Part 1. Overview Information

Key Dates

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

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

No late applications will be accepted for this Funding Opportunity Announcement.

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

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

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

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

The NIH Director's Pioneer Award supports individual scientists of exceptional creativity who propose highly innovative and broadly impactful research towards the ultimate goal of enhancing human health.

In order to support the most innovative and impactful research, the NIH recognizes the need to foster a diverse research workforce across the nation. See, e.g., Notice of NIH's Interest in Diversity, NOT-OD-20-031. Applications to this award program should reflect the full diversity of potential PD/PIs, applicant institutions, and research areas relevant to the broad mission of NIH. Researchers from diverse backgrounds, including those from underrepresented racial and ethnic groups, persons with disabilities, and women are strongly encouraged to work with their institutions to develop applications for this Funding Opportunity Announcement. 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. Since outstanding research is conducted at a broad spectrum of institutions, it benefits the national scientific enterprise for NIH to support exceptionally innovative and impactful science that represents this breadth. Therefore, this Funding Opportunity Announcement encourages applications from the full range of eligible institutions, including minority serving institutions and those serving primarily underrepresented groups, those that may be less research-intensive, and from all domestic geographic locations. Applications are welcome in all research areas broadly relevant to the mission of NIH. These areas include, but are not limited to, the behavioral, medical, natural, social, applied, and formal sciences. Research may be basic, translational, or clinical. The primary requirements are that the research be highly innovative and have the potential for unusually broad impact.

In the Pioneer Award program, emphases are on the qualities of the investigator, the innovativeness, and potential impact of the proposed research. Preliminary data and detailed experimental plans are not requested. To be considered pioneering and as an aspect of innovativeness, the proposed research must reflect substantially different ideas from those being pursued in the investigator’s current research program or elsewhere. The Pioneer Award is not intended to expand a current research program into the area of the proposed project. While the research direction may rely on the applicant’s prior work and expertise as its foundation, it cannot be an obvious extension or scale-up of a current research enterprise. Rather, the proposed project must reflect a fundamental new insight which may involve exceptionally innovative approaches and/or radically unconventional hypotheses. Applications for projects that are straightforward extensions of ongoing research should not be submitted.

Pioneer awardees are required to commit the major portion (more than 6 person-months or at least 51%) to activities supported by the Pioneer Award research project in the first three years of the project period. Effort expended toward teaching, administrative, or clinical duties should not be included in this calculation. Awardees may reduce effort to a minimum of 4 person-months (33%) and a minimum of 3 person-months (25%) in the fourth and fifth years, respectively, to help them transition to other sources of support since Pioneer Awards cannot be renewed. Applicants with current research commitments equal to 6 person-months or more must adjust their effort on existing grants during the award period to devote the required minimum effort to the Pioneer Award project. Investigators who will not be able to meet this requirement should not submit applications. Given the scientifically risky nature of the proposed research, awardees will be given unusual flexibility to pivot their research direction as warranted to maximize scientific impact during the project period.

Investigators who were not selected for an award in prior years may submit applications this year as long as they retain eligibility requirements described in this FOA; however, all applications must be submitted as new applications regardless of any previous submission to the program. No reference to any prior application may be included. Any reference to a prior application may be grounds for administrative withdrawal.

Prospective applicants are invited to a pre-application webinar on June 20, 2023, from 3:00-4:30 PM ET. NIH staff will discuss the initiative and answer questions about the application and review process. Questions for the webinar should be submitted ahead of time to [email protected] by 11:59 PM local time on June 15, 2023. Additional questions may be taken during the webinar if time allows. Register for the webinar and join on Webex. The webinar will be recorded and posted on the Pioneer Award website.

The NIH Director's Pioneer Award is part of the High-Risk, High-Reward Research (HRHR) Program funded through the NIH Common Fund, which supports cross-cutting programs that are expected to have exceptionally high impact. All Common Fund initiatives invite investigators to develop bold, innovative, and often risky approaches to address problems that may seem intractable or to seize new opportunities that offer the potential for rapid progress.

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

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

Section II. Award Information

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

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 Government

• Eligible Agencies of the Federal Government, which excludes NIH Intramural Program
• U.S. Territory or Possession

Other

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

Non-domestic (non-U.S.) Entities (Foreign Institutions) 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 allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• 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.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.

Only single PD/PI applications are allowed. Applications with multiple PD(s)/PI(s) will not be accepted.

2. Cost Sharing

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

3. Additional Information on Eligibility

Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct. Individuals may submit only one application as a PD/PI in response to this FOA.

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

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

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

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

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

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

with the following additional instructions:

Agency Routing Identifier Field (in Field 4b): Enter Science Area Designations. Designate two scientific areas (a primary and secondary) from the list below. For each area, enter the one-digit code and abbreviation (e.g., 1 BSS).

1 BSS - Behavioral and Social Science
2 CB - Chemical Biology
3 CTR - Clinical and Translational Research
4 IDI - Infectious Diseases and Immunology
5 IE - Instrumentation and Engineering
6 MCB - Molecular and Cellular Biology
7 NS - Neuroscience
8 HIB - High-Throughput and Integrative Biology
9 BCB - Bioinformatics and Computational Biology

The Science Area Designations are to assist in assigning applications to reviewers. The science areas are very broad and frequently overlap. Pioneer Award reviewers are chosen for their breadth of knowledge, expertise, and their ability to review a broad range of applications. Choose the primary and secondary science areas that are most appropriate for your proposed project.

IMPORTANT: For each of the two science area designations, enter the one-digit code followed by one space and then the corresponding abbreviation. Enter the primary area first, followed by a semicolon, then enter secondary area.
Correct Example: 1 BSS; 7 NS

Note: The two scientific area designations (one-digit code and abbreviation for each) must also be included at the beginning of the Essay. See information under Research Strategy below.

Type of Application: Must be New .

Proposed Project: Enter start date: 09/30/2024; enter end date: 07/31/2029.

Total Federal Funds Requested: Enter $3,500,000 (see note below).

Total Non-Federal Funds: Enter $0.

Total Federal & Non-Federal Funds: Enter $3,500,000.

Estimated Program Income: Enter $0.

Note: The Budget Request is entered only in Fields "Total Federal Funds Requested" and "Total Federal & Non-Federal Funds" as described above. Funds may be requested for personnel (including collaborators), supplies, equipment, sub-contracts, and other allowable costs. Only the five-year direct cost total $3,500,000 should be entered in Fields "Total Federal Funds Requested" and "Total Federal & Non-Federal Funds." Applicable Facilities and Administrative (F&A) costs will be determined at the time of award and should not be included in the budget request. A detailed budget and other budget forms are not requested and will not be accepted.

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

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

Bibliography & References Cited: DO NOT USE. Reference citations are not required. Those considered to be essential may be included in the essay and will be included in the page limit.

Facilities & Other Resources Statement: 1 page maximum.

Equipment: DO NOT USE.

Other Attachments: DO NOT USE.

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

Profile Project Director/Principal Investigator Field Current and Pending Support: Attach a list of Current and Pending Support from all sources, including current year direct costs and effort devoted to each project.

Profile Senior Key Person 1: DO NOT USE. Submit information only for PD/PI. Information on collaborators or other key personnel is not required but may be included in the Essay.

Research and Related Senior/Key Person Profile (Expanded) - Additional Senior/Key Person Profiles(s): DO NOT USE. Only the PD/PI may serve as senior/key personnel.

Research and Related Senior/Key Person Profile (Expanded) - Additional Biographical Sketch(es): DO NOT USE. Only the PD/PI may submit a Biographical Sketch.

Modular Budget

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

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

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

Specific Aims: Do not use.

Research Strategy: Attach the Essay here, which should contain the following information. The pdf should be named "Essay.pdf."

Describe your innovative vision for addressing a major challenge or pursuing an opportunity of relevance to NIH, the importance of this challenge or opportunity, and your qualifications to engage in groundbreaking research. No detailed scientific plan should be provided since the research plan is expected to evolve during the tenure of the grant. The essay should include the following sections in the order given with the headings as shown below:

Scientific Areas: Provide 1-digit code and abbreviation for primary and secondary science areas at the beginning of essay. See "Agency Routing Identifier" information above for codes and format.

Project Title: The project title must be descriptive of the proposed project.

Project description: What is the scientific challenge or opportunity that will be addressed, and why is this important? What are the pioneering, highly innovative approaches that, if successful, would lead to groundbreaking or paradigm-shifting results? It is recommended to prominently indicate that neither a detailed experimental plan nor extensive preliminary data are being provided per the FOA. However, the reviewers must still have a clear sense of the overall research to be pursued and must be convinced that the research will be pursued in a robust and rigorous manner. The writing should be at a level that conveys the significance and impact of the application to broadly knowledgeable scientists with different expertise domains.

Evidence of PD's/PI's innovativeness: What concrete evidence can you provide for your claim of innovativeness? For example, qualities common to many highly innovative people include the ability to integrate disparate sources of information; an inclination to question paradigms; a willingness to work with intellectual uncertainties; persistence in the face of failure; an ability to work collaboratively with researchers from multiple disciplines; and the energy and concentration necessary to plan and execute effective strategies for accomplishing goals.

How the planned research differs from the PD's/PI's past or current work: How does the proposed project represent a new and distinct direction for your research? While a new research direction may have the PD's/PI's prior work and expertise as its foundation, it cannot be an obvious extension or scale-up of a current research enterprise which could be appropriate for a more conventional NIH funding mechanism, such as a new or renewal R01. Rather, a new research direction must reflect a fundamental new insight, and may involve development of exceptionally innovative approaches and/or the posing of radically unconventional hypotheses. Applications for projects that are extensions of ongoing research should not be submitted.

Suitability for Pioneer Award program: Why is the planned research uniquely suited to the stated goal of the Pioneer Award program rather than a more traditional grant mechanism?

Statement of research effort commitment: A statement must be included that, if chosen to receive an award, the PD/PI will commit more than 6 person-months (at least 51%) of his/her research effort to the project supported by the Pioneer Award in the first three years of the award and at least 4 months (33%) research effort and at least 3 months (25%) in years four and five, respectively. Applicants with current research commitments of 6 person-months or more must provide a compelling explanation describing how their effort on existing grants will be adjusted to permit them to devote the required minimum effort to the Pioneer Award project.

Applicants considering research involving clinical trials are strongly advised to discuss their research ideas with the scientifically most relevant NIH Institutes or Centers (ICs) to ensure that such research would conform to the clinical trial research policies of those ICs. Funding of applications involving clinical trials is contingent upon conformance to the policies of the IC administering the award. For a list of IC staff contacts, see https://commonfund.nih.gov/highrisk/clinical.

Note: References are not required but if included, must fit within the page limit. Figures and illustrations may be included but must also fit within the page limit. Letters of collaboration will not be accepted. Information on collaborators may be included in the Essay and their names and affiliations should be listed in the PHS Assignment Request Form (see below).

Progress Report Publication List: Do not use.

Multiple PD/PI Leadership Plan: Do not use.

Consortium/Contractual Arrangements: Do not use.

Letters of Support: Do not use.

Resource Sharing Plan:

Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R& R ) Application Guide.

• For this FOA, the Resource Sharing Plans will be expected as Just in Time information if an award is being considered.

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 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.

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

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

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

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

Since all applications received in response to this FOA are assigned to a single Special Emphasis Panel and initially to the Office of the Director, do not suggest assignment to a specific study section or awarding component (NIH Institute/Center). Since letters of collaboration and biosketches of collaborators are not allowed, provide the names and institutional affiliations of collaborators. Also, if you wish to request that certain individuals not review your application, list their names, institutional affiliations, and the reasons why they should not serve as reviewers. NIH will consider this request but is not obligated to accept it.

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

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

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

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

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

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

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

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

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

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential 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 FOA for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by the Office of Strategic Coordination (OSC), NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Letters of Reference

Letters of reference are an important part of the Pioneer Award application. Applicants must arrange to have three (and only three) letters of reference submitted on their behalf. Applications that are missing letters of reference will be considered incomplete and will not be reviewed. Late letters will not be accepted. Letters must be submitted using the link below paper copies or emails will not be accepted.

Applicants are responsible for monitoring the submission of their letters in the eRA Commons grant folder to ensure that three letters have been submitted prior to the submission deadline.

To submit a letter of reference, the referee (the individual submitting the letter) will need the following information:

Funding Opportunity Number (FOA) for this announcement: RFA-RM-23-004;

The PD/PI's (Applicant's) eRA Commons User ID (Note: Referees do not need to be registered in eRA Commons and do not need their own Commons User Name only the PD/PI's (Applicant's) Commons User ID is required);

The applicant’s last name (Note: The name must match exactly the applicant’s name in eRA Commons);

The URL to the letter submission page: https://public.era.nih.gov/commonsplus/public/reference/submitReferenceLetter.era.

The letter of reference submission deadline: The deadline for receipt of letters is 5:00 p.m. (local time of the referee) on the Application Due Date of the competition, September 8, 2023.

Letters of reference are confidential. Applicants will not have access to the letters. Email confirmations of receipt will be sent to both the applicant and the referee. The confirmation sent to the applicant will include the referee’s name and the date and time the letter was submitted. The confirmation sent to the referee will include the referee and applicant’s names, a confirmation number, and the date and time the letter was submitted.

Note: Since email can be unreliable, it is the applicant’s responsibility to check the status of their letters of reference periodically in eRA Commons.

Applicants are strongly encouraged to send the following to their referees or to send their referees the following link to this information: (https://commonfund.nih.gov/pioneerawards/references).

Instructions for Referees:

Letters must be submitted to eRA Commons by 5:00 p.m. (local time of the referee), on the Application Due Date of the competition, September 8, 2023. Late letters will not be accepted and applications with fewer than three letters will not be reviewed. Letters must be submitted using the link above paper copies or emails will not be accepted.

IMPORTANT: The applicant’s name should be placed at the top of the letter. Although signatures are not required, the letter must include a signature block with the referee’s full name, title, institution, and contact information.

In two pages or less, describe the applicant’s qualities that support the applicant’s claim to scientific innovativeness and creativity. When possible, give specific examples that illustrate these qualities. Address the likelihood that the applicant will conduct groundbreaking research in the proposed research area.

Note: The letter submission page can be accessed without signing into eRA Commons, and referees do not need to be registered in eRA Commons. Referees must enter the following information when submitting letters:

REFEREE INFORMATION (the individual providing the letter of reference):

Referee’s First and Last Name

Referee’s Email Address

Referee’s Institution/Affiliation

Referee’s Department

APPLICANT INFORMATION (applicants must send this information to their referees):

Applicant’s eRA Commons User Name (User ID), (Important this must be the applicant s, not the referee s, eRA Commons User Name (User ID). The letter will not be linked to the appropriate application if the Applicant’s User Name is not entered here.)

Applicant’s Last Name. (Note: Must match exactly the applicant’s name in eRA Commons).

Funding Opportunity Number (FOA) of this announcement: RFA-RM-23-004

Confirmation Number (Required only when resubmitting a letter, that is, when submitting a revised or changed/corrected letter for the current FOA).

Email confirmations will be sent to both the applicant and the referee following submission of the letter. The email confirmation will include a Confirmation Number that will be required when submitting revised or changed/corrected letters. Print the confirmation email for your records.

Note: Referees who submitted letters for Pioneer Award applicants in prior years must submit new letters of reference this year. Previously submitted letters will not be retrieved.

Please see the detailed instructions on submitting letters of reference and Frequently Asked Questions on the Pioneer Award website. Send questions to [email protected].

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

For this FOA, only documents to inform of unforeseen events, such as natural disasters, that substantially affect the ability to execute the proposed research will be accepted.

Section V. Application Review Information

1. Criteria

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

For this particular announcement, note the following:

NIH Director's Pioneer Award (DP1) applications are meant to support individual scientists of exceptional creativity who propose pioneering -- and possibly transformative -- research that, if successful, will have a major impact on a broad area of relevance to the NIH. Pioneer Award applications do not require preliminary data, specific aims, or a detailed research plan. Accordingly, reviewers will emphasize the following:

1) The significance and innovation of the proposed project.

2) The investigator's evidence for past innovation and the ability to commit effort that is sufficient for the proposed project.

3) A change in research direction. A change in research direction is considered to be one that is a not logical extension or scale-up of ongoing efforts, but rather one that is motivated by a fundamental new insight that prompts a new line of research or a substantial departure from an existing line of research.

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

Overall Impact

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Scored Review Criteria

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

Significance

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

In addition, for applications involving clinical trials

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

Investigator(s)

Is the PD/PI well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)?

In addition, for applications involving clinical trials

With regard to the proposed leadership for the project, do the PD/PI and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

Innovation

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

In addition, for applications involving clinical trials

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

In addition, for applications involving clinical trials

Does the application adequately address the following, if applicable

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

Environment

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

In addition, for applications involving clinical trials

If proposed, 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 at the proposed site(s) or centers? Are the 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?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

Additional Review Criteria

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

Study Timeline

Specific to applications involving 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 or gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

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

Biohazards

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

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

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

Applications from Foreign Organizations

Not Applicable.

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).

Not Applicable

Authentication of Key Biological and/or Chemical Resources:

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

Budget and Period of Support

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

2. Review and Selection Process

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

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

• Using the review criteria stated above, those candidates identified as the most outstanding will be invited for interviews that will take place in April 2024. Interviews will be held either virtually or in person in Bethesda, MD. Interviews will be conducted by a panel of distinguished outside experts. The same review criteria will be used during the interviews as used in the earlier stage.

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

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the Council of Councils. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities, including:
  • The potential for the investigator to lead research, despite its inherent risks, that is groundbreaking and broadly impactful.
  • Unusually cross-cutting science.
  • Scientific balance in the portfolio of Pioneer Award-supported research.
  • Potential to invigorate exceptionally innovative and impactful science broadly across the nation.
  • Conformance to the clinical trial research policies of the administering Institute or Center.

3. Anticipated Announcement and Award Dates

PDs/PIs will be notified in April 2024 of the outcome of the first review phase - whether or not they have been selected for an interview; awardees will be notified by August 2024. Awards will begin in September 2024.

Section VI. Award Administration Information

1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

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

Recipients must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

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

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 Research Terms and Conditions
• 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.

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS will be required to complete an HHS Assurance of Compliance form (HHS 690) in which the recipient agrees, as a term and condition of receiving the grant, to administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, age, sex and disability, and agreeing to comply with federal conscience laws, where applicable. This includes ensuring that entities take meaningful steps to provide meaningful access to persons with limited English proficiency; and ensuring effective communication with persons with disabilities. Where applicable, Title XI and Section 1557 prohibit discrimination on the basis of sexual orientation, and gender identity. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html

HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.

• Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.htmlandhttps://www.lep.gov.

• For information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including providing program access, reasonable modifications, and to provide effective communication, see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html.

• HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.

• For guidance on administering programs in compliance with applicable federal religious nondiscrimination laws and applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 and 2 CFR Part 200.206 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

Not Applicable

3. Data Management and Sharing

Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.

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

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.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement. NIH FOAs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipients of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

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

Section VII. Agency Contacts

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

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

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

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-480-7075

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

Patricia Labosky, Ph.D.
Office of the Director (OD)
Email: [email protected]

Center for Scientific Review (CSR)
Email: [email protected]

Michael Morse
Office of the Director (OD)
Telephone: 301-435-5446
Email: [email protected]

Section VIII. Other Information

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

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75 and 2 CFR Part 200.