core involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

Is there an adequate description of the facilities, resources, services and professional skills that the Core will provide? Does the plan provide evidence that the collective operation of the Core will be coherent? How well will any private (e.g., industry, organization) partners facilitate the activities of the Core? How effectively does each Project draw upon the Scientific Core and how effective is the plan to respond to Project needs?

If applicable, how sound is the scientific rationale for developing or applying new methodologies to the functions of the Core? How well do the Core activities facilitate experimental rigor and control of bias (e.g., with randomization, blinding, sample size estimation, data handling) as appropriate to the experimental designs of each Project? Are adequate plans in place for replication and transparency of data reporting/sharing among the NCRCRG performance sites? Are the milestones and timeline of Core activities adequate to judge progress?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment or collaborative arrangements? Has the Scientific Core demonstrated a track record in successfully providing the necessary resources on schedule and within the specified constraints? How well do the contributions of private partner(s) enhance the Scientific Core scope or goals? Are plans for any sabbaticals or academic-industry "cross-training" (if applicable) well-conceived and appropriately integrated within the scope or goals of the NCRCRG?

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

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Children

When the proposed Core involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

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

Biohazards

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

Resubmissions

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

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

Revisions

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

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

Select Agent Research

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

Resource Sharing Plans

Reviewers will comment on the Resource Sharing Plans, which are included only in the Overall Component of the application.

Budget and Period of Support

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

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

Significance

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

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the Research Project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? To what extent have collaborations been established or consultants identified to provide the appropriate depth and breadth of expertise necessary for the project? Has the Project Leader demonstrated leadership in development, implementation, and management of research programs? How adequate are the plans for ensuring effective intra-Group communication, interaction, cohesiveness, and coordination among the Group members? How well have the investigators demonstrated a commitment to collaborate extensively and provide transparency in detailed reporting, sharing and replicating results within the NCRCRG?

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? How well does the Project exploit unique advantages and capabilities that a public-private partnership can provide, such as tailoring experimental design to the availability of uncommon/valuable resources or translational expertise? How well do the components synergize beyond what could be achieved through a traditional research project?

Approach

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

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

Are the scientific disciplines represented in the Project adequate to achieving the NCRCRG Program objectives? How sound is the scientific rationale for patient/sample stratification based on gene association, drug response or other objective biological criteria? How well does the design incorporate various human subject data to enrich the sample characterization? How sound is the scientific rationale for developing new methodologies, or further developing the proposed cellular protocols/assays, e.g., if discovery-based or optimization approaches are proposed? If applicable, how useful are complementary studies (e.g., those involving clinical phenotyping or model organism analysis) in helping to validate cell-based results? How effectively will any private (e.g., industry, foundation) partners facilitate the development and evaluation of cell based protocols and assays? How relevant are these approaches to understanding the basis of pathophysiology or to therapeutic discovery for mental disorders? Does the study design adequately incorporate experimental rigor and control of bias (e.g., with randomization, blinding, sample size estimation, data handling) as appropriate to the specific plans for validated protocols or assays? Are adequate plans in place for replication and transparency of data reporting/sharing among the NCRCRG performance sites? Are the timeline and milestones clear and feasible? Are the plans for transparent protocol/methods dissemination to the greater research community appropriate to the goals of the NCRCRG program?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements? How well do the contributions of private partner(s) enhance the Project scope or goals? Is there evidence of institutional support and competence of the applying Institution to serve as the Administrative Core for the Group? Do the collaborating institutions demonstrate a commitment to and plan for transparency in detailed reporting, sharing and replicating results within the NCRCRG? If subject recruitment is involved, does the clinical research team demonstrate a track record in successfully recruiting subjects into clinical trials and research studies and completing proposed studies within projected timelines? For cell reprogramming and culture technologies, does the team demonstrate a track record in successfully optimizing tools/protocols/assays? Are plans for any sabbaticals or academic-industry "cross-training" (if applicable) well-conceived and appropriately integrated within the scope or goals of the NCRCRG?

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

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Children

When the proposed Project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

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

Biohazards

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

Resubmissions

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

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

Revisions

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

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

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 the Resource Sharing Plans, which are included only in the Overall Component of the application.

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) 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.

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

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

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

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

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

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

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

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

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

Cooperative Agreement Terms and Conditions of Award

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

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

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

• The PD/PI(s) will have primary authority and responsibility to define objectives and approaches and to plan and conduct the proposed research. She/he will assume responsibility and accountability to the applicant organization and to the NIMH for performance and proper conduct of all research supported in the NCRCRG (herein referred to as the "Group"), including the NIH intramural component, if applicable, in accordance with the Terms and Conditions of Award. The Principal Investigator will be a member of the NCRCRG Steering Committee.
• NIH intramural research scientists participating as Research Project Leaders or collaborators have the same rights and responsibilities as other members of the Group (see below for Participation of NIH Intramural Scientists).
• The Awardee Institution and/or Research Project Leader's Institution will retain primary custody of and have primary rights to data as specified under the NIMH approved data and research resource sharing plans (described above). These plans should include sharing clinical and genotypic data with the NIMH Center for Collaborative Genomic Studies, genotype-phenotype data with the database of Genotypes and Phenotypes (dbGaP), and/or clinical and associated genotype and phenotype data associated with autism spectrum disorders to the National Database for Autism Research (NDAR), as appropriate. The Government, via the NIMH Project Scientist(s), will have access to data generated under this cooperative agreement and may periodically review the data consistent with current DHHS, PHS, and NIH policies. Timely publication of major findings by the Group members is strongly encouraged. Publication or oral presentation of work done under this agreement will be accompanied by appropriate acknowledgment of NIMH support, including the assigned cooperative agreement award number.
• Ownership of reagents (including cell lines) developed during the course of the research rests with the respective Group member(s) who generated them. However, prior to award, the Group must formulate a plan for final disposition of the reagents and ownership rights in the event that the reagents are transferred to other parties who make discoveries using them. Disposition of biomaterials is expected to comport with NIMH policy NOT-MH-13-002 regarding source cell and reprogrammed cell sharing through to the NIMH Center for Collaborative Genomic Studies on Mental Disorders, Stem Cell Center (http://nimhgenetics.org). This plan is subject to approval by NIMH.
• Ownership of all other tools, protocols and assays developed during the course of the research rests with the respective Group member(s) who generated them. It is the intention that these new tools, protocols and assays be fully evaluated for potential utility in developing diagnostics or therapeutics for mental health disorders. The evaluation process should be described in the timeline(s) with milestones; investigators should describe progress toward milestones in each annual progress report and the final report of the cooperative agreement. The Group will follow the NIMH approved research resource and data sharing plans.

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

The Project Scientist(s) interact scientifically with the Group and may provide appropriate assistance, including assisting in research planning, suggesting studies within the scope of the Group's objectives and research activities, framing research directions within the context of NIMH priorities and the portfolio of supported research, participating in the design of experiments agreed to by the Group, participating in the analysis of results, and advising in management and technical performance. The Project Scientist(s) will be a member(s) of the Steering Committee. However, the total membership by NIMH staff will not exceed one-third (1/3) of the membership of the Steering Committee. In all cases, the role of NIMH will be to assist and facilitate and not to direct activities.

The NIMH Project Scientist(s) can recommend the use of other NIMH resources in support of the NCRCRG research activities if such resources are necessary on an occasional basis. The following is a list of resources that are readily available and may be supplied if they become desirable during performance. It is not anticipated that requests of services will be considered as a continuing need.

• Use of biomaterials, data or selected services from the NIMH Center for Collaborative Genomic Studies on Mental Disorders (e.g., Cell and DNA Repository, Stem Cell Center).
• Reference compounds for standardization of test systems, as analytical standards, and for related purposes.

Additionally, an NIMH Program Official will be responsible for the normal programmatic stewardship of the award, including monitoring implementation of the data and research resource sharing plans and will be named in the award notice. The NIMH conflict management plan is as follows: the Program Officer assigned will maintain the normal programmatic stewardship of the cooperative agreement. The NIMH Program Officer will not be in a supervisee relationship(s) under the NIMH Project Scientist. Substantial NIMH staff involvement is contemplated for the entire award period based on the need for such involvement as described above.

Participation of NIH Intramural Scientists. An NIH intramural scientist may not serve as the PD/PI of an NCRCRG but may participate in the Group as a Project Leader, Scientific Core Leader, collaborator, or consultant. However, an Intramural scientist may not receive salary, equipment, supplies, or other remuneration from awards resulting from this FOA. The Intramural scientist must obtain written approval of his/her NIH Institute Scientific Director for the amount of resources that may be allocated to the project. The approval must also specify that the conduct of the project will comply with the DHHS regulations for research involving human subjects (if applicable) and with the PHS policy on vertebrate animal research. The participation of an intramural scientist is independent of and unrelated to the role of the NIMH Project Scientist. For NCRCRG applications that include NIH intramural components, the intramural resource level will be included in the total cost of the overall application. The involvement of Intramural scientists needs to be consistent with NIH Policy and all applicable federal laws and regulations: http://www1.od.nih.gov/oir/sourcebook/ethic-conduct/ethical-conduct-toc.htm.

Areas of Joint Responsibility include:

A governing NCRCRG Steering Committee composed of the PD/PI, Research Project Leaders, Core Directors, NIMH Project Scientist(s), External Consultation Panel scientists (see below) and an NIMH Program Official (as a non-voting member) will be established in each NCRCRG to assist in monitoring and developing the scientific content and direction of the program. The Steering Committee members will meet periodically to review progress, plan and design research activities, and establish priorities. The frequency of meetings, not fewer than two per year, will be determined by the PD/PI who will be responsible for scheduling, in consultation with NIMH program staff (meetings to be located in or near Bethesda, MD, or web/teleconference-based as appropriate), and for preparing concise proceedings or minutes (two or three pages), which will be delivered to the members of the Group within 2 weeks of the meeting. The meetings will be thematically based and structured around the opportunities and needs of the Group as they arise.

• Three or more External Consultation Panel scientists, to be nominated by the PD/PI and Project Leaders after application review, approved by the NIH Program Official and named at the time of award, will participate as members in Steering Committee meetings, provide expert advice on critical technical and strategic elements of the NCRCRG (e.g., tool, protocol and assay development, validation/qualification measures, statistical analysis) and will serve in an independent advisory capacity to NIMH Project and Program staff. The Panel will meet at least once annually (meetings to be located in or near Bethesda, MD, or web/teleconference-based as appropriate), usually during one of the Steering Committee meetings. Panel scientists may be added or substituted by two-thirds majority vote of the Steering Committee members during the course of the project.

Should more than one NCRCRG be funded, the Groups will be federated through a NCRCRG Consortium Committee composed of the PD/PI and additional project leader from each Group, NIMH Project Scientist(s), and NIMH Program Official (as a non-voting member). The Consortium Committee members will meet periodically in person or by teleconference to review progress and identify emerging opportunities for strategic partnerships. The Consortium Committee will select, by majority vote, a Chair from among the PD/PIs for a two-year term. The frequency of meetings, not fewer than one per year, will be determined by a Consortium Committee Chair, who will be responsible for organizing the meeting (to be located in or near Bethesda, MD, or web/teleconference-based as appropriate) and for preparing concise proceedings or minutes (two to four pages) which will be delivered to the members of the Group within 2 weeks of the meeting. In the spirit of strategic alliances to meet the objectives of the program, the Consortium Committee may agree by two-thirds majority vote to ad hoc participation of PD/PIs from one or more relevant research projects, centers, networks or consortia, e.g., with NIH R01, P50, U01, U19, U54, U24 awardees, as well as other qualified scientists, to gain the advantages of broader consideration of research methods for validation, qualification, or creation of public research resources for translational research. Investigators from such projects may be invited to NCRCRG Consortium-wide workshops upon agreement of the Consortium Committee.

The principal end products of NCRCRG activities for NIMH are expected to include: 1) utilization of sufficient patient-derived samples to achieve appropriate statistical power; 2) research tools; 3) robust and well-validated cell differentiation protocols, datasets and functional assays relevant to pathophysiology; and 4) preclinical cell-based platforms to evaluate novel therapeutics. Resource contributions from collaborating partners are strongly encouraged for any phases of study.

Dispute Resolution:

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

Intellectual Property and Patent Rights for New Inventions:

Since the NCRCRG is designed primarily as a pre-competitive public-private partnership with a focus on methodological and data reproducibility and standardization within and beyond the Group, collaborations should be designed with the overarching goal of rapidity and transparency in reporting and disseminating new methods and data. However, patent coverage may exist or may be expected for certain technologies used or developed as part of the collaboration; it is essential that NIMH Program staff be made aware of this and applicants are expected to provide plans to address the handling of intellectual property in a manner consistent with the purpose and scope of this FOA.

Successful applicants will supply the following confidential materials to the NIMH Program Official listed under Section VII. Agency Contacts.

• Each applicant Group is expected to provide a detailed description of the approach to be used for handling intellectual property and for licensing where appropriate, in particular where the invention may involve investigators from more than one institution. Procedures must be described for resolution of legal problems should they arise. Your attention is drawn to the NIH Extramural Technology Transfer Policies and Documents.
• A formal statement of Intellectual Property among all Group members and their institutions as well as a detailed description of procedures to be followed for resolution of legal problems which may develop, must be signed and dated by the organizational official authorized to enter into intellectual property arrangements for each Group member and member institution. The signed agreement must be submitted prior to award to the appropriate NIMH staff at the addresses provided under Section VII. Agency Contacts.
• A plan must be developed for disposition of reagents, methods and assays in Research Projects, where appropriate, in conformance with the Cooperative Agreement Terms and Conditions of Award, consistent with achieving the goals of the program. The signed document must be submitted prior to award to the appropriate NIMH staff at the addresses provided under Section VII. Agency Contacts.
• Prior to the award, the PD/PI and each Project Leader must provide a signed statement of acceptance of the participation of NIMH staff during performance of the award as outlined above.

Note: Do NOT submit documents relating to Intellectual Property and Patent Rights with the application. However, awards will not be made until these documents are received and approved by NIMH.

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

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

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

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

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David M. Panchision, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-443-5288
Email: [email protected]

David Armstrong, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-443-3534
Email: [email protected]

Terri Jarosik
National Institute of Mental Health (NIMH)
Telephone: 301-443-3858
Email: [email protected]

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

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