Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

Office of Strategic Coordination (Common Fund)

This Funding Opportunity Announcement (FOA) is developed as a Common Fund initiative (http://commonfund.nih.gov/) through the NIH Office of the NIH Director, Office of Strategic Coordination (https://dpcpsi.nih.gov/). All NIH Institutes and Centers participate in Common Fund initiatives. The FOA will be administered by the National Institute of Drug Abuse (NIDA) on behalf of the NIH.

Funding Opportunity Title
Somatic Mosaicism across Human Tissues (SMaHT) Program: Genome Characterization Centers (UM1 Clinical Trial Not Allowed)
Activity Code

UM1 Research Project with Complex Structure Cooperative Agreement

Announcement Type
New
Related Notices

None

Funding Opportunity Announcement (FOA) Number
RFA-RM-22-013
Companion Funding Opportunity
RFA-RM-22-009 , U24 Resource-Related Research Project (Cooperative Agreements)
RFA-RM-22-010 , UM1 Research Project with Complex Structure Cooperative Agreement
RFA-RM-22-011 , UG3/ UH3 Phase 1 Exploratory/Developmental Cooperative Agreement/Exploratory/Developmental Cooperative Agreement Phase II
RFA-RM-22-012 , U24 Resource-Related Research Project (Cooperative Agreements)
Assistance Listing Number(s)
93.310
Funding Opportunity Purpose

This funding opportunity announcement invites applications to establish the Genome Characterization Centers (GCCs) for the Somatic Mosaicism across Human Tissues (SMaHT) Network.  The purpose of the SMaHT Network is to enable discovery of new biology and disease mechanisms mediated by genomic variation in somatic tissues. The GCCs will be responsible for generating state of the art, high throughput genomic data characterizing somatic variants in a set of 10-15 human tissues from 150+ donors. The GCCs will work closely with the SMaHT Data Analysis Center to build the framework for a comprehensive catalog of variants.

Key Dates

Posted Date
February 23, 2022
Open Date (Earliest Submission Date)
June 08, 2022
Letter of Intent Due Date(s)

June 8, 2022

Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS Scientific Merit Review Advisory Council Review Earliest Start Date
July 08, 2022 Not Applicable Not Applicable November 2022 January 2023 April 2023

All applications are due by 5:00 PM local time of applicant organization. 

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

Expiration Date
July 09, 2022
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

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.

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

  1. Use the NIH ASSIST system to prepare, submit and track your application online.
  2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.

  3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.


  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Background

The genomics era has revolutionized medicine and biomedical research by uncovering the genetic basis of thousands of diseases, congenital birth defects, and biological processes. However, genetic studies, which rely on DNA primarily isolated from blood and saliva, fail to fully capture all DNA variation in affected cells, tissues, and organs, yielding an incomplete snapshot of somatic variations and their contribution to health and disease. Variants occur widely throughout the genome and across the lifespan via a variety of genomic and biological mechanisms, creating stochastic, clonal, and dynamic somatic mosaicism. Although small-scale studies show causal roles for somatic variants in development, aging processes, and several diseases, the functional consequences of somatic variation are largely unknown.

The purpose of the Somatic Mosaicism across Human Tissues (SMaHT) Network is to propel discovery of new biological processes in human health and disease that are mediated by genomic variation in somatic tissues. The role of somatic variants in human health will be elucidated through: 1) Building a scaffold and foundational datasets that catalog somatic variation across a set of common tissues from a diverse donor pool, 2) developing tools focused on increasing the sensitivity of detection and specificity of the pipelines to detect multiple types of variations, and 3) creating a variant catalog, portal and integrated workbench that facilitates access to the tools, technologies, and data developed by the Network.

Five initiatives will be used to achieve the goals of this NIH Common Fund program:

  • The Tissue Procurement Center will collect, process, and distribute a set of 10-15 high quality human tissues from a diverse donor cohort
  • The Genome Characterization Centers will use state-of-the-art genomics sequencing technologies to identify all types of somatic variation in tissues from the biorepository
  • The Data Analysis Center will integrate the data generated by the Network to build the variant catalog, portal and workbench
  • The Organizational Center will coordinate Network activities and establish strong links with related NIH and international programs
  • The Technology and Tools Development Projects will develop next generation tools focused on significantly improving detection and characterization of somatic variants

To develop this program, the NIH SMaHT Working Group solicited expertise from the biomedical research community through Think Tank Meetings focused on somatic variation, a Request for Information, and meetings with NIH staff and outside experts. Please see the Common Fund’s SMaHT website for the summary of these activities.

The success of this Common Fund Program depends on the formation of a highly interactive, collaborative Network that has the expertise and common vision to create a framework for cataloging somatic variants in a wide variety of post-mortem, non-pathological human tissues. The NIH SMaHT Working Group invites investigators to develop bold, innovative approaches to address the challenges this program will face and that will catalyze our understanding of the role of somatic variants in human health and disease.

Objectives and Scope

This funding opportunity aims to fund Genome Characterization Centers (GCCs) that will identify and characterize multiple types of human somatic variation (SNVs, structural variants, and mobile DNA elements) in a set of 10-15 tissues from 150+ donors. By funding multiple GCCs, the intent is to encourage some degree of diversity of approaches. There are multiple ways to characterize somatic variation, some of which have advantages for detection of certain types of variants. Moreover, the state-of-the art moves rapidly. Nonetheless, high-throughput genomic and RNA sequencing for the detection of somatic mosaicism in a variety of human tissue and cell types is a key requirement to form the basis of a common data set. It is expected that by the end of the five years of funding, the GCCs will have well characterized at least 2250 samples that will form the basis for the SMaHT Variant Catalog. NIH is particularly interested in understanding how different factors correlate with the timing, amount, tissue distribution, type, etc. of somatic variation. Understanding these variables is an important part of specifying what is needed to develop a full SMaHT catalog.

Genome Characterization Centers will be expected to work closely together and with the other components of the SMaHT network. Most importantly, they will provide their data to the Data Analysis Center; these data will be used to generate a tissue-specific catalog of human somatic genomic variation. The catalog will be made available to the community through the SMaHT Variant Catalog Portal and Integrated Data Workbench. The Integrated Data Workbench will seamlessly integrate with current genome browsers, such that somatic variation can be analyzed alongside the reference sequence. The Tissue Procurement Center will supply the GCCs with the common set of 10-15 non-pathological tissues covering the three germ layers from at least 150 donors over the funding period. Although NIH expects that the state-of-the-art is sufficiently advanced to start production of data for a catalog in the first year of funding, it is also clear that there is room for improvement of methods, technologies, and research strategies. Therefore, although GCCs will not be developing technologies themselves, they will be expected to work with the Tool Development Projects to improve the ultimate value of the catalog.

GCCs will need flexibility in their data production pipelines over time in order to respond to the availability of biospecimens, changing state-of-the-art, or changing needs in Catalog construction, such as the proportion of effort devoted to cell type specific or single cell vs. bulk analyses.

Data Production

Biospecimens. The Tissue Procurement Center (TPC) will provide biospecimens to the GCCs. During the first year, existing biospecimens will be used for benchmarking until new biospecimens are ready for distribution by the TPC. The TPC will make all efforts to accommodate the sample input requirements of the GCCs; however, the GCCs will be responsible for any specialized sample validation and preparation that is required for specific protocols, for example cell sorting and nucleic acid preparation for single cell methods. Further details of the TPC's responsibilities can be found here.

Assay Types. Each GCC will be expected to devote at least two-thirds of its data production capacity to producing data from a common core set of assay types. NIH intends that these core assays will be used on every biospecimen to simplify data integration, analysis, and construction of a Variant Catalog. The common core assay types that all GCCs are expected to propose are: 1) short-read, and 2) long-read DNA sequencing, and 3) RNA-seq. In addition, each GCC should propose additional assays utilizing their specialized expertise in one or more of the following areas: single cell RNA and/or DNA analyses; large and/or small structural variants; transposable elements and mobile DNA; multi-omic analysis. Applicants should justify all proposed data modalities thoughtfully, in terms of the ability to detect somatic variants, depth of coverage to achieve adequate frequency resolution, utility across a range of tissues, biological and experimental variability, etc. GCCs are expected to generate reproducible data within the first year of funding and to meet data generation goals every six months, so it is important that any data generation that is proposed be mature and robust enough to constitute a reliable production pipeline.

New technology adoption. This FOA does not fund new technology development. However, GCCs are expected to remain at the state-of-the-art in terms of their data production activities. Applicants may propose to adopt modifications, new platforms, or pilot projects in collaboration with other Network members during the grant period and will be strongly encouraged to work with funded projects supported by the companion Tools Development funding opportunity.

Benchmarking. Once applications are funded, the GCCs will be asked to design and execute a benchmarking exercise which will entail each center characterizing several identical samples in their production pipeline and comparing results. Applicants are welcome to include proposed details to support this exercise in their application, as well as other benchmarking studies that would give insight into the production pipelines and encourage effective collaboration, though final details will be decided post award.

Cost and scale. Once data production pipelines are established, the program will develop a framework for understanding production costs, in order to plan allocation of resources for efficient generation of a comprehensive variant catalog. It is expected that costs will decrease, and quality and throughput of data will increase during the project period. Applicants are strongly encouraged to include full analysis of costs per biospecimen in their application and to plan for data generation goals to be revised annually in coordination with NIH staff.

Data Processing and Analysis

All SMaHT data will be sent or otherwise made available to the SMaHT Data Analysis Center, which will harmonize and process the data across centers (particularly from the “common data set”, see above), make it available to the SMaHT Network as well as the broader research community, and do the analyses needed (variant frequency and tissue type, etc.) to produce the SMaHT catalog. GCCs may also undertake analyses of their own data and are encouraged to participate in collaborative analyses across the entire data set.

Therefore, this FOA seeks applications that, along with the data production, include well-integrated data management, processing as required for the data generated by individual centers, and analysis plans. GCCs will work closely with the SMaHT DAC to ensure harmonization and compliance with data and metadata standards, data formats and annotation, as well as having a robust and effective data processing pipeline in-house.

Research Focus

The success of SMaHT is dependent on establishing a Network that can rapidly build a robust and comprehensive catalog of somatic variants in multiple human tissues. The Genome Characterization Centers will play a central role in collecting the data that will form the catalog, so applicants are strongly encouraged to optimize or adapt appropriate existing resources, tools and infrastructure and to create new ones only when required. Applicants are also strongly encouraged to optimize or adapt solutions from other communities.

Applications addressing the following topics will be deemed non-responsive and will not be reviewed:

  • Do not propose to identify and characterize human somatic variants in normal tissue; propose work on somatic variation related to cancer or other diseases or conditions;
  • Do not propose work on an established, robust data production pipeline for somatic variant discovery and characterization;
  • Narrowly focus on only a single somatic variant type, rather than seeking to characterize a broad range;
  • Do not include a substantial “common data set” element including high-coverage DNA short- and long-read sequence data, and RNA seq of bulk tissues;
  • Propose new technology development, that goes beyond incremental pipeline; modification or adoption of existing methods into existing production pipelines;
  • Do not include an integrated data processing and analysis component;
  • Do not describe how they will work with the SMaHT Network to obtain all samples from, and to make their data available to, other Initiatives within the SMaHT program.

Network Coordination and Collaboration

Successful applicants will become members of the larger SMaHT Network composed of investigators who have been funded by one of the SMaHT Network FOAs. A key aspect of this program is the formation of a close partnership amongst all SMaHT awardees, aligned around the overall goal of the program. All proposals for this program will be asked to include annual goals and milestones that contribute to the overall Network to help achieve this alignment. Shared responsibilities derived from the use of the cooperative agreement mechanism are described later in this FOA and will be further articulated during the kickoff meeting that will take place a few months after awards are made. All funded investigators will be required to attend this initial Kickoff meeting, annual investigator meetings as well as regular teleconferences with Network members and NIH Staff for the duration of the funding cycle.

In addition to completing the research goals outlined in their applications, successful applicants will be expected to work collaboratively with all members of the Network to maximize the success of the program. Therefore, all potential awardees are asked to plan and budget for approximately 20% of their total budget to go towards collaborative activities. Collaborative project activities may include adaptive tissue sampling approaches for regions with high rates of somatic variance, benchmarking of similar methods across sites, comparison of adjacent tissue slices by complementary methods, development of common analytical pipelines and quality assessment metrics, visualization tools or joint analysis of data from the same tissue across multiple donors. Applicants do not need to include these collaborative activities as a separate budget item and are encouraged to include details of potential activities as part of their applications; however, the final set of activities will be determined post-award through discussion with Network members and NIH staff.

NIH intends that the products of the Network be broadly available to the research community to establish the foundations for a somatic variant catalog that other NIH programs and the international community can build upon; this includes methods, tools, reagents, biospecimens, datasets, and software. Awardees will be expected to abide by Network policies such as assay and data standards; the rapid sharing of data, methods, and standards; publication of data and results; partnerships and participation of similar projects and programs and sharing of resources. The robustness and reproducibility of results are critical to the success of SMaHT. In some cases, conducting additional critical validations will be important for assessing progress.

Therefore, NIH Program staff, in consultation with the PD/PI, may modify or add work to be conducted during the duration of an award.

As the Network moves towards realizing its goals, new technologies will become available and unanticipated circumstances will arise. An important aspect of using cooperative agreements to support the Network is the ability to modify metrics, goals and milestones to respond to opportunities and challenges. Applicants should expect, and applications should anticipate, the need for such flexibility. Any changes in goals will be made with input from NIH Program Staff. It is possible that some changes may, if needed, be accompanied by changes in the distribution of resources within the Network.

Technical Assistance Webinar

All applicants are strongly encouraged to contact NIH Staff to discuss the alignment of their proposed work with the goals of this FOA and the SMaHT Network. A Technical Assistance teleconference will be held for potential applicants from 12-1pm Eastern Time on April 29, 2022. NIH staff will be available to answer questions related to this FOA. Dial in information for the call is posted on the SMaHT website and slides will be made available on the website for those unable to attend. A list of frequently asked questions (FAQs) related to the program are also posted on the website: https://commonfund.nih.gov/smaht. The information session is open to all prospective applicants, but participation is not a prerequisite to apply.

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

Section II. Award Information

Funding Instrument

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.

Application Types Allowed
New

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.

Clinical Trial?

Not Allowed: Only accepting applications that do not propose clinical trials.

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

The Office of Strategic Coordination (Common Fund) intends to commit $10M total costs in FY2023, $12M total costs in FY2024, $14M total costs in FY2025, $16M total costs in FY2026 and $16.5M total costs in FY2027 to fund 4-6 awards.

Award Budget

Application budgets need to reflect the actual needs of the proposed project.

Award Project Period

The project period cannot exceed 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.

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

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)

Local 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)

Federal Government

  • Eligible Agencies of the Federal Government - including the NIH Intramural Research Program
  • U.S. Territory or Possession

Other

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

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. 

Required Registrations

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.

  • 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.
    • Unique Entity Identifier (UEI)- A UEI is issued as part of the SAM.gov registration process. SAM registrations prior to fall 2021 were updated to include a UEI. For applications due on or after January 25, 2022, the UEI must be provided on the application forms (e.g., FORMS-G); the same UEI must be used for all registrations, as well as on the grant application.
    • Dun and Bradstreet Universal Numbering System (DUNS) – Organization registrations prior to April 2022 require applicants to obtain a DUNS prior to registering in SAM. By April 2022, the federal government will stop using the DUNS number as an entity identifier and will transition to the Unique Entity Identifier (UEI) issued by SAM. Prior to April 2022, 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.
  • eRA Commons - Once the unique organization identifier (DUNS prior to April 2022; UEI after April 2022) is established, organizations can register with eRA Commons in tandem with completing their full SAM and Grants.gov registrations; 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 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.

Eligible Individuals (Program Director/Principal Investigator)

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.

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

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, per 2.3.7.4 Submission of Resubmission Application. 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 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

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

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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:

Amy Lossie, Ph.D.
Telephone: 301-827-6092
Email: SMaHT@mail.nih.gov

Page Limitations

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed, with the following additional instructions:

The Research Strategy must consist of the following subsections with the indicated page limits:

Subsection A: Center Overview --one required -- 6 pages

Subsection B: Genome Characterization -- one required -- 12 pages

Subsection C: Data Management -- one required -- 12 pages

Instructions for Application Submission

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.

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

SF424(R&R) Senior/Key Person Profile

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

Key personnel are strongly encouraged to highlight in their biosketch experience generating and analyzing data as part of a large research consortia, conducting milestone-driven multidisciplinary research, and collaborating on the development of community resources.

R&R Budget

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

PD/PIs: The Center Director must devote a minimum of 1.8 person months of effort to the Center through the individual components. For applications with multiple PDs/PIs, a minimum effort of 1.2 person-month is required for the Contact PD/PI and 1 person-month of effort per additional PD/PI is required.

Program Manager: Based on the complexity of the SMaHT Network, GCCs are strongly encouraged to include and budget for a full-time Program Manager to manage day-to-day operations and work with the Center team, the rest of the Network, and NIH staff to efficiently and effectively manage and coordinate the Centers' activities.

Equipment: If pieces of specialized equipment or computers exceeding $5,000 are requested, the application must provide a clear justification for the purchase in Budget Justification.

Travel: Include travel costs for the Center Director and pertinent members of the Center to attend annual Network investigator meetings and workshops.

Data Analysis: Include details for of data analysis costs beyond routine data management processing and QC. Costs should be limited to less than 15% of the total budget and applicants should note that any proposed cloud computing plans may be modified and consolidated to optimize Network collaboration.

Collaboration: In all years, reasonable costs must be allocated to support shared work with other Network members. Specific tasks will be determined post-award in consultation with NIH staff and a proportion of the award may be restricted pending agreement of goals and milestones.

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Specific Aims: Describe the specific goals of the GCC and its role in achieving the overall objectives of the SMaHT Network.

Research Strategy: In the Research Strategy, applicants should propose plans, approaches, and potential alternative strategies for carrying out the goals of the GCC. Applicants are strongly encouraged to highlight their track record in managing large distributed research projects and any resources, instrumentation, data resources or institutional support available for this proposal. The Research Strategy section must consist of a single attachment consisting of subsections A-C, as designated below.

Milestones and Timeline: A timeline (Gantt chart) including milestones is required for each subsection. Milestones are go/no-go decision points in the project and must include clear and quantitative objective criteria for success. Yearly quantitative milestones are required to provide clear indicators of continued progress or emergent difficulties and will be used to evaluate the application not only in peer review but also in consideration of the awarded project for funding of non-competing award years. The application must include well-defined milestones: e.g., amount of data that will be generated by each data types in each six-month period; expected quality performance measures to be reached each year and criteria for prioritizing selection of biospecimens and incorporating of new technologies.

Subsection A. Center Overview and Management

The purpose of this subsection is to provide an overview of the proposed GCC and how it will be structured to achieve the Center’s goals and the major objectives of the FOA, in addition to allowing applicants to discuss the Significance and Innovation aspects of the application. This subsection should include a high-level description of the strategic approach along with the high-level rationale behind those choices. The overview should provide a sense of how the proposed effort will contribute data, methods, and knowledge to the efforts to build the SMaHT catalog, and, more generally, contribute to the understanding or interpretation of gene and/or pathway function or other biological processes. Applicants should also discuss the wider significance of their approach for understanding somatic variation. Any planned technical, strategic, methodological, analytical, or other innovation may be highlighted.

  • Outline the expertise of the research team (without duplicating information in the Biosketches) and explain how their expertise aligns with the key components of the FOA (e.g., DNA/RNA sequencing, high-throughput data production, somatic variant discovery, integration, see above).
  • Describe the management structure of the proposed center, including the role of the Project Manager responsible for day-to-day operations, experience of the Project Manager with programs of similar or larger efforts, components of the center and how they will be integrated to form a cohesive center, key personnel, and their responsibilities (such as those responsible for data collection, data analyses, and data submission), and overall center leadership.
  • Discuss how the encouragement of diversity of investigators has been addressed.
  • Discuss past experiences (if any) in working as part of interdisciplinary teams and/or large collaborative research efforts. Describe how Network interactions will be managed, including how this proposed center will work collaboratively with other components of the Network in component-specific and Network-wide activities such as coordinating with the TPC and DAC components, developing a common data set, establishing formats, standards, annotations, pipelines, and polices for data, comparing across approaches, and planning joint analyses. This section should include descriptions of consents or material transfer agreements that allow for sharing of research products with other Network-supported centers and projects. This section should also include plans for management of any external collaborations, if relevant.
  • As part of the management plan, applicants should give an overview of how they will ensure the essential elements of reproducibility in their own laboratories, as well as propose the key elements for ensuring reproducibility and comparability among Network members, including e.g., overlap in genes tested, assays, and common controls. This also includes validation of samples, reagents or data taken in or released by the center. Details about ensuring data reproducibility should be included in the appropriate subsections below.
  • Describe how the elements of the Center will be brought together and what you think the critical issues are likely to be and how to address them, either just within your GCC or across the Network. How will the overall effort contribute to lessons about how, and whether, to pursue a more comprehensive effort?
  • Describe plausible routes by which your overall plan could work in combination with those of other SMaHT awards to ultimately produce high quality, consistent data across the program. Although the details of the other centers cannot be known in advance, applicants should discuss the potential for their proposed data to be used by others, for example to allow comparisons between centers or to maximize the throughput.
  • For this subsection, applicants should define a clear set of semi-annual goals and quantitative milestones with metrics that will logically contribute towards the achievement of the ultimate goals of the Center. Whenever feasible, milestones should provide quantitative metrics for assessing the center’s progress. Milestones will be reviewed and updated, as needed, in consultation and with the approval of NIH Staff.

Subsection B. Genome Characterization

The elements below must be clearly addressed in the application. However, applicants may use a different order (or combine or split elements) if the rationale for each, and the factors to be considered in integrating them, will be clearer or will fit better with their proposed approach. It is expected that all methods proposed will be ready for use in an integrated production pipeline. Choices should be supported by publications or preliminary data.

  • Describe potential problems, alternative strategies, how you will evaluate whether the element is successful (including benchmarks), and how you will respond if issues arise.
  • Provide detailed descriptions of, and rationales and justifications for, how the SMaHT samples will be characterized for a broad range of somatic variants. This subsection should discuss both the required “common data set” using high coverage short- and long-read DNA sequencing and RNA sequencing of bulk samples as well as the “applicant-initiated” component and its complementarity with the common data set.
  • Describe the sequencing production pipeline, from receipt/QA of incoming samples, through data deposition with the DAC (details of data processing and analysis should be in the separate subsection, below; applicants may wish to refer to those details in this subsection without duplicating them here). Describe how any other data types will be generated. Describe how the proposed production will meet or exceed production/throughput targets implied by the number of samples (10-15 tissues, from 150+ individuals, across the program, in five years).
  • Justify all proposed data modalities thoughtfully. Describe the quality and value of the data that you propose to generate on somatic variants, with consideration of all key factors such as depth of coverage, sensitivity and specificity, limits of detection/allele fraction, ability to resolve different types of somatic variant, performance across multiple different human tissues (which may have different “spectra” of somatic variation with respect to type, frequency, and significance), biological and technical variability. Please discuss how you have considered your data production strategy in light of these factors, and the overall biological significance of the data you plan to generate. How will your strategy address potential biological, technical, and interpretation issues, including e.g., small clone size/low frequency; variable biological origin of the variants; work across different variant and tissue types; statistical power, coverage, bias, and error rates; and biological and experimental variability?
  • What are the likely most important challenges that these factors represent to the SMaHT goals, and how will you address them? Discuss how the applicant-initiated component will add value to the common data set, or other value to the overall SMaHT effort. Address how different center data sets will be integrated.
  • Discuss how your proposed pipeline will adapt to the provision of samples by an outside entity, the SMaHT DAC. What are the input requirements? What QC will be done on input samples? If your data production pipeline has unique input sample requirements, please identify them.
  • Discuss estimated sample throughput, and how the effort will allow the characterization of a total of at least 2250 samples (10-15 drawn from each of 150+ donors), together with up to four other GCCs, and accounting for the need for each GCC to characterize a small set of “benchmark” samples. Plans for scale-up, if needed, should be clear for different data types, and should consider the planned budget amounts in each year.
  • Applicants should indicate how they track costs internally, and how the data production will be organized (e.g., subcontracted, internal service center, etc.). Regarding scale, applicants should discuss the estimated relationship between resources potentially available through this program, and scale. Is the relationship linear?
  • Discuss flexibilities in pipelines to adopt new platforms or methods as they mature, with the aim of improving production over the life of the grant. Describe your standard procedures for testing and adopting new methods or platforms into your production efforts, as well as changes in consumables and batch to batch variation.
  • For this subsection, applicants should define a clear set of semi-annual goals and quantitative milestones with metrics that will logically contribute towards the achievement of the ultimate goals of the Center.

Subsection C. Data Management, Processing, and Analysis

For this FOA, we make a practical distinction between data management and processing, on the one hand, and analysis, on the other. Data management and processing are integral and required to produce high quality data and metadata, for handoff to other components of the Network.

  • Applicants should propose data management and processing plans including all steps from handling incoming sample data through routine processing and QC and handoff. Please consider ensuring completeness, quality assessment and control, appropriate tracking, preservation, integration, and availability of the data, data wrangling, and transmission to the DAC. For this subsection, please describe your laboratory information management system, how it will be implemented for this project, why it will be adequate over the life of the project, and what incremental improvements may be needed or undertaken to adapt it to the SMaHT program.Please include a "sample/data flow" diagramillustrating the path that data generated internally will follow, from sample logging and data generation, to internal lab management systems, to analysts, to handoff to the DAC, including what specific data types could be transmitted.
  • Although the SMaHT program envisages that the DAC will be responsible for developing a single aggregate data set for the SMaHT catalog, until the Network is funded the details cannot be provided, so it is difficult to specify now what data will be handed off. The DAC is highly likely to be able to perform variant calling on the data from the “common data set”, but for particular “applicant-initiated” data types, it may be a reasonable course for the GCC to hand off more fully processed data.
  • Although these elements should be described in a separate subsection, applicants should articulate how their data management and processing will be integrated with data production, including data storage and backup protocols.
  • In addition to the required management and processing, applicants may propose to analyze the data; either just the data that they produce, or the aggregate data. Note that the funding available in this FOA for analyses is limited, so applicants should prioritize analyses that are designed to characterize the quality and utility of their data for downstream applications (e.g., consistency, biological, and technical variability), or demonstrate the added value of the data for the SMaHT catalog. Any proposed analyses should be described and justified.
  • For all Data Management, Processing, and Analysis elements, applicants should consider the following:
  • If not already detailed in the elements above, please discuss any specialized analytical software, statistical/computational methods, and algorithms to be used, for example, in processing raw data, for all data modalities that you propose to produce.
  • Applicants are encouraged to identify analytical or data processing steps that are likely to represent common challenges across the Network, and that represent opportunities to develop solutions that are more uniform or reproducible across the Network.
  • Processing and analysis plans should take into account that the data will be derived from diverse samples (populations, ages, sex).
  • Applicants should also take into account that the SMaHT DAC and other GCCs will be doing analyses of their own choosing, using the data. It will be useful to have coordination within the Network on proposed analyses.
  • For this subsection, applicants should define a clear set of semi-annual goals and quantitative milestones with metrics that will logically contribute towards the achievement of the ultimate goals of the Center.

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:

  • All applications, regardless of the amount of direct costs requested for any one year, must address a Resource Sharing Plan.
  • Because the ultimate aim of the Program that this RFA is part of is to produce a community resource, the quality of the Resource Sharing Plan will be considered as part of the Approach criterion
  • In their Resource Sharing Plan, applicants should indicate their willingness to abide by all policies related to resource sharing developed by the SMaHT Steering Committee and approved by NIH staff. Awardees are expected to develop such policies as members of the Network's Steering Committee in collaboration with NIH and should indicate their willingness to participate in the development of such policies and to abide by them. These policies will remain consistent with NIH policies on data and resource sharing.
  • After initial review, NIH program staff will conduct an additional administrative review of the plans for sharing data, software, data analysis, as well as resources and may negotiate modifications of these plans with the prospective awardee. The final negotiated version of these plans will become a term and condition of the award of the cooperative agreement.

The Resource Sharing Plan should include the following sections as appropriate:

  • Data Sharing: Implementation of FAIR (Findable, Accessible, Interoperable, Reusable) Principles is essential for the success of SMaHT. Consistent with achieving these principles, the NIH expects that information such as collected data, technical protocols, and any other metadata collected under this FOA is to be rapidly deposited as appropriate into the DAC and in a recognized and reusable format. The DAC will serve as the central access point for information regarding data, tools, and reagents being developed by the SMaHT Network. Applicants must abide by the NIH Genomic Data Sharing Policy (https://osp.od.nih.gov/scientific-sharing/genomic-data-sharing/) and should indicate their agreement to abide by it in the data sharing plan. The Network will be expected to work closely with the Common Fund Data Ecosystem (https://www.nih-cfde.org/) to assess FAIRness and ensure data and resources from SMaHT are interoperable with other Common Fund resources. In addition, NIH staff will work closely with SMaHT awardees to leverage other NIH initiatives, such as STRIDES (https://cloud.nih.gov/) and the Researcher Auth Service (https://datascience.nih.gov/researcher-auth-service-initiative), to ensure the long-term sustainability of key resources generated by the program beyond its lifetime.
  • Public Access: The NIH Common Fund intends to maximize the availability of publications and the sharing of underlying data for the SMaHT Program and encourages publication of preprints and the use of open access journals. Applicants should describe their proposed process for making resulting publications and to the extent possible, the associated data immediately and broadly available to the public or provide a justification if such sharing is not possible. Underlying primary data is expected to be made as widely and freely available as possible while safeguarding the privacy of participants and protecting confidential and proprietary data. Applicants are encouraged to use existing, open licensing approaches and preprint repositories, and may include anticipated charges for publication or data sharing and resources that may be needed to support a proposed Resource Sharing Plan in the budget plan of their application.
  • Protocol, Tool, and Reagent Sharing: As one of the primary goals of this program is to advance research through development, establishment, broad dissemination and use of community resources across the research community, NIH intends that protocols, tools, and reagents generated by the SMaHT Network to be broadly available and distributed at minimal cost, and without undue intellectual property constraints, so that they can be as widely used as possible, thus enabling downstream investigations of understudied biomolecules by the larger scientific community. For all applications and where otherwise applicable, the applicant should discuss plans for sharing and distribution of non-data resources that will be generated by the proposed project, including mathematical models, protocols, biomaterials, and reagents. The DAC will work with all SMaHT teams to collect, curate, and disseminate information regarding tools and reagents being developed to be disseminated through the DAC and other sources as appropriate.
  • Biological Samples: In order to maximize the utility of the data, any human biological samples collected and studied or that are derived from existing biospecimens or cell line sources are expected to have been obtained using a documented informed consent process that explicitly allows for future research use and broad data sharing (NOT-HG-20-011). Sources with participant consent for unrestricted access is strongly encouraged. Sources consented for sharing through a controlled-access environment, such as General Research Use (GRU) or Health, Medical, and Biomedical (HMB) without additional restrictions, will also be considered and should be well justified. The consent process for human biological samples should be described at a high level in the Research Plan and detailed in the Resource Sharing Plans.
  • Intellectual Property: Intellectual property rights asserted by proposers must be aligned with the open-source regime used to distribute software made under the award. Exceptions to open- source technology will be considered only in compelling cases. Awardees will own the software and data developed under this award, subject to the Government’s royalty-free, nonexclusive, irrevocable right to use, disclose, reproduce, prepare derivative works, distribute copies to the public, and perform publicly and display publicly, in any manner and for any purpose, and to have or permit others to do so. In addition, inventions, technical solutions and methods developed under this solicitation will remain the property of the awardees, who may freely use them for their own commercial purposes, subject to a nonexclusive, nontransferable, irrevocable, paid-up license to the Government to practice, or have practiced for or on its behalf, the inventions, technical solutions and methods throughout the world. Applicants should also be familiar with the NIH statements regarding intellectual property of resources developed with Federal funds (NIH Research Tools Policy (http://grants.nih.gov/grants/intell-property_64FR72090.pdf) and other related NIH sharing policies at http://sharing.nih.gov).
  • Sharing Software: Applicants are asked to propose a plan to manage and disseminate the improvements or customizations of their tools and resources by others and to have a plan for versioning software. 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. There is no prescribed single license for software produced in this project; however, the terms of software availability should include the ability of researchers outside SMaHT and its collaborating projects to modify the source code and to share modifications with other colleagues as well as with SMaHT and reviewers will be asked to evaluate the software sharing and dissemination plan based on its likely impact. Any software dissemination plans represent a commitment by the institution (and its subcontractors as applicable) to support and abide by the plan. A software sharing plan guided by the following principles is thought to promote the largest impact:
  • The software should be freely available to biomedical researchers and educators in the non-profit sector, such as institutions of education, research institutions, and government laboratories.
  • The terms should also 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.
  • To preserve utility to the community, the software should be transferable such that another individual or team can continue development if the original investigators are unwilling or unable to do so.

Network Participation: Applicants should indicate their willingness to abide by all data deposition, quality control metrics, standardization, metadata requirements, data and software release, and public copyright license policies developed by the SMaHT Network, consistent with NIH-wide policies and approved by NIH staff. A primary goal of the SMaHT is to build a census of somatic variants across multiple human tissues, which will require data and resources to be shared quickly and openly once validated, consistent with achieving the goals of the program. Restrictive licensing and sharing practices for SMaHT-generated data, tools, and resources could substantially diminish their value and public benefit. Accordingly, awardees should manage data, resources, protocols, tools, and software in a way that achieves this goal.

Appendix:
Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
PHS Human Subjects and Clinical Trials Information

When involving human subjects research, clinical research, and/or NIH-defined clinical 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.

Delayed Onset Study

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

PHS Assignment Request Form

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

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 fieldof the Senior/Key Person Profile form. 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 unique entity identifier (DUNS number or UEI as required) provided 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.

 

Use of Common Data Elements in NIH-funded Research

Many NIH ICs encourage the use of common data elements (CDEs) in basic, clinical, and applied research, patient registries, and other human subject research to facilitate broader and more effective use of data and advance research across studies. CDEs are data elements that have been identified and defined for use in multiple data sets across different studies. Use of CDEs can facilitate data sharing and standardization to improve data quality and enable data integration from multiple studies and sources, including electronic health records. NIH ICs have identified CDEs for many clinical domains (e.g., neurological disease), types of studies (e.g. genome-wide association studies (GWAS)), types of outcomes (e.g., patient-reported outcomes), and patient registries (e.g., the Global Rare Diseases Patient Registry and Data Repository). NIH has established a “Common Data Element (CDE) Resource Portal" (http://cde.nih.gov/) to assist investigators in identifying NIH-supported CDEs when developing protocols, case report forms, and other instruments for data collection. The Portal provides guidance about and access to NIH-supported CDE initiatives and other tools and resources for the appropriate use of CDEs and data standards in NIH-funded research. Investigators are encouraged to consult the Portal and describe in their applications any use they will make of NIH-supported CDEs in their projects.

Applications Involving the NIH Intramural Research Program

Should intramural scientists submit an application through this FOA, or should an extramural application include a collaboration with NIH intramural scientists, the requests by NIH intramural scientists will be limited to the incremental costs required for participation. As such, these requests will not include any salary and related fringe benefits for career, career conditional or other Federal employees (civilian or uniformed service) with permanent appointments under existing position ceilings or any costs related to administrative or facilities support (equivalent to Facilities and Administrative or F&A costs). These costs may include salary for staff to be specifically hired under a temporary appointment for the project, consultant costs, equipment, supplies, travel, and other items typically listed under Other Expenses. Applicants should indicate the number of person-months devoted to the project, even if no funds are requested for salary and fringe benefits.

If selected, appropriate funding will be provided by the Common Fund through the NIH Intramural Program. NIH intramural scientists will participate in this program as PD/PIs in accord with the Terms and Conditions provided in this FOA. Intellectual property will be managed in accord with established policy of the NIH in compliance with Executive Order 10096, as amended, 45 CFR Part 7; patent rights for inventions developed in NIH facilities are NIH property unless NIH waives its rights.

Should an extramural application include the collaboration with an intramural scientist, no funds for the support of the intramural scientist may be requested in the application. The intramural scientist may submit a separate request for intramural funding as described above in the NIH Intramural Source Book.

Post Submission Materials

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.

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.

Overall Impact

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).

Scored Review Criteria

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.

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?

Specific to this FOA:

  • What is the likelihood of the proposed project producing high-quality data on human somatic variation at the scale described in this FOA?
  • What is the likelihood that: (1) the “applicant-initiated” data component will add high value to the other data types proposed in this application and to the SMaHT Variant catalog, and (2) the application addresses one or more key biological considerations specific to human somatic variation, such as variant type, origin tissue type, allele or cellular frequency, etc.?
  • Have (1) data production, processing, analysis plans, (2) key questions related to characterizing human somatic variation, including origin, type, tissue, frequency, and (3) an understanding of key biological and experimental variables (if proposed); and (4) analysis of data from participants from diverse populations, been adequately considered?

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?

Specific to this FOA:

  • What evidence demonstrates the Investigative team’s track record in interdisciplinary research and/or team science?
  • What evidence demonstrates (1) adequate leadership for day-to-day project management activities (e.g., have the efforts of a project manager or sufficient PD(s)/PI(s) been described), (2) how will the management plan be implemented, and (3) are there clearly described roles and reporting relationships for key personnel?
  • What evidence demonstrates (1) the applicant’s willingness to work with other centers and participate in Network activities, and (2) that the research team is likely to contribute to the SMaHT Network beyond supplying high-quality data?

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?

Specific to this FOA:

What evidence is there that the proposed work will breakdown siloing of data types and result in new biological insights?

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?

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?

Specific to this FOA:

  • What is the likelihood that the proposed assays and approach will deliver high quality data of sufficient depth, length and sensitivity across many tissue types to build a comprehensive, reliable variant catalog? e.g. is are there adequate plans for quality control, benchmarking, and validation
  • What evidence is there that the data will be correctly interpreted? e.g. is there consideration of small clone size/low frequency; biological origin of the variants; statistical power, coverage, bias, and error rates; natural biological variability?
  • What evidence is there that the Center is prepared to work seamlessly with the SMaHT Network, adapt and refine its workflow, participate in cross-Network collaborative activities, maintain sample and data integrity, and generate publication data in a consistent manner and transfer to the Data Analysis Center within the first year of operations?
  • Does the resource sharing plan adequately address how the applicants will ensure rapid release of data, including metadata, in a way that will be useful to the community?

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?

Specific to this FOA:

  • What is the likelihood that the resources, equipment and infrastructure will be available and in place (or readily obtainable) to generate publication quality data within the first year?
  • What is the likelihood that the instrumentation and data science resources will be in place (or readily obtainable) and adequate to support the project and interactions with the rest of the SMaHT Network?

Additional Review Criteria

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.

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.

Additional Review Considerations

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

Applications from Foreign Organizations

Not Applicable.

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).

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 the 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.

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

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

  • Scientific and technical merit of the proposed project as determined by scientific peer review.
  • Availability of funds.
  • Relevance of the proposed project to program priorities.
  • Evidence of previous productive, cooperative, collaborative interactions as part of a Consortium.
  • Evidence that the Center will contribute significantly to the overall goals of the SMaHT program.
  • Programmatic balance, including diversity of perspectives and approaches.

3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information

1. Award Notices

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

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

Recipients 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: Recipient 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 recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

2. Administrative and National Policy Requirements

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, Recipients, and Activities, including of note, but not limited to:

If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Should the applicant organization successfully compete for an award, 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 (including gender identify, sexual orientation, and pregnancy). This includes ensuring programs are accessible to persons with limited English proficiency and persons with disabilities. 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 https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/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 and 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, 2 CFR Part 200, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this award will be managed as a cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the recipients is anticipated during the performance of the activities. Under the cooperative agreement, the NIH's 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 reside with the recipients. Specific tasks and activities may be shared among the recipients, within the Network and with NIH staff as defined below.

Definitions

  • NIH Working Group (NIH WG): Consists of NIH programmatic staff from multiple Institutes, Centers, and Offices of the NIH as well as the Office of the Director. This group will be primarily responsible for the stewardship of the SMaHT Program and will participate as non-voting members in Network committees. The NIH SMaHT WG is led by the Program Coordinator(s) and the Program Leader and co-chaired by the Directors of NIDA, NIEHS, NINDS, NIMH, and NHGRI. It reports to the Directors of the Office of Strategic Coordination / Common Fund and the Division of Program Coordination, Planning, and Strategic Initiatives for final funding decisions.
  • SMaHT Program Coordinator(s): One or more NIH Program Staff will serve as Program Coordinators. The SMaHT Coordinator(s) will have substantial programmatic involvement that is above and beyond the normal stewardship role.
  • SMaHT Program Leader: The Office of Strategic Coordination will designate a Program Leader to represent the Office of the Director in the WG. The SMaHT Program Leader will have a similar management and oversight role as the program coordinator(s) with specific responsibilities including compliance with NIH Common Fund policies, coordination with other Common Fund programs, and informing the NIH Office of the Director of progress.
  • NIH Program Officer: A NIH Program Officer (PO) is responsible for the normal scientific and programmatic stewardship of each award, including monitoring progress and compliance with general statutory, regulatory, or policy requirements; discussing and approving milestones and significant changes to the project; and technical assistance to correct performance and facilitate interactions. The PO must approve in advance and in writing annual milestones and any significant changes to the award. The PO also has the option to recommend to the NIH WG, following consultation with the Project Scientist(s) or EPCs, restricting an award based on progress towards milestones, to incentivize rapid development and implementation of policies or collaboration between members of the Network, or generation of data or resources for use by Network members or the wider community.
  • NIH Project Scientist(s): One or more NIH Program Staff will serve as Project Scientists (PSs), for each SMaHT award and, as appropriate, to oversee collaborative projects amongst recipients and/or other Network members. The PS(s) will serve as the scientific representatives of the NIH to the investigators in accordance with the policies and the procedures of the cooperative agreement mechanism. If there is more than one PS, one of them will be designated as the Lead PS.  The PS(s) will provide substantial NIH scientific programmatic involvement with the recipient that is anticipated during the performance of the activities supported by this Cooperative Agreement, including review of milestones. PS(s) will work closely with the PD/PI, the Steering Committee, and other NIH resources to maximize progress towards the goals of the project and the program.
  • Steering Committee (SC): The purpose of the SC is to recommend direction for the SMaHT Network consistent with the program goals, develop Network policies and projects to build synergy and improve communication and collaboration between the projects, and provide a forum for discussing progress, challenges, and opportunities for the Network.
  • External Program Consultants (EPCs): As part of the SMaHT program, NIH staff will engage 5-10 external program consultants (EPCs) not funded as part of the program but with relevant scientific and Network experience to provide input and advice to the NIH WG.
  • SMaHT Network:  The Network is made up of recipients from the SMaHT FOAs, the NIH WG, and other scientists and groups the SC agrees to include in the Network. The Network structure is meant to efficiently and effectively guide all the funded projects to meet the overall goals of the SMaHT Program.

PD(s)/PI(s) Responsibilities

The PD(s)/PI(s) will have the primary responsibility for:

  • Determining research approaches, designing protocols, setting project milestones and timelines, and conducting research.
  • Ensuring that the data, software, resources, methods, materials, etc. produced as part of this project are released appropriately and in a timely manner according to NIH and Network Policies
  • Preparing abstracts, presentations, reports, and publications in a timely manner.
  • Adhering to Network and NIH policies including those related to data and resource sharing, data access, and publications.
  • Ensuring proper stewardship of biospecimens, data, documents, and other resources, including not disclosing confidential information, maintaining the privacy of the information, and ensuring appropriate use.
  • Interacting with other relevant NIH activities, as needed, to promote synergy and consistency among similar or related projects.
  • Actively collaborating and sharing information and resources with other members of the Network.
  • Ensuring that necessary approvals, including IRB, Data Use Agreement, and Material Transfer Agreement, are obtained in a timely manner.
  • Collaborating with the Network to establish data formats, standards, transfer protocols, and transferring data, metadata, and protocols in a timely manner to appropriate databases as defined by the Network.
  • Submitting periodic progress or summary reports in a standard format, including data production summaries and metrics of the use and impact on the community
  • Abiding by common definitions, protocols, and procedures established by the Network.
  • Attending and participating in Network Meetings, including the Steering Committee, Annual Meeting, and working group meetings and accepting and implementing decisions made by the Network.

NIH Responsibilities

The NIH will designate staff, including a Program Officer and Project Scientist(s), to provide stewardship and administrative oversight of the cooperative agreement. Designated staff will be named in the Notice of Grant Award. NIH reserves the right to modify the budget or duration of funding or to curtail an award in the event of: (a) substantive changes in the project not approved in advance, (b) use of funds for activities not within the scope of the specific aims, (c) failure to make sufficient progress toward the project milestones, including timely pre-publication deposition of data or reagents in accordance with approved Network policies, (d) failing to comply with the terms and conditions of the award or establish necessary statutory, regulatory, policy approval required for conducting the project, or (e) ethical or conflict of interest issues.

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

  • NIH staff and their respective Institutes and Centers will manage Conflicts of Interest and Management of Bias as detailed in the NIH Policy Manual.
  • The Program Officer is the NIH point-of-contact for the project, except for special circumstances designated by NIH. The Program Officer will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. The Program Officer must approve in advance: (i) changes in the roster and effort of the PD(s)/PI(s) and key personnel, (ii) changes in the goals and milestones for the project, (iii) changes in the scientific scope of the project, (iv) changes to the frequency of business meetings, (v) changes in goals of collaborative projects, and (v) any exceptions to the Network’s policies. The Program Officer will not co-author publications with project investigators.
  • The Project Scientists(s) will provide advice and guidance to ensure that the project adheres to the objectives of the FOA, the Terms and Conditions of the award, and other agreements between the recipients and NIH. The Project Scientist(s) will keep the PD(s)/PI(s) informed of any issues and concerns involving the project and provide advice on how to address them. The Project Scientist may provide scientific and programmatic assistance to the PD/PI, including contributing to data analysis, key personnel selection, and promoting the availability of data and resources. The Project Scientist(s) will attend all official business meetings of the project's leadership and must be kept informed of all substantive deliberations and developments affecting the project. The Project Scientist(s) will not make decisions about the funding of this project and will not be involved in any special reviews of the project that make recommendations about funding.
  • The Program Coordinator(s) and Program Leader will be responsible for program management and oversight, outreach, and budget management for the program. This includes monitoring progress, assessing the effect of the program on the scientific community, proposing revisions to individual awards to meet program goals, developing initiatives, promoting outreach, liaising with other NIH programs, periodically reporting progress to NIH senior management, and meeting regularly with the NIH WG and SMaHT recipients. The Program Coordinator(s) and Program Leader will not co-author publications with project investigators.
  • Progress evaluations by the Program Officer, Program Coordinator(s), and Program Leader will be based on the non-competing application and annual project progress report, interim progress reports, and assessments by the Project Scientist(s). The Program Officer, Program Coordinator(s), and Program Leader will review the management, performance, and utilization of the project. If concerns are identified from this review, the Project Scientist(s) will work with the PD(s)/PI(s) to develop plans to address them in the next year of support . In addition, NIH staff may conduct interim reviews of scientific progress beyond the normal yearly non-competing progress review to determine progress and use information from progress reviews to inform future funding for the project.
  • Special Reviews. In addition, if concerns are identified about the performance or the management of the project, the Program Officer may conduct special reviews of the project as he/she deems necessary. NIH may engage outside experts to assist in these reviews. If concerns about the project arise and are not resolved, NIH may reduce or restrict the budget or reduce the term of support to phase out the project. In the event of long-term incapacitation of resource facilities, NIH may reduce the budget or term of support to phase out the project. Though the Cooperative Agreement mechanism does provide options for restricting, reducing, or terminating awards, it also provides options for interacting supportively with recipients to help ensure program success. Before any modifications are made, NIH staff will engage with the recipients in a positive manner and as allowed by the Cooperative Agreement mechanism to resolve performance issues where possible in a timely manner. 
  • External Program Consultants. The EPCs will be senior, scientific experts who are not directly involved in the activities of the and who agree to a confidentiality policy, engaged on an as-needed basis to advise on specific issues.  NIH is solely responsible for appointing EPCs for variable durations of service. EPCs are invited to participate in Network meetings, Steering Committees calls, and the annual investigators’ meeting. A subset of EPCs may also meet by phone or web at other times of the year, as needed. Annually, the EPCs will provide individual assessments to the NIH of the progress of the Network and will present individual expert recommendations regarding any changes in the program as necessary. The assessments and recommendations will be provided through the NIH WG to the Director of the Office of Strategic Coordination, NIH.

Areas of Joint Responsibility

If there are multiple awards working toward a common goal, close interaction between the participating grantee(s) and NIH staff will be required, to manage, assess, and implement the award(s), goals of the Network, etc. Areas of joint responsibility include:

  • Steering Committee (SC): The SC will be the main governing body of the Network. The SC will include PDs/PIs of each of the awards and NIH WG members. The SC will be chaired by two PD/PIs that are approved by the NIH WG. An Executive Committee (EC) composed of the co-chairs and the NIH Program Team Leads will meet to set the agenda for SC meetings and make time-critical decisions on behalf of the Network. The SC may establish subcommittees to oversee the development and implementation of Network policies including data, software, or other releases, publications and standards, to coordinate analyses, and etc. Subcommittees may be either permanent or time limited, may include additional experts, depending on the needs of the research. The PD(s)/PI(s) will be expected to play an active role in these working groups, as appropriate.  It is expected that most of the decisions on the activities of the SMaHT Steering Committee will be reached by consensus.  If a vote is needed, each project PD/PI (or Contact PI in the case of multi-PI projects) will have one vote.   NIH staff will be non-voting members of the SC. When a vote is required, at least 60% of the quorum will be required for approval. NIH staff will review and approve policies developed by the SC. Recipients will be required to implement policies approved by the SC in a timely manner.
  • Responsibilities of the SC will include:
  • Ensuring the Network is collegial, collaborative, and representative and activities are consistent with the NIH vision for the program
  • Setting research priorities, deciding optimal research approaches and protocol designs, and contributing to the adjustment of research protocols or approaches as warranted.
  • Establishing and monitoring Network policies including policies for data sharing, material sharing, informed consent, tissue collection, publications, and associate membership
  • Establishing and implementing data and metadata standards, transfer protocols, quality assessments, and collaborative projects
  • Outreach and engagement with the wider research community
  • Sharing resources, methodologies, analytical tools, data analyses, preliminary results, etc. in a timely manner
  • Generating responses to EPC recommendations

Dispute Resolution
Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be addressed by convening a Dispute Resolution Panel. It will be composed of three members: a designee of the SC chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of disagreement for one award, the first member may be chosen by that recipient. This special dispute resolution procedure does not alter the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

3. Reporting

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

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement. NIH FOAs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All recipients 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

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

Application Submission Contacts

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

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

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

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

Scientific/Research Contact(s)

Amy C. Lossie, Ph.D.
National Institute on Drug Abuse
Telephone: 301-827-6092
Email: SMaHT@mail.nih.gov

Peer Review Contact(s)

Center for Scientific Review (CSR)
FOAReviewContact@csr.nih.gov

Financial/Grants Management Contact(s)

Christina Rinaldi
National Institute on Drug Abuse (NIDA)
Telephone: 301-827-0937
Email: christina.rinaldi@nih.gov

Section VIII. Other Information

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.

Authority and Regulations

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 2 CFR Part 200, 42 CFR Part 52, and 45 CFR Part 75.

NIH Office of Extramural Research Logo
Department of Health and Human Services (HHS) - Home Page
Department of Health
and Human Services (HHS)
USA.gov - Government Made Easy
NIH... Turning Discovery Into Health®


Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.