Part 1. Overview Information

Key Dates

All applications are due by 5:00 PM local time of applicant organization. 

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

No late applications will be accepted for this Notice of Funding Opportunity (NOFO).

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts).

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

Applications that do not comply with these instructions may be delayed or not accepted for review.

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

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.

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Purpose

This Notice of Funding Opportunity (NOFO) invites applications for the reissuance of the Cancer Intervention and Surveillance Modeling Network (CISNET) (U01 Clinical Trial Not Allowed). The CISNET consortium uses simulation modeling to extend evidence provided by trial, epidemiologic, and surveillance data to guide public health research and priorities across the cancer continuum. The purpose of the NOFO is to expand and extend the work of CISNET systematically in specific priority areas where modeling can help optimize the translation of cancer research into practice.

The NOFO invites multiple-PI applications for collaborative research projects using simulation and other modeling techniques for specific cancer types. Each proposal should focus on one of the following ten cancer types: bladder, breast, cervix, colon/rectum, esophagus, gastric, multiple myeloma, lung, prostate and uterine. It is expected that a cancer-type specific proposal will be comprised of 2-6 independent modeling teams and one coordinating center. All applicants must have established models for the cancer type with a demonstrated history of comparative modeling among the modeling teams for the selected cancer type.

The NOFO is open to all qualified investigators as described below. Prior involvement in CISNET, while welcomed, is not required. Accordingly, proposed research is expected to reflect new projects and directions even for the current CISNET awardees.

Key Terms in this NOFO

Modeling: Modeling is defined as the use of simulation and mathematical techniques within a logical framework to integrate and synthesize known biological, epidemiological, clinical, behavioral, genetic, and/or economic information. De novo models are defined as ones which are developed from scratch, while modified models are ones that already have a history of development and are being extended, refined, merged with another existing modeling or reformulated using a more robust statistical and/or mathematical framework.

Modeling Group: A modeling group is defined as a team of researchers using a single model or a suite of interrelated model components for a single cancer type that is applicable to cancer control. A modeling group may include investigators from multiple institutions.

Cancer Type: Cancers of specific organs or systems on which the proposed application is focused. 

Background

There is a formidable gap between the rapid pace of biomedical innovation and our ability to harness it to improve population health. Today, that gap is particularly notable with respect to advances in the molecular and biological understanding of cancer, emerging technologies for cancer detection, novel treatments, and the challenges and opportunities they present. While biomedical advances have enabled the collection of health-related data, enormous challenges remain to integrate the information into optimal decision making tools for guiding cancer research and public health priorities. CISNET closes this gap by providing a suite of rigorously tested models to respond to emerging cancer control questions. CISNET research informs clinical practice and guidelines by synthesizing existing knowledge in a modeling framework under clearly specified assumptions. Modeling helps extend trial results beyond the limited regimens or eligibility criteria in any one study; estimate longer-term results from short-term studies and clarify the impact of interventions over the entire life course; estimate important but unobservable quantities (e.g., overdiagnosis); and disentangle conflicting trial results. Results like these are usually not directly observable, as they involve the preclinical “natural history” of disease, and many studies exclude key subgroups (e.g., the elderly) and rarely have enough follow-up time to reflect the full life course of individuals. CISNET models translate evidence from trials and epidemiological studies to the population setting by extrapolating beyond study protocols to the general population, accounting for patterns of care in less controlled settings. 

For more information on the current CISNET consortium, including its history, see: https://cisnet.cancer.gov/. 

Specific Objectives, Research Scope, and Requirements for this NOFO

General Requirements and Expectations

This NOFO encourages projects aligned with NCI priorities that translate cancer research into practice across the cancer control continuum. Applications should advance the practice of simulation modeling with the overarching goal of informing pressing decisions about cancer prevention and control.

Overall Characteristics of the CISNET Approach to Modeling: CISNET conducts comparative analyses using population-based models to answer critical questions informing patient care and use of technologies and services for cancer control. Distinguishing features of CISNET’s modeling capabilities and perspective include:

• Flexible broad-based disease models: CISNET models incorporate a central cancer model (usually including preclinical natural history), which can be modified by cancer control interventions (e.g., prevention, screening, treatment and surveillance regimens). The models can be readily adapted to characterize new technologies. Outputs can include the interventions' observable benefits, harms, and costs as well as unobservable quantities such as overdiagnosis and over-treatment of cancers.
• Multiple birth-cohort modeling: Modeling a hypothetical cohort often does not fully capture the intervention's impact or cost-effectiveness as implemented in a broad population. CISNET modeling captures a series of birth cohorts and shifting risk factor profiles, screening behaviors, and treatments used as each cohort ages, enabling complete representation of an intervention's impact in the U.S. or other populations of interest.
• Comparative modeling: All proposed projects must employ a comparative modeling approach with multiple models addressing the same research questions. While independent modeling often yields disparate results that are difficult to reconcile, a unique feature of CISNET is to use a comparative modeling approach that evaluates results from multiple models together, allowing for systematic investigation of differences and producing a range of results across models. Such a process brings additional transparency to the modeling process. Further, when consensus is achieved, this reproducibility strengthens the credibility. Situations where results across models are disparate can indicate evidence gaps and help generate new hypotheses about cancer natural history, for example, and guide further research. These highly desirable attributes are of fundamental importance in cancer control planning, guideline development and implementation decisions.
• Transparency in modeling and assumptions: The proposed projects must follow the implemented CISNET approaches to model documentation to accommodate audiences who have different objectives and technical familiarity with modeling.

For more information on these important characteristics of CISNET, please see: https://cisnet.cancer.gov/modeling/

Required attributes and areas of focus: The main attributes of CISNET projects include the following:

Models: Proposed modeling efforts must adhere to the approaches and characteristics of CISNET models described above. Most models should include a "natural history" component, modeling the initiation, growth, and metastatic spread of the tumor, relevant precursor lesions, and relevant biomarkers. Models without a natural history component can be included; however, the application must provide justification for their inclusion, including how they complement the suite of other models proposed. Investigators may propose the use, extension, refinement and/or merging of existing models, including extension or incorporation of a multi-scale model if well justified. If well justified, an existing model can be reformulated using a more robust statistical/mathematical framework. However, de novo model development will not be supported.

Cancer Types of Focus: Each proposed project must be limited to one of ten cancer types: bladder, breast, cervix, colon/rectum, esophagus, gastric, multiple myeloma, lung, prostate and uterine. Applications focused on other cancer types will be viewed as non-responsive and will not be reviewed. Applicants should also be aware that NCI's general intent is to fund one project per each "eligible" cancer type. Although individual applications must focus on a single cancer type, cross-cancer site work along certain themes (e.g., prevention, biomarkers, targeted therapy) or methods (e.g., model calibration, enablement of high-performance computing, clinical trial design and value of information) could be proposed. It is noted that cross-cancer site collaborations would be dependent on the other cancer types that are funded and their interests. Cross-cancer collaborations across different CISNET cancer site awardees are encouraged for pilot projects (using rapid response funds as noted below) although to be responsive to this NOFO, the vast majority of the proposed work must focus on a single cancer type.

Applicability to Public Health Issues and Comprehensive Coverage: The emphasis of the proposed research must be on the applied use of modeling approaches to important public health issues. Applicants for this NOFO are expected to propose collaborative, interactive projects involving groups of researchers that put forward a program of comparative modeling with coverage across the important cancer control issues and relevant specific focus areas for the selected cancer type.

External Collaborations and Outreach: To fully achieve CISNET's goals, proposed activities should emphasize not only the extension of models and their use but also the communication and translation of modeling results to users who may utilize the results for decision making. Accordingly, one of CISNET's core values is to make the cancer community aware of the modeling capacity and encourage collaborations. Applicants are strongly encouraged to establish scientific collaborations and partnerships and develop mechanisms for inviting new ones during the award period. Examples include:

• Outside modelers or other researchers with special expertise, who may be willing to join the collaborative activities as an “affiliate member”.
• Investigators who are involved with cancer-relevant clinical prevention, screening, or treatment, or trials and/or epidemiologic or observational studies.
• Guideline setting organizations/entities/government agencies.
• Professional societies.
• Patient, caregiver, and other relevant stakeholder organizations.

Targeted Priority Areas: There are nine specific priority research areas encompassing pressing evidence gaps across the cancer control continuum, from prevention through survivorship targeted by this NOFO. Each application should propose projects in as many of these areas as feasible and as relevant for the cancer type of interest. Applicants are not expected to address all priority areas but should select and justify those most pertinent. 

Area 1) Modeling to assist understanding of contributions of cancer control efforts to achieve goals and milestones such as those in the National Cancer Plan and Healthy People 2030. CISNET models provide rich and rigorous laboratories for asking and answering questions about the past and present to inform future cancer control efforts and evidence-based cancer control approaches. CISNET modeling differs from other forecasting methods, as these methods explicitly incorporate observable secular trends in cancer risk, natural history and interventions across the cancer spectrum. By changing assumptions, models can be used to make future predictions about whether and how future goals could be achieved under a range of options—from questions about prevention, screening, diagnosis, treatment, and surveillance to end-of-life care and what the population impact might be.

Area 2) Understanding past trends with a special emphasis on risk factors and downstream implications of the increasing incidence of early onset cancer. Modifiable risk factors like smoking, obesity, alcohol use, and HPV may contribute to up to 40% of all new cancers. Further, such factors have been suggested as potential drivers of recent increases in cancer incidence prior to age 50. Because they capture the underlying cancer natural history including the often long latency periods, CISNET models can be used to investigate hypotheses about trends, which helps focus biologic and epidemiologic research. Often underpinning this type of CISNET research are detailed “risk factor generators” developed by the investigators. Such generators, like the existing generators for smoking history and obesity, capture detailed birth cohort-specific lifetime trajectories of risk factors in individuals that together aggregate to replicate U.S. or other area population-level trends. These risk factor generators are used as common inputs into the cancer models. With new data and evidence, work to develop new generators for other risk factors like alcohol use or emerging trends like e-cigarettes, adding other dimensions to existing generators and modeling multiple risk factors together should be considered. Similar generators have also been developed to model the dissemination of new screening modalities and treatments in the population. There have been efforts to release these generators to the research community at large, and similar efforts to disseminate generators are encouraged.

Area 3) Evaluating the potential for emerging technologies in Artificial Intelligence (AI), liquid-biopsy, and biomarkers, or other technologies to improve precision prevention, screening and/or surveillance. Given the rapid dissemination of new technologies into practice, often prior to solid evidence about performance and effectiveness, understanding their potential impact early is critical for decision making about use. Modeling can evaluate the potential of technologies with established operating characteristics and ask also “what-if” questions about the necessary characteristics, costs, or other factors that a new technology, like an AI tool for cancer detection in radiologic imaging, would need to achieve to be incorporated into clinical practice. For example, blood-based tests may be more acceptable and thus increase uptake compared with traditional screening tests like colonoscopy. “What if” questions about operating characteristics should be well justified and bounded based on what is currently known about the technology. Analyses that proposed unconstrained explorations of the feasible parameter space are discouraged. Novel technologies for self-sampling or self-testing may have lower accuracy yet improve access and in turn, cancer outcomes. Modeling is uniquely suited to understanding the benefits and harms of such testing options and how they may compare with or complement current age and/or risk-based screening practices. Models can quantify the impact of compliance, estimate overdiagnosis, and project diagnostic burden and long-term mortality outcomes. 

Area 4) Opportunities for precision treatment and survivorship care. With new linkages between electronic health data and population-based cancer registry data, opportunities exist for more detailed modeling of cancer progression—including local and metastatic recurrence as well as cancer treatments, side effects and toxicities, downstream consequences, and the population-level impact. For example, modeling can help inform the design of multi-modal treatment strategies involving use of radiation, surgery, chemotherapies in neoadjuvant, adjuvant and metastatic settings by quantifying trade-offs in dimensions such as quality and length of life. Examining trade-offs from de-escalation of treatment is also of interest. Cost and economic considerations are other dimensions for decision making that modeling can incorporate. CISNET modeling can also inform trial design and conduct Value of Information (VOI) analyses that aid in prioritizing research needs. Further, given the estimated 18 million cancer survivors in the U.S. currently, modeling can be useful for assessing future care needs (including end-of-life). Survivors face lifelong health risks, such as treatment side effects and cancer recurrence, affecting both quality and quantity of life. Opportunities exist for modeling to inform other decisions such as workforce needs to care for survivors, assessment of overall cancer control progress accounting for quality of life and side effects as well as length of life, and evaluating surveillance strategies to monitor disease progression including imaging, liquid-biopsy and other biomarkers.

Area 5) Informing decisions about implementation and de-implementation of cancer control interventions and strategies in real-world settings across the cancer spectrum. Real-world effectiveness is often attenuated from efficacy observed in idealized study settings. Modeling informed by real-world data which accounts for local factors affecting both under- and overuse of appropriate care can help elucidate whether and how to adopt and/or scale a new intervention in different geographic areas, communities and care settings. Similarly, it can be used to understand the value of an existing intervention and whether de-implementation is merited. Examples of modeling analyses include how changing care delivery (e.g., adding nurse navigators) could facilitate adherence, improve follow-up, reduce delays and impact cost; how breakdowns in care processes could reduce effectiveness and increase cost; or how new screening or surveillance modalities could improve outcomes. Careful consideration of how models could be customized to model outcomes for different geographic settings or demographic subgroups is needed, as often the data needed to inform such work are sparse. Modelers must consider what parameters can and should be customized for each area, how the models can be validated.

Area 6) Designing strategies to improve outcomes in populations at risk across the cancer control continuum. CISNET models offer powerful platforms for exploring sources of differences in outcomes and designing cancer prevention, screening, treatment and survivorship strategies to efficiently and effectively improve them. Incorporating area-level context including geography and rurality into the models is encouraged.  

Area 7) Modeling as the information backbone for individual and population-level decision-making tools. Decision support tools can help inform patients and physicians about the potential harms and benefits of screening and treatment options and facilitate decision making based on individual values and preferences. Such tools tailored to an individual’s risk or clinical factors have been shown to be more effective than generic tools. CISNET modelers can partner with experts in shared decision making to embed models, model components or model results into tools for use by the public and/or health care professionals. CISNET model results can also be used to inform population-level tools that generate outcomes across relevant dimensions for evaluating cancer control programs considering specific care delivery settings, locations, and resource availability.

Area 8) Methods for complex model calibration, reporting of comparative modeling results, and other modeling methodology. CISNET modelers have been at the forefront in developing rigorous and reproducible modeling and calibration methods, yet challenges remain especially for improving computational algorithms and efficiency. For example, one complex step in model development and extension is the calibration of unobservable model parameters such that models can replicate observable phenomenon over time. Improvement of computational efficiency for CISNET models, their calibrations, and the analyses via use of high-performance computing platforms and related algorithms is also of interest. In addition, methodologic opportunities exist to enhance the synthesis and interpretation of comparative modeling results for decision makers, especially when reporting model or parameter uncertainty and differences in results across models. Applicants should keep in mind that CISNET is primarily focused on informing issues in cancer control, and all proposed methodology development should explicitly relate to this primary goal. Therefore, methods can be developed if directly motivated and justified by important issues in proposed modeling analyses and projects.

Area 9) Cancer-Type Specific Opportunities. Opportunities may exist for cancer-type specific modeling that are critical for that cancer type but may not fit into the eight areas above.

Organizational Structure and Coordination of Proposed CISNET Applications

Each proposal must have the following functional elements:

• Modeling groups (two to six groups per application). 
• Coordinating Center (one per application).

Other Expectations

• Leadership. To facilitate collaborative research and comparative modeling across the cancer control spectrum, applicants are required to designate multiple Program Directors/Principal Investigators (PDs/PIs), one of whom should be responsible for the Coordinating Center. In addition, it is generally expected that there will be a PD/PI for each modeling group, although other arrangements are also allowable with proper justification.
• Professional enhancement activities for junior investigators. In conducting research activities, applicants will be expected to actively plan for and create opportunities for junior investigators that will facilitate their professional development. Opportunities for mentorship, guidance and cross-site learning will be critical for junior investigators to gain exposure to the broad range of approaches to modeling across the consortium.
• Trans-network activities. All CISNET awardees will be expected to participate in cross-consortium activities. Examples include collaborative projects with other CISNET awardees of different cancer types (e.g., multi-cancer detection tests), working groups on common issues such as model accessibility, conflict of interest, and professional enhancement activities for junior investigators.

CISNET Governance and Advisory Committees

CISNET will be governed by a Consortium Steering Committee. For details, see Section VI.2. Cooperative Agreement Terms and Conditions of Award.

Cancer-type specific external advisory committees are suggested to consult on evolving areas of focus.

Non-Responsive Applications

Applicants are strongly encouraged to consult with scientific contacts to assure responsiveness to the NOFO prior to submission. The following types of research activities are outside the scope of this NOFO and will be considered non-responsive. Non-responsive applications will not be reviewed.

• Applications that do not focus on a single selected "eligible" cancer type.
• De novo development of models.
• Applications that focus on more than one cancer type. Research conducted for one cancer type (especially methods related work) may occasionally have cross-cancer applicability. Nevertheless, to be responsive to this NOFO, the vast majority of proposed work must focus on a single specified cancer type.
• Applications that do not use a comparative modeling approach.
• Applications that involve primary data collection.

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

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions - Includes all types

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

• 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
• Non-domestic (non-U.S.) Entities (Foreign Organizations)

Applications Involving the NIH Intramural Research Program

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. Intellectual property will be managed in accord with established policy of 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.

Foreign Organizations/International Collaborations

Non-domestic (non-U.S.) Entities (Foreign Organizations) are 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.

NIH will no longer issue awards (i.e., new, renewal, or non-competing continuation) to domestic or foreign entities that involve foreign subawards/subcontracts. All NIH-funded research involving foreign subawards/subcontracts must be submitted in response to a NOFO that is specifically designated for funded international collaborations. This new requirement was effective, May 1, 2025.

Applications involving foreign subawards/subcontracts submitted in response to this NOFO will be deemed noncompliant and will not be considered for funding. This policy applies to all monetary international collaborations resulting in foreign subawards/subcontracts, however, it does not preclude unfunded international collaborations or foreign components, funding for foreign consultants, or procurement of unique equipment or supplies from foreign vendors.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the How to Apply- Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information.

• System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
  • Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registrations; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov – Applicants must have an active SAM registration in order to complete the Grants.gov registration.

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

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

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the How to Apply-Application Guide.

For this NOFO, applicants are required to designate multiple PDs/PIs including at least one who is responsible for the Coordinating Center. Other PDs/PIs are expected to lead individual modeling groups. Alternative arrangements may be proposed if justified. For example, the Coordinating Center PD/PI does not have to be modeling group PD/PI, and additional PDs/PIs can be added for specialized aims.

It is suggested that the contact PD/PI be the Coordinating Center PD/PI and that the Coordinating Center be located at the institution submitting the application in response to this NOFO.

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1.2 Definition of Terms.

3. Additional Information on Eligibility

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, per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NIH Grants Policy Statement 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise (in this NOFO, in a policy notice, or other notice from NIH Guide for Grants and Contracts). 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.

Page Limitations

All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed.

For this NOFO, the Research Strategy section is limited to 30 pages.

The following section supplements the instructions found in the How to Apply- Application Guide and should be used for preparing an application to this NOFO.

SF424(R&R) Cover

All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the How to Apply- Application Guide must be followed.

SF424(R&R) Other Project Information

All instructions in the How to Apply- Application Guide must be followed.

Facilities & Other Resources: In addition to following the standard instructions:

• List the main characteristics of the research environment at the institutions of each modeling group that are relevant to the modeling activities; and
• List available high-performance computing facilities at the site for each modeling group and specify on what basis such resources will be available to the modeling group at that site (e.g. in-lab, freely available, fee-for-service).

The following additional materials must be included. Each attachment should be uploaded as a separate PDF using the indicated filenames. The Other Attachments files combined must not exceed 10 pages and are not counted against the 30-page limit for the Research Strategy section.

Attachment 1: Model Characteristics (use filename "Models"). Provide a table summarizing differences and similarities across the models. Table should use columns for models and rows for model characteristics such as key assumptions, structure, components, data used to parameterize/calibrate/validate, etc.

Attachment 2: Prior Modeling Analyses (use filename "Analyses"). Provide a table summarizing the prior modeling analyses. The table should use rows for prior model analyses and columns to describe important attributes such as model groups participating, key findings and related publications/products. Analyses can be clustered area of coverage in the cancer control continuum (e.g., prevention, screening, diagnosis, treatment, surveillance, end-of-life) as applicable.

Attachment 3: Proposed Modeling Projects (use filename "Projects"). Provide a table summarizing the modeling projects that are being proposed in applications responding to this funding announcement using rows for projects. Columns should indicate items such as the specific aim to be addressed, area of coverage (e.g., prevention, screening, diagnosis, treatment, surveillance, end-of-life) and/or priority area represented, modeling groups included, timeline, coordinator/project leaders, outside collaborators or key additional data resources as appropriate, etc.

SF424(R&R) Senior/Key Person Profile

All instructions in the How to Apply- Application Guide must be followed.

R&R or Modular Budget

All instructions in the How to Apply- Application Guide must be followed.

It is anticipated/expected that requested budgets will vary, depending on the scale of work and the number of modeling groups proposed. The budget request (direct costs) for the entire application per year must not exceed $570K, $750K, $950K, $1.15M and $1.24M for 2, 3, 4, 5, and 6 (or more) modeling groups, respectively.

The PI level of effort must comply with requirements described in NOT-CA-21-096. 

Budget Justification Section. In the budget justification section, applicants should break out the time commitment and responsibilities of each individual (in particular, for the PDs/PIs) involved with respect to modeling and Coordinating Center activities.

The budget justification section should include the approximate direct costs for:

• The Coordinating Center.
• Each modeling group. 
• Rapid response funds.

Coordinating Center. The budget allocation for the Coordinating Center should generally not exceed $110K direct costs per year. 

Modeling Groups. Budget allocations for individual modeling groups should generally not exceed $180K direct costs per year and collectively the sum must not exceed the direct cost caps noted above based on the number of modeling groups to be included. For applications with 6 or more modeling groups, the budget allocations for the modeling groups will need to be adjusted to meet the overall direct cost cap. Further, for all applications, it is expected that budget allocations for the modeling groups with specialized focus and/or limited participation in aims including leadership roles should be substantially smaller. In exceptional situations, budget allocations for a particularly complex modeling group could be slightly larger if well justified. For example, this extra amount would include specialized expertise needed to address some of the priority areas (e.g., decision aid development, implementation science), and junior modelers. Persons with specialized expertise in one modeling group would generally be expected to be shared across the groups as needed. To be included, a modeling group must have demonstrated evidence of prior collaborative modeling with the other groups included in the application. 

"Rapid Response" Funds. Applicants must budget for special funds that will be used for support of post-award projects/activities developed to address emerging opportunities. The amount allocated to these "rapid response" funds should be based on the number of modeling groups per application and generally should not exceed $100K, $120K, and $140K direct costs per year for 3 or fewer, 4, and 5 or more modeling groups, respectively. Further, it is expected that approximately $30K, $35K, and $40K of this amount for applications with 3 or fewer, 4, and 5 or more modeling groups, respectively, will be designated for projects providing professional enhancement activities for junior investigators within the cancer site and across the consortium. These funds should be presented in the Other Direct Costs category under the heading “Rapid Response Funds”. Funds will be activated following discussion and approval of proposed projects by the respective Cancer-Type Leadership Group.

Travel. Applicants must budget travel funds for up to three persons per modeling group to participate in two consortium meetings per year, including: (1) an annual meeting and (2) a mid-year meeting. The structure of both includes approximately 2 days for a cancer-type specific meeting and a full day for a cross-cancer plenary session. The mid-year meeting is at one of the modeling groups' home institutions, selected on a rotating basis, and that group is expected to host the meeting, providing administrative support and information about on-campus meeting rooms and other local details. Since the mid-year meetings are generally held at a common location to facilitate modelers who are part of more than one cancer type, each application should budget for additional administrative support to host one meeting during the five-year award period.

R&R Subaward Budget

All instructions in the How to Apply - Application Guide must be followed.

PHS 398 Cover Page Supplement

All instructions in the How to Apply - Application Guide must be followed.

PHS 398 Research Plan

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

Specific Aims: Describe the specific objectives and aims of the proposal (generally 4-6 aims are expected). Indicate how the proposed aims correspond to the priority areas.  

Research Strategy: Research Strategy must consist of the following sub-sections:

Sub-section A. Overall Objectives and Significance.

Sub-section B. Project Leadership and Coordination, Rapid Response and Professional Enhancement, and Advisory Committee.

Sub-section C. Modeling Groups, Their Models, and Previous Modeling Projects.

Sub-section D. Proposed Model Extensions, Analyses and Comparative Modeling Activities.

See detailed instructions below for the content of these sub-sections.

Sub-section A. Overall Objectives and Significance:

Describe the background leading to the proposed specific aims, critically evaluating existing knowledge, and specifically identifying the gaps in evidence and knowledge that the project overall and the aims specifically are intended to fill. In addition, this sub-section should include the following:

• The overarching objectives and goals of the specific research proposed. 
• The importance and health relevance of the proposed research. Highlight innovations and the potential impact of both the modeling analyses and the methods.
• Describe how scientific knowledge, public health guidelines, and/or clinical practice will be advanced if the specific aims and objectives are achieved.
• Provide a rationale for choice of selected priority areas to be addressed for the cancer site in terms of gaps, available evidence and impact and why comparative modeling is well suited to fill the gaps.
• Introduce the participating modeling groups (including models and institutions) to be included.

Sub-Section B. Project Leadership and Coordination, Rapid Response and Professional Enhancement, and Advisory Committee:

This section should describe how the activities across the modeling groups within the cancer site and across CISNET will be integrated and coordinated. 

B.1 Project Leadership and Coordination. Each application must include a Coordinating Center and a Coordinating Center PD/PI. The Cancer Site Leadership Team may be comprised of all the PDs/PIs and/or model group or topic leads depending on organizational structure. Applicants must describe their plan for the following activities:

• Formulating, prioritizing, and coordinating work on joint comparative modeling projects and other research questions including outside requests with new funding opportunities.
• Acting as the point of contact for the cancer site for new external cancer control and surveillance questions and inquires.
• Coordinating review of new and relevant literature and issues relevant for the cancer site.
• Negotiating common requests for outside data sources.
• Preparing inputs and collecting and processing common outputs for model comparisons.
• Coordinating collaborative papers and other group analyses including responses to scientific inquires.
• Consensus building and coordinating critical evaluation of disparate results.
• Vetting of proposed affiliate members and prioritizing the use of rapid response funds.
• Organizing conference calls, setting meeting agendas and inviting meeting guests.

Although the Coordinating Center will provide oversight, it is expected that certain coordination activities will be distributed across the leadership team and modeling groups. For example, if there is a collaborative modeling activity among a subset of modeling groups, coordination of that work might be done by one modeling group rather than through the Coordinating Center. If a meeting is held at a particular investigator's institution, they would be responsible for making local arrangements. Local specialized expertise included in one group (e.g., specific clinical, methodological or topical expertise) might be shared across the group. Even though there is one Coordinating Center, it is expected that decision making will be conducted through consensus across the leadership team that includes the modeling groups.

B2. Rapid Response and Professional Enhancement. Outline plans and processes for projects that will use the rapid response funds, listing examples of anticipated activities (e.g., plans for professional enhancement activities for junior investigators, collaboration with external researchers regarding anticipated clinical trial results). Address aspects such as:

• How the anticipated activities will enhance the specific aims of the proposal, recognizing that rapid response projects will be smaller in scale.
• The expertise needed including access to data sources, and how the funds will be allocated to modeling groups.
• How the projects will contribute to professional enhancement activities for junior investigators at the doctoral, post-doctoral, or junior faculty levels within the cancer site and across the consortium. This may include special lectures and webinars, mini meetings coordinated by junior investigators in conjunction with the annual or mid-year meetings, a program to learn methods or techniques from other modeling groups or cancer sites, a program for funding projects for junior investigators, etc. It is expected that representatives from each awarded application will form a central working group across CISNET to determine which professional enhancement activities would be feasible and most productive under the anticipated budgets, and then implement them.  
• How these activities will expose junior investigators to situations that will test and improve their skills and leadership abilities, provide enhanced opportunities for professional growth, and create an atmosphere and setting that is conducive to learning.
• How the Coordinating Center will coordinate project development and selection. The plans should assume that ultimate decisions about the use of rapid response funds will involve a consensus process through the Coordinating Center and leadership team.

B.3 Advisory Committee (optional). An external committee to advise the CISNET team on evolving areas of focus is strongly encouraged. If such a committee is considered, outline the anticipated range of expertise and stakeholder interests. Explain how input will be solicited from the Advisory Committee (ad hoc, regular teleconferences, etc.). Do NOT provide names of prospective members and do NOT contact such individuals prior to review.

Sub-Section C. Modeling Groups, Their Models, and Previous Modeling Projects:

Modeling Groups

Applicants should carefully consider the modeling groups to include. To be included, each modeling group must have demonstrated productive comparative modeling experience leading and/or collaborating with other models included in the application. Explain how the modeling groups will collectively be able to conduct proposed comparative modeling with respect to important cancer control issues and relevant priority areas for the selected cancer type. Applicants are expected to present a coherent and well-conceived plan that will permit the group work to proceed efficiently. Justify the number and types of modeling groups proposed by addressing issues such as:

• The optimal number of groups needed to conduct comparative modeling across the range of relevant topics for the cancer type.
• The expected roles of individual modeling groups and their contributions to collectively achieve a reasonable coverage of issues relevant to the cancer type across the cancer control spectrum.
• Identify comprehensive, "full-fledged" modeling groups that are expected to participate in the full range of work across the cancer control spectrum, and possibly also smaller, narrowly specialized modeling groups that may be involved in a limited range of activities.
• Characterize the proposed groups in terms of providing conceptual and structural differences in modeling approaches as well as a wide range of approaches expected to enhance comparative modeling.
• Summarize the accomplishments of each modeling group and joint accomplishments. If more than six groups are planned, also provide appropriate justification (e.g., some groups may play only a limited role and/or an extra group is essential to provide a unique perspective).

Models and Prior Modeling Projects

• Give an overview of each model, summarizing clearly underlying model structures and assumptions. In particular, briefly describe the natural history component (expected for most models), including initiation, growth, and metastatic spread of the cancer, as well as relevant precursor lesions and biomarkers and other distinguishing model components.
• If a model without a natural history component is included, briefly describe and justify how it complements the suite of models proposed.
• Explain how the models complement each other in terms of different modeling perspectives or ways of synthesizing available evidence.
• Describe the breadth and depth of prior modeling analyses and publications including comparative modeling work.

Note: Supplementary information for this sub-section is requested under "Other Attachments" (Attachments 1 and 2).

Sub-Section D. Proposed Model Extensions, Analyses and Comparative Modeling Activities:

Provide a coordinated analysis plan for the proposed modeling projects to address the specific aims. It is expected that the set of projects will provide comprehensive coverage of the cancer site specific relevant issues across the cancer control spectrum (i.e., prevention, screening, diagnosis, treatment, surveillance, and end-of-life care) amenable to modeling. The analysis plan should cover the modeling projects related to current issues facing the cancer type as well as anticipated emerging issues that will become more important or will become amenable to modeling during the course of the project (for example, the anticipated release of results from a major trial and/or other relevant study results). Outline proposed modeling projects and their potential and significance in terms of substantial cancer control opportunities and expected impact on population health. Consideration should also be given to the ability to scale up to take on new projects when additional funding or collaborative opportunities arise. Plans should include the following considerations: 

• Justify number and choice of models. Not all modeling groups are expected to cover the full cancer control spectrum, and not all portions of the spectrum are equally applicable, or of current critical interest, for all cancer sites. Limited availability of data and studies for certain cancers may limit the ability to include certain areas. Efforts in specific areas should be commensurate with the potential of emerging findings in that area to ameliorate morbidity and mortality from the disease.
• As applicable, indicate the corresponding priority area(s). Note: If a modeling method is proposed, additional justification is required. The emphasis must be on applied use of models to important public health issues including (but not limited to) the priority areas stated in this announcement.
• Describe any model extensions, additional model calibration, and/or validation necessary. If well justified, an existing model can be reformulated using a more robust statistical/mathematical framework. 
• Provide background information such as data resources or evidence available to support the analysis. Include development of shared common inputs for models. For projects examining emerging interventions, “what if” analyses can be conducted especially in the context of informing regulatory or other decision making about key parameters such as the operating characteristics of the intervention. However, technologies should be sufficiently well understood that plausible and justifiable assumptions can be made wherever possible (e.g., pure “guesses” should be minimized and justified). 
• Indicate whether the analysis will be a collaborative modeling exercise involving all modeling teams (a “base case”), among a subset of the models (a "mini-base case"), or it will be sufficient for a single modeling group to conduct the analysis. 
• Outline key endpoints, analysis methods, synthesis of modeling results, etc.
• Describe plans to disseminate and effectively communicate the results of modeling to planners and decision makers in the cancer community. This may include development of user interfaces or websites as applicable for target audiences.
• Indicate collaborations with outside experts or groups as relevant. 

Note: Supplementary information for this sub-section is requested under "Other Attachments" (Attachment 3).

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply - Application Guide.

All applicants must also include a “Model Accessibility Plan” that details activities designed to promote the transparency and utility of the CISNET models to wider audiences. Note: This section is not included in Peer Review. NCI Program Staff will oversee review and approval prior to award. 

Guidance for a Model Accessibility Plan:

• NCI is committed to maximizing the transparency and accessibility of cancer control research and methods. In the context of CISNET modeling, model accessibility includes the transparency and accessibility of models as well as modeling results with the goal of maximizing the dissemination and utility of model inputs, assumptions, code, runs, and results including components such as risk factor or other common input generators for use by the scientific community. 
• It is acknowledged that methods and standards for model accessibility are evolving and at present, there are no currently accepted universal standards for the release and accessibility of complex computer simulation models like those in CISNET. While each applicant should put forward a plan for model accessibility for their cancer type, there will be a cross-CISNET working group on this topic to support implementation and determine best practices. The goal of the working group will be to develop consensus and support the use of common formats and standards across CISNET models and cancer sites wherever possible. It is expected that a cancer type-specific plan for model accessibility may therefore evolve and expand based on cross-CISNET discussions and/or as new standards or methods for model accessibility are developed. 
• The plan must address model accessibility for the following three internal and external audiences: 1) those who wish to better understand or interpret model results, 2) those who may wish to explore model results or conclusions beyond what has been published in a manuscript, and 3) those who wish to conduct their own tailored analyses.
• New and expanded approaches are encouraged. Current approaches include the following:
  • Enhanced technical documentation of model code and parameters including use cases that document strengths and limitations of the models, parameters and their results. Note: Up-to-date Model Profiles and other documentation such as that through the public CISNET Model Registry are required.
  • Provision for public release of model executables with selected parameter sets, “limited model interfaces” or other tools that allow users to interact with the models in predefined ways.  
  • Active solicitation of inquiries and engagement in new collaborations from those outside of CISNET to pose questions or scenarios amenable to modeling which could be supported through rapid response funds, funds from the individual or organization posing the research question, or other funding avenues.
  • Development of “Model Use Agreements” (akin to Data Use Agreements) and/or software licensing options that allow for sharing and use of models and/or their components, including generators for risk factors or other common parameters. Such agreements could specify predefined limited purposes or analyses.
• Multiple approaches can be proposed for each audience. Recognizing that any approach has its own distinct purpose as well as strengths, limitations and costs, the plan should include justification for selection of approach(es) for each audience. Further, each activity should include documentation appropriate for the audience that describes the purpose, intended uses (including potential misuse such as use beyond the defined scope) and foreseeable limitations of the model and/or model results. 
• As a whole, the approaches and activities selected for the plan must significantly expand upon the current state of model accessibility activities for the cancer site.
• All plans should be well justified and must include specific goals, timeline for implementation and milestones to achieve completion of the plan within the 5 year grant award period. While individual modeling groups may go beyond, all modeling groups within the cancer site are expected to meet the goals of the plan. Plans should not exceed 3 pages.
• The plan should also address issues of reproducibility including model versioning and model evaluation/validation.

Note: While transparency and dissemination of model inputs/outputs are linked to model accessibility, specific plans for the management and sharing of model input parameters and model outputs/modeling analysis results including documentation and protocols should be covered in the Data Management and Sharing Plan.

 Other Plan(s): 

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.

Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply - Application Guide.

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

PHS Human Subjects and Clinical Trials Information

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the How to Apply - Application Guide must be followed.

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 How to Apply- Application Guide must be followed.

PHS Assignment Request Form

All instructions in the How to Apply- Application Guide must be followed.

Foreign Organizations

Foreign (non-U.S.) organizations must follow policies described in the NIH Grants Policy Statement, and procedures for foreign organizations described throughout the How to Apply- Application Guide.

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

See Part 2. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

4. Submission Dates and Times

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

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time.  If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

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

Information on the submission process and a definition of on-time submission are provided in the How to Apply-Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

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 Section 7.9.1 Selected Items of Cost.

Applications must be submitted electronically following the instructions described in the How to Apply Application Guide. Paper applications will not be accepted.

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

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

Important reminders:

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

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the How to Apply 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 components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed. 

Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. See Mandatory Disclosures, 2 CFR 200.113 and NIH Grants Policy Statement Section 4.1.35.

Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at grantdisclosures@oig.hhs.gov.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described 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 NOFO is on research that uses a rigorous comparative simulation modeling approach to address the major cancer control issues, for which there is an opportunity to make a public health impact for a given cancer site. The strength of each application will be judged on the various dimensions described above in the Research Strategy section and, recognizing that no application is likely to be strong on every dimension, the various trade-offs involved will be considered.

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 scored review criteria and additional review criteria (as applicable for the project proposed). An application does not need to be strong in all categories to be judged likely to have a major scientific impact.

Reviewers will consider Factors 1, 2 and 3 in the determination of scientific merit, and in providing an overall impact score. In addition, Factors 1 and 2 will each receive a separate factor score. 

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

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.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s), convened by CSR, 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.

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

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. Following initial peer review, recommended applications will receive a second level of review by the National Cancer Advisory 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. Programmatic priority will be to ensure that all awards collectively provide optimal coverage across cancer types. Therefore, it is anticipated that there will be no more than one award per cancer type.

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 Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.

Prior to making an award, NIH reviews an applicant’s federal award history in SAM.gov to ensure sound business practices. An applicant can review and comment on any information in the Responsibility/Qualification records available in SAM.gov. NIH will consider any comments by the applicant in the Responsibility/Qualification records in SAM.gov to ascertain the applicant’s integrity, business ethics, and performance record of managing Federal awards per 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

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 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

A Notice of Award (NoA) is the official authorizing document notifying the applicant that an award has been made and that funds may be requested from the designated HHS payment system or office. The NoA is signed by the Grants Management Officer and emailed to the recipient’s business official.

In accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Any pre-award costs incurred before receipt of the NoA are at the applicant's own risk.  For more information on the Notice of Award, please refer to the NIH Grants Policy Statement Section 5. The Notice of Award and NIH Grants & Funding website, see Award Process.

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

2. Administrative and National Policy Requirements

The following Federal wide and HHS-specific policy requirements apply to awards funded through NIH:

• The rules listed at 2 CFR Part 200, Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.
• All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the terms and conditions in the Notice of Award (NoA). The NoA includes the requirements of this NOFO. 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.

All federal statutes and regulations relevant to federal financial assistance, including those highlighted in NIH Grants Policy Statement Section 4 Public Policy Requirements, Objectives and Other Appropriation Mandates.

Applicants and recipients are strongly encouraged to refer to the NIH Director’s Statement of Priorities, entitled “Advancing NIH’s Mission Through a Unified Strategy.” 

Recipients are responsible for ensuring that their activities comply with all applicable federal regulations. Pursuant to 2 CFR 200.340, by accepting an NIH award, the recipient agrees that continued funding for the award is contingent upon the availability of appropriated funds, recipient satisfactory performance, compliance with the Terms and Conditions of the award, and may also otherwise be terminated, to the extent authorized by law, if the agency determines that the award no longer effectuates the program goals or agency priorities, in line with 2 CFR 200.340(a)(4).

Pursuant to the Cybersecurity Act of 2015, Div. N, § 405, Pub. Law 114-113, 6 USC § 1533(d), the HHS Secretary has established a common set of voluntary, consensus-based, and industry-led guidelines, best practices, methodologies, procedures, and processes.

Successful recipients under this NOFO agree that:

When recipients, subrecipients, or third-party entities have:

1. ongoing and consistent access to HHS owned or operated information or operational technology systems; and 
2. receive, maintain, transmit, store, access, exchange, process, or utilize personal identifiable information (PII) or personal health information (PHI) obtained from the awarding HHS agency for the purposes of executing the award.

Recipients shall develop plans and procedures, modeled after the NIST Cybersecurity framework, to protect HHS systems and data. Please refer to NIH Post-Award Monitoring and Reporting for additional information. 

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75 and 2 CFR 200, 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 recipients 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 resides with the recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and the NIH as defined below.

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

• Determining research approaches and procedures, developing and applying their models, and analyzing/interpreting results and publishing their results.
• Serving as a member of the Cancer-Type Specific Leadership Team. The Coordinating Center PD/PI also serves as a voting member on the CISNET Steering Committee and the chair of the Cancer-Type Specific Leadership Team.
• Collaborating on research including modeling activities, sharing information, as appropriate, about model structure and assumptions at working groups meetings, as well as strategies and data resources for parameter estimation, calibration and validation.
• Ensuring that up-to-date detailed descriptions of models are made publicly available in a timely manner through the Model Profiles and model registry portions (and any other common model documentation approved by the CISNET Steering Committee) of the CISNET public website.
• Abiding by the Model Accessibility Plans and by policies and procedures developed by the Coordinating Center for their award, as well as policies and procedures as developed for the entire Consortium by the CISNET Steering Committee to the extent the decisions are consistent with the terms and conditions of the grant award and applicable grant regulations. Awardees are expected to harmonize procedures at their Coordinating Centers with those established by the Steering Committee.
• With all other key PD(s)/PI(s) co-investigators and key co-investigators, attending two in-person meetings a year along and participating in regular conference calls. One meeting will be in the Washington DC area, and the second meeting at one of the PD/PI's home institutions. If their institution is selected, that PD/PI is expected to assist in hosting the meeting by helping to find on campus meeting space and providing administrative assistance to help the NCI organize the meeting and to provide support during the meeting.
• Providing an annual progress report and other information on study progress as might be needed.
• Working cooperatively with the contractor who maintains the common model documentation and the members-only interactive website.
• Approving cancer-type specific affiliate members (groups funded elsewhere but who are interested in joining the collaboration).
• Participating in program-wide activities, such as the model accessibility, conflict of interest, and professional enhancement working groups.

In addition, the rights and responsibilities of the Coordinating Center PDs/PIs include the following:

• Serving as a voting member on the CISNET Steering Committee and the chair of the Cancer-Type Specific Leadership Team.
• Coordinating communications, conference calls and meetings including agenda setting for the cancer site.
• Formulating goals, prioritizing, and coordinating work on base case and other questions.
• Setting (in consultation with the other PDs/PIs for the cancer type) the publication agenda and schedule.
• Negotiating common requests for outside data sources.
• Building consensus and coordinating critical evaluation of disparate results.
• Preparing inputs and collecting and processing common outputs for model comparisons or delegating that responsibility for specific modeling projects.
• Coordinating synthesis papers and group responses.
• Fielding outside requests and working with the modeling groups to determine priorities.
• Coordinating the preparation of the annual progress and mid-year reports by the individual PDs/PIs for the cancer type.
• Coordinating use and allocation of rapid response funds.
• Maintaining a set of policies and procedures within the cancer-type specific group that are in compliance with the procedures and policies of the CISNET Steering Committee.
• Following, to the extent consistent with Grant Regulations, the overall Consortium policies and procedures established by CISNET Steering Committee.

Recipients 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. 

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below: 

• An NCI Program staff member will be designated as the NCI Overall Project Scientist for CISNET. The individual will serve as a voting member for NCI on the CISNET Consortium Steering Committee.
• The NCI will also designate NCI Project Scientists for each of the cancer sites. These cancer-type specific coordinators will be voting members of the Cancer-Type Specific Leadership Teams, along with the PDs/PIs from that cancer type, and any other members as designated by consensus of the cancer-type specific steering subcommittee.
• The NCI Project Scientists will have access to all modeling results generated under this award consistent with current HHS, PHS, and NIH policies.
• The NCI Project Scientists will contribute scientifically to the process of model applications and will have opportunities to participate in analyses of model results and publication efforts of the CISNET Consortium.
• The NCI Project Scientists will assist the awardees by sharing information about a wide range of data resources that can be used for parameter estimation and population trends in modeling and/or serve as a conduit to access these resources as is feasible.
• The NCI Project Scientists will provide advice on other specific scientific and technical issues as needed to the Consortium.
• The NCI Project Scientists will serve as liaisons to other NCI scientific staff members if additional expertise or resources are needed.
• The NCI Project Scientists will provide information about possible collaborative opportunities with relevant NCI-sponsored consortia, and other relevant government and non-governmental organizations doing related work.
• NCI will maintain a website for internal use by CISNET investigators. This website will be a communications portal for internal sharing of analysis plans, inputs, data sets, and model documentation.
• NCI will maintain a public website for the CISNET Consortium. NCI Project Scientists will work with the PDs/PIs to create content on topics such as new publications of interest and help maintain CISNET public resources for model accessibility including the CISNET model registry, model profiles, limited model interfaces, etc.
• NCI, in consultation with the Coordinating Center PDs/PIs, will set the location of the two annual meetings, and will coordinate the organization of these meetings. Generally, one meeting per year will be at the NCI, and a second meeting will be hosted at one of the participating institutions. NCI will provide support for the annual and mid-year meetings.
• Additionally, an agency program official or IC administrative program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. 

The substantially involved NCI Project Scientists will not attend peer review meetings of renewal (competing continuation) and/or supplemental applications. If such participation is deemed essential, these individuals will seek NCI waiver according to the NCI procedures for management of conflict of interest.

The NCI reserves the right to reduce the budget or withhold an award in the event of substantial awardee underperformance.

 Areas of Joint Responsibility include:

• The Steering Committee will serve as the CISNET main governing board. The Steering Committee will consist of the following voting members: the Coordinating Center PDs/PIs from each CISNET award and the NCI Overall Project Scientist. Other individuals may be invited on an ad-hoc basis as non-voting members. Steering Committee will meet 4 times per year or more frequently if needed.
• Responsibilities of the Steering Committee will include the following activities:
  • Setting overall consortium policies and procedures.
    • Providing guidance to Cancer-Type Specific Leadership Teams and other subcommittees or working groups to assist them in interpreting and adhering to consortium policies and procedures.
    • Establishing and providing oversight for standing and ad-hoc subcommittees and working groups.
      • NCI Project Scientists and Coordinators may serve on such subcommittees, as appropriate. Other NCI staff members may also be involved as needed.
      • Standing subcommittees and working groups include:
        • Cancer-Type Specific Leadership Teams will consist of the PDs/PIs from that cancer type, the NCI Project Scientist for that cancer type, and any other members as designated by consensus of the cancer-type specific leadership team. These leadership teams are chaired by Coordinating Center PDs/PIs, and the role of this subcommittee is to work with the chair and advise and assist in the chair's responsibilities and duties as described above.
        • Model Accessibility Working Group will support model accessibility activities across CISNET. There may be some activities taken up by an individual model, or a specific cancer type group, but the purpose of this group will be to convene cross-CISNET informational activities, develop standards and support implementation of model accessibility plans.
        • Conflict of Interest (COI) Working Group will develop guidance for management of conflict of interest issues that may arise in the conduct of modeling analyses involving external collaborators. This working group will serve as a resource and consultative body to CISNET investigators. Investigators are required to inform and consult with this group where possible COI issues exist.
        • Professional Enhancement Working Group will coordinate professional enhancement activities for junior investigators across CISNET. Activities may be cancer site-specific or CISNET-wide.
    • Coordinating communication between the Cancer-Type Specific Leadership Teams and various subcommittees and working groups.
    • Setting CISNET publication policies and establishing recommendations/guidelines for elements to be included in publications reporting CISNET comparative modeling.
    • Suggesting and setting policies for common model documentation platforms.
    • Setting the timing and location of the two annual CISNET investigators meetings, coordinating the organization of these meetings (organization of the meeting will be a joint responsibility of NCI, the Coordinating Center PDs/PIs, and the PD/PI at the host site of the meeting for meetings outside the Washington DC area).

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 recipient. This special dispute resolution procedure does not alter the recipient'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.

Consistent with the 2023 NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

4. Reporting

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement Section 8.4.1 Reporting. To learn more about post-award monitoring and reporting, see the NIH Grants & Funding website, see Post-Award Monitoring and Reporting.

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 Section 8.6 Closeout. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR Part 200.301.

Section VII. Agency Contacts

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, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues.

Grants.gov Support Center - Questions regarding Grants.gov registration and services (e.g., Workspace, subscriptions).

NCI DCCPS CISNET Program Office
National Cancer Institute (NCI)
Telephone: 240-478-8909
Email: NCI_DecisionModelingPriorities@mail.nih.gov

Center for Scientific Review (CSR)
Email: NOFOReviewContact@csr.nih.gov

Office of Grants Administration

National Cancer Institute (NCI)
Telephone: 240-276-6277
NCIFinancialContact@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.

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 2 CFR Part 200.