Clinical Characterization of Cancer Therapy-induced Adverse Sequelae and Mechanism-based Interventional Strategies (R01 Clinical Trial Optional) is a grant from the National Institutes of Health (NIH), administered by the National Cancer Institute (NCI).

This R01 funding opportunity supports basic, translational, and clinical research aimed at identifying the mechanisms underlying adverse side effects of cancer therapies that persist as chronic comorbidities or emerge as delayed post-treatment effects. Eligible applicants include universities, nonprofits, state and local governments, for-profit organizations, and foreign institutions. Clinical trials are optional.

Applicants should carefully review current funding opportunity priorities, as this announcement was updated in March 2025 to align with agency priorities.

PAR-25-145: Clinical Characterization of Cancer Therapy-induced Adverse Sequelae and Mechanism-based Interventional Strategies (R01 Clinical Trial Optional) 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 Cancer Institute ( NCI ) Funding Opportunity Title Clinical Characterization of Cancer Therapy-induced Adverse Sequelae and Mechanism-based Interventional Strategies (R01 Clinical Trial Optional) R01 Research Project Grant 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 See Section III. 3.

Additional Information on Eligibility . Assistance Listing Number(s) Funding Opportunity Purpose The purpose of this Notice of Funding Opportunity (NOFO) is to promote research studies designed to address adverse sequelae of cancer therapies that persist and become chronic co-morbidities or develop as delayed posttreatment effects.

This NOFO supports basic, translational, and clinical research projects that seek to identify the mechanisms of therapy-induced adverse sequelae, clinically characterize the adverse sequelae, and translate the mechanistic understanding into therapeutic approaches to prevent or minimize the development of long-term sequelae.

The scope of research projects includes mechanistic studies with translational endpoints and longitudinal clinical phenotyping to identify and validate clinical endpoints (biomarkers, imaging, patient-reported outcomes or combined elements) for future use in clinical trials that will evaluate the efficacy of interventions designed to prevent or reduce specific adverse sequelae.

Open Date (Earliest Submission Date) The following table includes NIH standard due dates marked with an asterisk. 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 purpose of this Notice of Funding Opportunity (NOFO) is to promote research studies designed to address adverse sequelae of cancer therapies that persist and become chronic co-morbidities or develop as delayed posttreatment effects.

This NOFO supports basic, translational, and clinical research projects that seek to identify the mechanisms of therapy-induced adverse sequelae, clinically characterize the adverse sequelae, and translate the mechanistic understanding into therapeutic approaches to prevent or minimize the development of long-term sequelae.

The scope of research projects includes mechanistic studies with translational endpoints and longitudinal clinical phenotyping to identify and validate clinical endpoints (biomarkers, imaging, patient-reported outcomes or combined elements) for future use in clinical trials that will evaluate the efficacy of interventions designed to prevent or reduce specific adverse sequelae.

Research projects may be conducted in basic science and/or clinical settings. Successful applications should identify the specific adverse sequelae, which may include a cluster of adverse events that occur sequentially or in tandem with rationale for the cluster. The adverse sequelae may be chronic, progressive or later adverse effects for which current management or treatment strategies are limited or ineffective.

Many advances have been made in the treatment of cancer, with an increasing number of treatment options available to cancer patients, including surgery, radiation, and/or systemic therapy (chemotherapy, immunotherapy, targeted or hormonal therapies), from which severe adverse sequelae may result.

The number of cancer survivors continues to grow, with more than 18 million alive today, of which 47% have lived more than 10 years since diagnosis. Often, the extent of the toxicity burden is unknown until the therapy is administered to a large population of “real-world” patients with comorbidities who were not included in the definitive clinical trials.

Cancer registries do not typically collect information on treatment-related adverse effects, and identifying chronic or late-onset adverse effects can be challenging. Commonly, systemic cancer treatment can result in acute, cumulative, progressive and/or chronic toxicities.

Some acute drug-related adverse events (e.g., acute nausea and vomiting, neutropenia infections) can be mitigated by implementing evidence-based treatments or altering treatment doses and will resolve once therapy has been completed. Similarly, acute inflammatory responses resulting from immunotherapy can be managed by discontinuing therapy or treating with immunosuppressive corticosteroids.

Other adverse effects persist after completion of therapy or develop as late effects of therapy. For radiation therapy, adverse effects can develop acutely, resulting in dosing modifications, or occur as an intermediate or late effect. Adverse sequelae that result in dose modifications or discontinuation of therapy may have a negative impact on cancer outcomes.

Some of the chronic or late adverse effects may reduce the overall benefit from therapy by reducing patient quality of life following therapy and/or introducing additional morbidities that impair overall survival.

These adverse sequelae include, but are not limited to, therapy-induced peripheral neuropathy, neurocognitive impairments, cardiovascular toxicity, lymphedema of the upper and/or lower extremities, pulmonary fibrosis, arthralgias, fatigue, nephrotoxicity, ototoxicity, and various immune system-related adverse events.

While a variety of acute inflammatory adverse reactions have been reported with anti-checkpoint immunotherapy, the long-term consequences of checkpoint blockade or cellular immunotherapy are not known. With the introduction of newer treatment approaches, whether drugs, radiation therapy, immunotherapy or novel combinations, adverse events not seen with older therapies are emerging.

A careful assessment of pretreatment baseline characteristics may not be completed, impairing the ability to understand individual variability and subclinical risk factors. To date, little is known about the rates and severity of these newer adverse effects, particularly for immunotherapy agents and combination therapies involving immunotherapies.

Further, it is unknown how age, race/ethnicity, and co-morbid conditions will affect the development, progression or severity of these adverse events. In some cases, it is not a single adverse event, but a cluster of events that may herald the development of significant sequelae.

Given the high prevalence and significant impact of cancer treatment-related adverse effects, there is a need to understand both the mechanisms for their acute development and the clinical trajectory of the events that become chronic sequelae, including the variability in severity and duration of specific chronic or late effects.

For most of the cancer treatment-related adverse effects, no approved mitigating therapies or evidence-based management strategies are in place.

Efforts to develop nontoxic interventions to relieve treatment-related toxicities are hampered by a lack of mechanistic insight into these adverse events, difficulties in objectively measuring treatment-related toxic effects, insufficient characterization of the clinical phenotype, and insufficient studies validating preclinical biomarkers in the clinical setting.

Specific Areas of Research Interest NCI is interested in pre-clinical and clinical grant applications that extend the mechanistic understanding of cancer therapy-induced adverse sequelae to address one or more of the research gap areas outlined below. Applications should address hypotheses supported by mechanistic data focused on clinical and translational outcomes in adult or pediatric populations.

Applications may focus on adverse sequelae that persist and become chronic comorbidities or develop as delayed posttreatment effects related to radiation and/or systemic therapy (chemotherapy, immunotherapy, targeted or hormonal therapies). Collaborations between clinical and basic science investigators are encouraged, and projects that couple the mechanistic knowledge with clinical phenotype will be prioritized.

It is highly recommended that preclinical studies validate their findings in human tissue or human-derived cells with direct applicability to human conditions. A focus on understudied and underserved cancer populations and emerging cancer treatments is encouraged.

Research areas of interest include, but are not limited to, the following: Clinical characterization/phenotyping of chronic or progressive cancer therapy-induced adverse events or cluster of events Investigation of the trajectory of adverse sequelae that progress or become chronic Development and/or validation of objective measures of treatment-related adverse events Validation of clinical markers (biomarkers, imaging, patient-reported outcomes) of adverse sequelae in the clinical setting Conducting translational research to evaluate prevention or mitigation strategies Identification of risk factors and/or individual differences that contribute to the trajectory of adverse sequelae Examining the effect of the interaction between cancer treatment and cancer/tumor biology on adverse sequelae Translating knowledge of known and emerging clinical and genetic profiles and biological mechanisms into improvements in risk stratification, prevention, and detection Non-responsive Applications Applications with the following attributes will be deemed non-responsive and will not be reviewed.

Studies focused on acute, reversible, and non-progressive adverse sequelae; Exploring resistance to cancer treatment; Using Pre-clinical models to determine adverse events of non-FDA approved anti-cancer agents; and Exploring the development of symptomatic adverse events in non-cancer conditions. 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 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. Application budgets are not limited but need to reflect the actual needs of the proposed project.

The scope of the proposed project should determine the project period. 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) Non-domestic (non-U.S.) Entities (Foreign Organizations) are eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are 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 ). 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.

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. 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 should clearly describe the following within the appropriate section (i.e., Factor 1: Importance of the Research; Factor 2: Rigor and Feasibility): Information to be included in each grant application, but not limited to bulleted items, are listed below: Factor 1: Importance of the Research (Significance, Innovation) Succinctly discuss how the proposed research clinically characterizes adverse sequelae and how it can be translated into developing therapeutic approaches to prevent or minimize the development of long-term sequelae.

Summarize how the proposed research utilizes mechanistic knowledge of adverse sequelae to bring novel insight and understanding to preventing or minimizing long-term adverse sequelae. Discuss how any advances in the mechanistic understanding of specific adverse sequelae could be ultimately applied to clinical phenotyping and/or the development of biomarkers that could be used in clinical trials.

Summarize how the mechanistic knowledge is being used to evaluate the acute development and/or clinical trajectory of events that become chronic sequelae in the proposed research. Summarize how the proposed research uses novel methodology for clinical phenotyping. Discuss and highlight the innovative aspects of the research design.

Factor 2: Rigor and Feasibility (Approach) The approach and methodology proposed will be unique to the clinical need specifically addressed by each application. It is strongly encouraged that the proposed approach be succinctly described in detail and that it addresses possible weaknesses while clearly stating the clinical impact.

The potential difficulties and limitations of the proposed methodology and alternative approaches to achieve the aims should be identified and succinctly discussed. Describe and define the specific adverse event or cluster of events being studied in the proposed research. 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.

The following modifications also apply: All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

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. A Data Management and Sharing Plan is not applicable for this NOFO. 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 Clinical Trials Information form or Delayed Onset Study record. Study Record: PHS Human Subjects and Clinical Trials Information All instructions in the How to Apply- Application Guide must be followed. Section 2 - Study Population Characteristics Section 2.

5 Recruitment and Retention Plan Recruitment and referral sources: include the number of potentially available participants per proposed site annually; Enrollment rate (e.g., number of participants meeting eligibility criteria for enrollment per month); Discussion of potential recruitment delays or challenges and alternative strategies that can be implemented if there are enrollment delays or shortfalls; Procedures to monitor enrollment and track/retain participants for follow-up assessments; Evidence to support the feasibility of enrollment, including prior experience and yield from research efforts using similar referral sources and/or strategies; Strategies to ensure the study population has scientifically appropriate complexity and representativeness; Decision points for terminating the trial.

The study timeline should describe key milestones throughout the project and trial that need to be met to achieve the goals of the study. A milestone is defined as a scheduled event in the project timeline that signifies the completion of a project stage or activity. Applicants are required to provide detailed project performance and timeline objectives as outlined below.

Investigators must indicate where within the Plan the clinical trial or trials are scheduled and when the required documents will be available if not included at the time of submission. Program staff will review the milestones and timelines which can be negotiated, as needed, at the time of the award.

This section should include an estimated timeline for the following general milestones, as applicable: Complete finalized Clinical Trial Protocol for submission to NCI; Registration of clinical trial in ClinicalTrials.

gov; Completion of regulatory approvals; Enrollment of the first subject; Enrollment of 25%, 50%, 75%, and 100% of the projected recruitment for all study participants including women, minorities, and individuals across the lifespan (as appropriate); Completion of data collection time period; Completion of primary endpoint and secondary endpoint data analyses; Completion of final report of the primary outcome; Reporting of results in ClinicalTrials.

gov; Status of the FDA-regulated product requiring IND or IDE if applicable. In addition to meeting the above recruitment and other targets, applicants should give contingency plans if they do not meet the milestones and address other implementation activities necessary such as start-up tasks to achieve trial completion. Future year support is contingent on satisfactory achievement of performance milestones.

If milestones are not achieved fully, NCI may request development of a remedial plan and more frequent monitoring of progress, and/or take other remedial actions. Section 3 - Protection and Monitoring Plans Section 3. 3 Data and Safety Monitoring Plan In addition to the description of safety monitoring, address plans to monitor trial performance, including plans to assure fidelity to the protocol and integrity of the data.

Information about Data and Safety Monitoring Plans are available at https://humansubjects. nih. gov/data_safety .

Section 3. 5 Overall Structure of the Study Team In addition to the standard requirements for this item, provide a description of methods to identify additional collaborators, including enrollment/participation sites, if applicable.

Investigators who are new to the conduct of clinical trials should identify an appropriate mentor and establish the right composition for the clinical trial team (e.g., trial manager, statistician, data manager, study coordinator(s), research assistants, institutional review board [IRB] and ethics coordinator, etc.). In this situation, only the names and titles of key team members should be listed in a table.

Section 4 - Protocol Synopsis Section 4. 1. a Detailed Description It should summarize the necessary elements of the trial and supplements the Research Strategy, which includes an overview of the state-of-science and relevance of the trial and is meant to justify the need, its potential impact, and provide supporting preclinical and/or clinical evidence to justify the proposed trial, its design, and likelihood of successful completion.

Applications submitted without the Clinical Protocol Synopsis are considered incomplete and will not be reviewed. Please include the dose and intensity of the intervention in the description, if applicable. Applicants proposing behavioral intervention research are encouraged to use an existing framework, such as the ORBIT model for developing behavioral treatments ( http://dx.

doi. org/10. 1037/hea0000161 ), to determine the clinical trial phase being proposed and for guidance on study designs and methods appropriate for early-phase (Phase I and II) translational behavioral research.

4. 3 Statistical Design and Power The sample size and statistical power calculations should contain enough detail, including sufficient information on the assumptions made, so that a reviewer can readily duplicate the projected sample size for primary and secondary endpoints.

The power analysis should include a discussion of non-compliance, potential cross-over (if applicable), account for rates of follow-up (i.e., drop out/lost to follow up) during key outcome collection contacts. A discussion of how missing data will be handled should be included. Planned interim analyses for safety, efficacy, and/or futility should be described, if applicable.

For single-case design and other small-N study designs where traditional power analyses may not be applicable, provide a detailed description of the approach to sample size and analysis being used. Section 5 - Other Clinical Trials-Related Attachments 5.

1 Other Clinical Trials-related Attachments For applications that have the complete Clinical Trial Protocol available, submit the Clinical Trial Protocol as a single PDF that combines all clinical documents. Applicants should provide a list of clinical trials that demonstrate their experiences in trial coordination over the last 5 years, without duplicating information in biosketches.

The table should be provided as an attachment using the filename Clinical Trial Experience." The table should also include the following for each trial listed: start and completion date; percent of target accrued; whether the trials reached completion; and, if applicable, the date of first publication. 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 How to Apply- Application Guide must be followed. PHS Assignment Request Form All instructions in the How to Apply- Application Guide must be followed. Foreign (non-U.S.) organizations must follow policies described in the NIH Grants Policy Statement , and procedures for foreign organizations described throughout the How to Apply- Application Guide.

3. Unique Entity Identifier and System for Award Management (SAM) See Part 2. Section III.

1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants. gov 4. Submission Dates and Times Part I.

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

Organizations must submit applications to Grants. gov (the online portal to find and apply for grants across all Federal agencies). 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. 7. Other Submission Requirements and Information Applications must be submitted electronically following the instructions described in the How to Apply - Application Guide .

Paper applications will not be accepted. Applicants must complete all required registrations before the application due date. Section III.

Eligibility Information contains information about registration. For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide . If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance.

For assistance with application submission, contact the Application Submission Contacts in Section VII . 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