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

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

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

This funding opportunity announcement (FOA) is a continuation of Cancer Intervention and Surveillance Modeling Network (CISNET - https://cisnet.cancer.gov) program. This FOA invites applications for collaborative research projects using simulation and other modeling techniques for cancers of specific organs (also referred to as "cancer types").

This FOA is open to all qualified investigators and prior involvement in CISNET, while welcomed, is not required. Accordingly, the proposed research is expected to reflect new projects/directions even for the current CISNET awardees.

The proposed research is expected to generate sophisticated, evidence-based decision tools that could inform international/national/regional/local decisions on the most efficient utilization of existing and emerging technologies and strategies for the control of cancer. These tools should allow for the following:

• Enhanced understanding of the impact of cancer control interventions (screening, treatment, prevention) on current and future trends in incidence and mortality;
• Determination of the most efficient and cost-effective strategies for implementing technologies in the population, based on extrapolated evidence from clinical trials, epidemiologic studies, and observational studies; and
• Helping to determine which new, emerging technologies are the most promising for scaling up to the population level, based on data from limited-scale studies.

Key Terms for the FOA

Modeling: Modeling, in the context of this FOA, 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 reformulate using a more robust statistical/mathematical framework

Modelling Group: a modeling group is defined as a group of researchers using a single model or a set of interrelated components of models for a single cancer type that are applicable to cancer control and/or policy related issues. A modeling group may include investigators from a single institution or multiple institutions.

Cancer Type: cancers of specific organs on which the proposed project is focused.

Overall goals of CISNET Program:

Recent biomedical advances have enabled the collection and analysis of vast health-related data from patients, medical record and billing systems, and the general population. However, enormous challenges remain to integrate the information into optimal decision-making tools to inform public policy. CISNET's goal has been to close this gap by providing a suite of rigorously tested models to respond to emerging cancer control questions. CISNET research can inform clinical practice and guidelines by bridging existing knowledge in a modeling framework under clearly specified assumptions.

The purpose of the FOA is to expand and extend the work of CISNET systematically, in line with NCI priorities where modeling can help optimize the translation of cancer research to policy and practice.

This FOA will support CISNET activities in a systematic manner across all four main phases of the translation process (i.e., T1 initial discovery to health application; T2 health application to evidence-based practice guidelines; T3 practice guidelines to health practice; and T4 health practice to population health impact). CISNET models proposed should provide a platform for evaluating the potential downstream consequences of decisions and strategies that are made in earlier phases. Applications of these models should provide effective tools for helping to optimize cancer-relevant decisions.

The Concept of CISNET Program: CISNET was built upon the concept of creating virtual laboratories, which incorporate evidence to perform in silico experiments of potential public health strategies that go beyond what can be directly observed in trials, epidemiologic studies, and observational cohorts. Simulation models, in this context, recreate individual life histories with respect to birth, development of risk factors, development of cancer precursors (if relevant), detection and treatment, and death from cancer or other causes. The models incorporate data from randomized controlled trials (RCTs), meta-analyses, observational studies, national surveys, and patterns of care studies to evaluate the past and potential future impact of cancer control interventions beyond the studies inclusion/exclusion criteria and/or protocols. A systematic comparative modeling approach brings transparency to the modeling process. The key factor in the CISNET modeling approach is a joint evaluation of results from a range of models, as opposed to a single estimate from one model. This multi-model approach increases the overall credibility of the modeling process and enhances the accuracy and reproducibility of the results. These highly desirable attributes are of fundamental significance for cancer control planning and policy guidelines and decisions.

CISNET research can inform clinical practice and guidelines by bridging existing knowledge in a modeling framework under clearly specified assumptions. Modeling can help extend trial results beyond the limited regimens that can be studied directly (e.g., age to start, age to stop, and periodicity of screening) or beyond limited trial eligibility criteria; help estimate longer-term results from short-term studies and clarify the impact of interventions over the entire life course; help to estimate important but unobservable quantities (e.g., rate of overdiagnosis); and help disentangle conflicting trial results where the trials are conducted under very different study protocols. Results like these are usually not directly available, as they involve the preclinical natural history of disease, and many studies exclude the elderly and rarely have enough follow-up to reflect the full life course of individuals. CISNET models can translate evidence from randomized trials and epidemiological studies to the population setting by extrapolating evidence beyond study protocols to the general population, accounting for patterns of care in less controlled settings. CISNET provides a suite of models that are able to meet the challenges of the increasing pace of scientific discovery and are poised to address emerging questions, and to determine the most efficient and cost-effective strategies for implementing technologies in the population.

CISNET currently consists of six U01 awards, each focusing on a single cancer type. Each award includes a coordinating center and multiple independent modeling groups that utilize statistical simulation and other modeling approaches. A summary of the prior rounds of CISNET funding can be found at https://cisnet.cancer.gov/about/history.html.

Accomplishments: Since the inception of CISNET, the program has resulted in many significant contributions to translational research and public health, reflected by over 470 publications (for the full list see https://cisnet.cancer.gov/publications/).

The highlights of completed or ongoing work for the current funding cycle include the following (for details see https://cisnet.cancer.gov/publications/):

• CISNET work in support of the U.S. Preventive Services Task Force (USPSTF) guidelines;
• Using modeling to design and interpret trial results;
• Impact on screening efficacy of delays in diagnosis after an abnormal screening exam;
• Development of policy tools;
• Understanding the impact of mammography and adjuvant therapy on breast cancer mortality;
• Exploring the potential benefits of new screening and treatment technologies in esophageal adenocarcinoma;
• Clarifying the effects of racial differences in screening, treatment, and natural history on incidence and survival;
• Estimating overdiagnosis and its role in informed decision making in prostate, breast, and lung cancer;
• Strategies for risk-stratified screening;
• Screening in special populations;

General Requirements and Expectations

Overall Characteristics of the CISNET Approach to Modeling: Major goals of CISNET include building the capacity and an approach for comparative analysis using population-based models to answer important policy-based questions. The CISNET approach to modeling includes the following required attributes/characteristics:

• Flexible broad-based disease models: CISNET models incorporate a central cancer model (usually including natural history prior to clinical appearance), which can be modified by evolving cancer control interventions prevention strategies, screening modalities, and treatment and follow-up regimens. Outputs can include the interventions' benefits, harms, and costs. The models can be readily adapted to characterize new technologies. For example, CISNET breast models, which were originally developed based on film mammography, have been adapted to incorporate the costs, performance characteristics, and logistics of digital mammography and, more recently, tomosynthesis (3D mammography).
• 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 actual US or other populations (see https://cisnet.cancer.gov/modeling/multi-cohort.html).
• Comparative modeling: All U01 projects proposed must employ a comparative modeling approach (see https://cisnet.cancer.gov/modeling/comparative.html).
• Transparency in modeling and assumptions: The proposed projects must follow the implemented CISNET approaches to model documentation (see https://cisnet.cancer.gov/resources/documentation.html) to accommodate audiences who have different objectives and levels of technical familiarity with modeling.

Main areas of focus and key required attributes for U01 CISNET projects: The main characteristics of CISNET projects include the following:

• Models: Modeling efforts proposed must adhere to the definition given 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, but the application should describe how they complement the suite of models proposed. Investigators may propose the application, 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 cancers of one of six organ sites listed here: prostate, colon/rectum, breast, esophagus, lung, and cervix. Applications focused on other cancer types will be viewed as non-responsive and will not be reviewed. Applicants should also be aware that the NCI's general intent is to fund one project per each "eligible" cancer type. Even though applications will focus on a single cancer type, cross-cancer site work along certain themes (e.g. active surveillance, biomarkers, targeted therapy, overdiagnosis) could be proposed, although cross-cancer site collaborations would be dependent on the other cancer types that are funded, and their interests.
• Important Notes:
• Studies conducted on one cancer type (especially methodology) may occasionally have cross-cancer type applicability.
• Accordingly, cross-cancer collaborations across CISNET awardees focused on different cancer-types are encouraged, especially for pilot projects (using rapid response funds).
• Nevertheless, to be responsive to this FOA, the vast majority of 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 applications of modeling approaches to important public health issues. Each application submitted in response to this FOA is expected to provide a coordinated plan of reasonably comprehensive coverage of the cancer control issues amendable to modeling facing that cancer type. Applicants are expected to propose collaborative, interactive projects involving groups of researchers that would 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, it is essential that the proposed activities emphasize not only the extension of models and their application but also the communication and transfer of modeling results to policy makers and members of other organizations who could utilize the results for decision-making. Accordingly, one of CISNET core values has been making the research communities and policy-making entities aware of existing modeling capacity and encouraging collaborations.

Applicants are strongly encouraged to form (or plan for), as appropriate, scientific collaborations as well as partnerships with policy-making entities. Examples of such interactions include:

• Outside modelers or other researchers with special expertise , who may be willing to join the collaborative activities as "affiliate members";
• Investigators who are involved with cancer-relevant clinical prevention, treatment, or screening trials and/or epidemiologic or observational studies;
• Investigators involved in other cancer-relevant programs;
• Regulatory/policy and/or guideline setting organizations/entities;
• Professional societies;
• Other relevant government agencies; and
• Patient, caregiver, and other relevant stakeholder organizations.

Targeted Priority Areas: There are nine specific priority areas that are targeted by this FOA. Each application should provide coverage in as many of these areas as feasible and appropriate for the cancer type of interest. Nonetheless, these areas are listed as suggestive and are not mandatory, i.e., applicants could exclude areas that are less appropriate for a particular cancer type, and are encouraged to add different areas that are more germane.

Area 1) Precision Screening and New Screening Technologies;

Area 2) Precision Treatment;

Area 3) Overdiagnosis and Active Surveillance;

Area 4) Decision Aids (Individual and Policy);

Area 5) Understanding Screening in Real-World Settings and Determining the Best Routes to Optimize the Processes;

Area 6) State, Local, and International Cancer Control Planning;

Area 7) Suggesting Optimal Routes to Reduce Health Disparities;

Area 8) Methods Development;

Area 9) Cancer-Type Specific Opportunities.

Details pertaining to these Areas of Special Interest are given below:

Area 1) Precision Screening and New Screening Technologies

Risk-based screening, whether based on polygenic risk, family history, behavioral risk factors, or a combination, holds promise to make screening more effective and efficient. Yet challenges to its implementation are considerable. Simulation modeling can translate a risk model’s risk scores into an optimal program of screening regimens. The larger the model’s discriminatory ability, the more screening regimens could be justified across the different levels of risk. However, optimal screening regimens are often too complex to implement in a population or health care setting. CISNET modeling can be used to determine the best ways to step back from optimal complex implementation schemes while retaining most of the efficiencies gained with risk-based screening. The results of prior screens and the changing comorbidities and life expectancy of the individual can be used to interactively modify a screening schedule. Simulation modeling over the life course is an ideal way to set guidelines for future screens, dependent on prior screening events and the individual’s evolving health status. New screening technologies and potential biomarkers (and their relationship to the natural history of disease) constantly change the landscape for evaluating screening strategies. Noninvasive technologies obviate some of the need for risk-based strategies, as they may be inexpensive to conduct on the whole population; however, downstream costs and harms must be considered. As we understand more about the natural history of disease and the signatures of cancers that are more or less likely to progress, the balance of screening’s harms and benefits changes.

Area 2) Precision Treatment

Evolving data from electronic claims, labs, and health records, and their potential linkage to population-based registry data, will generate detailed information on first and second-line treatment regimens and dose, recurrence, and genomic disease characterization. These big data resources will enable more thorough modeling of treatments, their sequelae, and their population-level impact, especially treatment in the recurrent setting (e.g. including recurrent and de novo Stage IV disease) and for newer targeted therapies and immunotherapy. With the rising cost of therapies, modeling can assist in threshold pricing of regimens i.e., setting the cost of a new, more effective treatment so that its cost-effectiveness equals that of existing regimens or other value-based schemes. Modeling can also establish the situations in which genetic tumor characterization and potential biomarkers are cost-effective. CISNET modeling can inform trial design and evaluation and is especially useful in non-inferiority treatment de-escalation trials. Modeling can help estimate the non-inferiority margin (the point of equipoise where the lower recurrence or death rate of the standard therapy is counterbalanced by the higher outcome rate but improved morbidity burden of the alternative in terms of quality-adjusted life years). Value of Information (VOI)/ Value of Research (VOR) methods in decision modeling can quantify the losses associated with choosing suboptimal policies when that decision is made with uncertain information, and they can be used as a framework for prioritizing trials.

Area 3) Overdiagnosis and Active Surveillance

Overdiagnosis rates depend on the screening technology s operating characteristics, the screening regimen, and the health care setting. Modeling can help identify the screening regimens that most effectively thread the needle in maximizing mortality benefit while minimizing overdiagnosis. Overdiagnosis is relevant not only to initial disease, but also potentially to recurrent disease, especially in prostate cancer where recurrence is often determined only through rising PSA (i.e. biochemical recurrence). Active surveillance (AS) can help ameliorate the harms of overdiagnosis.

Modeling is useful in setting standards for selecting AS, formulating AS regimens, and deciding to terminate AS and initiate treatment. Modeling can help quantify the QALYs of an individual who selects AS vs. active treatment and help justify choosing AS even if outcomes are slightly less favorable (but counterbalanced by better quality of life). Collaborations with those conducting trials of AS (such as for DCIS breast disease) should inform and improve models' representation of DCIS, and may help evaluate trial results.

Area 4) Decision Aids (Individual and Policy)

Preference-sensitive screening and treatment decisions should be shared between the patient and physician based on the patient s values. Decision support tools can help inform patients and physicians about the potential harms and benefits of screening and treatment options and enable decisions based on individual values and preferences. In gathering data to develop these tools, decision analysts often find a gap between available direct evidence from trials and observational studies with limited-duration follow-up. Models can estimate lifetime metrics of harms and benefits that are more appropriate for patient decision making. Models can also estimate quantities such as overdiagnosis and overtreatment that are not directly observable in trials. CISNET modelers can team with decision analysts to develop tools for use by the public and/or by health care professionals to guide shared decision making incorporating patient values. CISNET models can also help policy makers decide among the potential benefits, harms, and costs of multiple policy alternatives.

Area 5) Understanding Screening in Real-World Settings and Determining the Best Routes to Optimize the Processes

The number of cancer deaths averted as projected from idealized trial settings may be markedly attenuated when screening is implemented in clinical practice. PROSPR (Population-based Research to Optimize the Screening Process - https://healthcaredelivery.cancer.gov/prospr/) and the Breast Cancer Surveillance Consortium (BCSC - https://www.bcsc-research.org/) are NCI sponsored consortia that collect and analyze data in different health care settings in recognition that screening is not a singular event, but rather a process (recruitment, screening, positive screen evaluation, diagnosis, referral for treatment), and that all phases must be optimally completed to maximize screening benefits. Modeling can quantify the reduced screening effectiveness that occurs with breakdowns in the process and identify key leverage points for improving efficiency. CISNET modeling can be used to extrapolate long-term consequences of shortcomings in the process. Results in the community setting may also be better than those demonstrated in a trial. For example, although the National Lung Screening Trial showed a 20% mortality decline with low-dose computed tomography (LDCT), the management of suspicious nodules was viewed as a potential area for improvement. In response, in 2015 the American College of Radiology (ACR) launched Lung-RADS management recommendations, significantly cutting the false positive rate and vastly reducing follow-up scans, but with lower sensitivity. Modeling can supplement these efforts by estimating long-term savings in terms of number of scans, quality of life, and mortality outcomes of lung cancer screening at the population level, and can be the basis of personalizing screening regimens depending on one's aversion to false positives test results.

Area 6) State, Local, and International Cancer Control Planning

Advancing state, local, and global research to address specific challenges in cancer control is an NCI priority, and modeling can play a key role. CISNET modelers have overcome challenges in customizing a model to a new local, state, or international geographic area. Obstacles include a dearth of data in many locales for customizing the model and the time required to fully calibrate it. Model development for specific locales can be considered, but also novel approaches to model customization across a range of areas with different levels of data resources, and also differing demographic, medical, political, economic, and cultural contexts. The range of areas could represent different areas within a state, different states, different areas within a country, or different countries. Modelers must consider what parameters must by customized for each area, and which can be shared, how the models can be validated, and how to incorporate comparative modeling (if even in a very limited way).

Area 7) Suggesting Optimal Routes to Reduce Health Disparities

Applicants are encouraged to explore both the sources of disparities and the best leverage points to reduce them. In considering health disparities, consideration must be given to the social and behavioral determinants of health for different population sub-groups. Modelers are encouraged to move beyond racial/ethnic characterization and utilize data sources that enable disparities to be modeled based on income/education, insurance status, geography, and health care access. Disparities and their downstream consequences can be studied in terms of factors such as smoking rates, obesity, and other risk factors; screening rates; follow-up to abnormal screening; treatment; and quality of care.

Area 8) Methods Development

Methods development in CISNET must be directly motivated by applications, and then must be applied after development to demonstrate its practical utility. Examples of methods development include porting complex simulation models and advanced algorithms to high-performance computing platforms. Advances in computing workflow management can promote efficient model evaluation and refinement by allowing native-coded models (i.e., no need to port or re-code) or any model evaluation and refinement tool to be used within an automated dynamic workflow. This can allow modelers to develop advanced algorithms for high-dimensional model calibration and probabilistic sensitivity analyses on supercomputers. Investigators can use this structure to explore more combinations of possible model fits, and the automated dynamic workflow allows other CISNET modelers to plug their model in with limited effort and try the same algorithms. CISNET modelers could also support the integration of existing or statistical prognostic models (e.g., of cancer recurrence or risk models) into simulation models. Many of these risk models involve factors not currently simulated, and it is challenging to incorporate new risk factors consistent with specific birth cohorts and maintain the appropriate population correlation structure of those with multiple factors. Other methodologic areas of interest include the use of simulation emulators (statistical models which "emulate" the relationships between CISNET model inputs and outputs providing simplified ways to make model results available to stakeholders), characterizing the degree of structural uncertainties across models investigating when a group of models does not represent adequate structural variability, and improved methods for summarizing or averaging of results across models. Other methodologies can be developed, but must be well motivated by important issues in model application.

Area 9) Cancer-Type Specific Opportunities

Opportunities may exist for cancer-type specific modeling (e.g., those outlined under Continued Scientific Need for CISNET) that are critical for that site but may not fit into the eight areas above.

Organizational Structure and Coordination of Proposed CISNET Teams

Each proposed CISNET team must have the following functional elements:

• Modeling Groups (three to six groups per application generally expected); and
• Coordinating Center (one per application).

Other Expectations

• Leadership. To facilitate collaborative, transdisciplinary research, comparative modeling, and coverage across the cancer control spectrum and of the specific area of interest, 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 opportunities for junior investigators. In conducting its research activities, each CISNET team will be expected to actively plan for and create opportunities for junior investigators that would facilitate their professional enhancement, for example opportunities for visiting other modeling groups 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 trans-consortium activities that may include collaborative projects with other CISNET awardees, developing common strategies to enhance model accessibility, etc. An important aspect of these activities will be cross-consortium projects providing professional enhancement activities for junior investigators.

CISNET Governance and Advisory Panels

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 panels are suggested to consult on evolving areas of focus.

Non-Responsive Applications

The following types of research activities are outside the scope of this FOA and will be considered non-responsive. (Non-responsive applications will not be reviewed.)

• De novo development of models; and
• Applications that do not focus on a single selected "eligible" cancer type.

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

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

Higher Education Institutions

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

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

o Hispanic-serving Institutions

o Historically Black Colleges and Universities (HBCUs)

o Tribally Controlled Colleges and Universities (TCCUs)

o Alaska Native and Native Hawaiian Serving Institutions

o Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

• State Governments
• U.S. Territory or Possession

Other

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

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

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

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) 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.
• o NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number 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.

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.

For this FOA, applicants are required to designate multiple PDs/PIs. One of the PDs/PIs should be responsible for the Coordinating Center, other PDs/PIs are expected to be responsible for individual modeling groups. Other arrangements may also be proposed, if justified. For example, a PD/PI responsible for the Coordinating Center may also lead one of the modeling groups.

It is expected, although not required, that the contact PD/PI will be the same person as the PD/PI responsible for the Coordinating Center. (The Coordinating Center will generally be located at the institution submitting the CISNET application in response to this FOA.) The PD/PI responsible for the Coordinating Center may also be responsible for a Modeling Group.

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

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

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.

It is critical that applicants follow 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.

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:

Eric J. (Rocky) Feuer, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6772
email: rf41u@nih.gov

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed, with the following exceptions or additional requirements:

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

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

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

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

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

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).

Other Attachments: Applicants must provide the following additional materials in support of their application. Each attachment should be uploaded as a separate PDF using the indicated filenames (which will serve as application bookmarks). All these Other Attachments combined must not exceed 10 pages.

Attachment 1: Model Characteristics (use filename "Models"). Provide a table summarizing key model differences and similarities.

Attachment 2: Model Applications (use filename "Applications"). Provide a table summarizing prior model applications.

Attachment 3: Modeling Projects (use filename "Projects"). Provide a table summarizing modeling projects indicating items such as the area of coverage (e.g. prevention/screening/treatment and/or which priority area it represents, modeling groups included, timeline, coordinator, etc.).

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

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

It is anticipated that requested budgets will vary, depending on the scale of work, especially the number of modeling groups proposed. It is anticipated that the approximate budget request (direct costs) for the entire application per year will not exceed approximately $790K, $970K, $1.15M, and $1.33M for 3, 4, 5, and 6 (or more) modeling groups, respectively.

Any individual designated as a PD/PI must commit and maintain through the life of the award a minimum of 1.2 person-months of effort, except in situations where a modeling group has a specialized focus, limited anticipated roles, and/or other special circumstances which should be described.

Budget Justification Section. In the budget justification section, applicants should break out the time commitment and responsibilities of each person (in particular 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 $110,000 direct costs per year.

Modeling Groups. Budget allocations for individual modeling groups should generally not exceed $180,000 direct costs per year. Budget allocations for modeling groups with specialized focus and/or limited anticipated roles should be substantially smaller. In exceptional situations, budget allocations for a particularly complex modeling group could be slightly larger if well justified. This amount would include special expertise needed to address some of the priority areas (local, state, or international cancer control planners, genetic epidemiologists, developers of decision aids), and junior modelers. Persons with specialized expertise in one modeling group would generally be expected to be shared across the groups as needed.

"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" fund should generally not exceed $140,000 per year (direct costs) It is expected that approximately $40,000 of this amount will be designated for cross-consortium projects providing professional enhancement activities for junior investigators. 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 (approximately 2 days for a cancer-type specific meeting, with an additional half day for a cross-cancer type plenary session) and (2) a mid-year meeting with individual cancer-type specific meetings of approximately 2 days. 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 on-campus meeting rooms. 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 to host one meeting during the five-year award period.

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

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

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

Specific Aims: Outline Specific Aims (generally 4-6 aims are expected). Indicate how the Aims proposed correspond to the priority areas to be addressed.

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

Sub-section A. Overall Objectives and Significance

Sub-section B. Team Leadership and Coordinating Center

Sub-section C. Models and Their Prior Applications

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

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

Sub-section A. Overall Objectives and Significance

Briefly sketch the background leading to the present application, critically evaluate existing knowledge, and specifically identify the gaps that the project is intended to fill. In addition, this subsection should include the following:

• List the participating modeling groups to be included;
• State concisely the importance and health relevance of the research described in this application by relating the specific aims to the broad, long-term objectives;
• If the aims of the application are achieved, state how scientific knowledge, public health guidelines, or clinical practice will be advanced;
• Describe the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions for this specific cancer type;
• List the broad, long-term objectives and the goal of the specific research proposed;
• The goals should be stated in both in terms of the modeling work that needs to be done, but also in terms of the broader objective of the modeling exercise; and
• A rationale for determining which of the priority areas will be addressed.

Sub-Section B. Project Leadership and Coordination, Advisory Groups, Professional Enhancement, and Model Accessibility

This section should describe how the activities across the modeling groups within a cancer type and across CISNET will be integrated and coordinated. This section should have four subheadings:

B.1 Team Leadership and Coordination - Each proposed CISNET project must include a Coordinating Center and a Coordinating Center PD/PI. Applicants must plan for and describe in their applications the following coordination activities of the Unit:

• Formulating, prioritizing, and coordinating work on base case and other questions (including outside requests with new funding opportunities);
• Negotiating common requests for outside data sources;
• Consensus building and coordinating critical evaluation of disparate results;
• Preparing inputs and collecting and processing common outputs for model comparisons;
• Coordinating synthesis papers and group responses bringing together disparate information to inform policy makers;
• Coordinating review of new and relevant literature, inviting guests to meetings, vetting of proposed affiliate members, and prioritizing the use of rapid response funds; and
• Organizing conference calls and setting meeting agendas.

Although the Coordinating Center will provide oversight, it is expected that certain coordination activities will be distributed across the modeling groups. For example, if there is a collaborative modeling activity among two groups, coordination of that work might be done by one of the modeling groups rather than through the Coordinating Center. If a meeting is held at a particular PD/PI’s institution, that group would be responsible for making local arrangements. Local specialized expertise included under one PD/PI (e.g., genetic epidemiologist, cancer control planner, specialists in the development of decision aids, specific clinical expertise) might be shared across the group. This section should describe not only the activities of the Coordinating Center, but also how some of the coordination activities will be shared across the modeling groups. Through the Coordinating Center, each CISNET cancer type group will constitute an established expert knowledge base that can provide technical advice on evolving policy-relevant cancer control and surveillance questions. Even though one group will be tasked with being the Coordinating Center, CISNET would be run through consensus.

B2. Rapid Response Projects. Outline plans and processes for projects that will use the rapid response funds, listing examples of anticipated activities.

Address such aspects as:

• Explain how the envisaged small innovative and creative projects will enhance the main CISNET work;
• Expertise needed for specific tasks, gaining access to data sources, and providing funds to modeling groups to mount important efforts not originally anticipated;
• How these projects will contribute to providing cross-CISNET professional enhancement activities for junior investigators (pre-docs, post docs, junior faculty);
• Explain 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 conducive to learning; and
• Outline 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 Cancer-Type Leadership Groups).

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

B.4 Model Accessibility. Explain the proposed approaches to model accessibility in the context of adherence to the general CISNET tenet:

While it is recognized that there are no standards for the release and accessibility of complex microsimulation models, continued thinking about barriers to accessibility and how to overcome them, and the evolving development of policies, methods and standards for model accessibility are critically important. CISNET is committed to the transparency of models, and dissemination of modeling results, models runs, and software (whenever possible) to the scientific community.

Specifically, describe strategies considered to enhance the broad accessibility of the models (but without repeating the specific aspects to be covered under the Data Sharing Plan). If applicable, highlight any innovative aspects of the proposed approaches.

Address, for example, such aspects as:

• An evolving plan for model accessibility within the specific cancer type of focus that may be applicable also for consortium-wide activities and/or standard approaches, including pilot projects to test specific approaches;
• Applicable target audiences for model accessibility, including, e.g.:
• Members in an individual modeling group, various members across modeling groups within a cancer type, and/or members across cancer type groups within the consortium;
• Outside collaborators; and
• Outside model developers and model users.
• Key technical aspects of model accessibility such as:
• Specific criteria under which the model executable or model source code (or model subcomponents) would be shared;
• Cost-effective methods to better document older models with a potentially large source code base;
• Standards for model versioning, release and documentation of complete sets of model parameters associated with specific publications; and
• Types of licenses for model executable and source code sharing, cross CISNET standards for the use of sharing portals such at GitHub.

Sub-Section C. Modeling Groups, Their Models, and Previous Model Applications.

Groups

Explain how the proposed modeling groups will collectively be able to conduct comparative modeling with respect to important cancer control issues and relevant priority areas for the selected cancer site.

Define the number and types of modeling groups proposed, following the general guideline that CISNET teams should have between three to six modeling groups. Within this general guideline, applicants are expected to present a coherent and well-conceived plan that will permit group work to proceed efficiently.

To justify the number and types of modeling groups proposed, address issues such as:

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

Models

• Give an overview of each model, summarizing clearly underlying model structures and assumptions;
• Include a natural history component (expected for most models), modeling the initiation, growth, and metastatic spread of the tumor, relevant precursor lesions, and biomarkers prior to (and possibly after) disease onset;
• If models without a natural history component are included, justify how they complement the suite of models proposed;
• Explain how these models complement each other in terms of providing implementations of different modeling perspectives, or different ways of synthesizing available evidence; and
• Describe the breadth and depth of prior model applications.

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

Sub-Section D. Proposed Model Extensions, Applications and Comparative Modeling

Provide a coordinated plan among the modeling groups of reasonably comprehensive coverage of the cancer control issues amenable to modeling for the cancer type of focus. Wherever applicable, indicate the corresponding priority area(s) from those listed in Section I. Describe any model extensions, additional model calibration, or validation necessary to accomplish this modeling. Investigators responding to this FOA may propose the application, extension, refinement and/or merging of existing models. If well justified, an existing model can be reformulated using a more robust statistical/mathematical framework.

Describe also model applications, development of user interfaces, web sites, and plans to disseminate and effectively communicate the results of modeling to planners and policy makers.

In addition:

• If modeling methodology is proposed (priority area 8) justify the development of the methods in terms their direct applicability to model applications. The emphasis must be on model applications to important public health issues including (but not limited to) the priority areas stated in this announcement;
• Address modeling projects not only related to recognized current issues, but also projects addressing anticipated emerging issues that will become more important or will become amenable to modeling during the course of the project (reflecting, e.g., the anticipated release of results from a major trial and/or other relevant study results);
• Address projects that include relevant issues across the cancer control spectrum (i.e., prevention, screening, diagnosis, treatment, surveillance, and end-of-life care). Not all individual models 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 types. 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 death and suffering from the disease;
• Focus modeling efforts on interpreting past trends and evolving trends in incidence and mortality, future trends, and informing cancer control and policy related issues. Describe how modeling will allow for assessing the value of new and existing health care technologies in a novel way;
• Describe which areas are important and central enough to warrant full base cases, i.e., collaborative modeling exercises among the entire group, which areas warrant mini-base cases, among a subset of the models, and which areas it will be sufficient for a single group to cover;
• Provide background information documenting data and research results that will support modeling applications beyond simple "what if" exercises;
• Outline proposed modeling projects and their potential and significance in terms of substantial cancer control opportunities. As applicable, indicate any reasonable expectation of significant impact that the modeling outcomes may have on the quality of life, costs, morbidity, or mortality at the population level; and
• Describe any outside groups that will be involved in specific modeling applications.

Note: Supplementary information for this subsection 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 SF424 (R&R) Application Guide, with the following modification:

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

In addition to the stated NIH data sharing policies, Data Sharing Plan must address the following specific aspects:

• Expectation to adhere to CISNET policies regarding the transparency of models, and dissemination of modeling results, models runs and software whenever possible to the scientific community, releasing source code as appropriate (e.g., in the context of collaborations), etc.;
• Inclusion of various types of model documentation to address the needs of users with different interests and levels of technical sophistication (e.g. clinicians, public health officials, policy makers, those who run models, those who build models);
• Providing other researchers with the ability to run the models directly, e.g., by releasing public versions of executable model software or model interfaces (sometimes in the form of interactive patient decision aids or policy decision tools);
• Openness to inquiries from those outside of CISNET to pose questions or scenarios (possibly based on national or regional issues of interest) amenable to modeling, which could be supported by those making the inquiries, rapid response, or other funds.

Appendix:

Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

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.

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

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

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

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

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

For assistance with your electronic application or for more information on the electronic submission process, visit 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, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

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.

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 on research that uses 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 type.

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

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

Does the project address an important problem or a critical barrier to progress in the field? Is 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 proposed project balance efforts devoted to the various priority areas and cancer control issues and special areas of interest appropriate for the selected cancer type? What will be the potential effect of these studies on medical care practice, cancer control strategies and guidelines, and public health policy if the aims of this application are achieved? Does the application address realistic strategies and issues that have a real potential for being implemented in the population?

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

Specific for this FOA: How strong is the team in terms of expertise to conduct the proposed modeling? Does the team have the appropriate interdisciplinary expertise to cover the relevant biological, medical, and technological (e.g. new screening technologies) areas relevant to the proposed work? How strong are these investigators in terms of their ability to communicate modeling results to a wide variety of audiences? Does the PD/PI responsible for the proposed Coordinating Center have the appropriate qualifications and experience to lead and coordinate a modeling program of this size and complexity?

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

Specific for this FOA: Will the proposed approaches allow for assessing the value of new and existing health care technologies in a novel way? How likely is the proposed approach to generate mathematical and statistical innovations that would serve the need to expand the model capabilities to address important public health and cancer control problems?

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?

Specific for this FOA: How well does the suite of models proposed complement each other in terms of providing different perspectives and/or different ways of synthesizing/integrating available evidence? Are the areas of expansion or combining of existing models well justified? Will there be adequate data sources to inform the models in the key areas of application? Does the approach ensure sufficient flexibility to address, when needed, emerging cancer control issues and technologies that are not apparent now? How adequate are the proposed steps after the publication of study results in terms of ensuring that the published findings are efficiently disseminated, including their clarity to policy makers and cancer control planners?

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?

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

Specific for this FOA: Do the proposed modeling groups come from institutions where modeling activities are an established element of the research environment? Are the planned collaborative arrangements with appropriate clinical trial and clinical study groups adequate to ensure timely access to new data for incorporation in the models?

Coordinating Center and Program Integration

Will the Coordinating Center, as proposed, be able to provide adequate coordination for all the participating groups and facilitate integration of their research as one unified effort? Are the plans for the Coordinating Center sufficiently flexible to promote and incorporate group input and consensus decisions? Does the Coordinating Center plan include creative options of comparing models, reaching group consensus, and synthesizing results for use by cancer control planners and policymakers? Are the plans adequate for conducting base cases, fielding outside inquiries, and other group activities? Are the plans adequate to keeping abreast of current policy related controversies, and the latest research results across the spectrum of treatment, screening, and prevention for their cancer type? Is there an adequate plan for making decisions about the use of rapid response funds? Are the proposed plans for career enhancement and model accessibility reasonable?

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

For research that involves human subjects but does not involve one of the 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.

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.

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

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

Not Applicable.

Not Applicable.

Not Applicable.

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

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

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

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

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

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

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the 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:

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

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

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications. Following initial peer review, recommended applications will receive a second level of review by the 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.

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

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

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

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

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

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

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

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

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html. 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. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

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 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 Parts 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 resides with the awardees for the project as a whole, 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:

• Determining research approaches and procedures, developing and applying their models, and analyzing/interpreting results;
• Defining objectives and approaches, and to plan, conduct, analyze, and publish results; interpretations, and conclusions of their studies.
• Collaborating with their Coordinating Center and the other PDs/PIs on their CISNET award;
• Serving as a member of an appropriate Cancer-Type Specific Leadership Team;
• Participating in collaborative 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 and calibration;
• Ensuring that up-to-date detailed descriptions of models will be made publicly available in a timely manner through the model profiles and model registry portions (and any other common model documentation platforms approved by the CISNET steering committee) of the CISNET public website (https://cisnet.cancer.gov/resources/documentation.html);
• Abiding 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;
• Attending two meetings a year along with key co-investigators and participating in regular conference calls. One meeting will be in the Washington DC area, and the second meeting at one of the PI/PD's home institutions. If their institution is selected, that PI/PD 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;
• Abiding by the Resource Sharing Plan, as appropriate, as well as specific procedures to be developed for the entire Consortium by the CISNET Steering Committee;
• Working cooperatively with the contractor who maintains the common model documentation (https://cisnet.cancer.gov/resources/documentation.html) and members only interactive web site;
• Approving affiliate members (groups funded elsewhere but whose are interested in joining the collaboration). Affiliate membership will be approved by the PD/PIs in the applicable cancer type;
• Participating in program-wide activities, such as the Model Accessibility and Professional Enhancement subcommittees.

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 the agendas of the cancer-type-specific meetings;
• Formulating goals, prioritizing, and coordinating work on base case and other questions;
• 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 bringing together disparate information to inform policy makers;
• Fielding outside requests and working with the modeling awardees to determine priorities;
• Coordinating conference calls and communication within the cancer-type specific group;
• Setting (in consultation with the other PD/PI s) the publication agenda and schedule;
• Coordinating the preparation of the annual progress and mid-year reports by the individual PD/PIs;
• 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; and
• Following to the extent consistent with Grant Regulations the overall Consortium policies and procedures established by Steering Committee.
  
  

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.

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

Designated NCI Program staff members serving as Projects Scientists will 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 Overall NCI Project Scientist for CISNET, who will serve as a voting member for NCI on the Consortium Steering Committee;
• The NCI will also designate NCI Project Scientists for each of the cancer organ sites. These cancer-type specific coordinators will be voting members of the Cancer-Type Specific Leadership Teams, along with the PI's from that cancer type, and any other members as designated by consensus of the cancer-type specific steering sub-committee;
• 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 joint model results and publication efforts of the 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 modelling and/or serve as a conduit to the potential utility and access to these resources;
• 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 web site for the internal use by CISNET investigators. This web site will be a communications portal for posting papers, base case inputs, data sets, and model documentation. In addition, NCI will maintain a public web site for CISNET (http://cisnet.cancer.gov/);
• NCI, in consultation with the Coordinating Center PI/PD's, 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 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.

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 as defined below. The NCI Overall Project Scientist and the Coordinating Center PDs/PIs for each cancer type will be responsible for forming a Steering Committee.

The Steering Committee will consist of the following voting members:

• The Coordinating Center PDs/PIs from each CISNET award; and
• The NCI Project Scientist.

Other individuals may be invited on an ad hoc basis as non-voting members.

Subcommittees. The Steering Committee may establish subcommittees for specific purposes, but there will be several standing subcommittees. The NCI Project Scientist and Coordinators may serve on such subcommittees, as they deem appropriate. Other NCI staff members may also be involved as needed.

The following standing subcommittees will be established:

• Cancer-Type Specific Leadership Teams - this subcommittee will consist (for each cancer type) 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 steering sub-committee. The chair of this subcommittee is the coordinating center PD/PI, 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 Subcommittee - this subcommittee will coordinate model accessibility activities across CISNET as suggested by applicants. 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, demonstration projects, and/or develop standards.

The 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 to assist them in interpreting and adhering to consortium policies and procedure;
• Coordinating communication between the Cancer-Type Specific Leadership Teams and various subcommittees (e.g. Model Accessibility and Professional Enhancement);
• 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 PI/PDs, and the PD/PI at the host site of the meeting , for meetings outside the Washington DC area);
• Setting policies and coordinating across CISNET the implementation of professional enhancement opportunities for junior investigators.

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.

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.

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)

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

Eric J. (Rocky) Feuer
National Cancer Institute (NCI)
Telephone: 301-276-6772
Email: rf41u@nih.gov

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

Carol Perry
National Cancer Institute (NCI)
Telephone: 240-276-6282
Email: perryc@mail.nih.gov

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

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