National Institutes of Health (NIH)
National Institute of Mental Health (NIMH)
Funding Opportunity Title
Solicitation of Validated Hits for the Discovery of in vivo Chemical Probes (R01)
R01 Research Project Grant
Funding Opportunity Announcement (FOA) Number
Catalog of Federal Domestic Assistance (CFDA) Number(s)
93.242, 93.393, 93.394, 93.395, 93.396, 93.399, 93.867, 93.866, 93,273, 93.846, 93.865, 93.173, 93.279, 93.859, 93.273
This Funding Opportunity Announcement (FOA) intends to support investigators who have interest and capability to join efforts for the discovery of in vivo chemical probes. 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 studying disease treatment relevant to the missions of the participating NIH Institutes, and 2) discovery and/or validation of novel, biological targets that will inform studies of disease mechanisms. Emphasis will be placed on assays that provide new insight into important disease targets and processes.
December 13, 2011
Open Date (Earliest Submission Date)
January 5, 2012
Letter of Intent Due Date
30 days prior to the anticipated application due date.
Application Due Date(s)
Standard dates apply, by 5:00 PM local time of applicant organization.
AIDS Application Due Date(s)
Standard dates apply, by 5:00 PM local time of applicant organization.
Scientific Merit Review
Standard dates apply
Advisory Council Review
Standard dates apply
Earliest Start Date(s)
Standard dates apply
September 8, 2014
Due Dates for E.O. 12372
Required Application Instructions
It is critical that applicants follow the instructions in the SF 424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the 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 the 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
Recent technological innovations in chemical synthesis, cheminformatics, 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 environment. This provides an unprecedented opportunity for investigators to translate knowledge about diseases into tangible tools and to reshape their research frontier toward a cure. This Funding Opportunity Announcement (FOA) is to support investigators who have interest and capability to join effort for the discovery of in vivo chemical probes. Applicants to this FOA must have in hand the starting compounds (“validated hits”) for chemical optimization and bioassays for testing new analog compounds.
Through this FOA, NIH aims to stimulate research in 1) discovery and development of novel in vivo chemical probes for their potential use in studying disease treatment 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 disease mechanisms. Emphasis will be placed on the research that provides new insight into important disease targets and 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, which ultimately allows the researchers to take a holistic approach and make rapid progress toward successful development of in vivo chemical probes. The iterative bioassay and chemical optimization cycles may encompass:
The above-mentioned areas of investigation are representative and not meant to be all-inclusive. Investigators are encouraged to explore novel cost effective approaches to the discovery of in vivo chemical probes. Extensive studies required for the clinical development of candidate therapeutics, such as IND-directed toxicological testing and GMP synthesis, are beyond the scope of this FOA, but the participating institutes provide funding opportunities and resources available to investigators for some of these efforts as listed below in section "Institute Interests."
In addition, the NIH Rapid Access to Interventional Development (NIH-RAID) Program (www.nihroadmap.nih.gov/raid), offers investigators access to preclinical development resources on a competitive basis.
Note: Applicants are encouraged to take advantage of the resources provided by the NIH Clinical & Translational Science Awards (CTSAs) program, (http://www.ctsacentral.org/) to leverage resources for therapeutic discovery in areas described in this FOA. CTSA resources include, for example, core facilities, super computer centers, biostatistics, bioinformatics, community engagement network, tissue repositories, and animal models. For more information about resources available at individual CTSAs, please contact the Program Officials listed at http://www.ctsaweb.org/index.cfm?fuseaction=home.showProgGrantOfficials.
1. Validated Hits. Various approaches may be adopted to 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 one-bead one-compound library screening, and structure-based de novo design. For a hit compound to be accepted as the starting point of this program, it must have the following well-characterized properties:
When possible, multiple series of scaffolds may be submitted for parallel optimization to enhance the success likelihood of the project.
2. 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 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 proteomic 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 rapid generation of assay data to enhance SAR iteration efficiency.
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.
A Chemical Probe Development Plan (CPDP) should be developed at the beginning of the project based on the awarded research proposal by a team composed of the screening staff, the assay submitter, and an NIH program staff. The CPDP outlines the projected probe development path and predicts appropriate benchmarks and timelines. Importantly, the CPDP defines the specific criteria that a compound must meet to be considered a probe for the project. The CPDP discussion should include discussion of prior art of chemical probes, probe definition, assay responsibilities, planned follow-up assays, structure-activity relationships of bioactive compounds, and a flowchart to summarize critical path to the probe discovery.
Since an important goal of the NIH is to rapidly disseminate new and important information, awardees will work together with the PubChem staff to ensure fidelity of the data (http://pubchem.ncbi.nlm.nih.gov). Awardees will submit annual Progress Report to summarize the project progress and data generated in all assays.
NIH program staff will review the success of the project based on the Progress Report and the PubChem data to determine feasibility of advancing the project.
A goal of the program is to further research advancements across the scientific community as rapidly as possible. This will require synergies that can be achieved through broad sharing of research efforts in a collaborative and cooperative research environment. It will take the combined resources of researchers in the public and private sectors many years to use small molecule probes to characterize the biology of genes and proteins of interest, cellular processes, and disease processes, and then to use that information to develop products and other approaches that will improve public health. The open sharing of data, research tools, and resources will not only encourage scientific rigor in probe discovery process, but also lead more rapidly to the identification and validation of novel targets for drug discovery, and will facilitate more rapid development of therapeutics by both the private and public sectors, with resulting benefits to public health, especially for rare and neglected disorders. In order to reap the maximum benefit from this program, assay data, assay protocols, and chemical structures of compounds tested will be made publicly available.
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: (1) all assay data, (2) protocols for assays implemented, and (3) the chemical structure of compounds tested in assays.
Applications in response to this FOA should include a statement of willingness to deposit the aforementioned data to PubChem.
Projects awarded under this FOA are subject to oversight and review by each of the following entities.
The participating NIH ICs will be responsible for making the award according to their respective missions to support basic and clinical research. For each awarded research project, the participating IC will delegate a program staff to join meeting discussions on the Chemical Probe Development Plan and participate in coordination of the project.
NIH PROJECT TEAM. The NIH Project Team composed of the participating IC staff will serve as the governing body that oversees the data deposition to PubChem.
NIMH: The NIMH is especially interested in applications for novel clinically relevant targets with the goal of transforming target discovery into therapeutic treatment of mental disorders such as depressive disorder, bipolar disorder, schizophrenia, anxiety disorders, panic disorder, autism, etc. Proposed projects should be relevant to NIMHs mission of supporting basic science discoveries and translating these discoveries into new therapeutic interventions that will relieve the suffering of people with mental disorders. NIMH encourages cross-disciplinary collaboration among NIMH-funded existing research, such as Psychopharmacology, Neuropharmacology, Molecular Pharmacology Research, and Genetic Basis of Mental Disorders Programs. Investigators should consider the following funding opportunities: Drug Discovery for Nervous System Disorders PAR-10-001, PAR-10-002, and Optimization of Small Molecule Probes for the Nervous System PAR-09-251, in case they do not plan to access the MLPCN resources.
NCI: Validated hits that are pertinent to the mission of NCI should be justified in the application as relevant to cancer. The NCI is particularly interested in validated hits for targets that address unmet needs in the prevention, treatment, or diagnosis of cancer. Strategies that include testing of in vivo chemical probe activity in primary human tumor cells are encouraged. In vivo chemical probes may be appropriate for entry in the NCI Experimental Therapeutics Program (NExT) for further development to clinical candidate status and testing in clinical trial. See http://next.cancer.gov/ for the NExT application process. Applicants may also find the NCI Developmental Therapeutics Program (http://dtp.nci.nih.gov) resources to be helpful.
NEI: The NEI is especially interested in applications to develop novel, clinically-relevant targets, which can be transformed into therapeutics for 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.
NIA: NIA is interested in 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, progeroid syndromes, 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.
NIAAA: NIAAA is interested in applications for novel clinically-relevant targets with the goal of transforming target discovery into treatment of alcohol dependence. NIAAA is also interested in as the development of novel ligands to be used as tools for investigating biological processes contributing to alcohol dependence. Alcohol dependence is a complex disorder involving many neurotransmitter receptors and transporters, ion channels, neuromodulators, hormones, and intracellular signaling networks. This provides a number of potential target sites for which new pharmaceutical agents may be developed. Examples of interest include: effectors of opioid, glutamate, GABA, cannabinoid, and adenosine receptors, modulators of neuropeptide systems (e.g., NPY, CRF, substance P, orexin), agents that alter signal transduction pathways (such as protein kinase effectors, protein phosphatase inhibitors, G-protein regulators and calcium signaling disruptors), and modulators of neuroimmune and neuroinflammatory pathways. In case a screening campaign yields promising bioactive hits, investigators are encouraged to consider the following funding opportunities: Drug Discovery for Nervous System Disorders PAR-10-001, PAR-10-002; Optimization of Small Molecule Probes for the Nervous System PAR-09-251.
NIAMS: NIAMS is interested in discovery and development of novel small molecules that can be used to treat diseases or understand disease mechanisms in the areas of arthritis and musculoskeletal and skin diseases. Potential applicants are encouraged to review the NIAMS mission (http://www.niams.nih.gov/About_Us/Mission_and_Purpose/mission.asp) and the NIAMS long-range plan (http://www.niams.nih.gov/About_Us/Mission_and_Purpose/long_range.asp) for more information.
NICHD: NICHD is interested in projects that will lead to discovery of chemical probes of developmental targets relevant to pregnancy and pediatric-related conditions. Potential applicants are encouraged to review the NICHD mission http://www.nichd.nih.gov/about/overview/mission/ and vision http://www.nichd.nih.gov/vision/ and to contact NICHD program listed on this FOA prior to submitting an application.
NIDA: NIDA is particularly interested in novel targets that may lead to the development of pharmacotherapeutics for drug addiction as well as novel targets for pharmacotherapeutics to treat chronic pain that are likely to have low addiction liability. NIDA is also interested in compounds that are selective for or against reported human genetic and epigenetic variants of known targets for drug addiction, where the variant is associated with risk for or protection against dependence or addiction. Projects that are further along in the medications development pipeline, may want to consider applying under PAR-11-109.
NIDCD: The NIDCD is interested in the development of chemical probes that might have potential therapeutic value in the treatment, protection or prevention of communication disorders, including hearing, balance, smell/taste, voice, speech and language. Applications could include, but are not limited to, identification of clinically-relevant targets that might lead to translatable therapeutics in hearing/balance areas of otoprotection, regeneration, otitis media, tinnitus, and normal/abonormal development; chemosensory abnormalities such as they relate to serious diseases of obesity, diabetes, Parkinson’s disease, Alzheimer’s disease, and multiple sclerosis; disorders involving voice speech, language, including swallowing, aphasia or dysarthria, and laryngeal replacement. Potential applicants are encouraged to review the NIDCD mission http://www.nidcd.nih.gov prior to submitting an application.
NIGMS: The NIGMS welcomes projects that are relevant to the Institute's mission: basic scientific research that increases understanding of life processes and lays the foundation for more applied advances in disease diagnosis, treatment, and prevention. NIGMS-funded researchers seek to answer important scientific questions in fields such as cell biology, biophysics, genetics, developmental biology, pharmacology, physiology, biological chemistry, bioinformatics, computational biology, selected aspects of the behavioral sciences, and specific cross-cutting clinical areas that affect multiple organ systems.
NINDS: The NINDS is exclusively interested in applications to optimize probes for preclinical, in vivo proof-of-concept experiments for the purposes of drug discovery. The disease indication must be a neurological disease or disorder within the NINDS mission, for which NINDS serves as the lead NIH institute. An NINDS application must include both medicinal chemistry optimization and an in vivo proof-of-concept study with the optimized compound. Projects that complete both phases may then be eligible for the NINDS Cooperative Program in Translational Research (http://www.ninds.nih.gov/research/translational/index.htm). There is increasing awareness among neurological disease communities that to assess the predictive value of preclinical research, sufficient information must be available about study design, execution, analysis, and interpretation. Examples of the critical elements of a well-designed study are summarized on the NINDS website (http://www.ninds.nih.gov/funding/grant_policy.htm). NINDS urges applicants to consider these elements when describing supporting data and designing the proposed in vivo studies. Investigators are strongly encouraged to consult the NINDS Program Officer listed in Section VII in preparing an application for this FOA.
Application Types Allowed
The OER Glossary and the SF 424 (R&R) Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards
The number of awards is contingent upon NIH appropriations, and the submission of a sufficient number of meritorious applications.
Application budgets need to reflect the actual needs of the proposed assay and chemical optimization costs.
To prevent budget overlap , applicants who will access assay and chemistry resources at an MLPCN center or other funded resources, may only request a budget to cover costs outside the funded resources.
Award Project Period
The total project period for an application submitted in response to this funding opportunity may not exceed 3 years.
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to 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
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.
Applicant organizations must complete the following registrations
as described in the SF 424 (R&R) Application Guide to be eligible to apply
for or receive an award. Applicants must have a valid Dun and Bradstreet
Universal Numbering System (DUNS) number in order to begin each of the following
All Program Director(s)/Principal Investigator(s) (PD(s)/PI(s))
must also work with their institutional officials to register with the eRA Commons
or ensure their existing eRA Commons account is affiliated with the eRA Commons
account of the applicant organization.
All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least 4-6 weeks prior to the application due date.
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 PD(s)/PI(s), visit the Multiple Program Director(s)/Principal Investigator(s) Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (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.
NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.
Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the “Apply for Grant Electronically” button in this FOA or following the directions provided at Grants.gov.
It is critical that applicants follow the 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.
For information on Application Submission and Receipt, visit Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.
Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.
By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:
The letter of intent should be sent to:
Yong Yao, Ph.D.
Division of Neuroscience and Basic Behavioral Science
National Institute of Mental Health
6001 Executive Boulevard, Room 7175, MSC 9641
Bethesda, MD 20892-9641
Telephone: (301) 443-6102
The forms package associated with this FOA includes all applicable components, mandatory and optional. Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate “optional” components.
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.
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 (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modifications:
Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
Foreign (non-US) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.
Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit in advance of the deadline to ensure they have time to make any application corrections that might be necessary for successful submission.
Organizations must submit applications via 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.
Applicants are responsible for viewing their application 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 SF 424 (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 Applying Electronically.
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF 424(R&R) Application Package. Failure to register in the Commons and to include a valid PD(s)/PI(s) Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.
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 Central Contractor Registration (CCR). 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 by the Center for Scientific Review, NIH. Applications that are incomplete will not be reviewed.
Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact NIH program staff 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 SF 424 (R&R) Application Guide.
Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.
Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.
Reviewers will provide an overall impact/priority 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? 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? Are there important and well-defined goals for the use of chemical probes identified with the proposed assays, either as research tools or for therapeutics development?
Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or 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(s)/PI(s), do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? Are the investigators reasonably knowledgeable and experienced about the biological target area of science? Are the investigators reasonably knowledgeable and experienced to carry out the assays and capable of advancing active compounds? Are the investigators reasonably knowledgeable and experienced to conduct chemical optimization efficiently in a cost effective manner?
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? Is this project for a novel biological target or process? Does the application address whether or not there are known small molecule modulators available for this biological target or process? Is there a need for better small molecule modulators against the target or process?
Are the overall strategy, methodology, and analyses
well-reasoned and appropriate to accomplish the specific aims of the project?
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
If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?
Has the biological activity of the hits been adequately characterized and validated by orthogonal assays? Are the biological and physicochemical qualities of the hits adequate as the starting material for in vivo probe development? Are the proposed assays adequate for the iterative study of structure-activity relationships? If so, are the proposed assay reagents and protocols in place and will they be readily implemented? Is the proposed chemical optimization approach adequate and efficient?
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/priority 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 six 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 six 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 Human Subjects Protection and Inclusion Guidelines.
Inclusion of Women, Minorities, and Children
When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.
The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.
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.
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.
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.
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/priority 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) Genome Wide Association Studies (GWAS).
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), in accordance with NIH peer review policy and procedures, using the stated review criteria. Review assignments will be shown in the eRA Commons.
As part of the scientific peer review, all applications:
Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the appropriate National Advisory Council or Board. The following will be considered in making funding decisions:
After the peer review of the application is completed, the PD(s)/PI(s) will be able to access his or her Summary Statement (written critique) via the eRA Commons.
Information regarding the disposition of applications is available in the NIH Grants Policy Statement.
If the application is under consideration for funding, NIH
will request "just-in-time" information from the applicant as described
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 the DUNS, CCR Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.
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.
Cooperative Agreement Terms and Conditions of Award
When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.
A final progress report, 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.
We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
GrantsInfo (Questions regarding application instructions and
process, finding NIH grant resources)
eRA Commons Help Desk(Questions regarding eRA Commons
registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
National Institute on Drug Abuse (NIDA)
Telephone: (202) 526-0108
Lisa A Moeller
National Institute of General Medical Sciences (NIGMS)
Telephone: (301) 594-3914
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 Parts 74 and 92.
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