RFA-HG-27-013-Full-Announcement.html

Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Human Genome Research Institute (NHGRI)

Note: Not all NIH Institutes, Centers, and Offices (ICOs) participate in Announcements. Applicants should carefully note which ICOs participate in this announcement and view their respective areas of research interest at the ICO-Specific Scientific Interests website. ICOs that do not participate in this announcement will not consider applications for funding.

Funding Opportunity Title

GREGoRi Innovation Projects (U01 Clinical Trial Optional)

Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type

New

Related Notices

Check for any recent Notices of NIH Policy Changes that may impact application requirements.

Funding Opportunity Number (FON)

RFA-HG-27-013

Companion Funding Opportunity

RFA-HG-27-011

, U01 Research Project (Cooperative Agreements)

RFA-HG-27-012

, U01 Research Project (Cooperative Agreements)

Number of Applications

See Part 2, Section III. 3. Additional Information on Eligibility.

Assistance Listing Number(s)

93.172

Funding Opportunity Purpose

The Genomics Research to Elucidate the Genetics of Rare Diseases:innovation (GREGoRi) initiative seeks to accelerate a paradigm shift in rare disease diagnosis by reimagining the tools, molecular technologies and analytical approaches used to identify the causal gene(s) and/or variant(s) underlying rare genetic disorders. This Notice of Funding Opportunity is intended to stimulate the development and testing of highly innovative experimental or computational approaches for rare disease diagnosis, that have the potential to make transformative improvements to the current state of the art.

Funding Opportunity Goal(s)

As a leading authority in the field of genomics, the mission of the National Human Genome Research Institute (NHGRI) is to accelerate scientific and medical breakthroughs that improve human health by driving cutting-edge research, developing new technologies, and studying the impact of genomics on society. Congress initially established NHGRI to characterize the structure and function of the human genome, including the mapping and sequencing of individual genes. This also includes reviewing and funding research proposals, developing training programs, coordinating international genome research, communicating advances in genome science to the public, and reviewing and funding proposals to address the ethical and legal issues associated with this research. NHGRI supports the development of methods, resources and technologies to improve the health of all humans through advances in genomics research. NHGRI supports research that accelerates foundational resources, technology development, and experimental and computational approaches for basic genomics and functional genomics research; for the application of genomics to medical science and clinical care; and to support ethical, legal and social implications (ELSI) research concerning societal issues that need to be addressed, especially as genomic science advances. For years, NHGRI has participated in the NIH effort to turn discovery into health by helping small businesses develop innovative genomics technologies that improve health and save lives. NHGRI also develops and supports initiatives that expand opportunities for genomics education and careers, cultivating genomics training programs and workforce development initiatives.

Key Dates

Posted Date

June 18, 2026

Open Date (Earliest Submission Date)

September 30, 2026

October 30, 2026

Not Applicable

Not Applicable

July 2027

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.

No late applications will be accepted for this Notice of Funding Opportunity (NOFO).

Due Dates for E.O. 12372

Not Applicable

Expiration Date

October 31, 2026

Required Application Instructions

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the Application Guide and the NOFO) 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.

Table of Contents

Part 1. Overview Information Key Dates Part 2. Full Text of Announcement Section I. Notice of 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

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Background and Program Overview Over the last decade, rapid advancements in the development of high throughput and cost-effective genome sequencing technologies have made it possible to obtain a precise molecular diagnosis for many individuals with an undiagnosed but likely genetic disease. However, a substantial proportion of individuals with a suspected genetic disease – more than 50% - remain undiagnosed after undergoing clinical genetic testing. In 2021, NHGRI launched the GREGoR (Genomics Research to Elucidate the Genetics of Rare Disease) Consortium, with the goal of developing new approaches to identify causal variants in individuals with rare genetic disease, particularly where whole exome sequencing was not successful. The research centers funded in phase I of GREGoR use approaches such as whole genome sequencing, RNA sequencing, and other methods to solve these more challenging cases. The data generated in GREGoR are shared with the broader research community via NHGRI's Analysis, Visualization, and Informatics Lab-space (AnVIL) through the AnVIL Portal.

Today, whole exome sequencing (WES) is considered to be a first-line approach for identifying the underlying cause of rare genetic disorders. While powerful, whole exome sequencing has a number of critical limitations that may contribute to the high rate of unsolved cases. First, WES cannot readily identify more complex variants such as copy number variants (CNV), repeat expansions, or structural variants (SV) that may contribute to disease. An additional challenge is that WES focuses primarily on protein coding regions of the genome, and is unable to detect potential causal variants in regulatory regions, introns, or other non-coding functional elements in the genome. Due to advances in the development of genomic and other molecular technologies, it is now possible to investigate many aspects of genome organization and function comprehensively and at scale, including RNA, protein and metabolites, genomic interactions, and the epigenome. In order for these technologies to be used to their fullest potential in the clinical genetics setting, more concrete guidance and the development of best practices supporting their use for rare disease diagnosis are needed.

A number of computational and analytical challenges also need to be addressed in order to fully realize the potential of these molecular approaches. For example, the integration of multiple molecular data types (including those generated by large-scale programs such as the Encyclopedia of DNA Elements (ENCODE), the Roadmap Epigenomics Program, or the Impact of Genomic Variation on Function (IGVF) Consortium could inform variant prioritization, however doing so requires specialized domain knowledge or expertise that diagnostic labs may not have access to. Many current analytical approaches have other significant limitations, such as excluding many regions of the genome that may harbor disease-causing mutations, such as centromere, telomeres, repeat regions, and sex chromosomes, or not adequately accounting for more complex modes of inheritance. Finally, new genome representations such as the Human Pangenome Reference have the potential to better enable the identification of disease associated variation in whole genome sequence data, but most currently available tools rely on older, outdated reference genomes.

To close the diagnostic gap for rare diseases, there is a need for continued innovation in how such technologies are used in the clinical genetics setting, and in the computational tools and analytical methods that are used to identify and prioritize candidate genes or variants. In the second phase of GREGoR, GREGoR:innovation (GREGoRi), NHGRI seeks to catalyze a dramatic shift in rare disease diagnosis through the development of highly innovative solutions to some of the current challenges that face this field. In particular, GREGoRi will focus on accelerating the use of new or emerging molecular approaches in clinical genetics, on applying more established molecular technologies in innovative ways to obtain a molecular diagnosis, and on addressing significant computational challenges or analytical blind spots that have the potential to unlock new diagnoses.

To achieve the goals of GREGoRi, NHGRI is issuing an open call for applications through three notices of funding opportunity (NOFOs). These NOFOs are open to any investigator with ideas aligned with the goals of the program, regardless of whether they participated in the initial phase of the GREGoR Research Program.

The three NOFOs are:

Scope and Objectives This NOFO solicits proposals to develop and test highly innovative approaches for identifying the gene(s) and/or variant(s) that contribute to rare genetic diseases. These approaches should have the potential to make transformative improvements to the current state of the art. Projects should focus on either Technology Innovation or Computational Innovation as described below.

Technology Innovation Projects GREGoRi Technology Innovation Projects will perform proof-of-concept studies that leverage new and emerging experimental technologies, or make innovative use or greatly extend the capabilities of existing technologies, to advance the stated goals of the GREGoRi program. A major goal for the Technology Innovation Projects is to move beyond the current state-of-the-art approach for diagnosing rare genetic disorders, which is primarily based on DNA sequencing (i.e., WES and WGS) as initial steps in variant or gene identification. These approaches should be applicable to a broad range of rare genetic disorders, although proof-of-concept studies may be carried out in a limited number of exemplar phenotypes.

Examples of work that could be within scope include but are not limited to:

In addition to experimental work, Technology Innovation Projects may propose the development of complementary computational or analytical tools or methods that support or enable the use of experimental approaches.

Technologies that show potential in proof-of-concept studies may be integrated into the activities of the Technology Integration Center in later years.

Computational Innovation Projects GREGoRi Computational Innovation Projects will develop novel analytical methods and/or user-friendly tools that facilitate the identification of the gene(s) or variant(s) that contribute to rare genetic diseases. Applicants may propose innovative early-stage work such as algorithm or model development and proof-of-concept approaches. Applicants may also propose the development of user-focused end-stage tools. Resulting tools and approaches should be useful for analysis of the GREGoR dataset, or other similar rare disease datasets. Tools or approaches may also leverage other datasets that are or could be made publicly available, including those from programs described below (see: Relationship to Outside Collaborations). Approaches that leverage machine learning, and artificial intelligence are encouraged.

Examples of work that could be in scope include but are not limited to the development of:

Tools or algorithms developed under this NOFO are expected to be made available in AnVIL where they can access the GREGoR, GREGoRi, and other datasets. Computational approaches that show potential in proof-of-concept studies may be integrated into the activities of the Technology Integration Center in later years.

Projects that require concurrent development of computational and experimental approaches should apply as Technology Innovation Projects.

Program formation and governance The award funded under this NOFO will be a cooperative agreement. The recipient will become a member of the GREGoRi Research Consortium, made up of investigators funded in response to the three related NOFOs. The recipient will be expected to work collaboratively with the other components of the GREGoRi Program and with NIH staff towards meeting consortium goals, in addition to the specific research goals outlined in their application.

Recipient responsibilities will include:

Outside Collaborations Collaboration with stakeholder research communities outside of the GREGoRi Consortium helps maximize the impact of the Consortium's efforts. Recipients will also be expected to explore collaboration opportunities with other research projects and consortia with related interests or goals, such as the Impact of Genomic Variation on Function (IGVF) Consortium, the Human Pangenome Reference Consortium (HPRC), the Atlas of Variant Effects (AVE) Alliance, the Clinical Genome Resource (ClinGen), Molecular Phenotypes of Null Alleles in Cells (MorPhiC), Multi-Omics for Health and Disease (MOHD), or the Somatic Mosaicism across Human Tissues (SMaHT) Network. This may include participating in cross-consortium activities, such as working group meetings.

Data Sharing and Consents in GREGoRi A major deliverable of the GREGoRi Research Consortium is the GREGoR Data Resource, which makes all molecular and phenotype data collected under this program available to researchers through controlled access via NHGRI's Genomic Data Science Analysis, Visualization, and Informatics Lab-space (AnVIL). In order to streamline access to this valuable resource, NHGRI expects GREGoRi researchers to use samples that have been consented for the broadest possible data sharing. It is expected that samples will be consented for General Research Use (GRU) or Health/Medical/Biomedical (HMB) without any additional data use limitations, although for proof-of-concept Technology Innovation Projects exceptions will be considered with strong justification. Projects that will enroll participants should aim to enroll them with an informed consent process that meets these guidelines.

For More Information Prospective applicants are strongly encouraged to contact the email address as the Scientific/Research Contact below to discuss the responsiveness of their planned project, and the alignment of the proposed work with the goals of the GREGoRi initiative.

In addition, NHGRI staff will hold an informational webinar for prospective applicants. At this webinar, staff will present an overview of the GREGoRi NOFOs and answer questions that applicants may have about the NOFOs. The time, date, and links to the webinar will be posted on the NIH website. The webinar is open to all interested applicants, but participation is not required to apply.

Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.

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

Section II. Award Information

Funding Instrument

Cooperative Agreement: A financial assistance 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 NOFO.

Application Types Allowed

New

The OER Glossary and the How to Apply Application Guide provide details on these application types. Only those application types listed here are allowed for this NOFO.

Clinical Trial?

Optional: Accepting applications that either propose or do not propose clinical trial(s).

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

NHGRI intends to commit a total of $7.5 million in FY 2027 to fund 8-10 awards.

Award Budget

Application budgets are limited to $500,000 in direct costs per project year, and must reflect the actual needs of the proposed project.

Award Project Period

The maximum project period is 3 years.

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

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Nonprofits Other Than Institutions of Higher Education

For-Profit Organizations

Local Governments

Federal Governments

Eligible Agencies of the Federal Government

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 Organizations)

Foreign Organizations/International Collaborations

Non-domestic (non-U.S.) Entities (Foreign Organizations) 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.

NIH will no longer issue awards (i.e., new, renewal, or non-competing continuation) to domestic or foreign entities that involve foreign subawards/subcontracts. All NIH-funded research involving foreign subawards/subcontracts must be submitted in response to a NOFO that is specifically designated for funded international collaborations. See NIH Grants Policy Statement 16.8 Collaborative International Research Awards.

Applications involving foreign subawards/subcontracts submitted in response to this NOFO will be deemed noncompliant and will not be considered for funding. This policy applies to all monetary international collaborations resulting in foreign subawards/subcontracts, however, it does not preclude unfunded international collaborations or foreign components, funding for foreign consultants, or procurement of unique equipment or supplies from foreign vendors.

Required Registrations

Applicant Organizations Applicant organizations must complete and maintain the following registrations as described in the How to Apply- 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. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information.

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. Foreign organizations must obtain a NATO Commercial and Government Entity (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. The same UEI must be used for all registrations, as well as on the grant application.

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.

All PD(s)/PI(s) must be registered with ORCID. The personal profile associated with the PD(s)/PI(s) eRA Commons account must be linked to a valid ORCID ID. For more information on linking an ORCID ID to an eRA Commons personal profile see the ORCID topic in our eRA Commons online help.

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 their organization to develop an application for 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 How to Apply-Application Guide.

2. Cost Sharing This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1.2 Definition of Terms.

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 NIH Grants Policy Statement Section 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 NIH Grants Policy Statement 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 NOFO. 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 How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise (in this NOFO, in a policy notice, or other notice from NIH Guide for Grants and Contracts). 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.

Page Limitations All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed.

Instructions for Application Submission

The following section supplements the instructions found in the How to Apply- Application Guide and should be used for preparing an application to this NOFO.

SF424(R&R) Cover All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations All instructions in the How to Apply- Application Guide must be followed.

SF424(R&R) Other Project Information

SF424(R&R) Senior/Key Person Profile

R&R or Modular Budget

R&R Subaward Budget

PHS 398 Cover Page Supplement

PHS 398 Research Plan All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

The Research Plan should describe plans to address the major objectives of the GREGoRi Innovation Projects, described in Section I above. Proposals should be scoped as either a Technology Innovation Project or a Computational Innovation Project. A proposal for technology development can also include complementary computational or analytical tools or methods that support the use of experimental approaches; such a project should still be scoped as Technology Innovation Project.

Both categories of projects should clearly describe the following:

Technology Innovation Projects should specifically address:

Computational Innovation Projects should specifically address:

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply - Application Guide.

The following instructions also apply:

The Resource Sharing Plan should summarize whether and how resources (e.g., educational materials; methods; models; physical products, materials, and reagents; protocols; research findings and products; and software) will be made available. Applicants should include a description of the format, an indication of who will be responsible for implementation and plans for long-term maintenance, whether there will be opportunities for community input and feedback, platform(s) or mechanism(s) that will be used to make resources publicly accessible, and proposed timeline for implementing the Resource Sharing Plan. Resource Sharing Plans should not duplicate other sections of the main Research Plan but should refer to them when appropriate. After initial review, NHGRI program staff may negotiate revisions of this plan with the prospective awardee. The final negotiated version of this plan will become a term and condition of the award.

Other Plan(s):

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

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 How to Apply- 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

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 How to Apply- Application Guide must be followed.

PHS Assignment Request Form

Foreign Organizations Foreign (non-U.S.) organizations must follow policies described in the NIH Grants Policy Statement, and procedures for foreign organizations described throughout the How to Apply- Application Guide.

3. Unique Entity Identifier and System for Award Management (SAM) See Part 2. 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. 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 Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

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 How to Apply-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 Section 7.9.1 Selected Items of Cost.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the How to Apply – Application Guide. Paper applications will not be accepted.

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

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

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile 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 NOFO for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization's profile in the eRA Commons and for the System for Award Management. Additional information may be found in the How to Apply – 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.

Mandatory Disclosure

Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. See Mandatory Disclosures, 2 CFR 200.113 and NIH Grants Policy Statement Section 4.1.35.

Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at grantdisclosures@oig.hhs.gov.

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 scored review criteria and additional review criteria (as applicable for the project proposed). An application does not need to be strong in all categories to be judged likely to have a major scientific impact.

Scored Review Criteria

Reviewers will consider Factors 1, 2 and 3 in the determination of scientific merit, and in providing an overall impact score. In addition, Factors 1 and 2 will each receive a separate factor score.

Factor 1. Importance of the Research (Significance and Innovation)

Innovation

If the proposal is clinical trial-oriented, evaluate if there is innovation in trial design. For example, innovative designs such as platform trials, adaptive, including real-time adaptive methods, seamless Phase I/II designs, and Bayesian designs are encouraged as applicable. Decentralized trial elements, including remote informed consent, remote study visits, and use of wearables are also encouraged as applicable.

Factor 2. Rigor and Feasibility (Approach)

Rigor:

For applications involving human subjects, including clinical trials, assess the adequacy of inclusion plans as appropriate for the scientific goals of the research. Considerations of appropriateness may include disease/condition/behavior incidence, prevalence, or population burden, population representation, and/or current state of the science.

Feasibility:

Factor 3. Expertise and Resources (Investigator(s) and Environment)

Investigator(s) Evaluate whether the investigator(s) have demonstrated background, training, and expertise, as appropriate for their career stage, to conduct the proposed work. For Multiple Principal Investigator (MPI) applications, assess the quality of the leadership plan to facilitate coordination and collaboration.

Environment Evaluate whether the institutional resources are appropriate to ensure the successful execution of the proposed work.

Additional Review Criteria

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

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,…