National Institutes of Health (NIH)
National Institute of Mental Health (NIMH)
Funding Opportunity Title
Brain Somatic Mosaicism and its Role in Psychiatric Disorders (U01)
U01 Research Project – Cooperative Agreements
Funding Opportunity Announcement (FOA) Number
Companion Funding Opportunity
Catalog of Federal Domestic Assistance (CFDA) Number(s)
Funding Opportunity Purpose
This funding opportunity announcement (FOA) invites Cooperative Agreement (U01) applications from multi-disciplinary and synergistic teams of investigators proposing to identify and characterize the full spectrum of somatic variation in human brain samples and to assess the relationship of such variation with the pathophysiology of neuropsychiatric disorders. This FOA seeks to support applications exploring the extent of somatic variations across different brain regions in one or more psychiatric disorders using state-of-the-art genomic, computational and single-cell approaches. Awards made under this FOA will be governed by a Brain Somatic Mosaicism (BSM) Network Steering Committee to accelerate scientific progress through the coordination of research strategies, analytical methods and data. The ultimate goal of this FOA is to address gaps in our understanding of the role of somatic genomic perturbations in the etiology of neuropsychiatric disorders.
April 9, 2014
Open Date (Earliest Submission Date)
May 24, 2014
Letter of Intent Due Date(s)
30 days before the application due date
Application Due Date(s)
June 24, 2014; February 24, 2015; October 23, 2015; June 24, 2016; February 24, 2017, by 5:00 PM local time of applicant organization.
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.
AIDS Application Due Date(s)
Scientific Merit Review
October 2014; June 2015; February 2016; October 2016; June 2017
Advisory Council Review
January 2015; October 2015; May 2016; January 2017; October 2017
Earliest Start Date
February 25, 2017
Due Dates for E.O. 12372
Required Application Instructions
It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). 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 to submit your application to the agency through Grants.gov. You can use the ASSIST system to prepare, submit and track your application online. You can download an application package from Grants.gov, complete the forms offline, submit the completed forms to Grants.gov and track your application in eRA Commons. Or, you can use other institutional system-to-system solutions to prepare and submit your application to Grants.gov and track your application in eRA Commons. Learn more.
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 genetic architecture of psychiatric disorders is complex. Psychiatric disorders display strong heritability, as demonstrated in family and twin genetic studies. Recent large-scale, genome-wide studies have identified associations of psychiatric disorders with several common genetic variants, rare de novo copy number variants (CNVs), and loss of function or missense mutations. However, these findings explain only a small proportion of the heritability of psychiatric disorders. The “missed” or unexplained heritability could be attributed to complex genetic architecture and interactions between genetic and environmental factors. In addition to heritable genetic factors, the idea that de novo somatic variations are involved in central nervous system disorders is gaining traction.
Somatic mosaicism, the phenomenon whereby not all cells of the human body have identical DNA sequence, occurs as part of the normal developmental process. Retrotransposon activity, replication errors during rapid mitotic expansion of neurons during fetal brain development, and electrophysiological activity of the neurons have been implicated in the generation of somatic variations. Recent studies suggest that such variations might accumulate throughout the lifespan and be widespread in the brain.
Somatic genomic variations could occur in the form of single nucleotide variants (SNVs), copy number variants (CNVs), structural variants (SVs), or retrotransposon insertions. Such variations could alter epigenetic and transcriptome patterns, creating functional diversity among brain cells which could result in alteration of cell signaling pathways and neural circuit function leading to behavioral perturbations and disease. Somatic mosaicism has been studied extensively in the context of cancer, but this work has only recently begun to focus on brain disorders, particularly neurodevelopmental disorders. For example, in hemimegalencephaly (HMG), mutations in ATK3, PI3KCA, and mTOR genes in as few as 8% of the brain cells were found to result in cortical perturbations in an entire cerebral hemisphere. Recent technological progress in single-cell genome sequencing has made it possible for researchers to explore somatic variations at a single-cell level. Through such single-cell approaches, studies have identified several somatic Long Interspersed Nuclear Elements (LINE-1) insertions that occur in neural cell lineages during normal brain development.
Although there is increasing evidence of somatic mosaicism in the brain, the extent of such variation and its functional significance in normal brain development and in psychiatric disorders remain poorly understood. Elucidating the architecture of genetic perturbations in somatic cells of normal and diseased brains may provide new insights into genetic susceptibility of complex psychiatric disorders and lead to the identification of novel therapeutic targets.
The key objective of this FOA is to solicit interdisciplinary collaborative applications aimed at understanding the role of somatic mosaicism in the development of neuropsychiatric disorders. Preference will be given to projects which are proposed by a highly interactive and synergistic team of investigators with complementary expertise. Successful applications will include expertise in genetics, neuro-developmental biology, psychiatry, high-throughput single-cell analysis, whole genome sequence analysis, computational bioinformatics, and or other fields relevant to the FOA. All awards supported under this FOA and the companion FOA (PAR-14-174) will be governed by a Brain Somatic Mosaicism (BSM) Network Steering Committee to accelerate scientific progress through the coordination of research strategies, analytical methods and genomic data.
An integral part of this FOA is identifying somatic variations in human brain and characterizing their role in one or more psychiatric disorders. Under the scope of this FOA, specific areas of research interest include, but are not limited to the following:
Applications submitted to this FOA should include the following elements: 1) comprehensive characterization and comparison of somatic variations in healthy control and diseased brains, and 2) determination of functional roles for these variations in psychiatric disorders. Since the primary focus of this FOA is to identify and characterize somatic variations in diseased human brains, the projects could utilize a phased approach. For example, the initial focus of the applications might be discovery of somatic variations across human brain; subsequent aims might focus on functional follow-up experiments to investigate the role of somatic mosaicism in the development of psychiatric disorders.
Research applications could explore the extent of somatic variations across neuronal cell types and lineages, from different brain regions, and/or for one or more psychiatric disorders. For example, one approach might be to combine state-of-the-art genomic and single-cell approaches to rapidly characterize and generate a high resolution map of different types of somatic variations across multiple brain regions implicated in the pathophysiology of psychiatric disorders.
Applications are encouraged to apply unbiased genomic approaches to evaluate somatic mosaicism using appropriate human brain samples from patient populations to correlate findings with psychiatric disorders. Comprehensive assessments could include identifying a range of somatic variations in different cell types or cell lineages, across brain regions in a large number of individuals covering one or more lifetime periods. For initial discovery of somatic genomic variations, applicants are encouraged to propose studies using brain samples from human patient populations, rather than induced pluripotent stem cell (iPSC) lines or model organisms as primary source. However, iPSC cell lines or animal models could be employed for functional follow-up analysis.
To the extent possible, investigators are encouraged to leverage existing large-scale, genome-wide data sets and brain sample collections from publicly available resources, including but not limited to Brainspan ( http://www.brainspan.org/), The Genotype-Tissue Expression Project (GTEx, http://www.gtexportal.org/home/), NIH NeuroBiobank (https://neurobiobank.nih.gov/), CommonMind Project (http://commonmind.org/WP/), and Autism Tissue Program (ATP, http://www.autismtissueprogram.org/).
All awards supported under this FOA and the companion FOA (PAR-14-174) will be governed by Brain Somatic Mosaicism (BSM) Network Steering Committee. Through the BSM Network Steering Committee, members are encouraged to address gaps in our understanding of the prevalence and distribution of somatic variations in the human brain, and their role in the development of neuropsychiatric disorders. The BSM Network Steering Committee members will 1) share ideas, approaches, technologies and methods, 2) identify synergies across projects, 3) coordinate across projects for data standardization and validation, 4) facilitate immediate data and resource sharing among the BSM Network members, 5) set overall milestones for the BSM Network, and 6) guide and evaluate progress and direction of the BSM Network. U01 applicants applying for future submission dates under this FOA and the companion FOA (PAR-14-174) will also be governed by the BSM Network Steering Committee and are expected to align their research with the overall BSM Network research priorities.
Applicants are strongly encouraged to consult the appropriate Scientific/Research Contacts, listed in Section VII, to discuss the structure of the collaborations, and research topics of interest for alignment of their proposed work with the Program objectives and the BSM Network research priories.
Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities.
Application Types Allowed
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards
The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.
NIH intends to fund two to three applications under this FOA and the companion FOA. The estimated amount of funds is $5 million for fiscal year 2015. Future year amounts will depend on annual appropriations.
Application budgets are not limited but need to reflect the actual needs of the proposed project.
Award Project Period
The maximum period is 5 years.
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.
Higher Education Institutions
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
Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.
Applicant organizations must complete 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.
Any individual(s) with the skills, knowledge, and resources
necessary to carry out the proposed research as the Program Director(s)/Principal
Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to
develop an application for support. Individuals from underrepresented racial
and ethnic groups as well as individuals with disabilities are always
encouraged to apply for NIH support.
For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
Applicant organizations may submit more than one application, provided that each application is scientifically distinct.
NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:
Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the “Apply for Grant Electronically” button in this FOA or following the directions provided at Grants.gov.
It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.
For information on Application Submission and Receipt, visit Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.
Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.
By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:
The letter of intent should be sent to:
Geetha Senthil Ph.D.
Office of Genomics Research Coordination
National Institute of Mental Health (NIMH)
6001 Executive Boulevard, Room 7200
Bethesda, MD 20892-9643
Rockville, MD 20852 (for courier/express mail service)
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.
The forms package associated with this FOA includes all applicable components, required and optional. Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate “optional” components.
The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional information:
Facilities and Other Resources: Applicants are advised that the Facilities and Other Resources section should address not only physical resources, but also the intellectual and collaborative resources for executing the project. Instructions for this section include the following:
Describe how the scientific environment in which the research will be done contributes to the probability of success (e.g., institutional support, physical resources, and intellectual rapport). In describing the scientific environment in which the work will be done, discuss ways in which the proposed studies will benefit from unique features of the scientific environment of subject populations or will employ useful collaborative arrangements.
Other Attachments: Applicants should upload a single pdf attachment, with the title "Project Management Plan", that includes the following information.
Project Management Plan: Provide a detailed plan by which different elements of the project would operate in a synergistic and integrated manner. The following guidelines and framework should be followed in developing this plan:
All instructions in the SF424 (R&R) Application Guide must be followed. It is expected that the projects will include synergistic research teams comprised of outstanding scientists from diverse scientific disciplines with expertise in neurodevelopmental biology, genetics, psychiatry, computational bioinformatics, analysis of genome-wide data, psychiatry, high-throughput single-cell technologies, and/or other fields relevant to the FOA. As appropriate, Senior/Key Personnel should demonstrate their experience and expertise in these areas.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
Specific Aims: All applications must provide a succinct list of Specific Aims of the project.
Research Strategy: Applications should conform with current guidelines taking care to address important elements related to Significance, Approach, and Innovation. As a part of the Research Strategy section, applicants are requested to clearly address the following aspects:
Letters of Support:
Applications should include provide signed letters of support confirming access to adequate brain tissue samples from psychiatric cases as well as healthy controls.
Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modifications:
Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.
When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.
Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.
Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission.
Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). 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. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.
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.
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.
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.
Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review, NIH. Applications that are incomplete will not be reviewed.
In order to expedite review, applicants are requested to notify the NIMH Referral Office by email at NIMHReferral@mail.nih.gov when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.
Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact NIH program staff at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide.
NIH encourages the use of common data elements (CDEs) in basic, clinical, and applied research, patient registries, and other human subject research to facilitate broader and more effective use of data and advance research across studies. CDEs are data elements that have been identified and defined for use in multiple data sets across different studies. Use of CDEs can facilitate data sharing and standardization to improve data quality and enable data integration from multiple studies and sources, including electronic health records. NIH ICs have identified CDEs for many clinical domains (e.g., neurological disease), types of studies (e.g. genome-wide association studies (GWAS)), types of outcomes (e.g., patient-reported outcomes), and patient registries (e.g., the Global Rare Diseases Patient Registry and Data Repository). NIH has established a “Common Data Element (CDE) Resource Portal" (http://cde.nih.gov/) to assist investigators in identifying NIH-supported CDEs when developing protocols, case report forms, and other instruments for data collection. The Portal provides guidance about and access to NIH-supported CDE initiatives and other tools and resources for the appropriate use of CDEs and data standards in NIH-funded research. Investigators are encouraged to consult the Portal and describe in their applications any use they will make of NIH-supported CDEs in their projects.
Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.
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.
Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project 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 project 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 project that by its nature is not innovative may be essential to advance a field.
Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? Does the project address the objectives of the FOA to transform our knowledge of the potential role of somatic genomic variations in brain function and pathophysiology of psychiatric disorders? Are the plans sufficiently bold to constitute a substantial advance in the ability to characterize somatic genomic variations at high resolution, including rare somatic mutations at single-cell level in human brain cells/tissues? Does the proposed work have a strong likelihood of revealing the extent of genomic mosaicism in human brain and its impact on brain dysfunction related to psychiatric disorders?
Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? Do the PD(s)/PI(s) have prior experience with coordinating collaborative research? Do the investigators have documented experience in genetics, neuro-development, psychiatry, analysis of high-throughput sequencing data, computational bioinformatics, single cell analysis, and other relevant fields appropriate to this FOA? Is there complementary and synergistic expertise across the consortium? Will the leadership plan optimize the management of a milestone-driven, multidisciplinary project?
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? Will the data arising from these studies support the identification of a full spectrum of human brain-specific somatic genomic variations in patient populations to understand their role in brain function and psychiatric disorders? Are there innovative strategies for analysis of genomic data that will lead to the development of new paradigms for analyzing somatic variations at high resolution? Does the application represent an innovative technological solution which overcomes current scientific or technical barriers?
Are the overall strategy, methodology, and analyses
well-reasoned and appropriate to accomplish the specific aims of the project?
Are potential problems, alternative strategies, and benchmarks for success presented?
If the project is in the early stages of development, will the strategy
establish feasibility and will particularly risky aspects be managed? Does the
project employ unbiased genomic approaches using appropriate cells or tissues
derived from patient populations and controls to correlate findings with the
pathophysiology of psychiatric disorders? Do the applicants provide an
adequate rationale for choice of cell-types, brain regions, number of samples,
technologies, validation strategies, and functional readouts for elucidating
the role of somatic genetic perturbations in the pathophysiology of psychiatric
disorders? Is the primary focus of the application discovery using global
mapping approaches across the genome across different brain regions from
multiple individuals? Does the proposed project adequately address issues of
statistical power? Are the proposed samples of sufficiently high quality to
provide high quality results? Are there clear plans for validation of novel
rare somatic variants? Does the project propose to conduct comprehensive
assessment and comparison of the full spectrum of somatic variations across
brain regions in diseased and healthy brains? Does the project propose
realistic timeline and milestones? Are key technical barriers and dependencies
identified? Is sufficient information provided about sample size, choice of
cell types and brain regions, and demographics, including an inventory of
existing brain samples and phenotypic measures? If new data collection is
proposed, is the justification appropriate and compelling?
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?
As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.
Project Management Plan
Does the application include a Project Management Plan describing how different components of the project would operate in a synergistic and integrated manner? Does the plan include procedures to assure reliability and quality control, comprehensive transparency of data reporting? Does the application include plans for maintenance of close collaboration and effective communication among members?
Protections for Human Subjects
For research that involves human subjects but does
not involve one of the six categories of research that are exempt under 45 CFR
Part 46, the committee will evaluate the justification for involvement of human
subjects and the proposed protections from research risk relating to their
participation according to the following five review criteria: 1) risk to
subjects, 2) adequacy of protection against risks, 3) potential benefits to the
subjects and others, 4) importance of the knowledge to be gained, and 5) data
and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.
Inclusion of Women, Minorities, and Children
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 five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.
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.
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.
Applications from Foreign Organizations
Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.
Select Agent Research
Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).
Resource Sharing Plans
Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genome Wide Association Studies (GWAS).
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 NIMH, 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:
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:
After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons.
Information regarding the disposition of applications is available in the NIH Grants Policy Statement.
If the application is under consideration for funding, NIH
will request "just-in-time" information from the applicant as
described in the NIH Grants
A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.
Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.
Any application awarded in response to this FOA will be subject to the DUNS, SAM Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.
All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.
Cooperative Agreement Terms and Conditions of Award
The following special terms of award are in addition to, and
not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB)
administrative guidelines, U.S. Department of Health and Human Services (DHHS)
grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is
applicable when State and local Governments are eligible to apply), and other
HHS, PHS, and NIH grant administration policies.
The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.
All awardees under this FOA and the companion FOA (PAR-14-174) will be governed by the BSM Network Steering Committee composed of the PDs/PIs of each project within the network, NIMH Project Scientist(s), and the NIMH Program Officer to assist in motoring and developing scientific content and direction of the program.
The PD(s)/PI(s) will have the primary responsibility for:
NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
The NIMH Project Scientist (or designated alternate in the event the Project Scientist is not available) will have substantial programmatic/scientific involvement:
In addition, an NIMH Program Officer has 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 BSM Network Steering Committee meetings as a non-voting participant. The Program Officer negotiates throughput, quality control, validation, and cost goals with the awardees as necessary and suggests reprogramming efforts, including options to modify projects/programs when certain objectives of this FOA are not being met.
Participation of NIH Intramural Scientists:
An NIH intramural scientist may serve as a co-investigator, 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. The involvement of Intramural scientists needs to be consistent with NIH Policy and all applicable federal laws and regulations: http://www1.od.nih.gov/oir/sourcebook/ethic-conduct/ethical-conduct-toc.htm.
Areas of Joint Responsibility include:
All awardees under this FOA and the companion FOA (PAR-14-174) will be governed by the BSM Network Steering Committee composed of the PDs/PIs of each grant, NIMH Project Scientist(s), and the NIMH Program Officer to assist in motoring and developing scientific content and direction of the program. The BSM Network Steering Committee will select, by majority vote, a Chair from among the PD/PIs for a two-year term.
The BSM Network Steering Committee will:
It is expected that decisions made or actions taken by the BSM Network Steering Committee will be by consensus, or majority vote when needed; the contact PI of each award will have one vote, with NIMH Project Scientist (or alternate) having one vote. The NIMH Program Officer will not have a vote. All the BSM Network Steering Committee members will attend in person at least an annual meeting to discuss progress and share research findings. Outside consultants/experts may be asked to participate in BSM Network Steering Committee meetings and discussions, but not have a vote on committee decisions. Membership on the BSM Network Steering Committee becomes effective upon issuance of the Notice of Grant Award. The PIs agree to accept the close coordination, cooperation, and participation of a NIMH Project Scientist and the Steering Committee to facilitate coordination amongst all the U01 awards under this initiative.
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 BSM Network Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.
When multiple years are involved, awardees will be required to submit the annual Non-Competing Progress Report (PHS 2590 or RPPR) and financial statements as required in the NIH Grants Policy Statement.
Recruitment Reporting and Trial Registration
NIMH requires reporting of recruitment milestones for participants in clinical trials as noted at http://grants.nih.gov/grants/guide/notice-files/NOT-MH-05-013.html. While trials in response to this FOA may not seek 150 subjects or more (the level at which this reporting has been required), we expect reporting for all trials, even those with less than 150 subjects.
The NIMH expects the registration and results reporting for all NIMH-supported clinical trials in ClinicalTrials.gov, regardless of whether or not they are subject to FDAAA (see http://grants.nih.gov/ClinicalTrials_fdaaa/at-a-glance.htm). We plan to include language regarding this expectation in the notice of grant award.
The applicants are expected to refer to the project 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 project.
Awardees are expected to report on progress with the data sharing milestones as established in the NIMH approved data sharing plan.
A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.
The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.
We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
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Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
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Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.
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