NIDA Animal Genomics Program (U01 – Clinical Trial Not Allowed)

NIDA Animal Genomics Program (U01 – Clinical Trial Not Allowed) is sponsored by National Institute on Drug Abuse (NIDA). Supports research on the genomics of animal models to advance understanding of substance use disorders.

PAR-24-269: NIDA Animal Genomics Program (U01 Clinical Trial Not Allowed) This funding opportunity was updated to align with agency priorities. Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating Organizations National Institute on Drug Abuse ( NIDA ) Funding Opportunity Title NIDA Animal Genomics Program (U01 – Clinical Trial Not Allowed) U01 Research Project – Cooperative Agreements March 31, 2025 - This funding opportunity was updated to align with agency priorities.

Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. April 4, 2024 - Overview of Grant Application and Review Changes for Due Dates on or after January 25, 2025. See Notice NOT-OD-24-084 .

August 31, 2022 - Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023. See Notice NOT-OD-22-198 . August 5, 2022 - Implementation Details for the NIH Data Management and Sharing Policy.

See Notice NOT-OD-22-189 . Funding Opportunity Number (FON) Companion Funding Opportunity See Section III. 3.

Additional Information on Eligibility . Assistance Listing Number(s) Funding Opportunity Purpose The purpose of the National Institute on Drug Abuse (NIDA) Animal Genetics Program is to identify genetic, genomic, and molecular (epi)genetic variants that underlie neural and behavioral processes and phenotypes relevant to SUD risk, the SUD trajectory and SUD comorbidities.

This opportunity supports research that links genetic, genomic and molecular mechanisms to neural circuit function and behavior. Applications may seek to identify any type of genomic and/or epigenomic variants that contribute to the genetic architecture of addiction, including single nucleotide variants (SNVs), indels, large and small structural variants, and all types of mobile DNA.

NIDA encourages applications that take genomics, multi-omics, data-based, and/or artificial intelligence/machine learning approaches that integrate multi-level ‘omics data, delineate gene networks, and/or uncover the function of known or newly discovered genetic or epigenetic variants.

Other areas of interest include variant identification at the circuit level and the application of neuroscience to variant identification studies in tissues and cells. NIDA expects these studies to uncover novel mechanisms that contribute to various stages across the SUD trajectory and inform future studies about potential targets and therapeutic strategies for addiction.

Open Date (Earliest Submission Date) Letter of Intent Due Date(s) Renewal / Resubmission / Revision (as allowed) AIDS - New/Renewal/Resubmission/Revision, as allowed 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.

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.

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.

Use the NIH ASSIST system to prepare, submit and track your application online. 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. Workspace to prepare and submit your application and eRA Commons to track your application. Part 1.

Overview Information 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 Addiction is a complex disease that encompasses periods of uncontrolled use, abstinence, and relapse that results from a series of vulnerabilities to different stages of use (e.g., initial/acute use, escalation of use, acquisition of tolerance, dependence, uncontrolled use, abstinence and relapse or recovery) that occur throughout the lifespan.

While these stages are shared across different addictive substances, recent data indicate that the genetic architecture of addiction varies by stage, genetic background, substance, sex, behaviors, and comorbidities.

Behavioral genetics studies indicate that alleles influencing these and other addiction-related phenotypes and endophenotypes can be identified in many model organisms including worms, flies, rodents, non-human primates, and other emerging model organisms.

It is likely that multiple molecular genetic variants contribute to these individual phenotypes and behaviors, and the culmination of these variants, along with environmental insults, results in substance use disorders (SUD).

This rich behavioral knowledge, coupled with emerging genome analysis tools, gene network methods, multi-omics studies, and multi-species data integration enables the discovery of the genetic variants underlying addiction-related phenotypes, behavioral traits, and comorbid conditions, across species and within circuits, tissues, and cells.

The purpose of the National Institute on Drug Abuse (NIDA) Animal Genetics Program is to identify genetic, genomic, and molecular (epi)genetic variants that underlie neural and behavioral processes and phenotypes relevant to SUD risk, the SUD trajectory and SUD comorbidities. This opportunity supports research that links genetic, genomic and molecular mechanisms to neural circuit function and behavior.

Applications may seek to identify any type of genomic and/or epigenomic variants that contribute to the genetic architecture of addiction, including single nucleotide variants (SNVs), indels, large and small structural variants, and all types of mobile DNA.

NIDA encourages applications that take genomics, multi-omics, data-based, and/or artificial intelligence/machine learning approaches that integrate multi-level ‘omics data, delineate gene networks, and/or uncover the function of known or newly discovered genetic or epigenetic variants.

Other areas of interest include variant identification at the circuit level and the application of neuroscience to variant identification studies in tissues and cells. NIDA expects these studies to uncover novel mechanisms that contribute to various stages across the SUD trajectory and inform future studies about potential targets and therapeutic strategies for addiction.

Neurobehavioral and cognitive processes of interest include reward processing, volition, executive functions involved in decision-making and choice behavior, sensitivity to risk/threat or punishment, affective and behavioral regulation and social behavioral processes.

Relevant phenotypes include anhedonia, avolition, anxiety, impulsive behavior, compulsive behavior, drug/substance-seeking and substance-related biases in decision-making and choice behavior, social exploratory drive, social aversion or insensitivity, and other genetically-associated phenotypes.

Of particular importance is for the applicant to relate the neurobehavioral process or phenotype of interest to vulnerability or psychopathology at distinct stages along the SUD trajectory (e.g. initial/acute use, escalation of use, acquisition of tolerance, dependence, uncontrolled use, abstinence and relapse or recovery). Other considerations . Applicants are encouraged to contact program staff with their questions.

We anticipate interdisciplinary teams will be necessary for successful completion of the proposed work. Such teams could include expertise in genetics, genomics, structural variation, somatic variation, single cell studies, behavioral phenotyping, phenotype analyses, bioinformatics, data analysis, network analyses, and modeling.

Some types of studies that would be appropriate for this NOFO include, but are not limited to: Identification of genetic, genomic, and molecular (epi)genetic variants underlying phenotypes: 1. Along the addiction trajectory; 2. Neurobehavioral and cognitive processes associated with addiction or resilience to addiction; and 3.

Comorbidities with demonstrated or potential genetic correlations with addiction phenotypes Studies assessing multiple phenotypes, projects that incorporate environmental stressors, and/or screens designed to identify phenotypic enhancers and/or suppressors Analyses that uncover regions of the genome that have been excluded from most genetic studies (e.g., structural variants, repetitive DNA, transposable elements, etc.) Exploration of somatic mutations in addiction studies Studies that test a constellation of variants in animal model systems Studies designed to assess gene networks, epistasis, as well as gene x drug interactions, sex differences, and other systems-based approaches Development of analysis tools and pipelines, including artificial intelligence/machine learning approaches, to integrate data across species, delineate gene networks, analyze multi-omics data, and/or examine at least two levels of genetic architecture (e.g., DNA sequence and epigenetic mark(s), splice variants and DNA level data, RNA sequence and epigenetic mark(s), etc.) Studies in multiple species that probe neuroscience components of addiction (e.g., within circuits, tissues, and cells), or that use more sophisticated behavioral analyses that better model human phenotypes and behaviors Applications Not Responsive to this NOFO The following types of studies are not responsive to this NOFO and will not be reviewed:.

Applications whose primary aims are to study the effects of single gene mutations on addiction phenotypes Applications that solely focus on epigenetic analyses or gene transcription without a genomics, genetics, and/or systems-based component Applications that focus on the functional validation or characterization of a single gene or single gene variant.

For these types of studies, please see PAR-23-041, Functional Validation and/or Characterization of Genes or Variants Implicated in Substance Use Disorders (R21/R33 Clinical Trial Not Allowed) Applications that propose to examine the genetic underpinnings of psychiatric disorders without an addiction component See Section VIII. Other Information for award authorities and regulations. Section II.

Award Information 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 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.

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 number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

Application budgets are not limited but need to reflect the actual needs of the proposed project. The maximum project period is 5 years. NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO.

Section III.

Eligibility Information Higher Education Institutions Public/State Controlled Institutions of Higher Education Private Institutions of Higher Education 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 (Other than Small Businesses) City or Township Governments Special District Governments Indian/Native American Tribal Governments (Federally Recognized) Indian/Native American Tribal Governments (Other than Federally Recognized).

Eligible Agencies of the Federal Government U.S. Territory or Possession Independent School Districts Public Housing Authorities/Indian Housing Authorities Native American Tribal Organizations (other than Federally recognized tribal governments) Faith-based or Community-based Organizations Non-domestic (non-U.S.) Entities (Foreign Organizations). 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. 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 .

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.

The same UEI must be used for all registrations, as well as on the grant application. eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants. gov registration; 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 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. 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 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. 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. 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.

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 All instructions in the How to Apply-Application Guide must be followed.

SF424(R&R) Senior/Key Person Profile All instructions in the How to Apply- Application Guide must be followed. All instructions in the How to Apply- Application Guide must be followed. Applicants should include costs for at least one member of the team to attend the annual NIDA Animal Genetics Meeting.

All instructions in the How to Apply-Application Guide must be followed. PHS 398 Cover Page Supplement All instructions in the How to Apply- Application Guide must be followed.

All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions: All applicants must address the following in their Research Strategy: Describe the significance, including heritability, of the behavioral and other phenotypic assays and how the proposed studies will help to: 1.

uncover the underlying genomic architecture (e.g. DNA variants, epigenetic modifications and epimutations, copy number variants, structural variants, etc.) of the genes and genetic domains involved in phenotypes associated with SUD; 2. better understand how gene networks contribute to SUD; and/or 3. test the predictive risk for SUD using animal models with multiple genetic and/or epigenetic variants, as applicable to the study design.

Describe how/why these studies will advance the understanding of SUD and/or advance the field of research. Describe the scientific premise for choosing the phenotypes along SUD trajectory and/or co-comorbid conditions. Describe the rationale for choosing each assay, explain the reason for choosing the strains used in the analysis, and justify the number of animals through a power calculation.

As needed, describe which tissues will be used and include information about tissue handling, library preparation, types of cells and transcripts expected to be assayed, previous success conducting proposed studies, and potential pitfalls and alternative approaches. Describe the expertise of the research team with respect to SUD research, genetics, genomics, and bioinformatics, as applicable.

Describe how the team will develop and use common metadata and data standards, adopt data quality metrics, analyze 'omics and other data, and share protocols and data with the NAGP, as appropriate and consistent with achieving the goals of the program. Describe any methods that need to be developed and/or implemented for data integration. Describe any innovative analysis strategies that will be used.

Describe how the project proposes to take advantage of synergistic resources already available. Provide a timeline and delineate annual milestones for the project. Milestones should be Specific, Measurable, Achievable, Relevant, and Time-bound.

Applicants must describe the total number of animals and total number of phenotypic, molecular and data-driven assays that will be completed for each year of the project period and by the end of the project period. Applicants should also indicate the total number of samples from each group that will be assayed by the end of the project period.

If selected for funding, applicants will work with NIH staff to develop more granular annual milestones.

Describe plans for participation in the NIDA Animal Genomics Consortium; include details of how the PIs, Co-Is, research associates, graduate students, and postdoctoral scientists will participate in monthly NIDA Animal Genomics Consortium Meetings and include travel costs to attend the annual NIDA Genetics Meeting and the satellite NIDA Animal Genomics Consortium Meeting.

Multiple-PD/PI Leadership Plan: Describe the qualifications of each team member without duplicating information in the biosketches and how they contribute to meet the goals of the project. Describe research management plans, including plans for regular meetings of the research team. Describe responsibilities for all PD/PIs, Co-Investigators, project managers, students, postdocs, and other pertinent research staff.

Describe how the expertise of each team member is important to meet the goals of the project. Applicants should plan for PDs/PIs and essential team members to travel to the Annual NIDA Genetics Meeting, hosted by the NIDA Genetics and Epigenetics Cross-Cutting Research Team and document plans to join and participate in the NIDA Animal Genetics Consortium, which meets monthly via webinar.

The NAGC consists of investigators funded by this NOFO, as well as the prior iterations of this NOFO (e.g. PAR-15-120, PAR-18-789, and PAR-21-244), investigators funded by RFA-DA-20-010, and investigators who hold Program Project grants that focus on the genetics/genomics of SUD.

Sex as a Biological Variable : Behavioral studies from animal and human laboratory studies as well as field and treatment studies have found differences in males and females in phenotypic characteristics along the trajectory to SUD. Applications under this NOFO should incorporate those phenotype differences into the study design and power the study to detect differences between males and females in outcomes.

Incorporating sex as a biological variable is an NIH requirement, but does not demand statistical power to detect differences between males and females. In the case of this NOFO, when the literature predicts sex differences in outcomes, powering studies to detect those differences is an important component of rigor and reproducibility.

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.

All instructions in the How to Apply-Application Guide must be followed, with the following additional instructions: All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan.

All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan. Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply- Application Guide.

No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

PHS Human Subjects and Clinical Trials Information When involving human subjects research, clinical research, and/or NIH-definedclinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the 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 All instructions in the How to Apply- Application Guide must be followed.

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the How to Apply-Application Guide must be followed. PHS Assignment Request Form All instructions in the How to Apply-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 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. 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 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. 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 . 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 NIDA, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Requests of $500,000 or more for direct costs in any year 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.

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 [email protected] .

Post Submission Materials Applicants are required to follow the instructions for post-submission materials, as described in the policy Section V. Application Review Information Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

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

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 Evaluate the importance of the proposed research in the context of current scientific challenges and opportunities, either for advancing knowledge within the field, or more broadly.

Assess whether the application addresses an important gap in knowledge in the field, would solve a critical problem, or create a valuable conceptual or technical advance. Evaluate the rationale for undertaking the study, the rigor of the scientific background for the work (e.g. prior literature and/or preliminary data) and whether the scientific background justifies the proposed study.

Evaluate the extent to which innovation influences the importance of undertaking the proposed research. Note that while technical or conceptual innovation can influence the importance of the proposed research, a project that is not applying novel concepts or approaches may be of critical importance for the field.

Evaluate whether the proposed work applies novel concepts, methods or technologies, or uses existing concepts, methods, technologies in novel ways, to enhance the overall impact of the project. Factor 2. Rigor and Feasibility Evaluate the scientific quality of the proposed work.

Evaluate the likelihood that compelling, reproducible findings will result (rigor) and assess whether the proposed studies can be done well and within the timeframes proposed (feasibility). Evaluate the potential to produce unbiased, reproducible, robust data. Evaluate the rigor of experimental design and whether appropriate controls are in place.

Evaluate whether the sample size is sufficient and well-justified. Assess the quality of the plans for analysis, interpretation, and reporting of results. Evaluate whether the investigators presented adequate plans to address relevant biological variables, such as sex or age, in the design, analysis, and reporting.

For applications involving human subjects or vertebrate animals, also evaluate: the rigor of the intervention or study manipulation (if applicable