Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute of Neurological Disorders and Stroke (NINDS)

National Institute on Aging (NIA)

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

National Institute of Dental and Craniofacial Research (NIDCR)

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

National Institute on Drug Abuse (NIDA)

National Center for Complementary and Integrative Health (NCCIH)

National Cancer Institute (NCI)

Funding Opportunity Title
HEAL Initiative: Development and Validation of Non-Rodent Mammalian Models of Pain (R01 Clinical Trial Not Allowed)
Activity Code

R01 Research Project Grant

Announcement Type
New
Related Notices

NOT-OD-22-190 - Adjustments to NIH and AHRQ Grant Application Due Dates Between September 22 and September 30, 2022

Funding Opportunity Announcement (FOA) Number
RFA-NS-22-070
Companion Funding Opportunity
None
Assistance Listing Number(s)
93.853, 93.279, 93.396, 93.395, 93.399, 93.121, 93.847, 93.846, 93.213, 93.865, 93.273, 93.866
Funding Opportunity Purpose

This funding opportunity announcement (FOA) invites research to develop, characterize, and rigorously validate non-rodent mammalian models of pain, associated outcome measures and/or endpoints that will significantly advance translational research for effective pain management. These models are expected to recapitulate molecular, cellular, pathological, behavioral, and/or cognitive aspects of human pain disorders and conditions. Research supported under this FOA is expected to provide well-validated models and measures that facilitate the development of non-opioid analgesic therapeutic interventions with little or no addiction liability.

Key Dates

Posted Date
August 09, 2022
Open Date (Earliest Submission Date)
October 04, 2022
Letter of Intent Due Date(s)

30 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
November 04, 2022 November 04, 2022 Not Applicable March 2023 May 2023 July 2023
March 07, 2023 March 07, 2023 Not Applicable July 2023 October 2023 December 2023
July 06, 2023 July 06, 2023 Not Applicable November 2023 January 2024 April 2024
November 07, 2023 November 07, 2023 Not Applicable March 2024 May 2024 July 2024
March 06, 2024 March 06, 2024 Not Applicable July 2024 October 2024 December 2024

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.

Expiration Date
March 07, 2024
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

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

Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

  1. Use the NIH ASSIST system to prepare, submit and track your application online.
  2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.

  3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.


  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose

This funding opportunity announcement (FOA) supports research to develop, characterize, and rigorously validate non-rodent mammalian models of pain, associated outcome measures and/or endpoints that will significantly advance translational research for effective pain management. These models are expected to recapitulate molecular, cellular, pathological, behavioral, and/or cognitive aspects of human pain disorders and conditions. Research supported under this FOA is expected to provide well-validated models and measures that facilitate the development of non-opioid analgesic therapeutic interventions.

This FOA is not specific for any one or group of pain conditions. Projects focused on acute pain, chronic pain, painful neuropathy, musculoskeletal pain, headache disorders, osteoarthritis, diabetic neuropathy, chemotherapy-induced neuropathy, eye pain, sickle-cell pain, post-surgical pain, cancer pain, visceral pain, obstetric pain, gynecologic pain, post stroke pain, myofascial pain, painful disorders of the orofacial region, pain co-occurring with substance use disorders, pain across the lifespan and in the context of aging, and other conditions will be considered.

Background

This funding opportunity announcement 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/.

More than 25 million Americans suffer from daily chronic pain, a highly debilitating medical condition that is complex and difficult to manage. In recent decades, there has been an overreliance on the prescription of opioids for chronic pain despite their poor ability to improve function and high addiction liability. This contributed to a significant and alarming epidemic of opioid addictions and overdose deaths. Innovative scientific solutions to develop alternative pain treatment options are thus critically needed.

Animal models are critical to the understanding of pain biology and development of effective therapeutics. To date, basic and translational research in pain has predominantly been done using rodent models. These models have substantially advanced the field of pain research, and their utility for drug discovery has been well-documented. However, limitations remain regarding the value of rodent models to accurately predict analgesic efficacy in human clinical populations, which may be due in part to species differences. Additional models are needed to address gaps for pain conditions that cannot or have not been adequately modeled in rodents due to, for example, anatomical considerations, species-specific pharmacology, discordant time course of disease progression, or lack of diversity of experienced symptoms often associated with human pain conditions. Non-rodent mammalian models such as canines, felines, and swine, among others, have similarities to humans in genetics, anatomy, size, metabolism, and physiology that may be advantageous for their recapitulation of certain disease phenotypes. These model systems also present unique translational opportunities for developing and testing novel devices and pain therapies for humans. Knowledge of the validity and utility of different pain models and associated outcome measures, combined with a more comprehensive understanding of the mechanisms of pain across species, will allow researchers to make well-informed decisions regarding model selection based on specific translational goals and stage of therapeutic development. Thus, diversifying validated models available for translational research is likely to increase the probability of developing effective pain therapeutics and management strategies with little or no addiction liability.

Research Objectives

This FOA solicits applications to develop and rigorously validate non-rodent mammalian models of pain. This includes associated outcome measures and/or endpoints that enable translational research for effective pain management. To be considered responsive to this FOA, applications must address at least one of the following areas:

  • Development, characterization, and validation of non-rodent mammalian models of pain indications/conditions and/or pain associated with diseases. This includes validation of existing non-rodent mammalian models of pain that have not been well-validated and/or validation of existing models of pathologies or diseases, in the context of pain.
  • Development and validation of pain-associated outcome measures and endpoints in non-rodent mammalian models

Applicants are highly encouraged to take advantage of naturally occurring diseases, pathologies, and pain conditions in non-rodent mammalian species. For example, companion animals and livestock provide potential opportunities for translationally relevant models of arthritic, back, post-surgical, and cancer pain, among others. These models may also provide more generalizable findings due to increased complexity of factors that parallel those of human populations, such as genetic diversity, varied environments, complex behaviors, and the presence of co-occurring conditions.

Applications must provide strong rationale for why the proposed model is relevant to human pain conditions and how it will be used to advance therapeutic development. Such rationale could include a physiological or clinically based argument for why the proposed model will have better translational fidelity than those currently utilized in the field. Investigators should discuss both the potential values and limitations of the animal model and associated outcome measures, including the overall feasibility of the model/measure in both research and therapeutic development settings.

Applications will be expected to include multiple, rigorous validation studies. For instance, the underlying pathophysiology of the model should be characterized to determine whether relevant aspects of pain pathology represent clinical manifestations of human pain conditions. Depending on the underlying hypotheses of the model, such characterization should include relevant analyses at the molecular, cellular, tissue, and/or organism levels; examples include, but are not limited to molecular profiling, histopathology, imaging, physiology, and behavioral assessments. Validation studies should also address the overall consistency and reliability of key attributes of the model as well as evaluation of the sensitivity, precision, and dynamic range of the characteristics, outcome measures, and endpoints that would be used to assess the effect of therapeutic or physiological interventions in the model.

Applicants will need to provide strong rationale for what features or attributes of the model are the most relevant and important for a particular pain indication or condition. This rationale should be based on what is known about the human clinical condition and patient population, the species of the model, and potentially other currently existing models.

Based on the underlying variables and key attributes of the model, applicants should indicate types of manipulations that would effectively modulate the pain response (i.e., what the model will likely respond to and/or not respond to). Applicants may consider utilizing established pharmaceutical or non-pharmacological therapies as reference standards and/or a means to benchmark such treatments in the model, which could provide preliminary evidence of predictive validity and inform future extrapolation of findings in the model. When using control and active agents/manipulations, however, applicants should consider what is known about the pharmacokinetics and pharmacodynamics of the agent (or similar characteristics for non-pharmacological manipulations) specifically within that species rather than rely on inference. Note that experimental therapeutics should not be used to validate an experimental model.

As pain is a multidimensional experience, applicants are highly encouraged to consider the sensory/discriminative, affective/motivational, and cognitive aspects of pain in the context of the chosen species and model(s). Preferred measures of pain in animals are those that are non-invasive, non-evoked, objective, and that permit a behavioral or functional assessment of pain and pain treatment outcomes. Objective measures of non-evoked, spontaneous pain in validated animal models of chronic pain conditions are encouraged.

Applicants are also encouraged to incorporate the following into their studies, as appropriate:

  • Preclinical assessments and behavioral outcome measures that are homologous to clinically relevant outcomes in humans.
  • Restoration of function, including species-relevant naturally occurring behaviors, as indication(s) of effective pain management.
  • CNS-dependent responses that include activation of cortical circuits, rather than spinal reflexes alone.
  • Evaluation of human disease relevant biomarkers if they exist.

It will be essential that the general experimental design procedures are conducted in a rigorous manner, utilizing randomization, blinding, and independent replication where feasible. Applying rigorous and reproducible designs, controls, and statistical power for realistic and meaningful effect sizes will maximize confidence in experimental outcomes. Optimization and standardization of data acquisition protocols and pain assessments are also critical, especially when utilizing subjective measures such as observer-scored data. Projects involving subjective measures in companion animals, for instance, should carefully consider caregiver placebo effects and other potential biases. Development or use of automated systems for tracking and analyzing behavior to assess normal variations in species-specific behavior as well as reduce observer bias are highly encouraged. Regardless of the type of measurement (objective vs. subjective), investigators should take into consideration applicable variable factors related to the owner, handler, subject, and environment when designing experiments (including statistical designs) and interpreting results, in addition to biological factors such as animal strain, sex, and age.

Collaborations

This FOA strongly encourages the establishment of research teams that are multidisciplinary with the complementary expertise required for development and validation of models and measures that have translational utility. Investigators are encouraged to form collaborations with individuals knowledgeable in animal model development, biostatistics, pain biology and (patho)physiology, veterinary medicine, clinical experience appropriate for the type of pain, as well as behavioral science/ethology and translational research.

Investigative teams must include members with appropriate experience and expertise working with the proposed model species. Although not required, this person may be a veterinarian. Applications must also include a collaborating clinician with demonstrated experience appropriate for the type of pain that is the focus of the application. It is preferred that the collaborating clinician is listed as a co-investigator or a formal member of the investigative team. Alternatively, a letter of support from a collaborating clinician can be used to demonstrate active involvement in the project.

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. In spite of tremendous advancements in scientific research, information, educational and research opportunities are not equally available to all. NIH encourages institutions to diversify their student and faculty populations to enhance the participation of individuals from groups that are underrepresented in the biomedical, clinical, behavioral, and social sciences. Please refer to Notice of NIH's Interest in Diversity NOT-OD-20-031 for more details.

For this FOA, investigators are strongly encouraged to use the existing national resource and research centers for non-rodent mammalian models supported by the NIH Office of Research Infrastructure Programs for existing engineered or naturally occurring genetic models, for creating new transgenic animals, or as a repository of new models if they will be generated as an outcome of the project for the distribution to the wide biomedical community. Investigators considering these resources or collaborative projects should discuss available resources and services with the Center(s) and allocate necessary funds in their proposed budget.

Ethical Considerations

Although animal models can hold promising potential to advance translational efforts, the specific rationale for their use must be sufficiently justified, and compliance with the Public Health Service (PHS) Policy on Humane Care and Use of Laboratory Animals (Policy) is an absolute requirement. All institutions are required to comply, as applicable, with the Animal Welfare Act, and other Federal statutes and regulations relating to animals. We encourage applicants to carefully consider any potential ethical challenges related to their proposed research, ideally in consultation with a bioethicist. To the extent possible, applicants are encouraged to minimize negative effects on animal welfare in as far as possible for achieving the scientific aims and maximizing the scientific benefits of this research. For example, this could be implemented through minimizing the number of animals needed to obtain valid results through effective collaborations, multi-disciplinary approaches, and/or obtaining data through multiple levels of analysis from the same cohort of animals. Broad data sharing efforts can also have a significant impact towards the reduction and refinement principals of biomedical research in animals; Regardless of the experimental outcomes, dissemination of information about efforts to validate new models regarding their ability to accurately reflect human conditions is critical.

HEAL Initiative Requirements

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.

As part of its response to the national opioid public health crisis, the NIH intends to maximize the impact of HEAL Initiative-supported projects through broad and rapid data sharing (see HEAL Public Access and Data Sharing Policy). Rapid availability of publications and the primary data behind them promotes dissemination of new knowledge, enhances reproducibility and accelerates the ability of researchers to build upon NIH HEAL Initiative research to make new discoveries. Applicants are encouraged to ensure maximal data discoverability, interoperability, and reuse by aligning with the FAIR (Findable, Accessible, Interoperable, and Reusable) principles.


Non-Responsive Applications

The following applications will be considered non-responsive to this FOA and withdrawn from consideration without review:

  • Applications focused on the development, characterization, or validation of rodent models (see NOT-NS-22-095)
  • Research to develop, characterize, and/or validate animal models in non-mammalian species
  • Natural history studies aimed at understanding disease pathophysiology or mechanisms in the absence of model and/or outcome measure validation.
  • Studies aimed at evaluating a potential therapeutic agent or device for efficacy or safety
  • Applications focused primarily on technology development
  • Development of in vitro model systems
  • Clinical Research (Defined as Human subjects research with the exception of studies falling under 45 CFR 46.101(b) (4) (Exemption 4)

Pre-Application Consultation 

Applicants are strongly encouraged to consult with HEAL Scientific/Research Staff early on during the planning for an application. This early contact will provide an opportunity to discuss and clarify NIH policies and guidelines, including the scope of project relative to the HEAL initiative mission and intent of this FOA.


NIH Institute and Center Interests and Guidance

National Cancer Institute (NCI)
NCI is particularly interested in applications developing and characterizing models, outcome measures, and relevant endpoints for cancer- or cancer-treatment related pain. Pain conditions of interest include, but are not limited to: bone cancer pain, oral cancer pain, metastasis-related pain, post-surgical pain, radiation pain (including skin), aromatase inhibitor-induced arthralgia, chemotherapy-induced peripheral neuropathy, and immunotherapy-related pain. We are interested in examining these pain conditions in both tumor-bearing and non-tumor-bearing models. If the proposed projects examine pet dogs with cancer, we highly encourage applicants to submit your data to the Integrated Canine Data Commons (https://datacommons.cancer.gov/repository/integrated-canine-data-commons) in addition to complying with HEAL data sharing policies.

National Institute of Neurological Disorders and Stroke (NINDS)
NINDS is interested in the development and validation of fit for purpose animal models, outcome measures, and endpoints that will facilitate the development of non-addictive therapeutics for pain related to disorders within the mission of NINDS. These disorders include, but are not limited to headache, migraine, post-stroke pain, neuropathic pain, pain following traumatic brain injury, pain associated with spinal cord injury, pain associated with Alzheimer’s disease and other dementias, pain associated with Parkinson’s Disease and chronic overlapping pain conditions. NINDS, as part of NIH, strives for rigor and transparency in all research it funds. For this reason, NINDS explicitly emphasizes and provides supplemental guidance to NIH application instructions related to rigor and transparency (https://grants.nih.gov/policy/reproducibility/guidance.htm). For example, the biological rationale for the proposed experiments must be based on rigorous and robust supporting data, e.g., by minimizing the risk of bias and transparently reporting methods and results as described at https://www.ninds.nih.gov/Funding/grant_policy. As stated in the NIH application guidelines, if previously published or preliminary studies do not meet these rigor standards to an acceptable degree, applicants should address how the current study design addresses the deficiencies. Proposed experiments should likewise be designed in a manner that minimizes the risk of bias and ensures validity and transparency of experimental results.

National Institute on Aging (NIA)
NIA is interested in the development and validation of non-rodent animal models of pain that will facilitate the development of non-addictive therapeutics for pain related disorders in aging. NIA is particularly interested in models that account for aging and age-related changes in molecular, cellular, pathological, behavioral, and cognitive processes that may influence the underlying normal and pathophysiological mechanisms of pain and therapeutic responses across the lifespan. NIA is most interested in understanding the age-related changes in mechanisms with advancing age. Investigators developing non-human primate models in the context of aging specifically using aged rhesus macaques may consider use of NIA-supported aged rhesus macaques resource. Investigators are encouraged to contact NIA program staff for additional details.

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
NIAMS is interested in research that develops, characterizes, and rigorously validates non-rodent mammalian models of pain, associated outcome measures and/or endpoints that will advance translational research for effective pain management related to rheumatic, musculoskeletal and/or skin diseases.

National Institute of Diabetes and Digestive and Kidney Disease (NIDDK)
The development and evaluation of non-rodent models of pain in diseases and conditions within the scope and mission of NIDDK are of interest. Examples include but are not limited to diabetic peripheral neuropathy, painful interstitial cystitis, chronic pelvic pain syndrome, irritable bowel syndrome, inflammatory bowel disease, non-ulcer dyspepsia, as well as acute and chronic pancreatitis.

National Center for Complementary and Integrative Health (NCCIH)
NCCIH is interested in the development and/or validation of non-rodent animal models that would further our mechanistic understanding of interventions that fit within NCCIH’s mission, including biophysical force-based interventions (e.g., massage, acupuncture, chiropractic manipulations, osteopathic treatments) and other non-pharmacological interventions as well as natural products (e.g., probiotics and microbial based therapeutics, herbs, or supplements). NCCIH is also interested in development of novel or rigorously validated animal models that further our understanding of pain pathophysiology in a variety of chronic pain conditions with special emphasis on Sickle Cell Disease Pain, Myofascial Pain, Irritable Bowel Disease Pain, and Joint Pain.

National Institute on Alcohol Abuse and Alcoholism (NIAAA)
NIAAA is interested in research that develops, characterizes, and rigorously validates non-rodent mammalian models of pain, associated outcome measures and/or endpoints that will advance translational research for effective pain management for pain conditions associated with Alcohol Use Disorder or exacerbated by chronic alcohol misuse.

National Institute of Dental and Craniofacial Research (NIDCR)
NIDCR is interested in the development and validation of models of various orofacial pain conditions. Of particular interest are complex pain conditions that include, but are not limited to, burning mouth syndrome, myofascial or other temporomandibular disorders resulting in persistent or chronic pain, persistent idiopathic dentoalveolar pain, persistent idiopathic facial pain, and peripheral neuropathic complications of Sjögren syndrome.

See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information

Funding Instrument

Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

Application Types Allowed
New
Resubmission

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.

Clinical Trial?

Not Allowed: Only accepting applications that do not propose clinical trials.

Funds Available and Anticipated Number of Awards

The NIH HEAL (Helping to End Addiction Long-term) Initiative intends to commit an estimated total of $6 million to fund 4-5 awards in FY 2023. Awards issued under this FOA are part of funds set aside to support the NIH HEAL Initiative. Future year amounts will depend on annual appropriations.

Award Budget

Application budgets need to reflect the actual needs of the proposed project and are limited to direct costs of $750,000 per year.

Award Project Period

The scope of the proposed project should determine the project period. The maximum project period is 5 years.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

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 Government

  • Eligible Agencies of the Federal Government, including the NIH Intramural Program
  • 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)
Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed. 

Required Registrations

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. The same UEI must be used for all registrations, as well as on the grant application.
  • eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their 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.

Eligible Individuals (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women 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).

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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
  • Non-rodent mammalian species and therapeutic condition that the proposal plans to model
  • 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:

HEAL Animal Models
Email: HEALanimalmodels@nih.gov

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, with the following additional instructions:

Facilities and Other Resources
In addition to standard items and as applicable and pertinent to the proposed research, describe existing facilities, other resources, and/or partnerships (e.g., with industrial entities) that will provide relevant capabilities. Infrastructure and available resources should be appropriate for the species that is the subject of the proposed research, taking into consideration the number of animals needed to achieve expected results and in line with the expected timeline.

SF424(R&R) Senior/Key Person Profile

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

In the biosketches, outline knowledge and experience working with the proposed model species and/or relevant clinical population, where applicable.

R&R 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:

Specific Aims: Briefly provide the context and overall rationale for the proposed set of studies, with an emphasis on the reason that the proposed model and/or outcome measures and endpoints will significantly improve the translational quality of existing tools used for the development of effective non-opioid analgesics and pain management strategies. Outline the major objectives and/or aims of the proposed set of studies, including the technical questions to be answered to determine the feasibility and the validity of the proposed model/measure(s).

Research Strategy: The Research Strategy should include the following sections:

A. Significance

  • Provide translational rationale for the proposed model, including any existing clinical evidence that the model could be relevant to specific human pain type(s)/indication(s) and/or disease-associated pain conditions.
  • Outline the biological rationale for the proposed model as it relates to the current knowledge of pain processing and pathology, disease etiology, or targeted pathway for a potential therapeutic.
  • Describe the unmet need for the proposed model/outcome measure(s)/endpoint(s). Summarize the current gaps and challenges and provide a comparative view of other/existing animal models and/or outcome measures in relation to the specific pain type(s)/indication(s) and/or disease-associated pain conditions.
  • Discuss the advantages of the proposed model/measure and why it’s likely to have better translational fidelity than those currently utilized in the field.
  • Describe the value of the proposed model/measure to the drug discovery and development process and how it would be utilized to advance the development of non-opioid analgesic therapies (i.e., preliminary efficacy testing, proof of concept, as a surrogate for efficacy, for eventual hypothesis testing, etc.).
  • Discuss the overall feasibility for its use in both research and therapeutic development settings.

B. Innovation

  • Describe the novel attributes of the proposed animal model, outcome measures and/or endpoints.
  • Discuss whether the concepts, approaches, and methodologies to be used are innovative in the context of modeling pain.

C. Approach

  • Provide a detailed description of the overall strategy, methodology, analyses, and other considerations that will be used to accomplish the development, characterization, and validation of the model, outcome measure(s) or endpoints, including:
    • Characterization of the underlying pathophysiology to determine whether relevant aspects of pain pathology represent clinical manifestations of human pain conditions
    • Any plans for optimization and standardization of data acquisition protocols and/or pain assessments
    • A detailed plan for evaluation of internal validity, such as the sensitivity, precision, dynamic range, consistency, and overall reliability of utilized metrics
  • If utilizing established pharmaceutical or non-pharmacological therapies as reference standards, describe the added value of these experiments towards validation of the model/measures/endpoints.
  • Describe and offer evidence for the feasibility of the proposed approach, the advantages of any new methodologies, and potential pitfalls and alternative approaches for the project.
  • Describe how the study design balances potential benefits to human health and/or science with the goals of refining experimental methodology and minimizing negative impact on animal welfare.
  • Outline a collaboration plan between the preclinical and clinical applicants. The collaboration plan should include the roles and responsibilities of the preclinical and clinical scientists in developing the model or outcome measure as it relates to the pathophysiology and/or disease etiology of clinical populations typically recruited in drug development programs focused on a specific pain indications or conditions. Highlight the specific contribution(s) of a collaborating clinician(s) that demonstrate an active role in the design and validation plans.

D. Timeline and Metrics for Success: A project timeline in the form of a Gantt chart or similar must be included as part of the Research Strategy and should include expected annual progress towards the achievement of the overall project goals. The application should also include a distinct final section, entitled “Metrics for Success”, that proposes clear, quantitative, and objective criteria that would ultimately support further use of the validated model, measures, and/or endpoints in the therapeutic discovery and development process. Quantitative metrics should be provided to define, for example, sufficient reproducibility and dynamic range for outcome measures and endpoints within the model and what constitutes a clinically meaningful difference relative to the specific human pain type/condition (i.e., what represents a meaningful effect size, rather than merely a statistically significant change).


Investigators are urged to follow the NIH guidance for rigor and transparency in grant applications (https://grants.nih.gov/policy/reproducibility/guidance.htm) and additionally recommends the research practices described at https://www.ninds.nih.gov/Funding/grant_policy to ensure that robust experiments are designed, potential experimenter biases are minimized, results and analyses are transparently reported, and results are interpreted carefully. These recommended research practices include, where applicable, rationale for the chosen model(s) and primary/secondary endpoints, clear descriptions of tools and parameters, blinding, randomization, ensuring adequate sample size, pre-specified inclusion/exclusion criteria, handling of missing data and outliers, appropriate controls, preplanned analyses, appropriate quantitative techniques, clear indication of exploratory vs. confirmatory components of the study, consideration of limitations, and plans for transparent reporting of all methods, analyses, and results so that other investigators can evaluate the quality of the work and potentially perform replications.

Investigators should indicate whether data presented or cited in the application as key support for the proposed work were collected, analyzed, and reported in a rigorous and transparent manner as indicated above. A plan to address any ambiguity, weaknesses, or limitations in the prior research should be included in the application. Proposed experiments should similarly adhere to these high standards of rigor and transparency.


Letters of Support: Statements of individual and Institutional Commitment, as appropriate to the overall application, should be included in this section.

  • If a clinical collaborator is not included as key personnel, applications must include a letter of support from a clinical collaborator with experience appropriate for the type of pain that is the focus of the application. The letter should reinforce the collaboration plan outlined in the research strategy and support an active role of the clinical collaborator.
  • If collaborating with a private entity and/or contract research organization, include a letter of support that addresses any agreement to provide agent(s) or animals, to develop animal models or conduct studies, and any potential limitations on sharing of data (including negative results). This letter should provide assurance of timely availability and/or access to animals needed for the proposed study and should come from an official within the private entity who has authority to speak on these issues.
  • If an application plans to utilize the infrastructure or resources of existing projects, whether funded by NIH, other governmental or non-governmental entities, letters of support detailing the terms of collaboration and data sharing must be included.

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:

NIH intends to maximize the impact of HEAL Initiative-supported projects through broad and rapid data sharing. Consistent with the HEAL Initiative Public Access and Data Sharing Policy (https://heal.nih.gov/about/public-access-data), all applications, regardless of the amount of direct costs requested for any one year, are required to include a Data Management and Sharing Plan outlining how scientific data and any accompanying metadata will be managed and shared. The plan should describe data types, file formats, submission timelines, and standards used in collecting or processing the data. Data generated by HEAL Initiative-funded projects must be submitted to study-appropriate domain-specific or generalist repositories in consultation with the HEAL Data Stewardship Group to ensure the data is accessible via the HEAL Initiative Data Ecosystem. Guidelines for complying with the HEAL Public Access and Data Sharing Policy can be found at https://heal.nih.gov/data/complying-heal-data-sharing-policy. Resources and tools to assist with data related activities can be found at https://www.healdatafair.org/.

To maximize discoverability and value of HEAL datasets and studies, and facilitate data integration and collaboration, applications submitted in response to this FOA are strongly encouraged to incorporate standards and resources where applicable:

  • Applicants are encouraged to ensure that data collected by the study conform to Findable, Accessible, Interoperable, and Reusable (FAIR) principles.
  • Applicants are specifically encouraged to incorporate into their planning, an alignment with the guidelines, principles and recommendations developed by the HEAL Data Ecosystem, including but not limited to preparing data to store in selected specified repositories, applying minimal metadata standards, use of core HEAL Clinical Data Elements (CDEs, https://heal.nih.gov/data/common-data-elements), and other necessary requirements to prepare data to connect to the HEAL Data Ecosystem.
  • All new HEAL clinical pain studies are required to submit their case-report forms/questionnaires to the HEAL Clinical Data Elements (CDE) Program. The program will create the CDE files containing standardized variable names, responses, coding, and other information. The program will also format the case-report forms in a standardized way that is compliant with accessibility standards under Section 508 of the Rehabilitation Act of 1973 (29 U.S.C § 794 (d)), which “require[s] Federal agencies to make their electronic and information technology accessible to people with disabilities.” HEAL Initiative clinical studies that are using copyrighted questionaries are required to obtain licenses for use prior to initiating data collection. Licenses must be shared with the HEAL CDE team and the program officer prior to use of copyrighted materials. For additional information, visit the HEAL CDE Program.
  • To the extent possible, HEAL awardees are expected to integrate broad data sharing consent language into their informed consent forms and align study consent language with data access and re-use requirements as defined by repository HEAL investigators select to store their HEAL data long-term.

The NIH notices referenced below provide additional NIH guidance that should be considered in developing a strong data management and sharing plan. The list is instructive but not comprehensive.

  • Elements of an NIH Data Management and Sharing Plan (NOT-OD-21-014)
  • NIH has provided guidance around selecting a repository for data generated by NIH-supported research and has developed desirable characteristics for all data repositories (NOT-OD-21-016).
  • NIH encourages the use of data standards including the PhenX Toolkit (www.phenxtoolkit.org) (for example, see NOT-DA-12-008, NOT-MH-15-009)
  • Data should be organized according to a standard model that is widely accepted within the field. An example for the clinical research studies would be the OMOP Common Data Model, which has also been successfully adapted for use with observational (including survey) studies more generally. In addition, the HL7 FHIR® (Fast Healthcare Interoperability Resources) standard (NOT-OD-19-122) may facilitate the flow of data with EHR-based datasets, tools, and applications.
  • NIH encourages clinical research programs and researchers to adopt and use the standardized set of data classes, data elements, and associated vocabulary standards specified in the United States Core Data for Interoperability (USCDI) standards, as they are applicable (NOT-OD-20-146). Use of the USCDI can complement the FHIR® standard and enable researchers to leverage structured EHR data for research and enable discovery. In addition to USCDI, OMOP, and FHIR standards for enhanced interoperability, investigators and data centers should align their data collection and management practices with recommended guidance emerging from the HEAL CDE and Data Ecosystem programs.

Awardees conducting research that includes collection of genomic data should incorporate requirements under the NIH Genomic Data Sharing Policy (NOT-OD-14-124, NOT-OD-15-086).

Appendix:
Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
PHS Human Subjects and Clinical Trials Information

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

If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed.

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.

Foreign Institutions

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

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 provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the 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.

 

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.

Section V. Application Review Information

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 through the NIH peer review system.

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 should evaluate the overall potential for the proposed studies to substantially advance translational research and drug development for non-opioid analgesic therapeutic interventions

Scored Review Criteria

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

Significance

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Specific to this FOA:

  • Is there strong rationale for developing the proposed non-rodent mammalian model(s), pain-related outcome measures and/or endpoints for the targeted pain type, including the unmet need, limitations of existing models and potential advantages of the new model/measure(s)?
  • Is there strong biological rationale to support the plans proposed?
  • Have the investigators thoughtfully considered the potential to produce models/measures that will be feasible to implement, meaningfully translate to human biology, and play a significant role in the drug discovery and development process?
  • Does the application adequately describe whether prior research that serves as the key support for the proposed research component employed rigorous practices such as minimization of potential experimenter biases, robust experimental designs, transparent reporting of results and analyses, and careful interpretation? Does the application adequately describe ambiguity, weaknesses, or limitations in rigor of the prior research, if applicable?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance, and organizational structure appropriate for the project?

Specific to this FOA:

  • Do the investigators have adequate expertise and experience conducting research in the proposed model species?
  • Have the investigators formed collaborations with clinicians with experience appropriate for the type of pain that is the focus of the project?
  • Is there evidence that the clinical collaborator will play an active role in the design and validation plans?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Approach

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?

Specific to this FOA 

  • Are the methods proposed to characterize the model appropriate for the type of pain that is the focus of the application?
  • Have methods for evaluating how well the model recapitulates features characteristic of the human pain condition being modeled been systematically outlined in the application?
  • Does the proposed approach adequately incorporate studies that would demonstrate rigorous validation of the models and/or measures?
  • Is the strategy proposed for validating the model/measure well-reasoned and appropriate?
  • For outcome measures and endpoints, have methods for addressing internal validity characteristics such as sensitivity, precision, dynamic range, etc., as well as overall reliability been adequately addressed?
  • Are the proposed statistical analyses appropriate for the experimental design and the quantitative characteristics of the outcome measures/endpoints?
  • Have the applicants demonstrated adequate feasibility of the approach?
  • Have the investigators thoughtfully considered strategies to balance potential benefits to human health and/or science with goals to refine experimental methodology and minimize the negative impact on animal welfare?
  • Does the proposed research incorporate adequate methodological rigor where applicable, including, but not limited to, rationale for the chosen model(s) and primary/secondary endpoints, clear descriptions of tools and parameters, blinding, randomization, adequate sample size, pre-specified inclusion/exclusion criteria, adequate consideration of potential biases, appropriate handling of missing data and outliers, appropriate controls, appropriate quantitative techniques, clear indication of exploratory vs. confirmatory components of the study, consideration of limitations, and plans for transparent reporting of all methods, analyses, and results so that other investigators can evaluate the quality of the work and potentially perform replications?
  • How well does the Data Management and Sharing Plan provide a summary of the shared data, a description of the data standards, a plan for the data archiving, and a timeline for data submission to the archive and sharing data with the research community?

    "Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) will not be evaluated at time of review."

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment, and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Specific to this FOA:

  • Does the team have the necessary infrastructure to support this project, taking into consideration the number of animals they need to achieve their expected results?

Additional Review Criteria

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.

Timeline and Metrics of Success

Is the timeline reasonable for the work proposed? Are the proposed metrics clear and quantifiable, and if achieved, would they support the use the of the validated model, measures, and/or endpoints in the therapeutic discovery and development process?

Protections for Human Subjects

For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animals Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

Not Applicable

 

Revisions

Not Applicable

Additional Review Considerations

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Applications from Foreign Organizations

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable:(1) Sharing Model Organisms; and (2)  Genomic Data Sharing Plan (GDS).

Authentication of Key Biological and/or Chemical Resources:

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the Center for Scientific Review, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications will receive a written critique.

Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.

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. 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:
  • Scientific and technical merit of the proposed project as determined by scientific peer review.
  • Availability of funds.
  • Relevance of the proposed project to program priorities.

3. Anticipated Announcement and Award Dates

After the peer 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 peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

Section VI. Award Administration Information

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.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

Institutional Review Board or Independent Ethics Committee Approval: 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:

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.

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.

Cooperative Agreement Terms and Conditions of Award

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.

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 $25,000.  See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period.  The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS).  This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313).  As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available.  Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 – Award Term and Conditions for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

Application Submission Contacts

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-637-3015

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

Scientific/Research Contact(s)

HEAL Animal Models
Email: HEALanimalmodels@nih.gov

Peer Review Contact(s)

Center for Scientific Review (CSR)
Email: FOAReviewContact@csr.nih.gov

Financial/Grants Management Contact(s)

Shellie Wilburn
Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS)
Email: ChiefGrantsManagementOfficer@ninds.nih.gov

Section VIII. Other Information

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.

Authority and Regulations

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.

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