EXPIRED
National Institutes of Health (NIH)
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 Center for Complementary and Integrative Health (NCCIH)
National Cancer Institute (NCI)
U19 Research Program Cooperative Agreements
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
The purpose of this funding opportunity announcement is to support research that uses human tissue or cells to generate comprehensive datasets for the discovery and characterization of functional genetic elements, epigenetic signatures, and molecular/cellular pathways that underlie human pain transduction, transmission, and processing. This FOA will support concerted multidisciplinary team science efforts that apply large-scale high-throughput approaches on tissues involved in human pain processing as part of the NIH HEAL Initiative’s Program to Reveal and Evaluate Cells-to-gene Information that Specify Intricacies, Origins, and the Nature of Human Pain (PRECISION Human Pain). U19 Centers will operate as a cooperative network to promote collaboration and coordination of research activities. U19 Centers will also coordinate with the U24 HEAL Initiative: Human Pain-associated Genes & Cells Data Coordination and Integration Center that will curate, harmonize, and integrate datasets generated by this U19 research program.
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 |
March 17, 2022 | March 17, 2022 | Not Applicable | July 2022 | October 2022 | December 2022 |
July 07, 2022 | July 07, 2022 | Not Applicable | November 2022 | January 2023 | April 2023 |
October 11, 2022 | October 11, 2022 | Not Applicable | March 2023 | May 2023 | July 2023 |
March 09, 2023 | March 09, 2023 | Not Applicable | July 2023 | October 2023 | December 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.
Not Applicable
It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.
Purpose
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 treatments are critically needed.
Through targeted research efforts, the NIH HEAL Initiative aims to accelerate the discovery and successful translation of new pain therapeutics by supporting collaborative efforts to gain a better, more direct understanding of human pain-associated genes, cells, and tissues that underly specific human pain types, conditions and/or diseases. Towards that end, this funding opportunity announcement (FOA) is designed to support multidisciplinary research teams that will perform highly collaborative and coordinated research to use human tissue and cells to generate comprehensive datasets characterizing the functional genetic elements, epigenetic signatures, and molecular/cellular pathways that contribute to human pain signal transduction, transmission, and processing. These datasets will serve as the basis for a future integrated knowledgebase that will facilitate the discovery and validation of therapeutic targets for specific human pain conditions and/or diseases, including in conditions of chronic drug use, substance use disorders (SUDs), and other co-morbid and/or overlapping pain conditions.
Background
This funding 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/.
The advent of single cell -omics and high throughput electrophysiologic technologies provide an immense opportunity to significantly expand currently available datasets concerning gene expression and cellular function of human pain processing cells and/or tissues. For example, several recent transcriptomic and single-cell functional studies utilizing primary neurons from human pain processing tissues; namely dorsal root ganglia (DRG), spinal cord (SC), trigeminal ganglia (TG), and tibial nerves, have identified a number of potential genetic and cellular differences in human sensory neuron electrophysiologic signatures with translational implications. In addition, recent comparative transcriptomic studies of [whole] DRGs obtained from human subjects with or without pain conditions suggest several common genes associated with a small subset of neuropathic and cancer pain conditions. While promising, these data only begin to uncover the breadth of knowledge to be gained in this space and highlight the need to expand datasets to include heterogeneities across specific pain type/conditions comparing variables such as chronic analgesic or other drug use and co-morbid and/or overlapping pain conditions. It also highlights the need for standardization of methods, as approaches for tissue collection, processing, and analysis often vary across individual laboratories, thus posing a tremendous challenge for harmonized data collection, analysis, and reporting that would enable cross-comparison and rigorous validation.
To capitalize on recent technological advances in high throughput analyses of molecular, anatomic, and physiological measurements for single cell and tissue-level characterizations and address the increasing need to enhance data interoperability and harmonization among data producers, the NIH Heal Initiative has created the Program to Reveal and Evaluate Cells-to-gene Information that Specify Intricacies, Origins and the Nature of Human Pain (PRECISION Human Pain). The PRECISION Human Pain network will be composed of a group of centers supported via two companion FOAs: the subject of this FOA is the U19 Centers for Discovery and Functional Evaluation of Human Pain-associated Genes & Cells. The companion FOA RFA-NS-22-021 will support a U24 Human Pain-associated Genes & Cells Data Coordination and Integration Center that will curate, harmonize, and integrate core datasets generated by the U19 Centers to generate digital resources.
Rapid progress in the discovery and understanding of the role of functional genetic elements, epigenetic signatures, and molecular/cellular pathways that underlie human pain processing, as well as integrated data analysis and development of digital assets will require collaborations across disciplines. To effectively achieve the goals of the PRECISION Human Pain network and facilitate advances in pain research, the NIH HEAL Initiative encourages the formation of multidisciplinary research teams including neurobiologists, pain biologists, human pain scientists and/or physicians, and scientists from statistics, physics, mathematics, engineering, and computer and information sciences. NIH and the NIH HEAL Initiative also strongly encourage input from patients and caregivers on the scientific and research goals of this U19 research program.
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. In addition, it is expected that PRECISION Human Pain projects will work together, operating as a cooperative network to achieve its overall goals. This will include regular meetings and other coordinated activities within the PRECISION Human Pain network as well as the NIH HEAL Initiative, and the NIH more broadly. In particular, network Centers will work closely with the HEAL Data Ecosystem, which coordinates data sharing across the HEAL Initiative.
Research Objectives
The NIH HEAL Initiative - PRECISION Human Pain network
The objectives of this FOA are to support multidisciplinary groups of researchers to conduct collaborative, team-based science utilizing cutting-edge technologies and approaches and large-scale, high throughput tissue and single-cell analysis on primary human tissues involved in human pain processing, including but not limited to DRG, SC, TG, sympathetic ganglia (SG), brainstem, brain, peripheral nerve bundles/fibers, and skin to:
Studies should focus on large-scale analysis of human genes, epigenetic elements, proteome, metabolome, and phenotyping of neuronal and non-neuronal cells at single-cell and tissue levels, as well as their functional crosstalk that leads to hyper/hypo-activation of sensory neurons under individual pain types or pain conditions and/or diseases, including pain conditions in the context of chronic drug use, SUDs or co-morbid and/or overlapping pain conditions. Ex vivo tissue analyses (including, but not limited to DRG, TG, brainstem, brain and SC slices) are highly encouraged, as they could provide critical first-hand information on pain signal processing pathways and circuits in humans. This FOA will also support studies on functional and pharmacological consequences of causal and genetic manipulations in primary human cell cultures and ex vivo human tissue slice preparations. In addition, this FOA will support parallel human tissue proteomic, metabolomic and histological analysis to generate cellular and histological phenotypic information for specified pain conditions, in relation to the goals of individual research projects and/or centers.
This FOA embraces the existing efforts of the research community to enable a collaborative cross-center harmonization of human pain-associated tissue procurement and processing, optimization of experimental protocols, standardized assays, data collection, data harmonization, analysis, and reporting with high rigor, reproducibility and validation across centers. The U19 Centers will be expected to extensively collaborate on harmonizing the procurement of human tissues through individual or consortia of local and regional transplant and trauma centers, human tissue resources for research purposes (e.g.: NIH NeuroBioBank, National Disease Research Interchange, and other similar resources), and contract research organizations providing such resources. Applicants will also be expected to develop inclusion and exclusion criteria that will minimize the risk of abnormal or degraded tissue.
In order to maximize the utility of the data, any human biological samples collected and studied or that are derived from existing biospecimens or sources are expected to have been obtained using a documented informed consent process that explicitly allows for future research use and broad data sharing (NOT-HG-20-011; see ENCODE project for informed consent examples). Sources with participant consent for unrestricted access is strongly encouraged. Sources consented for sharing through a controlled-access environment, such as General Research Use (GRU) or Health, Medical, and Biomedical (HMB) without additional restrictions, will also be considered and should be well justified. Applicants are also expected to consider Ethical, Legal and Social Issues (ELSI) of tissue collection and to consider return of results to donors or their families.
The U19 centers, along with the companion U24 Data Coordination and Integration Center, will collaboratively generate comprehensive, integrated datasets by curating and harmonizing U19 Center-generated data and metadata elements, including but not limited to transcriptome, cellular function phenotypes, and disease/condition-specific transcriptome, proteome, metabolome and/or cellular functions, and tissue analysis.
The expected outcomes of the NIH HEAL Initiative PRECISION Human Pain network include:
The comprehensive -omics and cellular function datasets generated from this initiative will significantly accelerate validation of therapeutic targets in human pain-relevant cells and tissue as well as facilitate the identification and development of potential markers that reflect target engagement, thus providing valuable assets for translational research and therapeutic development. These studies would be highly informative for multiple ongoing and future pre-clinical and translational programs in the NIH HEAL initiative and the NIH more broadly. As such, all PRECISION Human Pain network centers will work closely with the purview of the NIH HEAL Initiative’s Data Ecosystem (https://heal.nih.gov/data/heal-data-ecosystem) to maximize sharing and dissemination of optimized protocols, data, and digital assets generated from this initiative to the broader pain research and therapeutics development communities.
Information Relevant to Specific Institutes/Centers/Offices:
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 propose a multidisciplinary team-based approach to collect data on molecular signatures, cell types, and cellular function phenotypes or signatures associated with human pain signal processing with relevance across a variety of pain conditions in the context of aging both healthy and pathological. 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 encourages applications that include the human genes, epigenetics, proteomics, metabolomics, and molecular/cellular phenotypes associated with craniofacial disorders and orofacial pain, including temporomandibular disorders, periodontal and/or chronic dental pain, trigeminal neuropathies, burning mouth syndrome, head and neck cancer pain, and other orofacial pain, to enable and accelerate the discovery and validation of therapeutic targets for these pain conditions.
National Center for Complementary and Integrative Health (NCCIH): NCCIH is particularly interested in human genes, epigenetic elements, proteome, metabolome data using neural and associated non-neural (such as myofascial and musculoskeletal) tissues, which are potential therapeutic targets for complementary and integrative health approaches in the context of pain and SUDs. 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.
National Cancer Institute (NCI): NCI is interested in research on human genes, cellular phenotypes, and biomarkers related to cancer- or treatment-related pain conditions. Examples of areas of interest include, but are not limited to, susceptibility to chemotherapy-induced peripheral neuropathy, post-surgical pain, or cancer-induced bone pain, mechanisms underlying progression of chemotherapy-induced peripheral neuropathy, post-surgical pain, cancer treatment-related pain or cancer-induced bone pain or predicting responses to different therapies.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) is particularly interested in applications relevant to (a) persistent pain of women with endometriosis, chronic pelvic pain, vulvodynia/vestibulodynia, dysmenorrhea, and other gynecologic pain syndromes, (b) pain (acute and chronic) after minor and major surgical procedures, and (c) pain conditions (acute and chronic) in children, women of reproductive age, pregnant and lactating individuals, people with physical disabilities, and health disparity populations (i.e. racial/ethnic groups, sexual and gender minorities, underserved rural and socioeconomically disadvantaged populations, people with limited English proficiency).
Research Scope and Organizational Structure of the U19 Centers
To support the objectives of the PRECISION Human Pain network, each U19 Center is expected to include the following required cores: an Administrative Core, a Human Tissue Procurement and Processing Core, and a Data Core. U19 Centers may also include specialized Resource Cores; however these are optional. Each U19 Center is also expected to contain up to three Research Projects for collecting data on molecular signatures, cell types, and cellular function phenotypes or signatures associated with human pain signal processing, including, but not limited to specific pain types, conditions and/or diseases. Overall, applicants should propose to use methods that have been demonstrated to generate high-quality data, to be cost-effective, and to have the capability to accurately and efficiently define cell types. Scalable and multiplexed approaches are expected to enable a comprehensive cell type survey. In addition, applicants are encouraged to adopt technology platforms capable of acquiring multimodal datasets from the same cells with adequate throughput. Examples of such approaches include fluorescence in situ hybridization (FISH) combined with immunohistochemistry labeling to monitor both RNA and protein molecules and track spatial expression information of genes related to pain, as well as collection of cell morphology and RNAseq data from individual neurons following electrophysiological recordings.
Administrative Core (required)
Each U19 Center must have an Administrative Core that will support the coordination of efforts across the Research Projects and Cores within the Center, as well as activities to advance integration into the broader PRECISION Human Pain network. The effective management of a Center project requires a significant commitment by the Program Director(s)/Principal Investigator(s) (PD/PI). A full-time program manager may in addition strengthen the Center administration. This core will be responsible for organization, management, decision-making, and periodic evaluations of individual groups within the Center, involvement of institutional and other resources, and shared publications. The Administrative Core is expected to create and implement administrative and leadership mechanisms that will foster effective interactions with other PRECISION Human Pain network PDs/PIs and institutions to promote synergistic research efforts. The Administrative Core lead will also be expected to participate in meetings as part of the network’s Steering Committee (see Section VI Cooperative Agreement Terms and Conditions for more information).
Human Tissue Procurement and Processing Core (required)
Each U19 Center must have a Human Tissue Procurement and Processing Core that will coordinate with individual research projects within the Center as well as with other U19 Centers within the PRECISION Human Pain network on the procurement of human pain-associated tissues, including harmonization of tissue extraction procedures, storage, and processing, based on specific experimental types (e.g., dissociation, cell sorting, culturing, tissue slice preparations, tissue fixation for histologic and/or imaging analysis, etc.). Applicants should adopt scalable experimental approaches that will maximize the discovery and classification of all pain-associated cell types in brain, brainstem, TG, SC, DRG, and peripheral nerves. This Core will be responsible for ensuring documented informed consent processes are in place that explicitly allows for future research use and broad data sharing; this may be part of a coordinated and standardized process across the network, as appropriate. The Core Leader, or their designate, will represent the Center in a cross-network human pain-associated tissue procurement, processing and analysis sub-committee that will operate under the network’s Steering Committee to promote coordination and collaboration among all PRECISION Human Pain network Centers. This sub-committee will be responsible for the development and/or optimization of experimental protocols and procedures for: 1) procurement and processing of human tissues associated with pain signal transduction and transmission, for specific experimental and analytic needs, 2) primary cultures and co-cultures of human neurons and non-neuronal cells (e.g., ganglionic cells) from the collected tissue, 3) preparation of tissue slices for functional analysis, 4) fixation and processing of tissue for histological and imaging analysis, 5) dissemination of these human tissue procurement and processing protocols and procedures to pain research communities.
Data Core (required)
Each U19 Center must have a Data Core that will provide central data storage, management and information security services to all researchers within the Center and will be responsible for ensuring the timely submission of data and data analyses to the U24 HEAL Initiative: Human Pain-associated Genes & Cells Data Coordination and Integration Center (DCIC) within the PRECISION Human Pain network. The Data Core will also provide bioinformatics expertise and data integration and analysis support according to the Center’s research objectives, including mining and integrating other existing data and information to fill knowledge gap(s). The Data Core may perform statistical analyses of single cell -omics and/or cellular function electrophysiologic signature data to identify cell types, discover unique cell type markers, predict spatiotemporal relations, and infer gene expression regulatory mechanisms underlying the role of specific cell types in pain signal transduction and transmission. The Data Core may also provide study design and statistical support/services for the researchers within the Center. The Data Core Leader, or their designate, will represent the Center in a cross-PRECISION Human Pain network data sub-committee that will operate under the network’s Steering Committee to promote coordination and collaboration among all PRECISION Human Pain network Centers, including data sharing, data harmonization, refinement of data standards, data analysis and integration, data mapping to common brain, spinal cord, ganglia and cellular coordinate systems, and data visualization. Furthermore, it will closely work with the NIH HEAL Initiative’s Data Ecosystem to maximize sharing and dissemination of data and digital assets to the pain research and therapeutics development communities.
Resource Core (optional)
Each U19 Center may have up to two Resource Cores that are expected to generate, acquire, optimize, and adapt necessary tools and reagents for cellular and molecular characterizations and/or histological and imaging analyses. The Core may also support technology improvements that will increase the efficiency and/or decrease the cost of generating comprehensive data on human pain-associated genes and cells. The adaptation of necessary and validated tools, reagents, and technologies should address limitations and gaps of those currently used as a benchmark against which proposed improvements or competitive advantages will be measured. Possible improvements include throughput, sensitivity, selectivity, scalability, spatiotemporal resolution, and reproducibility in cellular and -omic analyses
Research Projects (required)
Each U19 Center is expected to contain up to three Research Projects to collect data on molecular signatures, cell types, and cellular function phenotypes or signatures, in order to generate comprehensive datasets for the discovery and characterization of functional genetic elements, epigenetic signatures, and molecular/cellular pathways that underlie human pain signal transduction, transmission, and processing, including, but not limited to specific pain types, conditions and/or diseases, and/or under conditions of chronic analgesic use, other drug use, SUDs and other co-morbid and/or overlapping pain conditions. Each Research Project must be organized around a central dataset and research theme incorporating scalable and cross-validating methods and analyses wherever possible. Goals for data production should be as comprehensive and complete as possible with a broad coverage of multiple different cell types and tissue structures/regions and adequate depth in characterizing multiple cellular properties. Research objectives may include, but are not limited to:
Additional PRECISION Human Pain Network Elements and Concepts: The comprehensive datasets of functional genetic elements, epigenetic signatures, and molecular/cellular pathways generated by the PRECISION Human Pain network will be an important and unique resource for use by the broader research community, and thus the following issues related to large-scale data and knowledgebase production are paramount to the success of the program.
Data Quality. Two of the cornerstones of science advancement are rigor in designing and performing scientific research and the ability to reproduce biomedical research findings (https://www.nih.gov/research-training/rigor-reproducibility). The PRECISION Human Pain network is expected to establish stringent data quality standards, quality control and quality assurance processes for the experimental and statistical approaches, so that the data generated will be broadly referenced and used by the research community.
Data Comprehensiveness. The data production goals should be as comprehensive as possible with a broad coverage and adequate depth in characterizing functional genetic elements, epigenetic signatures, and molecular/cellular pathways that underlie human pain signal transduction, transmission, and processing. In practice, achieving a comprehensive signature of human pain-associated genes and cells that include neurons, glia cells, and other cell types will require careful planning of workflow, strategic allocation of resources, and optimal lineup of complementary technologies. To ensure comprehensive coverage of cell diversity and avoid overcommitting resources to a limited number of tissue types, regions and cell types in the context of specific pain conditions and/or diseases, NIH program staff may consider portfolio balance when making funding decisions and negotiating project milestones. The purpose is to establish a network with complementary capabilities and capacities toward generating a comprehensive functional mapping of human genes and cellular phenotypes underlying the heterogeneity, pathogenesis and susceptibility to specific pain conditions, including conditions of chronic analgesic or other drug use, SUDs and other co-morbid and/or overlapping pain conditions.
Data Utility. The ultimate utility of PRECISION Human Pain network data for the broad research community may reside in an effective integration of different data elements including molecular content, cell anatomy, and physiology to define a cell type. Each element of data may be limited in its own value, but combined the data collected by individual projects should inform and cross validate each other to arrive at an integrative description closer to nature. Rapid data exchange and integration are critical for defining a cell type and unveiling the organizational rules behind cellular makeup and pain transmission and processing circuits. PRECISION Human Pain network Centers are expected to abide by the agreed data sharing policy and process to ensure unhindered data exchange and sharing, coordinating with the U24 Human Pain-associated Genes & Cells Data Center and Biomedical Knowledgebase within the PRECISION Human Pain network. In addition, all Centers are expected to work closely with the NIH HEAL Initiative’s Data Ecosystem (https://heal.nih.gov/data/heal-data-ecosystem), to maximize sharing and dissemination of data and digital assets to the pain research and therapeutics development communities.
Production Workflow. The ultimate long-term goal is to establish comprehensive functional mapping of human genes and cellular phenotypes underlying the heterogeneity, pathogenesis and susceptibility to specific pain conditions. The PRECISION Human Pain network should attain a high level of production at an affordable cost by adopting scalable technology platforms and streamlined workflows. As with other large-scale data generation efforts, the PRECISION Human Pain network Centers are expected to have the capability to operate at scale at the inception of the project, establish adequate process control with quantitative quality metrics at key points in the production workflow, and have plans to improve production workflow and cost efficiency.
Milestones. Success of the PRECISION Human Pain network will be facilitated by the adoption of clear, quantitative milestones by each of the participating U19 Centers as well as the DCIC. Applicants will propose annual milestones that reflect the Center’s ability to produce data and overall progress towards the achievement of the Center’s goals. Prior to funding an application, NIH Program staff may contact the applicant to discuss the proposed milestones and any changes suggested by the review panel or Program staff. Applications lacking milestones will be deemed incomplete and will not be reviewed (see Section IV.2).
Collectively, the accomplishments from these U19 Centers will result in a high likelihood of identifying information at single gene and cellular levels on individual susceptibility to chronic pain in humans, as well as provide a path forward for the development and management of personalized therapeutic modalities for different human pain conditions or pathologies. Successful establishment and execution of this collaborative network and the generation of an integrated knowledgebase through the DCIC would also be highly informative for developing research and therapeutic development programs for human pain conditions and/or diseases.
Activities that are Not Responsive:
The following research areas are considered outside the research scope of this FOA, and such applications will be considered non-responsive and will not be reviewed:
See Section VIII. Other Information for award authorities and regulations.
Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this FOA.
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 2-3 awards, for fiscal year 2022. Future year amounts and number of awards will depend on annual appropriations.
Application budgets are limited to direct costs of $1.5 million per year
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.
1. Eligible Applicants
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
For-Profit Organizations
Local Governments
Federal Governments
Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.
Applicant organizations
Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.
Program Directors/Principal Investigators (PD(s)/PI(s))
All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.
Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.
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:
1. Requesting an Application Package
The application forms package specific to this opportunity must be accessed through ASSIST or an institutional system-to-system solution. A button to apply using ASSIST is 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 Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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:
The letter of intent should be sent to:
D.P. Mohapatra, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9964
Fax: 301-402-2060
Email: [email protected]
Page Limitations
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.
Component | Component Type for Submission | Page Limit | Required/Optional | Minimum | Maximum |
---|---|---|---|---|---|
Overall | Overall | 12 | Required | 1 | 1 |
Administrative Core | Admin Core | 6 | Required | 1 | 1 |
Human Tissue Procurement and Processing Core | Core | 6 | Required | 1 | 1 |
Data Core | Core | 6 | Required | 1 | 1 |
Resource Core | Core | 6 | Optional | 0 | 2 |
Research Project | Project | 12 | Required | 1 | 3 |
Instructions for the Submission of Multi-Component Applications
The following section supplements the instructions found in the SF424 (R&R) Application Guide, and should be used for preparing a multi-component application.
These above-mentioned page limits refer to the research strategy section only; a separate "Specific Aims" page for each individual component of the U19 application should be submitted in accordance with the SF424 (R&R) Application Guide Instructions.
Revision applications must include an Overall component and the components that are affected by the revision.
Overall Component
When preparing your application, use Component Type Overall .
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.
SF424(R&R) Cover (Overall)
Complete entire form.
PHS 398 Cover Page Supplement (Overall)
Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.
Note: Proposed use (if any) of Human Embryonic Stem Cell lines and Human Fetal Tissue should be described in each relevant research projects and cores, as well as in the overall component.
Research & Related Other Project Information (Overall)
Follow standard instructions.
Human Subjects
Answer only the Are Human Subjects Involved? and Is the Project Exempt from Federal regulations? questions.
Vertebrate Animals
Answer only the Are Vertebrate Animals Used? question.
Project Narrative:
All instructions in the SF424 (R&R) Application Guide must be followed.
Facilities and Other Resources:
In this section, describe the institutional, commercial, and industrial investments and resources that constitute the environment for this research program. New cost-sharing commitments are not required. Some examples of institutional environment could include recruitment and salary support of new faculty or professional staff positions to support the resource components, startup packages, space renovations for team investigators, new facilities within the research and core components, dedicated equipment for research and resource components, dedicated budget lines or facilities for a team consortium, dedicated use of commercial products and technologies, equipment and technology contributions from commercial collaborators, etc. Summarize how the facilities and resources under each component are complimentary, and critical to the overall research goals and plan for this U19 center application. Facilities and resources specific for individual Research Projects and Cores should be detailed under the respective component sections.
Equipment:
Summarize on the availability and accessibility of all necessary equipment for the proposed U19 research program and center, and how they are complimentary and critical to the overall research goals and plan of this application. Equipment specific for individual Research Projects and Cores should be detailed under the respective research project and core sections.
Required Other Attachments:
Milestones (maximum 2 pages): Applications to this FOA must define a clear set of overall goals that are aligned with the expected PRECISION Human Pain network’s objectives and outcomes. This attachment should be entitled "Milestone Plan.pdf . Milestones must include clear, quantitative, and objective criteria for success. Annual quantitative milestones should establish feasibility for all aspects of the proposed research and provide clear indicators of continued progress or emergent difficulties and will be used to evaluate the application, not only in peer review, but also in consideration of the awarded project for funding of non-competing award years. The application must include well-defined milestones: e.g., amount and quality of data that will be generated by each data types each year, data comprehensiveness in terms of cell or tissue types, pain conditions and/or diseases, or pain conditions in the context of chronic analgesic or other drug use, etc., expected quality performance measures to be reached each year, and criteria for prioritizing selection of biospecimens and incorporation of new technologies, where applicable. Annual milestones should reflect the current ability to produce data from the beginning of the project and include plans for critically evaluating and revising these milestones on a regular basis.
Project/Performance Site Locations (Overall)
Enter primary site only.
A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.
Research and Related Senior/Key Person Profile (Overall)
Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this FOA) for the entire application.
In the biosketches, outline the PD(s)/PI(s) knowledge and past leadership experience in the relevant area of science. Outline his/her ability to organize, direct and administer a complex research project. Outline the Research Project and Core leaders' knowledge, past leadership experience, and past collaborative, teamwork experience.
A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.
Budget (Overall)
The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.
A minimum total effort for the overall PD/PI or MPI of the U19 center application is 2.4 person months. Effort cannot be reduced below this level during the entire project period.
A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.
PHS 398 Research Plan (Overall)
Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing (DMS) Plan will be attached in the Other Plan(s) attachment of the Overall Component in FORMS-H and subsequent application forms packages. For due dates on or before January 24, 2023, the Data Sharing Plan and Genomic Data Sharing Plan GDS) will continue to be attached in the Resource Sharing Plan attachment in FORMS-G application forms packages.
All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan. The Data Management and Sharing (DMS) Plan must be provided in the Overall component.
Introduction to Application: For Resubmission and Revision applications, an Introduction to Application is required in the Overall component.
Specific Aims: Describe concisely the central scientific, data and resource production goals of the proposed U19 Center, and state in priority order the overall aims of the Center to generate data on molecular signatures, cell types, and cellular function phenotypes or signatures that underlie human pain signal transduction, transmission, and processing. List the titles of all Research Projects and Cores. Outline how the Research Projects and Cores will synergistically contribute to attaining the aims of the proposed U19 Center and the overall goals of the NIH HEAL Initiative’s PRECISION Human Pain network.
Research Strategy: This section provides applicants an opportunity to present conceptual wholeness and research, data and knowledge integration of the U19 Center.
Letters of Support: Statements of individual and Institutional Commitment, as appropriate to the overall application, should be included in this section.
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. It is expected that data generated by HEAL Initiative-funded projects will 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. Additional guidance on 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:
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.
Recipients 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).
Authentication of Key Biological and/or Chemical Resources: Individuals are required to comply with the instructions for authentication plans for key biological and/or chemical resources as provided in the SF424 (R&R) Application Guide, with the following modification:
Briefly describe methods to ensure the identity and validity of key biological and/or chemical resources used in the proposed studies.
Information in this section must focus only on authentication of key biological and/or validation of key resources to be used in the study; all other methods and preliminary data must be included within the page limits of the research strategy. See NOT-OD-16-011 and NOT-18-228 for detailed information on authentication of key biological and/or chemical resources. Applications identified as non-compliant with this limitation will be withdrawn from the review process (see NOT-OD-17-105).
Reviewers will assess the information provided in the Authentication of Key Biological and/or Chemical Resources section. Any reviewer questions associated with key biological and/or chemical resource authentication will need to be addressed prior to award.
Appendix:
Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.
PHS Human Subjects and Clinical Trials Information (Overall)
When involving human subjects research, clinical research, and/or NIH-defined clinical trials 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, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.
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 (Overall)
All instructions in the SF424 (R&R) Application Guide must be followed.
Administrative Core
When preparing your application, use Component Type Administrative Core.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.
SF424 (R&R) Cover (Administrative Core)
Complete only the following fields:
PHS 398 Cover Page Supplement (Administrative Core)
Enter Human Embryonic Stem Cells in each relevant component.
Research & Related Other Project Information (Administrative Core)
Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.
Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.
Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.
Project /Performance Site Location(s) (Administrative Core)
List all performance sites that apply to the specific component.
Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.
Research & Related Senior/Key Person Profile (Administrative Core)
In the biosketches, document the ability of the Core Director to organize, direct and administer a complex research project.
Budget (Administrative Core)
Budget forms appropriate for the specific component will be included in the application package.
The U19 overall PD/PI(s) is/are expected to serve as a Project Lead of the Administrative Core with a minimum effort of 0.6 person months. If multiple PD/PIs serve as co-leads for the Administrative Core, eachof themareexpected to devote at least 0.6 person months.
Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.
PHS 398 Research Plan (Administrative Core)
Introduction to Application: For Resubmission and Revision applications, an Introduction to Application is allowed for each component.
Specific Aims: State in priority order the aims of the Administrative Core to address issues of the U19 Center coordination, communication, and management, indicating how the Core will contribute to the Center’s goals, as well as to the overarching goal of the NIH HEAL Initiative PRECISION Human Pain network.
Research Strategy:
Additional information required in the Administrative Core Research Strategy:
Governance Plan: Provide a detailed governance plan describing how the Team Director and a Project Manager (if proposed) will organize and direct efforts across the Research Projects and Cores. When multiple institutional sites are involved, a detailed description of the cooperative administrative arrangements should be included. Documentation of these arrangements should be included in the Overall Letters of Support section. This section should include acknowledgement of the need for quarterly reporting to the NIH HEAL Initiative program staff of the progress and accomplishments. Additional meetings with the NIH HEAL Initiative program staff will be arranged on a frequency appropriate for the development stage of the project, as determined by the NIH HEAL Initiative.
Letters of Support: Provide any letters of support from collaborators that are specific to the Administrative Core.
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, with the following modification:
Note: Do not submit the Resource Sharing and Data Sharing Plans here. The Resource Sharing and Data Sharing Plans should be submitted only in the Overall component.
Appendix:
Only limited items are allowed in the Appendix.Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.
PHS Human Subjects and Clinical Trials Information (Administrative Core)
When involving human subjects research, clinical research, and/or NIH-defined clinical trials 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 a 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.
Human Tissue Procurement and Processing Core
When preparing your application, use Component Type Human Tissue Procurement and Processing Core.'
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.
SF424 (R&R) Cover (Human Tissue Procurement and Processing Core)
Complete only the following fields:
PHS 398 Cover Page Supplement (Human Tissue Procurement and Processing Core)
Enter Human Embryonic Stem Cells in each relevant component.
Research & Related Other Project Information (Human Tissue Procurement and Processing Core)
Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.
Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.
Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.
Project /Performance Site Location(s) (Human Tissue Procurement and Processing Core)
List all performance sites that apply to the specific component.
Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.
Research & Related Senior/Key Person Profile (Human Tissue Procurement and Processing Core)
In the biosketches, outline the experience of personnel with human tissue procurement and processing for various downstream bulk tissue and single-cell molecular analyses.
Budget (Human Tissue Procurement and Processing Core)
Budget forms appropriate for the specific component will be included in the application package.
The Human Tissue Procurement and Processing Core Lead(s) must commit to a minimum of 0.6 person months of effort.
Budgets are also required for each consortium (subcontract), if they are part of the Human Tissue Procurement and Processing core.
Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.
PHS 398 Research Plan (Human Tissue Procurement and Processing Core)
Introduction to Application: For Resubmission and Revision applications, an Introduction to Application is allowed for each component.
Specific Aims: State in priority order the aims of the Human Tissue Procurement and Processing Core, indicating how this core will contribute to the proposed goals of the U19 Center, as well as to the overarching goal of the NIH HEAL Initiative PRECISION Human Pain network.
Research Strategy:
Include evidence for feasibility, including any supporting general and background preliminary findings.
Describe how this core will coordinate with other U19 centers to disseminate resources related to optimized protocols and procedures for human pain-associated tissues to pain research communities.
Describe how each of the Research Project(s) and Core(s) of the U19 Center will draw upon the Human Tissue Procurement and Processing Core, and how it in turn will respond to Research Project or Core needs. Include a timeline as well as a description of plans for appropriate stabilization, suitable storage and rapid shipment of biospecimens as needed by the Center’s Research Projects and Cores.
Letters of Support: Provide any letters of support from collaborators that are specific to the Human Tissue Procurement and Processing Core.
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, with the following modification:
Do not submit Resource Sharing or Data Sharing Plans here. The Resource Sharing and Data Sharing Plans should be submitted only in the Overall component.
Authentication of Key Biological and/or Chemical Resources: Individuals are required to comply with the instructions for authentication plans for key biological and/or chemical resources as provided in the SF424 (R&R) Application Guide, with the following modification:
Briefly describe methods to ensure the identity and validity of key biological and/or chemical resources used in the proposed studies.
Information in this section must focus only on authentication of key biological and/or validation of key resources to be used in the study; all other methods and preliminary data must be included within the page limits of the research strategy. See NOT-OD-16-011 and NOT-18-228 for detailed information on authentication of key biological and/or chemical resources. Applications identified as non-compliant with this limitation will be withdrawn from the review process (see NOT-OD-17-105).
Reviewers will assess the information provided in the Authentication of Key Biological and/or Chemical Resources section. Any reviewer questions associated with key biological and/or chemical resource authentication will need to be addressed prior to award.
Appendix:
Only limited items are allowed in the Appendix.Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.
PHS Human Subjects and Clinical Trials Information (Human Tissue Procurement and Processing Core)
When involving human subjects research, clinical research, and/or NIH-defined clinical trials 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 a 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.
Data Core
When preparing your application, use Component Type Data Core.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.
SF424 (R&R) Cover (Data Core)
Complete only the following fields:
PHS 398 Cover Page Supplement (Data Core)
Enter Human Embryonic Stem Cells in each relevant component.
Research & Related Other Project Information (Data Core)
Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.
Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.
Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.
Project /Performance Site Location(s) (Data Core)
List all performance sites that apply to the specific component.
Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.
Research & Related Senior/Key Person Profile (Data Core)
Budget (Data Core)
Budget forms appropriate for the specific component will be included in the application package.
The Data Management Core Lead(s) must commit to a minimum of 0.6 person months of effort.
Budgets are also required for each consortium (subcontract) if they are part of the data core.
Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.
PHS 398 Research Plan (Data Core)
Introduction to Application: For Resubmission and Revision applications, an Introduction to Application is allowed for each component.
Specific Aims: State in priority order the aims of the proposed Data Core, indicating how the core will contribute to the proposed goals of the U19 Center as well as to the overarching goal of the NIH HEAL Initiative PRECISION Human Pain network.
Research Strategy: Explain how the Data Core will serve the proposed U19 Center. Provide an overview as well as a detailed plan on data management and analysis practices.
Letters of Support: Provide any letters of support from collaborators that are specific to the Data Core.
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, with the following modification:
Do not submit Resource Sharing or Data Sharing Plans here. The Resource Sharing and Data Sharing Plans should be submitted only in the Overall component.
Appendix:
Only limited items are allowed in the Appendix.Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.
PHS Human Subjects and Clinical Trials Information (Data Core)
When involving human subjects research, clinical research, and/or NIH-defined clinical trials 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 a 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.
Resource Core
When preparing your application, use Component Type Resource Core.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.
SF424 (R&R) Cover (Resource Core)
Complete only the following fields:
PHS 398 Cover Page Supplement (Resource Core)
Enter Human Embryonic Stem Cells in each relevant component.
Research & Related Other Project Information (Resource Core)
Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.
Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.
Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.
Project /Performance Site Location(s) (Resource Core)
List all performance sites that apply to the specific component.
Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.
Research & Related Senior/Key Person Profile (Resouce Core)
Budget (Resource Core)
Budget forms appropriate for the specific component will be included in the application package.
Resource Core Lead(s) must commit to a minimum of 0.6 person months of effort.
Budgets are also required for each consortium (subcontract) if they are part of any resource core.
Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.
PHS 398 Research Plan (Resource Core)
Introduction to Application: For Resubmission and Revision applications, an Introduction to Application is allowed for each component.
Specific Aims: State in priority order the aims of the proposed Resource Core, indicating how the core will contribute to one or more of the Research Projects and Cores of the U19 Center. Provide a concise description of the broad activities and services of the proposed Core. Indicate why the Resources Core is an essential part of the U19 application, and how the proposed services will facilitate accomplishment of the proposed goals of the U19 Center and of the PRECISION Human Pain network
Research Strategy: Explain how the Resource Core will contribute to the research activities for one or more Research Projects and Cores of the U19 Center. Note: Resource Cores should not duplicate resources already available at the institution. Also, the activities of Resource Cores must not overlap with each other or with the activities of a Research Project(s) and/or of other Cores.
Letters of Support: Provide any letters of support from collaborators that are specific to the Resource Core.
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, with the following modification:
Note: Do not submit the Resource Sharing and Data Sharing Plans here. The Resource Sharing and Data Sharing Plans should be submitted only in the Overall component.
Authentication of Key Biological and/or Chemical Resources: Individuals are required to comply with the instructions for authentication plans for key biological and/or chemical resources as provided in the SF424 (R&R) Application Guide, with the following modification:
Briefly describe methods to ensure the identity and validity of key biological and/or chemical resources used in the proposed studies.
Information in this section must focus only on authentication of key biological and/or validation of key resources to be used in the study; all other methods and preliminary data must be included within the page limits of the research strategy. See NOT-OD-16-011 and NOT-18-228 for detailed information on authentication of key biological and/or chemical resources. Applications identified as non-compliant with this limitation will be withdrawn from the review process (see NOT-OD-17-105).
Reviewers will assess the information provided in the Authentication of Key Biological and/or Chemical Resources section. Any reviewer questions associated with key biological and/or chemical resource authentication will need to be addressed prior to award.
Appendix:
Only limited items are allowed in the Appendix.Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.
PHS Human Subjects and Clinical Trials Information (Resource Core)
When involving human subjects research, clinical research, and/or NIH-defined clinical trials 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 a 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.
Research Projects
When preparing your application, use Component Type Research Project.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.
SF424 (R&R) Cover (Research Project)
Complete only the following fields:
PHS 398 Cover Page Supplement (Research Project)
Enter Human Embryonic Stem Cells in each relevant component.
Research & Related Other Project Information (Research Project)
Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.
Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.
Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.
Facilities and Other Resources:
In this section, describe the institutional, commercial, and industrial investments and resources that constitute the environment for this research program. New cost-sharing commitments are not required. Some examples of institutional environment could include recruitment and salary support of new faculty or professional staff positions to support the resource components, startup packages, space renovations for team investigators, new facilities within the research and core components, dedicated equipment for research and resource components, dedicated budget lines or facilities for a team consortium, dedicated use of commercial products and technologies, equipment and technology contributions from commercial collaborators, etc. Summarize how the facilities and resources under each component are complimentary, and critical to the overall research goals and plan for this U19 center application. Facilities and resources specific for individual Research Projects and Cores should be detailed under the respective component sections.
Equipment:
Summarize on the availability and accessibility of all necessary equipment for the proposed U19 research program and center, and how they are complimentary and critical to the overall research goals and plan of this application. Equipment specific for individual Research Projects and Cores should be detailed under the respective research project and core sections.
Project /Performance Site Location(s) (Research Project)
List all performance sites that apply to the specific component.
Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.
Research & Related Senior/Key Person Profile (Research Project)
Budget (Research Project)
Budget forms appropriate for the specific component will be included in the application package.
The PD/PI is expected to devote a minimum effort of 1.8 person months. If multiple PD/PIs serve as co-leads for this research component, they are expected to devote a combined minimum effort of 1.8 person months
Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.
PHS 398 Research Plan (Research Project)
Introduction to Application: For Resubmission and Revision applications, an Introduction to Application is allowed for each component.
Specific Aims: State in priority order the aims of the proposed Research Project, indicating how the project will contribute to the U19 Center’s objectives as well as to the overarching goal of the PRECISION Human Pain network to generate data on molecular signatures, cell types, and cellular function phenotypes or signatures that may underlie human pain signal transduction, transmission and processing, including, but not limited to specific pain types, conditions and/or diseases, and/or under conditions of chronic analgesic use, other drug use, SUDs and other co-morbid and/or overlapping pain conditions. Provide a concise description of the rationale for the specific aims and questions proposed, and the overall approach to address the goals of the research project.
Research Strategy:
1. Significance
2. Innovation
3. Approach
Letters of Support: Provide any letters of support from collaborators that are specific to the Research Project.
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, with the following modification:
Note: Do not submit the Resource Sharing and Data Sharing Plans here. The Resource Sharing and Data Sharing Plans should be submitted only in the Overall component.
Authentication of Key Biological and/or Chemical Resources: Individuals are required to comply with the instructions for authentication plans for key biological and/or chemical resources as provided in the SF424 (R&R) Application Guide, with the following modification:
Briefly describe methods to ensure the identity and validity of key biological and/or chemical resources used in the proposed studies.
Information in this section must focus only on authentication of key biological and/or validation of key resources to be used in the study; all other methods and preliminary data must be included within the page limits of the research strategy. See NOT-OD-16-011 and NOT-18-228 for detailed information on authentication of key biological and/or chemical resources. Applications identified as non-compliant with this limitation will be withdrawn from the review process (see NOT-OD-17-105).
Reviewers will assess the information provided in the Authentication of Key Biological and/or Chemical Resources section. Any reviewer questions associated with key biological and/or chemical resource authentication will need to be addressed prior to award.
Appendix:
Only limited items are allowed in the Appendix.Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.
PHS Human Subjects and Clinical Trials Information (Research Project)
When involving human subjects research, clinical research, and/or NIH-defined clinical trials 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 a 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.
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) using ASSIST or other electronic submission systems. 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.
For information on how your application will be automatically assembled for review and funding consideration after submission go to: http://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.
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) and component Project Leads 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.
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, NIH. Applications that are incomplete or non-compliant will not be reviewed.
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 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 to the NIH Intramural Program, not through the extramural awardee's institution. 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.
Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) as part of the Resource Sharing Plan will not be evaluated at time of review.
Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.
A meritorious U19 application is expected to be well-balanced in interdisciplinary science that spans expertise in pain biology, including human pain, high-throughput genome, proteome and metabolome experimentation and analysis, including single-cell analysis, human tissue processing, medium- and large-scale single-cell functional analysis, tissue histological and imaging analysis, bioinformatics, statistics, and data science. In addition, the proposed number and composition of Research Projects and Cores are expected to adequately reflect the overall theme(s) of the Center and requirements of the PRECISION Human Pain network to achieve its goals
The entire research application will receive one Impact Score based on critical consideration of all the components of the entire application. To guide the final scoring, reviewers will make interim assessment scores of the Overall and each Research Project (scores 1-9), and each Core (exceptional, adequate, or inadequate).
Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).
Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.
Significance
Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?
Specific to this FOA:
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:
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?
Specific to this FOA:
Note: Since this FOA specifically seeks applications to systematically generate human pain-associated genes, cellular function and tissue analysis datasets, and possibly related tools, the NIH expects that some applications may propose mature and well-established approaches that may not be innovative per se to produce robust high-quality datasets for broad use by the research community.
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?
Specific to this FOA:
If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?
Environment
Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?
As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.
Overall Coordination
Does the center as a whole serve a purpose to be greater than the sum of the individual Research Projects and Core components? Does the overall organizational chart clearly present an overview of the performance sites and responsibilities of the Research Projects and Cores? Are the roles clearly defined and divided among the different entities? Is there a clear and sound plan for communication and coordination across entities demonstrating an integrated Center project capable of performing the functions specified in the FOA?
Milestones
Are proposed milestones clear and quantitative? Do the milestones establish feasibility for all aspects of the proposed research? Does the application include plans for critically evaluating and revising milestones on a regular basis? Are there additional key experiments that need to have milestones? Will the milestones provide adequate information to evaluate yearly progress of the Center project as a whole?
Protections for Human Subjects
For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.
Inclusion of Women, Minorities, and Individuals Across the Lifespan
When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.
Vertebrate Animals
The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.
Biohazards
Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.
Resubmissions
For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.
Renewals
Not Applicable
Revisions
For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.
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).
Does the application adequately address the issues related to the public release of data and data analyses (see the rationale for FAIR (Findability, Accessibility, Interoperability, and Reusability) Data Principles)? Does the application adequately describe for shared data, when it will be made available, where it will be stored, how it will be maintained, and how others will be able to find, access, and reuse it? Does the application adequately describe specific plans for resource sharing and distribution in the application?
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.
Center Components
Individual Center Components (i.e., Research Projects and Cores) will be assessed for relevant strengths and weaknesses in the context of the Overall Center; Research Projects will receiveindividual criterion scores (1-9), whereas and each Core will be assessed as exceptional, adequate, or inadequate.
Scored Review Criteria Research Project(s)
Significance
Does the Research 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 Research 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:
Investigators
Are the PD(s)/PI(s), collaborators, and other researchers well-suited for the Research 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?
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?
Specific to this FOA:
Approach
Are the overall strategy, methodology, available tools, and analyses well-reasoned and appropriate to accomplish the specific aims of the Research 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 and human tissue or 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:
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?
Scored Review Criteria Administrative Core
Scored Review Criteria Human Tissue Procurement and Processing Core
Scored Review Criteria Data Core
Scored Review Criteria Resource Core(s)
2. Review and Selection Process
Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NINDS, 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.
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:
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.
1. Award Notices
If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in theNIH 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: Grantee institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.
Prior Approval of Pilot Projects
Awardee-selected projects that involve {clinical trials or studies involving greater than minimal risk to human subjects} require prior approval by NIH prior to initiation.
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: Generaland 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 identity, 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 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.
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.
The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 75 and 2 CFR Part 200, and other HHS, PHS, and NIH grant administration policies.
The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the recipientsis anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the recipientsfor the project as a whole, although specific tasks and activities may be shared among the recipientsand the NIH as defined below.
The PD(s)/PI(s) will have the primary responsibilities as described below:
NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
Areas of Joint Responsibility include:
PRECISION Human Pain network Steering Committee:
The Steering Committee will be composed of the PD(s)/PI(s), Project Scientist(s) and External Scientific Panel members (experts to be named after award). The Steering Committee may also include designated representatives from the HEAL Data Sharing Ecosystem, as appropriate. The Steering Committee will be established to help monitor progress, encourage improvements, and coordinate the production of human pain-associated genes, cellular function and tissue analysis datasets and resources through the PRECISION Human Pain network. It is anticipated that additional coordination mechanisms might be set up with other U.S. and international groups that may join this effort. The PRECISION Human Pain network Steering Committee members will meet periodically to plan and design activities, review, and discuss progress, and establish priorities and policies. A chair will be designated on a rotating basis as needed. Each PD(s)/PI(s), and external scientific advisor will have one vote each and the NIH will have one vote through the participation of the Project Scientist(s). The frequency of meetings will be determined by the Project Scientist(s) who will be responsible for scheduling the time and place and for preparing concise proceedings or minutes which will be delivered to the Steering Committee members within 30 days after the meeting. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.
The PRECISION Human Pain network Steering Committee will:
External Scientific Panel (ESP):
The ESP will provide recommendations to the NIH HEAL Initiative PRECISION Human Pain network Project Team and the PRECISION Human Pain network about the progress and scientific direction of all components of the program. The ESP will be composed of four to six senior scientists who represent broad research community and have relevant expertise, although the membership may be enlarged permanently or on an ad hoc basis as needed. The ESP will meet at least twice a year; some meetings may be conducted by telephone conference. At least once a year, there will be a joint meeting with the Steering Committee for the members of both ESP and Steering Committees to interact directly. Twice a year the ESP will make recommendations regarding progress of the PRECISION Human Pain network and present advice to the NIH HEAL Initiative PRECISION Human Pain network Project Team about changes, if any, that may be necessary in the HEAL Initiative PRECISION Human Pain program.
Dispute Resolution:
Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.
Data Management and Sharing
Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.
Consistent with the NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.
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 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 75.113and 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 75and 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]
D.P. Mohapatra, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9964
Fax: 301-402-2060
Email: [email protected]
Michael L. Oshinsky, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9964
Email: [email protected]
Julia L. Bachman, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-827-7383
Email: [email protected]
Dana K. Andersen, M.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Phone: 410-868-0638
Email: [email protected]
Inna Belfer, MD, Ph.D.
National Center for Complementary and Integrative Health (NCCIH)
Phone: 301-435-1573
Email: [email protected]
Xincheng Zheng (Ted), M.D., Ph.D.
National Institute Of Arthritis And Musculoskeletal And Skin Diseases (NIAMS)
Phone: 301-594-4953
E-mail: [email protected]
Devon Oskvig, Ph.D.
National Institute on Aging (NIA)
Phone: 301-827-5899
Email: [email protected]
Melissa Ghim, PhD
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-529-6570
Email: [email protected]ov
Rachel Altshuler, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-5873
Email: [email protected]
Joe Bonner, PhD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-827-8303
Email: [email protected]
Mark Egli
National Institute On Alcohol Abuse And Alcoholism (NIAAA)
Phone: 301-594-6382
E-mail: [email protected]
Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke (NINDS)
Email: [email protected]
Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS)
Email: [email protected]
Elizabeth Gutierrez
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Phone: 301-594-8844
Email: [email protected]
Debbie Chen
National Center for Complementary and Integrative Health (NCCIH)
Phone: 301-594-3788
Email: [email protected]
Erik Edgerton
National Institute Of Arthritis And Musculoskeletal And Skin Diseases (NIAMS)
Phone: 301-594-7760
E-mail: [email protected]
Diana Rutberg, MBA
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-4798
Email: [email protected]
Sean Hine
National Cancer Institute (NCI)
Telephone: 240-276-6291
Email: [email protected]
Margaret Young
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-642-4552
Email: [email protected]
Judy Fox
National Institute On Alcohol Abuse And Alcoholism (NIAAA)
Phone: (301) 443-4704
E-mail: [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.