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.

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

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

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

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

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



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

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Research Objectives and Purpose:

The development and implementation of clinical interventions is a complex, iterative, and time-consuming process that takes years before discoveries in biomedical research result in health benefits for patients and communities. The National Center for Advancing Translational Sciences (NCATS) has the unique charge of examining the translational research ecosystem at a systems level to determine where common pitfalls exist in the translational process and developing innovative solutions that will ultimately benefit research across a range of diseases and conditions. This disease-agnostic approach to enhancing the efficiency and effectiveness of all translational research is known as translational science, which focuses on building the evidence base for effective scientific and operational approaches in translational research. NCATS conducts and supports research in the science of translation to discover the scientific, mechanistic, and operational principles of the intervention development and dissemination processes, thereby providing the scientific foundation for improvements in translational efficiency that will accelerate the realization of interventions that improve human health.

The purpose of the High Impact Specialized Innovation Programs (SIPs) is to support unique activities, resources, capabilities and/or expertise at awarded CTSA UM1 (PAR-21-293) hubs to help advance one or more of the NCATS CTSA Program goals. The SIPs initiative is envisioned as part of the current innovation ecosystem to support the generation of a research resource and/or foster discovery-based or hypothesis-generating science that can have a significant impact in Clinical and Translational Science (CTS). Specifically, this FOA seeks to support novel approaches in areas that address specific knowledge gaps, scientific opportunities, new technologies/platforms, data generation and/or analysis, or novel research methods that will advance clinical and translational science (CTS) and research (CTR) at CTSA UM1 hubs . Resources, activities, and expertise supported through the RC2 mechanism are expected to be available to enhance the development and demonstration activities or projects within a CTSA hub. These include utilization of resources, expertise, tools and platforms for pilot projects, research projects and other CTS activities within hubs. Examples of SIPs areas in clinical and translational science include but are not limited to digital health, decentralized clinical trials, pragmatic trials, artificial intelligence/machine learning algorithms, point-of-care clinical decision support systems, data science and statistical methods, real-world data and real-world evidence, innovative clinical trial designs, genetics and genomics. In addition, novel strategies and/or approaches for dissemination and implementation, rural health and health disparities, clinical informatics, biostatistics, community outreach and engagement, regulatory science, telehealth, and other areas of need for specialized programs.

Scope and Specific Requirements:

Through the RC2 mechanism, SIPs should address one or more of the following objectives:

• Groundbreaking, innovative, high impact and cross-cutting research, resources and/or activities that address one or more of the CTSA Program Goals and have the highest potential to improve and accelerate biomedical research at UM1 hubs.
• Programs in Clinical and Translational Science that could fundamentally enhance the research enterprise and that require the participation, interaction, coordination, and integration of activities within a CTSA UM1 hub .
• Creation of unique resources and/or development of transformative technologies and/or platforms that can benefit a wide range of projects and/or activities related to CTS at CTSA UM1 hubs.
• High-impact discovery-based projects or hypothesis-generating science.

While preliminary data is not required, it is important to provide strong rationale and justification for the goals of the application. Applications for SIP must include: a UM1 and RC2 Coordination and Integration Plan, a Program Milestones table and a Program Evaluation and Sustainability Plan as separate attachments (see Section IV. Application and Submission Information SF424(R&R) Other Project Information)

Potential applicants are highly encouraged to contact NCATS Scientific/Research Contacts listed in this NOFO to discuss the scope of the project, required materials, responsiveness, and clinical trials status designation prior to submission of an application.

Collaborations with other components of the CTSA UM1 hub and/or with institutions listed as partners and/or collaborators are encouraged. Also, collaborations with other CTSA UM1 and UL1 hubs and with non-CTSA organizations are encouraged. The requested project period may be up to 5 years.

Applications Not Responsive to this NOFO:

The following types of studies are not responsive to this NOFO. Applications proposing such studies will be considered non-responsive and will not be reviewed or considered for funding.

Applications that propose:

• Feasibility/Pilot projects intended to: (1) explore possible innovative new leads or new directions for established investigators; (2) stimulate investigators from other areas to lend their expertise in research in CTS; and (3) provide initial support to establish proof of concept. Pilot projects are supported through the CTS Pilot Module within the UM1.Traditional investigator-initiated, hypothesis-driven and highly focused studies (best supported through CTSA UM1 CTS Research Projects) or specific projects requiring multiple collaborators (best supported through CTSA Collaborative Innovation Awards).
• Dissemination and implementation of novel resources/activities/projects at other hubs.
• Ancillary studies or research that is a logical extension of ongoing work.
• Core (or related) services to supplement the budgets of existing UM1 efforts.
• Applications with Studies with a major emphasis outside of the NCATS Strategic Plan and the goals of the CTSA Program.

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 NOFO.

Section III. Eligibility Information

1. Eligible Applicants

All applicant organizations and/or active award recipients for PAR-21-293 Clinical and Translational Science Award (UM1 Clinical Trial Optional) are eligible to apply under this NOFO.

Only the primary UM1 CTSA program hub organization is eligible to apply (not partner or collaborator institutions).

RC2 companion optional applications may be submitted under the following scenarios:

• concurrently with the UM1
• while the UM1 application is under review consideration
• after the UM1 application is funded
• while the UM1 is under consideration for funding

RC2 applications will only be awarded if there is an awarded UM1 application from the RC2 applicant organization.

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 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. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information.

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

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

The single PD/PI (or contact PD/PI for a multiple PI application) must be employed by and/or a recipient of funding and/or have an academic appointment from a CTSA Program UM1 hub prime institution as defined above in Eligible Organizations. Investigators from UM1 hub partners or collaborators who wish to co-lead a SIP, can co-direct in partnership with a contact PD/PI who is employed by and/or a recipient of funding and/or has an academic appointment at a CTSA Program UM1 prime hub institution using the multiple PD/PI option.

See required Letters of Support. (see Section IV. Application and Submission Information, 2. Content and Form of Application Submission, PHS 398 Research Plan.)

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

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

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

Other information on eligibility and number of applications:

• An active (not in an extension period) UM1 hub institution can submit up to two RC2 applications for SIPs per cycle as the primary institution.
• A CTSA UM1 hub may have up to two RC2 SIPs awards as the primary recipient at a given time.
• No more than two RC2 applications may be submitted by a UM1 hub as a primary per application due date and no more than two RC2 applications may be awarded to an active (not in an extension period) CTSA UM1 hub as a primary recipient, at a given time.
• A UM1 hub that is in an extension period is not allowed to submit an RC2 application as the primary institution unless a pending UM1 application has been submitted or is under review or funding consideration. Resubmission of a RC2 application without the required UM1 application is only allowed if the companion UM1 application is awarded.
• For the purpose of this NOFO, an RC2 in an extension period counts towards the maximum of two RC2s that may be awarded to an active UM1 hub as a primary, at a given time.

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

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

Letter of Intent

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

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

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

The letter of intent should be sent to:

NCATS Letters of Intent
Telephone: 301-827-9549
Email: ncatslettersofintent@mail.nih.gov

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.

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. The additional instructions apply:

The application must include the following 3 attachments. Please use the filenames suggested below. The filename provided for each document added to the section Other Attachments will be the name used for the bookmark in the electronic application in eRA Commons.

Attachment #1 (Up to 2 pages in length) called "UM1 and RC2 Coordination and Integration Plan" must be uploaded under Other Attachments. The UM1 and RC2 Coordination and Integration Plan must provide a specific plan describing the collaboration, support, equipment, coordination, synergy and integration between the UM1 hub and any of its elements and modules and other UM1 companion NOFOs and the proposed RC2 Program. Applications that do not include UM1 and RC2 Coordination and Integration Plan will not be reviewed.

Attachment #2 (Up to 1 page in length) called Program Milestones must be uploaded under Other Attachments. The Program Milestones must include a table with key milestones to be achieved throughout the RC2 program period. Both short-term/interim (monthly or quarterly) and long-term (yearly) milestones should be clearly outlined in word table format. Each milestone should be constructed to succinctly include: (a) the goals and timeline for completion, (b) the criteria for success, including quantitative and/or qualitative metrics that will be used to assess success. Final program milestones for each RC2 may be changed based on suggestions from reviewers or NIH program staff and will be negotiated with program staff prior to funding the application. The final agreed upon and approved milestones will be specified in the Notice of Award (NoA). Applications that do not include Program Milestones will not be reviewed.

Attachment #3 (Up to 2 pages in length) called Program Evaluation and Sustainability Plan must be uploaded under Other Attachments. The Program Evaluation and Sustainability Plan must provide a clear plan to evaluate the success and impact of the proposed program based on the pre-determined milestones and SIP utilization at participating institutions. List key metrics and measures of success to be utilized to evaluate the overall impact of the program and how success will be measured in an objective and tangible manner on a regular basis. In addition, outline plans for sustainability of the SIP beyond the RC2 grant period (once grant funding ends) and how do applicants envision their Specialized Innovation Program to continue through partnerships, collaborations, support, etc. after the RC2 ends. Applications that do not include the Program Evaluation and Sustainability Plan will not be reviewed.

Applications that do not include one or more of these attachments will be considered incomplete and will not be reviewed.

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

R&R Budget

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

• Key Personnel salaries derived from the grant will depend on the effort provided and institutional salary as well as existing NIH policies. It is recommended that the contact PD/PI devote at least one to two person months of his/her efforts to the project. No overlap of time or effort between this award and separately funded projects is permitted.
• Consultants and any associated costs (consultant fees, per diem, travel) may be included when their services are required and justified within the award.
• RC2 budget should include travel expenses for appropriate personnel (up to three people) to attend a yearly in-person meeting to present RC2 progress, lessons learned and impact. If additional staff are identified to attend, additional justification is required as part of the Budget Justification.

R&R Subaward 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:

Briefly state the specific aims of the project indicating how the hub will develop and/or demonstrate a highly innovative and specialized clinical and translational science program that addresses one or more of the CTSA Program goals.

Research Strategy:

This opportunity may support high impact unique activities, resources, expertise or capabilities that may lay the foundation for new fields of investigation; accelerate breakthroughs; stimulate early and applied research on cutting-edge technologies/platforms; foster new approaches to improve the interactions among multi- and interdisciplinary research teams to help advance the clinical and translational research enterprise in a way that could stimulate future growth and investments and advance public health and health care delivery. This activity code may support either a specific question related to the advancement of clinical and translational science or propose the creation of a unique infrastructure/resource designed to accelerate clinical and translational science at UM1 hubs. A description of the specialized team(s) that is/are part of the proposed SIP as well as their experience is expected.

In addition, applicants must concisely describe the significance of the problem/roadblock or gap being addressed and their relevance to the goals of the CTSA Program. Applicant should specifically address why the proposed SIP is best suited to respond to UM1 hub needs, as described below. The application must provide an explanation of how the proposed program will empower research, generate new hypotheses, or contribute a significant resource, platform, tool, data or technology that is currently lacking and could help advance the development of new approaches, solutions, therapeutics, devices and/or diagnostics to improve human health. Programs are expected to demonstrate the following:

• The work cannot be reasonably expected to be carried out successfully without support provided by this NOFO.
• Specific outcomes of the proposed program promote and advance the NCATS Strategic Plan and, specifically addresses one or more of the CTSA Program Goals.
• Funding will accelerate the development of innovative resources, approaches, tools, solutions, therapies, diagnostics, devices and/or applications and help overcome roadblocks in clinical and translational science.
• The proposed project is something that will help catalyze clinical and translational science locally at UM1 hubs and no other existing project/resource is likely or able to do.
• The project or generated results and resources can be expected to become integrated into the broader clinical and translational science community locally, regionally and/or nationally.
• There is a plan for evaluation and sustainability of applicable research efforts and resources beyond the RC2 funding.

Critical Need/Gap Area Addressed:

Describe how is the proposed project is unique and how it is expected to solve a real gap or overcome a key roadblock in clinical and translational science. The capability must directly address one or more of the current CTSA Program Goals. It is expected that the capability or resource will be in an area of need where there are currently no clearly available solutions/tools/resources or where the existing solutions are suboptimal. The identification of a critical gap(s) or area(s) of need should be based on evidence and supported by most up-to-date science in the field.

Impact:

In addition, applicants must justify how the local innovations developed through their proposed RC2 could impact health and medicine by meaningfully advancing clinical and translational science within their UM1 hub and, if successful, how their proposed RC2 could be more broadly disseminated throughout the CTSA consortium. Also how does the proposed RC2 changes the landscape of what’s currently being done in the specific field and how it can help advance clinical and translational science and make a difference in medicine and health.

Letters of Support: Applicants must provide a letter from the UM1 hub Principal Investigator describing how the proposed SIP is expected to be integrated within the CTSA hub as well as the resources, expertise that the CTSA hub will provide. In addition, any resources or expertise outside of the team of investigators, including institutional support through core facilities or resources, must be evidenced by appropriate letters of support from the relevant individual(s). Applications that do not include a letter from the UM1 hub Principal Investigator will not be reviewed.

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.

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:

The CTSA Program encourages sharing of resources with broad availability of policies, practices, materials, and tools to facilitate collaboration, reuse, and replication. To provide further clarification of the NIH policy on disseminating unique research resources, NIH published Principles and Guidelines for Recipients of NIH Research Grants and Contracts on Obtaining and Disseminating Biomedical Research Resources (64 FR 72090, December 23, 1999; http://- grants.nih.gov/grants/intell-property_64FR72090.pdf). This document will assist recipients in determining reasonable terms and conditions for disseminating and acquiring research tools.

For the purposes of this NOFO the research tool may include, but is not limited to, software, algorithms, and code. This may be for extraction and use of data for research from clinical systems; implementation of new efficient workflows for research studies; innovative networking to connect scientists, patient communities, industry, resources, data, and ideas; novel analytic and analysis programs; and educational tools. The Resource Sharing Plan must include the following:

• The software should be freely available to biomedical researchers, health care systems, and research institutions or organizations.
• The terms should also permit the dissemination and commercialization of enhanced or customized versions of the software, or incorporation of the software or components of it into other software packages.
• The terms of software availability should include the ability of individuals outside the applicant institution and its collaborating organizations to modify the source code and to share modifications with other colleagues.
• Genomic Data Sharing Plan: Awardees are strongly encouraged to deposit large-scale, human genetic data in the database for Genotype and Phenotype dbGaP (https://www.ncbi.nlm.nih.gov/gap). For other data and biospecimens from human genetic or non-genetic studies, awardees are encouraged to use the NICHD Data and Specimen Hub DASH (https://dash.nichd.nih.gov/) or other equivalent broad-sharing data and/or biospecimen repositories.
• The CTSA Program encourages sharing of resources with broad availability of policies, practices, materials, and tools to facilitate collaboration, reuse, and replication. To provide further clarification of the NIH policy on disseminating unique research resources, NIH published Principles and Guidelines for Recipients of NIH Research Grants and Contracts on Obtaining and Disseminating Biomedical Research Resources (64 FR 72090, December 23, 1999; http://- grants.nih.gov/grants/intell-property_64FR72090.pdf). This document will assist recipients in determining reasonable terms and conditions for disseminating and acquiring research tools.

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.

Prior to funding, NIH Program Staff may negotiate modifications to the Resource Sharing Plan with the applicant.

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

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.

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 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.

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

Pre-award costs are allowable only as described in the NIH Grants Policy Statement Section 7.9.1 Selected Items of Cost.

Applications must be submitted electronically following the instructions described in the 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 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 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 NCATS, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

In order to expedite review, applicants are requested to notify the NCATS Referral Office by email at ncatsreferral@mail.nih.gov when the application has been submitted. Please include the NOFO number and title, PD/PI name, and title of the application.

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.

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 and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

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

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?

Specific to this NOFO:

If successful, to what degree will the results of this program help advance clinical and translational science and expedite the development of new science, resources, approaches, therapeutics, devices, software applications and/or other tools/platforms at UM1 hubs?

In what way does this application fill a gap or address a problem/roadblock or area of need that will help advance clinical and translational science at the CTSA hub?

If successful, what is the impact that the RC2 is expected to have in clinical and translational science and medicine?

If the application proposes the generation of a research resource or tool, to what degree will successful completion of this project generate a research resource or tool that will be highly useful and/or transformative for the broader clinical and translational science community? If so, how will it be sustained beyond the funding period?

How adequate is the justification that the project or generated results and resources could be generalizable to the broader CTSA consortium community?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance, and organizational structure appropriate for the project?

In addition, for applications involving clinical trials

With regard to the proposed leadership for the project, do the PD/PI(s) 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?

Specific to this NOFO:

To what extent is the SIP expertise adequate to successfully advance the program goals?

To what degree are the team member's areas of expertise clearly appropriate for accomplishing the proposed research plan?

To what extent are the team's experience and effort complementary and sufficient to accomplish the goals of the program?

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?

Specific to this NOFO:

To what extent do the proposed innovations help to meaningfully advance clinical and translational science?

Is the proposed program uniquely positioned to address one or more of the CTSA program goals?

How does the proposed RC2 changes the landscape in clinical and translational science and medicine?

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?

Specific to this NOFO:

To what extent does the rationale for the approach support the proposed SIP being well suited to respond to UM1 hub needs?

To what extent does the project propose unique approaches to solve a real gap or overcome a key roadblock in clinical and translational science?

To what degree are the program milestones well-defined and realistic to complete the project within the time requested?

To what extent is the program evaluation and sustainability plan adequate to evaluate the program's impact and its sustainability beyond the RC2 funding?

To what degree does the UM1 and RC2 Coordination and Integration Plan provide evidence of a clear integration of the SIP activities and teams with the UM1 hub activities, expertise, resources and equipment?

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?

Specific to this NOFO:

To what extent are the institution, and, when applicable, partners and/or collaborators recognized and possess an excellent track record of developing research programs/activities in the proposed specialized area?

Describe the extent to which there are sufficient and appropriate resources available at the hub (including specialized equipment, expertise and capabilities) to make the proposed approach successful?

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/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

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

Renewals

Not applicable.

Revisions

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).

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.

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 NCATS, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

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

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

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications. Following initial peer review, recommended applications will receive a second level of review by the NCATS Advisory Council. 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.

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.

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 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 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 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

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

4. Reporting

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

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 Part 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 $25,000. 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 (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 2 CFR Part 200 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: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-480-7075

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

Pablo Cure, MD., MPH.
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-827-2014
Email: RC2NOFO@nih.gov

Victor Henriquez, Ph.D.
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-435-0813
Email: RC2NOFO@nih.gov

Nichol Cleveland, M.Ed.
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-451-6331
Email: RC2NOFO@nih.gov

Section VIII. Other Information

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

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