Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Background:

The National Human Genome Research Institute (NHGRI) 2011 Strategic Plan, "Charting a course for genomic medicine from base pairs to bedside", outlines a vision for how genomics can advance our understanding of human biology and contribute to improving the diagnosis, prevention and treatment of human disease. This strategic vision is organized around five domains, extending from basic research to health applications, and projects increasing levels of activity over time in the domains of advancing the science of medicine and improving the effectiveness of health care. As outlined in the Strategic Plan, advancing the science of medicine includes studying how genomics can impact prevention, diagnosis and treatment; building an evidence base for genomic medicine; understanding how genomic information may contribute to the reduction of health disparities; and improving how we interpret genomic data to facilitate the return of information to clinicians and patients. Improving the effectiveness of health care includes developing innovative approaches to incorporate genomic data into electronic health records (EHRs); demonstrating effectiveness and clinical utility of genomic information; and increasing access to genomic information across different healthcare systems.

Over the past decade genome sequencing has increasingly been used in clinical settings. To date, NHGRI has primarily funded research on clinical genome sequencing through multi-disciplinary programs, including the Electronic Medical Records and Genomics (eMERGE) Network, the Clinical Sequencing Evidence-generating Research (CSER and CSER2) programs, and the Newborn Sequencing in Genomic Medicine and Public Health (NSIGHT) program. The Undiagnosed Diseases Network (UDN), funded through the NIH Common Fund, and NHGRI's Implementing Genomics in Practice (IGNITE) consortium and Clinical Genome (ClinGen) Resource, along with other projects both in the US and internationally, are also addressing critical aspects of genomic medicine involving the application of genomic sequencing. NHGRI has also held a number of recent workshops that included recommendations for research in clinical genome sequencing: Future Opportunities for Genome Sequencing and Beyond; Genomic Medicine VIII; Integrating Genomic Sequencing into Clinical Care: CSER and Beyond; and the NHGRI Roundtable on Inclusion and Engagement of Underrepresented Populations in Genomics.

The growing application of genome sequencing in clinical settings, combined with the knowledge gained to date from the first generation of clinical genomics research, has generated intriguing findings that suggest the need for discrete, focused research projects. These include projects carried out in unique clinical applications or settings, which can be creatively proposed and answered at a single site, can take nimble, flexible approaches to problems, and do not require large-scale coordinated consortia approaches. This motivates the proposed FOA to expand NHGRI's portfolio of investigator-initiated projects in clinical genomic sequencing and to develop robust and rigorous science in this area that complements ongoing consortia work at NIH.

Definitions

In the context of this FOA, the following definitions apply:

• "Genome sequencing" refers broadly to DNA-based sequencing approaches that interrogate a significant fraction of each patient's genome sequence using next generation sequencing technologies, including but not limited to targeted multi-gene sequencing panels of at least 100 genes, whole exome sequencing (WES) or whole genome sequencing (WGS). Large-scale targeted genotyping arrays would not be considered genome sequencing.
• "Clinical genome sequencing" is defined as the use of genome sequencing in a clinical context to inform disease prevention, diagnosis or treatment.
• "Genomic medicine" is defined as a medical discipline that involves using genomic information about an individual as part of their clinical care (e.g., for diagnostic or therapeutic decision-making) and the health outcomes and policy implications of that clinical use.

Research Objectives

This FOA will stimulate innovation and advance our understanding of when, where and how best to implement clinical genome sequencing. The FOA encourages targeted scientific research studies focused on advancing the use of clinical genome sequencing in genomic medicine, including, but not limited to, studies of whether and how clinical genome sequencing impacts disease diagnosis and treatment, research to address current barriers to implementation of clinical genome sequencing, and approaches to improve the identification and interpretation of genomic variants in clinical settings.

Specific Areas of Research Interest

This FOA centers on addressing research gaps related to the use of clinical genome sequencing to advance the science of medicine and improve the effectiveness of health care, as outlined in the 2011 NHGRI Strategic Plan. Application of novel concepts, approaches, methodologies, and/or instrumentation to these questions is encouraged. Projects should be broadly applicable to clinical genome sequencing as a field, rather than being applicable only to a specific disease. Studies that focus on a specific gene, or limited set of genes, should be paradigm-setting and yield findings of relevance at a genomic level. Studies should address clinical translation or implementation and should not be focused solely on variant discovery or on functional assays. Research focused on Ethical, Legal and Social Implications (ELSI) of clinical sequencing will continue to be supported under PA-14-276 (R01), PA-14-277 (R03), and PA-14-278 (R21), and will not be supported by this FOA. NHGRI encourages applications that address how genomic information may contribute to the reduction of health disparities, and applications that include population groups traditionally under-represented in genomic research. PD(s)/PI(s) are also encouraged to include investigators and trainees who are members of under-represented minority groups.

The following are examples of the types of research studies that would be appropriate for this FOA. This list is provided as a set of examples, and should not be considered exhaustive. Applicants are encouraged to propose creative and innovative research topics and approaches that go beyond the specific examples listed here:

• Examination of patient-specific factors (such as age or developmental stage, treatment, co-existing illness, socio-demographic factors, or other modifiers) that influence or mediate the relationship between genomic variants and the spectrum of associated phenotypes seen in patients.
• Development of computational, health-economic, or other analytical approaches that identify characteristics of diseases likely to derive the greatest and least value from clinical genome sequencing. Applicants considering health-economic approaches should review NOT-OD-16-025, Clarifying NIH priorities for Health Economics Research, https://grants.nih.gov/grants/guide/notice-files/NOT-OD-16-025.html.
• Integration of data types, such as environmental data, family history, or omics data (e.g., transcriptomics, epigenomics, etc), to improve assessment of clinical validity or clinical utility of genome sequencing.
• Development or refinement of clinical sequencing pipelines that allow for the assessment of the pathogenicity of structural variants and variation in complex regions of the genome.
• Assessment of the impact of re-analysis of clinical genome sequencing data, including improvements in variant detection and changes in variant annotation, on the clinical utility of genome sequencing.
• Improvement of methods to integrate clinical genome sequence data from heterogeneous sources into EHRs, to facilitate clinical implementation.
• Development of novel clinical decision support tools for clinical genome sequencing that incorporate point-of-care education for physicians.
• Assessment of how to best incorporate sequencing standards and quality control metrics into clinical reports of next generation sequencing to enhance interpretation of both positive and negative sequencing findings.
• Development of novel analysis methods for the interpretation of clinical genome sequencing in ancestrally diverse populations.
• Development of methods that automate, or otherwise improve the efficiency of, the interpretation of genome sequencing data for implementation in clinical settings.

All applicants are strongly encouraged to contact NHGRI Staff (see contacts) to discuss the alignment of their proposed work with the goals of this FOA.

Projects examining ways in which clinical genome sequencing can be applied to improve the understanding of HIV/AIDS prevention, diagnosis, treatment, and related complications will also be considered in accordance with the high priority topics listed in the NIH AIDS Research Priorities document (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-137.html). Applicants are encouraged to include HIV/AIDS patients to address these high priority areas for clinical sequencing research, if appropriate. Applicants are also strongly encouraged to contact NIH staff (see contacts) before submitting an AIDS application to this FOA.

Successful awardees will be expected to attend a yearly grantee meeting designed to facilitate the sharing of approaches, progress and findings in clinical genome sequencing research. Awardees will also be encouraged to participate in meetings organized by CSER2 or other relevant NHGRI programs, as appropriate.

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

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• 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
• Non-domestic (non-U.S.) Entities (Foreign Institutions)

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

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

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

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

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

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

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

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

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

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

Awards will not be made to the same PDs/PIs in any of the CSER2 FOAs (RFA HG-16-010, HG-16-011, or HG-16-012) and this FOA. Investigators are allowed to apply for both the CSER2 FOAs and this PAR, but should be cautioned that they will not be eligible to be funded for both

Applicants must obtain the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

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

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

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:

Carolyn M. Hutter
Telephone: 301-451-4735
Fax: 301-480-2770
Email: [email protected]

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

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

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

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

All instructions in the SF424 (R&R) Application Guide must be followed. Applicants should detail the previous experience of the research team in clinical genomic sequencing. If bioinformatic or computational biology approaches are proposed applicants should detail the prior experience of investigators, collaborators and staff in this area.

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

Applicants should budget for the PD/PI and up to two other personnel to attend a yearly grantee meeting in the Bethesda area. Applicants may also budget for the PD/PI to attend up to two additional NHGRI program meetings per year. This could include CSER2 Steering Committee meetings, other meetings coordinated by NHGRI DGMed Programs, or other relevant NHGRI meetings subject to approval by the NHGRI Program Official. Attendance at these additional NHGRI meetings is optional, and direct links to NHGRI Programs are not required. However, if applicable, applicants should detail which Program's meetings they wish to attend, and how their proposed work relates to the goals of that specific program. This is in addition to any budgeted travel to present findings at scientific meetings.

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

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

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

Research Strategy

As part of the significance section, applicants should describe the generalizability and broader relevance of the proposed research to clinical sequencing in settings beyond any targeted genes or diseases included in their specific application. Applicants should clarify how their proposed work will improve understanding of how clinical genome sequencing may impact disease prevention, diagnosis or treatment, and accelerate the appropriate implementation of genomic sequencing in clinical settings. As part of the innovation section, applicants should describe the novelty of their research, and detail how it is distinct from existing research efforts in clinical genomic sequencing.

If bioinformatic or computational biology approaches are proposed applicants should detail the prior experience of staff other than Key Personnel in this area.

Applicants proposing generation of new clinical genome sequence data should include a description of plans to recruit and retain participants. They should also provide details on the costs, turn-around-time and computational requirements, including data analysis and storage, for the proposed sequencing. They should address appropriateness of consent for genomic data sharing, and plans for return-of-results to patients and participants. Due to regulatory requirements for using research results in clinical care, some sequencing data will be expected to be in compliance with the Clinical Laboratory Improvement Amendments (CLIA). In addition, a Food and Drug Administration (FDA) Investigational Device Exemption (IDE) may be needed for new sequencing methods used in clinical care, separate from the requirement for the test to have been conducted within a CLIA-certified environment. Applicants may wish to consult the following Points to Consider in Assessing When an Investigational Device Exemption (IDE) Might be Needed: http://www.genome.gov/27561291.

Applicants proposing use of existing clinical genome sequence data should provide details on the source of the data, including quality control metrics, demographics of participants, appropriateness of existing consent for proposed aims and genomic data sharing, and potential for recontacting the participants to collect additional information as needed.

Applications researching the potential role of genomic information on the reduction of health disparities should clearly identify the evidence for health disparities for the disease(s) or outcome(s) studied, the role of non-genetic factors that may contribute to the health disparities, and how their specific project will inform the potential reduction of health disparities. Applications that include population groups traditionally under-represented in genomic research should clearly identify the evidence that the population(s) is under-represented in clinical genomic sequencing research, and the scientific questions that will be addressed within the population(s).

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, with the following modification:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
• Applications should adhere to the NIH Genomic Data Sharing Policy, including general NHGRI expectations for implementation of this policy.
• Resource sharing plans should specify plans for sharing of both genomic and non-genomic (environmental, clinical, demographic, etc.) data, including all metadata and descriptive information needed to support future use of the data. If the proposed work includes use of existing data, plans or constraints for sharing such data should also be described. As part of this plan, all final datasets, not just those generated to support a publication should be submitted to appropriate data repositories, or made available through NHGRI-approved alternative data sharing plans.
• Resource sharing plans should include plans for deposition of any variant-level data and assertions generated through these projects into the ClinVar public archive.
• Resource sharing plans should include plans for open sharing of software tools. Software is expected to be well-documented and made available on version-controlled public repositories.
• Resource sharing plans should include clear milestones and timelines for data deposition and software release. Milestones should adhere to standard data release timelines as outlined in the NIH Genomic Data Sharing Policy, and NHGRI expectations for implementation of this policy.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

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

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review, NIH. Applications that are incomplete or non-compliant will not be reviewed.

Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Is the proposed work generalizable with broad relevance to clinical sequencing in settings beyond any targeted genes or diseases included in the specific application? Will the proposed work enhance our understanding of disease prevention, diagnosis and treatment? If the proposed work is investigating the implementation of clinical genomic sequencing, will it advance or otherwise accelerate the appropriate use of sequencing in clinical settings?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Do the PD(s)/PI(s), collaborators, and other researchers have appropriate background in clinical genomic sequencing? If bioinformatic or computational biology approaches are proposed, do they have appropriate collaborator and staff support in these areas, both in terms of expertise and in terms of time dedicated to this project?

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

Does the application utilize novel or creative approaches to address gaps in knowledge that are distinct from existing research efforts in clinical genomic sequencing??

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

If applicants are generating new data, have they sufficiently described the costs, turn-around time, computational requirements, and timeliness and completeness of data sharing? For clinical genome sequencing data to be generated, are the proposed plans for sequencing technically sound and cost-effective? If they are using existing data, have they sufficiently described the source, QC metrics and consent process? If applicants are working with patient populations, have they demonstrated that they can recruit and retain participants as proposed? Does the application address how genomic information may benefit underserved populations or contribute to the reduction of health disparities, if appropriate?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

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

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

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

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

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

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

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

Not Applicable

Not Applicable

Not Applicable

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

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS). The reviewers may also comment on the appropriateness and adequacy of the proposed plans to make data, software and analysis tools available to the broader research community. Reviewers may comment on whether the investigators presented adequate plans for research using newly generated or existing clinical genome sequence data.

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

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

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by 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:

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

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications . 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 including:
• Broad applicability to clinical genomic sequencing as a field
• Contribution to the reduction of health disparities
• Inclusion of population groups traditionally underrepresented in genomic research
• Expansion of the community of genomic medicine researchers to new investigators, experienced investigators who are new to this field, and investigators from demographic groups or institutions that are generally underrepresented in genomic medicine.
• Expansion of the scope of research questions to those suited to be studied by individual investigators, rather than a consortium approach.
• Awards under this FOA will not be made to PD(s)/PI(s) funded in the CSER consortium through the CSER2 FOAs.
• Programmatic balance among diseases to be studied, approaches to be implemented, and research questions being addressed.
• Compliance with data and resource sharing policies.
• Appropriateness of costs for proposed sequencing or other technologies in the application.

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.

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 grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

When multiple years are involved, awardees 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 progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: https://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

Carolyn M. Hutter, Ph.D.
National Human Genome Research Institute (NHGRI)
Telephone: 301-451-4735
Email: [email protected]

Gabriel Fosu, Ph.D.
Center for Scientific Review (CSR)
Telephone: 301-435-3562
Email: [email protected]

Deanna Ingersoll
National Human Genome Research Institute (NHGRI)
Telephone: 301-435-7858
Email: [email protected]

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.