NCCIH NOFO for Natural Products for Chronic Pain Management (Forecast)

NCCIH NOFO for Natural Products for Chronic Pain Management (Forecast) is sponsored by National Center for Complementary and Integrative Health (NCCIH), National Institutes of Health (NIH). This opportunity supports mission-aligned projects and measurable outcomes.

PAR-25-271: NCCIH Natural Product Mid Phase Clinical Trial (R01 Clinical Trial Required) This funding opportunity was updated to align with agency priorities. Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. 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 ) Funding Opportunity Title NCCIH Natural Product Mid Phase Clinical Trial (R01 Clinical Trial Required) R01 Research Project Grant January 28, 2026 - NIH Removing AIDS Application Due Dates from NOFOs.

See Notice NOT-OD-26-029 September 8, 2025 - Notice of Correction to Section IV Application Form Instructions for PAR-25-271 "NCCIH Natural Product Mid Phase Clinical Trial (R01 Clinical Trial Required)". See Notice NOT-AT-25-010 . March 31, 2025 - This funding opportunity was updated to align with agency priorities.

Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. 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 Cooperative Agreement/Exploratory/Developmental Cooperative Agreement Phase II Resource-Related Research Project (Cooperative Agreements) Phase 1 Exploratory/Developmental Grant/ Exploratory/Developmental Grants Phase II Exploratory/Developmental Grants Phase II See Section III. 3.

Additional Information on Eligibility. Assistance Listing Number(s) Funding Opportunity Purpose This Notice of Funding Opportunity (NOFO) encourages applications for investigator-initiated mid-phase clinical trials of natural products (i.e., botanicals, dietary supplements, and probiotics), which have a strong scientific premise to justify further clinical testing.

For this NOFO, natural products include promising nutritional regimens that standardize the amount of a specific naturally occurring nutritional compound (e.g., omega-3 fatty acids, anthocyanidins, or polyphenols) and have compelling preliminary evidence.

All applications submitted under this NOFO must be supported by sufficient preliminary data demonstrating bioavailability (if applicable) and documentation that the natural product produces a reproducible and measurable impact on target engagement (i.e., measure of the mechanism of action).

Only in cases when it is not possible/practical to measure target engagement in the patient population of interest or when there is a fundamental understanding of the product’s mechanism of action will this preliminary data requirement be waived.

Applications submitted to this NOFO should propose a mid-phase clinical trial to do the following: determine the optimal dose or formulation of a given natural product for use in a future multi-site efficacy trial; or determine which patient phenotypes will be responders versus non-responders to the natural product to inform inclusion/exclusion criteria of a future efficacy trial.

Clinical trials submitted under this NOFO are expected to be hypothesis based, milestone-driven, and directly related to the research priorities and mission of NCCIH. This NOFO will not support single-site or multi-site efficacy or effectiveness trials, nor will it support trials to test natural products for the treatment or prevention of cancer.

Applicants are encouraged to contact the appropriate NCCIH Scientific/Research contact for the area of science for which they are planning to develop an application prior to submitting to this NOFO. Funding Opportunity Goal(s) The National Center for Complementary and Integrative Health (NCCIH) provides funding for research into complementary and integrative health approaches.

Research constituting a rigorous evidence base for complementary health approaches will be developed through a range of research strategies including basic and translational research, and clinical investigation. Open Date (Earliest Submission Date) 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.

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 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.

Use the NIH ASSIST system to prepare, submit and track your application online. 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. Workspace to prepare and submit your application and eRA Commons to track your application. 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 National Center for Complementary and Integrative Health (NCCIH) is committed to the rigorous investigation of promising complementary and integrative health approaches with nutritional therapeutic inputs (often called natural products).

Promising natural products (i.e., botanicals, probiotics, and products marketed as dietary supplements) have compelling preclinical or preliminary clinical evidence for potential health benefit.

For this notice of funding opportunity (NOFO), natural products include promising nutritional regimens that standardize the amount of a specific naturally occurring nutritional compound (e.g., omega-3 fatty acids, anthocyanidins, or polyphenols) and have compelling preliminary evidence suggesting potential benefit in treating a condition, disorder, or disease.

Nutritional intervention research in humans is complicated by the complex and varied background nutritional status and dietary intake of participants in clinical trials.

To enhance rigor, reproducibility, and generalizability, it is important that trials of natural products that are part of the regular or occasional dietary intake include rigorous methods to account for the dietary intake and heterogeneity across participants (e.g., assessment of nutritional status; collection of data about dietary intake at baseline and throughout the trial; collection of data about factors that may impact absorption or metabolism of the natural product; rigorous study design to ensure balance across study arms with strategies such as stratified randomization; or rigorous statistical methods to examine treatment heterogeneity through prespecified subgroup analyses or analyses of effect modification by background nutritional status or other participant characteristics on target engagement or clinical outcomes).

Clinical trials of natural products are maximally informative if they incorporate well-formulated hypotheses built on a sound foundation of basic mechanistic and pharmacologic understanding. The first step in clinical trials of natural products is to demonstrate that the intervention exerts a measurable effect on a hypothesized “target” or mechanism of action rather than just focusing on demonstrating a change in clinical symptom(s).

“Target engagement” refers to verification that the intervention has had the predicted effect on the target. Targets may be molecular, cellular, circuit, biological, tissue, organ, somatic, psychological, behavioral, or interpersonal.

Following the initial demonstration of target engagement, the next step of novel intervention development involves replicating target engagement and evaluating whether intervention-induced changes in the target are associated with clinical benefit.

In some cases, a fundamental understanding of a given natural product’s biologic target or mechanism of action has been clearly established (e.g., compound’s affinity for a specific receptor is well established). It is also recognized that for certain conditions (e.g., pain), demonstrating target engagement may not be possible or practical with human participants.

When a mechanism of action has already clearly been established or when measuring target engagement is not possible, investigators should contact a member of the program staff at NCCIH to discuss what funding mechanism is appropriate. There is a need for research to evaluate natural products to determine whether they are safe and efficacious or effective for given conditions or disorders.

To accomplish this goal, mid-phase clinical trials conducted through the R01 are important to determine optimal dosing of and participant characteristics for the natural product’s use prior to conducting a fully powered clinical trial. NCCIH has designed a framework for research to describe the broad spectrum of complementary and integrative health research it supports ( https://www. nccih.

nih. gov/grants/nccih-clinical-trials-funding-opportunities/research-framework ). NCCIH supports investigators working on the continuum of the research framework, from basic science and demonstrating reproducible impact on a target engagement measure through high impact efficacy trials ( https://www.

nccih. nih. gov/grants/nccih-clinical-trials-funding-opportunities/natural-products-clinical-trials-funding-opportunities ).

We encourage investigators to examine the full suite of natural product research NOFOs to determine which one best aligns with the proposed stage of intervention development and testing. NCCIH has an oversight process to provide stewardship and maintain excellence, integrity, and rigor in our supported clinical studies ( https://www. nccih.

nih. gov/grants/toolbox ). Investigators are encouraged to review the NCCIH Clinical Terms of Award for Human Subjects Research ( https://www.

nccih. nih. gov/research/nccih-clinical-terms-of-award-for-human-subjects-research ) to learn more about NCCIH’s requirements for clinical research.

Prior to submitting an application, NCCIH strongly encourages consultation with the NCCIH Scientific/Research contacts relevant to the area of science for which they are planning to develop an application. Early contact provides an opportunity for NCCIH staff to discuss the scope and goals, and to provide information and guidance.

Purpose of the Mid-Phase Clinical Trial Award (R01) The objective of this NOFO is to support clinical trials to increase the evidence base for a natural product. The following are examples of types of mid-phase clinical trials appropriate for this NOFO.

Dosing and formulation optimization of the natural product to evaluate the impact on the target engagement measure(s) to be used in a future multi-site, randomized clinical trial Determining which patient phenotypes will be likely “responders” versus “non-responders” to the natural product to inform inclusion/exclusion criteria of a future efficacy trial In addition, investigators can also collect additional data documenting ability to recruit, accrue, and retain participants; achieve adherence to the study protocol; and complete collection of follow-up data The objective of this NCCIH R01 mid-phase clinical trial NOFO is to gain additional knowledge about a natural product in order to plan and conduct a future multi-site, randomized clinical trial.

Investigators are encouraged to include relevant stakeholders (e.g., patients, providers, health care systems, etc.) in the planning and execution of exploratory and larger clinical trials.

Several outcomes from a grant awarded under this NOFO are possible: (1) the product does not warrant further study for the particular target, condition, or disorder of interest; (2) additional studies must be completed before proceeding to a full-scale multi-site efficacy trial; or (3) the data generated under this award are informative and sufficient to warrant moving ahead with a well-executed multi-site efficacy clinical trial.

If warranted by the results of studies conducted, awardees may prepare and submit an application for a subsequent clinical trial when the R01 trial is complete and results have been analyzed. Prospective applicants should note that funding of a trial under this NOFO does not guarantee that NCCIH will accept, or fund, a subsequent multi-site clinical efficacy trial application.

Investigators should propose a randomized controlled trial design with at least one intervention arm and one comparator arm. There should be a strong rationale for the comparator condition (e.g., time and attention control, usual care, standard of care, placebo, and/or active comparator(s)) based on the research question you plan to address in the future powered trial.

Due to lack of rigor and potential expectancy effects, NCCIH will not support studies proposing a waitlist comparator condition. This R01 is a mid-phase clinical trial that is meant to support research activities that will inform future large-scale efficacy or effectiveness trials.

Studies supported by this NOFO should be adequately powered to test a hypothesis/hypotheses related to the natural product dose, participant phenotype, or study process metrics identified as being essential to inform a future fully powered efficacy or effectiveness trial.

The sample sizes that can be supported under this NOFO are limited; therefore, proposing to conduct fully powered tests of clinical outcomes (i.e., efficacy) or underpowered tests of outcomes (i.e., “preliminary efficacy”), or attempting to utilize the highly variable point estimate of an effect size for power calculations would not be appropriate and are noted as nonresponsive below.

Regulatory Requirements To Consider: The U.S. Food and Drug Administration (FDA) establishes and enforces the regulatory requirements for clinical research on natural products when they may be 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 Study Record: PHS Human Subjects and Clinical Trials Information description of the availability of Investigational Product (IP) and IND/Investigational Device Exemption (IDE) status. Guidance on the IND evaluation process can be found on the NCCIH Natural Products Clinical Trials Resource webpage: https://www.

nccih. nih. gov/grants/natural-products-clinical-trials-resource For applications that propose the use of a mobile device, similar app, or clinical decision support software, applicants must consult with their Institutional Review Board (IRB) to determine whether the approach may qualify as a medical device.

If so, applicants must contact the FDA prior to applying to determine whether an IDE application is necessary for the proposed clinical research ( https://www. fda. gov/medical-devices/software-medical-device-samd/your-clinical-decision-support-software-it-medical-device ).

Preliminary data requirements This NOFO is appropriate when there is a compelling rationale, a rigorous empirical basis, and scientific premise, which should include preliminary data from animal studies and previously published and citable human studies.

The following preliminary data from human studies (published and citable data from the peer-reviewed literature) on the same product and specific formulation as proposed in the current application will provide a strong justification for the proposed work: Demonstration that the natural product can produce a clinically meaningful change in measurable target engagement (e.g., mechanism of action) in the human population of interest.

There must also be evidence that the change in target engagement has been replicated in a separate human study with the same natural product to be used in the proposed project, unless it is impossible or impractical to do so or when a mechanism of action has been clearly established .

Evidence that evaluates the pilot study data for strength of correlation between the impact on target engagement and changes in the clinical outcome that will be studied in the proposed clinical trial (unless waived by condition below). Evidence that the specific natural product is bioavailable in humans. Note that for prebiotics or probiotics this may be demonstrated by documenting short-term retention in the gastrointestinal tract.

Evidence that the natural product does not produce frequent or severe adverse events in human pilot trials. For the purposes of this NOFO, it is preferred that there be an established, measurable, reproducible, well-characterized target engagement measure for a given natural product in human subjects.

However, NCCIH acknowledges that for some conditions, it may be impossible or impractical to directly measure the target engagement of a natural product.

In these circumstances the study should be justified by: (1) a clear rationale for why studying a target engagement measure in human participants is impossible or impractical; (2) potentially proposing other objective, reproducible measures that may be proxy to or indicative of target engagement for the natural product; and (3) strong compelling preliminary data to warrant further study of the natural product in clinical studies.

In other cases, a fundamental understanding of a given natural product’s biologic target or mechanism of action has been clearly established (e.g., compound’s affinity for a specific receptor is well established). In these situations, investigators are encouraged to contact NCCIH Scientific/Research staff to determine whether the R01 is the appropriate NOFO for the proposed clinical trial.

For applications that include a mind and body approach as part of a multi-component intervention, the application must provide published data that the mind and body intervention proposed has demonstrated efficacy for the condition being studied from at least one fully powered controlled trial.

For this NOFO, investigators should design a realistic timeline for the startup and completion of the clinical trial and provide contingency plans to proactively confront potential delays or disturbances to the planned trial.

NCCIH Priorities for Developing and Pilot-Testing Natural Products Symptom management, particularly the use of natural products for sleep disorder/disturbance, management of pain conditions, common gastrointestinal disorders, post-acute sequelae of SARS-CoV-2 infection (PASC), or mental health conditions such as those commonly managed in primary care (e.g., chronic stress, depression, anxiety disorders, and post-traumatic stress).

Studies that examine the effects of prebiotics/probiotics and other natural products on gut microbiome-brain interactions. Of particular interest are studies of prebiotics/probiotics for depression, anxiety disorders, irritable bowel syndrome (IBS), or chronic pain. Studies that examine the effects of cannabinoids and terpenes in conditions noted above.

Studies that examine the effects of naturally occurring psychedelics and entheogens in conditions noted above. Studies that address minority health and reduce disparities in conditions noted above. Studies that examine the effects of natural products to address comorbidities, coinfections, and/or complications from HIV ( https://www.

oar. nih. gov/hiv-policy-and-research/strategic-plan ).

Trials that examine the effects of natural products across the continuum of background dietary intake. Trials that evaluate whether nutritional status moderates target engagement or clinical outcomes. All NIH-funded research must adhere to the Code of Federal Regulations ( https://grants.

nih. gov/policy/humansubjects/policies-and-regulations/vulnerable-populations. htm ).

The Inclusion Across the Lifespan policy requires that individuals of all ages, including children (i.e., individuals under the age of 18) and older adults, must be included in all human subjects research conducted or supported by NIH, unless there are scientific or ethical reasons not to include them ( https://grants. nih. gov/grants/guide/notice-files/NOT-OD-18-116.

html ). Applications proposing research topics not identified above as high programmatic priority can be submitted but are likely to be considered of lesser or low programmatic priority, which will significantly influence programmatic relevance and reduce the likelihood of funding.

Applications proposing research studies using an intervention and patient population that are the same as or very similar to those used in studies already in progress, conducted, or published by other groups are likely to be of lower programmatic priority. Applications that do not address dietary intake and nutritional status when appropriate will also be deprioritized.

Clinical Trials Not Responsive to This NOFO The following types of clinical trials are not responsive to this NOFO, and applications proposing such activities will be deemed nonresponsive and will not be reviewed: Phase I/first in human trials. Studies proposing to analyze data from the trial to assess efficacy of the natural product or estimate effect size ( https://www. nccih.

nih. gov/grants/pilot-studies-common-uses-and-misuses ). Trials proposing to measure or replicate the effect of a natural product through target engagement.

Trials that do not include a natural product or standardized nutritional regimen. Studies utilizing a natural compound that has been synthetically modified (e.g., conjugates, derivatives, or pro-drugs). Studies that propose a waitlist control.

Trials that propose to test natural products for the treatment or prevention of cancer. (Investigators interested in cancer treatment or prevention trials should contact the National Cancer Institute.) Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.

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

Award Information 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.

Required: Only accepting applications that 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.

Application budgets are not limited, but it is strongly recommended that applications not request more than $350,000 per year in direct costs per year. A strong rationale must be provided for budgets that exceed this recommendation. Budgets should reflect the actual needs of the proposed project.

The scope of the proposed project should determine the project period, but it is strongly recommended that applications not request more than three years of funding support. A strong rationale must be provided for project periods that exceed this recommendation. The maximum project period is 5 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 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 the NIH Grants Policy Statement Section 2.

3. 9. 2 Electronically Submitted Applications for additional information.

System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually . The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.

NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM. Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM. gov registration process.

The same UEI must be used for all registrations, as well as on the grant application. eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants. gov registrations; all registrations must be in place by time of submission.

eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application. Grants. gov – Applicants must have an active SAM registration in order to complete the Grants.

gov registration. Program Directors/Principal Investigators (PD(s)/PI(s)) All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons.

If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

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.

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 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 ). Applications with Foreign components are encouraged to read NCCIH International Health Research page . Foreign components can include foreign collaborators or consultants, but should not include foreign sites outside of the U.S. or Canada, according to NCCIH’s policy.

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. 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. Facilities and Other Resources: Applicants must provide strong evidence of the availability of appropriate institutional resources and suitable patient populations. Documentation of availability of eligible subjects at clinic sites, presented in tabular format, must be provided.

The application must include relevant information that addresses the feasibility of recruiting participants who are eligible for the clinical trial. Specifically, applicants must provide evidence that each recruiting center in the trial has access to a sufficient number of participants who meet the eligibility criteria as defined in the submitted protocol.

For multi-site applications, information must be provided for each participating site. Discussion of engagement with different types of institutions and organizations (e.g., research-intensive, undergraduate-focused, community-based). Description of any planned partnerships that may enhance geographic and regional representation.

Plan to utilize the project infrastructure (i.e., research and structure) to support career-enhancing research opportunities for junior, early- and mid-career researchers. Description of any training and/or mentoring opportunities available to encourage participation of students, postdoctoral researchers and co-investigators from varied backgrounds.

Plan to develop transdisciplinary collaboration(s) that require unique expertise to address research question(s). Publication plan that enumerates planned manuscripts and proposed lead authorship. Outreach and planned engagement activities to enhance recruitment efforts.

SF424(R&R) Senior/Key Person Profile All instructions in the How to Apply- Application Guide must be followed. Biographical Sketches: Document the PD’s/PI’s experience in leading clinical trials and expertise in the content area of the trial.

Even exploratory clinical studies will require a multidisciplinary team (clinician, biostatistician, data manager, study coordinator, etc.), and the application should reflect their hands-on involvement in the design and implementation of the study protocol.

Applicants are encouraged to provide strong evidence of the study team’s qualifications and ability to conduct the proposed as well as future research, experienced investigative team members, and previous investigative experience in related clinical trials. All instructions in the How to Apply- Application Guide must be followed. The budget for the first year of the grant should reflect the implementation timeline.

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: Note: Discuss the overall approach but do not duplicate information collected in the PHS Human Subjects and Clinical Trials Information Form.

The Research Strategy should be organized in a manner that will facilitate peer review. The body of the application must present an overview of the state of the science, current status and relevance of the trial, a discussion of the specific protocol, and the approach to data collection, analysis, and dissemination.

The following criteria must be addressed: Importance of Research : The significance and innovation of the proposed clinical trial and importance of