National Institute of Mental Health (NIMH)
National Eye Institute (NEI)
National Institute on Aging (NIA)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institute on Deafness and Other Communication Disorders (NIDCD)
National Institute on Drug Abuse (NIDA)
National Institute of Neurological Disorders and Stroke (NINDS)
National Center for Complementary and Integrative Health (NCCIH)
Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
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.
There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.
The BRAIN Initiative: The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative® is aimed at revolutionizing our understanding of the human brain. By accelerating the development and application of innovative technologies, researchers will be able to produce a new dynamic picture of the brain that, for the first time, will show how individual cells and complex neural circuits interact in both time and space. It is expected that the application of these new tools and technologies will ultimately lead to new ways to treat and prevent brain disorders.
NIH is one of several federal agencies involved in the BRAIN Initiative. Planning for the NIH component of the BRAIN initiative is guided by the long-term scientific plan, “BRAIN 2025: A Scientific Vision,” which details seven high-priority research areas and calls for a sustained federal commitment of $4.5 billion over 12 years. This FOA is based on careful consideration by the NIH of the recommendations of the BRAIN 2025 Report, and input from the NIH BRAIN Multi-Council Working Group. Videocasts of the NIH BRAIN Multi-Council Working Group are available at http://www.braininitiative.nih.gov/about/mcwg.htm.
To enable rapid progress in development of new technologies as well as in theory and data analysis, the BRAIN Initiative encourages collaborations between neurobiologists and scientists from statistics, physics, mathematics, engineering, and computer and information sciences; and NIH welcomes applications from investigators in these disciplines.
NIH encourages BRAIN Initiative applications from investigators that are underrepresented in the biomedical, behavioral, or clinical research workforce (see data at http://www.nsf.gov/statistics/showpub.cfm?TopID=2&SubID=27 and the most recent report on Women, Minorities, and Persons with Disabilities in Science and Engineering). Such individuals include those from underrepresented racial and ethnic groups, those with disabilities, and those from disadvantaged backgrounds.
NIH also encourages businesses to participate in the BRAIN Initiative. It is possible for companies to submit applications directly to BRAIN Initiative program announcements or to collaborate with academic researchers in joint submissions. Small businesses should consider applying to one of the BRAIN Initiative small business FOAs (http://braininitiative.nih.gov/funding/index.htm).
In addition to the National BRAIN initiative, the NIH continues to have a substantial annual investment in neuroscience research. The Institutes and Centers contributing to the NIH BRAIN Initiative (http://braininitiative.nih.gov/) support those research efforts through investigator-initiated applications as well as through specific FOAs. Potential applicants to this FOA are strongly encouraged to contact Scientific/Program staff if they have any questions about the best FOA for their research.
The BRAIN Initiative will require a high level of coordination and sharing between investigators.
This FOA is related to the Recommendations in Section III.1 and 2 of the Final Report (http://braininitiative.nih.gov/2025/index.htm) of the BRAIN working group. Specifically, this FOA solicits applications that will address the recommendations in "Section III.1. Discovering Diversity" and "Section III.2. Maps at Multiple Scales."
The mammalian brain contains an astronomical number of cells. There are an estimated 1.13 x 10^8 cells in the mouse brain and an estimated 1.7 x 10^11 cells in the human brain, with each neuron making thousands of synapses with other cells. Since the early work of Ramón y Cajal, beginning with the elegant staining of individual neurons in the brain using the Golgi method, brain cell types have been increasingly defined by their location, morphology, connectivity, neurotransmitter type, physiology, and most recently, their transcriptional profile. Cataloging brain cell types and their connectivity is a prerequisite to understanding how they are organized in circuits, and how they change in brain disorders. In addition, a detailed understanding of cell classes and subclasses will enable the development of novel tools that allow researchers to target specific cell types and manipulate circuits for further study. However, there is not yet a consensus on what a brain cell type is, since a variety of factors including experience, cell interaction, and neuromodulators can diversify the molecular, electrical, and structural properties of similar cells, and cell phenotypes may change over time. Nonetheless, there is general agreement that cell types can be defined provisionally by invariant and generally intrinsic properties, and that this classification can provide a good starting point for a census. A workshop co-sponsored by the BRAIN Initiative and the NIH Single Cell Analysis Program shared information on how investigators are currently describing cellular phenotypes and novel approaches to better quantify, evaluate, understand, and communicate the brain cell classification. The consensus is that classification of cell types will be facilitated by a systematic collection and integrative analysis of three data elements at the cellular level: (1) molecular signature (e.g., transcriptome, epigenome, proteome, metabolome), (2) anatomy (e.g., location, size, orientation, morphology, and connectivity), and (3) function (e.g., electrophysiology, functional connectivity). Current technological capabilities promise a new era in the call for a brain cell census hallmarked by high dimensionality of molecular information at an unprecedented scale and resolution. Single cell ‘omics’ analyses (transcriptomics, epigenomics, and proteomics) will likely help define unique cell type markers and unveil the regulatory code that controls cell type formation, maintenance, and transition in health and disease. The new molecular insights gained may thus transform our understanding of cells types by revealing fundamental biological principles with mechanistic underpinnings to define discreet cell classes as well as relevant transition states.
The BRAIN Initiative Cell Census Network (BICCN)
The BRAIN Initiative Cell Census program awarded nine collaborative projects in 2017 and five in 2018, which collectively constitute the BRAIN Cell Census Network (BICCN). The overarching goal of the BICCN is to generate comprehensive 3D common reference brain cell atlases that will integrate molecular, anatomical, functional, and cell lineage data for describing cell types in mouse, human, and non-human primate brains.
The expected outcomes of the BICCN include:
The BICCN operates as a cooperative network to promote collaboration and coordination among the projects within the Network and the BRAIN Initiative, as well as with any external research entities that have similar goals. Currently the BICCN has established close collaboration and coordination relationship with Data Archive projects funded under RFA-MH-17-255. It is expected that the BICCN awardees and their collaborators will work together to achieve the common goals. This will involve regular meetings and other coordinated activities within the BICCN as well as in the BRAIN Initiative and more broadly with the research and education communities. Thus, the BICCN will leverage existing atlases and common coordinate systems to facilitate collaborative efforts for the data annotation and 3D spatial mapping.
Common Brain Tissues and Coordinate Systems
A large amount of data concerning brain anatomy and physiology exists and continues to grow rapidly. With the advent of single-cell ‘omics’ technologies, new biomolecular data are expected to flourish, adding to the existing expansion of data sets. Correspondingly, there is an increasing need to enhance data interoperability and harmonization among data producers and data accessibility to the broad research community, and to reduce unnecessary repetition in data generation. Atlases and common coordinate systems play a fundamental role in gathering, analyzing, communicating, and standardizing data. This FOA embraces the existing effort of the research community (e.g., the International Neuroinformatics Coordination Facility) to collaboratively build up brain atlases with broadly accessible common brain coordinate systems to integrate and disseminate the brain cell census data. Thus, this FOA supports the use of common brain samples, and common brain coordinate systems to minimize source variability and maximize resource sharing. Accordingly, the NIH expects that imaging–based cell census data will be registered to common coordinate systems, which include in-situ hybridization, immunohistochemistry, cell morphology, and neuronal connectivity mapping. In case non-imaging-based approaches are used, applicants should propose how to spatially assign the data to the brain regions as accurately as possible. For example, microdissection and computational tools may help map single cell data onto a reference brain atlas spatially.
Much progress has been made to develop and implement common coordinate systems for human brain (e.g., Allen Human Brain Atlas, BigBrain, BrainSpan, Talairach Coordinate System, MNI Coordinate System) and image segmentation and registration tools (e.g, Insight Segmentation and Registration Toolkit (ITK)) that allow individual labs to integrate their data to the common coordinate systems.
Research Scope of U01 Specialized Collaboratory on Human and Non-Human Primate Brains
As primate brains are several orders of magnitude larger than the mouse brain in size and number of cells, the NIH expects that the U01 Specialized Collaboratory on Human and Non-Human Primate Brains will begin to implement high throughput approaches and to establish experimental feasibility towards the generation of comprehensive reference brain atlases for larger brains at cellular resolution. The data production goals should be as comprehensive and complete as possible with a broad coverage of multiple different brain structures/regions and adequate depth in characterizing multiple cellular properties. Applicants should propose to use methods that have been demonstrated to generate high-quality data, to be cost-effective, and to have the capability to accurately and efficiently define cell types. Scalable and multiplexed approaches are expected to enable a comprehensive cell type survey. In addition, applicants are encouraged to adopt technology platforms that are capable of acquiring multimodal datasets from the same cells with adequate throughput. For example, RNA fluorescence in situ hybridization (FISH) may be combined with immunohistochemistry labeling to monitor both RNA and protein molecules in the same cells. Overall, the projects will strive to:
Applicants are expected to provide tissue collection approaches and criteria to ensure the quality of the brain tissue specimens and describe plans for biospecimen management and minimization of tissue degradation.
For the proposed use of human brain specimens, applicants are expected to develop inclusion and exclusion criteria that will minimize the risk of abnormal or degraded tissue. While postmortem healthy human brain tissues were previously collected by different projects (e.g., NIH NeuroBioBank; GTEx program, Biopreserv Biobank. 2015 Oct;13(5):311-9), new tissue sources may need to be established for the brain cell census research. Applicants are strongly encouraged to pursue broad donor consent for unrestricted sharing of data for research purposes to maximize the utility of biospecimens and data (see ENCODE project for Informed Consent examples). Applicants are also encouraged to consider Ethical, Legal and Social Issues (ELSI) of tissue collection and to consider return of results to donors or their families.
Examples of responsive research activities include but are not limited to the following 3 themes:
1. Molecular Signatures
Applicants should adopt scalable experimental approaches that will maximize the discovery and classification of all brain cell types. The research objectives may include but are not limited to:
Applicants should leverage existing reference anatomical atlases and adopt scalable experimental approaches that will maximize the discovery and classification of all brain cell types and/or neuronal connections. The research objectives may include but are not limited to:
3. Functional Measures
Applicants should adopt scalable experimental approaches that will maximize the discovery and classification of all brain cell types. The research objectives may include but are not limited to:
The brain cell census data will be an important and unique resource for use by the broad research community, and thus the following issues related to the large-scale data production are paramount to the success of the program.
Data Quality. Two of the cornerstones of science advancement are rigor in designing and performing scientific research and the ability to reproduce biomedical research findings. (http://grants.nih.gov/reproducibility/index.htm). The BICCN is expected to establish stringent data quality standards and quality control and quality assurance processes for the experimental and statistical approaches, so that the data generated will be broadly referenced and used by the research community.
Data Comprehensiveness & Completeness. The data production goals should be as comprehensive and complete as possible with a broad coverage of different brain structures/regions and adequate depth in characterizing multiple cellular properties. In practice, achieving a “comprehensive and complete” census of brain cells that include neurons, glia cells, and other cell types will require careful planning of workflow, strategic allocation of resources, and optimal lineup of complementary technologies. The purpose is to establish a Network with complementary capabilities and capacities toward generating a comprehensive and complete brain cell atlas.
Data Utility. The ultimate utility of cell census data for the broad research community may reside in an effective integration of different cell census data elements including molecular content, cell anatomy, and physiology to define a cell type. Each element of data may be limited in its own value, but combined, the data collected by individual projects should inform and crossvalidate each other to arrive at an integrative description closer to nature. Rapid data exchange and integration are critical for defining a cell type and unveiling the organizational rules behind cellular makeup and neural circuits. The BICCN Collaboratories are expected to abide by the agreed data sharing policy and process to ensure unhindered data exchange and sharing.
Production Workflow. As the ultimate long-term goal is to establish comprehensive reference brain cell atlases, the BICCN should attain a high level of production at an affordable cost by adopting scalable technology platforms and streamlined workflows. As with other large-scale data generation efforts, the BICCN Collaboratories are expected to have the capability to operate at scale at the inception of the project, establish adequate process control with quantitative quality metrics at key points in the production workflow, and have plans to improve production workflow and cost efficiency.
Each U01 Collaboratory must include data management and analysis activities to provide central data storage, data management and information security services to all researchers within the Collaboratory, and will be responsible for ensuring the timely submission of data and data analyses to the Brain Cell Data Center (BCDC) funded under RFA-MH-17-215. In addition, the Collaboratory should have bioinformatics expertise to support data integration and analysis according to the Collaboratory’s research objectives, including mining and integrating existing data and information, and assisting study design. As appropriate, the Collaboratory may perform statistical analysis of single cell ‘omics data to identify and classify cell types, discover unique cell type markers, predict spatiotemporal relations, and infer gene expression regulatory mechanisms underlying cell type formation, maintenance, and transitional states. The Collaboratory’s data expert(s) will represent the Collaboratory in a cross-BICCN data sub-committee that will operate under the Steering Committee to promote coordination and collaboration among all BICCN Centers and Collaboratories including data sharing, data harmonization, refinement of data standards, data analysis and integration, data mapping to common brain coordinate systems, and data visualization.
Each U01 Collaboratory must also include administrative activities to coordinate the Collaboratory activities and facilitate its integration into the broader BICCN, as well as include mechanisms that will foster effective interactions with other BICCN network Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) and institutions to promote synergistic research efforts. The effective management of a production collaboratory requires a significant commitment by the PD/PI. A program manager may in addition strengthen the collaboratory administration. The Collaboratory administration will be responsible for organization, management, decision-making, and periodic evaluations of individual groups within the Collaboratory, involvement of institutional and other resources, and shared publications.
Milestones and timeline: The success of BICCN will be facilitated by the adoption of clear, quantitative milestones by each of the participating Centers and Collaboratories with a realistic and efficient timeline. Applications lacking milestones and timeline will be deemed incomplete and will not be reviewed (See Section IV.2).
Activities that are not responsive: The following research areas are considered outside the research scope of this FOA, and such applications will be considered non-responsive and will not be reviewed:
Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this FOA.
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
Issuing IC and partner components intend to commit an estimated total of $8 M for FY 19 to fund 3-6 awards.
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
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.
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.
For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.
The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:
Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.
For information on Application Submission and Receipt, visit Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.
Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.
By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:
The letter of intent should be sent to:
All instructions in the SF424 (R&R) Application Guide must be followed.
The Collaboratory is expected to perform the following activities aligned with the research objectives: (1) data and resource generation, (2) data management and analysis, and (3) administrative plan. In addition to the information requested in the application guide, the applicant should also address the following four parts.
(1) The data and resource generation part is expected to:
(2) The data management and analysis part is expected to:
(3) The administrative part is expected to:
Milestones and Timeline: Applications to this FOA must define a clear set of overall goals that are aligned with the expected BICCN’s outcomes and must include annual milestones with metrics that will document progress towards the achievement of the overall goals. Applications lacking milestones and timelines will be considered incomplete and will not be reviewed. For each approach, clear, quantitative outcomes should be set and described. Annual milestones should reflect the current ability to produce data from the beginning of the project and include plans for critically evaluating and revising these milestones on a regular basis. Specific items in milestones include but are not limited to:
Letters of Support: Include letters of support/agreement for any collaborative/cooperative arrangements, subcontracts, or consultants. Letters of support should indicate the specific activities the individual or organization will perform in pursuit of the Collaboratory goals; letters of support from individuals or organizations without a specific role in the Collaboratory should not be included.
The applications are expected to include written statements from the officials responsible for intellectual property issues at all of the applicant institutions (including subcontractors) to the effect that the institution supports and agrees to abide by the resource sharing plans put forth in the application if applicable. Such letters would be clear expressions of commitment. A separate letter should be sent by each participating organization including each subcontractor. Please note that institutional sign-off on the grant application signifies that all relevant components of the institution, including the relevant office handling intellectual property matters have reviewed and approved the document.
The following modifications also apply:
A central goal of this FOA is to build up a comprehensive brain cell census data resource that will be widely used throughout the research community. It will take the combined resources of researchers in the public and private sectors many years to catalog and characterize the biology of brain cells, neuronal connectivity of interest, to understand brain function, and then to use that information to improve public health. The open sharing of the brain census data, research tools, and resources will not only lead more rapidly to their broad use by the research community, but also encourage scientific rigor in data production and analysis, with resulting benefits to public health. In order to reap the maximum value from this program, all molecular, anatomical, and physiological data, experimental protocols, tools generated are expected to be made publicly available. Applications must include a detailed plan for sharing data and resources and include the following key elements:
Data Sharing. Applicants must provide a specific proposal for data sharing in the application, and address the issues related to the public release of data and data analyses (see the rationale for FAIR (Findability, Accessibility, Interoperability, and Reusability) Data Principles). After the initial review, the BRAIN program staff will be responsible for any additional administrative review of the plan for sharing data and may negotiate modifications of the data sharing plan with the prospective awardee prior to award. The final negotiated version of the data sharing plan will become a term and condition of the award of the cooperative agreement. After all of the awards have been made, the BICCN Steering Committee, of which all awardees will be members, will develop a final, common data release plan as appropriate for the project that will address the interests of the data producers and analysts, as well as the users of the BICCN brain cell census atlases. Applicants should indicate their willingness to participate in the development of such a final plan and to accept it. The NIH expects that verified raw data will be submitted ”in real time” or other agreed-upon timeframe depending on the data types and verification requirements to long-term publicly accessible archives such as GEO or others as appropriate. Applicants should address whether they anticipate any of their data will require controlled access. Agreement to abide by that policy is a requirement for anyone to join the Network.
Resource Sharing. As the BICCN is generating a community resource, in addition to data, resources generated by the BICCN projects should be made rapidly available to the research community. Rapid dissemination of these resources would accelerate scientific exploration and avoid duplicative resource development effort. The applicant should provide specific plans for resource sharing and distribution in the application. After the initial review, the BRAIN program staff will be responsible for any additional administrative review of the plan for sharing resources and may negotiate modifications of the resource sharing plan with the prospective awardee prior to award. The final negotiated version of the resource sharing plan will become a term and condition of the award of the cooperative agreement.
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 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.
All instructions in the SF424 (R&R) Application Guide must be followed.
Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.
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). 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.
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.
Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.
For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.
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. Additional information may be found in the SF424 (R&R) Application Guide.
See more tips for avoiding common errors.
Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.
Since this FOA specifically seeks applications to systematically generate brain cell census data and possibly related tools, the NIH expects that some applications may propose mature and well-established approaches that may not be innovative per se to produce robust high quality datasets for broad use by the research community. In their evaluation of Innovation reviewers will be asked to weigh the potential of the applications to generate novel cell census data and/or tools that may lead to transformative, paradigm-shifting advances.
Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?
Will the proposed aims and scientific questions contribute to the overarching goals and the expected outcomes of the BICCN ? Are the expected results likely to provide significant data related to the identification and classification of brain cell types?
Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?
Are the PD/PI and other key personnel devoting sufficient time/effort to achieve the goals? Has adequate leadership for day-to-day project management activities been described?
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?
Does the application describe evidence that demonstrates the novelty of cell census data to be generated? Will the novel data and/or tools lead to transformative, paradigm-shifting advances of the field?
Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the 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?
Does the application adequately describe and discuss experimental designs to ensure the data quality, comprehensiveness & completeness? Are potential pitfalls clearly discussed and minimized accordingly? Does the application adequately provide a rationale and supporting data on the adequacy of the cell sampling? Will experimental designs ensure novel, high-quality cell census data will be generated? Does the application adequately address issues related to the data mapping to a common brain coordinate system?
Does the application demonstrate the capability to operate at scale as proposed? Does the application provide evidence of how production goals are set and can be attained? Does the application present sufficient preliminary data to support feasibility of the proposed scalable methods and adequate throughput? Are rate-limiting steps identified and appropriately addressed? Are plans included for improving the pipeline adequate?
Does the application adequately demonstrate an effective workflow? Does the application describe workflow assessments and proposed improvements? Does the application provide current estimates of data quality and plans for how data quality will be evaluated during the course of the project?
Is the data management and analysis plan appropriate to facilitate attainment of the objectives of the proposed Collaboratory project? Is the plan for data registration to a brain atlas and/or common brain coordinate system adequate? Are there appropriate data infrastructure(s) and pipeline(s) to support data sharing?
Is the administrative plan appropriate to ensure the Collaboratory will meet the performance objectives and milestones?
If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?
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?
Milestones and Timeline
Are clear, quantitative, and actionable, milestones and timelines proposed? Do the milestones establish feasibility for all aspects of the proposed research? Does the application include plans for critically evaluating and revising milestones on a regular basis? Are there additional key experiments that need to have milestones? Will the overall milestones provide adequate information to evaluate yearly progress of the Collaboratory project as a whole? Are the timelines proposed for achieving the milestones realistic and inclusive of necessary steps, but also efficient without adding unnecessary steps?
Is there a clear and sound plan for communication and coordination within the Collaboratory demonstrating an integrated Collaboratory project capable of performing the functions specified in the FOA?
For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.
When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.
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.
For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.
For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.
Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.
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 (GDS).
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.
Information regarding the disposition of applications is available 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.
Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.
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.
For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. 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. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.
The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 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 project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.
The PD(s)/PI(s) will have the primary responsibility for:
The PD(s)/PI(s) will have primary authority and responsibility to define objectives and approaches and to plan and conduct the proposed research. She/he will assume responsibility and accountability to the applicant organization and to the NIMH for performance and proper conduct of all research, including the NIH intramural component, if applicable, in accordance with the Terms and Conditions of Award.
The Principal Investigator will be a member of the Steering Committee and will be responsible for scheduling Steering Committee meetings and disseminating meeting notes to all participants within 2 weeks of each meeting (see below under Collaborative Responsibilities).
The Awardee Institution and/or Research Project Leader's Institution will retain primary custody of and have primary rights to data as specified under the NIMH approved Intellectual Property Patent Rights Agreements for New Chemical Entities or the data and research resource sharing plans (described below). The PD/PI will provide to the NIMH Program Official and Project Scientist(s) access to data generated under this cooperative agreement to allow them to periodically review the data consistent with current DHHS, PHS, and NIH policies.
Timely publication of major findings by the Steering Committee members is encouraged. Publication or oral presentation of work done under this agreement will require appropriate acknowledgment of NIMH support, including the assigned cooperative agreement award number.
NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
The Project Scientist(s) interacts scientifically with the funded PIs and the collaborators on their cooperative agreement grants, and may provide appropriate assistance, including: 1) assisting in research planning, 2) suggesting studies within the scope of the cooperative agreement objectives and research activities, 3) presenting experimental findings from published sources or from relevant contract projects, 4) participating in the design of experiments, 5) participating in the analysis of results, and 6) advising in management and technical performance.
The Project Scientist(s) will be a member(s) of the Steering Committee.
FIH, EFS, Phase Ib and Phase II/PoC studies will be reviewed by an appropriate NIMH Data and Safety Monitoring Board (DSMB) to ensure the safety of participants and the validity and integrity of the data. The study protocol(s) and consent form(s) will be reviewed by the DSMB prior to initiation of the project. The DSMB will review study reports on a regular basis to monitor subject enrollment and retention, safety, quality of data collection, and integrity of the study. Applicants should refer to NIH’s policy on data and safety monitoring (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-038.html) as well as the NIMH Guidelines for Data and Safety Monitoring (http://www.nimh.nih.gov/funding/grant-writing-and-application-process/nimh-policy-on-data-and-safety-monitoring-in-extramural-investigator-initiated-clinical-trials.shtml.
Additionally, an NIMH Program Official will be responsible for the normal scientific and programmatic stewardship of the award, including monitoring implementation of the data and research resource sharing plans and will be named in the award notice.
As noted previously, both NIMH Project Scientist and Program Official will be given access to the data generated under this cooperative agreement, which will allow them to periodically review the data to ensure consistency with current DHHS, PHS, and NIH Policies.
Participation of NIH Intramural Scientists:
An NIH intramural scientist may not serve as the PD(s)/PI(s) but may participate as a collaborator, or consultant. However, an Intramural scientist may not receive salary, equipment, supplies, or other remuneration from awards resulting from this FOA. The Intramural scientist must obtain written approval of his/her NIH Institute Scientific Director for the amount of resources that may be allocated to the project. The approval must also specify that the conduct of the project will comply with the DHHS regulations for research involving human subjects (if applicable) and with the PHS policy on vertebrate animal research. The participation of an intramural scientist is independent of and unrelated to the role of the NIMH Project Scientist. For 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. http://www1.od.nih.gov/oir/sourcebook/ethic-conduct/ethical-conduct-toc.htmÂ
Intramural research scientists participating as collaborators have the same rights and responsibilities as other researchers who are participating investigators in the funded cooperative agreement grants. Most often these investigators will be members of the Steering Committee, since they will likely be considered as key personnel.
Areas of Joint Responsibility include:
A governing Steering Committee composed of the PD(s)/PI(s), a CRO lead or CTSA lead (as applicable), key personnel, NIMH Project Scientist(s), and NIMH Program Official will be established to assist in monitoring and developing the scientific content and direction of the program. The total membership by NIMH staff will not exceed one-third (1/3) of the membership of the Steering Committee. In all cases, the role of NIMH will be to assist, participate in deliberations, and facilitate discussion and not to direct activities.
Steering Committee will serve as the governing board for awardees. All awardees under this initiative program are bound by the policies and procedures developed by the Steering Committee; adoption of such policies and procedures requires a majority vote. Awardees under this FOA will be required to accept and implement policies approved by the Steering Committee.
Membership in the Steering Committee will include the PD(s)/PI(s) of each U01 award, or a designated representative in the case of Multiple PD/PI award. Each member will have one vote.
The NIMH Project Scientist will be a voting member of the Steering Committee.
The chair will be chosen by a majority vote of the Steering Committee, with years of service as chair determined by the committee. The chair is responsible for preparing meeting agendas, for scheduling and chairing meetings, and for preparing concise minutes which will be delivered to Steering Committee members within 30 days of the meeting. Virtual meetings are appropriate. The NIMH Project Scientist may not serve as the Chair of the Steering Committee.
The Steering Committee members will meet periodically to review progress, plan and design research activities, and establish priorities. The frequency of meetings, not fewer than two per year, will be determined by the PD(s)/PI(s) who will be responsible for scheduling the time and place (generally at one of the performance sites) and for preparing concise proceedings or minutes (action items and one-two page summary) which will be delivered to the members of the Committee within 2 weeks of the meeting.
Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.
Intellectual Property and Patent Rights for New Chemical Entities or Devices
Since the development of new pharmacological treatments for psychiatric disorders is a major objective of this effort and active involvement by pharmaceutical laboratories is encouraged and would be facilitated by the existence of appropriate patent coverage, it is expected that applicants provide plans to address the handling of intellectual property for new chemical entities or devices under this FOA.
Under the earlier National Cooperative Drug Discovery/Development Groups (NCDDG) for the Treatment of Mental Disorders, Drug or Alcohol Addiction program, successful applicants were required to supply the following confidential materials to the NIMH Program Official listed under Section VII. Agency Contacts. Similar to the NCDDG, applicants are expected to address the three items noted below under this FOA, consistent with achieving the goals of this program:
1. Each applicant are expected to provide a detailed description of the approach to be used for handling intellectual property and for licensing where appropriate, in particular where the invention may involve investigators from more than one institution. Procedures are expected to be described for resolution of legal problems should they arise, consistent with achieving the goals of the program. Your attention is drawn to the NIH Extramural Technology Transfer Policies and Documents [https://grants.nih.gov/grants/intell-property.htm].
2. A formal statement of Intellectual Property among the PD(s)/PI(s) and their institutions as well as a detailed description of procedures to be followed for resolution of legal problems which may develop, is expected to be signed and dated by the organizational official authorized to enter into intellectual property arrangements for each PD(s)/PI(s) and their institution(s). The signed agreement is expected to be submitted prior to award to the appropriate NIMH staff at the addresses provided under Section VII. Agency Contacts.
3. Prior to the award, the PD(s)/PI(s) is expected to provide a signed statement of acceptance of the participation of NIMH staff during performance of the award as outlined under "NIH Staff Responsibilities" in Section VI.2 - Cooperative Agreement Terms and Conditions of Award.
Note: Do NOT submit documents 1-3 above with the application. However, awards will not be made until these documents are received and approved by NIMH.
Progress of the project will be reviewed annually by the NIMH Project Officer at the time of each non-competing continuation application to assure that satisfactory progress is being made in achieving the project objectives, especially with respect to enrollment and quality of data collection, timely data sharing as appropriate and consistent with achieving the goals of the program, and to ensure the site is following the procedures recommended and approved by the project Steering Committee.
By acceptance of these awards, the awardees agree to abide by decisions and policies of the project Steering Committee and the other terms and conditions listed above or referenced in the Notice of Grant Award.
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.
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