National Institutes of Health (NIH)
National Center for Advancing Translational Sciences (NCATS)
National Institute on Aging (NIA)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
National Institute of Dental and Craniofacial Research (NIDCR)
National Institute on Drug Abuse (NIDA)
National Institute of Neurological Disorders and Stroke (NINDS)
National Center for Complementary and Integrative Health (NCCIH)
National Cancer Institute (NCI)
R21 Exploratory/Developmental Research Grant
NOT-OD-23-012 Reminder: FORMS-H Grant Application Forms and Instructions Must be Used for Due Dates On or After January 25, 2023 - New Grant Application Instructions Now Available
NOT-OD-22-190 - Adjustments to NIH and AHRQ Grant Application Due Dates Between September 22 and September 30, 2022
NCATS is issuing this FOA in response to the declared public health emergency issued by the Secretary, HHS. Please see Determination that a Public Health Emergency Exists Nationwide as the Result of the Opioid Crisis as renewed in Renewal of the Determination that a Public Health Emergency Exists Nationwide as the Result of the Continued Consequences of the Opioid Crisis.
The purpose of this funding opportunity announcement (FOA) is to support early-stage research projects focusing on the identification of new druggable targets for pain, opioid use disorder and/or overdose within the understudied druggable proteome. This FOA is part of the NIH Helping to End Addiction Long Term (HEAL) initiative to accelerate the development of novel medications to treat all aspects of the opioid addiction cycle, including progression to chronic use, withdrawal symptoms, craving, relapse, and overdose.
15 days prior to the application due date
| Application Due Dates | Review and Award Cycles | ||||
|---|---|---|---|---|---|
| New | Renewal / Resubmission / Revision (as allowed) | AIDS | Scientific Merit Review | Advisory Council Review | Earliest Start Date |
| February 28, 2022 | Not Applicable | Not Applicable | Not Applicable | Not Applicable | July 2022 |
| August 22, 2022 | Not Applicable | Not Applicable | Not Applicable | Not Applicable | January 2023 |
| May 22, 2023 | Not Applicable | Not Applicable | Not Applicable | Not Applicable | October 2023 |
All applications are due by 5:00 PM local time of applicant organization.
Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
No late applications will be accepted for this Funding Opportunity Announcement.
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.
Purpose
NCATS is issuing this FOA in response to the declared public health emergency issued by the Secretary, HHS. Please see Determination that a Public Health Emergency Exists Nationwide as the Result of the Opioid Crisis as renewed in Renewal of the Determination that a Public Health Emergency Exists Nationwide as the Result of the Continued Consequences of the Opioid Crisis.
The NIH HEAL Initiative:
This study is part of the NIH’s Helping to End Addiction Long-term (HEAL) initiative to speed scientific solutions to the national opioid public health crisis. The NIH HEAL Initiative bolsters research across NIH to (1) improve treatment for opioid misuse and addiction and (2) enhance pain management. More information about the HEAL Initiative is available at: https://heal.nih.gov/.
This funding opportunity announcement (FOA) aims to support early-stage research to increase our knowledge of understudied proteins of the druggable proteome and enable the scientific community to identify and validate new targets for pain, opioid use disorder (OUD), and/or overdose (OD). These awards will support generation of preliminary data and tools around eligible understudied protein(s) identified by the HEAL Program with the intent of elucidating the function of these proteins in the context of pain, OUD and/or OD and obtaining sufficient preliminary data and/or research resources for subsequent R01 applications and/or drug discovery/development projects.
This Funding Opportunity Announcement does not accept applications proposing clinical trial(s).
Background
The human genome has revealed a great deal about the human proteome, though significant portions of the genome remain understudied. Only a subset of expressed proteins demonstrate the requisite properties to serve as targets for the development of therapeutics. Many bona fide drug targets likely remain to be discovered in the Druggable Proteome (DP), which can be defined as the fraction of proteins which have the ability to bind drug-like molecules. The term "drug-like" refers to the physical, biochemical, and pharmacological attributes of small molecule compounds that are generally recognized to be required for efficacious clinical drugs in humans. While the number of proteins in the DP is upwards of 4,500, the existing clinical pharmacopeia is represented by only a few hundred targets, leaving a huge swath of biology remaining unexploited.
The discovery of a disease association or the development of a useful tool or reagent can accelerate research into a previously understudied protein. Identifying new targets associated with pain, OUD, and overdose is a critical first step in the development of novel, efficacious treatments, with improved safety profiles, for these conditions. Many interesting and critical biological processes and potential therapeutic avenues remain unexplored because an initial catalyzing event has not yet occurred. The purpose of this FOA is to spark such catalyzing events through the support of small R21 awards to identify novel drug targets for the development of safe and efficacious medications to treat and/or prevent pain, OUD and OD.
Objectives and Scope
The goal of this specific solicitation would be to provide a needed opportunity for the collection of preliminary data around the role of understudied proteins in pain, opioid use disorder (OUD), and/or overdose (OD). This FOA would provide funding to support research that will identify new targets for pain, OUD, and/or OD among the understudied proteins of the Druggable Proteome. Many understudied proteins have been linked to pain or pain perception, opioid dependence and chronic pain. This indicates that there could be many more proteins within the DP that could serve as markers and/or drug targets for novel OUD treatment, OD and/or pain management.
Pharos, the user interface for the Common Fund Program Illuminating the Druggable Genome (IDG), provides facile access to a variety of data types around all proteins in the druggable proteome, including those proteins that are considered significantly understudied. Proteins listed within Pharos are assigned a target development level, which indicates the level of illumination of that particular protein. These development levels were used to determine which proteins are most understudied within the Druggable Proteome. Proteins eligible for study under this funding announcement are pulled from commonly druggable protein families and are classified on Pharos as Tdark or Tbio, the two lowest illumination levels.
A protein is considered Tdark if it meets the following criteria:
- Pubmed score of <5 (derived from text mining Pubmed extracts, this counts the number of publications that focus on a particular protein, and includes fractional counting of abstracts that mention multiple proteins [Pletscher-Frankild’s et al. 2015])
- Gene References Into Functions (RIFs) <3 (GeneRIFs document experiments that add to our understanding of a gene and its function)
- Available antibodies <50
A protein is considered Tbio if it meets the following criteria:
- Pubmed score of = 5
- Gene RIFs > 3
- Antibodies >50
- Availability of a Gene Ontology Molecular Function, which provides a role for a protein within a cell or tissue (e.g., catalysis, transport)
- Availability of an Online Mendelian Inheritance in Man phenotype provides a molecular relationship between genetic variation and phenotypic expression.
The full list of eligible targets can be found here. The list of eligible targets will not change while this FOA is active. ONLY APPLICATIONS THAT FOCUS ON PROTEINS LISTED ON THIS LIST, AS WELL AS MEETING THE RESPONSIVENESS CRITERIA BELOW, WILL BE CONSIDERED RESPONSIVE TO THIS FOA. ALL OTHER APPLICATIONS WILL BE CONSIDERED NON-RESPONSIVE AND WILL BE RETURNED TO THE APPLICANT WITHOUT REVIEW.
Applicants should provide the Uniprot number for the protein(s) that will be the focus of their application at the top of page one of their Research Plan, which will allow NIH to quickly identify those projects that are responsive to this FOA.
A significant percentage of the proteins within the druggable proteome are classified either Tdark or Tbio, thus there is sizable opportunity for the discovery and development of new targets for pain, OUD and/or OD within the understudied druggable proteome. Sufficient justification should be provided to indicate why particular protein(s) were chosen for study in the context of their potential role in pain, OUD and/or OD. Those projects employing methods that identify multiple proteins for study from the above link are acceptable but require justification as to why those proteins were chosen for study within the context of pain, OUD and/or OD, beyond the fact that they are on the eligible protein list provided.
Examples of potential research areas could include:
- Isolation and purification of understudied proteins and in vitro/in vivo characterization with the intent of developing novel therapeutics;
- Verification or placement of understudied protein(s) in signaling cascades, including upstream signals and downstream activities in order to better understand pain, OUD, and/or OD targets;
- Identification and validation of new pain, OUD, or OD biomarkers;
- Pre-clinical animal studies of understudied proteins focused on therapeutic development;
- Characterization of cell- and tissue-specific protein expression, localization, and function of understudied protein(s) in native environments as they pertain to pain, OUD, and/or OD;
- Use of novel tools to validate preliminary disease or physiological associations with understudied proteins in animal models, biomimetic systems, or ex vivo human samples;
- Studies to establish preliminary structure-activity-relationships (SAR) between functions of an understudied protein and its ligands (e.g., small molecules, macrocycles, synthetic peptides) for future drug discovery projects.
In addition to scientific diversity, applicants should strive to incorporate diversity in their team development plan. Research shows that diverse teams working together and capitalizing on innovative ideas and distinct perspectives outperform homogenous teams. Scientists and trainees from diverse backgrounds and life experiences bring different perspectives, creativity, and individual enterprise to address complex scientific problems. There are many benefits that flow from a diverse NIH-supported scientific workforce, including: fostering scientific innovation, enhancing global competitiveness, contributing to robust learning environments, improving the quality of the research, advancing the likelihood that underserved or health disparity populations participate in, and benefit from health research, and enhancing public trust. Please refer to Notice of NIH's Interest in Diversity NOT-OD-20-031 for more details.
The NIH HEAL Initiative will require a high level of coordination and sharing between investigators. It is expected that NIH HEAL Initiative awardees will cooperate and coordinate their activities after awards are made by participating in Program Director/Principal Investigator (PD/PI) meetings, including an annual HEAL Investigators Meeting, as well as other activities.
The following will be considered non-responsive under this FOA and applications will be returned to the applicant without review:
- Projects that meet the NIH definition of a clinical trial;
- Projects where the majority of the proposed work focuses on proteins outside of those featured on this list;
- Applications that propose clinical drug development studies for understudied protein(s);
Information Relevant to Specific Institutes/Centers/Offices:
National Center for Complementary and Integrative Health (NCCIH)
NCCIH supports research exploring novel therapeutic targets for complementary and integrative health intervention to treat pain, opioid use disorder (OUD), and/or overdose (OD). Complementary interventions include dietary (e.g., special diets, dietary supplements, herbs, probiotics, and microbial-based therapies), psychological (e.g., meditation, hypnosis, music-based interventions, relaxation therapies), physical (e.g., acupuncture, massage, chiropractic manipulation, devices) approaches, or a combination of psychological and physical approaches (e.g., yoga, tai chi, dance therapies, some forms of art therapies). The dietary approaches include what have been previously categorized as natural products, whereas psychological and/or physical approaches encompass what have been commonly referred to as mind and body interventions. NCCIH is particularly interested in identification and validation of understudied proteins within druggable proteome that can be modulated with complementary and integrative health approaches in the context of pain, OUD and/or OD.
See Section VIII. Other Information for award authorities and regulations.
National Cancer Institute (NCI)
NCI is interested in supporting research examining the causes and treatment for cancer-related pain. NCI is particularly interested in supporting studies in the following areas that include, but are not limited to:
- Identifying novel mechanisms and biomarkers for sequelae with pain as a common phenotype
- Identifying novel targets for therapeutic development to treat pain-related sequelae where opioids are a less than optimal form of therapy
National Institute on Aging (NIA)
NIA strongly encourages investigators to discuss their research interests with NIA program staff prior to submitting their grant application. NIA encourages applications that investigate understudied, novel targets associated with pain in the context of aging and dementias to facilitate the development of safe and efficacious medications to treat and/or prevent pain in older adults and comorbidities including Alzheimer’s disease and related dementias. NIA intends to administer applications under this FOA that meet requirements central to NIA’s mission of improving the health and well-being of older adults through research.
National Institute of Dental and Craniofacial Research (NIDCR)
NIDCR strongly encourages investigators to discuss their research interests with NIDCR program staff prior to submitting their grant application. NIDCR encourages applications that investigate understudied, novel targets associated with orofacial pain conditions such as temporomandibular disorders, trigeminal neuropathic pain, orofacial dyskinesias and dystonias, and burning mouth syndrome.
National Institute of Neurological Disorders and Stroke (NINDS)
NINDS strongly encourages investigators to discuss their research interests with NINDS program staff prior to submitting their grant application. NINDS encourages applications that investigate understudied, novel targets associated with neuropathic pain, migraine, and headache.
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.
Not Allowed: Only accepting applications that do not propose clinical trials.
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.
NIH intends to fund an estimate of 15 awards for fiscal year 2022. Future year amounts will depend on annual appropriations.
The combined budget for direct costs for the two-year project period may not exceed $275,000. No more than $200,000 may be requested in any single year.
The total project period may not exceed two years.
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.
1. Eligible Applicants
Higher Education Institutions
- Public/State Controlled Institutions of Higher Education
- Private Institutions of Higher Education
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
- Hispanic-serving Institutions
- Historically Black Colleges and Universities (HBCUs)
- Tribally Controlled Colleges and Universities (TCCUs)
- Alaska Native and Native Hawaiian Serving Institutions
- Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)
Nonprofits Other Than Institutions of Higher Education
- Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
- Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)
For-Profit Organizations
- Small Businesses
- For-Profit Organizations (Other than Small Businesses)
Local Governments
- State Governments
- County Governments
- City or Township Governments
- Special District Governments
- Indian/Native American Tribal Governments (Federally Recognized)
- Indian/Native American Tribal Governments (Other than Federally Recognized)
Federal Governments
- Eligible Agencies of the Federal Government
- U.S. Territory or Possession
Other
- Independent School Districts
- Public Housing Authorities/Indian Housing Authorities
- Native American Tribal Organizations (other than Federally recognized tribal governments)
- Faith-based or Community-based Organizations
- Regional Organizations
Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are not 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.
- System for Award Management (SAM) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
- NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
- Unique Entity Identifier (UEI)- A UEI is issued as part of the SAM.gov registration process. SAM registrations prior to fall 2021 were updated to include a UEI. For applications due on or after January 25, 2022, the UEI must be provided on the application forms (e.g., FORMS-G); the same UEI must be used for all registrations, as well as on the grant application.
- Dun and Bradstreet Universal Numbering System (DUNS) Organization registrations prior to April 2022 require applicants to obtain a DUNS prior to registering in SAM. By April 2022, the federal government will stop using the DUNS number as an entity identifier and will transition to the Unique Entity Identifier (UEI) issued by SAM. Prior to April 2022, after obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
- In the case of Emergency awards, if the applicant is unable to comply with the requirement to complete and maintain SAM registration at the time of application submission, contact the agency immediately.
- eRA Commons - Once the unique organization identifier (DUNS prior to April 2022; UEI after April 2022) is established, organizations can register with eRA Commons in tandem with completing their full SAM and Grants.gov registrations; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
- Grants.gov Applicants must have an active SAM registration in order to complete the Grants.gov registration.
Program Directors/Principal Investigators (PD(s)/PI(s))
All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.
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.
2. Cost Sharing
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
3. Additional Information on Eligibility
Number of Applications
Applicant organizations may submit more than one application, provided that each application is scientifically distinct.
The NIH will not accept duplicate or highly overlapping applications under review at the same time, per 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:
- A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
- A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
- An application that has substantial overlap with another application pending appeal of initial peer review (see 2.3.9.4 Similar, Essentially Identical, or Identical Applications).
1. Requesting an Application Package
The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.
2. Content and Form of Application Submission
It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.Letter of Intent
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:
- Descriptive title of proposed activity
- Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
- Names of other key personnel
- Participating institution(s)
- Number and title of this funding opportunity
The letter of intent should be sent to:
NCATS Letters of Intent
Telephone:301-827-9549
Email: [email protected]
Page Limitations
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.
Instructions for Application Submission
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.
SF424(R&R) Cover
All instructions in the SF424 (R&R) Application Guide must be followed.
SF424(R&R) Project/Performance Site Locations
All instructions in the SF424 (R&R) Application Guide must be followed.
SF424(R&R) Other Project Information
All instructions in the SF424 (R&R) Application Guide must be followed.
SF424(R&R) Senior/Key Person Profile
All instructions in the SF424 (R&R) Application Guide must be followed.
R&R or Modular Budget
All instructions in the SF424 (R&R) Application Guide must be followed.
R&R Subaward Budget
All instructions in the SF424 (R&R) Application Guide must be followed.
PHS 398 Cover Page Supplement
All instructions in the SF424 (R&R) Application Guide must be followed.
PHS 398 Research Plan
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
Research Strategy:
The full list of eligible targets can be found here. ONLY APPLICATIONS THAT FOCUS ON PROTEINS LISTED ON THIS LIST, AS WELL AS MEETING THE OTHER RESPONSIVENESS CRITERIA LISTED, WILL BE CONSIDERED RESPONSIVE TO THIS FOA. ALL OTHER APPLICATIONS WILL BE CONSIDERED NON-RESPONSIVE AND WILL BE RETURNED TO THE APPLICANT WITHOUT REVIEW.
Applicants should provide the Uniprot number for the protein(s) that will be the focus of their application at the top of page one of their Research Plan, which will allow NIH to quickly identify those projects that are responsive to this FOA.
The proposed project must focus on one or more of the understudied proteins within the link above. The proposed research must be suitable and appropriate for generating preliminary data and/or research resources for subsequent submission of an R01 application or initiation of a drug discovery project. Sufficient justification should be provided to indicate why particular protein(s) were chosen for study in the context of their potential role in pain, OUD and/or OD. Those projects employing methods that identify multiple proteins for study from the above link are acceptable but require justification as to why those proteins were chosen for study within the context of pain, OUD and/or OD, beyond the fact that they are on the eligible protein list provided. Appropriate justification for the proposed approach can be provided through literature citations, data from other sources, or from investigator-generated data. The project should address critical barriers to understanding the role of understudied proteins in pain/OUD/OD and/or as novel therapeutic agents.
Well studied proteins may only be used in projects proposed for this FOA as controls for experiments involving eligible understudied proteins from the approved link above and shall not be the focus of experimental work.
The research strategy should describe the experimental design for obtaining robust and unbiased results, consideration of relevant biological variables, and authentication of key biological and/or chemical variables. Please refer to https://grants.nih.gov/policy/reproducibility/guidance.htm for guidance on NIH policy on enhancing reproducibility through rigor and transparency. For resources on preparing a rigorous application, please refer to https://grants.nih.gov/policy/reproducibility/resources.htm.
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:
Appendix:
Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
- No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.
PHS Human Subjects and Clinical Trials Information
When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the 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.
Delayed Onset Study
Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.
PHS Assignment Request Form
All instructions in the SF424 (R&R) Application Guide must be followed.
3. Unique Entity Identifier and System for Award Management (SAM)
See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov.
4. Submission Dates and Times
Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.
Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.
Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.
Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.
5. Intergovernmental Review (E.O. 12372)
This initiative is not subject to intergovernmental review.
6. Funding Restrictions
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Pre-award costs are allowable only as described in the NIH Grants Policy Statement.
7. Other Submission Requirements and Information
Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.
Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.
For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply 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 fieldof the Senior/Key Person Profile form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.
The applicant organization must ensure that the unique entity identifier (DUNS number or UEI as required) provided 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.
In order to expedite review, applicants are requested to notify the NCATS Referral Office by email at [email protected] when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.
Applications Involving the NIH Intramural Research Program
The requests by NIH intramural scientists will be limited to the incremental costs required for participation.As such, these requests will not include any salary and related fringe benefits for career, career conditional or other Federal employees (civilian or uniformed service) with permanent appointments under existing position ceilings or any costs related to administrative or facilities support (equivalent to Facilities and Administrative or F&A costs). These costs may include salary for staff to be specifically hired under a temporary appointment for the project, consultant costs, equipment, supplies, travel, and other items typically listed under Other Expenses. Applicants should indicate the number of person-months devoted to the project, even if no funds are requested for salary and fringe benefits.
If selected, appropriate funding will be provided by the NIH Intramural Program. NIH intramural scientists will participate in this program as PDs/PIs in accord with the Terms and Conditions provided in this FOA. Intellectual property will be managed in accord with established policy of the NIH in compliance with Executive Order 10096, as amended, 45 CFR Part 7; patent rights for inventions developed in NIH facilities are NIH property unless NIH waives its rights.
Should an extramural application include the collaboration with an intramural scientist, no funds for the support of the intramural scientist may be requested in the application. The intramural scientist may submit a separate request for intramural funding as described above.
Post Submission Materials
Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.
1. Criteria
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.
Review Process
Applications will be evaluated for scientific and technical merit by an appropriate merit review panel convened by NIH staff, in accordance with the review criteria specified in the FOA.
For this particular announcement, note the following:
The R21 exploratory/developmental grant supports investigation of novel scientific ideas or new model systems, tools, or technologies that have the potential for significant impact on biomedical or biobehavioral research. An R21 grant application need not have extensive background material or preliminary information. Accordingly, reviewers will emphasize the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Preliminary data are not required for R21 applications; however, they may be included if available.
Overall Impact
Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).
Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.
Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?
Specific to this FOA: Does the project help to elucidate the function and/or structure of the understudied protein(s) in pain, OUD and/or OD? Does the stated hypothesis provide sufficient justification to indicate why particular protein(s) were chosen?
Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?
Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?
Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have 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?
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? For this particular announcement, note the following How well does the Data Management and Sharing plan address the requirements of the HEAL Public Access and Data Sharing Policy?
Specific to this FOA: Is the proposed approach suitable and appropriate for generating preliminary experimental data and/or research resources for subsequent submission of an R01 application or initiation of a drug discovery project?
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.
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.
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.
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.
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.
Not Applicable.
Not Applicable.
Not Applicable.
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.
Not Applicable.
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).
Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1)) Genomic Data Sharing Plan (GDS).
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) and whether they address HEAL Initiative Public Access and Data Sharing Policy requirements.
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.
Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.
2. Review and Selection Process
Applications will be evaluated for scientific and technical merit by an appropriate review group using the stated review criteria.
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 assessment score.
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. The following will be considered in making funding decisions:
- Scientific and technical merit of the proposed project.
- Availability of funds.
- Relevance of the proposed project to program priorities.
- Increasing the diversity of approaches applied to the study of understudied proteins.
Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.
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. The following will be considered in making funding decisions:
- Scientific and technical merit of the proposed project.
- Availability of funds.
- Relevance of the proposed project to program priorities.
- Increasing the diversity of approaches applied to the study of understudied proteins.
3. Anticipated Announcement and Award Dates
After the merit review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for merit review, and earliest start date.
Information regarding the disposition of applications is available in the NIH Grants Policy Statement.
1. Award Notices
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 recipient's business official.
Recipients must comply with any funding restrictions described in Section IV.6. 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: Recipient 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 recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.
2. Administrative and National Policy Requirements
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, Recipients, and Activities, including of note, but not limited to:
- Federalwide Research Terms and Conditions
- Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
- Acknowledgment of Federal Funding
If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.
Should the applicant organization successfully compete for an award, 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 (including gender identify, sexual orientation, and pregnancy). This includes ensuring programs are accessible to persons with limited English proficiency and persons with disabilities. 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 https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/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.
- Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov.
- For information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including reasonable accommodations and making services accessible to them, see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.
- HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.
- For guidance on administering programs in compliance with applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.
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 and 2 CFR Part 200.206 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.
Not Applicable
3. Reporting
When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.
Funds awarded using appropriations provided by the Extending Government Funding and Delivering Emergency Assistance Act-September 20, 2021 will be issued in unique subaccounts in the HHS Payment Management System, and will require separate financial reporting from any other funds awarded.
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. NIH FOAs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.
The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipients 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 the threshold. 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 2 CFR Part 200.113 and Appendix XII to 45 CFR Part 75 and 2 CFR Part 200, 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 and 2 CFR Part 200 Award Term and Condition 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: [email protected] (preferred method of contact)
Telephone: 301-480-7075
Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]
Karlie Sharma, Ph.D.
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-451-4965
Email: [email protected]
Inna Belfer, MD, Ph.D.
National Center for Complementary and Integrative Health (NCCIH)
Phone: 301-435-1573
Email: [email protected]
Rachel Altshuler, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-5873
Email: [email protected]
Devon Oskvig, Ph.D.
National Institute on Aging (NIA)
Phone: 301-827-5899
Email: [email protected]
Mark Egli
National Institute On Alcohol Abuse And Alcoholism (NIAAA)
Phone: 301-594-6382
E-mail: [email protected]
Rebecca Lenzi, Ph.D.br />
National Institute Of Arthritis And Musculoskeletal And Skin Diseases (NIAMS)
Phone: 301-402-4735
E-mail: [email protected]
Subramaniam Ananthan
National Institute On Drug Abuse (NIDA)
Phone: 301-435-2199
E-mail: [email protected]
Melissa M Ghim, Ph.D.
National Institute Of Dental & Craniofacial Research (NIDCR)
Phone: (301) 529-6570
E-mail: [email protected]
Michael Oshinsky, PhD
National Institute of Neurological Disorders & Stroke
Phone: (301) 496-9964
Email: [email protected]
Alumit Ishai, Ph.D.
National Center for Advancing Translational Sciences (NCATS)
Phone: 301-496-9539
E-mail: [email protected]
Shannon Oden
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-594-3028
Email: [email protected]
Shelley Headley
National Center for Complementary and Integrative Health (NCCIH)
Phone: 301-594-3788
Email: [email protected]
Sean Hine
National Cancer Institute (NCI)
Telephone: 240-276-6291
Email: [email protected]
Paolo Arguinzoni-Urrutia
National Institute on Aging (NIA)
Phone: 301-827-5985
Email: [email protected]
Judy Fox
National Institute On Alcohol Abuse And Alcoholism (NIAAA)
Phone: (301) 443-4704
E-mail: [email protected]
Erik Edgerton
National Institute Of Arthritis And Musculoskeletal And Skin Diseases (NIAMS)
Phone: 301-594-7760
E-mail: [email protected]
Pamela G Fleming
National Institute On Drug Abuse (NIDA)
Phone: 301-480-1159
E-mail: [email protected]
Diana Rutberg, MBA
National Institute Of Dental & Craniofacial Research (NIDCR)
Phone: (301) 594-4798
E-mail: [email protected]
Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS)
Email: [email protected]
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 and 2 CFR Part 200.
and Human Services (HHS)
