Part 1. Overview Information

Key Dates

All applications are due by 5:00 PM local time of applicant organization. 

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

No late applications will be accepted for this Notice of Funding Opportunity (NOFO).

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

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

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

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

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



Table of Contents
Part 1. Overview Information
Key Dates
Part 2. Full Text of Announcement
Section I. Notice of Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Purpose

The purpose of this Notice of Funding Opportunity (NOFO) is to solicit applications for multi-PI team-based, challenging, high impact projects to improve understanding of mechanisms of chronic pain in infants, children, and adolescents and to accelerate the development of age-appropriate, patient/family centered prevention and therapeutic approaches. This research will seek to advance an integrated understanding of the biological, psychological, and social factors that contribute to pediatric chronic pain. NIH is interested in pain research in infants, children, and adolescents that includes those with intellectual and physical disabilities and/or those who experience health disparities (e.g., diverse race/ethnicity, sexual and gender minorities, socioeconomically disadvantaged, medically underserved communities, people with limited English proficiency). Studies should integrate relevant behavioral and social influences and contexts on pain experience. These may include but are not limited to social determinants of health, social and other influences on the incidence of pain, the impact on perception and experience of pain, and the influences on pain reporting. Integration of behavioral and social sciences in pain research is critical to fully understand pain experiences, addressing disparities, and developing effective interventions. NIH encourages applicants to consider community-engaged research and interdisciplinary, collaborative applications to be developed in partnership with patient communities and/or community organizations where possible. The long-term goal is to develop improved knowledge of specific pediatric pain conditions as well as pain associated with diverse diseases/disorders; to improve understanding of pain in the context of child development; and, to facilitate the stratification of patients with specific pain conditions and co-morbidities to accelerate chronic pain prevention and therapeutic clinical trials.

This effort is part of the NIH HEAL (Helping to End Addiction Long-term) Initiative to speed the development and implementation of scientific solutions to the national opioid public health crisis. The NIH HEAL Initiative will bolster research across NIH to (1) improve treatment and prevention of opioid misuse and opioid use disorder and (2) enhance pain management. More information and periodic updates about the Initiative are available at: https://heal.nih.gov/.
The goal of HEAL KIDS PAIN (Knowledge, Innovation and Discovery Studies on pediatric Pain) Initiative is to advance understanding, assessment, measurement, treatment, and prevention of pain in infants, children, and adolescents, including those with disabilities and/or experiencing health disparities. The Chronic Pain Research Teams program (CPT) (this NOFO) will focus on pediatric chronic pain. Applicants to this CPT NOFO are strongly encouraged to closely review the related NOFO (RFA-HD-24-011) for the Acute Pain Trials Program and the NOFO (RFA-HD-24-12) for the Resource Data Center (RDC) to understand the collaborative intent of the full HEAL KIDS Pain Initiative.

Structure
Research Teams. Each self-assembled Research Team will propose an interdisciplinary approach to address a critical challenge related to chronic pediatric pain, by leveraging existing, ongoing chronic pain cohorts. They will work together to relate the findings to clinical, psychological, and social factors that affect chronic pain to develop an integrated understanding of the pain experience at the individual patient and family level. To achieve the goal of the HEAL KIDS CPT program, awardees are expected to use team science approaches with collaboration between researchers from various disciplines, including pain and data science. Each Team will be expected to conduct research based on the focus, patient cohorts and analytic modalities proposed in the applications and engage in collaborative activities and projects designed after the award.

CPT Consortium

The Research Teams will form the CPT Consortium. All awarded teams will collaboratively engage in the analyses and broad sharing of biological data, methodologies, and, if appropriate, disease cohorts consistent with the overarching goals of the program. As members of the Consortium and in collaboration with the HEAL KIDS RDC, the teams will cooperatively define shared data elements and annotation and develop standardized protocols during an initial planning period. 
A HEAL KIDS RDC (RFA-HD-24-012) will assist with managing the data across the HEAL KIDS PAIN network. This will include support for the sharing of data, models, and analytical tools across the CPT. This will include coordinating network-wide definition of common data elements and data annotation working with the research teams. HEAL KIDS CPT awardees will be expected to work collaboratively to advance pediatric chronic pain research and with the awarded HEAL KIDS Pain RDC to develop data standards and achieve the data integration and harmonization goals of the program.
The CPT Consortium will be organized and led by the following:

• CPT Steering Committee (CPT SC): Composed of Research Teams' principal investigators, selected subject matter experts, and the NIH Project Officers and Coordinators. The CPT SC will have responsibility for collaboratively formulating research priorities, and for helping to develop, finalize, and implement all collaborative projects.
• CPT-Chair: The Chair will lead the CPT SC. Together with the CPT SC, the Chair will be responsible for leading the development of the collaborative and harmonization activities of the Consortium. As part of this process, the Chair will engage with other stakeholders, including the Institute and HEAL staff. NIH will name the Chair for the initial project period.
• CPT Working Groups: To be established after award, according to the areas of focus of collaborative activities. It is expected that a CPT Pain expert working group will provide scientific input in projects across the Consortium and become a resource for consultation with other HEAL pediatric projects.;

In consultation with the NIH, the CPT Consortium will work with the RDC in the following activities:

• Coordinate the flow of data between the Research Team sites and the RDC to facilitate data deposition.
• Deposit data generated by the CPT in a HEAL compliant data repository, using established NIH resources, for use by network investigators and the public.

Background and Scope
Pain in infants, children, and adolescents is common, often under-recognized, inconsistently assessed or measured, and inadequately treated. Moreover, the relationship between pain and human development, including any potential effects of repeated pain experiences on future physical dependency, remains largely unexplored.
Pediatric chronic pain is a significant public health problem and a major contributor to morbidity in children and adolescents. The World Health Organization Guidelines on the Management of Chronic Pain in Children definition of chronic pain is pain that persists or recurs for longer than three months; this definition is used in this NOFO. Pediatric chronic pain occurring as a symptom of chronic disease or as a primary pain disorder are both included within the scientific scope of this NOFO. 
Poorly controlled chronic or intermittent pain affects children’s development and well-being beyond the experience of pain itself (e.g., school days missed, difficulty maintaining peer relationships). Chronic pain in children can profoundly impact the functioning of the family unit and the parent(s)/caregiver(s) psychologically, socially, and financially. Therefore, the psychosocial model of chronic pain will be a common aspect of the expected CPT research program. 
There are important physiological, cognitive, developmental, and social differences between adults and children affecting the pain experience and limiting the value of data extrapolation for drug approval. New research approaches are needed to understand the developmental aspects of nociception and pain systems and identify age-appropriate therapeutic targets.;
Chronic pain may adversely affect the development of pain systems, related responses and psychological well-being. Children and adolescents who experience persistent pain are at increased risk for pain, anxiety, and depression in adulthood. Therefore, screening, preventing, and treating co-occurring mental health disorders within an integrative care model is essential. Effective and safe treatments and multidisciplinary strategies are needed to prevent and treat moderate to severe chronic pain and refractory chronic pain in children with chronic diseases.

Objectives
Areas of scientific interest include but are not limited to:

• Mechanisms of pain in children and adolescents, including studies to define the neurobiology of pain mechanisms in children and how they change with age, investigate the sex differences in pain mechanisms, and determine the effects of pain on the developing brain
• Identification of risk factors and underlying mechanisms that may predispose to chronic pediatric pain, including identification of early childhood factors that increase pain vulnerability and affect pain management. 
• Generating evidence for new approaches to preventing the acute to chronic pain transition in children and adolescents.
• Large-scale data resources and big data approaches to discover multi-level factors (biologic, clinical, psychosocial, behavioral, cultural, social, structural) related to pediatric chronic pain, and new patterns and trends that may translate to novel, targeted interventions for pediatric chronic pain.
• Evaluation and clinical validation of age-appropriate measures, tools, and technologies for the assessment of chronic pain across the continuum of care.
• Development and testing of innovative approaches for age-appropriate evaluation and measurement of chronic pain.
• Longitudinal evaluations of pediatric pain cohorts to establish risk factors and mechanisms by which early life pain experiences may affect adult pain vulnerability.
• Mechanistic studies to discover and validate potential targets for intervention.
• Studies including novel technologies for the identification and characterization of genetic elements, epigenetic signatures, and molecular/cellular pathways that contribute to pain signal transduction, transmission, and processing by age groups.
• Use of “omics”, imaging, and other high dimensional analytics to define chronic pain endotypes. Projects could be focused on more than one primary or secondary specific pain condition, including but not limited to primary chronic pain, painful neuropathy, arthritis and musculoskeletal pain, headache, chemotherapy-induced neuropathy, eye pain, sickle-cell pain, post-surgical pain, cancer pain, visceral pain, gynecologic pain, painful disorders of the orofacial region and pain co-occurring with substance use disorders, and other such conditions.

Projects could be focused on gender-specific child and adolescent development and areas of pain unique to females such as menstrual pain, dysmenorrhea, and pelvic pain or on other female-specific conditions associated with pain such as fibroids, endometriosis, vulvodynia, and vestibulitis.

Innovative designs targeting age related pain mechanisms across diseases are encouraged.

Research Activities
It is anticipated that the CPT Program research goals and objectives will be fulfilled through a combination of Research Team specific projects and a series of prioritized CPT Collaborative Projects designed by the CPT Consortium Steering Committee. Modifications to the Research Project Team projects resulting from early interactions with members of the CPT Consortium and with the RDC are anticipated. Thus, all studies proposed in the applications will be a starting point for discussions regarding the research to be undertaken following a short planning period. Activities may include, but are not limited to:

Planning:

• Research Teams collaboratively establish research priorities and synergies between analytic pipelines.
• Collaboratively define shared priorities and methodologies across projects.
• Establish common, harmonized clinical protocols and studies.
• Obtain regulatory and other approvals.
• Set up Research Team specific procedures and standards for data management and visualization.
• Coordinate data standards and data harmonization with the HEAL KIDS RDC
• Optimize and validate methods.
• Optimize next generation assays.
• Conduct small scale proof of concept studies to determine if clinical and analytic pipelines are robust.
• Develop and test new tools for data analysis.

Scale Up

• Implement Research Teams and Collaborative projects.
• Periodically update and release data and tools to facilitate analysis.
• Develop meta-analysis plans and strategies, develop, and deploy tools that researchers can use to interrogate the data, promote the identification of potential druggable targets based on new omics type data.
• Make data available via open or controlled access depending on the data type and data source and as determined by the informed consent documents for each study guided by the designated IRB.

Products generated by awardees will become part of a shared resource intended to support infrastructure and maximize endeavors in the HEAL KIDS Pain program.

• Large-scale human genetic data should be shared through the National Center for Biotechnology Information (NCBI's) database of Genotypes and Phenotypes (dbGaP) and Sequence Read Archive (SRA), as appropriate.

For applications proposing a clinical trial, note the following definitions and restrictions for this funding announcement:
Clinical trials are research studies in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes. For this funding announcement, only the following types of clinical trials will be accepted

1. Mechanistic trials, defined as studies designed to understand inter-individual differences in biological or behavioral process(s), the pathophysiology of pain and co-morbid condition to be studies, or the mechanism of action of an intervention (i.e., how an intervention works, but not if it works or is safe).
2. Basic Experimental Studies with Humans (BESH), defined as basic research studies involving humans that seek to understand the fundamental aspects of inter-individual differences in pain and co-morbid conditions.
   
   For further clarification on how NIH defines the different types of clinical trials, please refer to the following resources:

• NOT-OD-15-015: Notice of Revised NIH Definition of “Clinical Trial”
• NIH's Definition of a Clinical Trial
• Decision Tree for NIH Clinical Trial Definition
• Guidance for Basic Experimental Studies with Humans (BESH) Funding Opportunities
• NIH Definition of Clinical Trial Case Studies 
• Important points to consider before applying:
  
  HEAL Core Common Data Elements (CDE) The NIH HEAL Initiative research portfolio spans a broad array of data types that are a rich resource for future studies. Maximizing the value of data collected through the initiative is part of the initiative’s collective responsibility, given the magnitude of the opioid crisis and needs of individuals experiencing pain and addiction. To facilitate cross-study comparisons and improve the interoperability of findings, clinical pain research recipients will collaborate and agree to use common data elements for patient-reported outcomes (PROs). All HEAL studies collecting human subject data and planning to use CDEs (even studies outside the clinical pain research portfolio) are strongly encouraged to search for applicable CDEs within the HEAL database, and use questionnaires from this database if possible. Studies using CDEs, regardless of whether they are part of the HEAL repository, will be required to report which questionnaires are being used. Details of HEAL CDEs can be found at https://heal.nih.gov/data/common-data-elements. HEAL pain clinical studies must include plan to use HEAL core Common Data Elements (CDE) (https://heal.nih.gov/data/common-data-elements). HEAL Initiative clinical studies that are using copyrighted questionaries are required to obtain licenses for use prior to initiating data collection. Licenses must be shared with the HEAL CDE team and the program officer prior to use of copyrighted materials. To the extent possible, all other (non-pain) HEAL studies conducting clinical trials or research involving human subjects are expected to use questionnaires by the HEAL CDE program, if applicable and relevant to their research.
  Engaging People with Lived Experience and other Collaborators People with lived experience (e.g., patients, patient advocates, caregivers, families, community leaders) have important insights that can improve meaningful outcomes, uptake of research findings, and health equity across the continuum of research from basic through implementation studies. The perspectives of other relevant collaborators (e.g., health service providers, payors, public health agencies, community-based organizations, biotech, pharma) can further improve research impact. The NIH HEAL initiative strongly encourages applicants to specify their plan for meaningful engagement of people with lived experience and other collaborators in the research process. Meaningful engagement will vary with the focus of the research but should at minimum ensure that researchers are connecting with relevant collaborators and incorporating their perspectives throughout the conception, implementation, and dissemination of the research. Meaningful engagement should address what the researchers will learn and how the people with lived experience and/or collaborators will benefit from the partnership. In addition, NIH encourages outreach to people with lived experience from populations who experience health disparities. See this resource for more information in engaging people with lived experience: (https://aspe.hhs.gov/lived-experience).
  PI Meeting Attendance The NIH HEAL Initiative will require a high level of coordination and sharing between investigators. It is expected that NIH HEAL Initiative recipients 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, recipients are expected to participate in an annual meeting that brings together early-career pain researchers funded at NIH and their mentors. This meeting will be executed by the Coordinating Center for National Pain Scientists Career Development (CCNPS). The purpose of these meetings is to enhance mentorship and training, to collaborate with pain researchers across the continuum of pain research and build relationships to enhance research and potentially collaborate with researchers outside their institution. For more information on the CCNPS, please review RFA-NS-22-060.
  Prior Consultation with NIH HEAL Initiative Program staff The NIH HEAL Initiative intends to fund a limited number of applications for this NOFO. Therefore, consultation with relevant staff at least 6 weeks prior to the application due date is strongly encouraged. Once applicants have identified overall program objectives and PD/PI participants, HEAL Initiative staff may be able to advise applicants whether the proposed research goals and strategy meets the goals of The NIH HEAL Initiative and mission of the ICs, whether it addresses one or more high priority research areas, and whether it is appropriate for this NOFO. A proposed collaborative program that is closely related to the goal of a PD/PI's existing NIH-funded research might require that funding be relinquished to avoid overlap. HEAL Initiative staff will not evaluate the technical and scientific merit of the proposed program in advance; technical and scientific merit will be determined during the peer review process using the review criteria indicated in this NOFO.
  
  Pre-Application Technical Assistance Information: An informational pre-application technical assistance webinar, addressing the scientific and administrative issues associated with this initiative, is anticipated. The purpose of this webinar will be to (1) familiarize potential applicants with established NIH guidelines and criteria for review, (2) discuss the areas of programmatic emphasis, and (3) facilitate the submission of a well-organized application. Applicants interested in the pre-application technical assistance webinar can contact: niams_pain@mail.nih.gov or visit https://www.niams.nih.gov/grants-funding/funded-research/niams-role-in-nih-heal-initiative for webinar details. Participation in the webinar is not required to submit an application in response to this NOFO. Individual consultation, separate from the pre-application webinar, is also available upon request and encouraged for all interested applicants.
   

See Section VIII. Other Information for award authorities and regulations. Applications that are missing parts are deemed to be incomplete and will be withdrawn and not reviewed. Applications must include:;

• Attachment 1. Special Strengths (2 pages) (Required)
• Attachment 2. Collaborative Project (2 pages) (Required)
• Attachment 3. Collaboration Plan (1 page) (Required);
• Attachment 4. Plan for Enhancing Diverse Perspectives (PEDP) (2 page) (Required)

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

Plan for Enhancing Diverse Perspectives (PEDP)

The NIH recognizes that teams comprised of investigators with diverse perspectives working together and capitalizing on innovative ideas and distinct viewpoints outperform homogeneous teams. There are many benefits that flow from a scientific workforce rich with diverse perspectives, including: fostering scientific innovation, enhancing global competitiveness, contributing to robust learning environments, improving the quality of the research, advancing the likelihood that underserved populations participate in, and benefit from research, and enhancing public trust.

To support the best science, the NIH encourages inclusivity in research guided by the consideration of diverse perspectives. Broadly, diverse perspectives can include but are not limited to the educational background and scientific expertise of the people who perform the research; the populations who participate as human subjects in research studies; and the places where research is done.

This NOFO requires a Plan for Enhancing Diverse Perspectives (PEDP), which will be assessed as part of the scientific and technical peer review evaluation.  Assessment of applications containing a PEDP are based on the scientific and technical merit of the proposed project. Consistent with federal law, the race, ethnicity, or sex (including gender identify, sexual orientation, or transgender status) of a researcher, award participant, or trainee will not be considered during the application review process or when making funding decisions.  Applications that fail to include a PEDP will be considered incomplete and will be administratively withdrawn before review.

The PEDP will be submitted as Other Project Information as an attachment (see Section IV).  Applicants are strongly encouraged to read the NOFO instructions carefully and view the available PEDP guidance materials.

Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Local Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)

Federal Governments

• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign Organizations) are not 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 How to Apply - 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. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information

• System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
  • Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registrations; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov – Applicants must have an active SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account.  PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. 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 How to Apply - Application Guide.

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement NIH Grants Policy Statement Section 1.2 Definition of Terms.

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 NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NIH Grants Policy Statement 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

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

Letter of Intent

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

The letter of intent should be sent to:
Email: NIAMS_PAIN@mail.nih.gov

Page Limitations

All page limitations described in the How to Apply – Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the How to Apply – Application Guide and should be used for preparing an application to this NOFO.

SF424(R&R) Cover

All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Other Project Information

All instructions in the How to Apply - Application Guide must be followed.

Facilities and Other Resources: Describe the facilities and resources available for the coordination of a multi-site clinical trial as a Resource and Data Center, including any project management tools that will be used. Describe how the infrastructure at the Resource and Data Center will facilitate the efficient operation of the proposed multi-site clinical trials awarded under RFA-HD-24-011. If applicable, discuss any community participatory agreements and/or stakeholder agreements to support the protocol.

Other Attachments:The application must include the following documents, uploaded as separate pdf files.

Attachment 1. Special Strengths (2 pages) (Required)
The filename "Special Strenghts.pdf" should be used and will be reflected in the final image bookmarking for easy access for reviewers.

Provide a summary of the CPT’s special strengths as a pdf attachment. Applicants are encouraged to describe special or unique strengths and resources such as current cohorts, data, patient, family and community engagement systems that may be relevant to the application and to the HEAL KIDS Pain Program. This may include, but is not limited to, state-of-the art scientific capabilities that may be available for the HEAL KIDS Pain program, clinical research expertise (pediatrics, anesthesiology, neuroscience, imaging, behavioral, psychology, immunology, outcomes and measurement science) and technologies (e.g., genomic, proteomic, imaging, AI/ML, statistical analysis) that could be drawn upon on an as-needed basis, as well as any research resources that have established at the applicant’s institution. Indicate technical and other capabilities to evaluate acute to chronic pain transition in pediatric populations. NIH expects availability of well characterized acute pain cohorts to be supported by the HEAL KIDS Acute Pain Trial Networks. These cohorts would be available for the possible identification of risk factors, mechanisms, and possible biomarkers of the transition from acute to chronic pain. The cohorts may prove valuable to assess risk factors contributing to chronic pain in late adolescence of adulthood.

Attachment 2. Collaborative Project. (2 pages) (Required)

The filename "Collaborative Project.pdf" should be used and will be reflected in the final image bookmarking for easy access for reviewers.

The Collaborative Project concept should describe a pilot/exploratory/ or hypothesis testing project on a key aspect of chronic pediatric pain that builds on strengths of the applicant and engages other members of the CPT Consortium after award. It is recognized that applicants will NOT know in advance with whom they will be collaborating because the members of the CPT will not be known before award; therefore, applicants should make reasonable assumptions as to the types of collaborations that will be available and build flexibility into their research plans. Recent programs such as HEAL BACPAC and HEAL RE-JOIN have demonstrated the importance of the individual team’s themes in subsequent network/consortium collaborations. The CPT will fully develop the Collaborative Projects after award, and they will become part of the CPT research program. Collaborative Projects may be expanded or reduced after award depending upon how well they are ultimately integrated within the CPT. Collaborative Projects will be supported for three years; support in years 4 and 5 will depend on progress and funds available.

Attachment 3.;Collaboration Plan. (1 page) (Required)

The filename “Collaboration Plan.pdf" should be used and will be reflected in the final image bookmarking for easy access for reviewers.

This attachment must describe for the full team proposed in this application, including and beyond the PIs: the roles and responsibilities of each key member of the team, processes and strategies to ensure effective communication and interactions, and for resolving conflicts between members. Describe a plan to facilitate the interaction between the Team leadership and all key personnel at different sites for the team proposed in the application.

Attachment 4. Plan for Enhancing Diverse Perspectives (PEDP) (2 pages) (Required)

The filename “PEDP.pdf" should be used and will be reflected in the final image bookmarking for easy access for reviewers.

Plan for Enhancing Diverse Perspectives (PEDP)

• In an "Other Attachment" entitled "Plan for Enhancing Diverse Perspectives," all applicants must include a summary of actionable strategies to advance the scientific and technical merit of the proposed project through expanded inclusivity.
• Applicants should align their proposed strategies for PEDP with the research strategy section, providing a holistic and integrated view of how enhancing diverse perspectives and inclusivity are buoyed throughout the application.
• The PEDP will vary depending on the scientific aims, expertise required, the environment and performance site(s), as well as how the project aims are structured.
• The PEDP may be no more than 2 pages in length and should include:
  • Actionable strategies using defined approaches for the inclusion of diverse perspectives in the project;
  • Description of how the PEDP will advance the scientific and technical merit of the proposed project;
  • Anticipated timeline of proposed PEDP activities;
  • Evaluation methods for assessing the progress and success of PEDP activities.

Examples of items that advance inclusivity in research and may be appropriate for a PEDP can include, but are not limited to:

• Partnerships with different types of institutions and organizations (e.g., research-intensive; undergraduate-focused; HBCUs; emerging research institutions; community-based organizations).
• Project frameworks that enable communities and researchers to work collaboratively as equal partners in all phases of the research process.
• Outreach and planned engagement activities to enhance recruitment of individuals from diverse groups as human subjects in clinical trials, including those from underrepresented backgrounds.
• Description of planned partnerships that may enhance geographic and regional diversity.
• Outreach and recruiting activities intended to diversify the pool of applicants for research training programs, such as outreach to prospective applicants from groups underrepresented in the biomedical sciences, for example, individuals from underrepresented racial and ethnic groups, those with disabilities, those from disadvantaged backgrounds, and women.
• Plans to utilize the project infrastructure (i.e., research and structure) to enhance the research environment and support career-advancing opportunities for junior, early- and mid-career researchers.
• Transdisciplinary research projects and collaborations among researchers from fields beyond the biological sciences, such as physics, engineering, mathematics, computational biology, computer and data sciences, as well as bioethics.

Examples of items that are not appropriate in a PEDP include, but are not limited to:

• Selection or hiring of personnel for a research team based on their race, ethnicity, or sex (including gender identify, sexual orientation, or transgender status).
• A training or mentorship program limited to certain researchers based on their race, ethnicity, or sex (including gender identify, sexual orientation, or transgender status).

For further information on the Plan for Enhancing Diverse Perspectives (PEDP), please see PEDP guidance materials.

SF424(R&R) Senior/Key Person Profile

All instructions in the How to Apply - Application Guide must be followed.

R&R Budget

All instructions in the How to Apply - Application Guide must be followed.

Application budgets must plan for the following:

• The CPT budget must not exceed $1,300,000 in direct costs for any given year.

The following items must be included in the project budget:

• PD(s)/PI(s) are expected to commit a minimum of 2.4 person months per year. The level of commitment can be increased to be commensurate with the needs of the project (planning, pilot or scale up activities). Applications proposing Multiple PD(s)/PIs(s) must have a minimum combined PD/PI effort of 2.4 person months.
• Project Manager to serve as liaison to the HEAL KIDS RDC.
• Travel to two CPT program meetings and/or HEAL meetings per year; travel to two additional meetings or workshops within the five -year award period.
• Support for the activities of the HEAL KIDS CPT Consortium committees, (e.g., DSMBs or Steering or working groups) as requested, through provision of materials/documentation support, meeting planning and logistics and conference call/webinar coordination. 
• A budget line item for the Collaborative Project for $200,000 direct costs per year. 
• Administrative costs to support team activities and functions.
• Administrative costs to support the Consortium-wide administrative and logistical activities. Only one awardee will ultimately be responsible for the full administration of Consortium.

PEDP implementation costs:

Applicants may include allowable costs associated with PEDP implementation (as outlined in the Grants Policy Statement section 7): Plan For Enhancing Diverse Perspectives (PEDP) - NINDS COMBINE RM1 | National Institute of Neurological Disorders and Stroke (nih.gov)

R&R Subaward Budget

All instructions in the How to Apply - Application Guide must be followed.

PHS 398 Cover Page Supplement

All instructions in the How to Apply - Application Guide must be followed.

PHS 398 Research Plan

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

Specific Aims: Provide the overall goals for the entire application, and indicate separately, specific aims for the planning and the scale up phase.

Research Strategy: Organize the Research Strategy in the subsections identified below.

1. Background and Significance

• Identify and address a significant pediatric pain challenge or complex research question relevant to a single or multiple primary or secondary chronic pain conditions in children and adolescents.
• Discuss the research opportunities and needs that can be addressed with the proposed team science approach and accounting for the expected inclusion of state of the art and next generation technologies and analytics in the HEAL KIDS CPT program.
• Discuss existing and proposed patient populations and cohort(s) and relevant controls to address the challenges and opportunities to dissect underlying mechanism of pain in the biopsychosocial context.
• Address the heterogeneity of patient pain phenotypes and their relation to age and sex as it relates to the pain experience, progression, response to treatment and quality of life.
• Discuss ethical and safety issues in obtaining biospecimens, images and other data for research in participants with disease and controls.
• Discuss the challenges (if any) in obtaining pain qualitative and quantitative data and biospecimens for research, especially from underrepresented groups.

2. Preliminary Data

• Describe availability and access to patient cohorts including number and characteristics of the patients followed (i.e., private insurance, Medicaid), resources available (personnel) and cohort demographics.
• Document the clinical research experience of the team in clinical, laboratory and other clinical and patient reported outcomes assessments, including past collaborative activities.
• Demonstrate that the site(s) will ensure safety, minimize risk and conform to the highest ethical, research and clinical standards. This will likely involve diverse and multidisciplinary teams. Applicants should outline how such discussions will take place at the start of studies and as research progresses.
• Demonstrate pre-application involvement of an IRB, as appropriate for the disease focus of the application.
• Discuss other sources of data and samples (including archived tissue) from controls or patients to be used for discovery and validation efforts. (Note: any existing data or samples discussed in the application must be made available to the HEAL CPT program upon award).
• Discuss the experience of engaging patients, families and relevant communities with research and health care delivery activities.

3. Proposed Design

• Describe the inclusion and exclusion criteria, treatment regimens, clinical assessments and patient reported outcomes.
• Describe options for patient phenotyping and deep phenotyping within the CPT collaborating sites.
• Describe approach to obtaining biospecimen, images or other patient samples/data for research.
• Describe the approach to stakeholder engagement.
• Describe data analysis plans.

4. Management of the Interdisciplinary Team

• Describe the formal organizational structure of the disease multidisciplinary team, including lines of authority and responsibility, with attention to the relationship of the organizational structure to the major objectives of the CPT.
• Document willingness to accept the governance, common protocols, publication policies, collaborative procedures, confidentiality and data sharing and management plans to be developed by the HEAL CPT in collaboration with other sites and with the RDC.
• Confirm willingness to attend HEAL KIDS Pain CPT consortium-wide meetings virtually and in-person meetings at least twice yearly. Applicants should also state their willingness to work collaboratively with the other HEAL KIDS Pain investigators and with the NIH on conference calls, working groups, SC meetings, and in the dissemination of research findings through publication or presentation.

5. Timelines and Milestones

A timeline including milestones is required. Milestones should function as indicators of continued progress. Timelines must state when metrics for assessment of progress will be achieved, including specific milestones for progressing to the scale up project.

Letters of Support: Because this program requires a high degree of collaboration to be successful, departmental and institutional commitments to participate in the HEAL KIDS Pain program of research should be clearly documented. Provide letters of support from appropriate individuals at the applicant site detailing:

• Institutional support in areas of grants management, personnel provision, space allocation, procurement, IT infrastructure, as well as general logistical support of the research program. Evidence of previous experience in the unique needs of conducting pediatric research, as well as evidence of past support can be cited.
• Clearly expressed intent to:
  • Participate in a cooperative and collaborative manner with the HEAL KIDS Pain program investigators and research staff, NIH staff, as needed, in all aspects of research as outlined in this NOFO. o Prioritize HEAL KIDS Pain program research, including committing to safeguard staff time for the satisfactory conduct of the related work. ;
  • Comply with HEAL and HEAL KIDS Pain program Data Management and Sharing Plans, policies and requirements as outlined in this NOFO and as determined by the program investigators.
  • Keep confidential and do not disclose any confidential or proprietary information when working with program investigators and/or industry partners, other than outlined by HEAL KIDS Pain program developed policies and HEAL requirements.

Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

• No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.
  • Participate in a cooperative and collaborative manner with the HEAL KIDS Pain program investigators and research staff, NIH staff, as needed, in all aspects of research as outlined in this NOFO.
  • Prioritize HEAL KIDS Pain program research, including committing to safeguard staff time for the satisfactory conduct of the related work.
  • Comply with HEAL and HEAL KIDS Pain program Data Management and Sharing Plans, policies and requirements as outlined in this NOFO and as determined by the program investigators.
  • Keep confidential and do not disclose any confidential or proprietary information when working with program investigators and/or industry partners, other than outlined by HEAL KIDS Pain program developed policies and HEAL requirements.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply - Application Guide.

Other Plan(s): 

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

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 HEAL Initiative has additional requirements that must be addressed in the Data Management and Sharing Plan (DMSP). All HEAL-generated data must be shared through the HEAL Initiative Data Ecosystem;following HEAL’s compliance guidance (https://heal.nih.gov/data/complying-heal-data-sharing-policy). Specifically, HEAL applicants must include:

• Plans to submit data and metadata (and code, if applicable) to a HEAL-Compliant data repository (https://www.healdatafair.org/resources/guidance/selection) and follow requirements of the selected repository
• Plans to register your study with the HEAL platform within one year of award (https://heal.github.io/platform-documentation/study-registration/)
• Plans to submit HEAL-defined study-level metadata within one year of award (https://github.com/HEAL/heal-metadata-schemas/blob/main/for-investigators-how-to/study-level-metadata-fields/study-metadata-schema-for-humans.pdf) and;https://heal.github.io/platform-documentation/slmd_submission/).
• HEAL pain clinical studies must include plan to use HEAL core Common Data Elements (https://heal.nih.gov/data/common-data-elements).;HEAL Initiative clinical studies that are using copyrighted questionnaires are required to obtain licenses for use prior to initiating data collection. Licenses must be shared with the HEAL CDE team and the program officer prior to use of copyrighted materials.
• To the extent possible, all other (non-pain) HEAL studies conducting clinical trials or research involving human subjects are expected to use questionnaires by the HEAL Clinical Data Elements (CDE) Program (https://heal.nih.gov/data/common-data-elements) if applicable and relevant to their research.
• Studies using CDEs, regardless of whether they are part of the HEAL repository, will be required to report which questionnaires are being used.
• To the extent possible, HEAL awardees are expected to integrate broad data sharing consent language into their informed consent forms.

HEAL has developed additional details and resources to fulfill these requirements (https://www.healdatafair.org/resources/road-map).Budgeting guidance for data sharing can be found inNOT-OD-21-015 and the;NIH Scientific Data Sharing site.

Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply - Application Guide.

• No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

PHS Human Subjects and Clinical Trials Information

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the How to Apply - 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 How to Apply - Application Guide must be followed.

PHS Assignment Request Form

All instructions in the How to Apply - Application Guide must be followed.

3. Unique Entity Identifier and System for Award Management (SAM)

See Part 2. 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. contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time.  If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

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 How to Apply – 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 Section 7.9.1 Selected Items of Cost.

Applications must be submitted electronically following the instructions described in the How to Apply - Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this NOFO for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the How to Apply - Application Guide.

See more tips for avoiding common errors.

Applications must include a PEDP submitted as Other Project Information as an attachment. Applications that fail to include a PEDP will be considered incomplete and will be administratively withdrawn before review.

Applications Involving the NIH Intramural Research Program

Applications may include collaborative arrangements with NIH Intramural scientists. The requests by NIH Intramural Scientists will be limited to the incremental costs required for participation. As such, these requests will not include any salary and related fringe benefits for career, career conditional or other Federal employees (civilian or uniformed service) with permanent appointments under existing position ceilings or any costs related to administrative or facilities support (equivalent to Facilities and Administrative or F&A costs). These costs may include salary for staff to be specifically hired under a temporary appointment for the project, consultant costs, equipment, supplies, travel, and other items typically listed under Other Expenses. Applicants should indicate the number of person-months devoted to the project, even if no funds are requested for salary and fringe benefits.

If selected, appropriate funding will be provided by the NIH Intramural Program. 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.

Intramural Scientist may not serve as PD/PI on extramural awards.

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.

Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. See Mandatory Disclosures, 2 CFR 200.113 and NIH Grants Policy Statement Section 4.1.35.

Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at grantdisclosures@oig.hhs.gov. 

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in the policy

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process.  Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

For this particular NOFO, note the following:

• To what extent, are the proposed approaches likely to yield important contributions applicable to a range of populations that experience chronic pain?
• How well will the proposed project activities contribute to the overall HEAL KIDS Program?

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

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).

As part of the overall impact score, reviewers should consider and indicate how the Plan to Enhance Diverse Perspectives affects the scientific merit of the project.

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.

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.

To achieve the purpose and objectives of the HEAL KIDS Pain program, how well does the applicant’s team describe their capacity to meet the needs of a CPT in terms of:

• Is there evidence that investigators have a strong collaboration plan included and give assurance of strong team interactions?
• Is there evidence of the PI's willingness to participate in larger Consortium wide efforts?
• How strong is the evidence that the facilities and resources available for the CPT infrastructure will support and enable the research proposed in the application and the CPT Consortium activities?
• Are the milestones appropriate and feasible to the CPT goals, objectives and functions?
• Do the special strengths described provide evidence for enabling the goals of the CPT Consortium?

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.

2. Review and Selection Process

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

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

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

Appeals of initial peer review will not be accepted for applications submitted in response to this NOFO.

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 NOFO. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

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

Please note that the reviewers will not consider race, ethnicity, age, or gender (including gender identity, sexual orientation or transgender status) of a researcher, award participant, or trainee, even in part, in providing critques, scores, or funding recommendations. NIH will not consider such factors in making funding decisions.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.

Prior to making an award, NIH reviews an applicant’s federal award history in SAM.gov to ensure sound business practices. An applicant can review and comment on any information in the Responsibility/Qualification records available in SAM.gov.  NIH will consider any comments by the applicant in the Responsibility/Qualification records in SAM.gov to ascertain the applicant’s integrity, business ethics, and performance record of managing Federal awards per 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.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement Section 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

A Notice of Award (NoA) is the official authorizing document notifying the applicant that an award has been made and that funds may be requested from the designated HHS payment system or office. The NoA is signed by the Grants Management Officer and emailed to the recipient’s business official.

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.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Any pre-award costs incurred before receipt of the NoA are at the applicant's own risk.  For more information on the Notice of Award, please refer to the NIH Grants Policy Statement Section 5. The Notice of Award and NIH Grants & Funding website, see Award Process.

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain “applicable clinical trials” on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that all 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.

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

2. Administrative and National Policy Requirements

The following Federal wide and HHS-specific policy requirements apply to awards funded through NIH:

• The rules listed at 2 CFR Part 200, Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.
• All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the terms and conditions in the Notice of Award (NoA). The NoA includes the requirements of this NOFO. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities.
• If a recipient receives an award, the recipient must follow all applicable nondiscrimination laws. The recipient agrees to this when registering in SAM.gov. The recipient must also submit an Assurance of Compliance (HHS-690). To learn more, see the Laws and Regulations Enforced by the HHS Office for Civil Rights website. 
  • HHS recognizes that NIH 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 NOFO.

All federal statutes and regulations relevant to federal financial assistance, including those highlighted in NIH Grants Policy Statement Section 4 Public Policy Requirements, Objectives and Other Appropriation Mandates.

Recipients are responsible for ensuring that their activities comply with all applicable federal regulations.  NIH may terminate awards under certain circumstances.  See 2 CFR Part 200.340 Termination and NIH Grants Policy Statement Section 8.5.2 Remedies for Noncompliance or Enforcement Actions: Suspension, Termination, and Withholding of Support. 

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 (HHS) grant administration regulations at 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 recipients is 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 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 recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

1. Recipients will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.
2. Determine experimental approaches, design protocols, ensure participant safety, set project milestones, conduct experiments, and analyze and interpret research data.
3. Provide objectives for projects and protocols and costs to the NIH Project Officer (PO) and Project Scientist (PS), at the outset of the award, following re-negotiation of the milestones after the first meeting of the SC, in consultation with the CPT Consortium SC and NIH.
4. Serve as a voting member of the CPT Consortium SC, and participate, along with critical staff, in CPT meetings including two face-to- face meetings per year in the Bethesda MD/Washington DC area.
5. Adhere to the CPT Consortium guidelines and other policies that might be established, as agreed upon by the SC, and the PO.
6. Apprise the PO and PS of any potential impediments to execution of the objectives of the project.
7. Ensure that primary and secondary data, protocols, procedures and any other project-derived resources are made available to the CPT Consortium (e.g., deposited in a centralized database, as specified by the PO and PS) according to a timeline agreed upon by the SC and PO.
8. Providing representation on all relevant subcommittees and working groups established by the CPT Consortium SC. Issues to address in working groups may include pain evaluations, participant safety, quality control, PRO and other outcomes selection, molecular interrogation, pilot studies, publications, intellectual property, data access, etc.
9. Agree not to disclose confidential information obtained from other members of the CPT Consortium and agree to the CPT Consortium intellectual property agreements, consistent with the terms and conditions of the cooperative agreement awards, applicable regulations, and the policies and practices of the award recipient institutions.
10. Be solely responsible for the timely acquisition of all appropriate proprietary rights, including intellectual property rights, and all materials needed for the award recipient to perform the project.
11. Before, during, and subsequent to the award, the U.S. Government is not required to obtain for the award recipient any proprietary rights, including intellectual property rights, or any materials needed by the award recipient to perform the project.
12. Provide updates at least annually on progress in PEDP implementation. 

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

The NIH Project Scientist(s) (PS) will provide technical assistance to the clinical trial protocol team. Specifically, the NIH Project Scientist will:

1. Liaise with the NIH Project Officer and communication of progress and difficulties.
2. The NIH will name additional scientific consultants as necessary from within the NIH whose function will be to assist the Project Scientist(s) and protocol team in carrying out the goals and aims of the approved study. The NIH will have one vote (if voting body) regardless of the number of NIH personnel involved.
3. Have substantial scientific programmatic involvement in quality control, preparation of publications, research coordination and performance monitoring. The Project Scientist(s) will have the same access and privileges to any data generated by the recipient. The dominant role and primary responsibility for these activities resides with the recipients for the project as a whole, although specific tasks and activities in carrying out the studies will be shared among the recipients and the Project Scientist(s).
4. Serve as a resource with respect to other ongoing NIH activities that may be relevant to the protocol to facilitate compatibility and avoid unnecessary duplication of effort.
5. Serve as a voting member of the HEAL KIDS PAIN Executive Committee.
6. Review procedures for assessing data quality and monitor study performance.
7. Serve as a co-author on study publications. In general, to warrant co-authorship, the NIH staff must have contributed to one or more of the following areas: (a) design of the interventions being tested; (b) performance of significant portions of the activity; (c) participation in analysis and interpretation of study results; and (d) preparation and authorship of pertinent manuscripts.
8. Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

1. All parties will agree to work collaboratively in all activities of the HEAL KIDS Pain program, throughout the course of the award period.
2. Participating in protocol-related meetings, and all HEAL KIDS Pain program, and NIH HEAL Initiative investigator meetings and other required meetings.
3. The Steering Committee, if required, will be the governing body of the study. The Steering Committee chair will be selected by the steering committee via vote.
4. The CPT NIH Project Scientist will be a voting member of the CPT Steering Committee and the HEAL KIDS PAIN Steering Committee. The Program Officer(s) and other members of the project team will be non-voting participants.
5. The CPT SC may, as it deems necessary, invite additional, non-voting scientific consultants to meetings at which research priorities and opportunities are discussed. The NIH reserves the right to augment the expertise of the SC when necessary. 

3. Data Management and Sharing

Consistent with the 2023 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.

4. Reporting

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement Section 8.4.1 Reporting. To learn more about post-award monitoring and reporting, see the NIH Grants & Funding website, see Post-Award Monitoring and Reporting.

• Recipients will provide updates at least annually on implementation of the PEDP.

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 Section 8.6 Closeout. NIH NOFOs 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 2 CFR Part 200.301.

Section VII. Agency Contacts

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: https://www.era.nih.gov/need-help (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-480-7075

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

Robert Walker, Jr Ph.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Email: robert.walker2@nih.gov

Rebecca Lenzi, PhD 
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
E-mail: rebecca.lenzi@nih.gov

Yan Wang, MD, PhD
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
E-mail: wangy1@mail.nih.gov

Beda Jean-Francois
National Center for Complementary and Integrative Health
beda.jean-francois@nih.gov

Vicki Shanmugam, MBBS, MRCP, FACR, CCD
Director, Office of Autoimmune Disease Research
Office of Research on Women’s Health
oadrinfo@nih.gov

Dena Fischer, DDS, MSD, MS
National Institue of Dental and Craniofacial Research (NIDCR)
dena.fischer@nih.gov 

Helena H. Ahn, PhD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-827-3207
Email: helena.ahn@nih.gov 

Annina Catherine Burns, Ph.D., RDN
ORWH - Office of Research on Women's Health
Phone: 301-402-1770
E-mail: annina.burns@nih.gov

Andrew Louden, PhD
National Heart, Lung and Blood Institute (NHLBI)
Telephone: 301.827.7353
Email: Andrew.louden@nih.gov

Rebecca Hommer, MD
National Institute of Neurological Disorders and Stroke (NINDS) 
Telephone: 301-827-2257 
Email: rebecca.hommer@nih.gov

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

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Sarisa Kowl
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Email: sarisa.kowl@nih.gov 

Gabriel Hidalgo, MBA
National Institue of Dental and Craniofacial Research (NIDCR)
gabriel.hidalgo@nih.gov 

Margaret Young
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-642-4552
Email: margaret.young@nih.gov

Anthony Agresti
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-827-8014
Email: agrestia@nhlbi.nih.gov

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

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

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 2 CFR Part 200.