Small Research Grant Program for the Next Generation of Researchers in AD/ADRD Research (R03 Clinical Trial Optional) is sponsored by National Institutes of Health (NIH). Supports small research projects for early-career researchers in Alzheimer's disease and related dementias.

Expired PA-25-246: Small Research Grant Program for the Next Generation of Researchers in AD/ADRD Research (R03 Clinical Trial Optional) This notice has expired. For NIH, in limited situations, applications may be accepted on a case-by-case basis for a short period after expiration to accommodate NIH late or continuous submission policies . Contact the eRA Service Desk for any submission issues.

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 Funding Opportunity Title Small Research Grant Program for the Next Generation of Researchers in AD/ADRD Research (R03 Clinical Trial Optional) 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 This Small Research Grant (R03) program will support meritorious projects to provide needed scientific insight to improve the prevention, diagnosis, treatment, and/or care for individuals with Alzheimer's disease and Alzheimer's disease-related dementias (AD/ADRD).

Specifically, this NOFO will support projects covering a wide range of topics related to AD/ADRD.

The overall goal of this NOFO is (i) to encourage the next generation of researchers to pursue research and academic careers in AD/ADRD research; and (ii) to stimulate established researchers who have not had a major award in AD/ADRD research to perform pilot studies to develop new, innovative AD/ADRD research programs that leverage and build upon their existing expertise.

Investigators who have not successfully competed for an award under this or prior versions of this announcement are specifically encouraged to apply. Funding Opportunity Goal(s) To encourage biomedical, social, and behavioral research and research training directed toward greater understanding of the aging process and the diseases, special problems, and needs of people as they age.

Open Date (Earliest Submission Date) The following table includes NIH standard due dates marked with an asterisk. 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 A major goal of the National Plan to address Alzheimer’s disease and Alzheimer’s disease-related dementias (AD/ADRD) is to accelerate the development of treatments that would prevent, delay, or reverse the course of the disease and improve early diagnosis; yet, there is a shortage of scientists to conduct the wide variety of necessary innovative and interdisciplinary research projects, including clinical, translational, prevention, and treatment research on AD/ADRD.

This Small Research Grant program will address the National Alzheimer’s Project Act (NAPA) Milestone 4. J: “Expand existing and create new integrative training programs for early career neuroscience, behavioral and social science researchers that include training in aging biology, systems biology, geriatrics, all aspects of data science as well as traditional and emerging drug discovery disciplines.

These efforts should include cross-disciplinary training programs in AD, aging, epidemiology, neuropsychology, environmental health, genomics, and data science to enhance the workforce needed for research on gene-environment interactions in AD and AD health disparities. ” A major barrier to non-AD researchers obtaining an R01 grant to conduct AD/ADRD research is the lack of critical preliminary data.

This Notice of Funding Opportunity (NOFO) is intended to help them overcome this barrier. The overall goal of this NOFO is to support important and innovative research in areas in which more scientific investigation is needed to improve the prevention, diagnosis, treatment, and care for AD/ADRD. The aim is to encourage the next generation of researchers to pursue research and academic careers in AD/ADRD.

Another aim is to stimulate novel research ideas from researchers in other fields. NIA expects applications from investigators who have expertise in their research field but have not had a major award in AD/ADRD. Examples of major awards from NIH include DP1, DP2, DP5, R01, R37, R56, RF1, RL1, U01 and R35, as well as serving as a PI/PD on Centers and Program Project grants.

NIA anticipates that at least half of the awards will be made to early stage investigators (ESIs) to achieve the goal of fostering their development. Each PI is eligible to receive up to one award through this program. Advance ESIs committed to pursuing careers in the field of AD/ADRD and aging research, including all qualified researchers from a variety of training and professional backgrounds.

Generate high-quality research projects from junior faculty in genetic, biological, clinical, behavioral, social, and economic research related to AD/ADRD. Advance opportunities for ESIs to launch research careers focusing on AD/ADRD by helping ESIs accrue pilot data to subsequently submit competitive applications for larger, independent funding awards. Build a pipeline of early career investigators committed to AD/ADRD research.

Invite clinical research investigators who are new to AD/ADRD research to pursue topic(s) focused on prevention, diagnosis, treatment, or management of AD/ADRD within their respective fields. Encourage an infusion of investigators from other health research areas to pursue important and novel approaches to research in AD/ADRD. Enhance opportunities for networking, collaboration, and retention in the field.

This NOFO will support projects on AD/ADRD covering a wide array of topics including, but not limited to, the following: Research aimed at understanding the AD/ADRD trajectory for persons with dementia and their caregivers, including studies of prevention, diagnosis, communication, and/or management of specific acute or chronic comorbid conditions in persons with AD/ADRD.

Basic science research in AD/ADRD to elucidate systemic, non-neuronal, or environmental factors associated with AD/ADRD including microbiome; exercise; nutrition; environmental toxicants; traumatic brain injury; circadian rhythms (in both peripheral and central organs); cerebrovascular, cardiovascular, immune system, and metabolic mechanisms; alterations in the blood-brain barrier; and the role of neuroinflammation in AD/ADRD.

Elucidation of biological underpinnings and molecular pathways in sensory (visual, auditory, chemosensory, somatosensory, pain) and motor systems and/or affective processes that may be associated with AD/ADRD initiation, progression, or outcome.

Social, behavioral, psychological, and economic research on AD/ADRD health disparities; cognitive and dementia epidemiology, including cross-national comparisons; investigations of behavioral and social mechanisms that operate as risk or protective factors for AD/ADRD; measurement of AD/ADRD-related cognitive and functional changes; non-pharmacological interventions for dementia prevention, dementia care, and caregiving; and research on the economic impact of dementia on individuals, families, health systems, and society ( learn more about NIA's AD/ADRD research priorities ).

Early Stage (Stage 0 or I of the NIH Stage Model) clinical trials that capitalize on and integrate basic research to inform the development of efficacious interventions, defined by their governing principles. Proposed projects may be focused on individuals, dyads, families, communities, organizations, and/or systems.

Systems biology approaches involving repeated cycles of experimental data generation, analysis, and integration; modeling of system-wide molecular network structure and dynamics; and validation through predictions of responses to perturbations of experimental conditions or alteration of selected components of the network.

Use of genetic, omics, and other types of data from existing molecular profiling studies is strongly encouraged, particularly where AD/ADRD endophenotypes can be defined. Development of innovative computational approaches for integration of multiple data types generated by high-throughput experimental technologies such as long-read genetic sequencing approaches could be supported if justified appropriately.

Exposomics research involving data measured from various physical, chemical, social, psychological, and economic exposures across multiple levels and across the life course in the etiology and social disparities of AD/ADRD.

Of particular interest is research to systematically analyze phenotypic, metabolomic, and epigenomic data in response to physical, built, social, and environmental exposures to inform the interplay between genes, behavior, biology, and environment, and to assess its impact on AD/ADRD outcomes.

Health disparities research to understand the prevalence of AD/ADRD in populations that experience health disparities, including studies to investigate disease pathways that contribute to demographic complexity in the biology and neuropathology of AD/ADRD; studies to estimate the effect of educational attainment and occupational exposures on dementia risk, diagnosis, and cognitive assessment; disease pathways that create or sustain AD/ADRD disparities; and the unique challenges related to the provision of advanced AD/ADRD care in disparity populations, including disparities in access, utilization, and quality of care.

Evaluation of existing clinical guidelines, standards of care, and/or preventive medicine recommendations for persons with AD/ADRD. NIA encourages applicants to pursue professional development activities in parallel with the R03 award. NIH supports several centers and other programs through which applicants may receive support for developmental activities complementary to the R03 award.

Also, a number of professional societies have funds available to support researchers in their specialties.

A brief list of example resources to support professional development activities includes: The applicant’s sponsoring institution and/or affiliated Veteran’s Administration hospital Clinical and Translational Science Award (CTSA) Specialty societies, foundations, and non-profits, such as the American Geriatrics Society , the Alzheimer's Association , the Lewy Body Dementia Association , the Association for Frontotemporal Degeneration , and the American Federation for Aging Research Training or research education components within NIH-funded research centers: Alzheimer's Disease Centers (ADCs) Artificial Intelligence and Technology Centers (AITCs) Claude D.

Pepper Older Americans Independence Center (OAICs) Resource Centers for Minority Aging Research (RCMAR) Centers on the Demography and Economics of Aging Edward R. Roybal Centers for Translational Research in the Behavioral and Social Sciences of Aging NOTE TO APPLICANTS CONSIDERING A CLINICAL TRIAL: The limited time and budget provided by this NOFO will constrain the types of clinical trials that can be proposed.

In general, only mechanistic trials or small pilot trials are likely to be feasible. Applicants considering a clinical trial are highly encouraged to contact NIA program staff early to discuss the feasibility of leading a clinical trial under this program. Refer also to NIH's policies and requirements for clinical trials .

Applicants may also find useful information on the NIH Research Methods Resource page. Clinical Research Operations Management System: NIA supports a central resource to NIA staff and extramural investigators to facilitate/support the conduct and management of clinical research.

This resource, the Clinical Research Operations Management System (CROMS), is a comprehensive data management system to support the business functions, management, and oversight responsibilities of NIA grants that support the conduct of clinical research with human subjects.

It is the expectation by NIA that all successful applicants will interface, integrate, or adapt their information system(s) and processes to interact with existing and future components of the CROMS as necessary, including the use of CROMS data templates as specified.

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 Grant: A financial assistance 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 How to Apply Application Guide provide details on these application types.

Only those application types listed here are allowed for this NOFO. 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 The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications. Applications may request budgets of up to $100,000 in direct costs per year for up to two years. The scope of the project should determine the project period.

The maximum project period is 2 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 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.

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 registrations; all registrations must be in place by time of submission.

eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application. Grants. gov – Applicants must have an active SAM registration in order to complete the Grants.

gov registration. Program Directors/Principal Investigators (PD(s)/PI(s)) All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons.

If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal Investigator) Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with 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 award is not intended for individuals with substantial experience in AD/ADRD research.

Moreover, it is generally expected that applicants will not have had prior research funding as an independent PD/PI on a major NIH grant in AD/ADRD research (e.g., DP1, DP2, DP5, R01, R37, R56, RF1, RL1, U01 and R35, or serving as a PD/PI in Centers and Program Project grants). Applicants are strongly encouraged to discuss their eligibility with NIA program staff early in the application process.

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 ). Each PI is eligible to receive up to one award through this program.

Recipients of awards made under PAR-23-179 , PAS-19-391 , PAS-19-392 , PAS-19-393 , and predecessors are not eligible. 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. 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: 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-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 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.) 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. 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 components of participating organizations , NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

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.

For this particular announcement, note the following: The R03 small grant supports discrete, well-defined projects that realistically can be completed in two years and that require limited levels of funding. Because the research project usually is limited, an R03 grant application may not contain extensive detail or discussion. Accordingly, reviewers should evaluate the conceptual framework and general approach to the problem.

Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or from investigator-generated data. Preliminary data are not required, particularly in applications proposing pilot or feasibility studies.

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 (Significance and Innovation) 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 (Approach) 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 to the study design). whether outcome variables are justified.

whether the results will be generalizable or, in the case of a rare disease/special group, relevant to the particular subgroup. whether the sample is appropriate and sufficiently diverse to address the proposed