Department of Health
and Human Services (HHS)
and Human Services (HHS)
EXPIRED
National Institutes of Health (NIH)
R01 Research Project Grant
Reissue of PAR-17-336
PAR-21-028 - Discovery of Cell-based Chemical Probes for Novel Brain Targets (R21 Clinical Trial Not Allowed), R21 Exploratory/Developmental Grant
93.242, 93.279, 93.867, 93.866
The purpose of this Funding Opportunity Announcement (FOA) is to support investigators who have interest and capability to join efforts for the discovery of in vivo chemical probes for novel brain targets. It is expected that applicants will have, in hand, the starting compounds ( validated hits ) for chemical optimization and bioassays for testing new analog compounds.
Through this FOA, NIH wishes to stimulate research in 1) discovery and development of novel, small molecules for their potential use in understanding biological processes relevant to the missions of NIMH, NIDA, NEI, and/or NIA and 2) discovery and/or validation of novel, biological targets that will inform studies of brain disease mechanisms. Emphasis will be placed on projects that provide new insight into important disease-related biological targets and biological processes.
The main emphasis of projects submitted under this FOA should be the discovery of in vivo chemical probes. Applicants interested in developing cell-based chemical probes may wish to apply using the companion R21 mechanism, (PAR-21-028).
Not Applicable
Standard dates apply.
The first standard due date for this FOA is February 5, 2021.
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.
Standard AIDS dates apply, , by 5:00 PM local time of applicant organization. All types of AIDS and AIDS-related applications allowed for this funding opportunity announcement are due on these dates.
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.
Standard dates apply
Standard dates apply
Standard dates apply
Not Applicable
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.
Research Scope
Technological innovations in chemical synthesis, cheminformatics, structural biology, and high throughput bioactivity and drug property assays have allowed rapid discovery of novel, small-molecule probes for the study of disease-related biological processes and mechanisms in academic environments.
Through this Funding Opportunity Announcement (FOA), NIMH, NIDA, NEI and/or NIA encourage applications to advance the discovery of small molecule chemical probes that would enable, by modulating the function of a novel biological target, mechanistic questions to be addressed in animal studies. The NIH aims to stimulate research in 1) discovery and development of a novel in vivo chemical probes for their potential use in understanding biological processes relevant to the missions of the participating NIH Institutes, and 2) use of chemical probes to discover and/or validate novel biological targets that will inform studies of brain disease mechanisms. Emphasis will be placed on research that provides new insight into important disease-related biological targets and biological processes. For example, applications may involve emerging therapeutic targets and mechanisms for the discovery of chemical probes that may lead to further development of therapeutics or provide insight into the biology of relevant diseases.
This program creates an opportunity for integrated research in biology and chemistry on structure-activity relationships (SAR) of novel compounds through an iterative and parallel optimization process, to advance the successful development of in vivo chemical probes. Applicants to this FOA should have, in hand, the starting compounds ( validated hits ) for chemical optimization and bioassays for testing new analog compounds. The iterative bioassay and chemical optimization cycles may encompass:
The above-mentioned areas of investigation are representative and not meant to be all-inclusive.
The main emphasis of projects submitted under this FOA should be on chemical probes development rather than drugs or therapeutic discovery, the latter of which are beyond the scope of this FOA.
Applications Not Responsive to this FOA
Applications on the following research topics are not responsive to this FOA and will be withdrawn prior to review:
Data Sharing
A goal of the program is to further research advancements across the scientific community as rapidly as possible. In order to reap the maximum benefit from this program, assay data, assay protocols, and chemical structures of compounds tested are expected to be made publicly available, consistent with achieving the goals of the program.
For the purpose of this FOA, the following data generated or developed under this FOA are expected to be released to PubChem: (1) all assay data, (2) protocols for assays implemented, (3) the chemical structure of compounds tested in assays, and (4) synthetic protocols of chemicals.
Institute Interests
NIMH
NIMH is interested in applications proposing the optimization of chemical probes aimed at novel molecular, cellular, or circuit targets relevant to mental disorders, especially treatment-resistant depression, bipolar disorder, schizophrenia, Post-Traumatic Stress Disorder (PTSD), HIV-induced Central Nervous System (CNS) dysfunction and autism spectrum disorder (see From Discovery to Cure: Accelerating the Development of New and Personalized Interventions for Mental Illnesses). Studies aimed at the development of new ligands for targets where a high-quality probe or therapeutic already exists are generally of lower priority.
Projects aimed at the discovery of cell-based chemical probes should consider applying to the companion R21 initiative PAR-21-028. Projects at early stages of drug discovery and development should consider the Drug Discovery for Nervous System Disorders PAR-19-147 (R01) and PAR-19-146 (R21), and the National Cooperative Drug/Device Discovery/Development Groups (NCDDG) for the Treatment of Mental Disorders, Substance Use Disorders, or Alcohol Use Disorder PAR-20-119 (U19) and PAR-20-118 (U01). Projects for developing commercially focused products should consider applying to the NIMH SBIR/STTR Programs. Projects at the early clinical trials phase should consider the NIMH SBIR Program or the First in Human and Early Stage Clinical Trials of Novel Investigational Drugs or Devices for Psychiatric Disorders (U01) PAR-18-427. Details on these and additional funding opportunity announcements and therapeutic discovery resources are listed on the NIH/NIMH Therapeutics Discovery Research webpage.
The purpose of in vivo measures should be carefully considered. Given the lack of predictive preclinical behavioral measures of clinical efficacy for mental disorders, the NIMH is particularly interested in the development and testing of novel interventions that target operationally defined, biologically linked functional domains whose disruption is hypothesized to drive functional deficits in mental disorders. For example, NIMH Research Domain Criteria (RDoC) constructs may inform mechanism-based hypotheses and the selection of interventions, outcome measures, and clinical subjects. Intervention targets related to RDoC constructs and underlying circuits are of interest for this FOA, but other, biologically relevant targets are also of interest.
Scientific rigor and transparency in conducting biomedical research are key to the successful application of knowledge toward improving health outcomes. In support of this important goal, investigators must follow NIH Guidance on addressing rigor and reproducibility in grant applications.
Further information on NIMH research priorities can be found in the NIMH Strategic Plan, Strategic Research Priorities, and the Interventions Workgroup Report. Applicants are strongly encouraged to discuss applications with NIMH staff listed in Section VII prior to submission to determine the alignment of the planned studies with NIMH priorities and to assess whether this or other NIMH funding opportunities are most appropriate.
NIDA:
NIDA is interested in funding projects that will lead to the discovery and early development of chemical probes for the treatment of substance use disorders (SUDs). Proposal topics might include, for example, target identification/validation, assay development, lead discovery and/or preliminary, iterative chemical probe development (SAR). Chemical probes could be used as: (i) tools for elucidating SUD-related mechanistic processes, or (ii) future lead pharmacotherapeutic candidates for the treatment of SUDs. Projects that are further along in the medications development pipeline (e.g., lead optimization or preclinical IND-preparatory studies) should consider applying to alternative FOAs, such as PAR-19-327. Investigators are strongly encouraged to discuss potential research plans with the scientific contact below prior to submission.
NIA:
NIA is interested in High-Throughput Screening (HTS) assays and chemical probes that are relevant to the process of normal aging (including normal cognitive aging) and age-related diseases and conditions in a variety of tissues. Examples include Mild Cognitive Impairment (MCI), Alzheimer’s disease and other dementias of aging, osteoporosis, sarcopenia, and other age related changes that occur during the human lifespan. NIA is particularly interested in assays and chemical probes that will be useful in identifying new therapeutic targets and, novel therapeutic and imaging agents. NIA is also interested in assays to screen for compounds that affect protective factors or processes that may contribute to slowing or reversing the progression of age-related adverse molecular, biochemical, genetic, cellular, or physiological changes that contribute to multiple age-related diseases, and which hence could contribute to longer health span
NEI:
The NEI is especially interested in applications to develop novel, clinically relevant targets, which can be transformed into therapeutics for the treatment of visual diseases and disorders. Appropriate research areas include, but are not limited to, inflammatory, vascular, and degenerative diseases of the eye, such as diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa, glaucoma, ocular infections, corneal wound healing, and dry eye syndrome. Proposed projects should be relevant to NEI’s mission of supporting basic science discoveries and translating these discoveries into new therapeutic interventions that will lead to sight-saving treatments, reduce visual impairment and blindness, and improve the quality of life for people of all ages.
See Section VIII. Other Information for award authorities and regulations.
Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.
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.
Need help determining whether you are doing a clinical trial?
The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.
The total project period may not exceed 4 years.
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
For-Profit Organizations
Local Governments
Federal Governments
Other
Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.
Applicant organizations
Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.
Program Directors/Principal Investigators (PD(s)/PI(s))
All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.
Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
Applicant organizations may submit more than one application, provided that each application is scientifically distinct.
The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:
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.
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.
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.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
Other Plan(s):
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:
Research Strategy: In the Research Strategy section, applicants must address the following topics as they pertain to the research project proposed:
1. Biological Target. The applicants should address the novelty and significance of the biological target or biological process. The applicant should clearly describe any known small molecule modulators and the need for better small molecule modulators against the intended biological target or biological process.
2. Validated Hits. Various approaches may be adopted toward pursuing a validated hit, including high throughput screening (HTS) of a large collection of structurally diversified or privileged compounds, virtual screening, fragment-based screening, affinity-based compound library screening, and structure-based de novo design. For a hit compound to be accepted as the starting point of this program, it should have the following well-characterized properties:
To enhance the likelihood of success of the project, the parallel optimization of multiple validated hits is highly encouraged.
3. Assays. A cascade of in vitro and in vivo assays needs to be in place to efficiently test analog compounds derived from the submitted hits. The applicants are expected to perform in vitro and in vivo SAR assays related to their research fields. The in vitro SAR assays may include target-, pathway-, and phenotype-based assays. Some examples are a) target-based biochemical or cellular assays that measure activities of enzymes, receptor-ligand bindings, protein-protein interactions, ion channels, transporters, nuclear receptors, and other new targets emerging from genetic and other omics research in model systems and in human diseases; b) cell- or organism-based assays that detect phenotypic changes that may involve unidentified molecular targets; and c) non-traditional targets of interest such as nucleic acids, protein folding, polymorphic gene products, post-transcriptional editing or splicing of gene products, and protein or RNA stabilization. The assay detection methods may include fluorescence, luminescence, absorbance, fluorescence resonance energy transfer (FRET), time-resolved fluorescence resonance energy transfer (TR-FRET), fluorescence polarization, flow cytometric measurements, fluorescence imaging, bioluminescence resonance energy transfer (BRET), AlphaScreen, scintillation proximity assay (SPA), electrophysiology, and varieties of biophysical readouts. Assays adaptable to microtiter plates (96-, 384-well plates) are advantageous in the rapid generation of assay data to enhance SAR iteration efficiency.
Applicants should clearly demonstrate that the proposed assays are adequate for the iterative study of structure-activity relationships and that the proposed assay reagents and protocols are in place and will be readily implemented.
The in vivo activity assays may be proof-of-concept assays using one, well-characterized animal species model. Recognizing that very few disease models are clinically validated, applicants are expected to present a convincing argument that the models selected, endpoints measured, and levels of activity observed are likely to be clinically relevant. These preclinical "proof-of-concept" studies must be sufficiently powered, controlled, and replicated to lend a high degree of confidence to the results.
4. Probe criteria. The application should (1) define the specific criteria that a compound must meet to be considered a probe for the project, (2) provide thorough literature and informatics analysis about any known small molecule probe for the intended biological target or biological process, and (3) provide evidence that the validated hit to be optimized is engaging its target in vivo.
5. Critical path. The application should include a flow diagram to outline all critical steps in sequential and/or parallel manners with appropriate benchmarks and timelines, including but not limited to iterative chemical optimization and bioassays to be implemented, alternative approach (e.g., computational docking) to ensure the success of the probe discovery, in vivo pharmacokinetic/pharmacodynamic assays to characterize chemical probes, the study of structure-activity relationships, assay and chemistry responsibilities of each party involved.
6.Future plan. The application should also include a plan to briefly describe existing and potential follow-up assays to advance chemical probes in the future.
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:
For the purpose of this FOA, the following data generated or developed under this FOA are expected to be released to PubChem, consistent with achieving the goals of this program:
Applications should include a statement of willingness to deposit the aforementioned data to PubChem within the Data Sharing section of the application.
Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
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.
All instructions in the SF424 (R&R) Application Guide must be followed.
Foreign Institutions
Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.
See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov
Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.
Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.
Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.
Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.
This initiative is not subject to intergovernmental review.
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Pre-award costs are allowable only as described in the NIH Grants Policy Statement.
Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.
Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.
For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.
Important reminders:
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile 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 and responsiveness by components of participating organizations, 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.
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.
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.
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.
Significance
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?
How well are the goals defined for the use of the identified chemical probes as research tools?
Investigator(s)
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?
How knowledgeable and experienced are the investigators to carry out the proposed assays for advancing active compounds? How knowledgeable and experienced are the investigators to conduct chemical optimization of the starting hit compounds?
Innovation
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?
How novel is the proposed biological target or biological process? How well does the application address whether or not known small molecule modulators are available for this biological target or biological process? How well does the application describe the need for better small molecule modulators against the biological target or biological process?
Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?
How well has the biological activity of the proposed hits been characterized and validated by orthogonal assays? How well have the biological and physicochemical qualities of the proposed hits been characterized for in vivo probe development? How appropriate are the proposed assays for the iterative study of structure-activity relationships? How readily available are the proposed assay reagents and protocols? How well described is the proposed chemical optimization approach?
If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?
Environment
Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?
As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.
Protections for Human Subjects
For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.
Inclusion of Women, Minorities, and Individuals Across the Lifespan
When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.
Vertebrate Animals
The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.
Biohazards
Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.
Resubmissions
For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.
Renewals
Not applicable
Revisions
For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.
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.
As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.
Applications from Foreign Organizations
Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.
Select Agent Research
Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).
Resource Sharing Plans
Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).
Authentication of Key Biological and/or Chemical Resources:
For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.
Budget and Period of Support
Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.
Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the Center for Scientific Review, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.
As part of the scientific peer review, all applications will receive a written critique.
Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
Information regarding the disposition of applications is available in the NIH Grants Policy Statement.
A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.
Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.
Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.
Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.
All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.
Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html.
HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.
Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.
In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.
Not Applicable
Data Management and Sharing
Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.
Consistent with the NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.
A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.
The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.
In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.
We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-637-3015
Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov
Enrique L. Michelotti, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-443-5415
Email: michelottiel@mail.nih.gov
Lorenzo M. Refolo, PhD
National Institute on Aging (NIA)
Telephone: 301-594-7576
Email: refolol@nih.gov
Paek Lee, Ph.D.
National Eye Institute (NEI)
Telephone: 301-451-2020
Email: paek.lee@nih.gov
Sam Ananthan, Ph.D.
National Institute on Drug Abuse (NIDA)
Telephone: 301-435-2199
Email: sam.ananthan@nih.gov
Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).
Tamara Kees
National Institute of Mental Health (NIMH)
Telephone: 301-443-8811
Email: tkees@mail.nih.gov
Traci Lafferty
National Institute on Aging (NIA)
Telephone: 301-496-8987
Email: laffertt@nia.nih.gov
Ms. Karen Robinson Smith
National Eye Institute (NEI)
Telephone: 301-451-2020
Email: kyr@nei.nih.gov
Pam Fleming
National Institute on Drug Abuse (NIDA)
Telephone: 301-480-1159
Email: pfleming@mail.nih.gov
Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.