Department of Health
and Human Services (HHS)
and Human Services (HHS)
EXPIRED
National Institutes of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Human Genome Research Institute (NHGRI)
National Institute of Mental Health (NIMH)
National Institute of Neurological Disorders and Stroke (NINDS)
All applications to this funding opportunity announcement should fall within the mission of the Institutes/Centers. The following NIH Offices may co-fund applications assigned to those Institutes/Centers.
Office of Research on Women's Health (ORWH)
U24 Resource-Related Research Projects Cooperative Agreements
New
RFA-HG-20-039, U24: Laboratory, Data Analysis, and Coordinating Center (LDACC) for the Developmental Genotype-Tissue Expression Project
93.865, 93.172, 93.242, 93.853, 93.313
The NIH is coordinating efforts for establishing a Developmental Genotype-Tissue Expression (dGTEx) project, to catalog and analyze transcriptional profiles from a wide variety of tissues obtained from neonates, children, and adolescents in a post-mortem setting. The purpose of this funding opportunity is for support of a Biospecimen Procurement Center (BPC) to enroll suitable pediatric donors and provide high quality tissue samples for analyses to the Laboratory, Data Analysis, and Coordinating Center (LDACC). The BPC will work closely with the LDACC to optimize tissue collection, preservation and transfer of specimens.
30 days prior to application due date
December 3, 2020
All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).
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.
Not Applicable
March 2021
May 2021
July 2021
Not Applicable
It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide,except where instructed to do otherwise (in this FOA or in a Notice from 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.
Purpose
The NIH is coordinating efforts for establishing a Developmental Genotype-Tissue Expression (dGTEx) project, to catalog and analyze transcriptional profiles from a wide variety of tissues obtained from neonates, children, and adolescents in a post-mortem setting. The purpose of this funding opportunity is for support of a Biospecimen Procurement Center (BPC) to enroll suitable pediatric donors and provide high quality tissue samples for analyses to the Laboratory, Data Analysis, and Coordinating Center (LDACC). The BPC will work closely with the LDACC to optimize tissue collection, preservation and transfer of specimens.
Background
This initiative is based on the NIH-wide Common Fund Genotype-Tissue Expression (GTEx) project (https://commonfund.nih.gov/gtex) that began in 2010. The purpose of GTEx was to build a comprehensive public resource to study gene expression patterns and regulation in adult tissues. The goals of GTEx were to correlate gene expression and genetic variation within the same individual across numerous tissues and examine individual variation within a tissue across an adult population. The GTEx Portal (https://www.genome.gov/Funded-Programs-Projects/Genotype-Tissue-Expression-Project)provides open access to data including tissue gene expression profiles, expression and splicing quantitative trait loci (eQTLs and sQTLs) and sample statistics. This resource has been extensively used and benefits the scientific community, such as in drug discovery and repurposing as well as in drug safety and toxicity studies. The success of GTEx in adults lays the groundwork to initiate a similar project to understand the typical patterns of gene expression during human development.
Organs and tissues are made up of a complex mixture of different cell types, each with essentially the same genetic code but distinct biology, due presumably, in part, to differences in gene expression patterns. Just as some genes are differentially expressed across different cell types, some are turned on and off at different times during development within the same cell type. Despite considerable variation in expression patterns across tissues and across individuals, these patterns are relatively stable throughout adulthood, when most human gene expression studies have been done. The changes in gene expression that occur during postnatal development are largely unstudied, and yet lead to important milestones in health and disease such as the onset or cessation of growth spurts or puberty, and the development of childhood conditions such as asthma or attention deficit-hyperactivity disorder.
The primary goal of the Developmental Genotype-Tissue Expression (dGTEx) project is to establish a resource database and associated tissue bank to study gene expression patterns in multiple relatively healthy reference neonatal, pediatric, and adolescent tissues, and to make this resource broadly available for furthering research. This will aid in the interpretation of genome-wide association study (GWAS) and other genomic study findings, many of which do not correlate with protein-coding changes, but instead point to regulatory regions of the genome. In addition, a major advance since the previous GTEx project (that measured gene expression in whole tissue samples) is the availability of tools to study RNA expression at the single-cell level. The dGTEx resource will be a powerful tool to provide a comprehensive dataset of gene expression across a wide range of human tissues throughout development, filling a gap in genomic databases across developmental stages.
Scope
The Biospecimen Procurement Center (BPC) will consist of components supporting the procurement of pediatric post-mortem biospecimens which include identifying potential donors; acquiring multiple tissue and fluid samples from each donor; and using appropriate methods to collect, handle, and store samples. Additional responsibilities include, but are not limited to, providing expert pathological review of each specimen, collecting clinical and other types of data, and conducting ethical, legal, and social implication (ELSI) research. The BPC will incorporate the following components:
Administration and Data Management
This component will provide oversight for the BPC and be responsible for the coordination and management of the entire biospecimen procurement project. It will establish effective administrative structures for the day-to-day management of the project, including arrangements for internal quality control and quality assessment. It will create data collection forms and maintain appropriate data repositories. This component will also coordinate efforts of pathological evaluation and quality management teams to perform acquisition of biospecimens and associated clinical data. This component is also responsible for the formulation of standard operating procedures and compliance for donor enrollment and sample collection. This component will also coordinate communication with NIH program staff regarding the BPC.
Biospecimen Collection
This component will coordinate biospecimen procurement and associated clinical data from donors. It is highly likely that collaboration with multiple tissue source sites (TSS) will be required for meeting the procurement goals. Due to the sensitive nature of collecting pediatric tissues it may be helpful to collaborate with organ donor organizations and medical examiners to facilitate donor recruitment. In addition, these samples will be collected under broad consent for general research use without any restrictions, according to NIH data sharing policies. This component will collect tissues from a minimum of 30 donors (preferably more) from each of the four age intervals indicated below. Post-mortem tissues will be collected from individuals who died after experiencing an acute event, such as but not limited to asphyxiation, brain hemorrhage or death, sudden infant death, trauma, cardiac death, drowning or suicide. This component will be responsible for ensuring the collection of specimens using best practices for each tissue that will minimize the risk of abnormal or degraded tissue and that will result in the generation of high-quality nucleic acids for whole tissue and single-cell analyses in close collaboration with the LDACC. Special expertise will be necessary for the collection of some tissue types (e.g. brain) for optimal collection and precise localization of dissected material (see additional considerations). As many tissues as practicable will be collected (at least 20-30 tissues per donor), similar to what was collected in GTEx. The actual tissues collected, and their prioritization for collection, will be determined in conjunction with the dGTEx Steering Committee. Maintaining adequate donor diversity, in terms of sex/gender, race, and ethnicity will be an essential factor for donor selection. The four age intervals to be collected are:
Early post-natal (0-2 years)
Early childhood (2-8 years)
Pre-pubertal (8-12.5 years)
Post-pubertal (12.5-18 years)
Biospecimen Evaluation, Processing and Transport
This component will work closely with the LDACC to optimize tissue collection, preservation and transfer for genomic analyses. Collected organs will be evaluated, dissected, sampled and preserved by an experienced team for whole tissue and single cell gene expression analyses using best practices for each tissue type. This BPC component is also responsible for providing standardized collection kits for biospecimen collection to the TSS. Upon receipt of samples from the TSS, this component will conduct an initial evaluation and provide a centralized temporary storage of biospecimens, with the exception of brains, which will be processed separately (see below). The initial evaluation includes preparation of histological slides of the samples and scanned images for pathological review by certified pathologist(s) to verify the organ source and to characterize both general and organ-specific pathological characteristics. In addition, this component is responsible for proper shipping of the samples to the LDACC for molecular analyses.
Ethical, Legal, Social Implications (ELSI)
Research should be done to assess the ethical, legal and social implications of the study, including: the attitudes and concerns of potential study participants, particularly those with diverse racial, ethnic, socioeconomic and religious backgrounds; the effectiveness of consent processes in informing participants of the risks and benefits of the study and ensuring informed decisions; and the psychosocial impact of participation in the study on families and healthcare staff. This component should include a plan to engage representatives of the affected communities before, during and after the project to ensure the research appropriately addresses the unique needs and expectations of grieving parents and to develop procedures for longer term follow up with families regarding research outcomes.
Additional Considerations
To minimize source variability, maximize resource sharing for the brain samples, and provide high quality location information, the BPC will also collaborate with an established team dedicated to human brain research, with expertise in the development/use of atlases and common coordinate systems (e.g., Allen Human Brain Atlas, BigBrain, BrainSpan, Talairach Coordinate System, Montreal Neurological Institute (MNI) Coordinate System), as well as image segmentation and registration tools (e.g, Insight Segmentation and Registration Toolkit (ITK)), for expert valuation, precise dissection, and optimal preservation of brain samples shipped to the LDACC for analyses. Brain tissue processing should be consistent with the most current approaches for omic studies at single cell resolution. These include the rapid freezing of unfixed slices, while minimizing the post-mortem interval (PMI) to ideally less than 8 hours, and the utilization of tissue preparation strategies that allow for direct comparison of the sampled frozen tissue with either immediately adjacent or contralateral fixed tissue. Whenever possible, long term storage of residual brains and specimens in coordination with existing publicly accessible brain banks such as the NIH NeuroBioBank is expected.
The award under this FOA will be a cooperative agreement (see Section VI.2 under Cooperative Agreement Terms and Conditions of the Award). The BPC will need to work with the Laboratory, Data Analysis and Coordinating Center (LDACC), and with NIH Staff in order to meet the goals of the dGTEx Project.
A Steering Committee will be the main governing body of the dGTEx Project. The Steering Committee will be composed of the PD/PI(s) from the Biospecimen Procurement Center funded by NICHD, the LDACC funded by NHGRI, and NIH program staff. In addition to the PD(s)/PI(s), key personnel from the BPC, including pre- and post-doctoral trainees, will be eligible to attend the Steering Committee meetings. The Steering Committee will establish subcommittees or working groups to facilitate collaborative work, standardize approaches, and achieve other goals of the dGTEx Project. The BPC will be expected to play an active role in these working groups which may include (but are not limited to) groups focused on specific project activities, such as providing general study results to participating families, Ethical, Legal, and Social Implications (ELSI) research, collaborative efforts with outside groups, or data sharing. In addition to the Steering Committee, an External Scientific Panel will be formed after awards are made to provide expert recommendations.
A Community Advisory Board will be established and throughout the project serve as liaison partnering with community-based representatives to address concerns from the family decision makers on tissue donation and general research results. Responsibilities may include, but are not limited to, educating the public about the project, impact of general research results, feedback on broad consent, and ensuring cultural and religious concerns are addressed.
Data Collection and Resource Sharing
Maintaining data security protection and the proper stewardship of data is of the utmost importance. Data security encompasses confidentiality, data integrity, and availability. Confidentiality includes managing data access to maintain data security and making data accessible to authorized users only for authorized purposes. The Notice for Use of Cloud Computing Services for Storage and Analysis of Controlled-Access Data Subject to the NIH Genomic Data Sharing (GDS) Policy (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-086.html) allows investigators to perform genomic analyses on a cloud platform. The NIH security best practices and provisions (https://www.ncbi.nlm.nih.gov/projects/gap/pdf/dbgap_2b_security_procedures.pdf) should be implemented to protect the privacy and confidentiality of research participants and prevent unauthorized access to data. Investigators are expected to develop policies and procedures for notifying NIH and managing and mediating any loss of data or compromise of data confidentiality.
NHGRI and NICHD recognize that specimen and data sharing is essential to advance medical research and will expect awardees to address and adhere to NIH data sharing policies. Since the obtained biospecimens and the data derived from their analyses will be broadly shared with the biomedical research community for general data use, the informed consent document should include language that both the biospecimens and the derived data will be broadly shared without any identifying subject information with the biomedical community.
NIH intends that Project Datasets (including phenotypic, and other relevant data) and associated genomic data from this study will be widely shared with the scientific community for research uses through NIH-supported databases, such as the AnVIL. In addition, it is expected that individual-level genomic datasets generated for the dGTEx program will be designated in institutional certification documents as General Research Use (GRU) as described at https://osp.od.nih.gov/scientific-sharing/researchers-institutional-certifications/ when submitting datasets to NIH-supported databases.
Although NIH expects all project datasets from genomic studies selected as part of this FOA to be available through databases such as AnVIL, NIH does not intend for any single database to become the exclusive source of this program’s data. Information such as study protocols, software code and algorithms, descriptions, and publications are expected to be made available through databases such as AnVIL; other public web sites; and/or publication in the scientific literature.
Data on gene expression, phenotypic information, and sample and data analysis should be deposited in AnVIL on a timely and regular basis.
The dGTEx Steering Committee will develop and implement network-wide approaches for resource deposition and use including submission to national repositories as appropriate.
Timeline
During the first year of the program, the BPC and LDACC will work together to develop protocols for the procurement of tissues, transfer of samples, sequencing, data sharing, and ELSI research. Years 2-4 of the program will ramp up recruitment for a minimum of 120 donors (preferably more), to perform sequencing and basic analysis of gene expression. The last year of the project will ramp down any remaining recruitment, sequencing or analysis functions and publications.
Helpful informational items for applicants regarding the dGTEx project is available at https://www.genome.gov/Funded-Programs-Projects/Developmental-Genotype-Tissue-Expression
See Section VIII. Other Information for award authorities and regulations.
Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this FOA.
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.
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The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.
The NICHD intends to fund 1 award in fiscal year 2021, corresponding to a total of $12.15M over the five-year budget period. The actual amounts distributed per fiscal year are dependent on annual appropriations but are anticipated to be the following:
$3.35M for fiscal year 2021
$3.60M for fiscal year 2022
$2.40M for fiscal year 2023
$1.40M for fiscal year 2024
$1.40M for fiscal year 2025
The following NIH components intend to contribute the following total amounts to the award above distributed during the five-year budget period:
NICHD $10.15M
NINDS $1M
NIMH $1M
NHGRI intends to fund 1 award in response to the complementary companion FOA (RFA-HG-20-039)
Application budgets are limited andneed to reflect the actual needs of the proposed project.
The scope of the proposed project should determine the project period. The maximum project period is 5 years.
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from 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
For-Profit Organizations
Local Governments
Federal Governments
Other
Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are not allowed.
Applicant organizations
Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.
Program Directors/Principal Investigators (PD(s)/PI(s))
All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.
Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
Applicant organizations may submit more than one application, provided that each application is scientifically distinct.
The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:
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.
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:
The letter of intent should be sent to:
John V. Ilekis, PhD
Telephone: 301-435-6895
Fax: 301-496-3790
Email: [email protected]
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.
The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing 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.
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.
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:
Research Strategy:
Research Strategy must consist of the Subsections A-D, as defined below. Each Subsection should include, but is not limited to, each of the elements listed.
Subsection A: Project Overview
Describe the following elements:
Subsection B: Administration and Data Management
Describe the following elements:
Subsection C: Donor Biospecimen Collection, Evaluation, Processing and Transport
Describe the following elements:
Subsection D: Ethical Legal and Social Implications (ELSI) Research
Describe the following elements
.
Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.
The following modifications also apply:
When involving human subjects research, clinical research, and/or NIH-definedclinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:
If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or 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.
All instructions in the SF424 (R&R) Application Guide must be followed.
Foreign Institutions
Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.
See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov
Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.
Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.
Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.
Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.
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 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.
Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.
Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.
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? 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?
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?
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?
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?
Additionally for this FOA, will the BPC’s conceptual design and overall operating plan effectively procure and preserve tissue samples across developmental stages? Does the BPC’s operating plan provide opportunity for collaboration, integration, and interaction with the LDACC? Are the BPC strategies adequate and appropriate for the dGTEx project? Is the data sharing plan appropriate?
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?
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.
For research that involves human subjects but does not involve one of thecategories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.
When the proposed 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.
The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.
Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.
Not Applicable
Not Applicable
Not Applicable
As applicable for the 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.
Not Applicable
Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).
Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).
For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.
Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.
Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by Center for Scientific Review, 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 will receive a written critique.
Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:
Information regarding the disposition of applications is available in the NIH Grants Policy Statement.
A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.
Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.
Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.
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.
All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.
Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html.
HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.
Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.
In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.
The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, and other HHS, PHS, and NIH grant administration policies.
The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.
The PD(s)/PI(s) will have the primary responsibility for:
Adopting a diversity first perspective, encouraging recruitment of non-European Ancestry (EA) donors, whenever possible.
The Project Scientist (PS) will have substantial scientific involvement during the conduct of this activity through technical assistance, advice, and coordination. Additionally, the program official will be responsible for the normal programmatic stewardship of the award and will be named in the award notice. The role of NIH staff will be to facilitate and not to direct the activities of the BPC and LDACC awardees. It is anticipated that decisions in all activities will be reached by consensus of the program and that NIH staff will be given the opportunity to offer input to this process. The PS will participate as a member of the SC and will have one vote. The PS will have the following substantial involvement:
Areas of Joint Responsibility:
Close interaction among the participating investigators will be required, as well as significant involvement from the NIH, to manage, assess, and implement dGTEx. In addition to the PD(s)/PI(s), key co-investigators and pre- and postdoctoral trainees, especially those who are members of under-represented minority groups or those from different but related disciplines, are eligible to attend these meetings.
Steering Committee: The SC will be the main governing body of the Project. The SC will be composed of all the PD(s)/PI(s) of each awarded cooperative agreement in this program (BPC and LDACC) and the PS for this Project. Cooperative agreements with multi-PI arrangements will have a single vote to be decided as desired within the multi-PI award. The SC may add additional members, and other government staff may attend the SC meetings as desired. It is anticipated that additional coordination mechanisms may be set up with other U.S. and international groups that may collaborate with the program. Awardees will be required to accept and implement policies approved by the SC.
The SC may establish subcommittees or working groups, in order to facilitate collaborative work and standardize approaches, or to achieve other goals of the Project. Members may include representatives from the program, other NIH staff and other experts, as appropriate.
The PI(s)/PD(s) will be expected to play an active role in these working groups, which may include (but are not limited to) groups focused on specific cross-project activities, such as data standardization, outreach and education, or international data sharing.
The awardees and the PS will meet as the program SC three times a year (2 in-person and 1 via webinar) to share information on data resources, methodologies, analytical tools, data analyses, preliminary results, etc.
NIH and the grantees will work with and provide information to an External Scientific Panel (ESP). The ESP will be responsible for reviewing and evaluating the progress of the project to facilitate members of the Project meeting their individual and collective goals. The ESP will provide recommendations to NIH Leadership. The ESP will meet at least once a year. During part of this meeting, there will be a joint meeting with the SC to allow the ESP members to interact directly with the awardees. The ESP will make recommendations regarding progress of the Project and present advice about changes, if any, which may be necessary in the Project to NIH Leadership.
Awardees and the PS agree to work collaboratively toward:
Dispute Resolution:
A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.
The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreementsare required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.
In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM)about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings.Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.
We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threatensubmission by the due date, and post-submission issues)
Finding Help Online:http://grants.nih.gov/support/(preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email:[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]
John V. Ilekis, PhD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6895
Email: [email protected]
Jyoti Dayal, MS
National Human Genome Research Institute (NHGRI)
Telephone: 301-280-2307
Email:[email protected]
Tara Dutka, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-451-3074
Email:[email protected]
Daniel Miller, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-5680
Email:[email protected]
Elena Gorodetsky, MD, PhD
Office of Research on Women’s Health (ORWH)
Telephone: 301-594-9004
Email:[email protected]
Mark G Caprara, PhD
Center for Scientific Review (CSR)
Telephone: 301-827-3076
Email: [email protected]
Bryan Clark, MBA
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6975
Email: [email protected]
Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.