Development of Animal Models and Related Biological Materials for Research (R21)

Development of Animal Models and Related Biological Materials for Research (R21) is sponsored by National Institutes of Health. This grant supports the development of animal models and related biological materials for research. While not exclusively focused on zebrafish, it is highly relevant for those working with zebrafish as a model organism.

Expired PAR-21-167: Development of Animal Models and Related Biological Materials for Research (R21 Clinical Trial Not Allowed) This notice has expired. Check the NIH Guide for active opportunities and notices. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating Organizations Division of Program Coordination, Planning and Strategic Initiatives, Office of Research Infrastructure Programs ( ORIP ) Funding Opportunity Title Development of Animal Models and Related Biological Materials for Research (R21 Clinical Trial Not Allowed) R21 Exploratory/Developmental Research Grant Notices of Special Interest associated with this funding opportunity November 15, 2024 - This PAR has been reissued as PAR-25-273 .

March 6, 2024 - Notice of Extension of the Expiration Date for PAR-21-167 "Development of Animal Models and Related Biological Materials for Research (R21 Clinical Trial Not Allowed).

See Notice NOT-OD-24-070 NOT-OD-23-012 Reminder: FORMS-H Grant Application Forms and Instructions Must be Used for Due Dates On or After January 25, 2023 - New Grant Application Instructions Now Available NOT-OD-22-190 - Adjustments to NIH and AHRQ Grant Application Due Dates Between September 22 and September 30, 2022 See Notices of Special Interest related to this funding opportunity October 28, 2021 - Reminder: FORMS-G Grant Application Forms & Instructions Must be Used for Due Dates On or After January 25, 2022 - New Grant Application Instructions Now Available.

See Notice NOT-OD-22-018 . September 13, 2021 - Updates to the Non-Discrimination Legal Requirements for NIH Recipients. See Notice August 5, 2021 - New NIH "FORMS-G" Grant Application Forms and Instructions Coming for Due Dates on or after January 25, 2022.

August 5, 2021 - Update: Notification of Upcoming Change in Federal-wide Unique Entity Identifier Requirements. See Notice NOT-OD-21-170 April 20, 2021 - Expanding Requirement for eRA Commons IDs to All Senior/Key Personnel. See Notice NOT-OD-21-109 Funding Opportunity Announcement (FOA) Number Companion Funding Opportunity See Section III.

3. Additional Information on Eligibility . Assistance Listing Number(s) Funding Opportunity Purpose This funding opportunity announcement (FOA) encourages innovative research to develop, characterize, and improve animal models, biological materials, and novel technologies to better understand human health and disease.

This FOA also seeks projects aimed at improving the diagnosis and control of diseases that interfere with animal use for biomedical research. The proposed project must have broad application to multiple NIH Institutes or Centers (ICs) to align with the Office of Research Infrastructure Programs (ORIP) trans-NIH mission . The proposed studies must explore multiple body systems or evaluate diseases that impact multiple body systems.

Applications that develop models focused on a specific disease or area of research, or only propose studies primarily relevant to a single NIH IC, will be considered not acceptable to this FOA and will be withdrawn. Open Date (Earliest Submission Date) Letter of Intent Due Date(s) The following table includes NIH standard due dates marked with an asterisk.

Dates in bold and italics reflect changes per NOT-OD-24-070 Renewal / Resubmission / Revision (as allowed) June 16, 2021 * July 16, 2021 * September 07, 2021 * November 2021 January 2022 April 2022 October 16, 2021 * November 16, 2021 * January 07, 2022 * March 2022 May 2022 July 2022 February 16, 2022 * March 16, 2022 * May 07, 2022 * July 2022 October 2022 December 2022 June 16, 2022 * July 16, 2022 * September 07, 2022 * November 2022 January 2023 April 2023 October 16, 2022 * November 16, 2022 * January 07, 2023 * March 2023 May 2023 July 2023 February 16, 2023 * March 16, 2023 * May 07, 2023 * July 2023 October 2023 December 2023 June 16, 2023 * July 16, 2023 * September 07, 2023 * November 2023 January 2024 April 2024 October 16, 2023 * November 16, 2023 * January 07, 2024 * March 2024 May 2024 July 2024 February 16, 2024 * March 16, 2024 * May 07, 2024 * July 2024 October 2024 December 2024 June 16, 2024 * July 16, 2024 * September 07, 2024 * November 2024 January 2025 April 2025 October 16, 2024 * November 16, 2024 * January 07, 2025 * March 2025 May 2025 July 2024 All applications are due by 5:00 PM local time of applicant organization.

All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s). Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date. New Date November 15, 2024 (Original Date: January 08, 2025) per issuance of PAR-25-273 .

Required Application Instructions It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide , except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts ). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced.

Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV . When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

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

Funding Opportunity Description Animal models are essential for studying biological processes underlying human health and diseases and for developing safe and effective therapeutic approaches prior to clinical trials in humans.

Advances made regarding our understanding of the complexity of human diseases have created increasing demands for developing new or improved animal models that are more predictable, accessible, and widely applicable for biomedical research.

The Office of Research Infrastructure Programs (ORIP) serves the research community by supporting research and resource-related research projects which collect, maintain, curate, and develop critical animal models and related biological materials that are made available to the biomedical research community.

This funding opportunity announcement (FOA) encourages innovative research to develop, characterize, preserve, and improve animal models, technologies, and biological materials for the study of human health and diseases.

This FOA also seeks projects aimed at improving the diagnosis and control of diseases that interfere with the use of animal models in biomedical research as a means of improving rigor and reproducibility of preclinical studies. Mammalian and non-mammalian models, cell/tissue culture systems, and integrative informatics models, such as those incorporating -omics and physiological data, are suitable for this FOA.

The trans-NIH nature of ORIP activities stipulates that ORIP supports the missions of the NIH Institutes and Centers (ICs) by strengthening existing programs, developing resources, advancing areas of emerging science, and establishing new initiatives to move biomedical research forward.

Proposed studies, models, technologies, and biological materials for this FOA must address research interests of multiple NIH ICs and must explore multiple body or organ systems or must evaluate diseases and processes that impact multiple body or organ systems.

Applications to develop models that relate strictly to a specific disease or area of research or are relevant to the mission and programs of a single IC are not suitable for this FOA and should be directed to the appropriate IC. For example, investigators interested in models or model systems with a primary focus on aging, cancer, heart disease, or neurological disorders should contact the respective ICs relevant to these topics.

Furthermore, applications proposing studies that are related predominantly to the interest of one IC and only peripherally to the interests of other ICs are also not acceptable and will be withdrawn.

Examples of projects suitable for this FOA include but are not limited to: Development or characterization of new and significantly improved genetically modified animal models, which are applicable to human health and diseases that impact multiple body or organ systems (e.g. phenotypic characterization of multiple organ systems in developed animal models).

Development of novel technologies for producing and improving animal models, such as gene editing or synthetic biology. Development of genetically encoded probes (i.e., reporters) to facilitate high resolution single cell analysis, cellular network analysis, and effective high-throughput screens for phenotypes.

Reliable, cost-effective preservation and distribution of animal models and related biological materials, including cloning of animal models, cryopreservation, or other long-term preservation of animal models for which effective and reliable preservation methods for gametes, embryos or whole animals have not been established (e.g., invertebrate, aquatic, and swine models), or significant improvement of preservation methods for animal species for which effective approaches have developed (e.g., worm, mouse, rat, and nonhuman primate).

Approaches complementary to the use of animals, such as animal-tissue-on-chip models, that can simulate physiological and pathophysiological processes and capture the complex dynamics of interacting molecules, cells, tissues, and organs outside of the whole organism. Such approaches or systems must be tested and compared to whole animals in vivo .

Informatics and artificial intelligence tools for deep phenotyping, including new tools for mapping molecular interactive networks, cellular networks, and behaviors in animal and cell models. Animal models for microbiome research aimed at understanding mechanisms of the causal effects of microbiota, virome, and eukaryome on human health and disease, and addressing reproducibility of animal models in biomedical research.

Animal models for investigating function of epigenetic factors that affect many areas of human health and disease and are generalizable across genomic regions or diseases. Improvement of animal models for stem cell-based regenerative medicine and for effective and sustained gene therapy using ex vivo engineered and endogenous stem cell populations to correct gene defects.

These include stem cell generation, reprogramming, characterization, and transplantation; stem cell-based therapeutic applications; analysis of the safety of newer technologies such as RNA-guided endonucleases (CRISPR/Cas9), optogenetics, and humanized animal models generated with non-fetal human tissues.

Studies focused on the fundamental biology of animal models with the goal to improve predictability, rigor, and reproducibility of animal studies. Such studies may investigate genetic, physiological, and behavioral aspects of animal models. Development of high throughput approaches for effective validation of animal models according to stringent criteria to improve predictability, rigor, and reproducibility of animal studies.

Characterization of animal diseases, which are potential confounders or otherwise interfere with the use of animal models for human health and diseases, such as detecting, characterizing, and controlling emerging and re-emerging pathogens, especially those affecting animal repositories supported by the NIH.

Development and refinement of animal models or tools for newly emerging human pathogens and in response to recent active trans-NIH public health initiatives.

Applications Not Responsive to the FOA Projects that ARE NOT suitable for this FOA and would be deemed nonresponsive and withdrawn include but are not limited to: Development of models that relate strictly to a specific disease or area of research or are primarily relevant to the mission and programs of only one NIH IC.

Development of cell lines of a single cell type that relate strictly to a specific disease or area of research or are primarily relevant to the mission and programs of only one NIH IC. Investigation of the effect of drug(s), toxin(s), infectious agent(s), diet, or other environmental factors on wild-type animals. Study of physical or surgical manipulation(s) in wild-type animals.

Development or maintenance of databases including genome and model organism databases. Development or maintenance of repositories of tissues and related bio-specimens from model organisms. Study primarily involving human subjects or human cell lines.

Applications for R21 awards should describe projects distinct from those supported through the traditional R01 mechanism. Long-term projects or projects designed to increase knowledge in a well-established area are not appropriate for R21 awards. The R21 mechanism is intended to encourage exploratory research projects that foster a constant infusion of new ideas, techniques, and points of view into biomedical research.

Such projects could assess a new experimental system that has the potential to enhance health-related research or propose an innovative use of an existing methodology, system, or model to explore a new scientific area.

These studies may involve considerable risk but may lead to: a breakthrough in a research area; the development of novel techniques, agents, methodologies, and models; or a major impact on a field of interests of multiple NIH ICs. Investigators interested in applying are strongly encouraged to contact ORIP program staff (see Scientific/Research Contacts in Section VII.

Agency Contacts) before submission to discuss whether their research plans are appropriate for and responsive to this FOA. Applications with projects outside areas of interests of this FOA will be considered nonresponsive and withdrawn. See Section VIII.

Other Information for award authorities and regulations. Section II. Award Information Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

Application Types Allowed The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA. 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. No more than $200,000 direct costs may be requested in any single year.

The combined budget may not exceed $275,000 direct costs for the two-year project period. The total project period may not exceed 2 years. NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.

Section III.

Eligibility Information 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 (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 Institutions) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply. Foreign components, as defined in the NIH Grants Policy Statement , are allowed. 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) 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 to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.

gov registration, but 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 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.

Eligible Individuals (Program Director/Principal Investigator) Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support.

Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support. For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

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

Application and Submission Information 1. Requesting an Application Package The application forms package specific to this opportunity must be accessed through ASSIST, Grants. gov Workspace or an institutional system-to-system solution.

Links to apply using ASSIST or Grants. gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced.

Applications that are out of compliance with these instructions may be delayed or not accepted for review. All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

Instructions for Application Submission Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing (DMS) Plan will be attached in the Other Plan(s) attachment in FORMS-H and subsequent application forms packages.

For due dates on or before January 24, 2023, the Data Sharing Plan and Genomic Data Sharing Plan GDS) will continue to be attached in the Resource Sharing Plan attachment in FORMS-G application forms packages. 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.

SF424(R&R) Project/Performance Site Locations All instructions in the SF424 (R&R) Application Guide must be followed. SF424(R&R) Other Project Information All instructions in the SF424 (R&R) Application Guide must be followed. SF424(R&R) Senior/Key Person Profile All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed. All instructions in the SF424 (R&R) Application Guide must be followed. PHS 398 Cover Page Supplement All instructions in the SF424 (R&R) Application Guide must be followed.

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H and subsequent application forms packages. For due dates on or before January 24, 2023, the Data Sharing Plan and Genomic Data Sharing Plan GDS) will continue to be attached in the Resource Sharing Plan attachment in FORMS-G application forms packages.

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.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions: Resource Sharing Plan : Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide. The following modifications also apply: All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Applications should describe a clear plan on how to distribute developed animal models, biological materials, or informatic tools to the scientific community after the termination of the grant cycle. Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

PHS Human Subjects and Clinical Trials Information When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions: If you answered Yes to the question Are Human Subjects Involved?

on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record. Study Record: PHS Human Subjects and Clinical Trials Information All instructions in the SF424 (R&R) Application Guide must be followed.

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

3. Unique Entity Identifier and System for Award Management (SAM) See Part 1. Section III.

1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants. gov. 4. Submission Dates and Times Part I.

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

Organizations must submit applications to Grants. gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons , NIH’s electronic system for grants administration.

NIH and Grants. gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.

gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission. Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide. 5.

Intergovernmental Review (E. O. 12372) This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement . Pre-award costs are allowable only as described in the NIH Grants Policy Statement . 7.

Other Submission Requirements and Information Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted. Applicants must complete all required registrations before the application due date.

Section III. Eligibility Information contains information about registration. For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply #8211; 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 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 nonresponsive, incomplete, or non-compliant will not be reviewed. 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 Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) as part of the Resource Sharing Plan will not be evaluated at time of review.

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.

For this particular announcement, note the following: The R21 exploratory/developmental grant supports investigation of novel scientific ideas or new model systems, tools, or technologies that have the potential for significant impact on biomedical or biobehavioral research. An R21 grant application need not have extensive background material or preliminary information.

Accordingly, reviewers will emphasize the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Preliminary data are not required for R21 applications; however, they may be included if available.

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

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

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved?

How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? If the focus of the proposed study is on a particular disease, does the disease impact multiple body systems? How does the project align with ORIP’s trans-NIH mission?

Is there a need for the proposed model, technology, or biological material(s) in order to address scientific hypotheses of interest to the biomedical research community? Do the developed animal models, biological materials, or tools address a gap(s) in multiple research fields? Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project?

If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)?

If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions?

Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed? Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project?

Have