Enhancing Mechanistic Research on Precision Probiotic Therapies (R33 Clinical Trial Optional) (PAR-24-239)

Enhancing Mechanistic Research on Precision Probiotic Therapies (R33 Clinical Trial Optional) (PAR-24-239) is sponsored by National Institutes of Health (NIH), National Center for Complementary and Integrative Health (NCCIH), National Institute on Aging (NIA), National Institute of Dental and Craniofacial Research (NIDCR), National Cancer Institute (NCI). Enhancing Mechanistic Research on Precision Probiotic Therapies (R33 Clinical Trial Optional) (PAR-24-239) is sponsored by National Institutes of Health (NIH), National Center for Complementary and Integrative Health (NCCIH), National Institute on Aging (NIA), National Institute…

Expired PAR-24-239: Enhancing Mechanistic Research on Precision Probiotic Therapies (R33 Clinical Trial Optional) This notice has expired. Check the NIH Guide for active opportunities and notices. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating Organizations National Center for Complementary and Integrative Health ( NCCIH ) National Institute of Dental and Craniofacial Research ( NIDCR ) National Cancer Institute ( NCI ) All applications to this funding opportunity announcement should fall within the mission of the Institutes/Centers.

The following NIH Offices may co-fund applications assigned to those Institutes/Centers. Office of Dietary Supplements ( ODS ) Office of Research on Women's Health ( ORWH ) Office of Nutrition Research ( ONR ) Funding Opportunity Title Enhancing Mechanistic Research on Precision Probiotic Therapies (R33 Clinical Trial Optional) R33 Exploratory/Developmental Grants Phase II. October 31, 2024 - This PAR has been reissued as PAR-25-210 .

April 4, 2024 - Overview of Grant Application and Review Changes for Due Dates on or after January 25, 2025. See Notice NOT-OD-24-084 . August 31, 2022 - Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023.

See Notice NOT-OD-22-198 . August 5, 2022 - Implementation Details for the NIH Data Management and Sharing Policy. See Notice NOT-OD-22-189 .

Funding Opportunity Number (FON) Companion Funding Opportunity Phase 1 Exploratory/Developmental Grant/ Exploratory/Developmental Grants Phase II See Part 2, Section III. 3. Additional Information on Eligibility.

Assistance Listing Number(s) 93. 213, 93. 121, 93.

393, 93. 866, 93. 313 Funding Opportunity Purpose The purpose of this notice of funding opportunity (NOFO) is to support highly innovative mechanistic research to accelerate the development of effective precision probiotic interventions.

The NOFO aims to identify, understand, and develop strategies to address barriers in precision probiotic interventions' development to account for human heterogenicity resulting in inconsistent responses to probiotic treatments.

Specifically, this NOFO solicits R33 applications that will assess the causality of person-specific features or patterns affecting probiotic responses and identify subgroups of probiotic responders in order to enhance therapeutic outcomes.

This NOFO will support studies that assess whether host biological patterns (e.g., native microbiome, immune system, sex and/or gender, diet, age, genetic background, lifestyle, or health history) that are correlated with clinical probiotic effects can modulate responsiveness to probiotic interventions. Well-suited applications must offer rigorously designed mechanistic studies using relevant/innovative animal models or human subjects.

This NOFO is intended to support projects where potential host biological patterns that are correlated with probiotic usage or interventions have been identified, as demonstrated with supportive preliminary data, which require further mechanistic studies to test for causality. This NOFO will not support efficacy or effectiveness clinical trials.

Applicants pursuing early-stage research to identify host biological patterns that may affect probiotic health outcomes should consider the companion (R61/R33) PAR-24-238 . This Notice of Funding Opportunity (NOFO) requires a Plan for Enhancing Diverse Perspectives (PEDP).

Open Date (Earliest Submission Date) Letter of Intent Due Date(s) Renewal / Resubmission / Revision (as allowed) AIDS - New/Renewal/Resubmission/Revision, as allowed 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.

New Date October 31, 2024 per issuance of PAR-25-210 . (Original Expiration Date: June 03, 2027) Required Application Instructions It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide , except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts ).

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

Applications that do not comply with these instructions may be delayed or not accepted for review. Part 1. Overview Information 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 The purpose of this notice of funding opportunity (NOFO) is to support highly innovative mechanistic research to accelerate the development of effective precision probiotic interventions.

The NOFO aims to identify, understand, and develop strategies to address barriers in precision probiotic interventions to account for the heterogenicity in humans that causes inconsistent probiotic responses.

Specifically, this NOFO solicits R33 applications that will assess the causality of person-specific features or patterns affecting probiotic responses to identify subgroups of probiotic responders in order to enhance therapeutic outcomes.

This NOFO will support studies to assess whether host biological patterns (e.g., native microbiome, immune system, sex and/or gender, diet, age, genetic background, lifestyle, or health history) that are correlated with clinical probiotic effects can modulate probiotic responsiveness to probiotic interventions.

Well-suited applications must offer rigorously designed mechanistic studies using relevant/innovative animal models or human subjects. This NOFO is intended to support projects where potential host biological patterns that are correlated with probiotic usage or interventions have been identified, as demonstrated with supportive preliminary data, which require further mechanistic studies to test for causality.

This NOFO will not support efficacy or effectiveness clinical trials. Applicants pursuing early-stage research to identify host biological patterns that may affect probiotic health outcomes should consider the companion (R61/R33) PAR-24-238 . Naturally occurring microbial-based therapeutics include probiotics—living microorganisms such as bacteria and yeast that are reported to have beneficial health effects.

The broad range of reported effects may include alleviation of gastrointestinal symptoms, “strengthening” of the immune system, protection against infectious diseases, improvements in metabolic and mental health, and promotion of early development and general well-being.

A major challenge in probiotic research is variation in responses reported for the same intervention, both between trials and among individuals, resulting in significant variability in clinical effects and reported trial outcomes. Such variability may stem from heterogeneity in humans in terms of diet, age, genetic background, sex and/or gender, health history, lifestyle, and native gut microbial composition.

These factors may hamper effective evaluation of clinical efficacy of probiotics and their integration as well as implementation into treatment regimens. One potential solution to tackle this major challenge is to develop a precision probiotics intervention paradigm that has the capability to predict interindividual variations and tailor probiotic strains to individual-specific features.

However, this approach requires fundamental understanding of real-life variability of probiotic responses at the individual level as well as development of innovative research tools and strategies to address the complexity of person-specific characteristics.

In April 2022, the National Center for Complementary and Integrative Health (NCCIH) and the Office of Dietary Supplements (ODS) within the National Institutes of Health (NIH), in collaboration with other NIH Institutes, Centers, and Offices as well as the U.S. Department of Agriculture, convened a 2-day workshop, “Precision Probiotic Therapies—Challenges and Opportunities,” to better understand the status and potential future directions of precision probiotic research and to discuss the associated research questions and methodological challenges.

The video recordings (Day 1 and Day 2) and executive summary can be found here: https://www. nccih. nih.

gov/news/events/precision-probiotic-therapies-challenges-and-opportunities . During the workshop, several major view points emerged.

First, it was recognized that the study designs of most probiotic clinical trials did not fully capture the complex patterns of the gut microbiome, host genetic variability, dietary differences, and environmental exposures of both the microbes and hosts, although all of these are critical considerations for probiotic responsiveness within individuals.

Second, although many cross-sectional observational epidemiologic studies have examined these complex patterns, few of their insights have been effectively translated to robust mechanistic studies to test for causality or to rigorous mechanistic clinical trials.

Third, understanding the intricate relationships among multiple complex systems, including the microbiome, host, and environment, requires advanced computational and artificial intelligence (AI) approaches.

Research Objectives and Requirements The proposed projects must be focused on testing the causality of potential host biological patterns that have been identified as strongly correlated with probiotic usage or interventions, as demonstrated with supportive preliminary data. The choice of the potential patterns must be supported by a cogent biological rationale.

Examples of activities that are responsive for this NOFO include but are not limited to: Determining causal effects of the host biological patterns on modifying probiotic responses in clinically relevant preclinical models or human populations. Elucidating the mechanisms through which the host biological patterns modify probiotic responses.

Optimizing and verifying the ability of developed computational and AI tools to identify host biological factors in clinically relevant preclinical models or human populations.

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

The following types of clinical trials are considered to be in scope of this NOFO: Mechanistic trials , defined as studies designed to understand a biological or behavioral process, the pathophysiology of a disease, or the mechanism of action of an intervention (i.e., how an intervention works, but not if it works or is safe).

Clinical trials designed primarily to determine the clinical feasibility, efficacy, and effectiveness of a probiotic intervention will not be supported under this NOFO . Preliminary/Supporting Data Requirements Applications should be based on a clear scientific premise and compelling rationales should be presented for the proposed study and selection of probiotic usage or intervention.

The choice of the potential patterns must be supported by a cogent biological rationale including preliminary data. Regulatory Requirements to Consider The U.S. Food and Drug Administration (FDA) establishes and enforces the regulatory requirements for clinical research on probiotics when used as drugs. Because NCCIH is a Federal agency, any research supported with NCCIH funding must adhere to relevant FDA regulations.

Prior to submitting an application, investigators must contact the FDA to determine whether an Investigational New Drug (IND) application is necessary for the proposed clinical research. For trials using an FDA regulated product and requiring an IND application, the applicant must either hold or be able to reference an open IND for the trial, or the applicant must obtain an IND with no clinical hold prior to any award.

If the FDA has granted a waiver for the trial proposed in the application, the applicant can provide this letter as part of the Regulatory Communication Plan. Guidance on the IND evaluation process can be found on the NCCIH Natural Products Clinical Trials Resource web page: https://www. nccih.

nih. gov/grants/natural-products-clinical-trials-resource . Applications Not Responsive to This NOFO The following types of applications will be considered nonresponsive and will be withdrawn prior to review: Clinical trials designed primarily to determine the clinical feasibility, efficacy, or effectiveness of a probiotic intervention.

Applicants are encouraged to consult with the NIH scientific contacts listed in the NOFO before they begin developing their applications (see Section VII, Agency Contacts). This early contact will provide an opportunity to clarify whether the research topic is a fit with the NOFO’s purpose and priorities.

NIH Institute and Center Interests and Guidance The National Center for Complementary and Integrative Health (NCCIH) NCCIH is interested in projects focused on accelerating precision probiotic interventions for specific health conditions within the mission of NCCIH.

Topics of special interest include but are not limited to pain, stress, anxiety, sleep and other symptoms, health promotion and restoration, resilience, metabolic and mental disorders, and gastrointestinal dysfunction. Investigators are strongly encouraged to discuss their research plans with the NCCIH scientific/research contact prior to submitting their applications.

The National Institute of Dental and Cranial Facial Research (NIDCR) NIDCR is interested in projects focused on accelerating precision probiotic interventions for specific health conditions within the mission of NIDCR. Topics of special interest include but are not limited to prevention and treatment of caries, periodontal disease, and oral fungal disease and promotion or restoration of oral health.

Investigators are strongly encouraged to discuss their research plans with the NIDCR scientific/research contact prior to submitting their applications. NIDCR will accept Basic Experimental Studies involving Humans (BESH)clinical trial but not mechanistic clinical trial applications through this mechanism.

The NIH Office of Dietary Supplements (ODS) The NIH Office of Dietary Supplements (ODS) is interested in co-funding projects focused on probiotics for health conditions within the mission of ODS. Topics of special interest include, but are not limited to promoting mucosal immunity, preventing, and ameliorating symptoms associated with digestive diseases, and optimizing health and resilience in diverse populations across the lifespan.

The ODS will not support projects focused on diagnosis and/or treatment of disease. The ODS does not award grants; therefore, applications must be relevant to the objectives of at least one of the participating NIH Institutes and Centers (IC) listed in this announcement. Please contact the relevant IC Scientific/Research Contact(s) listed for questions regarding IC research priorities and funding.

The Office of Research on Women’s Health (ORWH) The National Institute on Aging (NIA) The Division of Aging Biology (DAB) in NIA is interested in pre-clinical and clinical research projects focused on understanding the host factors and mechanisms affecting age-related changes in probiotic responses (e.g. immune-senescence and other innate/adaptive immune responses in next-gen probiotic research).

Identification of bacterial strains and their metabolites that can be used as probiotics/postbiotics to improve health outcomes in older adults. Mechanistic research on the effects of probiotics applied to understudied anatomical niches (e.g. oral mucosa and periodontal disease; cervicovaginal and bacterial vaginosis; and skin probiotics that improve dermatosis associated with aging).

Interrogating mechanistic insights of the probiotic effects on health outcomes across the lifespan. Characterization of factors affecting the efficacy of probiotic intervention (e.g. microbial composition, quorum sensing, role of keystone species, and long-term effects of probiotic treatment).

Developing computational analysis and AI/ML algorithms to build predictive models to identify patient subpopulations and critical factors in response to probiotic treatment (e.g. in frailty and older individuals).

The National Cancer Institute (NCI) The National Cancer Institute (NCI) supports research on the microbiome's role in cancer, particularly the effects of pre/probiotics on cancer prevention, interception, progression, and treatment. This includes studies on how probiotics interact with host cells and other microbes, influencing cellular functions and tumor development.

The Division of Cancer Prevention ( DCP) is interested in investigating the potential benefits of probiotics in cancer prevention. Specifically, DCP is interested in understanding the interaction of probiotics with cancer-associated pathogens, alterations in metabolite production, and reduction of pro-carcinogens. Applications of biomarkers in measuring aforesaid counteractive interactions of probiotics are highly encouraged.

Additionally, DCP fosters research on how probiotics impact biofilm composition, functional changes, and their effectiveness in preventing cancer.

The Division of Cancer Biology is interested in basic and mechanistic studies on how probiotics affect tumor formation at the molecular level and the interactions between probiotics, host cells, and the resident microbiome, focusing on how these interactions influence cellular signaling, physiology, and metabolism.

The Division of Cancer Control and Population Sciences seeks to advance research to demonstrate whether genomic background in different racial and ethnic populations makes them responsive to pre/probiotic exposure and their effects on improving cancer outcomes. See Section VIII. Other Information for award authorities and regulations.

Plan for Enhancing Diverse Perspectives (PEDP) The NIH recognizes that teams comprised of investigators with diverse perspectives working together and capitalizing on innovative ideas and distinct viewpoints outperform homogeneous teams.

There are many benefits that flow from a scientific workforce rich with diverse perspectives, including: fostering scientific innovation, enhancing global competitiveness, contributing to robust learning environments, improving the quality of the research, advancing the likelihood that underserved populations participate in, and benefit from research, and enhancing public trust.

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

This NOFO requires a Plan for Enhancing Diverse Perspectives (PEDP), which will be assessed as part of the scientific and technical peer review evaluation. Assessment of applications containing a PEDP are based on the scientific and technical merit of the proposed project.

Consistent with federal law, the race, ethnicity, or sex of a researcher, award participant, or trainee will not be considered during the application review process or when making funding decisions. Applications that fail to include a PEDP will be considered incomplete and will be administratively withdrawn before review. The PEDP will be submitted as Other Project Information as an attachment (see Section IV).

Applicants are strongly encouraged to read the NOFO instructions carefully and view the available PEDP guidance materials . Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs. Section II.

Award Information Grant: A financial assistance mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity. Application Types Allowed The OER Glossary and the How to Apply - Application Guide provide details on these application types. Only those application types listed here are allowed for this NOFO.

Optional: Accepting applications that either propose or do not propose clinical trial(s). Need help determining whether you are doing a clinical trial? Funds Available and Anticipated Number of Awards The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

The application budget must not exceed $350,000 in direct costs per year. The scope of the project should determine the project period. The total project period request may not exceed 4 years.

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 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 (Other than Small Businesses) City or Township Governments Special District Governments Indian/Native American Tribal Governments (Federally Recognized) Indian/Native American Tribal Governments (Other than Federally Recognized) Eligible Agencies of the Federal Government U.S. Territory or Possession 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 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 must complete and maintain the following registrations as described in the How to Apply - Application Guide to be eligible to apply for or receive an award.

All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference NIH Grants Policy Statement Section 2.

3. 9. 2 Electronically Submitted Applications for additional information System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually .

The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code. NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.

Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM. gov registration process. The same UEI must be used for all registrations, as well as on the grant application.

eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants. gov registrations; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.

Grants. gov – Applicants must have an active SAM registration in order to complete the Grants. gov registration.

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

Obtaining an eRA Commons account can take up to 2 weeks. Eligible Individuals (Program Director/Principal Investigator) Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support.

Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities , NOT-OD-22-019 .

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the How to Apply - Application Guide . This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement NIH Grants Policy Statement Section 1. 2 Definition of Terms.

3. Additional Information on Eligibility Applicant organizations may submit more than one application, provided that each application is scientifically distinct. The NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 2.

3. 7. 4 Submission of Resubmission Application .

This means that the NIH will not accept: A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application. A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.

An application that has substantial overlap with another application pending appeal of initial peer review (see NIH Grants Policy Statement 2. 3. 9.

4 Similar, Essentially Identical, or Identical Applications ). Section IV. Application and Submission Information 1.

Requesting an Application Package The application forms package specific to this opportunity must be accessed through ASSIST, Grants. gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.

gov Workspace are available in Part 1 of this NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution. 2.

Content and Form of Application Submission It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the How to Apply - Application Guide is required and strictly enforced.

Applications that are out of compliance with these instructions may be delayed or not accepted for review. 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 Institute and Center (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: National Center for Complementary and Integrative Health (NCCIH) All page limitations described in the How to Apply – Application Guide and the Table of Page Limits must be followed.

Instructions for Application Submission 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 How to Apply - Application Guide must be followed. SF424(R&R) Project/Performance Site Locations All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Other Project Information All instructions in the How to Apply - Application Guide must be followed. Plan for Enhancing Diverse Perspectives (PEDP) In an "Other Attachment" entitled "Plan for Enhancing Diverse Perspectives," all applicants must include a summary of actionable strategies to advance the scientific and technical merit of the proposed project through expanded inclusivity.

Applicants should align their proposed strategies for PEDP with the research strategy section, providing a holistic and integrated view of how enhancing diverse perspectives and inclusivity are buoyed throughout the application. The PEDP will vary depending on the scientific aims, expertise required, the environment and performance site(s), as well as how the project aims are structured.

The PEDP may be no more than 2 pages in length and should include: Actionable strategies using defined approaches for the inclusion of diverse perspectives in the project; Description of how the PEDP will advance the scientific and technical merit of the proposed project; Anticipated timeline of proposed PEDP activities; Evaluation methods for assessing the progress and success of PEDP activities.

Examples of items that advance inclusivity in research and may be appropriate for a PEDP can include, but are not limited to: Partnerships with different types of institutions and organizations (e.g., research-intensive; undergraduate-focused; HBCUs; emerging research institutions; community-based organizations).

Project frameworks that enable communities and researchers to work collaboratively as equal partners in all phases of the research process. Outreach and planned engagement activities to enhance recruitment of individuals from diverse groups as human subjects in clinical trials, including those from underrepresented backgrounds. Description of planned partnerships that may enhance geographic and regional diversity.

Outreach and recruiting activities intended to diversify the pool of applicants for research training programs, such as outreach to prospective applicants from groups underrepresented in the biomedical sciences, for example, individuals from underrepresented racial and ethnic groups, those with disabilities, those from disadvantaged backgrounds, and women.

Plans to utilize the project infrastructure (i.e., research and structure) to enhance the research environment and support career-advancing opportunities for junior, early- and mid-career researchers. Transdisciplinary research projects and collaborations among researchers from fields beyond the biological sciences, such as physics, engineering, mathematics, computational biology, computer and data sciences, as well as bioethics.

Examples of items that are not appropriate in a PEDP include, but are not limited to: Selection or hiring of personnel for a research team based on their race, ethnicity, or sex. A training or mentorship program limited to certain researchers based on their race, ethnicity, or sex. For further information on the Plan for Enhancing Diverse Perspectives (PEDP), please see PEDP guidance material .

SF424(R&R) Senior/Key Person Profile All instructions in the How to Apply - Application Guide must be followed. All instructions in the How to Apply - Application Guide must be followed. PEDP implementation costs: Applicants may include allowable costs associated with PEDP implementation (as outlined in the Grants Policy Statement section 7): https://grants.

nih. gov/grants/policy/nihgps/html5/section_7/7. 1_general.

htm . All instructions in the How to Apply - Application Guide must be followed. PHS 398 Cover Page Supplement All instructions in the How to Apply - Application Guide must be followed.

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions: The Research Strategy section must provide a clear outline of the preliminary data supporting the biological rationale for studying the host biological patterns.

This section should also describe clear evidence of a meaningful and detectable health effect of the probiotic intervention from preclinical or clinical studies. Resource Sharing Plan : Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply - Application Guide .

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions: All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan.

All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan. Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply - Application Guide .

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

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

” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and