Part 1. Overview Information

Key Dates

It is critical that applicants follow the instructions in the Career Development (K) Instructions in the How to Apply - Application Guide except where instructed to do otherwise (in this NOFO or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the How to Apply - Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the How to Apply - Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the How to Apply - Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

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

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



Table of Contents
Part 1. Overview Information
Key Dates
Part 2. Full Text of Announcement
Section I. Funding Opportunity Description
Section II. Award Information
Other Award Budget 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. Funding Opportunity Description

The overall goal of the NIH Research Career Development program is to help ensure that a diverse pool of highly trained scientists is available in appropriate scientific disciplines to address the Nation's biomedical, behavioral, and clinical research needs. NIH Institutes and Centers (ICs) support a variety of mentored and non-mentored career development award programs designed to foster the transition of new investigators to research independence and to support established investigators in achieving specific objectives. Candidates should review the different career development (K) award programs to determine the best program to support their goals. More information about Career programs may be found at the NIH Research Training and Career Development website.

The objective of the NIH Mentored Patient-Oriented Research Career Development Award (K23) program is to provide salary and research support for a sustained period of “protected time” (3-5 years) to ensure a future cadre of well-trained scientists conducting NIH-supported Patient-Oriented Research (POR).  The specific objectives of the Mentored Patient-Oriented Research Career Development Award are to: (a) Encourage research-oriented clinicians to develop research skills and gain experience in advanced methods and experimental approaches needed to become independent investigators conducting  patient-oriented research; (b) Increase the pool of clinical researchers who can conduct patient-oriented studies, capitalizing on the discoveries of biomedical research and translating them to clinical settings; and (c) Support the career development of investigators who have made a commitment to focus their research endeavors on patient-oriented research.

For the purposes of the K23 award, Patient-Oriented Research is defined as research conducted with human subjects (or on material of human origin such as tissues, specimens and cognitive phenomena) for which an investigator (or colleague) directly interacts with human subjects. This area of research includes: 1) mechanisms of human disease; 2) therapeutic interventions; 3) clinical trials; and 4) the development of new technologies. Excluded from this definition are in vitro studies that utilize human tissues but do not deal directly with patients. In other words, patient-oriented research is research in which it is necessary to know the identity of the patients from whom the cells or tissues under study are derived. Studies falling under Exemption 4 for human subjects research are not included in this definition. See also the NIH Directors Panel on Clinical Research Report.

Background  

More than 25 million Americans suffer from high impact chronic pain, a highly debilitating biopsychosocial condition that is complex and difficult to manage. Innovative scientific solutions to develop effective and safe treatment options are thus critically needed. This Notice of Funding Opportunity (NOFO) is part of the NIH Helping End Addiction Long-term (HEAL) Initiative, an aggressive, trans-agency effort to speed scientific solutions to stem the chronic pain and opioid public health crisis. To achieve the ambitious goals of the NIH HEAL Initiative, a multitude of research programs are currently underway to better understand, manage, and treat pain. A robust workforce in clinical pain research is needed to support and advance these programs and innovative actionable care pathways to support patients, clinicians, and health systems.    

Feedback from the HHS Interagency Pain Research Coordinating Committee (IPRCC) related to issues in retaining and recruiting a pain research workforce led to a survey conducted by the Office of Pain Policy and Planning (OPPP) at NINDS that highlighted barriers for early-career clinician-scientists interested in pursuing research careers. Taken together, these data indicate there is a critical need to expand and better support the clinical pain research workforce, particularly in research areas supported by the NIH HEAL Initiative, to facilitate timely accomplishment of the NIH HEAL Initiative’s goals.  

To determine possible ways to support early-career clinician-scientists interested in clinical pain research careers, the OPPP conducted a portfolio analysis of NIH career development awards provided to early-career clinician-scientists from 2013-2023. In that timeframe, NIH funded 191 individual career development awards for early-career clinician-scientists studying pain. Compared to early-career clinician-scientists who applied for, but did not receive, a career development award to study pain, receiving a career development award led to a 2.5-fold greater odds of successfully competing for an R01 or equivalent award. Of the career development recipients  who received an R01 or equivalent award, more than half received this award within 5 years of career development award issuance. These findings  support the importance of NIH-funded mentored career development awards (K08, K23) as beneficial for promoting a clinical pain research workforce. Please visit the Training and Career Development Outcome Data for Early-Career Pain Clinician-Scientists webpage for more details about the pain research workforce analysis conducted by OPPP (https://www.painconsortium.nih.gov/training-and-career-development-outcome-data-early-career-pain-clinician-scientists). 

Purpose 

The purpose of this NOFO is to enhance career development for early-career clinician-scientists in areas supported by the NIH HEAL Initiative's Clinical Research in Pain Management program. This career development award program is intended to foster the development of well-trained, independent clinical pain researchers that will help advance the pain-related mission of the NIH HEAL Initiative.  

Research Areas:

Applications for this NOFO may propose biopsychosocial research within the clinical pain management research area (encompassing chronic pain, acute pain, recurrent/episodic pain, the transition from acute to chronic pain, and/or a combination of these).  Examples of such research programs include, but are not limited to: 

• advancing health equity in pain management (including interventions on social determinants of health and healthcare to shape pain outcomes)  
• biomarkers  
• chronic overlapping pain conditions (COPC)
• implementation science (the scientific study of the use of strategies to adopt and integrate evidence-based health interventions into clinical and community settings to improve individual outcomes and benefit population health)
• non-opioid treatments for pain (including nonpharmacological approaches and effectiveness/implementation studies)  
• pain across the lifespan  
• pain education  
• prevention of chronic pain  
• placebo analgesia  

Because pain research proposals do not always fully align with the missions of one specific IC, applications proposing cross-cutting research projects are allowed and may be prioritized.

Pre-Submission Consultation 

Applicants are strongly encouraged to consult with NIH scientific/research staff as early as possible before the due date when planning an application. Early contact provides an opportunity for NIH scientific/research staff to provide guidance on program scope and appropriateness of the proposed research training for potential funding in response to this NOFO. 

Clinical Trial Required: This NOFO is designed specifically for applicants proposing to serve as the lead investigator of an independent clinical trial, a clinical trial feasibility study, or a separate ancillary clinical trial, as part of their research and career development. 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.” Most implementation trials including those that randomize at the organization, system or community level meet this definition. For additional details and frequently asked questions, visit https://grants.nih.gov/policy/clinical-trials/definition.htm or read the notice describing the revised definition of a clinical trial  NOT-OD-15-015.  

Annual National Pain Scientist Career Development Program Meeting (R24) 

The HEAL R24 Coordinating Center for National Pain Scientists recipient has created a network of early-career pain scientists, pain trainees, and mentors (RFA-NS-22-060). The HEAL R24 Coordinating Center for National Pain Scientists has named their program Positively Uniting Researchers of Pain to Opine, Synthesize, and Engage (PURPOSE) https://heal.nih.gov/research/cross-cutting-research/training-next-generation-researchers/purpose-network-coordinating-center-pain-scientists.The HEAL R24 Coordinating Center for National Pain Scientists will work 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 (called the Annual Purpose Meeting for Pain Research) for established scientists as well as early career pain investigators. This meeting facilitates the creation of a network of pain research mentors and mentees; fosters communication between scientists and clinicians of different disciplines; and provides enhanced mentorship, leadership courses, and any additional trainings that might be helpful for early-career scientists. Recipients of this K23 award  are required to attend - and may be asked to present at - the HEAL R24 Annual National Pain Scientist Career Development Meeting. Recipients of this K23 award should build in travel to the HEAL R24 Annual Pain Scientist Career Development Meeting (also known as the PURPOSE Annual Meeting) as part of their proposed budget, which can cover up to $2,000 for travel costs for the K23 recipient.  

In addition, K23 recipients are strongly encouraged to participate in all other aspects of the PURPOSE network, including networking experiences and webinars. 

HEAL Annual Meeting 

In addition to the Annual PURPOSE Meeting for Pain Research, The NIH HEAL Initiative further encourages coordination and sharing between investigators through participation at the annual HEAL Scientific Meeting. NIH HEAL Initiative award Career development recipients  who receive a NIH HEAL Initiative PainCare Clinician Training Program (PCTP) grant are encouraged to participate in Program Director/Principal Investigator (PD/PI) meetings, including the annual HEAL Scientific Meeting, as well as other HEAL activities. 

Rigor and Transparency  

NIH strives for rigor and transparency in all research it funds. For this reason, this NOFO explicitly emphasizes the NIH application instructions related to rigor and transparency (https://grants.nih.gov/policy/reproducibility/guidance.htm) and provides additional guidance to the scientific community (https://www.ninds.nih.gov/Funding/grant_policy). For example, the 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. K23 recipients will need to receive training in this area to equip themselves with the following skills required for careers in the research workforce: 

• Technical (e.g., appropriate methods, approaches, technologies, and quantitative/qualitative/mixed-methods analyses and reasoning) 
• Operational (e.g., independent knowledge acquisition, appropriate data management, robust and unbiased experimental design, safe laboratory conduct, proper interpretation of data, transparent reporting of all results, and sharing of data and materials) 
• Professional (e.g., leadership, management, and teamwork) 
• Communication (e.g., how to communicate results to professional organizations, fellow clinicians, people with lived experience of pain, and the general public; how to give job talks) 

Note: This Notice of Funding Opportunity (NOFO) is designed specifically for candidates proposing to serve as the lead investigator of an independent clinical trial, a clinical trial feasibility study, or a separate ancillary clinical trial, as part of their research and career development.  

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

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

Section II. Award Information

Other Award Budget Information

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

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Local Governments

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

Federal Governments

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

Other

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

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

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

Foreign components, as defined in the NIH Grants Policy Statement, are not allowed. 

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the How to Apply - Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference NIH Grants Policy Statement 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 registration; 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.

All PD(s)/PI(s) must be registered with ORCID. The personal profile associated with the PD(s)/PI(s) eRA Commons account must be linked to a valid ORCID ID. For more information on linking an ORCID ID to an eRA Commons personal profile see the ORCID topic in our eRA Commons online help.

Any candidate with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director/Principal Investigator (PD/PI) is invited to work with their mentor and organization to develop an application for support. Individuals from diverse backgrounds, including individuals from 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. Multiple PDs/PIs are not allowed.

By the time of award, the individual must be a citizen or a non-citizen national of the United States or have been lawfully admitted for permanent residence (i.e., possess a currently valid Permanent Resident Card USCIS Form I-551, or other legal verification of such status).

Current and former PDs/PIs on NIH research project (R01), program project (P01), center grants (P50), Project Leads of program project (P01), or center grants (P50), other major individual career development awards (e.g., K01, K07, K08, K22, K23, K25, K76, K99/R00), or the equivalent are not eligible. Current and former PDs/PIs of an NIH Small Grant (R03), Exploratory/Developmental Grants (R21/R33), Planning Grant (R34/U34), Dissertation Award (R36), or SBIR/STTR (R41, R42, R43, R44) remain eligible, as do PD/PIs of Transition Scholar (K38) awards and individuals appointed to institutional K programs (K12, KL2).

Individuals with the PhD or other doctoral degree in clinical disciplines such as clinical psychology, nursing, clinical genetics, speech-language pathology, audiology or rehabilitation are also eligible. 

Candidates for the K23 award must have a health-professional doctoral degree. Such degrees include, but are not limited to, an MD, DO, DDS, DMD, OD, DC, PharmD, ND (Doctor of Naturopathy), as well as a doctoral degree in nursing research or practice. Individuals with a PhD or other doctoral degree in clinical disciplines such as clinical psychology, clinical genetics, speech-language pathology, audiology or rehabilitation are also eligible. Individuals holding a PhD in a non-clinical discipline but who are certified to perform clinical duties should contact the appropriate Institute concerning their eligibility for a K23 award. Candidates also must have completed their clinical training, including specialty and, if applicable, subspecialty training prior to receiving an award. However, candidates may submit an application prior to the completion of clinical training.

2. Cost Sharing

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

3. Additional Information on Eligibility

Applicant organizations may submit more than one application, provided that each application is scientifically distinct, and each is from a different candidate.

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. An individual may not have two or more competing NIH career development applications pending review concurrently. In addition, 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).

Candidates may submit research project grant (RPG) applications concurrently with the K application. However, any concurrent RPG application may not have substantial scientific and/or budgetary overlap with the career award application. K award recipients are encouraged to obtain funding from NIH or other Federal sources either as a PD/PI on a competing research grant award or cooperative agreement, or as project leader on a competing multi-project award as described in NOT-OD-18-157.

At the time of award, the candidate must have a full-time appointment at the academic institution. Candidates are required to commit a minimum of 75% of full-time professional effort (i.e., a minimum of 9 person-months) to their program of career development. Candidates may engage in other duties as part of the remaining 25% of their full-time professional effort not covered by this award, as long as such duties do not interfere with or detract from the proposed career development program. 

Candidates who have VA appointments may not consider part of the VA effort toward satisfying the full-time requirement at the applicant institution. Candidates with VA appointments should contact the staff person in the relevant Institute or Center prior to preparing an application to discuss their eligibility.

After the receipt of the award, adjustments to the required level of effort may be made in certain circumstances.  See NOT-OD-18-156  and NIH Grants Policy Statement, Section 12.3.6.4 Temporary Adjustments to the Percent Effort Requirement for more details.

recruitment Mentor(s)

Before submitting the application, the candidate must identify a mentor who will supervise the proposed career development and research experience. The mentor should be an active investigator in the area of the proposed research and be committed both to the career development of the candidate and to the direct supervision of the candidate’s research. The mentor must document the availability of sufficient research support and facilities. Candidates are encouraged to identify more than one mentor, i.e., a mentoring team, if this is deemed advantageous for providing expert advice in all aspects of the research career development program.  In cases where a candidate has identified a mentoring team, one individual must be identified as the primary mentor who will coordinate the candidate’s research. It is strongly encouraged that at least one mentor should conduct research within the field of clinical pain management research. The candidate must work with the mentor(s) in preparing the application. The mentor, or a member of the mentoring team, should have a successful track record of mentoring individuals at the candidate’s career stage.  The recruitment  of women, individuals from underrepresented  racial and ethnic groups, and individuals with disabilities as potential mentors is encouraged.
 

Mentor competencies: Previous work (Fleming et al., 2013; Michel et al., 2018; and Wiskur et al., 2020) has identified 6 core competencies for successful and culturally competent mentors.  In the mentoring section of the grant, mentors and co-mentors  should address how they have a track record of providing mentorship in line with these competencies. Consultants and collaborators should address the mentoring competencies in their letters of support. These competencies include:

• Address Self-Efficacy– a mentor’s ability to consider how to identify inequities, how to take accountability for personal biases they bring into the mentoring relationship, how to participate in and/or lead programs designed to promote diversity* in research, and how to work effectively with mentees whose personal backgrounds differ from their own
• Align Expectations – a mentor’s ability to consider how personal and professional differences between the mentor and mentee impact their respective expectations, how to work with mentees to set expectations for the mentoring relationship and research goals, and how to help mentees develop strategies to meet goals
• Assess Understanding – a mentor’s ability to accurately assess a mentee’s level of ability to publish research, submit grants, and conduct research as well as guidance for strategies to enhance their mentee’s scientific knowledge and skills
• Foster Independence – a mentor’s ability to build mentees’ confidence, motivate mentees, encourage mentees’ creativity, and acknowledge mentees’ professional contributions
• Maintain Effective Communication – a mentor’s ability to actively listen to mentees, accommodate different communication styles, coordinate effectively with other mentors, build trust, and provide constructive feedback
• Promote Professional Development – a mentor’s ability to help gain resources, maintain balance with personal life goals, set career goals, and network effectively

*Consistent with federal law, the race, ethnicity, or sex (including gender identify, sexual orientation, or transgender status) of a researcher, award participant, or trainee will not be considered during the application review process or when making funding decisions.

The mentor(s) or mentoring team must demonstrate appropriate expertise, experience, and ability to guide the applicant in the organization, management and implementation of the proposed research and clinical trial.

The applicant institution must have a strong, well-established record of research and career development activities and faculty qualified to serve as mentors in biopsychosocial and clinical research.

Section IV. Application and Submission Information

1. Requesting an Application Package

Buttons to access the online ASSIST system or to download application forms 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 Career Development (K) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the How to Apply - Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

For information on Application Submission and Receipt, visit Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.

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.

Other Project Information

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

Project Summary/Abstract

Include a description of your current research and the future research you propose during the K23 award period.

SF424(R&R) Senior/Key Person Profile Expanded

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

IMPORTANT REMINDER: The personal profile associated with the eRA Commons username entered in the Credential field for the PD/PI (candidate) must include an ORCID ID. For more information on linking an ORCID ID to an eRA Commons personal profile see the ORCID topic in our eRA Commons online help.

R&R 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 Career Development Award Supplemental Form

The PHS 398 Career Development Award Supplemental Form is comprised of the following sections:

Candidate
Research Plan
Other Candidate Information
Mentor, Co-Mentor, Consultant, Collaborators
Environment & Institutional
Commitment to the Candidate
Other Research Plan Sections
Appendix

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

Candidate Section

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

Candidate Information and Goals for Career Development

Candidate’s Background

• Describe the candidate's commitment to an academic career in Patient-Oriented Research (POR). Describe all of the candidate's professional responsibilities in the recipient institution, national/state organizations, various committees, participation on journal editorial boards, community engagement effort, etc. and describe their relationship to the proposed activities on the career award. 
• Present evidence of the candidate's ability to interact and collaborate with other scientists. 
• Describe prior training and how it relates to the objectives and long-term career plans of the candidate. 
• Describe the candidate's research efforts to this point in their research career, including any publications, prior research interests and experience. 
• Describe the candidate's committment to clinical pain research.
• Provide evidence of the candidate's potential to develop into an independent investigator. Usually this is evident from publications, prior research interests and experience, service in national/state organizations, participation in journals, engagement with community partners, role as an effective mentor, prior training, and reference letters.
• Candidates with limited research experience may propose a career development experience that includes a designated period of didactic training followed by a period of closely supervised research experience.
• The candidate must demonstrate they have received training or will participate in courses/training in areas such as: data management, epidemiology, study design (including statistics), hypothesis development, community engagement, health equity, etc., as well as the legal and ethical issues associated with research on human participants and clinical trials.

•  Describe the candidate's ability to organize, manage, and implement the proposed clinical trial, feasibility or ancillary clinical trial.
•  Describe the candidate's prior efforts, interests and experience in clinical trials research.
•  Describe the candidate's commitment to the field of clinical pain management. 

Career Goals and Objectives​

• Describe a systematic plan: (1) that shows a logical progression from prior research and training experiences to the research and career development experiences that will occur during the mentored career award period and then to independent investigator status in the field of pain management; and (2) that specifically identifies and justifies the need for further career development to become an independent investigator.

Candidate’s Plan for Career Development/Training Activities During Award Period

• The candidate and the mentor(s) are jointly responsible for the preparation of the career development plan.  A career development timeline is often helpful.  
• The didactic (if any) and the research aspects of the plan must be designed to develop the necessary knowledge and research skills in scientific areas relevant to the candidate's stated career goals.
• Describe the professional responsibilities/activities including other research projects beyond the minimum required 9 person months (75% full-time professional effort) commitment to the career award, if any. Explain how these responsibilities/activities will help ensure career progression to achieve independence as a clinical investigator..
• The candidate is encouraged to demonstrate how they will develop skills to meaningfully engage and consider the needs of people with lived experience of pain in their research, as well as how they will communicate the results of their research to various stakeholders (e.g., people with lived experience, policy makers, and journalists).

Research Plan Section

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

Research Strategy

• A sound research project that is consistent with the candidate’s level of research experience and that aligns with the research career goals and objectives of their career development plan must be provided. The research description should demonstrate the quality of the candidate’s research thus far and also the novelty, significance, creativity and approach, as well as the ability of the candidate to carry out the proposed research.
• The application must also describe the relationship between the mentor’s research and the candidate’s proposed research plan.
• While the focus of the K23 award is on Patient-oriented research (POR), complementary laboratory research directly related to patient-oriented research may be proposed in the application, thereby providing an opportunity for a career development experience in translational research.

• Describe the proposed timelines for the proposed clinical trial, feasibility study or ancillary clinical trial, including any potential challenges and solutions (e.g., enrollment shortfalls or inability to attribute causal inference to the results of an intervention when performing a small feasibility study).
• Describe how the proposed clinical trial or ancillary clinical trial will test the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy (This would not apply to a feasibility study).
• The research proposal should demonstrate an understanding of pain as a biopsychosocial phenomenon.
• The candidate may want to engage people with lived experience of pain, as advisors/partners on the proposed research project. If using community-engaged research methods, the proposed budget should reflect appropriate compensation for these individuals' time and expertise on the project. For more information about community-engagement in HEAL research please see the "Patient and Community Engagement" resources page (https://heal.nih.gov/resources/engagement).

Training in the Responsible Conduct of Research

• All applications must include a plan to fulfill NIH requirements for instruction in the Responsible Conduct of Research (RCR). See How to Apply - Application Guide for instructions.

Mentor, Co-Mentor, Consultant, Collaborators Section

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

Plans and Statements of Mentor and Co-mentor(s)

• The candidate must name a primary mentor who, together with the candidate, is responsible for the planning, directing, monitoring, and executing the proposed program.  The candidate may also nominate co-mentors as appropriate to the goals of the program.   
• The mentor should have sufficient independent research support to cover the costs of the proposed research project in excess of the allowable costs of this award. 
• Include a statement that the mentor and institution can commit to having the career development awardee commit at least 9 person months (75% of full-time professional effort) to the career development program and related career development activities.
• The application must include a statement from the mentor providing: 1) information on their research qualifications and previous experience and success as a research supervisor; 2) a plan that describes the nature of the supervision and mentoring that will occur during the proposed award period; 3) a plan for career progression for the candidate to move from the mentored stage of their career to independent research investigator status during the project period of the award; 4) a plan for monitoring the candidate’s research, publications, and progression towards independence; and 5) a plan for which areas of the proposed research will belong to the candidate versus the mentor(s) and which areas will overlap between the candidate and mentor(s). 
• The mentoring plan section should describe how he/she/they demonstrate the mentorship competencies outlines above under “Mentor(s”). 1) information on his/her/their research qualifications and previous experience as a research supervisor; 2) a plan that describes the nature of the supervision and mentoring that will occur during the proposed award period; 3) a plan for career progression for the candidate to move from the mentored stage of his/her/their career to independent research investigator status during the project period of the award; and 4) a plan for monitoring the candidate’s research, publications, and progression towards independence
• Similar information must be provided by any co-mentor.  If more than one co-mentor is proposed, the respective areas of expertise and responsibility of each should be described.  Co-mentors should clearly describe how they will coordinate the mentoring of the candidate. If any co-mentor is not located at the sponsoring institution, a statement should be provided describing the mechanism(s) and frequency of communication with the candidate, including the frequency of face-to-face meetings. 
• The application must include a description of why the mentor(s), consultant(s), and/or collaborator(s) are well-suited to the research proposed by the 
• The mentor must agree to provide annual evaluations of the candidate’s progress as required in the annual progress report.

• If the candidate is proposing to gain experience in a clinical trial as part of his/her/their research career development, the mentor or co-mentor of the mentoring team must include a statement to document leadership of the clinical trial, and appropriate expertise to guide the applicant in any proposed clinical trials research experience.
• The mentor or mentoring team must provide evidence of expertise, experience, and ability to guide the candidate in the organization, management and implementation of the proposed clinical trial, ancillary clinical trial or feasibility study and help the candidate to meet timelines.

Letters of Support from Collaborators, Contributors and Consultants

• Signed statements must be provided by all collaborators and/or consultants confirming their participation in the project and describing their specific roles. Unless also listed as senior/key personnel, collaborators and consultants do not need to provide their biographical sketches. However, information should be provided clearly documenting the appropriate expertise in the proposed areas of consulting/collaboration. 
• Advisory committee members (if applicable): Signed statements must be provided by each member of the proposed advisory committee.  These statements should confirm their participation, describe their specific roles, and document the expertise they will contribute.  Unless also listed as senior/key personnel, these individuals do not need to provide their biographical sketches. 

Environmental and Institutional Commitment to the Candidate

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

Description of Institutional Environment

• The sponsoring institution must document a strong, well-established research and career development program related to the candidate's area of interest, including a high-quality research environment with key faculty members and other investigators capable of productive collaboration with the candidate. 
• Describe how the institutional research environment is particularly suited for the development of the candidate's research career and the pursuit of the proposed research plan.
• Describe the resources and facilities that will be available to the candidate, including any oversight and mechanisms for fair resolution of disputes.

• Describe the resources and facilities that will be available to the candidate, including any clinical trial-related resources, such as specialized administrative, data coordinating, enrollment, and laboratory/testing support. If applicable, include a description of the resources and facilities available at international sites.

Institutional Commitment to the Candidate’s Research Career Development

• The sponsoring institution must provide a statement of commitment to the candidate's development into a productive, independent investigator and to meeting the requirements of this award. It should be clear that the institutional commitment to the candidate is not contingent upon receipt of this career award. 
• Provide assurances that the candidate will be able to devote the required effort to activities under this award. The remaining effort should be devoted to activities related to the development of the candidate’s career as an independent scientist. 
• Provide assurances that the candidate will have access to appropriate office and laboratory space, equipment, and other resources and facilities (including access to clinical and/or other research populations) to carry out the proposed research plan. 
• Provide assurance that appropriate time and support will be available for any proposed mentor(s) and/or other staff consistent with the career development plan.
• Candidates who will be using resources associated with a Clinical and Translational Science Award (CTSA) during the course of their career development award should include a letter of agreement from the CTSA PD/PI as part of their application.

Other Plan(s):

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

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.

HEAL Public Access and Data Sharing Policy:  

NIH intends to maximize the impact of 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.  Resources and tools to assist with data related activities can be found at https://www.healdatafair.org/.

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.  

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

All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan. 

The HEAL Initiative has additional requirements that must be addressed in the Data management and Sharing plan. 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: 

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

Data generated by 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 recipients  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 auto-populated 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 HEAL Initiative studies conducting clinical research or research involving human subjects.

These studies must meet the following additional requirements:

HEAL Initiative trials that are required to register in clinicaltrials.gov should reference support from and inclusion in the HEAL Initiative by including the standardized terms “the HEAL Initiative (https://heal.nih.gov/)” in the Study Description Section.

All new HEAL clinical pain studies are required to use core questionnaires required by the HEAL Clinical 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 HEAL clinical pain studies. The program has created the 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.   

HEAL Initiative clinical studies that are using copyrighted questionnaires  are required to obtain licenses for use prior to initiating data collection. Licenses must be shared with the HEAL CDE team and the program officer prior to use of copyrighted materials. For additional information, visit the HEAL CDE Program (https://heal.nih.gov/data/common-data-elements).

To the extent possible, all other (non-pain) HEAL studies conducting clinical trials or research involving human subjects are expected to use questionnaires by the HEAL Clinical Data Elements (CDE) Program (https://heal.nih.gov/data/common-data-elements) if applicable and relevant to their research.

To the extent possible, HEAL recipients  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 so 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.

Appendix:

Limited items are allowed in the Appendix.  Follow all instructions for the Appendix as described in the How to Apply - Application Guide; any instructions provided here are in addition to the How to Apply - Application Guide instructions.

PHS Human Subjects and Clinical Trials Information

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).

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

PHS Assignment Request Form

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

Reference Letters

Candidates must carefully follow the How to Apply - Application Guide, including the time period for when reference letters will be accepted. Applications lacking the appropriate required reference letters will not be reviewed. This is a separate process from submitting an application electronically. Reference letters are submitted directly through the eRA Commons Submit Referee Information link and not through Grants.gov. 

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) using ASSIST or other electronic submission systems. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time.  If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH 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 Section 7.9.1 Selected Items of Cost.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the 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.

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 or non-compliant will not be reviewed.

Post Submission Materials

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

Section V. Application Review Information

1. Criteria

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

Overall Impact

Reviewers should provide their assessment of the likelihood that the proposed career development and research plan will enhance the candidate’s potential for a productive, independent scientific research career in the field of clinical pain management, taking into consideration the criteria below in determining the overall impact score. 

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact.

The reviewers will consider that the clinical trial may include study design, methods, and intervention that are not by themselves innovative, but address important questions or unmet needs. Reviewers should also consider the scope of the clinical trial relative to the available resources, including the possibility that research support provided through career development awards may be sufficient to support only small feasibility studies.

  Candidate

• Does the candidate have the potential to develop as an independent and productive researcher in the field of clinical pain management?
• Are the candidate's prior training, research experience, and community engagement experience appropriate for this award? 
• Is the candidate’s academic, clinical (if relevant), and research record of high quality? 
• Is there evidence of the candidate’s commitment to meeting the program objectives to become an independent investigator in research? 
• Do the reference letters address the above review criteria, and do they provide evidence that the candidate has a high potential for becoming an independent investigator.

• Does the candidate have the potential to organize, manage, and implement the proposed clinical trial, feasibility or ancillary study?
• Does the candidate have training (or plans to receive training) in data management and statistics including those relevant to clinical trials?
• Does the candidate have the appropriate background and experience to pursue a career as a pain clinician scientist?

Career Development Plan/Career Goals and Objectives/Plan to Provide Mentoring

• What is the likelihood that the plan will contribute substantially to the scientific development of the candidate and lead to scientific independence? 
• Are the content, scope, phasing, and duration of the career development plan appropriate when considered in the context of prior training/research experience and the stated training and research objectives for achieving research independence? 
• Are there adequate plans for monitoring and evaluating the candidate’s research and career development progress?
• Is the mentor or mentorship team appropriate for the proposed research project and career development program?
• Will the proposed experiments and career development plan prepare the candidate to transition to an independent pain clinician-scientist?

•  Will the proposed clinical trial contribute to the candidate's research career development?

Research Plan

• Is the prior research that serves as the key support for the proposed project rigorous?
• Has the candidate included plans to address weaknesses in the rigor of prior research that serves as the key support of the proposed project? 
• Has the candidate presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed?
• Has the candidate presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?
• Is the proposed research question, design, and methodology of significant scientific and technical merit? 
• Is the research plan relevant to the candidate’s research career objectives? 
• Is the research plan appropriate to the candidate's stage of research development and does it support the candidate in developing the research skills described in the career development plan?
• Does the research plan explain the areas of research belonging to the candidate versus those belonging to the mentor(s), and any areas of research that overlap?
• Will the proposed research lead to an independent line of research for the candidate?
• Does the proposed research express appreciation for the biopsychosocial nature of pain?
• Will the proposed research project answer meaningful questions in the field of translational pain science or pain management? 

• Are the scientific rationale and need for a clinical trial, ancillary clinical trial, or feasibility or ancillary study well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms?
• If proposing a small feasibility study, is the study warranted and will it contribute to planning and preliminary data needed for design of future larger scale clinical trials?
• Is the clinical trial or ancillary clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention, or in the case of a feasibility study necessary to establish feasibility of future clinical tria
• For trials focusing on mechanistic, behavioral, physiological, biochemical, social, or other endpoints, is this trial needed to advance scientific understanding?
• "Is the study design justified and relevant to the hypothesis(es) being tested?
• Are the plans to standardize, assure quality of, and monitor adherence to, the protocol and data collection or distribution guidelines appropriate?
• Are planned analyses and statistical approaches appropriate for the proposed study design and methods used to assign participants and deliver interventions, if interventions are delivered?

Mentor(s), Co-Mentor(s), Consultant(s), Collaborator(s)

• Does the mentor or mentoring team have the expertise, experience, and ability to guide the candidate in the organization, management and implementation of the proposed clinical trial, ancillary clinical trial, or feasibility study and help to meet timelines?
• Do the mentors demonstrate mentorship competencies as defined in the Mentorship Competencies section?
• Does the mentor or any member of the mentoring team have experience as a clinician scientist in the field of pain?
• Do the mentors include individuals across diverse backgrounds, including a multidisciplinary mentoring team and scholars from underrepresented sociodemographic groups in research?
• Is there an explanation that distinguishes research areas belonging to the candidate versus the research areas belonging to mentor(s), as well as areas of overlap between the candidate and mentor(s)?
• Do the mentors, consultants, and/or collaborators have appropriate expertise in clinical pain research?
• Do the mentor(s), consultant(s), and/or collaborator(s) adequately address the candidate’s potential and their strengths and areas needing improvement?
• Is there adequate description of the quality and extent of the mentor’s, consultant’s, and/or collaborator’s proposed role in providing guidance and advice to the candidate?
• Is the mentor’s, consultant’s, and/or collaborator’s description of the elements of the research career development activities, including formal course work adequate?
• Is there evidence of the mentor’s, consultant’s, and/or collaborator’s previous experience in fostering the development of independent investigators?
• Is there evidence of the mentor's, consultant’s, and/or collaborator’s current and previous research productivity and peer-reviewed support?
• Is the mentor’s, consultant’s, and/or collaborator’s support in relation to the research project adequate and appropriate for the candidate’s career development?
• Are there adequate plans for monitoring and evaluating the career development recipient’s progress toward independence?
• Are the mentor’s, consultant’s, and/or collaborator’s research qualifications, scientific stature, experience, and mentoring track record appropriate for the candidate's research career development needs?
• Are the nature and extent of the proposed mentorship adequate and appropriate, and is the commitment of the mentor(s), consultant(s), and/or collaborator(s) to the candidate's advanced research career development appropriate?
• Do the mentors, consultants, and/or collaborators demonstrate a history of mentoring individuals from diverse backgrounds
• Do the mentors, consultants, and/or collaborators demonstrate mentorship competencies as defined in the Mentorship Competencies section?

• Does the mentor or mentoring team have the expertise, experience, and ability to guide the applicant in the organization, management and implementation of the proposed clinical trial, ancillary clinical trial, or feasibility study and help him/her to meet timelines?

Environment & Institutional Commitment to the Candidate

• Is there clear commitment of the sponsoring institution to ensure that the required minimum of 75% of the candidate’s effort will be devoted directly to the research described in the application, with the remaining percent effort being devoted to an appropriate balance of research, teaching, administrative, and clinical responsibilities? 
• Is the institutional commitment to the career development of the candidate appropriately strong? 
• Are the research facilities, resources and training opportunities, including faculty capable of productive collaboration with the candidate adequate and appropriate? 
• Is the environment for the candidate’s scientific and professional development of high quality? 
• Is there assurance that the institution intends the candidate to be an integral part of its research program as an independent investigator?

• Are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?
• Does the application adequately address the capability and ability to conduct the trial, ancillary clinical trial, or feasibility study at the proposed site(s) or centers? If applicable, are there plans to add or drop enrollment centers, as needed, appropriate?
• If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

Study Timeline for Clinical Trials

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following three points: (1) a complete description of all proposed procedures including the species, strains, ages, sex, and total numbers of animals to be used; (2) justifications that the species is appropriate for the proposed research and why the research goals cannot be accomplished using an alternative non-animal model; and (3) interventions including analgesia, anesthesia, sedation, palliative care, and humane endpoints that will be used to limit any unavoidable discomfort, distress, pain and injury in the conduct of scientifically valuable research. Methods of euthanasia and justification for selected methods, if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals, is also required but is found in a separate section of the application. For additional information on review of the Vertebrate Animals Section, please refer to the Worksheet for Review of the Vertebrate Animals Section.

Biohazards

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

Resubmissions

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

Revisions

The committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision  relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

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

Resource Sharing Plans

Reviewers will comment on whether the Resource Sharing Plan(s) (i.e., Sharing Model Organisms) or the rationale for not sharing the resources, is reasonable.

Training in the Responsible Conduct of Research

All applications for support under this NOFO must include a plan to fulfill NIH requirements for instruction in the Responsible Conduct of Research (RCR). Taking into account the level of experience of the candidate, including any prior instruction or participation in RCR as appropriate for the candidate’s career stage, the reviewers will evaluate the adequacy of the proposed RCR training in relation to the following five required components: 1) Format - the required format of instruction, i.e., face-to-face lectures, coursework, and/or real-time discussion groups (a plan with only on-line instruction is not acceptable); 2) Subject Matter - the breadth of subject matter, e.g., conflict of interest, authorship, data management, human subjects and animal use, laboratory safety, research misconduct, research ethics; 3) Faculty Participation - the role of the mentor(s) and other faculty involvement in the fellow’s instruction; 4) Duration of Instruction - the number of contact hours of instruction (at least eight contact hours are required); and 5) Frequency of Instruction –instruction must occur during each career stage and at least once every four years. Plans and past record will be rated as ACCEPTABLE or UNACCEPTABLE, and the summary statement will provide the consensus of the review committee. See also: NOT-OD-10-019.

Select Agent Research

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

Authentication of Key Biological and/or Chemical Resources

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

Budget and Period of Support

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s), 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:

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.

All applications will receive reviewers' written critique.

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. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board.

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

3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information

1. Award Notices

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

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the recipient’s business official.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

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

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

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:

• Federal-wide Standard Terms and Conditions for Research Grants
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions. 

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 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.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to System for Award Management (SAM.gov) requirements. SAM.gov requires Federal agencies to review and consider information about an applicant in the designated integrity and performance system (currently SAM.gov) prior to making an award. 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 addition to the information available in the responsibility/qualification records in SAM.gov, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 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. Data Management and Sharing

Consistent with the 2023 NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

HEAL Data Sharing Requirements 

NIH intends to maximize the impact of HEAL Initiative-supported projects through broad and rapid data sharing.  All 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. HEAL award recipients must following all requirements and timelines developed through the HEAL Initiative Data Ecosystem (https://heal.nih.gov/about/heal-data-ecosystem), as described in HEAL’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 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 recipients  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 auto-populated 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 HEAL Initiative studies conducting clinical research or research involving human subjects. 

These studies must meet the following additional requirements:  

HEAL Initiative trials that are required to register in clinicaltrials.gov should reference support from and inclusion in the HEAL Initiative by including the standardized terms “the HEAL Initiative (https://heal.nih.gov/)” in the Study Description Section. 

All new HEAL clinical pain studies are required to use core questionnaires required by the HEAL Clinical 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 HEAL clinical pain studies. The program has created the 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.   

HEAL Initiative clinical studies that are using copyrighted questionnaires  are required to obtain licenses for use prior to initiating data collection. Licenses must be shared with the HEAL CDE team and the program officer prior to use of copyrighted materials. For additional information, visit the HEAL CDE Program (https://heal.nih.gov/data/common-data-elements).  

To the extent possible, all other (non-pain) HEAL studies conducting clinical trials or research involving human subjects are expected to use questionnaires by the HEAL Clinical Data Elements (CDE) Program (https://heal.nih.gov/data/common-data-elements) if applicable and relevant to their research.  

To the extent possible, HEAL recipients  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 so 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

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement. The Supplemental Instructions for Individual Career Development (K) RPPRs must be followed. For mentored awards, the Mentor’s Report must include an annual evaluation statement of the candidate’s progress.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement. NIH 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 200.301.

The Federal Funding Accountability and Transparency Act of 2006 as amended (FFATA), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All recipients of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over the threshold. See the NIH Grants Policy Statement for additional information on this reporting requirement. 

In accordance with the regulatory requirements provided at 2 CFR Part 200.113 and Appendix XII to 2 CFR Part 200, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period.  The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (Responsibility/Qualification in SAM.gov, formerly FAPIIS).  This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313).  As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available.  Full reporting requirements and procedures are found in Appendix XII to 2 CFR Part 200 – Award Term and Condition for Recipient Integrity and Performance Matters.

5. Evaluation

In carrying out its stewardship of human resource-related programs, NIH may request information essential to an assessment of the effectiveness of this program from databases and from participants themselves. Participants may be contacted after the completion of this award for periodic updates on various aspects of their employment history, publications, support from research grants or contracts, honors and awards, professional activities, and other information helpful in evaluating the impact of the program.

The overall evaluation of the program will be based on metrics that will include, but are not limited to, the following:

• Subsequent participation in research or employment in pain research 
• Authorship of scientific publications in pain research 
• Subsequent independent research grant support from NIH or another source

Section VII. Agency Contacts

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

Prior consultation with NIH staff is strongly encouraged.

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten on-time submission, 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 processes and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-637-3015

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

Laura D. Wandner, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Email: [email protected]

Elizabeth Sypek, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Email: [email protected] 

Lanay M. Mudd, Ph.D., FACSM
National Center for Complementary and Integrative Health (NCCIH)
Phone: 301-594-9346
Email: [email protected]

Helena H. Ahn, PhD
Eunice Kennedy Shriver National Institute of Child Health and Human Development
Telephone: 301-827-3207
Email: [email protected]

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

NIA Training Office 
National Institute on Aging (NIA)
E-mail: [email protected]

Tina L Gatlin
NIBIB - NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING
Phone: 301.480.2280
E-mail: [email protected]

Kevin C Abbott, Ph.D
NIDDK - NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
Phone: 301.594.7714
E-mail: [email protected]

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

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

Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS)
Email: [email protected]

Debbie Chen
National Center for Complementary and Integrative Health (NCCIH)
Phone: 301-594-3788
Email: [email protected]

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

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

Jessica Perez
National Institute on Aging (NIA)
Phone: 301 496-1472
E-mail: [email protected]

Katie Ellis
NIBIB - NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING
Phone: 301-451-4791
E-mail: [email protected]

Erik Edgerton
NIAMS - NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES
Phone: 301-594-7760
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.

Please note that the NIH Loan Repayment Programs (LRPs) are a set of programs to attract and retain promising early-stage investigators in research careers by helping them to repay their student loans. Recipients of career development awards are encouraged to consider applying for an extramural LRP award (https://www.lrp.nih.gov/).

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.