Part 1. Overview Information

Key Dates

Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Genome-wide association studies (GWAS) identify statistical relationships between common single nucleotide variants (SNVs) across the genome and a trait of interest. Due to the correlated nature of nearby SNVs (i.e., linkage disequilibrium), GWAS implicate regions of the genome (loci) and do not necessarily pinpoint the causal variant(s), gene(s), isoform(s) or proximate molecular mechanism(s) underlying the trait association. Greater than 90% of genome-wide significant variants associated with traits fall within non-coding regions of the genome. A minority of these variants will be the actual causal variants and a majority will not affect the nearest genes. Moreover, functional annotation of the non-coding genome is still incomplete; the target genes of many genomic regulatory elements such as enhancers remain unknown. This presents a major challenge to mapping variants onto genes and genes onto traits. Thus, an immediate barrier to translating genetic associations into causal disease mechanisms is the uncertain relationship between statistically identified genetic variants and the resultant molecular changes influencing, directly or indirectly, a trait.

Fine-mapping procedures aim to overcome this by determining which variants in a genomic region of interest are most likely causally related to a trait given the known patterns of variant correlations and their immediate functional impact. These statistical approaches leverage information such as gene expression, functional annotations, deep resequencing or patterns of correlations across diverse populations and provide a “credible set” of casual variants for each associated region. Resolving genetic signals in this manner is critically important not only for disease associations but also molecular quantitative trait loci (QTLs) and transcriptome-wide association studies (TWAS), as well as other imputation methods that aim to connect disease and molecular traits.. For example, only 4-12% of the lead variant expression QTLs in the Genotype-Tissue Expression (GTEx) project are the actual causal variants affecting gene expression. The mismatch between causal variants of molecular traits and disease traits and the fact that they are often derived from different populations impedes direct comparisons across traits and functional understanding of genetic associations. Moreover, the lack of causal variants and their corresponding causal genes, or gene isoforms, indicates that current gene sets mapped onto disease risk are inaccurate and derived disease relevant tissues, pathways and cell-types should be considered provisional. More reliable biological insights into disease thus await establishing a more complete and accurate set of causal variants, genomic elements, genes and isoforms.

The objective of this Funding Opportunity Announcement (FOA) is to develop and apply resources and tools for the large-scale and systematic fine-mapping of serious mental illness related traits. This includes disease status as well as molecular features in relevant tissues and cell types. Proposed studies should generate or use existing population-scale human genomic and phenotypic data from well-characterized cohorts of diverse ancestries. They should also leverage robust causal inference methods to map causal variants onto causal genes, isoforms and pathways that may be prioritized for experimental studies relevant to serious mental illnesses. The ultimate goals are to provide the community with a high confidence set of causal variants, regulatory elements, genes and isoforms contributing to disease risk and allowing deeper insights into proximate disease mechanisms.

Specific Areas of Research Interest

For this FOA, the term “disease or trait” refers to psychiatric disorders, risk of these disorders, molecular phenotypes, organismal phenotypes, clinical phenotypes, and other traits relevant to human mental health and disease. It is expected that the fine-mapping methods and approaches utilized here may be broadly applicable to human diseases and traits, but the emphasis should be on severe mental illness.

Projects should develop new or apply existing statistical and computational methods for integrative analysis of new or existing genetic association and functional genomic data (e.g., single cell and/or tissue level gene expression/splicing, chromatin accessibility, chromatin architecture, transcription factor binding, DNA/RNA modifications) to identify credible sets of causal variants, gene regulatory elements, genes and/or isoforms. The approach should leverage large-scale, well-powered human genetic and genomic datasets from well-characterized cohorts and samples, and when possible, from diverse populations. Functional genomic data from other species may be utilized to complement gaps in human datasets. Importantly, all applications should include validation efforts to demonstrate that credible sets of newly identified causal factors have increased disease-relevant and disease-specific biological signals above and beyond current sets for serious mental illnesses. Examples of relevant research include, but are not limited to:

• Systematically narrowing down current credible sets of causal variants across genome-wide significant loci to the fewest number causally contributing to a disease or trait.
• Identifying credible sets of causal variants within shared genome-wide significant loci that are unique to or shared across different populations.
• Identifying credible sets of causal variants within shared genome-wide significant loci that are unique to or shared across different diseases or traits.
• Identifying credible sets of genomic elements, genes, isoforms, regulatory networks and/or biological pathways causally contributing to a disease(s) or trait(s).
• Deriving fine-mapped polygenic scores with improved performance within and across populations.
• Developing and applying novel molecular trait imputation methods to identify causal mediating factors between a causal variant and disease or higher-level trait.
• Leveraging large-scale functional genomic assays with cellular specificity to inform and set priors for identifying credible causal variants.
• Leveraging large-scale functional genomic assays to study how differences in sequence lead to differences in molecular or cellular function to identify credible causal variants.
• Developing novel computational methods to integrate functional data and other data types to identify causal variants, and how these variants lead to differences in function in relation to molecular or cellular phenotypes, disease risk or mechanism.

Section II. Award Information

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

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

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations
• Non-domestic (non-U.S.) Entities (Foreign Institutions)

Applicant organizations

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

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

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

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

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.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications  

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

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

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace 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.

2. Content and Form of Application Submission

Letter of Intent  

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

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

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

The letter of intent should be sent to:

Email: [email protected]

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

Research Strategy

The primary focus of applications responding to this announcement should be on resolving the signal underlying genome-wide significant loci associated with serious mental illnesses. These include schizophrenia, bipolar disorder, major depressive disorder, post traumatic stress disorder, attention deficit hyperactivity disorder, autism spectrum disorders, as well as relevant behavioral, cognitive, functional, cellular and molecular traits. Applications should focus on identifying the minimum credible set of functional elements that account for association signals within loci and leverage those findings to gain deeper insights into disease biology and mechanisms.

The research strategy should:

• Define the current state of the art of fine-mapping loci for complex traits in general and psychiatric disorders in particular.
• Address the goal of systematically and comprehensively identifying causal variants, genomic elements, genes, isoforms and/or networks and pathways in order to gain deeper and more specific insights into the proximate molecular mechanisms that increase risk for psychiatric disorders.
• Engage expert collaborators appropriate for the particular needs of the method being developed, e.g., genomics, statistics, mathematics a central tenet of the application.
• Employ rigorous and reproducible research practices:
• Employ open research practices (see Resource Sharing Plan).

The following modifications also apply:

• All applications, regardless of the amount of direct costs requested for any one year, should include Resource Sharing Plans.
• Prior to funding, NIMH program staff may negotiate modifications to the Resource Sharing Plans with the applicant.
• Manuscripts derived from support, in full or in part, from this award should be submitted to an appropriate preprint server no later than the first submission to a journal for peer review.
• Published, peer reviewed manuscripts should include all the necessary data, code and materials to fully reproduce all findings and figures in the paper.
• All data, code and materials should be made publicly available by the end of the award period (including the first no cost extension) regardless of whether the findings have been published or not.

Genomic Data Sharing Plan: Applicants are expected to comply with the NIH Genomic Data Sharing Policy, if appropriate. Applicants should provide a Genomic Data Sharing Plan containing the elements listed here https://gds.nih.gov/03policy2.html. The NIMH Data Archive (NDA) serves as the repository for genomic data funded by NIMH unless NIMH agrees to a different data archive during the negotiation of the terms and conditions of the grant award. Awardees who are measuring human genomic data will register with dbGaP (https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/GetPdf.cgi?document_name=HowToSubmit.pdf). After registration, all data (including but not limited to clinical, genomic, imaging, and phenotypic data) will be deposited in the NDA. A link to the NDA collection will be added to the dbGaP registration. Aggregating the genomic data in a single cloud based data archive will facilitate the re-analysis of these important data sets. Computational credits (https://nda.nih.gov/get/computational-credits.html) may be applied for to do such analysis in the cloud.

Data Sharing Plan: NIH and NIMH (see https://grants.nih.gov/grants/guide/notice-files/NOT-MH-19-033.html) expect that data, metadata, and technical protocols produced under this FOA will be deposited as appropriate into existing, publicly available data repositories that are easily accessible, in machine-readable formats. For any data produced, applicants should describe the data types, where the data and metadata will be deposited, the timeline and plans for data deposition, and the obtaining of broad consent for any human subjects data. For data types that lack suitable public repositories, applicants should indicate their willingness to identify an appropriate alternative solution. Applicants should ensure that data and other information produced or distributed by the resource follow the FAIR (Findable, Accessible, Interoperable, and Reusable) guidelines.

Protocol and Reagent Sharing Plan: As one of the primary goals of this program is to advance research through the development and broad dissemination of community resources, NIH intends that protocols and reagents produced under this FOA be broadly available, distributed at minimal cost, and without undue intellectual property constraints. Where appropriate, applicants should discuss plans for distributing non-data resources that will be produced, including models, protocols, biomaterials, and reagents.

Software Sharing Plan: A software sharing plan, with appropriate timelines, is expected in applications that are developing software.  . There is no prescribed single license for software produced in this project; however, reviewers will be asked to evaluate the software sharing plan based on its likely impact. A sharing plan guided by the following principles is thought to promote the largest impact:

1. The software should be freely available to biomedical researchers and educators in the non-profit sector, such as education institutions, research institutions, and government laboratories.

2. The plan should permit the dissemination and commercialization of enhanced or customized versions of the software, or incorporation of the software or pieces of it into other software packages.

3. To preserve utility to the community, the software should be transferable such that another individual or team can continue development in the event that the original investigators are unable to do so.

4. The terms of software availability should include the ability of researchers outside the awardee group and its collaborating projects to modify the source code and to share modifications with other colleagues as well as with the awardee group. Applicants should take responsibility for creating the original and subsequent “official” versions of a piece of software.

5. Applicants should propose a plan to manage and disseminate the improvements or customizations of their tools and resources by others. This proposal may include a plan to incorporate the enhancements into the “official” core software, may involve the creation of an infrastructure for plug-ins, or may describe some other solution.

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.

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

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.

3. Unique Entity Identifier and System for Award Management (SAM)

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

4. Submission Dates and Times

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.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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.

7. Other Submission Requirements and Information

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

Important reminders:

All PD(s)/PI(s) 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 and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Section V. Application Review Information

1. Criteria

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

For this particular announcement, note the following:

This FOA strongly encourages innovative and comprehensive approaches for fine-mapping disease or trait associated loci utilizing large-scale human genetic and genomic datasets for serious mental illnesses. The primary focus of applications responding to this announcement is identifying credible sets of variants, regulatory elements, genes and/or isoforms that causally contribute to the trait(s) of interest for psychiatric disorders. Reviewers should primarily assess merit based on the potential for novel biological insights into disease mechanisms based on the proposed studies. All applications should include plans for independent replication and validation.

Significance  

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the 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 have the potential to provide novel biological insights into disease mechanisms for serious mental illnesses above and beyond existing efforts? Does the proposed project address a need not currently covered by existing practices in the field of psychiatric disorders?

Investigator(s)  

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?

Innovation  

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

Approach  

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

Does the project provide well-defined benchmarks for assessing the success of the proposed approach for understanding psychiatric disorders? Will the findings be replicated and validated with independent datasets and/or orthogonal approaches? To what extent does the project include appropriate human genetic and genomic datasets from relevant traits, tissues and cell types? Does the project make appropriate use of large-scale genetic and genomic datasets from healthy controls, patients with neurodevelopmental or psychiatric disorders, or animals? Is there an explicit demonstration of how the approach is compatible with the principles of open science including but not limited to the development of open source software, assurance of data availability as well as a commitment to rigor and reproducibility?

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 individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Environment  

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

Rigor and Reproducibility

• Does the project adequately address issues of statistical, computational and/or experimental robustness and reproducibility?
• Are the primary and secondary statistical and/or experimental outcomes to be assessed (e.g., gene fold change, variance explained, etc) and how these relate to proposed objectives clearly stated?
• Are the number of experimental and control groups defined?
• Is there a clear definition of the ‘experimental unit’ in the analysis and the implications thereof (i.e., there is a difference between N samples from one cell line, as distinct from one sample from each of N cell lines, or combining samples from multiple lines)?
• Are the number of 'experimental units' in each experimental group defined?
• Is the total number of 'experimental units' to be measured defined?
• Is the number of times each 'experimental unit' will be measured defined?
• Is the number of independent replications of each experiment defined?
• Are there steps taken to minimize the effects of bias (e.g., batch effects, blinding, randomization) or an explanation of why this would not be appropriate?
• Have effect sizes been clearly calculated and justified how they are biologically relevant?
• Is there demonstration that statistical power calculations are grounded in justifiable and explicit assumptions about both anticipated effect size and variability of the experimental effects?
• If statistical power calculations cannot reasonably be applied, is there a principled explanation of the choice of numbers (explanations based solely in terms of ‘usual practice’ or with reference solely to previously published data will not be considered adequate)?
• Will the study be preregistered to maximize transparency and rigor?

Protections for Human Subjects  

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

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

Inclusion of Women, Minorities, and Individuals Across the Lifespan  

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

Vertebrate Animals  

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following 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.

Biohazards  

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

Resubmissions  

Not Applicable

Renewals  

Not Applicable

Revisions  

Not Applicable

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) Genomic Data Sharing Plan (GDS).

Open Science Practices

Reviewers will assess the extent to which the research strategy and research sharing plans conform to the ideals of open science such as the use of preregistration, open source software, code availability, open access data and preprints.

Data and Samples Plan

Are all proposed uses of existing data and samples adequately described? Is the proposed data and resource sharing plan explicit and detailed enough to ensure that all findings will be independently reproducible?

Authentication of Key Biological and/or Chemical Resources:  

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

Budget and Period of Support  

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

2. Review and Selection Process

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.

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

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

3. Anticipated Announcement and Award Dates

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

Section VI. Award Administration Information

1. Award Notices

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.

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

2. Administrative and National Policy Requirements

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 https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.htmlhttps://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

Not Applicable

3. Reporting

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.

Section VII. Agency Contacts

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

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

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

Alexander Arguello
National Institute of Mental Health (NIMH)
Telephone: 301-827-3547
Email: [email protected]

Nick Gaiano, Ph. D.
National Institute of Mental Health (NIMH)
Telephone: 301-827-3420
Email: [email protected]

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

Section VIII. Other Information