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

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

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

The human brain is a highly complex organ, involving genetic and molecular interactions operating within an intricate system of cells and circuits, driving higher order operations (e.g., mental processes, behaviors) that act upon and respond to the individual's environment. Alterations in this elaborate biological system can give rise to neurological and psychiatric conditions that collectively account for the largest proportion of years lived with disability worldwide. In the last decade, well-powered human genetic studies have illuminated the genetic architecture of psychiatric and neurodevelopmental disorders ranging from more penetrant, rare variants to less penetrant, common variants. Additionally, a wide array of novel technologies is now available to probe brain biology across levels of analysis.

Decoding the biological basis of psychopathology involves tackling the challenging problem of causally linking biological processes across multiple levels of analysis, from genetic factors to molecular processes, cells, circuits, networks, and behaviors. While individual computational models exist for genetic networks or specific biological / biophysical features and behaviors, what neuropsychiatric research currently lacks is a coherent theoretical framework that links and provides insights into the propagation of actions and consequences from one scale of biological processes to another.

The Convergent Neuroscience (CN) program aims to exploit a wealth of unbiased, large scale data being generated from genetic, neurobiological and clinical research by facilitating collaboration with experts from orthogonal disciplines (e.g., mathematics, computation, physics, engineering) who use multi-scale modeling and related computational methods such as machine learning. The objective of research under this FOA is to understand causal linkages across different scales (e.g., molecular, cellular, circuit, behavioral, clinical) relevant to neuropsychiatric disorders, using theoretical frameworks to model how specific constituent processes at one level of analysis contribute to quantifiable properties at other levels, either directly or as emergent phenomenon.

Applications responding to this FOA should incorporate four key features:

(1) A premise on identifying the causal and disease-relevant relationships between objective genetic/biological/clinical criteria at two or more contiguous levels of analysis, whether involving human subjects or experimentally tractable in vivo or in vitro paradigms (genetic variation can be one of the contiguous levels of analysis or can be the context in which other, higher levels of analysis are linked);

(2) Use of the large and diverse datasets existing or generated at these levels of analysis to develop testable theoretical models within three years of award;

(3) Experimental testing of the model-based predictions to confirm or reject their validity;

(4) Preferential utilization of scalable approaches to maximize analytic throughput, content, sensitivity, selectivity, spatiotemporal resolution and robustness.

Importantly, where studies are premised or focused on genetic factors, they should be based on unbiased genetic studies of disease risk (i.e., well-powered, statistically significant genome-wide association) in accordance with NIMH Council Genomics Workgroup recommendations described in NOT-MH-18-035. Where studies utilize non-human organisms, the research design should be framed by specific mechanistic neurobiological questions rather than as "models of mental illness", in accordance with NIMH guidelines in NOT-MH-19-053. Where studies involve human clinical endpoints, researchers are encouraged to use the Research Domain Criteria (RDoC) framework as a way to facilitate the integration of clinical endpoints with underlying neurobiological mechanisms. When combined with theoretical modeling, the integration of these approaches should yield causal linkages between levels of analysis and mechanistically explain key functional dimension(s) of neurobiology and behavior relevant to mental illness pathophysiology, with potential for the unbiased identification of novel targets for therapeutic intervention.

Note: this FOA supports the option to propose a mechanistic clinical trial (e.g., using an established intervention to elucidate a biological mechanism). It does not support therapeutic clinical trials (i.e., determining the safety or efficacy of a novel intervention).

Theoretician-Experimentalist Partnership and Group Governance:

Partnership: Co-participation of theoreticians and experimentalists is expected from year one of a CN Group (herein referred to as a "Group"). Each application must include an Overall Plan along with individual Research Project Plans that reflect a theoretician-experimentalist partnership that is either already ongoing or will be active at the time of award. Partnerships must include at least one theoretician and one experimentalist Principal Investigator (PI), although greater numbers of non-PI collaborators can be included see Section IV, Overall Budget, for effort commitment requirements for PD/PI and MPIs. All investigators are expected to collaborate on the proposed goals in a manner that would enable the entire joint endeavor to be administered in a unified manner. Groups should exploit the unique advantages and capabilities that theoretician-experimentalist collaborations provide, such as tailoring design to the availability of novel tools in multiple disciplines (e.g., mathematics, computation, physics, engineering, genetics, neurobiology, clinical research).

While there is no cost sharing requirement included in this FOA, the CN program encourages applicant and collaborating organizations, including private partners (e.g., information technology, biotechnology, pharmaceutical, or other private organizations), to contribute resources to this endeavor. 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 endeavor, should be included in the Letters of Support section of each respective Project or Core component. 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.

Governance: The basic outlines of the governance structure are described in Section VI, Cooperative Agreement Terms and Conditions of Award. Each Group will be encompassed in one application. If two or more CN applications are funded, the Groups will be federated into a "Consortium". Each Group:

• Will have a Governance and Organizational Structure that accommodates the unique features of the Group, facilitates collaboration and progress, and recognizes substantial involvement by NIH Program staff, following the Section IV, Overall component instructions.
• Will propose a series of Milestones integrating all Group project/core activities, following the Section IV, Overall component instructions. The milestones will be used to guide progress over the life of the Group and will be used as an objective progress metric by NIH Program staff.
• Will include an Administrative Core component to assist in governance, overall program management, project/core coordination (including milestones) and other administrative responsibilities, following Section IV, Administrative Core component instructions. A Project Manager with strong scientific, management and administrative expertise should be assigned to this Core to fulfill core duties in assistance and under the supervision of the PD/PI.

CN Research Project Features:

A CN Group will have two or more Research Projects, which should consist of at least one theoretical modeling project and at least one experimental or clinical project. Any project may involve multiple sites, teams and disciplines. Multiple orthogonal approaches can be used to raise confidence that the generated model and mechanisms are relevant and causal with respect to pathophysiology. Projects collectively should contribute to the four key features described above in the Program Objectives.

Theoretical modeling can integrate: deep-learning algorithms with effective explanatory techniques; theory-driven models with data-driven models; bottom-up models with top-down models; multi-modal data from distinct levels of analysis to predict, classify or explain one or multiple outcome measures (e.g., using multi-kernel learning, multimodal data fusion algorithms or similar technology). This can include, but is not limited to:

• Methods to assess fundamental features in large non-linear systems (e.g., phenotyping activity-patterns of molecules, cells, circuits);
• Adaptive/closed loop (supervised and/or un-supervised) computational methods to optimize protocols;
• Biophysically realistic bio-structural and functional models enabling both wide-angle investigations (of the full system dynamics in high-resolution) and focused perspectives on specific components, leveraging data from neuro-technologies (e.g., high-resolution transmission electron microscopy, voltage/calcium indicators, array tomography);
• Algorithms performing trial-by-trial, individual-level, and population-level predictions of behavior from neural data;
• Algorithms for dynamic tracking of activity from continuous data and real-time signal processing, novel methods for interactive data exploration and visualization, and/or innovative dimensionality reduction in high-dimensional data sets;
• Predictive analytic approaches to existing data from data systems to identify and classify subgroups;

Levels of analysis can include, but are not limited to:

• Genomic (e.g., DNA variation, epigenomic/chromatin, transcriptomic) or phenomic (e.g., proteomic, metabolomic) measures, including the multiplexing of these measures in the same cells;
• Molecular interactions and pathways (e.g., signal transduction, neurotransmitter-receptor interactions, protein-protein interactions);
• Small-scale multi-cellular function (e.g., synaptic activity, micro-circuitry);
• Cell population interactions across circuits (e.g., macro-circuitry);
• System-wide connections (e.g., neural networks);
• Behaviors in the context of their underlying neural organization (e.g., RDoC domains of function such as positive valence systems, negative valence systems, arousal/regulatory systems, cognitive systems, social process systems);
• Time-series (cross-sectional or longitudinal) measures, including those (a) causally linking events at short time scales with those at longer time scales, or (b) measuring developmentally relevant trajectories causally linking a pre-disease state with a disease state.

Paradigms from which data are derived can include human subjects or experimentally more tractable systems, including but not limited to:

• Human post-mortem specimens (e.g. for large scale genomic or molecular reference data);
• Clinical instruments (e.g., neurocognitive, electrophysiological, structural and functional connectivity, electronic health records, crowd-source measures);
• Human cell-based assays (e.g., induced pluripotent stem cells [iPSCs] to experimentally test predictions related to human-specific genomic architecture or cellular function);
• Comparative analysis in non-human species (e.g., non-human primates, rodents, zebrafish) provided the paradigms are genetically relevant and well-justified in terms of evolutionary conservation with respect to the scientific question;
• Paradigms involving genome-environment interactions, brain-peripheral organ system interactions, or activity/perturbation-based screens to measure state-dependent dynamics.

While primary data generation is permitted, projects should rely heavily on secondary analysis of existing large datasets whenever possible. Examples of such reference datasets include, but are not limited to the BRAIN Initiative Cell Census Network, Brainspan, CommonMind Consortium, GENCODE, Roadmap Epigenomics Mapping Consortium, International Human Epigenome Consortium, Psychiatric Genomic Consortium, Genotype Tissue Expression Program (GTEx), ENCODE, PsychENCODE, Autism Sequencing Consortium, Bipolar Sequencing Consortium, Human Connectome Project and the NIMH Data Archives. For experimental testing of predictions, applicants are encouraged to utilize novel technologies of the BRAIN Initiative as well as centralized resources such as the NIMH Repository and Genomics Resource. Projects that propose extensive, time-consuming or high-risk generation of novel tools and resources as a pre-requisite for theoretical modeling or experimental validation may not be appropriate for this FOA.

CN Resource Core Features:

These components are permitted when necessary for support needs that are distributed across two or more Projects. This will also support opportunities for sharing technology and expertise with external investigators, where appropriate. Resource Cores should contribute to the four key features described above in the Program Objectives and can include, but are not limited to:

• Resource or reagent distribution;
• Common instrumentation and analytics;
• Data management via a Data Science Core (DSC): In this case, the proposed science in each individual Group should drive the strategy for the DSC, such that the plan is customized to fit the specific data science needs of the proposed research projects and facilitate seamless workflows for aggregation and analysis of the heterogeneous data generated in Group.

CN Consortium Data Commons (CN-CDC) Features:

While optional, applicants are encouraged to propose a component dedicated to data harmonization and management across U19 awards; should more than one CN Group be funded, NIMH will support only one CN-CDC for all CN Groups. This CN-CDC may utilize the same personnel and infrastructure as a Group-specific Resource Core devoted to data science, but will include significant capabilities in development, outreach, training and coordination to manage data types and volumes from other U19 Groups. The CN-CDC should likewise have a data structure that is harmonized and federation-capable with relevant external data archives (e.g., BRAIN Initiative archives, NIMH Data Archives, Allen Brain Atlas) The operation of this component should be budgeted separately from other components of the application and will be evaluated as an independent component; while multiple applications may include a CN-CDC component, only one CN-CDC will be funded to serve all CN Groups.

Consortium Activities, Collaboration and Dissemination:

While each Group will be expected to operate autonomously, there may be opportunities for Consortium-level collaboration, depending on the number and nature of the funded Groups. In the spirit of strategic alliances to meet the objectives of the program, both investigators and NIH Program staff may recommend inclusion of 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 methods, resources and theoretical models for convergent neuroscience research. Beyond this, the Consortium will operate as follows:

• A workshop of the entire Consortium of CN Groups will be held every year (as applicable) to facilitate collaborative opportunities across CN Groups.
• In addition to harmonizing data management within each CN Group, such data harmonization will occur through the consortium structure and a CN Consortium Data Commons (CN-CDC). This will occur from the outset of the program - see Section IV instructions for developing the Overall Resource Sharing plan for experimental data.

Examples and features of responsive studies involving the combination of data-derived theoretical modeling followed by experimental prediction testing can include, but are not limited to:

• Studies on how the effect of highly penetrant genetic risk variation is causally propagated across levels of analysis (e.g., chromatin dynamics, cell type-specific processes, synaptic and circuit-specific function, emergent network properties like oscillations, behaviors linked to those circuits) in experimentally tractable paradigms.
• Systems biology "interactome" studies measuring effects of low- or moderate-penetrance genetic variation at multiple loci in high content assays (e.g., in protein-protein interaction or metabolomic networks) to identify common or unique pathways that are causally related to functional changes at higher order scales.
• Use of existing reference datasets (e.g., epigenomic, transcriptomic) to impute and theoretically model cell types, circuits and cognitive domains implicated in pathophysiology, whose predictions are then tested experimentally in human cell-based (e.g., iPSC) or whole organism studies.
• Integration of different multi-modal, multi-dimensional clinical data (e.g., interview, neurocognitive, high density electrophysiological, structural/functional connectivity, environmental) and/or further linkage with high content measures at smaller-scaled levels of analysis (e.g., genomic/molecular/cellular/microcircuit measures from specimens from those same subjects).
• Studies of circuit functions to identify pathological neuro-behavioral signals or modify performance in a relevant mental function by modulating neural circuits.
• Inclusion in the design of the effects of individual genetic risk background.
• Inclusion in the design of associating state-dependent cellular and circuit activity (e.g., in response to changing input or perturbations) with underlying genomic risk architecture.
• Inclusion in the design of developmental trajectories across multiple levels of analysis, including experientially sensitive/critical periods of development with respect to illness risk or resilience in clinical populations or key maturational milestones in model systems.

Examples of applications that are not responsive to this FOA and will be withdrawn include:

• Clinical studies based solely on Diagnostic and Statistical Manual of Mental Disorders (DSM) nosology;
• Therapeutic clinical trials (i.e., determining the safety or efficacy of a novel intervention);
• Genomic analyses that are not in accordance with NIMH Council Genomics Workgroup recommendations described in NOT-MH-18-035, such as "candidate" gene approaches or functional analysis of common genetic variation that has not yet been fine-mapped;
• Studies involving risk gene / risk locus discovery;
• Genetic- or molecular-level analyses correlated to behavioral/clinical phenotypes without considering data from any intervening levels (e.g., cellular, circuit, network), such as studies focusing on neuroimaging genetics;
• A focus on candidate mechanisms or therapeutic targets not derived from analysis of unbiased datasets;
• A focus on disorders not aligned with the NIMH mission and priorities.

Applicants are strongly encouraged to contact the Program Officer(s) listed in Section VII, Agency Contacts, as Scientific/Research Contact(s) in order to determine how well their application aligns with the objectives of this FOA and of overall NIMH priorities. Applicants should also carefully examine Section IV.2 for complete instructions on necessary application elements, including milestones and data management.

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

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

Higher Education Institutions

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

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

o Hispanic-serving Institutions

o Historically Black Colleges and Universities (HBCUs)

o Tribally Controlled Colleges and Universities (TCCUs)

o Alaska Native and Native Hawaiian Serving Institutions

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

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

Other

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

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

Applicant Organizations

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The letter of intent should be sent to:

Email: nimhpeerreview@mail.nih.gov

Available Component Types	Research Strategy/Program Plan Page Limits
Overall	12
Admin Core (use for Administrative Core)	6
Core (use for optional Resource Core[s])	6
Project (use for Research Projects)	12
Consortium Data Commons (optional)	6

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

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

The application should consist of the following components:

• Overall: required; maximum of 1
• Administrative Core: required; maximum of 1
• Resource Cores: optional; maximum of 3
• Research Projects: required; minimum of 2; maximum of 4
• Consortium Data Commons: optional; maximum of 1

When preparing your application, use Component Type Overall .

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

Complete entire form.

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

Follow standard instructions. When describing Facilities & Other Resources, indicate the institutional investments and resources that constitute the environment for this research program. New cost-sharing commitments are not required but are allowed. Some examples of institutional environment could include recruitment and salary support of new faculty or professional staff positions to support the resource components, start-up packages, space renovations for team investigators, new facilities within the component projects, dedicated equipment for research and resource components, dedicated budget lines or facilities for a team consortium, dedicated use of commercial products and technologies, equipment and technology contributions from commercial collaborators, etc. Institutional environment can include evidence of pre-application institutional investments, critical start up resources or evidence of institutional annual support in the budget.

Enter primary site only.

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

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

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

The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover. The contact PD/PI will be expected to devote at least 2.4 person months of effort to the CN program, which can be divided across Projects/Cores; each additional Multi-PD/PI will be expected to devote at least 1.8 person months of effort to the CN program, which can be divided across Projects/Cores. Any effort toward an optional CN Consortium Data Commons (CN-CDC) does not count toward this minimum effort requirement.

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

Specific Aims: Provide a concise description of overall CN aims. Outline how the Projects and Core(s) will contribute to attaining the theoretical and experimental objectives.

Research Strategy: Provide a synthesis of objectives, coordination and governance that addresses both scientific and logistical challenges for successful partnerships. This will include:

Significance: Provide an overview of the central theme and general objectives necessitating the formation of the CN Group, the importance of the problem(s) to be studied and how these will affect neurobiological and/or clinical research. The Group objectives should be relevant to and compatible with the NIMH priorities in Section I - Funding Opportunity Description.

Innovation: Highlight how the Group seeks to change current research paradigms for studying mental illness, including novel concepts, approaches, methodologies, instrumentation or collaborative structures, along with any advantages they provide over current practices. Applications should describe the unique advantages and capabilities that the collaborative structure will provide and how this synergizes beyond what could be achieved through a traditional research project grant mechanism.

Approach: Each CN Group should have a fully articulated Governance and Organizational Structure that lays out the overall organization, major tasks each partner will complete, and benefits each brings to this alliance to enhance prospects for completing specific aims. This should also delineate shared leadership, conflict resolution, technical, scientific and preclinical or clinical responsibilities where appropriate. Importantly, applicants should describe how they intend to incorporate NIMH involvement and adhere to other terms and conditions of the cooperative agreement. There should be a clear description of how each component Research Project, Resource Core (as applicable) and Administrative Core is necessary for the attainment of the CN program objectives, including available technical personnel to permit efficient and successful conduct of the proposed research. Applicants should describe how collaborators within each CN Group will interact on a frequent schedule dictated by the proposed design and will additionally hold teleconferences on a monthly schedule; collaborators within each group are also encouraged to include plans for partnered theoretical and experimental/clinical cross-training to bridge expertise in the respective disciplines.

Investigators: A flow chart of organizational governance, using as guidance the Section VI, Cooperative Agreement Terms and Conditions. This section should describe the major scientific or logistical responsibilities of each key multi-disciplinary collaborator, the benefits each brings to this alliance to enhance prospects for completing specific aims by virtue of their expertise (e.g., in mathematics, computation, physics, engineering, genetics, neurobiology, and/or clinical research, as applicable). The flow chart should also include the External Consultation Board; while the qualities and expertise of the consultants should be described, they should not be named in the application, contacted or appointed prior to review (Note: they will be named just prior to the time of award).

Environment: Evidence that each component Research Project, Core(s) and the Group as a whole has available facilities necessary for conduct of the proposed research. Do not duplicate information in the resource sections. Rather, emphasize how those resources contribute to the overall effort. As appropriate, applicants may include a broad description of how any resource contributions by the partners within the CN Group (e.g., academic, information technology, biotechnology, pharmaceutical, or other private organizations) enhance the environment in support of the overall goals of the endeavor. 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, as applicable.

Timeline and Milestones: A descriptive and graphic timeline must be included. Additionally, a distinct final section, entitled Milestones , should concisely propose indicators of progress at critical junctures. The milestones should be regarded as criteria for evaluating the progress and direction of the CN Group in line with the four key features of CN projects (as described in Section I, Program Objectives). They should not be a restatement of specific aims, but rather should be:

• Tailored to the unique scope of each CN Group and written concretely enough to evaluate what exactly will have been achieved. Milestones should be well-described, quantifiable, and scientifically justified;
• Written to benchmark key subcomponents of (a) initial data analysis, (b) theoretical modeling and achieving a testable model within three years of award, (c) prediction testing through experiment, and (d) iterative model improvement as time permits;
• Provided for each year (1-5) of the award and accounting for all Group Project/Core activities, clearly denoting which milestones are specific to an individual Project/Core and which integrate work of multiple Projects/Cores. Note that if an optional CN Consortium Data Commons component is included, those and only those milestones should be addressed separately in the CN-CDC component and not in this Overall component.

This section should be included within the page limit of the Overall Research Strategy and should reflect all project/core activities, including Administrative core activities like Board meeting scheduling. If funded, investigators should describe progress toward milestones in annual and final progress reports of the award.

Letters of Support: Include individual letters of commitment to the collaboration and agreement to the stated governance and communication plan (described in the Research Strategy) by all Research Project and Core Leaders. Note that letters detailing specific outside resource or intellectual 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 as provided in the SF424 (R&R) Application Guide, with the following modification:

• 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]) to the NIMH Repository and Genomics Resource (NRGR). The Resource Sharing Plan should describe biospecimen types, estimated numbers and a timeline for submitting these to NRGR.
• Clinical Data Sharing Section: All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. Applications that involve human subject recruitment are expected to submit clinical (e.g., interview, phenotypic instrument, clinical trial) data to the NIMH Data Archive (NDA) in a manner comporting with NIMH policy for clinical data sharing (NOT-MH-19-033). Note that central clinical coordination and local data management for data cleaning and entry and bio-statistical consulting will be the responsibility of the awardee; therefore, CN applications should budget appropriately in the relevant Project/Core component to comply with these data sharing expectations. Any proposed CN-specific data sharing infrastructure should comport with the data sharing expectations described above. Applicants are encouraged to use the NDA data sharing cost estimation tool within the Data Contribution link when preparing budgets.
• Genomic Data Sharing Section: Applications that propose to generate large scale genomic data should include a plan to share data in accordance with the NIH Genomic Data Sharing Policy NOT-OD-14-124. The NIMH Data Archive (NDA) will serve as the repository for human genomic data from primary biospecimens (per NOT-MH-19-033), unless NIMH agrees to a different data archive during negotiations prior to award.

Human subject consent language associated with the above biomaterials and data collection should be consistent with banking and wide sharing through centralized repositories.

• Non-Trial Experimental Data Sharing Section: Per the terms and conditions of this FOA, recipients of the cooperative agreement are required to work with the CN Consortium Data Commons (CN-CDC) to harmonize the structures through which experimental data is managed. For the purposes of this FOA, this category excludes data that would be submitted to NDA and instead includes but is not limited to human iPSC-based and model organism data (transcriptomic, proteomic, high content imaging, electrophysiology). The expectation is that experimental data from CN awards will be submitted to the CN-CDC every 6 months. Submitting data to the CN-CDC is distinct from sharing that data with the research community. Submitted data will generally be held in a private enclave until the data are shared with the research community. Frequent submission allows those measuring the data to perform quality control checks as the data are deposited. Submitting the data on an ongoing basis is often easier than trying to package the data at the end of an award period. After the data have been submitted to the CN-CDC, it will be shared with the research community when papers using the data have been published or at the end of the award period, whichever occurs sooner. The calendar for submitting data to the relevant archive and sharing data with the research community will depend on the exact details of the experiments that are being conducted.

Data Sharing Plans should include:

1) a summary of the data that will be shared;

2) a description of the standard(s) that will be used to describe the data set;

3) the data archive(s) that will house the data;

4) the proposed timeline for submitting data to the relevant archive and sharing data with the research community.

Applicants are strongly encouraged to consult with NIH 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 NIH Program staff and will be included in the terms and conditions of the Notice of Award.

Appendix:

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

PHS Human Subjects and Clinical Trials Information (Overall)

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

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

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

When preparing your application, use Component Type Administrative Core.

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

Complete only the following fields:

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

Enter Human Embryonic Stem Cells in each relevant component.

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

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

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

List all performance sites that apply to the specific component.

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

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

• Budget forms appropriate for the specific component will be included in the application package.
• A Project Manager with strong scientific, management and administrative expertise should be assigned to this Core to fulfill core duties in assistance and under the supervision of the PD/PI. The Project Manager is expected to commit at least 4.8 calendar months total effort to the U19, but that effort can be distributed between the Administrative Core and other Projects/Cores.
• The CN Group funded through this FOA will have an External Consultation Board to provide governance (see Section VI, Cooperative Agreement Terms and Conditions of Award). While Board meetings can be accomplished virtually, this budget section may include requests for travel funds (if not covered by private sources) for Board members to attend one annual Board meeting in person along with justification. This budget section should also include contingency travel funds for the Project/Core leaders (including PD/PI/MPIs) to attend an annual CN Consortium meeting in person in the event that more than one CN group is funded.
• Applicants should budget appropriately to comply with data sharing described in the Resource Sharing Plan instructions.
• While the CN program encourages applicant and collaborating organizations, including private partners (e.g., biotechnology, pharmaceutical, or other private organizations), to contribute resources to this endeavor, 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.

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 endeavor, including optimizing communication, decision-making and sharing between the Project and/or Resource Core teams.

Approach: Describe how each Project or Resource Core (as applicable) will draw upon the Administrative Core and how it in turn will respond to Project or Resource Core needs. The description of the Core should clearly indicate the facilities, resources, services and professional skills that the Core will provide, which will include the roles and duties of the PD/PI and Group Project Manager. Moreover, information must be provided about how the collective operation of the Core will be performed in a coherent manner, which includes monitoring progress toward milestones, coordinating efforts across Projects/Cores and organizing and moderating Group meetings. Describe how the Administrative Core will monitor, facilitate and ensure the engagement of each Resource Core and Project with the CN Consortium Data Commons (CN-CDC), should two or more CN Groups be funded, so that access-controlled data flows through the CN-CDC over the course of the award on the expected schedule.

A Timeline can optionally be included in this section or can be integrated into the obligatory Timeline in the Overall section. A Milestones section should not be included here; rather, milestones specific for this core must be included and integrated only in the Overall Section.

Letters of Support: As applicable, include a detailed description of any support, specific to the individual Project, that is provided by the applicant institution and/or collaborators (e.g., individual investigators or organizational partners in information technology, biotechnology, pharmaceutical, or other private endeavors) and which will enhance the potential for success and sustainability of the CN 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, 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 endeavor, should be included in this section. Organizational 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 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:

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

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

When preparing your application, use Component Type Resource Core.

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

SF424 (R&R) Cover (Resource Core)

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Resource Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Resource Core)

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

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

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

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

List all performance sites that apply to the specific component.

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

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

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• 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 (Resource Core)

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

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

PHS 398 Research Plan (Resource Core)

Specific Aims: Provide a concise description of Core aims.

Research Strategy:

Significance: Describe how the Resource Core will contribute to the goals of the overall Group. Issues to be addressed can include quality control, special expertise, cost effectiveness, and increased efficiency.

Innovation: Highlight any novel features of the Resource Core that enhance the collaborative endeavor, including the improved 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 performed in a coherent manner;

A Timeline can optionally be included in this section or can be integrated into the obligatory Timeline in the Overall section. A Milestones section should not be included here; rather, milestones specific for this core must be included and integrated only in the Overall Section.

Letters of Support: As applicable, include a detailed description of any support, specific to the individual Project, that is provided by the applicant institution and/or collaborators (e.g., individual investigators or organizational partners in information technology, biotechnology, pharmaceutical, or other private endeavors) and which will enhance the potential for success and sustainability of the CN 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, 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 endeavor, should be included in this section. Organizational 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 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:

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

PHS Human Subjects and Clinical Trials Information (Resource Core)

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

When preparing your application, use Component Type Research Project.

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

SF424 (R&R) Cover (Research Project)

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Research Project)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Research Project)

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

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

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

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

List all performance sites that apply to the specific component.

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

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

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of 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 (Research Project)

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

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

PHS 398 Research Plan (Research Project)

Specific Aims: Provide a concise description of Project aims.

Research Strategy:

Significance: Describe goals and the impact of the theoretical framework and/or science proposed in relation to the state of the field. This section should also explain the contribution of the Project to the overall goals of the CN program and how the component will interact with and benefit from other components.

Innovation: Highlight any novel features of the Project that contribute to the CN program goals. Explain how any unique and innovative contributions of the Project will be made possible by team synergy beyond the otherwise independent research projects.

Approach: Describe evidence for the feasibility of the proposed work, the advantages of any new methodologies, tools or resources, the potential pitfalls and alternative approaches for the project and how these might impact overall progress. Provide specific details on how the project will integrate with the research of other projects and resources of cores (as appropriate) in accordance with the four key features described in Section I, Program Objectives. Define key aspects of experimental rigor (as appropriate) and how they will be addressed in the study, including but not limited to:

• Issues of statistical, computational and/or experimental robustness and reproducibility;
• Primary and secondary statistical and/or experimental outcomes to be assessed (e.g., gene fold change, variance explained) and clearly state how these relate to proposed objectives;
• Number of experimental and control groups;
• The 'experimental unit' in the analysis and the implications thereof (e.g., there is a difference between N samples from one cell line, as distinct from one sample from each of N cell lines, or combining samples from multiple lines);
• The number of 'experimental units' in each experimental group;
• The total number of 'experimental units' to be measured;
• The number of times each 'experimental unit' will be measured;
• The number of independent replications of each experiment;
• Steps taken to minimize the effects of bias (e.g., batch effects, blinding, randomization) or an explanation of why this would not be appropriate;
• Having effect sizes clearly calculated and justified how they are biologically relevant;
• Demonstration that statistical power calculations are grounded in justifiable and explicit assumptions about both anticipated effect size and variability of the experimental effects;
• If statistical power calculations cannot reasonably be applied, providing a principled explanation of the choice of numbers (explanations based solely in terms of 'usual practice' or with reference solely to previously published data will not be considered adequate).

A Timeline can optionally be included in this section or can be integrated into the obligatory Timeline in the Overall section. A Milestones section should not be included here; rather, milestones specific for this project must be included and integrated only in the Overall Section.

Letters of Support: As applicable, include a detailed description of any support, specific to the individual Project, that is provided by the applicant institution and/or collaborators (e.g., individual investigators or organizational partners in information technology, biotechnology, pharmaceutical, or other private endeavors) and which will enhance the potential for success and sustainability of the CN 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, 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 endeavor, should be included in this section. Organizational 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 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:

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

PHS Human Subjects and Clinical Trials Information (Research Project)

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

When preparing your application, use Component Type Consortium Data Commons.

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

SF424 (R&R) Cover (Consortium Data Commons)

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 (Consortium Data Commons)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Consortium Data Commons)

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

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

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

Project /Performance Site Location(s) (Consortium Data Commons)

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 (Consortium Data Commons)

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

Budget (Consortium Data Commons)

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

• Applicants should budget appropriately to comply with resource and data sharing described in the Resource Sharing Plan instructions.
• The operation of this component should be budgeted as severable from other components of the application; while multiple applications may include a CN-CDC component, only one CN-CDC will be funded to serve all CN Groups.
• While the CN program encourages applicant and collaborating organizations, including private partners, to contribute resources to this endeavor, such resources for the 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 (Consortium Data Commons)

Specific Aims: Provide a concise description of CN Consortium Data Commons (CN-CDC) aims.

Research Strategy: Applicants are encouraged to propose a component dedicated to data harmonization and management across U19 awards; should more than one CN Group be funded, NIMH will support only one CN-CDC for all CN Groups. This CN-CDC may utilize the same personnel and infrastructure as a Group-specific Resource Core devoted to data science, but will include significant capabilities in development, outreach, training and coordination to manage data types and volumes from other U19 Groups. The CN-CDC should likewise have a data structure that is harmonized and federation-capable with relevant external data archives (e.g., BRAIN Initiative archives, NIMH Data Archives, Allen Brain Atlas). Note that the operation of this component will be budgeted separately from other components of the application and will be evaluated as an independent component; while multiple applications may include a CN-CDC component, only one CN-CDC will be funded to serve all CN Groups.

The CN-CDC will be responsible for coordinating management of experimental paradigm data (e.g., whole organism or in vitro preparations), which can include, but is not limited to single cell and bulk genomic / proteomic, high content imaging, anatomical, electrophysiology (e.g., whole cell, multielectrode array, EEG) and behavioral data. The CN-CDC will not be responsible for the management of clinical (e.g., interview, phenotypic instrument) data that is the purview of the NIMH Data Archives per policy (NOT-MH-19-033). However, the CN-CDC should have a data structure that is harmonized and federation-capable with relevant data archives (e.g., BRAIN Initiative archives, NIMH Data Archives, Allen Brain Atlas). The CN-CDC should be designed so that the consortium members and broader research community can access the data and platform utilities through an outward facing portal.

Data Coordination: This section of the research strategy should describe:

• how the CN-CDC will work with the Group awardees and other interested researchers to define and refine: all data and metadata types, experimental protocols, using and promoting common relational and semantic standards;
• how the CN-CDC will work with the Group awardees and other interested researchers to develop submission process and standards;
• how the CN-CDC will develop a streamlined workflow for upload, validation, and dissemination of all relevant types of experimental data as well as associated experimental and analytical protocols.
• how the CN-CDC will list and define the data to be shared with justification of the data quality and utility. For shared data, propose when it will be made available, where it will be stored, how it will be maintained, and how others will be able to find, access, and reuse it;
• how the CN-CDC will create a web site that allows anyone to explore the relationally linked data and knowledge.

Data Integration and Visualization: This section of the research strategy should describe:

• how the CN-CDC will lead the effort to coordinate with multiple interested parties to adopt and refine relational and semantic standards for linking heterogeneous data sets;
• how the CN-CDC will develop methods to visualize the datasets;
• how the CN-CDC will identify and be innovative to federate the CN-CDC with other data repositories and knowledge bases as appropriate, and to establish a unified and comprehensive open-access information system.
• how the CN-CDC will develop innovative strategies to collect and integrate datasets generated by the CN Group awardees as well as other datasets generated by the investigators outside of the CN consortium;
• how the CN-CDC will develop and disseminate user-friendly data registration, data analysis, and data visualization tools;
• how the CN-CDC will develop a database that can receive data and allows private collaboration among researchers prior to public release.

Management, Coordination and Communication: This section should describe:

• how the CN-CDC will be managed and who will oversee the day-to-day activities. CN-CDC leader should be recognized by the grantee institution as potentially being a PD/PI if not currently listed as such on the U19 application; may also include assistance by a CN-CDC Project Manager).
• how the management will support achievement of the proposed goals and milestones. Describe the organization of the proposed Center; its management structure of the Data Coordination Component, the Data Integration and Visualization Component, and other coordination and communication functions; key personnel; section leaders and reporting relationships; a management plan for fiscal accountability and communication; and any consultants, if relevant. Recruitment and training of personnel may also be discussed.
• how the proposed multiple efforts of the CN-CDC will be integrated;
• how collaborations or subcontracts, if proposed, will be managed;
• how the CN-CDC will facilitate communication across the consortium members and provide computational and data analysis support to identify knowledge gaps, prioritize research, and prepare reports;
• how the CN-CDC will facilitate the use of the data by the broad research and education community.
• how to enhance the collaborative effort among the Groups to ensure efficient cooperation, communication and coordination.

A Timeline and Milestones section must be included in the Research Strategy section for the CN-CDC. The timeline should describe the expected progression of the activities specific to the CN-CDC. (Note: this should be distinct from and independent of the timeline and milestones for the overall CN Group). Milestones should be identified along the timeline. These should be regarded as criteria for evaluating the progress and direction of the CN-CDC and should not be just a restatement of the specific aims. Milestones should be well described, quantifiable, and well-justified benchmarks with respect to key steps in the implementation of existing and development of new data/analytic platform features (e.g., deployment, automation, integration). 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: As applicable, include a detailed description of any support, specific to the individual Project, that is provided by the applicant institution and/or collaborators (e.g., individual investigators or organizational partners in information technology, biotechnology, pharmaceutical, or other private endeavors) and which will enhance the potential for success and sustainability of the CN 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, 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 endeavor, should be included in this section. Organizational 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 as provided in the SF424 (R&R) Application Guide.

Appendix:

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

PHS Human Subjects and Clinical Trials Information (Consortium Data Commons)

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

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

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

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

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

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

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

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

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

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

Does the CN Group address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the CN Group 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? How well is the question premised, with respect to the combined use of theoretical modeling and experimental prediction testing, for how specific constituent biological processes at one level of analysis contribute to quantifiable properties at other levels, either directly or as emergent phenomena?

In addition, for applications involving clinical trials

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? Regarding mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

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

In addition, for applications involving clinical trials

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

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed? How well does the CN Group exploit the unique advantages and capabilities that the collaborative structure will provide and how this synergizes beyond what could be achieved through a traditional research project grant mechanism?

In addition, for applications involving clinical trials

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

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

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

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

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

Overall, how well does each component Research Project, Resource Core (as applicable) and Administrative Core provide for the attainment of the CN Group's objectives? How well does the approach address the following expectations of the CN Group's ability to: (1) leverage the large and diverse datasets existing or generated at the selected levels of analysis to develop testable theoretical models within three years of award; (2) experimentally test the model-based predictions to confirm or reject their validity, (3) preferentially utilize scalable approaches to maximize analytic throughput, content, sensitivity, selectivity, spatiotemporal resolution and robustness?

In addition, for applications involving clinical trials

Does the application adequately address the following, if applicable:

Study Design:

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

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

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

Data Management and Statistical Analysis:

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

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

In addition, for applications involving clinical trials

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed? Does the application adequately address the capability and ability to conduct the trial at the proposed site(s)or centers? Are the plans to add or drop enrollment centers, as needed, appropriate? If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial? If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

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

Study Timeline

Specific to applications involving clinical trials

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

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

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

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

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

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

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

Not Applicable

Not Applicable

Not Applicable

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

Not Applicable.

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

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genomic Data Sharing Plan . In particular, reviewers should comment on the degree to which studies that involve human subject recruitment plan to submit clinical (e.g., interview, phenotypic instrument) data to the NIMH Data Archive (NDA) in a manner comporting with NIMH policy for clinical data sharing (NOT-MH-19-033). Reviewers should also comment on the degree to which studies that involve the generation or use of human subject-derived reprogrammed cells in their NIMH-funded research adequately plan 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 Repository and Genomics Resource (NRGR) per NIMH policy (NOT-MH-13-002). Finally, reviewers will comment on the degree to which the plan to harmonize and share experimental data through the CN Consortium Data Commons (CN-CDC) is reasonable.

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

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

CN Consortium Data Commons (CN-CDC)

Reviewers will consider each of the review criteria below in the determination of scientific merit and give a separate score for each, along with an overall impact score specifically for this component.

Significance

Does the proposed CN-CDC address the needs of the research consortium that it will serve? Is the scope of activities proposed for the CN-CDC appropriate to meet those needs? Will successful completion of the aims bring unique advantages or capabilities to the research consortium?

Investigator(s)

Are the PD(s)/PI(s) and other personnel well suited to their roles in the CN-CDC? Do they have appropriate experience and training, and have they demonstrated experience and an ongoing record of accomplishments in managing data and data analytics in research? Do the investigators demonstrate significant experience with coordinating collaborative multi-modal data in research? Does the applicant have experience overseeing selection and management of subawards, if needed?

Innovation

Does the application propose novel organizational concepts and data management strategies in coordinating the research consortium the CN-CDC will serve? Are the concepts, strategies, or instrumentation novel to one type of research program or applicable in a broad sense? Is a refinement, improvement, or new application of organizational concepts and data management strategies proposed?

Approach

Are the overall strategy, operational plan, and organizational structure well-reasoned and appropriate to accomplish the goals of the research consortium that the CN-CDC will serve? Will the investigators promote strategies to ensure a robust and unbiased scientific approach across the CN Groups, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the CN consortium is in the early stages of operation, does the proposed strategy adequately establish feasibility and manage the risks associated with the activities of the CN consortium? Are an appropriate plan for work-flow and a well-established timeline proposed? Have the investigators presented adequate plans to ensure consideration of relevant biological variables, such as sex, for studies of vertebrate animals or human subjects?

Environment

Will the institutional environment in which the CN-CDC will operate contribute to the probability of success in facilitating the research consortium it serves? Are the institutional support, equipment and other physical resources available to the investigators adequate for the CN-CDC proposed? Will the CN-CDC benefit from unique features of the institutional environment, infrastructure, or personnel? Are resources available within the scientific environment to support electronic information handling?

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.

Budget and Period of Support

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

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

As part of the scientific peer review, all applications:

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

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

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory 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.
• Compliance with resource and data sharing policies.

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

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

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

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

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

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

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

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

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

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

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

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

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html.

HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.

• Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. HHS provides guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at https://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.
• Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.
• HHS funded health and education programs must be administered in an environment free of sexual harassment. Please see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html; https://www2.ed.gov/about/offices/list/ocr/docs/shguide.html; and https://www.eeoc.gov/eeoc/publications/upload/fs-sex.pdf. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.
• Recipients of FFA must also administer their programs in compliance with applicable federal religious nondiscrimination laws and applicable federal conscience protection and associated anti-discrimination laws. Collectively, these laws prohibit exclusion, adverse treatment, coercion, or other discrimination against persons or entities on the basis of their consciences, religious beliefs, or moral convictions. Please see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.

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

Cooperative Agreement Terms and Conditions of Award

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 Part 75, 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 CN Group 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 to:

• Define objectives, approaches, and to plan and conduct the proposed research and assume responsibility and accountability to the applicant organization and to the NIH for performance and proper conduct of all research supported in this initiative, in accordance with the terms and conditions of award.
• Adhere to the agreed upon milestones negotiated with NIH Program staff at the outset of the award, with modifications of these milestones at other times as permitted by mutual agreement of PD/PI and NIH Program Officer. Each annual Research Performance Progress Report (RPPR) will describe progress toward meeting milestones for the prior year and plans for meeting milestones for the coming year.
• Coordinate and attend monthly teleconferences with Project/Core leaders, selected team members and NIH Program staff (e.g., Program Officer, Project Scientist(s)), for purposes of logistical planning, data presentations and discussion of challenges or alternative directions. The PD/PIs will be responsible for preparing an agenda prior to the meeting and concise proceedings or minutes of any key discussion points or action items (roughly one page), which will be delivered to participants within one week of the meeting. It is strongly encouraged that data presentations be an integral part of each meeting, with copies of the presentations available to the Group participants through a web-based collaborative data sharing platform.
• Accept close interaction with, and participation of, NIH staff in aspects of management of within-project activities and on the coordination of data format and metadata harmonization efforts.
• Demonstrate capability and flexibility for developing and modifying data formats and metadata, with the expectation that these will harmonize and be interoperable with data formats and metadata from other NIH-supported projects, which may include but are not limited to other awardees of the Convergent Neuroscience initiative.
• Nominate 3 or more research experts in theoretical modeling and experimental and/or clinical research relevant to the U19, but not involved in the U19 itself, to participate as consultants and voting members in an External Consultation Board that provides advice and guidance to the individual CN Group (U19). Note that the nominations will be subject to approval by the NIH Program Officer.
• Participate as a voting member of the External Consultation Board along with NIH Program staff (as described below) and attend annual External Consultation Board meetings.
• Submit data for quality assessment and/or validation, submit interim progress reports over and above regular annual Research Performance Progress Reports (RPPRs), and/or accept and implement any other common guidelines and procedures approved by the External Consultation Board
• Participate as a voting member of the Consortium Committee should two or more CN Groups be funded (as described below).
• Communicate and publish major findings in a timely manner, which includes posting all manuscripts to a preprint server upon initial submission to a journal. 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.
• Retain primary custody of, and have primary rights to, data as specified under the NIMH approved data and research resource sharing plans (described above). The Government, via the NIH 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.

Participation of NIH Intramural Scientists. An NIH intramural scientist may not serve as the PD/PI of a cooperative agreement 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 NIH Project Scientist. For 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

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

One or more NIH Project Scientist(s) (or designated alternate in the event the Project Scientists are not available) will be assigned for this award, from among NIH extramural program staff, based on subject matter expertise. The same person(s) may serve as the Project Scientist(s) for multiple CN awards. The NIH Project Scientists have substantial programmatic/scientific involvement to:

• Coordinate and facilitate the interactions among the research teams supported under this FOA.
• Serve as a resource with respect to other ongoing NIH activities that may be relevant to this endeavor to effectively leverage existing NIH resources and infrastructures and provide expert advice to the awardees on specific scientific and/or analytic issues.
• Be voting members of the External Consultation Board and assist in the design, development, and coordination of the different stages of the study within their role as Project Scientists.
• Participate in conference calls and annual meetings.
• Address questions about scientific content, feasibility, progress, and/or budget to inform actions by the NIH Program Officer, as needed.

In addition, an NIH Program Officer will have usual stewardship responsibility for monitoring the conduct and progress of the project to ensure milestones are accomplished in accordance with the timeline. The Program Officer carries primary responsibility for periodic review and approval of the study protocol in relation to stated recommendations regarding continuance of the project, receives all required reports and determines that satisfactory progress is being made, and attends the External Consultation Board meetings as a non-voting participant. The Program Officer negotiates key aspects of the award, including options to modify projects/programs when certain objectives of this FOA are not being met, and may recommend withholding of support, suspension, or termination of a U01 award for lack of adherence to required policies and/or procedures.

The NIH reserves the right to phase out or curtail the collaborative project, or an individual component, in the event of (a) failure to complete milestones as mutually agreed upon with program staff (b) substantial shortfall in consortium participation and collaboration with other awardees, (c) substantive changes in the agreed upon approaches with which NIH cannot concur, (d) human subject ethical issues that may dictate a premature termination, or (e) results that substantially diminish the scientific value of study continuation.

Areas of Joint Responsibility include:

• Formation of an External Consultation Board, which will be specific to the individual CN Group funded by the U19. The Board will:
• Consist of the PD/PI, any MPIs and Project/Resource Core leaders (between 2 and 6 persons), the external consultants (no fewer than 3 persons) and NIH Project Scientists (between 1 and 3 persons). Nominations of external consultants and assignment of NIH Project Scientists must be approved by the NIH Program Officer of the U19 award. Once assembled, it is expected that most decisions of the Board will be reached by consensus. If a vote is needed, each member of this Board will be allowed one vote, with the exception being that NIH Project Scientists will collectively be allowed one vote. When a vote is required, a simple majority will be required and sufficient for approval.
• Evaluate the project in terms of the CN program goals as stated in FOA, Section I, as well as the stated aims and milestones of the U19 award, which includes implementation of the framework for data integration, modeling and prediction testing across the proposed levels of analysis.
• Meet at least once yearly, mainly via internet assisted meeting software. In award years 2 and 4, there will be an in-person meeting on site. The NIH Program Officer will attend meetings but will not be a voting member. Other NIH staff and/or CN Group members can attend upon agreement by the PI/MPIs and NIH Program Officer.
• Formation of a Consortium Committee if two or more CN Groups are funded:
• The Committee will consist of the External Consultation Boards of each CN Group (minus the external consultants). However, each U19 Group will have a total of three votes divided by the number of PI's, while NIH Project Scientists assigned to each U19 will have a total of one vote. While it is expected that most decisions will be made by consensus, a simple majority vote will decide actions when needed.
• The Committee will strategize on harmonizing the data management plans for each U19 through the CN Consortium Data Commons (CN-CDC).
• The Consortium Committee will decide on the dates and locations of in-person CN Consortium meetings, which will be held annually with attendance by members of the Consortium Committee. The NIH Program Officer(s) for each U19 will attend meetings but will not vote. Other NIH staff and/or CN Group members can attend upon permission by the PI/MPIs. The agenda will be developed in consultation with the Consortium Committee.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. The three members include: a designee of the External Advisory Board chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16. - See more at: http://grants.nih.gov/grants/guide/rfa-files/RFA-NS-15-005.html#sthash.VD3On9ep.dpuf

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

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

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

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

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

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

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

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

For studies with a preponderance of molecular, cellular or circuit analysis, including human cell-based assays and model organism studies:

David M. Panchision, Ph.D.
Division of Neuroscience and Basic Behavioral Science
National Institute of Mental Health (NIMH)
Telephone: 301-443-5288
Email: panchisiond@nih.gov

For clinical trials and studies with a preponderance of clinical phenotype data analysis:

Geetha Senthil, Ph.D.
Division of Translational Research
National Institute of Mental Health (NIMH)
Telephone: 301-402-0754
Email: geetha.senthil2@nih.gov

Nick Gaiano, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-827-3420
Email: nick.gaiano@nih.gov

Rita Sisco
National Institute of Mental Health (NIMH)
Telephone: 301-443-2805
Email: siscor@mail.nih.gov

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

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.