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
Exercise and Nutrition Interventions to Improve Cancer Treatment-Related Outcomes (ENICTO) in Cancer Survivors Consortium (U01 Clinical Trial Required)
Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type
New
Related Notices

  • May 6, 2021 - Notice of Pre-Application Webinar for RFA-CA-21-031. See Notice NOT-CA-21-078.

Funding Opportunity Announcement (FOA) Number
RFA-CA-21-031
Companion Funding Opportunity
RFA-CA-21-032 , U24 Resource-Related Research Project (Cooperative Agreements)
Assistance Listing Number(s)
93.395, 93.399
Funding Opportunity Purpose

Through this Funding Opportunity Announcement (FOA), the National Cancer Institute (NCI) seeks to support exercise and/or medical nutrition intervention research designed to improve cancer treatment-related outcomes for therapies delivered with curative or life-extending intent to cancer survivors. Projects may include either pediatric or adult cancer patient populations and must identify a treatment-related outcome as a primary endpoint and specify a relevant patient-reported secondary outcome(s). Priority will be given to studies with direct clinical relevance and translational potential. Responsive applications will fill a research gap concerning the efficacy of specific exercise and dietary approaches to improve cancer treatment-related outcomes. Information gained should improve behavioral intervention protocols for cancer survivors undergoing cancer treatment and may also generate feasibility information concerning translation into clinical care. Awardees will participate in an Exercise and Nutrition to Improve Cancer Treatment-Related Outcomes (ENICTO) in Cancer Survivors Consortium.

Key Dates

Posted Date
May 3, 2021
Open Date (Earliest Submission Date)
June 14, 2021
Letter of Intent Due Date(s)

June 14, 2021

Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS Scientific Merit Review Advisory Council Review Earliest Start Date
July 14, 2021 Not Applicable Not Applicable October 2021 January 2022 April 2022

All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).

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.

Expiration Date
July 15, 2021
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide,except where instructed to do otherwise (in this FOA or in a Notice from 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.

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

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

  3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.


  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose

Through this Funding Opportunity Announcement (FOA), the National Cancer Institute (NCI) seeks to support exercise and/or medical nutrition intervention research designed to improve cancer treatment-related outcomes for therapies delivered with curative or life-extending intent to cancer survivors. Projects may include either pediatric or adult cancer patient populations and must identify a treatment-related outcome as a primary endpoint and specify a relevant patient-reported secondary outcome(s). Priority will be given to studies with direct clinical relevance and translational potential. Responsive applications will fill a research gap concerning the efficacy of specific exercise and dietary approaches to improve cancer treatment-related outcomes. Information gained should improve behavioral intervention protocols for cancer survivors undergoing cancer treatment and may also generate feasibility information concerning translation into clinical care. Awardees will participate in an Exercise and Nutrition to Improve Cancer Treatment-Related Outcomes (ENICTO) in Cancer Survivors Consortium.

Key Terms for this FOA

Body Composition: The quantification of the amount of fat, bone, water, and muscle in the human body.

Cancer Survivor: Any individual diagnosed with cancer from the time of diagnosis until the end of life.

CTCAE: Common Terminology Criteria for Adverse Events.

Exercise: Structured movement for a specific purpose (e.g., improve strength or cardiorespiratory fitness [CRF]) that is characterized by frequency, intensity, time, and type (FITT) criteria and follows exercise-training principles (e.g., overload, progression or specificity principles).

Exercise Dose: The quantification of an exercise exposure by frequency, intensity, time/duration for a specific type of exercise (i.e., dose of an exercise bout) and procedures for implementing and regimenting exercise exposures over time in an exercise program derived from an exercise prescription inclusive of type, frequency, intensity, duration criteria and exercise principles (i.e., dose of an exercise program in terms of volume, pattern, and progression).

FITT Criteria: Frequency, intensity, time, and type of exercise (FITT) criteria following exercise-training principles (e.g., overload principle) used to establish an exercise prescription.

Medical Nutrition Interventions: Manipulation of the subject's nutritional intake for the purpose of modifying one or more health-related endpoints. This includes both interventions that take place within a clinical setting and those in free-living environments to include a wide variety of nutritional manipulations (e.g., intermittent fasting, ketogenic diets).

Patient-Reported Outcome: Any report of the status of a patient’s health condition that comes directly from the patient, without interpretation of the patient’s response by a clinician or anyone else.

Physical Activity: Any voluntary bodily movement produced by skeletal muscles that require energy expenditure that may occur during leisure time, for transport to get to and from places, or as part of a person's work.

Treatment-related Outcomes: Any physical, social, or psychological effect that impacts one's well-being that results from cancer treatments, rather than the natural course of the disease. Specifically, this FOA is focused on: dose interruptions, reductions, or delays; related healthcare utilization (e.g., hospital admissions, length of stay, or emergency department visits); and/or severe adverse events (e.g., CTCAE = 3, or dose-limiting toxicities or organ-specific toxicities) that occur during or in close proximity to cancer treatment for curative or life-extending intent.

Background

Despite advances in treatment, cancer survivors are at risk of morbidity and mortality due to their disease and treatment, which can be exasperated by lack of exercise, low physical fitness, obesity, and inadequate nutrition. Exercise and medical nutrition interventions may improve fitness and body composition, are generally well-tolerated, can be tailored to the individual needs of cancer survivors, and can be delivered concurrently with cancer therapies. However, most of the exercise and nutrition intervention research has focused on cancer prevention or survivorship well past cancer treatment, rather than the period shortly before or during treatment, and few studies have principally targeted treatment-related outcomes. Through this FOA, the NCI is soliciting research proposals to determine how exercise and/or medical nutrition interventions affect cancer treatment-related outcomes that occur in close proximity to cancer treatment.

Rationale for exercise and/or medical nutrition intervention in conjunction with cancer treatment

There is strong evidence that physical activity may reduce morbidity and mortality, and generally improve the health of cancer survivors. However, considerable variability in physiological response (e.g., fitness or strength improvement) to general physical activity exists indicating the importance of exercise prescription. Evidence is needed to understand the optimal type, frequency, intensity, duration, and overall volume (i.e., dose) of exercise to benefit treatment-related outcomes in cancer survivors. Specific health outcomes among cancer survivors receiving treatment may require a specific exercise prescription. For example, benefit for some outcomes may be seen at exercise levels below the Physical Activity Guidelines for Americans (PAG), whereas others require more vigorous exercise prescriptions that have been shown to improve mental health, fatigue, quality of life, physical functioning, and cardiorespiratory fitness (CRF). Strength training alone has been shown to improve cancer survivor's strength, quality of life, and preserve lean mass, and was the only exercise modality to benefit breast-cancer lymphedema outcomes. Strength training plus impact exercises (i.e., activity that generates greater ground reaction force), in contrast to walking, was the only approach to improve bone health. These data demonstrate that exercise prescription imparts specific effects on CRF, skeletal muscle, sensory-motor, as well as pleiotropic effects that may lead to improved cancer treatment-related outcomes.

Research is needed to identify the appropriate dose of exercise (delivered alone or in combination with diet intervention) and to test exercise prescription effects on treatment-related outcomes as a primary study aim across a variety of cancer sites to better understand exercise effects on cancer treatment outcomes. Mixed results have been observed among studies that have prospectively tested exercise effects on chemotherapy and radiation treatment tolerance. While none reported significant worsening of outcomes, very few studies reported statistically significant improvement. Pre-surgery exercise training reportedly improved lung function, decreased length of hospital stays, and reduced hospital costs in a study of lung cancer patients, but other studies reported null effects or only considered patient-reported outcomes. Research concerning cancer treatment-related outcomes in response to exercise has often entailed retrospective secondary analyses of cancer treatment data, lacked cancer treatment information, and has largely been confined to breast cancer. Additionally, while exercise prescription is generally considered safe, feasible, and effective to improve cancer survivors’ physical fitness, there is heterogeneity in fitness change across patients and in relation to cancer treatment. Exercise dosing studies may be needed to identify the minimally and optimally effective exercise dose that optimizes patient exercise adherence and fitness change.

There is also strong evidence that a variety of medical nutrition interventions alter cancer outcomes.
Medical nutrition interventions before treatment (i.e., “prehabilitation”), alone or combined with exercise, have been associated with improved presurgical functional capacity, lean body mass, and decreased length of hospital stay in patients undergoing colorectal surgery. Limited evidence in individuals undergoing cancer treatment also suggests that medical nutrition interventions may improve therapeutic efficacy or completion of planned treatment. Fasting-mimicking diets (FMD), such as intermittent fasting, in combination with chemotherapy, immunotherapy, or other treatments, have been associated with increased treatment efficacy, tolerability, and fewer toxicities. Preliminary data suggest that the combination of a ketogenic diet with chemotherapy may provide better treatment response in stage IV colon cancer patients compared to receiving chemotherapy alone, and there is growing evidence for ketogenic diets to improve outcomes in cancer survivors. Similarly, a high-fiber diet reportedly reduced gastrointestinal toxicity when compared to the usual diet in patients undergoing pelvic radiation, and another study found high grain consumption improved chemotherapy-induced peripheral neuropathy among women undergoing breast cancer treatment. Consumption of high-quality protein intake during 5-fluorouracil-based chemotherapy was found to reduce hematological and gastrointestinal toxicities and improve nutritional status, as well as lower treatment cost and length of hospital stay for colorectal cancer patients. Medical nutrition interventions to prevent and actively manage secondary causes of anorexia and target optimal dietary intake or weight maintenance have been shown to improve tolerance to cancer treatments, quality of life, and survival. However, additional research is needed as most of these studies were not randomized controlled trials (RCTs), had small sample sizes, and did not include diverse survivor populations.

Body size is affected by both exercise and nutrition. An important question facing overweight and obese cancer survivors is whether they should attempt to lose weight during treatment. The metabolic response to cancer is varied. Certain tumors (e.g., pancreatic, head and neck) are associated with poor nutritional status and thus, weight loss is not indicated. Whereas survivors of other cancers (e.g., early-stage breast) may benefit from weight maintenance/loss programs. Weight loss, due to the loss of skeletal muscle, and impaired physical performance, is associated with an unfavorable prognosis, increased treatment-related toxicities, dose reductions or interruptions, and reduced quality of life. Studies of intentional weight loss in these patient populations incorporating strategies (e.g., resistance exercise training and adequate protein intake) to ameliorate muscle loss and stimulate muscle protein synthesis are needed. Body composition (i.e., the amount of adipose and lean mass) is also important to understanding treatment-related outcomes. Lower muscle and/or greater adiposity is associated with chemotherapy dose delays and reductions. Chemotherapy is typically dosed according to body surface area (BSA), but there is substantial variation in body composition at a given BSA or body mass index (BMI), which in turn, can affect the distribution of chemotherapy agents and a patient’s ability to receive the full dose of chemotherapy. These dose delays and reductions may partially explain the associations of mortality with obesity and poor physical fitness and should be further explored.

National health promotion recommendations advise cancer survivors to consume a healthy diet and to remain physically active, yet they also highlight the need for further research during treatment. Clinical trials are needed to provide evidence for specific exercise and medical nutrition interventions that will improve specific treatment-related outcomes among cancer survivors and inform their use in clinical settings across cancer sites and treatment regimens.

Research Objectives, Scope, and Requirements for this FOA

Research Objectives of this FOA
The overarching goal of this clinical trial required FOA is to support the development and testing of exercise and/or medical nutrition interventions designed to improve cancer treatment-related outcomes for therapies delivered with curative or life-extending intent to cancer survivors, defined by NCI as individuals from the day of diagnosis until the end of life. Responsive applications will fill a research gap concerning the efficacy of specific exercise and medical nutrition approaches to improve cancer treatment-related outcomes in cancer survivors. Information gained should inform behavioral intervention protocols for cancer survivors and generate feasibility information concerning translation into clinical care. For the purposes of this FOA, cancer treatment-related outcomes include dose interruption or delays, related healthcare utilizations (e.g., unscheduled visits or length of hospital stay) and serious adverse events (e.g., CTCAE = 3, dose-limiting toxicities or organ-specific toxicities) that occur in close proximity to cancer treatment for curative or life-extending intent. Priority will be given to studies with direct clinical relevance and translational potential.

Cancer Treatment and Exercise/Medical Nutrition Intervention: Applicants must measure cancer treatment(s), including planned and delivered doses for all modalities (e.g., chemotherapy, radiation therapy, hormonal, or immunotherapy), as well as the reason for deviations from the planned course of treatment. Interventions with an exercise component must specify prescribed exercise (e.g., FITT criteria), use valid measures of exercise adherence, and document related exercise effects (e.g., change in CRF, strength, or function). Studies of nutritional factors may focus on dietary patterns, macronutrients, timing of intake (e.g., intermittent fasting), body composition, and/or weight control/maintenance and must use validated measures of diet that are appropriate for the population selected. Research participants must be enrolled in the trial shortly before or during treatment, but they may be followed beyond the conclusion of treatment as is relevant to the primary treatment-related endpoint. Studies in any age group and cancer type are appropriate for this FOA and populations of special interest include, but are not limited to, persons who are obese/overweight, persons of diverse socio-economic or ethnic or racial groups, persons who reside in medically underserved areas, or have otherwise been justified by the investigator as under-represented in cancer research involving exercise or medical nutrition intervention.

Body Composition: Regardless of the intervention approach and primary endpoint, all studies shall include measures of body composition, diet, and physical activity. Careful consideration of the patient population and the factors that are likely to affect adherence to exercise and medical nutrition interventions, as well as medication adherence, should be considered. The collection of additional information such as metabolic biomarkers, biomarkers indicative of enhanced therapeutic effect of cancer treatment, quality of life, physical symptoms and functioning, and data pertaining to other health behaviors (e.g., smoking, alcohol use, sleep) that may affect the ability to complete interventions are strongly encouraged.

Clinical Trial: Applications must use research designs that adhere to NIH’s definition of a clinical trial and must propose an exercise, medical nutrition, or combined nutrition-exercise approach. This FOA supports a development process for exercise and/or medical nutrition intervention that is analogous to translation in the biomedical sciences where exercise (or diet) dose-finding, multiphase optimization strategy, adaptive designs, or other early-phase studies may be required to identify minimal and optimal dose of exercise or diet to ultimately test their impact on cancer treatment-related outcomes. Applicants may propose a phased approach and conduct an initial intervention-development study (e.g., an exercise dose-finding study) to fully specify the exercise (or diet) intervention protocol, but for all applicants, the primary study must employ an appropriately powered NIH clinical trial design with a treatment-related outcome as the identified primary endpoint and include a patient-reported outcome as a secondary outcome.

Expertise and Additional Focus: It is anticipated that each award will support transdisciplinary teams of investigators with expertise in fields such as nutrition, exercise science, behavioral science, oncology, epidemiology, cancer biology, biostatistics, and other basic and clinical science disciplines to enable the specific aims to be addressed. Applicants may refer to animal models demonstrating biological mechanisms, but applications may only include human studies of cancer survivors. The biological mechanisms and tissue-specific biomarkers underlying how exercise and nutrition affect cancer treatment outcomes should be considered and may be included as additional outcomes. Since clinical exercise and medical nutrition protocols will be developed and tested across research sites in the FOA, collection of implementation cost or feasibility information from research participants and potential clinical staff are encouraged where possible.

Requirements for this FOA
Design, Analysis, and Sample Size for Studies to Evaluate Group-Based Interventions: Investigators who wish to evaluate the effect of an intervention on a health-related biomedical or behavioral outcome may propose a study in which (1) groups or clusters are assigned to study arms and individual observations are analyzed to evaluate the effect of the intervention, or (2) participants are assigned individually to study arms but receive at least some of their intervention in a real or virtual group or through a shared facilitator. Such studies may propose a parallel-group- or cluster-randomized trial, an individually randomized group-treatment trial, a stepped-wedge design, or a quasi-experimental version of one of these designs. In these studies, special methods may be warranted for analysis and sample size estimation. Applicants should show that their methods are appropriate given their plans for the assignment of participants and delivery of interventions. Additional information is available here.

To meet the research goals of this program, all research applications must:

  1. Use an exercise, medical nutrition, or a combined intervention approach, specify the knowledge gap addressed, and justify the cancer survivor population under study (e.g., age-group and cancer site) and biological plausibility of the intervention to affect the treatment-related outcome(s).
  2. Employ an appropriately powered NIH clinical trial design with a treatment-related outcome as the identified primary endpoint and include a patient-reported outcome as a secondary outcome.
  3. Enroll research participants in the trial shortly before or during treatment.
  4. Collect robust treatment data including planned and delivered dose and type for all cancer treatment modalities (e.g., surgery, chemotherapy, radiation therapy, hormonal or immunotherapy), and where appropriate, supportive care measures (e.g., anti-emetics).
  5. Use validated measures of body composition (e.g., creatine D3, CT scans, DXA), diet (e.g., standardized and comprehensive 24-hour recall methods), and general physical activity.

Additionally, applications incorporating an exercise component in the intervention approach are required to:

  1. Specify details of exercise prescriptions (e.g., FITT criteria) that are in addition to a general measure of physical activity.
  2. Include validated measures of prescribed exercise, exercise adherence, and exercise-related biomarkers (e.g., CRF, strength, functional status) relevant to treatment outcomes.

Specific Areas of Research Interest include but are not limited to, the following:

  • What is the minimally and optimally effective “dose” of exercise to mitigate organ-specific toxicity in cancer survivors receiving a specific therapy?
  • Does the structure of calorically equated aerobic exercise prescription (e.g., continuous moderate-intensity or high-intensity interval training) differentially affect CRF, exercise adherence, and completion and proximal efficacy of planned treatment in cancer survivors?
  • Does strength training alone or in combination with medical nutrition supplementation improve muscle quality, body composition, and completion of planned treatments in pediatric and adult cancer survivors?
  • Does a tailored weight loss intervention for overweight/obese cancer survivors that is designed to preserve muscle, improve completion of planned cancer treatments?
  • Does medical nutrition intervention during treatment minimize adverse treatment-related outcomes and treatment efficacy?
  • Does intermittent fasting around the time of chemotherapy improve the ability to deliver a planned course of treatment?
  • Does an exercise, medical nutrition, or a combined “prehabilitation” intervention delivered before treatment improve treatment tolerance and minimize adverse outcomes?
  • Does exercise and/or access to medical nutrition therapy improve immediate post-surgical outcomes, including length of hospital stay, emergency visits, and readmissions?

Governance ENICTO Consortium

The ENICTO consortium will be governed by an ENICTO Steering Committee (SC). The SC will oversee and coordinate cross-site activities of all awardees and the ENICTO Coordinating Center supported under RFA-CA-21-032. Details on the composition and functions of the SC are provided in Section VI. Award Administration Information, Terms and Conditions of Cooperative Agreement, “Areas of Joint Responsibility.”

Evaluation of the Consortium

Awardees will be required to participate in an external evaluation process of the ENICTO consortium coordinated by NCI Program Staff. The purpose of the evaluation process is to monitor and assess the performance of awardees in achieving the goals of this FOA. Criteria for the evaluation part will be developed by NCI Program Staff (as described in Section VI).

Non-responsive Applications

The following types of analyses are outside the scope of this FOA and applications describing them will be considered non-responsive:

  • Applications testing exercise and medical nutrition effects only on general measures or biomarkers of health.
  • Applications that fail to identify a treatment-related outcome as a primary endpoint and a patient-reported outcome as a secondary outcome.
  • Applications proposing to analyze only secondary data on cancer treatment-related outcomes collected as part of completed trials.
  • Applications proposing an exercise intervention trial, alone or in combination with medical nutrition, that only compares a general physical activity guideline (PAG) approach to a control condition. Trials may include a PAG approach in comparison to a fully articulated exercise prescription approach inclusive of FITT criteria.
  • Applications proposing an exercise intervention trial, alone or in combination with medical nutrition, using only self-reported aerobic physical activity are not appropriate for this FOA.
  • Applications proposing only animal model experiments.
  • Applications proposing clinical trial designs that do not initiate the trial before or during primary cancer treatment.

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

Section II. Award Information

Funding Instrument

Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this FOA.

Application Types Allowed
New

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.

Clinical Trial?

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

NCI Division of Cancer Control and Population Sciences intends to commit up to $5 million in FY 2022 to fund four to five awards.
Future year amounts are anticipated to be at the same levels but will ultimately depend on annual appropriations.

Award Budget

Application budgets may not exceed $875,000 in direct costs (excluding sub-award F&A costs) per year and must reflect the actual needs of the proposed project.

Award Project Period

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 FOA.

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

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)

Local 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)

Federal Governments

  • Eligible Agencies of the Federal Government
  • 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
Foreign Institutions

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

Required Registrations

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) – 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.
  • eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but 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 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.

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 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.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time.  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)

Each application must have a different PD/PI and distinct research team than an application submitted in response to RFA-CA-21-032 PD/PI.

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 FOA. 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 SF424 (R&R) Application Guide 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.

Letter of Intent

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

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

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

The letter of intent should be sent to:

Frank M. Perna, Ed.D., Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6782
Email: pernafm@mail.nih.gov

Page Limitations

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

Instructions for Application Submission

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.

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

SF424(R&R) Senior/Key Person Profile

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

R&R or Modular Budget

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

In addition, applicant budgets must include provisions for the following:

Restricted funds for Pilot Projects and collaborative studies. The requested budget must include $35,000 (in other direct costs) in years 2, 3, 4, and 5 for use in cross-site pilot projects and collaborative studies. The use of these restricted funds shall be determined by the ENICTO Steering Committee and as described in Section VI.2.

Costs of participating in meetings. Applicants should budget for the PD/PI and/or alternative designated representatives (in aggregate, up to 3 members of the research team) to attend annual face-to-face ENICTO investigator meetings in each project year.

Note: Capital equipment requests (for equipment over $5,000) are not allowed under this FOA.
 

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Specific Aims: Describe the specific aims for how the project conforms to the primary purpose of the FOA to test an exercise, medical nutrition, or a combined intervention approach to improve a treatment-related outcome as the primary endpoint and a patient-reported outcome as a secondary outcome. In addition, applicants must include a statement summarizing the unmet clinical need and the relevance of the work for translation into clinical care. In addition to specific aims, describe the major milestones to be met especially if applications include early phase work (e.g. if an exercise dosing study is conducted, what criteria must be met to select the final intervention protocol?).

Research Strategy: ?Applicants must organize the Research Strategy to include the subsection elements identified below. Applicants may include other sub-sections as needed but must include the information requested below.

Sub-section A. Background and Significance

  • Concise overview of relevant literature with respect to the intervention approach selected and cancer treatment-related endpoint targeted.
  • The background should include the physiological mechanistic rationale to justify the intervention approach as well as the behavioral science justifying the exercise and/or medical nutrition approach selected.
  • Applicants must identify the scientific gap addressed by the proposed project and describe the relevance of the proposed research to meet an unmet clinical need and the relevance of the work for translation into clinical care.
  • Highlight, as relevant, how the project can address the burden of cancer health disparities and the needs of racially/ethnically diverse populations and those from urban and rural areas who are poor and medically underserved, who continue to suffer disproportionately from certain cancers and have higher morbidity and mortality rates.

Sub-section B. Innovation

  • Describe how the project is innovative overall and if there are elements that are unique in their own right and/or if innovation derives from the combination of project elements.

Sub-section C. Preliminary Data

  • Summarize preliminary data supporting the intervention approach.
  • Summarize the preliminary data demonstrating collaboration across multiple disciplines involved in the project and especially:
    • Ability to recruit the proposed research participants;
    • Ability to collect the robust cancer treatment data required in this FOA; and
    • Experience in the collection of secondary outcome data required in this FOA.

Sub-section D. Approach
In addition to describing the methods to identify, recruit, and retain research participants and the method for protocol delivery, describe the plans to:

  • Collect cancer treatment data including planned and delivered dose and type for all cancer treatment modalities (e.g., surgery, chemotherapy, radiation therapy, hormonal or immunotherapy), and where appropriate, supportive care measures (e.g., anti-emetics).
  • Collect general and intervention-specific physical activity-related and nutrition-related measures. Applicants must include validated measures of body composition (e.g., creatine D3, CT scans, DXA), diet (e.g., standardized and comprehensive 24-hour recall methods), and general physical activity. For applications incorporating an exercise intervention component, the exercise prescription must be adequately detailed (e.g., FITT criteria) and include measures of exercise adherence and measurement of exercise-related biomarkers (e.g., CRF, strength, functional status) relevant to the treatment-related outcome.
  • Describe how the timeline for the specific aims and recruitment milestones are appropriate and include information on strategies that may be implemented if obstacles to the recruitment plan arise. If exercise or medical nutrition dosing studies are used or other early-phase study designs are employed in the project, describe steps to ensure the transition to the next phase occurs.
  • Pilot research projects: No specific projects are to be included in the application. Specific pilot projects will be solicited, evaluated, and selected by the ENICTO Steering Committee (Section VI.2 for additional information).

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.

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.
  • Data Sharing Plan should be consistent with accomplishing the goals of the ENICTO consortium as further described in section VI.2. Specifically,
    • Data Sharing Plan must acknowledge that all ENICTO awardees will be required to upload all of their data identified by the ENICTO Steering Committee as a common data element, and upon request from NCI Program staff, to the ENICTO Coordinating Center.
    • Data Sharing Plan must acknowledge that all ENICTO awardees will be required to upload all of their data from ENICTO Pilot Projects and collaborative projects, as approved by the ENICTO Steering Committee, to the ENICTO Coordinating Center.
    • Any data linked to clinical trials will be uploaded once the requirements of clinical trial restrictions and clauses such as de-identification of patients are satisfied.
  • Sharing Additional Resources: Consistent with achieving the goals of this program, all resources generated by the ENICTO awardees (e.g., standards and SOPs) will promptly become available through an ENICTO Coordinating Center resource. It is anticipated that other distribution avenues will be made available by the NCI if determined to be necessary.
  • Note that the NCI Program Staff may negotiate modifications to these plans prior to funding.
  • ENICTO Intellectual Property Policy: Consistent with achieving the goals of this program and maximizing the benefit of all research funded as part of the ENICTO program for the improvement of public health through discoveries of the scientific community, ENICTO Data Sharing and Data Release policies expect a broad freedom-to-operate for all users of ENICTO data (e.g., by rapidly placing all data in the public domain).
  • All applications should address commitment to share resources and data with other selected project sites for the purposes of pilot projects as described in section VI.2.
Appendix:
Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
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 SF424 (R&R) Application Guide, with the following additional instructions:

If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

PHS Assignment Request Form

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

3. Unique Entity Identifier and System for Award Management (SAM)

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

4. Submission Dates and Times

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.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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.

7. Other Submission Requirements and Information

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

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

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile 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 and responsiveness by the NCI. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process.  Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

For this particular announcement, note the following: The emphasis of this FOA is to support the collection of robust cancer treatment data, the collection of well-validated measures of exercise and physical activity, diet and body composition, and the development and testing of exercise and/or nutrition interventions designed to fill a research gap concerning the efficacy of these approaches to improve cancer treatment-related outcomes. Information gained should also improve behavioral intervention protocols for cancer survivors, beyond heuristics from general guidelines, and generate feasibility information concerning translation into clinical care. The application should be consistent with all of these requirements.

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

Overall Impact

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

Scored Review Criteria

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

Significance

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

Specific for this FOA:

How well does the project, if successful, contribute to optimizing exercise prescription and/or medical nutrition to improve cancer treatment-related outcomes among cancer survivors in the U.S. treated for curative or life-extending intent? How well does the information gained from the project also inform behavioral intervention protocols for cancer survivors and generate feasibility information concerning translation into clinical care?

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

Investigator(s)

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

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

Innovation

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

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

Approach

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

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

Specific for this FOA
How well does the project identify a treatment-related outcome, as defined in the FOA, as the primary endpoint and how well is the approach described and justified to address utility for translation into clinical care? How adequate is the description of the plan to collect cancer treatment data including planned and delivered dose and type for all cancer treatment modalities (e.g., surgery, chemotherapy, radiation therapy, hormonal or immunotherapy), and where appropriate, supportive care measures (e.g., anti-emetics)? How adequate is the description of the plan to collect validated measures of body composition (e.g., creatine D3, CT scans, DXA), diet (e.g., standardized and comprehensive 24-hour recall methods), and general physical activity? For applications incorporating an exercise intervention component, how adequate are the details of the exercise prescription (e.g., FITT criteria), and how appropriate are the inclusion of validated measures of exercise adherence and measurement of exercise-related biomarkers (e.g., CRF, strength, functional status) relevant to the treatment-related outcome?

Does the application adequately address the following, if applicable

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

Environment

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

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

Additional Review Criteria

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

Study Timeline

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following 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.

Biohazards

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

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

Additional Review Considerations

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

Applications from Foreign Organizations

Not Applicable.

Select Agent Research

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

Resource Sharing Plans

Reviewers will comment on whether the 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).

Authentication of Key Biological and/or Chemical Resources:

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

Budget and Period of Support

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

2. Review and Selection Process

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

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

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

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

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 submitted in response to this FOA. 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.

3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information

1. Award Notices

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

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

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.

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain “applicable clinical trials” on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities. 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 laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html.

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.

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

The following special terms of the award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) 2 CFR Part 200 Administrative Regulations, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, NIH Grants Policy Statement (which implements the aforementioned HHS Regulations (45 CFR Part 75), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility for the project as a whole resides with the awardees, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

  • Defining goals and objectives; determining research approaches and procedures; planning, developing and applying the intervention protocol; collecting and managing data; analyzing, interpreting and publishing results;
  • Implementing strategies for participant recruitment and retention and implementing procedures for exercise and/or nutrition protocol calibration and delivery;
  • Prioritizing and collaborating with the Steering Committee on the collection, standardization, and delivery of common data elements and procedures for cross-site analyses and investigation;
  • Ensuring that up-to-date detailed descriptions of outcomes will be made publicly available in the appropriate scientific outlets, project website, or group presentations and publications in a timely manner;
  • Attending one in-person meeting a year along with key co-investigators and participating in regular (approximately monthly and additional as needed) conference calls;
  • Providing an annual progress report and other information on study progress as might be needed;
  • Abiding by the Resource Sharing Plan, as appropriate, as well as specific procedures to be developed by the ENICTO Steering Committee;
  • Participating in ENICTO program-wide activities, such as presentations at national meetings and conferences; and
  • Participating in ENICTO program evaluation activities.

Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

NCI program staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards. The substantially involved NCI program staff member(s), acting as Project Scientist(s) will coordinate in a centralized fashion various activities of the awardees. Specific responsibilities of the NCI Project Scientist(s) will include, but will not be limited to, the following aspects:

  • May serve on cross-site special scientific interest groups and pilot projects;
  • Administratively manage the Steering Committee and monitor implementation of its guidelines and procedures;
  • Organize and conduct regular meetings to share progress by teleconference and/or videoconference as needed amongst the ENICTO awardees, in addition to an annual face-to-face meeting of all awardees;
  • Contribute scientifically and participate in analyses of cross-site pilot project data and publication efforts;
  • Assist the awardees by sharing information about a wide range of NCI and NIH resources and/or serve as a conduit to the potential utility and access to these resources;
  • Provide advice on other specific scientific and technical issues as needed by the awardees;
  • Serve as liaisons to other NCI scientific staff members if additional expertise or resources are needed;
  • Provide information about possible collaborative opportunities with relevant NCI sponsored networks, and other relevant government and non-governmental organizations doing related work;
  • Facilitate collaborative research efforts that can involve awardees as well as investigators from other NCI-related initiatives;
  • Monitor the progress of the ENICTO awardees and make recommendations on cross-site project directions and oversight of allocations of U01 funds set aside for pilot projects per NCI policy; and
  • Conduct periodic site visits of awardees and take other actions as needed.

Additionally, an NCI program director acting as Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

The ENICTO Steering Committee will serve as the initiative’s main governing board of the ENICTO program. The Committee will be jointly established by the PDs/PIs from each ENICTO-U01 awardee site, the PD/PI from the companion ENICTO-U24 Coordinating Center (PD/PI), and NCI designated Program Staff members. The ENICTO Steering Committee will provide strategic coordination for the cross-site activities.

Details on the composition, functions, and responsibilities of the ENICTO Steering Committee are following.

Voting members of the ENICTO Steering Committee will include:

  • One representative from each ENICTO-U01 awardee site;
  • One representative from the ENICTO-U24 Coordinating Center;
  • One representative from the NCI.

Non-Voting Members:

  • The ENICTO Steering Committee may decide to add non-voting members as needed, e.g., representatives from NCI-supported research resources, scientific experts and/or patient advocates.

The ENICTO Steering Committee will formulate strategic decisions and policies for consortium-wide activities. The ENICTO awardees will be required to accept and implement these decisions and policies to the extent consistent with applicable grant regulations. All Steering Committee decisions and recommendations that require voting will be based on a majority vote. The chair of the steering committee will be elected by the members and have a term of one year but can serve consecutive terms.

The responsibilities of the Steering Committee will include the following activities:

  • Steering Committee will formulate strategic decisions and policies for consortium-wide activities and procedures; ;
  • The Steering Committee may establish subcommittees to support specific purposes (e.g., scientific interest groups related to exercise, nutrition, and translational science; data harmonization; or pilot project publication committee);
  • Providing guidance to subcommittees to assist them in interpreting and adhering to Steering Committee establishedpolicies and procedures of the consortium;
  • Developing policies and procedures for projects across the consortium and also for projects seeking to use designated pilot project funds;
  • Formulating policies and procedures for data collection and harmonization as well as for common data elements;
  • Coordinating communication between the awardee-site teams, possible subcommittees, and cross-site pilot project teams;
  • Setting ENICTO publication policies and establishing recommendations/guidelines for elements to be included in publications reporting on cross-site projects and publications deriving from pilot project funds within the award;
  • Building consensus and coordinating the critical evaluation of disparate results;
  • Setting (in consultation with the other PD/PIs) the publication agenda and schedule;
  • Determining the location of the annual meetings and coordinating the organization of these meetings; and
  • Setting policies and procedures that may arise in the consortium for the implementation of professional enhancement opportunities for junior investigators.

Pilot Projects and Collaborative Activities:

The ENICTO-U01 awardees, ENICTO Coordinating Center, and NCI project scientists will be jointly responsible for participating in initiative-wide activities and for establishing cross-site project collaborations. These activities may involve PIs and co-investigators across ENICTO awardee sites and include, but are not limited to, the following:

  • Serving as a member of an appropriate ENICTO cross-site scientific interest group;
  • Participating in collaborative pilot projects approved by the Steering Committee, sharing information, as appropriate, about intervention protocols and assumptions at working group meetings; and
  • Consulting on strategies for participant recruitment and retention and providing information for dietary and exercise protocols and calibration that may benefit the ENICTO in whole and be useful to the wider scientific community.


Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.
 

3. Reporting

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

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.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period.  The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS).  This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313).  As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available.  Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 – Award Term and Conditions for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

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

Application Submission Contacts

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

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

Scientific/Research Contact(s)

Frank M. Perna, Ed.D., Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6782
Email: pernafm@mail.nih.gov

Peer Review Contact(s)

Referral Officer
National Cancer Institute (NCI)
Telephone: 240-276-6390
Email: ncirefof@dea.nci.nih.gov

Financial/Grants Management Contact(s)

Crystal Wolfrey
National Cancer Institute (NCI)
Telephone: 240-276-6277
Email: wolfreyc@mail.nih.gov

Section VIII. Other Information

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

Authority and Regulations

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.


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