Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. 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

The purpose of this FOA is to encourage transdisciplinary research to improve traditional assessment of acute- and late-term cognitive changes following cancer treatment for non-central nervous system malignancies. Complaints of persistent cognitive deficits are common among the increasing population of cancer survivors, particularly those who have undergone adjuvant chemotherapy, hormone and/or molecularly-targeted cancer treatments. Systemically-treated cancer patients experience cognitive impairment during treatment, upon completion of regimens, and often as part of long-term survivorship. However, the specific nature and underlying mechanisms causing the cognitive impairments are often unclear. By leveraging advances in cognitive neuroscience, fundamental knowledge about the specific underlying mechanisms responsible for cognitive impairment may be obtained.

This FOA encourages transdisciplinary research that will apply cognitive neuroscience theory and task paradigms, developed in the last three decades, for improved measurement and assessment of acute- and late-term cognitive changes following cancer treatment. With the application of cognitive neuroscience tasks for the longitudinal assessment of cancer patients (prior to the start of treatment, during treatment, and following treatment over time), we can more specifically measure cognitive impairment and its prevalence.

In the absence of precise measurement, clinicians and survivors will remain uncertain about the nature of the cognitive difficulties and modes for remediation. Knowing whether a patient’s complaint, for example, about failing memory reflects poor attention and/or poor retrieval, can reduce uncertainty, inform care planning, and suggest possible accommodation strategies. The incorporation of cognitive neuroscience task paradigms into clinical assessment approaches has the potential to change cancer care planning. Traditional neuropsychological batteries, which are time consuming and complicated to administer, have been a barrier to widespread adoption of surveillance and clinical assessment of cognition in cancer patients and survivors exposed to systemic treatments.

This FOA is suitable for transdisciplinary research efforts where proof-of-principle of the proposed technology or methodology has already been established and supportive preliminary data are available. This FOA runs in parallel with an FOA of identical scientific scope, PAR-16-213, which utilizes the Exploratory/Developmental Grant (R21) mechanism.

The Clinical Problem: As the number of cancer survivors in the U.S. increases from the current 14.5 million to an estimated 19 million in the next decade the need to minimize chronic and late cancer treatment-related cognitive impairment becomes more urgent. Approximately one-third of patients with non-central nervous system malignancies treated with adjuvant chemotherapy experience clinically significant cognitive difficulties that persist for months or years following treatment. Survivors often report problems with memory, attention, verbal fluency, processing speed, multi-tasking, planning, and following directions. Complaints tend to be associated with exposure to chemotherapy agents, such as fluorouracil, cyclophosphamide, docetaxel and doxorubicin, regardless of whether these agents can cross the blood-brain barrier. Evidence of chemotherapy drugs causing cognitive impairment in patients is supported by preclinical findings and structural and functional neuroimaging studies that have documented gray and white matter volume changes. Studies implicate the neurotoxic effects of cytokine dysregulation, direct neurotoxic injury, and oxidative stress, and have ruled out diagnosable affective disorders as primary causes of the cognitive complaints. Furthermore, when anxiety or depressive symptomatologies are associated with cognitive complaints, the cause and effect are often ambiguous. There are reports, and plausible biological basis, of cognitive complaints after receipt of hormonal (tamoxifen, anastrosole) and molecular-targeted therapies. As treatment of early-stage cancers (e.g., breast cancer with low Onco DX scores) shifts away from conventional chemotherapy agents and toward adjuvant chemotherapy and molecularly-targeted treatments, cognitive effects of these targeted therapies also require empirical attention.

A better understanding of cancer treatment-associated cognitive impairment is important because cognitive difficulties can have a profound and pervasive impact on quality of life. Survivors may experience difficulty engaging in treatment decision making, resuming employment, and managing basic activities of daily living. Older survivors, many of whom live independently and need to work to support themselves, may suffer economic hardship if they are unable to return to work, and social isolation if they are unable to resume previous social roles.

What is Needed: If we are to understand and address cancer treatment-associated cognitive impairment, we must first be able to accurately and precisely evaluate it. Self-reports of cognitive functioning and traditional neuropsychological tests are the primary sources of current assessment. Patient-reported outcomes can identify general deficits but were not intended to identify the component processes underlying these complaints. Self-reports have intrinsic limitations (e.g., a patient reporting to her physician, I am forgetting things I just heard, may conclude this is due to a memory defect, which in fact may be due to an attentional deficit).

Traditional clinical neuropsychological test batteries may not be able to distinguish, for example, which aspects of executive function are affected (e.g., processing speed, planning, response inhibition) nor parse which facets of memory (e.g., encoding, storage [working-memory, short-term memory], and retrieval) are responsible for poor performance on a traditional clinical neuropsychological test. Poor performance may be due to a single impaired subcomponent or multiple sub-component cognitive processes, but the batteries lack the specificity to determine. Traditional neuropsychological tests also tend be insensitive to less severe, but still debilitating cognitive impairments, such as those observed in chemotherapy patients (when compared to patients of blunt trauma or stroke).

Recent developments in assessment such as the NIH Toolbox Cognitive Battery and the Cambridge Neuropsychological Test Automated Battery represent improvements and are briefer than traditional neuropsychological batteries, but were validated on the traditional measures, and share the same imprecision for several cognitive domains. The later limitation is not surprising, given that the neuropsychological tests were originally developed several decades ago, to diagnose severe brain pathology, such as dementia and traumatic brain injury. The types of cognitive impairments associated with chemotherapy are typically more subtle in comparison.

Preclinical models assessing effects of chemotherapy, immunotherapy, and/or molecularly-targeted agents in tumor-free and/or tumor-bearing animals with cognitive-science informed paradigms may also be informative.

Opportunity to Leverage Cognitive Neuroscience: Task paradigms and tools developed in cognitive neuroscience in the last 30 years (e.g., cognitive neuroscience task paradigms, computational modeling, and electrophysiological techniques), have the potential to measure discrete cognitive processes and parse which subcomponent processes underlie cognitive complaints. In addition to their higher precision, these cognitive neuroscience paradigms may require considerably less time and are easier to administer than traditional clinical neuropsychological batteries a significant potential asset for dissemination and implementation within the clinical setting.

With the exception of fMRI research on default mode network connectivity, modern cognitive neuroscience approaches have not been applied to diagnose cancer treatment-associated cognitive impairment (although these approaches have been used in brain imaging studies with cancer patients in a few studies). However, research on other brain disorders, such as autism, Parkinson’s disease, and attention deficit hyperactivity disorder (ADHD), has been informed by cognitive neuroscience tasks. For example, ADHD has long been characterized as a disorder of attentional processes, but with only a vague understanding of which attentional processes were impaired. However, recent cognitive neuroscience-based studies found that children with ADHD were normal with respect to visual selective attention but had difficulty keeping track of what they should have been looking for.

The success of cognitive neuroscience techniques in identifying the component processes of other neurologic disorders serves as a proof-of-principle that cognitive neuroscience task paradigms can elucidate specific components of cognition, impaired as a function of adjuvant cancer treatments, which are the source of patients complaints. This research can inform care planning and accommodation strategies for clinical populations.

This initiative seeks to produce a better understanding of the specific components of cognition affected by adjuvant cancer treatments for non-CNS malignancies by leveraging cognitive neuroscience approaches in assessment. Some projects might build on the extant evidence from early-stage breast cancer patients, while other projects may extend cognitive neuroscience tasks to other non-CNS malignancies (e.g., lymphoma, prostate cancer) for which cognitive complaints also have been reported. Other projects may propose to use preclinical animal models with translational relevance to identify specific components of cancer treatment cognitive impairment.

Projects that are suitable for this FOA are likely to include study design features that enable improved understanding of the acute- and late-term cognitive changes following exposure to adjuvant chemotherapy and molecularly-targeted treatments, including hormonal therapy, for non-central nervous system tumors. Prospective longitudinal designs with a pre-treatment baseline assessment prior to initiation of a first line adjuvant therapy regimen and repeated assessments over an appropriate time period are essential to evaluate acute and late-term changes.

Possible comparison groups to control for patient status and age might involve cancer patients not receiving chemotherapy and/or healthy aged-matched controls. The choice of comparison group will depend on the cancer site, stage, and treatment regimen chosen for study depending on the specific aims and hypotheses of the project. Researchers may study the effects of traditional chemotherapy; however, molecular targeted therapies are becoming more common in cancer care and may be associated with cognitive complaints.

Structural and/or functional neuroimaging may be included to test whether cognitive neuroscience task performance predicts gray and white matter damage and alterations in neural connectivity. Inclusion of traditional clinical neuropsychological assessment and/or tools, such as NIH Cognitive Toolbox or Cambridge Neuropsychological Test Automated Battery, is encouraged to compare performance with results from cognitive neuroscience paradigms. Inclusion of quality of life and functional outcomes to assess the predictive validity of cognitive neuroscience task performance as a function of cancer treatments may also be considered.

Projects that assess a broad range of cognitive ability via outreach/recruitment to understudied and demographically diverse samples (e.g., low socioeconomic status or educational attainment, rural, and race/ethnicity) are encouraged.

This FOA encourages transdisciplinary research projects that leverage advances in cognitive science, neuroscience and neuroimaging, and integrates expertise from diverse disciplines such as medical oncology, cancer epidemiology, neuropsychology, psychometrics, human development and aging, preclinical models of human cancer, statistical modeling, systems biology, genetics, and behavioral science.

Examples of research questions that fall within the scope of this FOA follow but are not limited to:

• Which specific cognitive functions are impaired following chemotherapy and/or molecular-targeted therapies for non-central nervous system malignancies? Alternatively, are impairments generalized across all or most cognitive domains?
• What impairment differences are found with cognitive neuroscience task paradigms versus patient-reported outcomes, traditional clinical neuropsychological test batteries, and/or tests derived from them such as the NIH Toolbox Cognitive Battery?
• To what extent does performance on cognitive neuroscience task paradigms predict reduction in gray matter volume, white matter integrity, and neural connectivity (measured via structural and functional neuroimaging) better than patient-reported outcomes, traditional clinical neuropsychological test batteries, and/or NIH Toolbox?
• To what extent can reliable and sensitive cognitive neuroscience task paradigms be integrated into the standard of cancer care for persons undergoing treatment for non-CNS malignancies?
• To what extent does poor performance on cognitive neuroscience task paradigms predict acute and late term indices of quality of life and functional outcomes better than traditional clinical neuropsychological testing or variants thereof?
• If cognitive neuroscience task paradigms are administered at several time points, what kinds of trajectories of cognitive change are detected (e.g., transient impairment, delayed impairment, improvements followed by reversals, or chronic long-term impairment) in persons treated for non-CNS malignancies?
• To what degree can advances made in the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative be leveraged to improve cognitive assessment of cancer-treatment associated impairment in patients with non-CNS malignancies?
• To what extent can preclinical research using translationally relevant animal models expand our mechanistic understanding of the impact of systemic treatments for non-CNS malignancies (e.g., chemotherapy, targeted therapies, biologics) on brain function and structure, cognition, and behavior?

This FOA is not intended to support applications or research projects that rely on:

• Analysis of existing data;
• Retrospective or cross-sectional research designs; or
• Brain imaging technologies, exclusively.

Contingent upon the aims of the proposed research projects, investigators from different disciplines should work in an integrated manner to create methodological and conceptual innovations that improve our understanding and assessment of acute- and late-term cognitive changes following cancer treatment for non-central nervous system malignancies. Use of the multiple-Program Director (PD)/Principal Investigator (PI) option is strongly encouraged to facilitate collaboration and expertise-sharing in order to address the scientific scope outlined in this FOA.

This FOA seeks to encourage applicant use of the National Cancer Informatics Program (NCIP) Hub platform (see https://nciphub.org/) to facilitate collaboration in which exchanging information, sharing resources, and integrating disciplinary perspectives achieve a common scientific goal. Applicants who propose to use this platform will be encouraged to take full advantage of the capabilities of the NCIP Hub resource. Not all projects that are submitted to this FOA will benefit from use of the NCIP Hub platform. Use of the NCIP Hub platform is at the discretion of the applicant/awardee.

Awardees of this FOA are encouraged to attend annual meetings of the Cancer and Cognition Forum and participate in forum workshops and webinars organized and hosted by the NCI and/or grantee institutions.

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

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Eligible Agencies of the Federal Government-Including the NIH Intramural Program
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations
• Non-domestic (non-U.S.) Entities (Foreign Institutions)

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

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

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) 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.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. 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 DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH 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 SF424 (R&R) Application Guide.

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

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. 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 NOT-OD-11-101).

Applicants must obtain the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

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

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

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

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

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

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

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

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

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

Applicants to this FOA are encouraged to budget for the PD(s)/PI(s) to attend annual meetings of the Cancer and Cognition Forum and participate in forum workshops and webinars organized and hosted by the NCI and/or grantee institutions.

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

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

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

Research Strategy. The Research Strategy should clearly describe or address the following:

• Rationale for choice of comparison groups to assess differences in cognitive changes as a function of cancer-related treatment.
• Clear justifications for inclusion of specific cancer treatment regimens (chemotherapy, hormonal and/or molecular targeted therapies) in the research protocol.
• Clear justifications for choice of cancer site, cancer stage, cognitive assessment approach and schedule for assessments.
• Sound recruitment strategies to obtain a broad range of cognitive ability via outreach/recruitment to understudied and demographically diverse samples (e.g., low socioeconomic status or educational attainment, rural, and race/ethnicity).
• If a preclinical animal model research project is proposed:
• Description of the translational relevance of the model and the cognitive science paradigms being used.
• Justification of the translational relevance of the use of tumor bearing or tumor na ve animal models.

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

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

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

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

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

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

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

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

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

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

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review, NIH. Applications that are incomplete or non-compliant will not be reviewed.

Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide.

The requests by NIH intramural scientists will be limited to the incremental costs required for participation. As such, these requests will not include any salary and related fringe benefits for career, career conditional or other Federal employees (civilian or uniformed service) with permanent appointments under existing position ceilings or any costs related to administrative or facilities support (equivalent to Facilities and Administrative or F&A costs). These costs may include salary for staff to be specifically hired under a temporary appointment for the project, consultant costs, equipment, supplies, travel, and other items typically listed under Other Expenses. Applicants should indicate the number of person-months devoted to the project, even if no funds are requested for salary and fringe benefits.

If selected, appropriate funding will be provided by the NIH Intramural Program. NIH intramural scientists will participate in this program as PDs/PIs in accord with the Terms and Conditions provided in this FOA. Intellectual property will be managed in accord with established policy of the NIH in compliance with Executive Order 10096, as amended, 45 CFR Part 7; patent rights for inventions developed in NIH facilities are NIH property unless NIH waives its rights.

Should an extramural application include the collaboration with an intramural scientist, no funds for the support of the intramural scientist may be requested in the application. The intramural scientist may submit a separate request for intramural funding as described above.

Applicants are required to follow our Post Submission Application Materials policy.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

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

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

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

Specific for this FOA:

• Does this study address an important problem in cancer treatment-related cognitive impairment?
• If the aims and milestones of the project are achieved, how will scientific knowledge be advanced?
• What will be the effect of these studies on concepts or methods important to understanding, preventing, or treating cancer treatment-related cognitive impairment?
• Does the project have clearly described, significant, and near-term translational potential for research or interventions associated with impaired cognition following cancer treatment?
• Does the project have implications for the cancer care treatment decision-making and cancer survivor quality of life or care planning?
• For preclinical studies, does the project have implications for the types of cognitive domains and neural systems most impaired by agents used in cancer treatment?

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

Specific for this FOA:

• Does the transdisciplinary research team include appropriate cognitive neuroscience expertise?
• If a preclinical model research project is proposed, does the research team include appropriate expertise on the translational relevance of the model being used?
• Does the team demonstrate an ability to work in an integrated manner?
• Are the investigators appropriately trained and well suited to carry out this work?
• Is the project proposed appropriate to the experience and expertise of the transdisciplinary research team?

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

Specific for this FOA:

• Does the application challenge traditional assessment approaches by leveraging cognitive science, neuroscience, and/or neuroimaging in a manner that creates methodological and conceptual innovations that improve our understanding and assessment of cancer treatment-related cognitive impairment?
• Does the applicant provide the best innovative method to solve the problem stated in the study?
• Are the aims original and innovative? Does the project challenge existing paradigms or develop new methodologies, theories, or technologies??

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

Specific for this FOA:

• Is the approach sufficiently informed by cognitive neuroscience, building on existing discoveries and leveraging basic experimental paradigms, emerging tools, methodological rigor; and knowledgeable of new trends in cancer treatment for non-CNS malignancies?
• Does the research strategy plan address the critical components and justifications as described in Research Strategy?

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

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

Specific for this FOA:

• Is the scientific environment conducive for the conduct of transdisciplinary research that integrates and moves beyond discipline-specific approaches to create methodological and conceptual innovations that improve our understanding and assessment of cancer treatment-related cognitive impairment?

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

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

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

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

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

Not Applicable

Not Applicable

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

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).

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

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

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

As part of the scientific peer review, all applications:

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

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

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

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

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

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

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

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

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

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

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: https://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

Jerry Suls, Ph.D..
National Cancer Institute (NCI)
Telephone: 240-276-6811
Email: [email protected]

Samuel C. Edwards, Ph.D.
Center for Scientific Review (CSR)
Telephone: 301-435-1246
Email: [email protected]

Rebecca Brightful
National Cancer Institute (NCI)
Telephone: 301-631-3011
Email: [email protected]

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

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