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

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

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

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



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 HEAL Initiative program is to: (1) support basic and mechanistic pain research from R15-eligible undergraduate-focused serving institutions, health professional schools or graduate schools; (2) promote integrated, interdisciplinary research partnerships between Principal Investigators (PIs) from R15-eligible institutions and investigators from U.S. domestic institutions; and (3) enhance the pain research environment at the R15-eligible institution for health professional students, undergraduate and/or graduate students through active engagement in pain research.

Applications in response to this notice of funding opportunity (NOFO) should include plans to accomplish these goals. Specifically, applications should include a rigorous plan for conducting basic and mechanistic pain research projects in the Research Strategy section of the application. In addition, a research partnership between the PI’s institution and at least one investigator from a separate U.S. domestic institution that provides resources and/or expertise that will enhance the proposed pain research program must be included in a separate Team Management Plan. The proposed partnership will be a sub-award agreement(s) with at least one partnering institution, which does not need to be R15-eligible. The budget of all sub-awards must not exceed one third of the total budget. Furthermore, applications must include a Facilities & Other Resources document  that demonstrates active involvement of health professional students or undergraduate and/or graduate students from the R15-eligible institution(s) in the proposed pain research projects.

Background

The National Institutes of Health (NIH) Helping to End Addiction Long-term^® Initiative, or 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 NIH HEAL Initiative is available at https://heal.nih.gov/. Research shows that diverse teams working together and capitalizing on innovative ideas and distinct perspectives outperform homogeneous teams. Scientists and trainees from diverse backgrounds and life experiences bring different perspectives, creativity, and individual enterprise to address complex scientific problems. See the Notice of NIH’s Interest in Diversity (NOT-OD-20-031) for more details. Promoting diversity in the pain research workforce is crucial to promoting future scientific advances in this area and to achieve the NIH HEAL Initiative’s workforce development goals.The initiative has funded multiple pain workforce enhancement programs that support early-career investigators. Despite these efforts, the NIH HEAL Initiative can benefit from additionally supporting R15-eligible institutions that involve undergraduate, graduate or health professional school/colleges students in pain research.

Since Fiscal Year (FY) 1985, NIH has made a special effort to stimulate research at educational institutions that provide baccalaureate and/or advanced degrees for a significant number of the nation’s research scientists who have not been major recipients of NIH support. NIH has implemented two parent award programs, the Academic Research Enhancement Award (AREA) program (PAR-21-155) and Research Enhancement Award Program (REAP) (PAR-22-060), to provide research experiences to health professional or undergraduate and/or graduate students pursuing biomedical or behavioral research at U.S. higher education institutions. Utilizing these two programs will further promote a diverse pain research workforce. This Pain Research Enhancement Program (“PREP”) will further support meritorious collaborative pain research from designated educational levels in the NIH HEAL Initiative, using the NIH Research Enhancement Award programs as a guide. Specifically, this NOFO aims to support new scientific solutions to the national opioid public health crisis by establishing new research partnerships that will lead to research experiences for undergraduate, graduate, and health professional students, to further enhance the pool of potential participants in the pain research pipeline.

Program Objectives:

The purpose of this HEAL Initiative program is to: (1) support basic and mechanistic pain research from R15-eligible undergraduate-focused serving institutions, health professional schools or graduate schools; (2) promote integrated, interdisciplinary research partnerships between Principal Investigators (PIs) from R15-eligible institutions and investigators from U.S. domestic institutions; and (3) enhance the pain research environment at the R15-eligible institution for health professional students, undergraduate and/or graduate students through active engagement in pain research.Successful applications will include plans detailing how they intend to accomplish all three goals. Please refer to Section III for specific R15 eligibility information. Although preliminary data are not required for an R15 application, they may be included if available. The scientific foundation for the proposed research should be based on published research and/or any available preliminary data.

Objective 1: Develop Small-Scale Basic and Mechanistic Pain Research Projects

Proposed research projects should be hypothesis driven and use a rigorous scientific design to generate research data/evidence and advance scientific knowledge. Applications should include objectives that are attainable within the 3-year grant period.

Pain research projects may include, but are not limited to, the study of: nociception and/or pain processing in non-pain populations, acute pain, cancer pain, chemotherapy-induced neuropathy, chronic pain, diabetic neuropathy, eye pain, gynecologic pain, headache, musculoskeletal pain, myofascial pain, obstetric pain, osteoarthritis, pain conditions across the lifespan (including in the context of aging), pain co-occurring with substance use disorders (SUDs), painful disorders of the orofacial region, painful neuropathy, post-stroke pain, post-surgical pain, sickle cell pain, and/or visceral pain. Innovative pain research topics that propose an interdisciplinary mechanistic pain research are considered high program priority under this initiative.

Projects may focus on basic pain research with pre-clinical (e.g., animal or in silico) models or involve research participants (e.g., observational studies, epidemiological studies, secondary data analyses, or device development). Alternatively, investigators may propose a mechanistic and/or “Basic Experimental Studies involving Humans” (BESH) clinical trial as described below. Clinical trials designed primarily to determine the safety, tolerability, and/or clinical efficacy of an intervention will be considered non-responsive to this NOFO and withdrawn without review.

For this NOFO, only the following types of clinical trials will be supported:

• Basic Experimental Studies with Humans (BESH), defined as basic research studies involving humans that seek to understand the fundamental aspects of phenomena and of observable facts without specific applications towards processes or products in mind.
• Mechanistic trials, defined as studies designed to understand a biological or behavioral process, the pathophysiology of a disease, or the mechanism of action of an intervention (i.e., how an intervention works, but not if it works or is safe)

NIH defines a clinical trial as a research study 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 (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-015.html). 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

Objective 2: Promote Integrated, Interdisciplinary Research Partnerships

A second key objective of this NOFO is to promote new research partnerships among investigators at R15-eligible institutions with separate (legally distinct) investigators at domestic research institutions. Investigators can have a multitude of research expertise that aligns with the proposed research projects and/or resources that can be shared to enhance the proposed research. Applications must propose a collaboration with at least one sub-award holder from a separate U.S. domestic research institution and should include details of how the collaboration will enhance the R15-research program must be described. Applications are permitted to have a subaward to a non-R15-eligible institution. However, it is expected that PD/PI(s) from R15-eligible institution(s) will lead the proposed project and complete most of the research at the R15-eligible institution. As such, PI(s) from R15-eligible institutions must serve as the contact program director (PD)/PI for the project. Additionally, no more than one third of the total budget for the project may be used by the identified sub-award institution.

Applications that propose new interdisciplinary are considered a high program priority under this NOFO. Interdisciplinary partnership could include, but are not limited to, any two or more areas of research expertise from the following:

• Clinical pain management (e.g., nonpharmacologic or pharmacologic interventions)
• Clinical pain research
• Preclinical/basic pain biology and modeling
• Specific disease and/or pathological conditions (either human or preclinical models)
• Animal behavior
• Artificial intelligence
• Data science

In addition, a Team Management Plan is required as part of Objective 2. Studies of team science have highlighted the need for effective management structures to achieve program goals. Many resources exist to aid in developing effective team-based programs (e.g., the National Cancer Institute Collaboration and Team Science Field Guide). The Team Management Plan focuses on management of the whole team/key personnel. Because teams will likely include individuals from widely divergent scientific backgrounds, teams must have a shared vision and a defined plan for communication and management of shared responsibilities, interpersonal interactions, and professional credit. The Team Management Plan should be included as an attachment (three pages maximum) to this application. It should address how the research team, including the PI from R15-eligible Instiution and collaborator(s), will work together to accomplish program objectives. See the application instructions for “Other Attachments” on the SF424(R&R) Other Project Information in Section IV.2 Instructions for Application Submission for details. The Team Management Plan should address the following points:

• Organizational structure and team composition and roles
• Shared leadership, contributions, and distributed responsibility for decision-making
• Resource sharing and allocation
• Credit assignment and/or intellectual property (IP) rights
• Coordination and communication plans
• Intra-team data sharing, archiving, and preservation

Objective 3: Enhance the Research Environment by Engaging Students

The third objective of this program is to enhance the pain research environment at the R15-eligible institution by engaging and providing research opportunities to health professional students or undergraduate and/or graduate students. A Facilities & Other Resources document is required to describe how the proposed research will enhance the pain research environment at the R15-eligible institution. Two-thirds of the proposed research project team should comprise personnel from the R15-eligible institutions, including health professional students, or graduate students or undergraduate students from the primary R15-eligible institution. Although the proposed research project must be led by the identified PD/PI, applications with strong and innovative student engagement are of high program priority. If participating students have not yet been identified, the number and academic stage of those to be involved should be provided. Applications should identify which aspects of the proposed research will include student participation. Student involvement may include participation in the design of experiments, collection and analysis of data, execution and troubleshooting of experiments, participation in research meetings, and discussion of future research directions. When applicable, it is highly desirable that student participation also include presentation of research at local and/or national meetings (including the HEAL Annual Scientific Meeting and "Positively Uniting Researchers of Pain to Opine, Synthesize, & Engage" {PURPOSE} meeting), publication of journal articles, and collaborative interactions. By engaging in these activities and collaborating on pain-focused research projects at early stages of training, students will be better prepared and motivated to pursue careers in  pain research. Please see Section III for a list of eligible students.

This NOFO aims to support pain research grants, not training or fellowship programs. As such, applications should not include training plans such as didactic training or non-research activities related to professional development. Likewise, applications should not include independent student research projects. For applications that propose a clinical trial, the PD/PI must be the responsible individual of record for oversight of the trial though students can take part in all components of a clinical trial. Oversight includes (but is not limited to): interacting with relevant Institutional Review Board (IRB) staff; reviewing all informed consent documents; reporting potential serious adverse events; and maintaining responsibility for patient safety. However, the student can gain experience in all these components in conjunction with the individual leading the trial. Applications submitted to this NOFO may include additional investigators to those outlined above, including additional collaborators or consultants, or other individuals such as high school students, post-baccalaureate participants, postdoctoral fellows, or clinical fellows. However, involvement of such individuals does not fulfill the goal of enhancing the R15-eligible institutional environment and should account for less than one third of the overall proposed project team.

Additional Information

Non-responsiveness Criteria:

Applications deemed to be non-responsive will not proceed to review and will be withdrawn. Applications with one or more of the following characteristics are considered non-responsive to this NOFO:

• Research that does not address the NIH HEAL Initiative mission to enhance pain management.
• Failure to describe a proposed Research plan and specific aims primarily led by a PI from a R15-eligible Institution.
• Omission of a domestic research partnership and accompanying sub award(s), or that include sub-award(s) that account for more than one third of the total project budget.
• Failure to include the required Facilities & Other Resources document and Other Attachments, including a Team Management Planand, letters of support, including a letter of support from the identified subaward holder(s) and a letter of support from the R15-eligible institution’s provost. Please see section IV.2 “Instructions for Application Submission” for details. 
• Proposing a clinical trial addressing safety, tolerability, efficacy, and/or effectiveness of pharmacologic, behavioral, biologic, surgical, or device (invasive or noninvasive) interventions.

Contacting Program Officers Prior to Submission

Applicants are strongly encouraged to consult with program staff as plans for an application are being developed.

Rigor and Reproducibility

NIH strives for rigor and transparency in all research it funds. For this reason, the NIH HEAL Initiative explicitly emphasizes the NIH application instructions related to rigor and transparency (https://grants.nih.gov/policy/reproducibility/guidance.htm) and provides additional guidance from individual NIH institutes and centers (ICs) to the scientific community. For example, the biological rationale for the proposed experiments must be based on rigorous and robust supporting data, which means that data should be collected via methods that minimize the risk of bias and be reported in a transparent manner. If previously published or preliminary studies do not meet these standards, applicants should address how the current study design addresses the deficiencies in rigor and transparency. Proposed experiments should likewise be designed in a manner that minimizes the risk of bias and ensures validity of experimental results.

Proposed research projects should incorporate adequate methodological rigor where applicable, including but not limited to a clear rationale for the chosen model(s) and primary/secondary endpoint(s), clear descriptions of tools and parameters, blinding, randomization, adequate sample size, prespecified inclusion/exclusion criteria, appropriate handling of missing data and outliers, appropriate controls, pre-planned analyses, and appropriate quantitative techniques.

Applications should also clearly indicate the exploratory vs. confirmatory components of the study, consider study limitations, and plan for transparent reporting of all methods, analyses, and results so that other investigators can evaluate the quality of the work and potentially perform replications. NIH intends to maximize the impact of NIH HEAL Initiative-supported projects through broad and rapid data sharing and immediate access to publications (https://heal.nih.gov/about/public-access-data). Guidelines for complying with the HEAL Public Access and Data Sharing Policy can be found at https://heal.nih.gov/data/complying-heal-data-sharing-policy. More details about NIH HEAL Initiative data sharing are described in Section IV.

Clinical Trial Accrual Policy:

For applications that are proposing to conduct a clinical trial, a series of clinical recruitment milestones detailing completion of the clinical trial and providing contingency plans to proactively confront potential delays or disturbances in attaining the clinical recruitment milestones must be included along with a study timeline in the PHS Human Subjects and Clinical Trials Information form. Continuation of the award is conditional upon satisfactory progress, availability of funds, and scientific priorities of the NIH HEAL Initiative. If, at any time, recruitment falls significantly below the projected milestones for recruitment, NIH will consider ending support and negotiating an orderly phaseout of the award. NIH retains the option of periodic external peer review of progress. NIH program staff will closely monitor progress at all stages for milestones, accrual, and safety. 

Expected Activities of Coordination

NIH HEAL Initiative awardees are strongly encouraged to cooperate and coordinate their activities. It is expected that NIH HEAL Initiative awardees will cooperate and coordinate their activities after post award by participating in PD/PI meetings, including:

NIH HEAL Initiative Scientific Meeting Attendance

Applicants and students are highly encouraged to attend the annual NIH HEAL Initiative Scientific Meetings. The NIH HEAL Initiative hosts an annual meeting of more than 800 NIH HEAL Initiative-funded researchers across the initiative’s research portfolio and career stage spectrum, NIH staff, people with lived and living experience, community partners advising initiative-funded projects, advocacy groups, and other stakeholders to

• Share research advances and cutting-edge science
• Discover opportunities, challenges, and approaches to build on the initiative’s progress
• Connect and explore collaboration with other NIH HEAL Initiative-funded researchers and collaborators to enhance initiative-funded research.

Annual National Pain Scientists Career Development Program (PURPOSE) Meeting

Applicants and students are also highly encouraged to enroll in the HEAL Initiative: Positively Uniting Researchers of Pain to Opine, Synthesize, and Engage (PURPOSE) network and attend its annual meetings. Details can be found at https://painresearchers.com. The HEAL R24 Coordinating Center for National Pain Scientists works to improve the collaboration between basic, translational, and clinical researchers who do not regularly collaborate or work together. One function of the HEAL R24 Coordinating Center for National Pain Scientists is to organize an annual meeting for established scientists as well as early-career pain investigators. This annual meeting facilitates the creation of a network of pain research mentors and mentees as well as fostering communication between scientists and clinicians of different disciplines and providing enhanced mentorship, leadership courses, and any additional training that might be helpful for early-career scientists. R15 recipients are encouraged to attend the annual PURPOSE meeting, either virtually or in person.

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 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.

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

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)

Non-domestic (non-U.S.) Entities (Foreign Organizations) are not eligible to apply.

In addition, applicant organizations must meet the following criteria at the time of submission:

• The applicant organization must be an accredited public or nonprofit private school that grants baccalaureate or advanced degrees in health professions (see section below for more details) or biomedical and behavioral sciences. The application must be submitted by the eligible organization with a unique entity identifier (such as UEI or DUNS) and a unique NIH eRA Institutional Profile File (IPF) number.
• At the time of application submission, determination of eligibility will be based in part on NIH institutional support.
• A year is defined as a Federal fiscal year: from October 1 through September 30.  
• Note that collaborating subawardees do not need to adhere to the R15 eligibility criteria stated above. However, they must be separate legal entities that fulfill the terms of an eligible subaward agreement. For this particular NOFO, they must also be U.S. domestic institutions. More details can be found at https://grants.nih.gov/policy/subawards.

Undergraduate Focused Institutions:

• At the time of application submission, all the non-health professional components of the institution combined must not have received support from the NIH totaling more than $6 million per year (in both direct and F&A/indirect costs) in 4 of the last 7 years. For institutions composed of multiple schools and colleges, the $6 million funding limit is based on the amount of NIH funding received by all the non-health professional schools and colleges within the institution as a whole. Note that all activity codes are included in this calculation except the following: C06, S10, and all activity codes starting with a G. Help determining the Organization Funding Level can be found at https://grants.nih.gov/grants/funding/Determing-Organization-Funding-Levels-R15-Eligibility.pdf   
• An academic component is any school/college that is not a Health Professional School or College.
• A qualifying academic component (i.e., school/college) within an institution (e.g., School of Arts and Sciences) has greater undergraduate student enrollment than graduate student enrollment.
• All types of Health Professional Schools and Colleges are not eligible to apply and are not considered in this calculation.
• For institutions with multiple campuses, eligibility can be considered for each individual campus (e.g., main, satellite, etc.) only if separate UEIs and NIH IPF numbers are established for each campus. For institutions that use one UEI or NIH IPF number for all campuses, eligibility is determined for all campuses (e.g., main, satellite, etc.) combined.
   

Health Professional and Graduate Schools 

• At the time of application submission, all components of the institution combined must not have received support from the NIH totaling more than $6 million per year (in both direct and F&A/indirect costs) in 4 of the last 7 years. For institutions composed of multiple schools and colleges, the $6 million funding limit is based on the amount of NIH funding received by all of the schools and colleges within the institution as a whole. Note that all activity codes are included in this calculation except the following: C06, S10, and all activity codes starting with a G.
• A graduate school offers advanced degrees, beyond the undergraduate level, in an academic discipline including M.A., M.S., and Ph.D. degrees.
• Health professional schools and colleges are accredited institutions that provide education and training leading to a health professional degree, including but not limited to: B.S.N., M.S.N., D.N.P., M.D., D.D.S., D.O., Pharm.D., D.V.M., O.D., D.P.T., D.C., N.D., D.P.M., M.O.T., O.T.D., D.P.T., M.S.-S.L.P., C.Sc.D., S.L.P.D., Au.D., M.S.P.O., M.S.A.T., and M.P.H.
• Eligible health professional schools/colleges may include schools or colleges of nursing, medicine, dentistry, osteopathy, pharmacy, veterinary medicine, public health, optometry, allied health, chiropractic, naturopathy, podiatry, rehabilitation medicine, physical therapy, orthotics and prosthetics, kinesiology, occupational therapy, and psychology. Accreditation must be provided by a body approved for such purpose by the Secretary of Education.
• For institutions with multiple campuses, eligibility can be considered for each individual campus (e.g., main, satellite, etc.) only if a unique identifier number and NIH IPF number are established for each campus. For institutions that use one identifier number or NIH IPF number for all campuses, eligibility is determined for all campuses (e.g., main, satellite, etc.) together.

Additional Eligibility Guidance

A signed letter is required from the provost or similar official with institution-wide responsibility verifying the eligibility of the applicant institution at the time of application submission according to the eligibility criteria indicated above. See the application instructions for “Other Attachments” on the SF424(R&R) Other Project Information form in Section IV.2 Instructions for Application Submission. Final eligibility will be validated by NIH prior to award.

To assist in determining eligibility, organizations are encouraged to use the NIH RePORT website under NIH Awards by Location & Organization.

A PREP application must provide evidence of a subaward to a separate institution, and the grantee may partner with a non-R15-eligible institution. However, applicants should keep the goals of the PREP in mind when preparing the application, which include strengthening the research environment of eligible institutions and engaging students from eligible institutions in pain research. It is expected that the project, and two-thirds of the total project budget, will be directed by the PD(s)/PI(s) at R15-eligible institution(s).

A letter of support from each collaborator is required verifying the research collaboration at the time of application submission according to the eligibility criteria indicated above. The Letter(s) should detail how the proposed research partnership will help to accomplish the proposed pain research project, enhance the R15-eligible institution’s research program, and promote synergy from an integrated, interdisciplinary research partnership(s) among the multiple proposed institutions. See the application instructions for “Other Attachments” on the SF424(R&R) Other Project Information form in Section IV.2 Instructions for Application Submission.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are 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 the 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, and Notice of NIH's Interest in Diversity, NOT-OD-20-031.

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.

To be eligible for support under a PREP grant, the PD(s)/PI(s) must meet the following additional criteria:

• Each PD/PI must have a primary appointment at either an R15-eligible institution, including professional or graduate schools, undergraduate-focused organizations, or a college within the applicant institution, as defined in “Eligible Organizations,” above. If proposing multiple PD(s)/PI(s), each PD/PI must be at an R15-eligible institution.
• Each PD/PI may not be the PD/PI of an active NIH research grant, including another R15 grant, at the time of award of a PREP grant, although they may be one of the Key Personnel for an active NIH grant held by another PD/PI.
• Each PD/PI may not be awarded support under more than one R15 grant at a time, although he or she may have support under successive New or Renewal grants.

2. Cost Sharing

This NOFO does not require cost sharing as defined in the 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 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:

Jessica McKlveen, Ph.D.
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-594-8018
Email: [email protected]

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 & Other Resources (Required):

• A profile of the scientific background, academic level, and expertise of the students of the applicant institution and any information or estimate of the number who have obtained a health professional baccalaureate or advanced degree and gone on to obtain an academic or professional doctoral or other advanced degree in the health-related sciences during the last 5 years.
• Description of plans to build a broad team of prospective researchers, including students, with a variety of backgrounds, expertise, and skills, and to arrive at major decisions, accounting for different points of view. Personnel from the primary R15-eligible institution(s) should compose a two-thirds majority of the project team.
• Description of the special characteristics of the applicant institution that make it appropriate for a PREP grant awarded through this NOFO to: (1) support the efforts by R15-eligible PIs at undergraduate-focused institutions or health professional schools and graduate schools to conduct small-scale basic and mechanistic pain research projects; (2) promote integrated, interdisciplinary research partnerships between R15-eligible PIs and additional investigators from U.S. domestic institutions; and (3) enhance the pain research environment at the R15-eligible institution for health professional students or undergraduate and/or graduate students by actively engaging them in the proposed pain research projects.
• Description of the likely impact of a PREP grant on the ability of the PD(s)/PI(s) to engage students in research.
• Description of the likely impact of a PREP grant on the research environment of the applicant institution.
• Description of the likely impact of the PREP grant on the ability of health professional or undergraduate and/or graduate students at the institution to gain experience conducting biomedical research.
• Description of the resources of the grantee institution available for the proposed research (e.g., equipment, supplies, laboratory space, release time, matching funds).
• Although the majority of the research project should be conducted at the R15-eligible institution, the use of special facilities or equipment at another institution is permitted. For any proposed research sites other than the applicant institution, provide a brief description of the resources and access students will need and have to these resources.

Applications without a Facilities & Other Resources document will be withdrawn. 

Other Attachments:

Applications that fail to include the following three required “other” attachments will be considered incomplete and will be withdrawn.

1.Team Management Plan (Required three pages maximum):

A key goal of this program is to establish new research partnerships among R15-eligible investigators and other domestic research centers, programs, or institutions with complementary research expertise and/or resources. To ensure that prospective research teams fit the goals of the PREP, a team management plan is required. Applications with team management plans that exceed the three-page limit will be withdrawn.

As an “Other Attachment” entitled Team-Management-Plan.pdf, applications should describe how the research collaborators will function to accomplish program objectives. Team management approaches raised in the subsections listed below should be described in the plan. Note that a “Multiple PD/PI Leadership Plan” may also be submitted as a separate attachment, and if it is included the information in that plan should not be duplicated here. Whereas the Multiple PD/PI Leadership Plan focuses on leadership by and interactions across the PD/PIs, the Team Management Plan focuses on management of the whole team/key personnel. Applicants are encouraged to consult resources to aid in developing effective team-based programs (see e.g., the National Cancer Institute (NCI) Collaboration and Team Science Field Guide).

Organizational structure and team composition: The Team Management Plan should clearly show the organizational structure and composition of the proposed project team. Two-thirds of the proposed research project team should be health professional student trainees or graduate students or undergraduate students from the primary R15-eligible institution. The plan should describe a management structure based on project objectives that effectively promote the proposed research. The structure should account for team composition, institutional resources, and policies that conform with PREP objectives outlined in Section I.

Shared leadership, contributions, and distributed responsibility for decision making: The Team Management Plan should include a description of how the proposed collaborators will work together to direct the overall scientific team to leverage the diverse perspectives, expertise, and skills of the team members to successfully accomplish the goals of the project. One key consideration is that teams employing multidisciplinary approaches and having diverse areas of intellectual and technical expertise are more productive if the process for making decisions incorporates different points of view. The Team Management Plan should describe how major decisions will be made or how conflicts will be resolved.

Resource sharing and allocation across the team: Applications should describe management and decision-making processes that promote collective input for allocation of program resources with flexibility when resources may need to be dynamically reallocated to achieve programmatic goals. A plan for how intra-team, institutional, and regional resources that are integral to the team goals will be shared and made accessible to team members should also be included.

Credit assignment: A plan for how credit and intellectual property (IP) will be shared, especially with the R15 institution’s students, should be included. Methods for attributing contributions to publications should be described to enable individual professional assessment in joint projects.

Coordination and communication plans: Practical aspects should be described, including frequency and logistics of real-time communication across all key personnel, consultants, scholars, early-stage investigators, etc., and other significant contributors regardless of effort level.

An important and meaningful impact of team science may come from shaping the next generation of pain scientists. Because of the interdisciplinary expertise of the research groups, students are exposed to and can learn a variety of scientific approaches and methodologies, resulting in multifaceted early-stage investigators. Plans for how student trainees will be immersed in and benefit from different approaches taken by the collective team program should be described. This could include shared mentorship, interlaboratory meetings, all-hands tutorials, shared meeting and document space, interlaboratory visits, and student presentations.

2. Provost Letter(s) of Support: The application must include a PDF-formatted letter named “ProvostLetter.pdf” (without quotation marks). For multiple principal investigator (MPI) applications a signed provost letter is required from each involved institution. The letter must be signed by the provost or similar official with institution-wide responsibility attesting to the following information:

For Undergraduate Focused Institutions:

• The eligible academic component(s) (i.e., the college/school level) must have more undergraduates than graduate students as of the date of submission.
• All the non-health professional components of the institution together have received support from NIH totaling no more than $6 million per year (in both direct and F&A/indirect costs) in 4 of the last 7 years, as described in Section III, “Eligible Organization.”
• Validation that the PD/PI has (or in the case of a multiple PD/PI application that all PD(s)/PI(s) have) a primary appointment at the qualifying component (i.e., the college/school level).
   

For Health Professional and Graduate Schools:

• The eligible academic component(s) (i.e., the college/school level) must be a health professional or graduate school that awards health professional baccalaureate or advanced degrees in biomedical and/or biobehavioral sciences.
• All components of the institution together have received support from NIH totaling no more than $6 million per year (in both direct and F&A/indirect costs) in 4 of the last 7 years, as described in Section III, “Eligible Organization.”
• Validation that the PD/PI has (or in the case of a multiple PD/PI application that all PD(s)/PI(s) have) a primary appointment at the qualifying component (i.e., the college/school level).

3. Collaborator Letter(s) of Support: Applications must include additional PDF-formatted letter(s) from collaborating subaward holder(s) named “CollaboratorLetter_Initials.pdf” (without quotation marks). For multiple collaborators, a signed letter is required from each involved collaborator. Note that collaborators do not need to meet the R15-eligibility criteria outlined above. The letter should demonstrate the collaborator’s willingness to collaborate with the study lead as well as briefly outline their contributions to the project that will result in a well-integrated, interdisciplinary research approach to the understanding of pain. If the proposed collaboration is a new research partnership among investigators, this information should also be included.

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.
• A training or mentorship program limited to certain researchers based on their race, ethnicity, or sex.

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.

Biographical Sketch: The PD(s)/PI(s) should include a summary of their previous and/or current experience supervising undergraduate and/or graduate students in research in the Personal Statement. The PD(s)/PI(s) should indicate which peer-reviewed publications or other research products involved undergraduate and/or graduate students under their supervision.

• The total budget for all years of the proposed project must be requested in Budget Period 1. Do not complete Budget Periods 2 or 3. They are not required and will not be accepted with the application.
• Applicants submitting an application with direct costs of $250,000 or less (total for all years, excluding consortium Facilities and Administrative [F&A] costs) must use the Modular Budget.
• Applicants submitting an application with direct costs of $250,001–$375,000 (total for all years, excluding consortium F&A costs) must use the R&R Budget.
• Students must be compensated for their participation in the laboratory’s research and in accord with institutional policies. Student salaries can be requested in the R15 budget, or other resources at the university can be used to pay them for their participation. Undergraduate students who are compensated from the R15 grant or other institutional funds should receive at least the national minimum wage. Compensation through course credit hours towards graduation is allowable but must be justified. If universities/colleges provide room and board for summer research students, details must be provided in the application.
• NIH does not fund stipends for undergraduates on R15 awards.

Budget Justification:

Personnel Justification: Since a primary objective of the PREP is to expose and incorporate students into multidisciplinary pain research, PD(s)/PI(s) must include health professional or undergraduate and/or graduate students from the applicant institution/applicant component in the proposed research. Students from the R15-eligible institution should compose the majority of the research team (two thirds or more). Indicate aspects of the proposed research in which students will participate. If participating students have not yet been identified, the number and academic level of those to be involved should be provided. Collaborators or consultants for the project should provide additional budget information, including their names, their organizational affiliations, and the services they will perform.

PEDP implementation costs:

Applicants may include allowable costs associated with PEDP implementation (as outlined in the Grants Policy Statement section 7): https://grants.nih.gov/grants/policy/nihgps/html5/section_7/7.1_general.htm.

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:

Research Strategy: 

The research strategy must address how the proposed project intends to accomplish all three objectives of this program, including: 1) Supporting the efforts by R15-eligible PIs at undergraduate-focused institutions OR health professional schools and graduate schools to conduct small-scale basic and mechanistic pain research; (2) promoting integrated, interdisciplinary research partnerships between R15-eligible PIs and additional investigators from U.S. domestic institutions; and (3) enhancing the pain research environment at the R15-eligible institution for health professional students or undergraduate and/or graduate students by actively engaging them in the proposed pain research projects.

Applications should include a detailed description of a research approach that will produce rigorous data that can be disseminated and advance our basic and mechanistic understanding of pain. Additionally, the research strategy should detail how the proposed research partnership includes sufficient integrative pain expertise and related resources and/or institutional infrastructure that increase the likelihood of success. The application should detail how the proposed scientific research and proposed program and research partnership will have a substantial effect on strengthening the research environment at the proposed applicant’s institution.

Applications should provide details on how the research project will be directed by the R15-eligible PI and how two-thirds of the research project will be conducted at the R15-eligible institution. The research strategy should detail how the research team will recruit additional prospective investigators, including students, from a range of backgrounds, skills, and expertise, for the broad pool of researchers who may apply to participate and contribute to the project. Applications should include details about how the investigators will cooperate and coordinate their activities with other NIH HEAL Initiative investigators at PD/PI meetings, including (but not limited to) other investigators in the R15 program, and the HEAL Annual Scientific and PURPOSE meetings. The proposed PD/PI(s) should include evidence of experience supervising students in previous research efforts, as well as describing any innovative approaches to engage students in the proposed pain research project. Applications should provide additional details outlining student involvement in the research project by addressing the following questions:

• How will students engage in conducting hands-on rigorous research?
• How will students participate in research activities such as planning, execution, and/or analysis of the research?
• Are there any additional plans for student involvement, such as presentation at local or national meetings, participation in publication of research findings, and development of, or participation in, collaborative activities?
• How will the project provide students with adequate opportunities to improve their research capabilities and support their progress toward a future career in pain research?
• Note: The purpose of this program is to support pain research projects, not student training. Formal training plans (e.g., nonresearch activities, didactic training, seminars) should not be provided, although a brief description of activities related to enhancing students’ research capabilities and progress (e.g., the use of individual development plans) is permitted. Furthermore, applications should not include independent student research projects.

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 NIH HEAL Initiative has additional requirements that must be addressed in the Data Management and Sharing Plan. 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 1 year of award (https://heal.github.io/platform-documentation/study-registration/).
• Plans to submit HEAL-defined study-level metadata within 1 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/.
• Plans to submit data dictionaries to the HEAL Data Ecosystem, if applicable.
• HEAL pain clinical studies must include a plan to use HEAL core Common Data Elements (CDEs) (https://heal.nih.gov/data/common-data-elements). NIH 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 (nonpain) HEAL studies conducting clinical trials or research involving human subjects are expected to use questionnaires by the HEAL 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, NIH HEAL Initiative awardees are expected to integrate broad data sharing consent language into their informed consent forms.

The NIH HEAL Initiative 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 in NOT-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.

Section 2 - Study Population Characteristics

2.5 Recruitment and Retention Plan

Describe the following: 

1. Recruitment milestones. 
2. The planned recruitment methods, including use of contact lists (participants and/or sites), databases or other prescreening resources, advertisements, outreach, media/social media, and referral networks or groups.
3. If there are known participant or study-related barriers to accrual or participation (based on literature or prior experience), please list these barriers and describe plans to address them to optimize success. 
4. Contingency plans for participant accrual if enrollment significantly lags behind accrual benchmarks. 
5. Participant retention and adherence strategies. 
6. Possible competition from other trials for study participants.

2.7 Study Timeline

Include a table or graph of the overall study timeline. This is expected to be a visual representation (such as a Gantt chart) of recruitment milestones and key project management activities. A narrative is not expected in this section.

The study timeline should include recruitment milestones that need to be met throughout the life cycle of the clinical trial to ensure its success, and the subtasks that will be used to reach the recruitment milestones. In the timeline, the study duration is expected to be displayed in months. The timeline should include, but is not limited to, the following:

(a) When the study opens to enrollment
(b) When recruitment milestones (see below) are met
(c) What subtasks are needed to reach of the recruitment milestones
(d) When final transfer of the data will occur
(e) When analysis of the study data will occur
(f) When the primary study manuscript will be submitted for publication

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.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

In order to expedite review, applicants are requested to notify the NCCIH Referral Office by email at [email protected] when the application has been submitted. Please include the NOFO and title, PD/PI name, and title of the application.

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 [email protected].

Post Submission Materials

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

In addition to the NIH policy allowed post-submission materials, the following post-submission materials are allowed: 

• Revised Team Management Plan (e.g., due to the hiring, replacement, or loss of an investigator).
• Provost letters may be solicited at the sole initiative and discretion of NIH.

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:
The purpose of this NIH HEAL Initiative program is to (1) support the efforts by R15-eligible principal investigators (PIs) at primarily undergraduate-focused serving institutions or health professional schools and graduate schools to conduct small-scale basic and mechanistic pain research projects; (2) promote integrated, interdisciplinary research partnerships between R15-eligible PIs and investigators from U.S. domestic institutions; and (3) enhance the pain research environment at the R15-eligible institution for health professional students or undergraduate and/or graduate students by actively engaging them in the proposed pain research projects.
Applications in response to this NOFO should include plans to accomplish these goals. Specifically, applications should include a rigorous plan for conducting basic and mechanistic pain research projects in the Research Strategy section of the application. In addition, a research partnership between the PI’s institution and at least one investigator from a separate U.S. domestic institution that provides resources and/or expertise that will enhance the proposed pain research program must be included in a separate Team Management Plan. The proposed partnership will be a sub-award agreement(s) with at least one partnering institution, which does not need to be R15-eligible. The budget of all sub-awards must not exceed one third of the total budget. Furthermore, applications must include a Facilities & Other Resources document that demonstrates active involvement of health professional students or undergraduate and/or graduate students from the R15-eligible institution(s) in the proposed pain research projects.

Although preliminary data are not required for an R15 application, they may be included if available. The scientific foundation for the proposed research should be based on published research and/or any available preliminary data.

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 make important scientific contributions to the research field(s) involved, while providing research opportunities to [undergraduate or graduate or health professional students] and strengthening the research environment of the institution, 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 Factors 1, 2 and 3 in the determination of scientific merit, and in providing an overall impact score. In addition, Factors 1 and 2 will each receive a separate criterion score. An application does not need to be strong in all categories to be judged as a high impact R15 application. For example, a solid and interesting scientific research project that is not by its nature innovative or paradigm-shifting, and includes a good plan to engage [undergraduate or graduate or health professional students] in primary research may be considered a strong R15 application.

As applicable for the project proposed, reviewers will consider the following additional items while determining scientific and technical merit, but will not give criterion scores for these items, and should consider them in providing an overall impact score.

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 NCCIH, 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, consistent with applicable law.

• 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 reviewers will not consider race, ethnicity, age, or gender of a researcher, award participant, or trainee, even in part, in providing critiques, scores, or funding recommendations. NIH will not consider such factors in making its 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. 

Successful recipients under this NOFO agree that:

Where the award funding involves implementing, acquiring, or upgrading health IT for activities by any funded entity, recipients and subrecipient(s) are required to: Use health IT that meets standards and implementation specifications adopted in 45 CFR part 170, Subpart B, if such standards and implementation specifications can support the activity.  Visit https://www.ecfr.gov/current/title-45/subtitle-A/subchapter-D/part-170/subpart-B to learn more.

Where the award funding involves implementing, acquiring, or upgrading health IT for activities by eligible clinicians in ambulatory settings, or hospitals, eligible under Sections 4101, 4102, and 4201 of the HITECH Act, use health IT certified under the ONC Health IT Certification Program if certified technology can support the activity. Visit https://www.healthit.gov/topic/certification-ehrs/certification-health-it to learn more.

Pursuant to the Cybersecurity Act of 2015, Div. N, § 405, Pub. Law 114-113, 6 USC § 1533(d), the HHS Secretary has established a common set of voluntary, consensus-based, and industry-led guidelines, best practices, methodologies, procedures, and processes.

Successful recipients under this NOFO agree that:

When recipients, subrecipients, or third-party entities have:

1. ongoing and consistent access to HHS owned or operated information or operational technology systems; and
2. receive, maintain, transmit, store, access, exchange, process, or utilize personal identifiable information (PII) or personal health information (PHI) obtained from the awarding HHS agency for the purposes of executing the award.

Recipients shall develop plans and procedures, modeled after the NIST Cybersecurity framework, to protect HHS systems and data. Please refer to NIH Post-Award Monitoring and Reporting for additional information. 

Not Applicable

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.

HEAL Data Sharing Requirements

NIH intends to maximize the impact of NIH HEAL Initiative-supported projects through broad and rapid data sharing. All NIH HEAL Initiative award recipients, regardless of the amount of direct costs requested for any one year, are required to comply with the HEAL Public Access and Data Sharing Policy. NIH HEAL Initiative award recipients must follow all requirements and timelines developed through the HEAL Initiative Data Ecosystem (https://heal.nih.gov/about/heal-data-ecosystem), as described in the initiative’s compliance guidance (See “Already Funded” section: https://heal.nih.gov/data/complying-heal-data-sharing-policy): 
 

1. Select a HEAL-compliant data repository (https://www.healdatafair.org/resources/guidance/selection)

• Data generated by NIH HEAL Initiative-funded projects must be submitted to study-appropriate, HEAL-compliant data repositories to ensure the data is accessible via the HEAL Initiative Data Ecosystem.
• Some repositories require use of specific data dictionaries or structured data elements, so knowing your repository’s requirements up front can help reduce the burden of preparing data for submission.
• HEAL-funded awardees must follow requirements for selected repository.

2. Within one year of award, register your study with the HEAL platform (https://heal.github.io/platform-documentation/study-registration/)

• This process will connect the platform to information about your study and data, including metadata, and identify the selected repository. HEAL requests initial submission within one year of award, with annual updates, and to be updated in accordance with any release of study data.

3. Within one year of award, submit HEAL-specific study-level metadata.

• Some of the required study-level metadata (https://github.com/HEAL/heal-metadata-schemas/blob/main/for-investigators-how-to/study-level-metadata-fields/study-metadata-schema-for-humans.pdf) will be autopopulated as part of the registration process.
   

4. Submit data and metadata (and code, if applicable) to HEAL-compliant repository

• At the completion of the study and/or when prepared to make the final data deposits in the repositor(ies) of choice, ensure your study registration (https://heal.github.io/platform-documentation/study-registration/) is complete.
• Submit data dictionaries to the HEAL data ecosystem, if applicable.
• The NIH HEAL Initiative expects data sharing timelines to align with timeline requirements stated in the Final NIH Policy for Data Management and Sharing (NOT-OD-21-013).

6. Additional Requirements for NIH HEAL Initiative studies conducting clinical research or research involving human subjects.

These studies must meet the following additional requirements:

• NIH HEAL Initiative trials that are required to register in clinicaltrials.gov should reference support from and inclusion in the NIH HEAL Initiative by including the standardized term “the HEAL Initiative (https://heal.nih.gov/)” in the Study Description Section.
• All new NIH HEAL Initiative clinical pain studies are required to use core questionnaires required by the HEAL Common Data Elements (CDE) Program (https://heal.nih.gov/data/common-data-elements). Outside of the core questionnaires, studies should select questionnaires from among the repository of supplemental questionnaires that are already being used by other NIH HEAL Initiative clinical pain studies. The program has created CDE files containing standardized variable names, responses, coding, and other information for all of these questionnaires. The program has also formatted the case report forms in a standardized way that is compliant with accessibility standards under Section 508 of the Rehabilitation Act of 1973 (29 U.S.C § 794 (d); https://www.govinfo.gov/content/pkg/USCODE-2011-title29/html/USCODE-2011-title29-chap16-subchapV-sec794d.htm) which “require[s] Federal agencies to make their electronic and information technology accessible to people with disabilities.”
  • Studies that wish to use questionnaires not already included in the HEAL CDE repository should consult with their program official and the HEAL CDE team. New questionnaires will be considered for inclusion in the repository on a case-by-case basis and only when appropriate justification is provided.
  • NIH HEAL Initiative clinical studies that are using copyrighted questionaries are required to obtain licenses for use prior to initiating data collection. Licenses must be shared with the HEAL CDE team and the program officer prior to use of copyrighted materials. For additional information, visit the HEAL CDE Program (https://heal.nih.gov/data/common-data-elements).
• To the extent possible, all other (nonpain) HEAL studies conducting clinical trials or research involving human subjects are expected to use questionnaires by the HEAL CDE Program (https://heal.nih.gov/data/common-data-elements) if applicable and relevant to their research.
• To the extent possible, NIH HEAL Initiative awardees are expected to integrate broad data sharing consent language into their informed consent forms.

Additional details, resources, and tools to assist with data-related activities can be found at https://www.healdatafair.org.  Budgeting guidance for data sharing can be found in NOT-OD-21-015 and the NIH Scientific Data Sharing site.

All data collected as part of the NIH HEAL Initiative are collected under a Certificate of Confidentiality and entitled to the protections thereof. Institutions who receive data and/or materials from this award for performance of activities under this award are required to use the data and/or materials only as outlined by the NIH HEAL Initiative, in a manner that is consistent with applicable state and Federal laws and regulations, including any informed consent requirements and the terms of the institution’s NIH funding, including NOT-OD-17-109 and 42 U.S.C. 241(d). Failure to adhere to this criterion may result in enforcement actions.

4. Reporting

Progress reports for multi-year funded awards are due annually on or before the anniversary of the budget/project period start date of award. The reporting period for multi-year funded award progress report is the calendar year preceding the anniversary date of the award. Information on the content of the progress report and instructions on how to submit the report using the RPPR are posted at http://grants.nih.gov/grants/policy/myf.htm. 

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

(To follow the next section):

Report and ensure immediate public access to HEAL-funded publications

Publications resulting from NIH HEAL Initiative-funded studies must be immediately publicly available upon publication. 

• For manuscripts published in journals that are not immediately open access, authors should arrange with journals in advance to pay for immediate open access. 
• Costs to ensure manuscripts are immediately publicly available upon publication should be included in budget requests. 

Prior to publication, the NIH HEAL Initiative expects investigators to alert their program officers of upcoming manuscripts to ensure coordination of communication and outreach efforts.

Award recipients and their collaborators are required to acknowledge NIH HEAL Initiative support by referencing in the acknowledgment sections of any relevant publication:

“This research was supported by the National Institutes of Health through the NIH HEAL Initiative (https://heal.nih.gov) under award number [include specific grant/contract/award number; with NIH grant number(s) in this format: R01GM987654].” 

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: [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]

Alex Tuttle, Ph.D.
National Center for Complementary and Integrative Health (NCCIH)
Phone: 301-814-6115
Email: [email protected]

Rebecca N Lenzi, Ph.D.
NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES (NIAMS)
Phone: (301) 402-2446
E-mail: [email protected]

Mark Egli, Ph.D.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Phone: 301-594-6382
E-mail: [email protected]

Susan Marden, PhD, RN
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6838
Email: [email protected] 

Rene Etcheberrigaray, M.D.
National Institute on Aging (NIA)
Phone: 301-451-9798
Email: [email protected]

Elizabeth Irene Sypek
NINDS - NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
E-mail: [email protected]

Melissa M Ghim, PhD
NIDCR - NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH
Phone: none
E-mail: [email protected]

Jessica McKlveen, Ph.D. 

National Center for Complementary and Integrative Health (NCCIH) 

Telephone: 301-594-8018

 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]

Judy Fox
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-4704
Email: [email protected]

Margaret Young
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-642-4552
Email: [email protected] 

Ryan Blakeney
National Institute on Aging (NIA)
Phone: 301-451-9802
Email: [email protected]

Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke (NINDS)
Email: [email protected]

Gabriel Hidalgo, MBA

NIDCR - NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH
Phone: 301-827-4630
E-mail: [email protected]

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.