Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Cancer Institute (NCI)

Funding Opportunity Title
Cancer Intervention and Surveillance Modeling Network (CISNET) Incubator Program for New Cancer Sites (U01 Clinical Trial Not Allowed)
Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type

New

Related Notices

None

Funding Opportunity Announcement (FOA) Number
RFA-CA-20-043
Companion Funding Opportunity

None

Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.393, 93.394, 93.395, 93.396, 93.399

Funding Opportunity Purpose

Through this funding opportunity announcement (FOA), the National Cancer Institute (NCI) invites multiple-PD/PI applications for collaborative research projects each with two to three independent modeling groups that will comprise a new “incubator” program within the Cancer Intervention and Surveillance Modeling Network (CISNET). The overarching goal of this FOA is to expand comparative simulation modeling approaches developed by CISNET to new cancer organ sites beyond the sites which have been previously funded (breast, colorectal, prostate, lung, esophageal, and cervical) under CISNET. This "incubator" FOA is open to any cancer organ site beyond these sites. Specifically, this program aims to translate CISNET’s framework of success to cancer sites that are not already part of the CISNET and for which there has been nascent/limited population modeling and little to no comparative modeling. For this FOA, "incubate" refers to accelerating the development and application of CISNET-type models for new cancer sites. Accelerating the development of comparative simulation modeling approaches for new cancer organ sites beyond those already funded is expected to generate sophisticated, evidence-based decision tools that could inform decisions on the most efficient utilization of existing and emerging technologies and strategies for the control of proposed cancers.

While open to all qualified investigators, to encourage broad participation from population modelers in cancer control, this FOA will allow no more than one Principal Investigator who is funded under the CISNET FOA RFA-CA-19-054 to also be a Principal Investigator on each Incubator application.

Key Dates

Posted Date
September 18, 2020
Open Date (Earliest Submission Date)
December 20, 2020
Letter of Intent Due Date(s)

30 days prior to the application due date

Application Due Date(s)

January 20, 2021

No late applications will be accepted for this Funding Opportunity Announcement.

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

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

AIDS Application Due Date(s)

Not Applicable

 

 

Scientific Merit Review

June 2021

Advisory Council Review

August 2021

Earliest Start Date

September 2021

Expiration Date
January 21, 2021
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

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

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

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

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

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

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


  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose

Through this funding opportunity announcement (FOA), the NCI invites multiple-PD/PI applications for collaborative research projects each with two to three independent modeling groups that will comprise a new “incubator” program within the Cancer Intervention and Surveillance Modeling Network (CISNET). The overarching goal of this FOA is to expand comparative simulation modeling approaches developed by CISNET to new cancer organ sites beyond the sites which have been previously funded under CISNET (breast, colorectal, prostate, lung, esophageal, and cervical). This "incubator" FOA is open to any new cancer organ site beyond these sites and any application, which includes previously funded cancer sites (breast, colorectal, prostate, lung, esophageal, and cervical), will not be reviewed (see Non-Responsive criteria below). Specifically, this program aims to translate CISNET’s framework of success to new cancer organ sites that are not already part of the CISNET and for which there has been nascent/limited population modeling and little to no comparative modeling. For this FOA, "incubate" refers to accelerating the development and application of CISNET-type models (see CISNET Modeling under Key Terms for this FOA) for new cancer sites.

While open to all qualified investigators, to encourage broad participation from population modelers in cancer control, this FOA will allow no more than one Principal Investigator who is funded under the CISNET FOA RFA-CA-19-054 to also be a Principal Investigator on each Incubator application.

The proposed research is expected to generate sophisticated, evidence-based decision tools that could inform decisions on the most efficient utilization of existing and emerging technologies and strategies for the control of proposed cancers. 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.

Priority will be given to applications demonstrating that opportunities exist at points across the cancer control spectrum to achieve a significant population impact for that cancer site. By accelerating the development of nascent CISNET-type models for additional cancer sites beyond those that have been previously funded under CISNET, this “incubator program" will help the cancer control community assimilate evolving research on those sites and help bridge the gap between new interventions and knowledge of how to best utilize them to optimize their population impact.

Key Terms for the FOA

Incubator Program: Incubate, in the context of this FOA, is defined as accelerating the development of CISNET-type models (see CISNET Modeling below) for new cancer sites beyond those previously funded under CISNET.

Population Modeling: Population 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. Population models recreate individual life histories and usually include many of the following features: birth and relevant demographics; development of risk factors, cancer precursors (if relevant), the preclinical natural history of the cancer; cancer detection and treatment; recurrence and subsequent treatment, and death from cancer or other causes, all modifiable under various interventions and cancer control strategies.

Nascent Models: A nascent model, in the context of this FOA, represents models in a wide range of current states of development, ranging from those in the early conceptual stages to those that have been programmed and undergoing model calibration and validation, to those that have produced published applications but could undergo extensions, expansions, or reconfiguration under this FOA.

Modeling 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 site that are applicable to cancer control and/or policy-related issues. A modeling group may include investigators from a single institution or multiple institutions.

CISNET Modeling: The CISNET approach to modeling includes the following 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 cancer 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: A key innovation of the CISNET modeling approach is a joint evaluation of results from a range of models, as opposed to a single estimate from one model. Independent modeling often yields disparate results that are difficult to reconcile, affecting the credibility of the modeling. The Incubator Program’s support of a multiple-PI U01 for each new cancer site will facilitate systematic, comparative modeling for that cancer. Although the CISNET models have been developed independently, the modeling groups develop and share specified common inputs and produce common outputs, allowing differences between models’ results to be explored systematically. Comparative modeling produces a range of results across models and, when consensus can be reached, greatly enhances the credibility of results by highlighting their reproducibility. When results diverge, it can help pinpoint areas where knowledge is insufficient and further research is needed.

Rationale and Goal of the CISNET Incubator Program

The formidable gap between the rapid pace of biomedical innovation and our ability to harness it to improve population health exists for cancer sites beyond those that are currently part of CISNET. That gap is particularly notable with respect to advances in the molecular/biological understanding of cancer, a better understanding of the viral and bacterial risk factors/causes of cancer and how to control them, emerging screening/diagnostic technologies, and the challenges and opportunities these advances present.

Advances in medical informatics have enabled the collection and analysis of health-related data from numerous sectors; examples include the ongoing linkage of population-based cancer registry data with claims, pharmacy, and other data sources. However, enormous challenges remain to integrate the information into optimal decision-making tools to inform public policy and clinical practice. CISNET closes 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 bringing 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 screening, age to stop, periodicity) or beyond limited trial eligibility criteria; help estimate longer-term results from short-term studies and clarify interventions’ impact over the entire life course; help estimate important but unobservable quantities (e.g., overdiagnosis rate); and help disentangle conflicting trial results where the trials are conducted under very different study protocols. Most importantly, CISNET models can translate evidence from randomized trials and epidemiological studies to the population setting by extrapolating that evidence beyond study protocols to the general population, accounting for population demographics and patterns of care in less-controlled settings.

Recognizing that the types of questions that CISNET-type models can address extend well beyond the cancer sites currently funded in CISNET, the goal of this FOA is to foster CISNET-type modeling (i.e., simulation and other related mathematical modeling techniques) for additional cancer sites. Work on the existing sites focuses on applying and extending the models (see RFA-CA-19-054), whereas this "Incubator" FOA will foster nascent modeling efforts at various stages of development and their application.

Background

The CISNET is a consortium of NCI-funded investigators who use simulation modeling to improve our understanding of the impact of cancer control interventions on population trends in incidence and mortality, guide public health research and priorities, and aid in the development of optimal cancer control strategies. CISNET was initiated in 2000 with modeling in breast, colorectal, and prostate cancers, and lung cancer was added in 2002. Esophageal (2010) and cervical (2015) cancers were more recent additions which, although less common, involve considerable complexities in how to most efficiently optimize cancer control opportunities for these cancers. Under RFA-CA-14-012, there were six U01 awards, each for a different cancer site, with between three and six models per cancer site (see https://cisnet.cancer.gov/grants/). Under RFA-CA-19-054, applications were requested for the same six cancer sites. Simulation models recreate individual life histories with respect to birth; development of risk factors, cancer precursors (if relevant), and invasive cancer; cancer detection and treatment; and death from cancer or other causes. Incorporating data from cancer registries, randomized controlled trials, meta-analyses, observational studies, national surveys, and studies of care patterns, the models are used to evaluate the past and potential future impact of cancer control interventions beyond the enrollment criteria and/or protocol of each trial or study.

Innovations in CISNET include comparative modeling, templated model documentation at varying levels of technical specificity; multiple birth cohort modeling, which captures changing risk factor profiles, screening behaviors, and treatments used by each cohort as they age; and broad-based disease models that can incorporate interventions from across the cancer control spectrum, and that can easily be adapted to model novel cancer control technologies.

Major goals of CISNET include building the capacity and an approach for comparative analysis using population-based models to answer important clinical and policy-based cancer control questions. CISNET has brought sophisticated evidence-based planning tools to population health and public policy by: informing our understanding of national trends in cancer incidence and mortality; evaluating the potential lifetime benefits and harms of new and existing prevention, screening, and treatment strategies and technologies (including costs and cost-effectiveness); informing the development of screening guidelines and individualized screening strategies; characterizing community screening practices and processes and local, state, and international cancer control planning; assisting in the interpretation of trial results and the design of new trials; characterizing and finding the best opportunities to alleviate health disparities; and serving as the basis for policy and individual clinical decision tools. These model applications have been part of many active collaborations. Most notably, CISNET has conducted work in support of screening guidelines for the US Preventive Services Task Force (USPSTF) for colorectal, breast, lung, and cervical cancers. The robustness of results achieved through comparative modeling provided the USPSTF the confidence to utilize CISNET models in the development of national screening guidelines.

CISNET’s research accomplishments can be seen in over 500 publications in 14 topic areas. For a full listing, see https://cisnet.cancer.gov/publications/.

By accelerating the development of CISNET-type models for additional cancer sites beyond those which have been previously funded under CISNET, the “incubator program" will help the cancer control community assimilate evolving research and help bridge the gap between new interventions and knowledge of how to best utilize them to optimize their population impact.

Specific Objectives, Research Scope, and Requirements for this FOA

Specific Objectives of the Incubator Program

Models: While work on the previously funded CISNET cancer sites has focused on substantive applications using well-developed models, the "incubator program" FOA will foster nascent modeling efforts for other cancer sites. This program will translate CISNET’s framework of success to cancer sites for which there has been limited population modeling and little to no comparative modeling. While there were between three and six modeling groups for the previously funded cancer sites, the incubator program will operate on a somewhat smaller scale, with between two and three independently developed models per cancer site. For the cancer sites previously included in CISNET, the state of simulation modeling is mature, and there are a rich array of studies and data resources as well as numerous cancer control opportunities. However, to “incubate” comparative modeling beyond these cancer sites, these conditions may not all be met. Consequently, applications comprising a more moderate two to three independent modeling groups, which will share common data sources and compare their models as they are developed, will be the focus of the incubator program.

The type of models developed in response to this FOA generally would start with birth cohorts, assigning specific demographics to each individual. Individuals generally proceed to develop risk factors relevant to the cancer of interest during the course of their life. The development of these risk factors can be modeled in detail (e.g. human papillomavirus (HPV) transmission models) or inferred based on population surveys of the prevalence of risk factors for individuals at specific ages born in specific years. This evolving risk profile of simulated individuals may then lead to precursors of cancer and eventually preclinical cancer, which in the absence of screening may lead to clinical cancer. Various screening modalities may be modeled, detecting either the precursors of cancer (if applicable) or preclinical cancer.

Progression rates from precursors of cancer to preclinical cancer, and growth rates of preclinical cancer, are generally modeled using statistical distributions whose parameters are calibrated using multiple target data sets, rather than mechanistic multi-scale modeling of specific biological processes (e.g. modeling at the cellular level with factors such as proliferation rate, transformation rate, angiogenesis etc.). Multi-scale modeling (as was conducted under PAR-13-081, Bridging the Gap Between Cancer Mechanism and Population Science) generally would not be included given the added complexity it brings and the budgetary limitations of these projects, but could be included if well justified to achieve the stated population oriented public health aims. Generally, this would utilize an existing or minor adaptation of an existing multi-scale model (or adding one mechanistic component to an existing model) and should not involve any new primary data collection to inform the model parameters.

At diagnosis, the simulated individual is assigned to either some form of active surveillance or a specific primary and adjuvant treatment and put on an appropriate survival curve until death from the cancer of interest or other causes. More recent adaptions in CISNET have started to include recurrence and secondary treatments.

Research Scope of the Incubator Program

Cancer Site Focus: Each proposed ‘Incubator’ project must be limited to a cancer site other than those previously funded (i.e. breast, prostate, colorectal, lung, esophageal, and cervical cancers previously funded by RFA-CA-19-054) under CISNET. Applicants should also be aware that the NCI's general intent is to fund one project per each "eligible" cancer site. Even though applications will focus on a single cancer site, cross-cancer site work along certain themes (e.g. active surveillance, biomarkers, targeted therapy, overdiagnosis) will be allowed; however, cross-cancer site collaborations would be dependent on the other cancer sites that are funded and their interests.

Important Notes:

  • The cancer site definition of an incubator application will generally be defined using commonly classified sites, such as the grouping of those found in SEER site recodes (ICD-O-3/WHO 2008 definitions or SEER Extent of Disease Cancer Schemas). These lists are defined by combining both topographic and morphology codes using the International Classification of Diseases Oncology, 3rd Edition (ICD-O-3). While there are no black and white rules as to what constitutes a valid incubator "cancer site", they should generally be defined along commonly classified broad groupings (e.g. breast cancer, colorectal cancer that are part of the ongoing program). Although the cancer subtypes included within the selected classification grouping should share some common traits (e.g. precursors, natural history, cancer control strategies, and interventions), heterogeneity across subtypes is to some extent inherent in their definitions. The selected grouping should, therefore, balance three somewhat opposing considerations: homogeneity (subtypes included within the selected grouping should share some common traits); potential population impact (having a reasonably large population “footprint” in terms of the grouping’s morbidity, mortality, and/or economic burden, and the portion of that burden that might be alleviated by strategic and feasible cancer control interventions); and simplicity (through the use of common broad groupings). Applicants are encouraged to include as many subtypes in the grouping as feasible in order to maximize population impact, but rare subtypes can be excluded if including them would pose excessive challenges scientifically (e.g., if modeling one or more rare subtypes would require an entirely different approach than modeling the more common subtypes). Justification for the selected classification should be provided.
  • Studies conducted on one cancer site (especially methodology) may occasionally have cross-cancer site applicability. Nevertheless, to be responsive to this FOA, the vast majority of proposed work (>95%) must focus on a single specified cancer site.

For this FOA, examples of potentially applicable cancer sites include, but are not limited to, the following:

  • Liver cancer, which has increasing incidence and mortality rates, significant health disparities, and hepatitis B and C and heavy alcohol use as risk factors with concomitant prevention, screening, and treatment challenges (e.g. the 1945-65 birth cohorts have high hepatitis C infection rates [largely undiagnosed] and high hepatitis C treatment costs);
  • Anal cancer, which has well-defined high-risk groups (e.g., men who have sex with men, HIV+, HPV+), potentially precancerous lesions (anal intraepithelial neoplasia), and for which a screening modality exists (anal Pap test) but is variably practiced;
  • Bladder cancer, which has smoking as a risk factor, for which low-risk cancers may undergo active surveillance or close post-treatment surveillance to prevent progression, and progressive disease is expensive to treat and associated with significant morbidity;
  • Thyroid cancer, where growing detection of indolent forms may have fueled unnecessary thyroidectomies, and active surveillance of incidental, asymptomatic and small papillary thyroid cancers may be feasible;
  • Stomach cancer, whose risk factors include Helicobacter pylori (H. pylori), smoking, obesity, and Lynch syndrome and for which there are precancerous conditions such as gastric epithelial dysplasia and adenomatous gastric polyps, and identification and surveillance of patients with such precursor conditions and lesions may lead to the prevention or early diagnosis of gastric cancer; and
  • Oropharyngeal cancer, which has HPV, smoking, and alcohol as risk factors, has quite toxic therapies, and there have been efforts to find alternative therapies that may be significantly less toxic (even if they give up some modest efficacy).

Requirements for the Incubator Program

Applications in response to this FOA should indicate that the research activities will adhere to the three key characteristics of the CISNET approach to modeling, which are described above under Key Terms. All U01 projects proposed must employ a comparative modeling approach (see https://cisnet.cancer.gov/modeling/comparative.html).

Transparency in Modeling and Assumptions: To ensure 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). Those approaches accommodate audiences who have different objectives and levels of technical familiarity with modeling. While CISNET investigators will have input into the evolving nature of this documentation, modeling groups will then adhere to common agreed-upon standards.

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 amenable to modeling that are facing that cancer site. 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. For more information, see ‘Targeted Priority Areas’, below.

External Collaborations and Outreach: To fully achieve CISNET's goals, it is essential that the proposed activities emphasize not only the development of models and their application but also the communication and transfer of modeling results to policymakers and members of other organizations who could utilize the results for decision making. Accordingly, one of CISNET's core values has been making the research communities and policy-making entities aware of existing modeling capacity and encouraging collaborations.

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 usually with other independent funding, who may share joint interests and may be willing to join some aspect of the collaborative activities as unpaid "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 targeted by this FOA. Each application should provide coverage in as many of these areas as feasible and appropriate for the cancer site of interest. Nonetheless, these areas are listed as suggestions and are not mandatory. For example, applicants could exclude areas that are less appropriate for a particular cancer site and are encouraged to add different areas that are more germane. Additionally, although this FOA lists the same nine broad, timely priority areas as the main CISNET program, applicants to this "incubator program" may tackle a smaller number of priority areas than sites funded by the main program, given that applicants funded under this "incubator program" will devote considerable time to model development/refinement and consideration of data sources to estimate model parameters. The first years of the application may focus on model development and refinement, while the later years would transition over to developing meaningful applications.

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; and

Area 9) Cancer Site-Specific Opportunities.

Details pertaining to these Targeted Priority Areas 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 relevant to recurrent disease, where there may be biomarkers providing early indications of 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 Quality Adjusted Life Years (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 may assist the modelers (e.g. data from these trials may shed light on the natural history of disease) as well as the trialists (e.g. using modeling to consider trial design alternatives and extrapolating long-term outcomes from short-term 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 researchers from other fields such as behavioral decision scientists or behavioral economists 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 policymakers 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. Data collected in different health care settings reflect 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 the long-term consequences of shortcomings in the process. Results in the community setting may also be better than those demonstrated in a trial when new technologies or strategies improve upon what was studied in Randomized Controlled Trials (RCTs). Modeling can supplement these efforts by estimating long-term savings of these improvements in terms of number of tests, quality of life, and mortality outcomes at the population level, and can be the basis for personalizing screening regimens depending on one's aversion to false-positive test results.

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

Advancing state, local, and international 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. Modelers must consider what parameters must be 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 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 subgroups. 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 the CISNET Incubator Program must be directly motivated by important 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 statistical or 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 examples of methodologic areas of interest include the use of simulation emulators (statistical models that "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, and improved methods for summarizing or averaging of results across models.

Area 9) Cancer Site-Specific Opportunities

Opportunities may exist for cancer site-specific modeling that is critical for that site but may not fit into the eight areas above. For the "incubator program" we especially emphasize Optimizing Strategic Opportunities in Prevention. While some cancer sites previously funded in CISNET have ongoing prevention modeling efforts (especially lung, colorectal, and cervical), cancer sites beyond those currently funded sites present many strategic prevention opportunities related to risk factors such as HPV, HIV, H. pylori, hepatitis B and C, smoking, and excessive alcohol consumption.

Organizational Structure and Coordination of Proposed CISNET "Incubator" Teams

Each proposed CISNET Incubator team must have the following functional elements:

  • Modeling Groups (two to three groups per application); 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 Incubator team must propose 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. While some activities will occur within a cancer site group, post-award representatives from each awarded application will form a central group across CISNET (including those funded under RFA-19-054 and the Incubator Program) and meet regularly to work through proposed ideas and determine which ideas would be feasible and most productive.
  • Trans-network Activities. All incubator program awardees must participate in trans-consortium activities including developing common strategies to enhance model accessibility, cross-consortium projects providing professional enhancement activities for junior investigators, and possibly cross-cancer site collaborations.
     

CISNET Incubator Program Governance and Advisory Panels

Post-award the CISNET Incubator Program awardees will join the awardees of RFA-CA-19-054, which will have already been funded for approximately one year. Incubator Program awardees will participate in all joint CISNET activities including participating in the annual and mid-year meetings, junior investigators' professional enhancement, and model accessibility activities. Coordinating center PIs for the Incubator Program will join the coordinating center PIs for the grants funded by RFA-CA-19-054 to form the Consortium Steering Committee. The incubator program will be governed by the Consortium Steering Committee. For details, see Section VI. 2. Cooperative Agreement Terms and Conditions of Award.

Cancer-site 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.

  • Applications focused on one of the cancer sites (i.e. breast, colorectal, prostate, lung, esophageal, and cervical) previously funded by CISNET.
  • Applications that focus on more than one cancer site (see Cancer Site Focus), e.g. cancers defined by a common genetic characterization across many cancer sites that would require developing several different cancer site models. Studies conducted on one cancer site (especially methodology) may occasionally have cross-cancer site applicability. Nevertheless, to be responsive to this FOA, the vast majority of proposed work (>95%) must focus on a single specified cancer site.
  • Applications with more than one Principal Investigator in the Incubator application who is also funded as a Principal Investigator under the CISNET FOA RFA-CA-19-054.
  • Applications focused on a specific narrowed focus of a cancer among a sub-population or portion of the cancer control spectrum (e.g. liver cancer among Asian Americans, anal cancer screening).
  • Applications that do not include 2-3 modeling groups.
  • Applications that do not use a comparative modeling approach.
  • Applications that involve primary data collection.
     

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

Section II. Award Information

Funding Instrument

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

Application Types Allowed
New

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

Clinical Trial?
Not Allowed: Only accepting applications that do not propose clinical trials

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

The NCI intends to commit $4 million (total cost) in FY 2021 to fund up to four awards.

Award Budget

The budget request (direct cost) for the entire application per year should not exceed $490,000 and $670,000 for two and three modeling groups, respectively.
 

Award Project Period

A project period of up to five years may be proposed.

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

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Local Governments

  • State Governments
  • County Governments
  • City or Township Governments
  • Special District Governments
  • Indian/Native American Tribal Governments (Federally Recognized)
  • Indian/Native American Tribal Governments (Other than Federally Recognized)

Federal Governments

  • U.S. Territory or Possession

Other

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

Required Registrations

Applicant organizations

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

  • Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
  • System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
  • Grants.gov – Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

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

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

Eligible Individuals (Program Director/Principal Investigator)

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

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

For this FOA, applicants are required to designate multiple PDs/PIs. Generally, one PD/PI would be expected for each modeling group, and one of these PD/PIs would also be responsible for the coordinating center. Other arrangements may also be proposed if justified. For example, the coordinating center PD/PI does not have to be a modeling group PD/PI, and additional PD/PI can be added for specialized aims.

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 incubator application in response to this FOA.

While open to all qualified investigators, to encourage broad participation from population modelers in cancer control, this FOA will allow no more than one Principal Investigator who is funded under the CISNET FOA RFA-CA-19-054 to also be a Principal Investigator on each Incubator application.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

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

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

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

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

Letter of Intent

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

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

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

The letter of intent should be sent to:

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

Page Limitations

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

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

Instructions for Application Submission

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

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

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).
SF424(R&R) Senior/Key Person Profile

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

R&R or Modular Budget

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

It is anticipated that requested budgets will vary, depending on the scale of work, especially the number of modeling groups proposed. The budget request (direct cost) for the entire application per year should not exceed $490,000 and $670,000 for two and three 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 down 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:

Coordinating Center. The budget allocation for the Coordinating Center should generally not exceed $130,000 in direct costs per year. Included as part of this budget will be a contribution to consortium-wide professional enhancement activities which would generally not exceed $40,000 in 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. If the development of a model to be included is being partially funded by another grant, then a smaller budget for this group would be expected. 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 for that cancer site if needed.

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 usually held at NCI (approximately 2 days for a cancer site-specific meeting, with an additional half-day for a cross-cancer site plenary session, as well as junior investigators and model accessibility sessions) and (2) a mid-year meeting with individual cancer-site specific meetings of approximately 2 days as well as junior investigators and model accessibility sessions. Both of these meetings are usually held at a common location and time for the entire consortium to facilitate cross-cancer site interactions as well as allowing modelers who are part of more than one cancer site group to easily participate.

The mid-year meeting is usually held at one of the modeling group’s home institutions, selected from the entire consortium on a rotating basis, and that group is expected to host the meeting, provide administrative support, and on-campus meeting rooms if possible. Applicants should budget to host one meeting during the 5-year grant period. NCI (or a designated contractor of NCI) would provide meeting support including paying for conference rooms and AV fees, creating and maintaining a registration website and preparing meeting materials (including preparation of agendas, name tags, list of attendees, signage, etc.) that would be sent to the site. The major necessary support is a local administrative staff who can assist NCI (or its contractors) by finding and reserving conference space (including AV equipment), determining the best hotel to secure a room block, suggesting local transportation options (including shuttles if needed), staffing the registration desk during the meeting, etc.

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Specific Aims: Outline Specific Aims (generally 3-6 aims are expected). Indicate how the aims proposed correspond to the priority areas to be addressed, although some aims could be devoted to model and data source development, validation against data sources not used to develop the model, and exploration of comparisons across models.

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

Sub-section A. Overall Objectives and Significance.

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

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

Sub-section D. Proposed Model Development, Refinement, Consideration of Data Sources, Model Validation, Model Comparisons, Model Extensions, and Applications.

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:

  • Justify why the selected cancer site fulfills as many of the criteria as possible for inclusion as an "incubator site” (i.e. data sources exist to inform the models -- especially the preclinical natural history of the disease, potential interventions or strategies are sufficiently well developed to provide data-driven estimates of their operating characteristics, there are cancer control opportunities at different points across the cancer control spectrum that are amenable to modeling, and these opportunities could have impactful public health benefits) and the specifications of the selected cancer site (e.g. selected ICD-O-3 codes).
  • 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 site;
  • List the broad, long-term objectives and the goal of the specific research proposed;
  • The goals should be stated both in terms of the modeling work that needs to be done and in terms of the broader health care objectives 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 site and across CISNET (including both those funded under the Incubator Program and RFA-19-054) will be integrated and coordinated. This section should have four subheadings:

B.1 Team Leadership and Coordination - Each proposed incubator 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 cases (i.e. joint comparative modeling projects) 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 policymakers;
  • Coordinating review of new and relevant literature, inviting guests to meetings, and vetting of proposed affiliate members; 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 site 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, the incubator team would be run through consensus.

Professional enhancement opportunities for junior investigators should be included as part of the coordinating center activities. The idea is to take advantage of the rich diversity of expertise and approaches across the CISNET consortium (including both Incubator Program members and those funded under RFA-CA-19-054). Some examples include (but are not limited to) regular lectures and webinars, extending annual or mid-year meetings to have a mini meeting coordinated by junior investigators, a program to allow visits to other modeling groups or cancer site groups, a program for funding projects for junior investigators, etc. Once the consortium is funded, one (or more) representatives from each awarded application will form a central group across CISNET to sort through these ideas and determine which ones would be feasible and most productive under the anticipated budgets, and then implement them.

B.2 Advisory Panel (optional) - An external panel to advise the incubator 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.3 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, 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 site 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 site, and/or members across cancer site 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 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.

While each application should put forward their vision for model accessibility, there will be a cross CISNET working group on this topic to discuss experiences and explore best practices. While variability will be allowed across cancer sites, and individual models within a cancer site, whenever possible common formats and standards across CISNET will be the desired goal.

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

Modeling 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 institutions of the modeling groups proposed. Applicants are expected to present a coherent and well-conceived plan that will permit the 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 site;
  • The expected roles of individual modeling groups and their contributions to collectively achieve a reasonable coverage of issues relevant to a given cancer site across the cancer control spectrum;
  • Identify comprehensive, "full-fledged" modeling groups that are expected to participate in the full range of work across the cancer control spectrum, 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.

Models

  • Give an overview of each model, summarizing clearly underlying model structures and assumptions.
  • For each proposed model, describe its current state of development, e.g. is it currently a model that:
    • Is still in its very early conceptual stages. While this is allowable, it must be well described and justified so that the viability of the model can be reasonably assured;
    • Has been programmed but is still undergoing basic model calibration and validation
    • Has been developed for a limited range of applications in a narrow range of the cancer control spectrum (e.g. a model that has just been applied to estimating the cost-effectiveness of treatment alternatives);
    • Is not a true "population-model", i.e. starting with the general population and modeling all of the steps through death due to the cancer of interest or other causes.
  • Describe how the model will be extended under this grant, making it a true population model covering the full cancer control continuum. Describe the level of specificity modeled for different portions of the continuum. Describe the amount of time that will be needed to develop these extensions, and when the model will be ready to be utilized for specific substantive applications;
  • Does the model 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 and publications.

 

Note: Summarize the results of this section in two tables:

Model Characteristics (required): Provide a table summarizing key model differences and similarities, and stage of development.

Model Applications: Provide a table summarizing prior model applications (referencing publications if applicable). Note that not all models will be at a stage at the start of the project where they will have developed applications. In this case, simply specify N/A. However, if at least one model has applications, the table is required.

Applications without the required table(s) will not be reviewed.

Sub-Section D. Proposed Model Development, Refinement, Consideration of Data Sources, Model Validation, Model Comparisons, Model Extensions, and Applications:

Provide a coordinated plan of model development, model validation, model comparisons (under both hypothetical scenarios and in realistic applications), and reasonably comprehensive coverage of the cancer control issues amenable to modeling for the cancer site 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. Describe the development of shared common inputs for models. For example, the CISNET lung group developed a shared common "U.S. smoking history generator" which given a set of characteristics of the person (e.g. year of birth, sex) generates the age they initiated smoking, how many cigarettes per day they smoked, and when (and if) they quit.

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

In addition:

  • If the models will be starting at various stages of development, how will the timing of cross-model activities (e.g. comparative modeling under both hypothetical and real applications) be coordinated?
  • If modeling methodology is proposed (priority area 8) justify the development of the methods in terms of 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 sites. Limited availability of data and studies for certain cancers may limit the ability to include certain areas. Efforts in specific areas should be commensurate with the potential of emerging findings in that area to ameliorate 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: To summarize the results of this section, one table is required:

Modeling Projects: Provide a table summarizing modeling projects including model development, development of data sources, common model input simulators (e.g. smoking history generator), model validation, comparative modeling under hypothetical scenarios, and applications 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.

Applications without the required table will not be reviewed.

NOTE: It is up to applicants to make the case that a cancer site is amenable to comparative simulation modeling and that opportunities exist for public health applications that would achieve substantial benefits in terms of mortality, morbidity, or even considering individual or societal economic impact of the disease. Applicants must bring together independent and complementary modeling efforts focusing on important cancer control applications at various points across the cancer control spectrum. This requires starting with modeling efforts that may be at various stages of development (from nascent to more developed), and sufficient data sources must exist to support further development of the models to represent as much of the cancer control continuum as possible, especially the preclinical natural history of the disease. The first years of the application may focus on model development and refinement, while the later years should develop meaningful applications. Proposed cancer sites must have existing, new, and/or evolving cancer control opportunities that are mature enough that policy and/or clinical interventions have been deployed or could be soon. The applicant will need to show that there are perceived inefficiencies or misapplication of evidence in how these cancer control strategies have been or might be deployed, or even cases where interventions should potentially be de-implemented. Potential interventions or strategies should be sufficiently well understood so that for most of the modeling efforts the modelers do not have to rely on pure “guesses” as to their operating characteristics (i.e. what-if analyses).

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

The following modifications also apply:

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. In addition to the stated NIH data sharing policies, the Data Sharing Plan must address the following specific aspects:

  • 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);
  • 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.; and
  • 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).
Appendix:

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

PHS Human Subjects and Clinical Trials Information

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

PHS Assignment Request Form

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

Foreign Institutions

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

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

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

4. Submission Dates and Times

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

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

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

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

Post Submission Materials

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

Section V. Application Review Information

1. Criteria

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

For this particular announcement, note the following:

The emphasis of this FOA is on research that uses a rigorous comparative simulation modeling approach to address the major cancer control issues, for which there is an opportunity to make a public health impact for a given cancer site. The strength of each application will be judged on the various dimensions described above in the Research Strategy section and, recognizing that no application is likely to be strong on every dimension, the various tradeoffs involved will be considered.

Overall Impact

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

Scored Review Criteria

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

Significance

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

Specific for this FOA

For the cancer site selected, how sufficient are the opportunities across the cancer control continuum that have the possibility of making a substantial population impact? 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 site? 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? How well does the application addresses realistic strategies and issues that have a real potential for being implemented in the population?Has the application address any important de-implementation issues for this cancer (i.e. where strategies or technologies that have been adapted should be modified or disbanded)?

Investigator(s)

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

Specific for this FOA

How strong is the team in terms of expertise to conduct the proposed modeling? How appropriate is the team’s 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? How appropriately does the application balance the need to have appropriately senior and mid-level leadership against the need to provide rising junior investigators the opportunity of leadership? How appropriate are the qualifications and experience of the PD/PI responsible for the proposed Coordinating Center to lead and coordinate a modeling program of this size and complexity?

Innovation

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

Specific for this FOA

 Does the application provide strong justifications for the approach to evaluate the value of new and existing health care technologies?

Approach

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

 

 

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

Specific for this FOA

How well does the suite of models proposed complement each other in terms of providing different perspectives and/or different ways of synthesizing/integrating available evidence? How well will the proposed models and future model development be sufficiently independent so that there will be sufficient heterogeneity of approaches to justify robust comparative modeling? How adequate are the data sources to build the models and to inform the models in the key areas of application? How well 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 policymakers and cancer control planners?

Environment

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

Specific for this FOA

Do the proposed modeling groups come from institutions where modeling activities will be nurtured and are an established element of the research environment? How adequate are the planned collaborative arrangements with appropriate study and trial groups to ensure timely access to new data for incorporation in the models?

Coordinating Center and Program Integration

How adequately 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? How robust are there plans to coordinate the timing of joint modeling activities for models that may start out at different stages of development, requiring differing amounts of time to become operational? How flexibile are the plans for the Coordinating Center to promote and incorporate group input and consensus decisions? How strong are the plans for the Coordinating Center to include creative options for comparing models, reaching group consensus, and synthesizing results for use by cancer control planners and policymakers? How adequate are plans for conducting base cases, fielding outside inquiries, and other group activities? How adequate are the plans to keep abreast of current policy related controversies, and the latest research results across the spectrum of treatment, screening, and prevention for their cancer site? How reasonable are the proposed plans for career enhancement and model accessibility?

Additional Review Criteria

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

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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

Vertebrate Animals

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

Biohazards

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

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

Additional Review Considerations

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

Applications from Foreign Organizations

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.

Select Agent Research

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

Resource Sharing Plans

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

Authentication of Key Biological and/or Chemical Resources:

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

Budget and Period of Support

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

2. Review and Selection Process

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

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

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

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

 Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the 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 sites. Therefore, it is anticipated that there will be no more than one award per cancer site.

3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information

1. Award Notices

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

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

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

2. Administrative and National Policy Requirements

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

HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.

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

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

Cooperative Agreement Terms and Conditions of Award

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

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

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

  • Determining research approaches and procedures, developing and applying their models, and analyzing/interpreting results;
  • Defining objectives and approaches, and to plan, conduct, analyze, interpret, and publish results;
  • Collaborating with their Coordinating Center and the other PDs/PIs on their incubator award;
  • Serving as a member of an appropriate Cancer-Site Specific Leadership Team;
  • Participating in collaborative modeling activities, sharing information, as appropriate, about model structure and assumptions at working group 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 generally be in the Washington, DC area, and the second meeting will generally be 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 and provide on-campus meeting space (if available) 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 who are interested in joining the collaboration). Affiliate membership will be approved by the PD/PIs in the applicable cancer site; and
  • 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-Site Specific Leadership Team;
  • Coordinating the agendas of the cancer-site-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 the 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 policymakers;
  • Fielding outside requests and working with the modeling awardees to determine priorities;
  • Coordinating conference calls and communication within the cancer-site specific group;
  • Setting (in consultation with the other PD/PI’s) the publication agenda and schedule;
  • Coordinating the preparation of the annual progress reports by the individual PD/PIs;
  • Maintaining a set of policies and procedures within the cancer-site 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.

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

  • An NCI Program staff member designated as the overall NCI Project Scientist for the ongoing CISNET program as well as the ‘incubator program’, which will be part of the CISNET network. The overall NCI Project Scientist will serve as a voting member for NCI on the CISNET Steering Committee that will include representatives from the ‘incubator program’ awardees and the ongoing CISNET program;
  • The NCI will also designate additional NCI Project Scientists for each of the newly funded cancer organ sites under the 'incubator program'. These cancer-site specific NCI Project Scientists will serve as voting members of the Cancer-Site Specific Leadership Teams, along with the PIs from that cancer site, and any other members as designated by consensus of the cancer-site specific steering sub-committee;
  • The specific roles of the substantially involved NCI staff members include the following activities:
    • Access modeling results generated under this award to coordinate and implement CISNET modeling approaches;
    • Contribute scientifically to the process of model applications and participate in analyses of joint model results and publication efforts;
    • Assist the awardees by sharing information about a wide range of data resources that can be used for parameter estimation and population trends in modeling and/or serve as a conduit to the potential utility and access to these resources;
    • Provide advice on other specific scientific and technical issues as needed to the awardees;
    • Serve as liaisons to other NCI scientific staff members if additional expertise or resources are needed;
    • Provide information about possible collaborative opportunities with relevant NCI sponsored consortia, and other relevant government and non-governmental organizations doing related work;
    • Support 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;
    • Monitor a public web site for CISNET;
    • In consultation with the Coordinating Center PI/PD's, set the location of the two annual meetings and 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;
    • Facilitating collaborative research efforts that can involve multiple cancer site groups both from the ongoing CISNET program as well as the ‘incubator program’;
    • Monitoring the operations of the CISNET and ‘incubator program’ awardees and making recommendations on overall project directions and allocations of U01 funds; and
    • Reviewing the progress of the ‘incubator program’ awardees (including Coordinating Center), conducting periodic site visits, and taking other actions as needed.
  • Additionally, an NCI program director acting as Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

The NCI Project Scientists and the PD/PI of the Cooperative Agreement awards funded under this initiative will be jointly responsible for participating in initiative-wide as well as CISNET-wide activities and for establishing inter-project collaborations. In addition to the interactions defined above, the NCI Project Scientists and awardees shall share responsibility for the following activities via a CISNET Steering Committee, which will serve as an organizational body for the NCI and awardees.

The Steering Committee will serve as the CISNET’s main governing board as defined below. The NCI Overall Project Scientist and the Coordinating Center PDs/PIs for each cancer site 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 from the main ongoing program and ‘incubator program’ awardees; and
  • The NCI Overall Project Scientist.
  • Other individuals may be invited on an ad hoc basis as non-voting members.
  • Each member of the Committee including NCI Overall Project Scientist (on behalf of NCI) will have one vote.
  • All Steering Committee decisions and recommendations that require voting will be based on a majority vote.
  • The chair of the steering committee will be elected by the members and have a term of one year but can serve consecutive terms.

Subcommittees: The Steering Committee may establish subcommittees for specific purposes, but the following will serve as the 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-Site Specific Leadership Team: these subcommittees will consist (for each cancer site) of the PDs/PIs from that cancer site, the NCI Project Scientist for that cancer site, and any other members as designated by consensus of the cancer-site specific steering sub-committee. The chairs of these subcommittees will be the coordinating center PD/PI for that cancer site, and the role of these subcommittees will be to review work progress and ensure utilization of resources developed by CISNET. All decisions and recommendations that require voting will be based on a majority vote.
    • Model Accessibility Subcommittee: this subcommittee will coordinate model accessibility activities across CISNET. There may be some activities taken up by an individual model, or a specific cancer site group, but the purpose of this group will be to convene cross-CISNET informational activities, demonstration projects, and/or develop standards. The chair of this subcommittee will be elected by the members, and will serve for one year, but can serve consecutive terms. All decisions and recommendations that require voting will be based on a majority vote.

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

    • Setting Network-wide consortium policies and procedures;
    • Providing guidance to Cancer-Site Specific Leadership Teams and other subcommittees to assist them in interpreting and adhering to Network policies and procedure;
    • Coordinating communication between the Cancer-Site 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 (for meetings outside the Washington DC area, 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); and
    • 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.

3. Reporting

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

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

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

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

Section VII. Agency Contacts

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

Application Submission Contacts

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

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

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

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

Scientific/Research Contact(s)

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

Peer Review Contact(s)

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

Financial/Grants Management Contact(s)

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

Section VIII. Other Information

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

Authority and Regulations

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


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