Required Application Instructions

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

Part 1. Overview Information
Part 2. Full Text of the Announcement
Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

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

All applications in response to this FOA will be new applications.

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

1. Enhanced understanding of the impact of cancer control interventions (screening, treatment, prevention) on current and future trends in incidence and mortality;
2. 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
3. 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.

Modeling - Definition: 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.

Overall goals of CISNET Program: The overall purpose of the CISNET Program is to explore the areas where modeling can assist in optimizing the translation of discoveries in basic cancer research to clinical practice. This FOA will support CISNET activities in a systematic manner across all four main phases of the translation process (i.e., T1 initial discovery to health application; T2 health application to evidence-based practice guidelines; T3 practice guidelines to health practice; and T4 health practice to population health impact). CISNET models must provide a platform for evaluating the potential downstream consequences of decisions and strategies that are made in earlier phases. Applications of these models should provide effective tools for helping to optimize cancer-relevant decisions.

The Concept of CISNET Program: CISNET program stems from the original concept to create virtual laboratories performing in silico experiments of potential public health strategies. Thus, the CISNET modeling approach advances the practice of modeling to inform clinical and policy decisions. Collaborative, interactive projects involving groups of researchers promote efficient gathering and sharing of the most important data resources, and critical evaluation of the strengths and weaknesses of these resources. A systematic comparative modeling approach brings transparency to the modeling process. The key factor in the CISNET modeling approach is a joint evaluation of results from a range of models, as opposed to a single estimate from one model. This multi-model approach increases the overall credibility of the modeling process, and enhances the accuracy and reproducibility of the results. These highly desirable attributes are of fundamental significance for cancer control planning and policy guidelines and decisions.

CISNET models are capable of translating evidence from randomized trials and epidemiological studies to the population setting. Key to such translation is the extrapolation of evidence from tightly controlled studies to the general population accounting for actual usage patterns of these technologies in less controlled settings. Modeling real and hypothetical scenarios allows for the identification of key factors influencing outcomes and efficient cancer control strategies. CISNET research can inform clinical practice and guidelines by synthesizing existing, although often incomplete, knowledge in a modeling framework under clearly specified assumptions, in order to better understand the impact of interventions over the entire life course. This type of information is not directly observable since it involves the pre-clinical natural history of disease, and many studies exclude the elderly and rarely have enough extended follow-up to reflect the full life course of individuals. CISNET provides a suite of models that are able to meet the challenges of the increasing pace of scientific discovery and are poised to address emerging questions, and to determine the most efficient and cost-effective strategies for implementing technologies in the population.

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

Accomplishments: Since the inception of CISNET, the program has resulted in many significant contributions to translational research and public health, reflected by over 290 publications (for the full list see http://cisnet.cancer.gov/publications/).

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

• A decision analysis in support of the U.S. Preventive Services Task Force (USPSTF) development of lung cancer screening;
• Quantifying the impact of smoking reduction on U.S. mortality from a century of population data;
• Addressing gaps and unanswered questions from the USPSTF guidelines for breast and colorectal;
• Extending interpretation of trial results using modeling;
• Development and application of meta-synthesis or model-based meta-analysis for combining trials when the study protocols are too different to combine under standard meta-analysis;
• Modeling a large number of candidate PSA screening policies;
• Development of a clinical decision tool for BRCA1/BRCA2 carriers;
• Modeling the impact of obesity on race specific breast cancer mortality;
• Interpreting estimates of overdiagnosis; and
• Model building, calibration, and application of esophageal cancer models.

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

Flexible broad-based disease models: CISNET models incorporate a central cancer model (usually including the natural history of the disease prior to its clinical appearance), which can be modified by the full range of cancer control interventions such as changing risk factor profiles of the population, evolving screening modalities, and new treatment regimens. Outputs can include the full range of the benefits and harms or costs of the interventions. Flexible models of this type are easily adapted to characterize new technologies as they are developed. For example, CISNET models were easily adapted to incorporate the costs, operating characteristics, and unique logistics (e.g., optical colonoscopy following a positive screen) of CT colonography.

Multiple birth-cohort modeling: There is increasing recognition that modeling a single hypothetical cohort often does not fully capture the entire impact or potential cost effectiveness of an intervention as implemented in a broad population. CISNET models should have the capability of being multi-cohort models, capturing a range of birth cohorts and the changing risk factor profiles, screening behaviors, and treatments used by each cohort as it ages, allowing full representation of the impact of intervention in the actual U.S. population.

Comparative modeling: A key factor in the CISNET modeling approach is the joint evaluation of results from a range of models, as opposed to a single estimate from one model. Independent modeling efforts often yield disparate results that are difficult to reconcile. A comparative modeling approach explores differences between models results in a systematic way. Comparative modeling produces a range of results across models and, when consensus can be reached, greatly enhances the credibility of modeling results by highlighting their reproducibility. When results are disparate, it can help to pinpoint areas where our knowledge base is insufficient and further research is needed.

Transparency in modeling and assumptions: CISNET has developed and implemented standardized documentation for their models. Model profiles (see http://cisnet.cancer.gov/profiles/ ) are standardized descriptions that facilitate the comparison of models and their results. Users can read documentation about a single model or read side-by-side descriptions that contrast how different components of the process are modeled. In addition to technical documentation, work is now underway to develop an alternative set of documentation designed to be accessed by policy makers or cancer control planners who want to collaborate with CISNET or understand model results, but are interested in a practical overview or a comparison of models rather than technical details.

Specific Objectives, Research Scope, and Requirements for this FOA

Main areas of focus and key required attributes: Whereas the overall theme of this FOA is similar to the previous issuance of the CISNET Program, there are several important differences. The main characteristics include the following:

Models: Modeling efforts proposed must adhere to the definition given above. Most models should include a natural history component , modeling the initiation, growth, and metastatic spread of the tumor, relevant precursor lesions, and biomarkers prior to (and possibly after). Models without a natural history component can be included, but the application should describe how they complement the suite of models proposed. Investigators may propose the application, extension, refinement and/or merging of existing models. If well justified, an existing model can be reformulated using a more robust statistical/mathematical framework. However, de novo model development will NOT be supported.

Cancer Sites: Each proposed project must be limited to cancers of one of six organ sites listed here: prostate, colon/rectum, breast, esophagus, lung, and cervix (cervical cancer is added for this CISNET re-issuance). Applications focused on other cancer sites will be viewed as non-responsive and will not be reviewed. Applicants should also be aware that the NCI’s general intent is to fund one project per each eligible cancer site.

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 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 organ site.

Outreach and Collaborations: To achieve the full goals of CISNET, a core value has been to make the research and policy communities aware of the existing modeling capacity and to encourage active collaborations. Examples of collaborations include the U.S. Preventive Services Task Force, the Center for Medicare and Medicaid Services, the CDC’s Division of Cancer Prevention and Control, the American Cancer Society, the American College of Radiology Imaging Network, the PCLO, NLST, and European Randomized Study on Screening for Prostate Cancer (ERSPC) trial groups, the Barrett's Esophagus Translational Research Network (BETRNet) and the Evaluation of Genomic Applications in Practice and Prevention (EGAPP) working group. In addition, CISNET encourages affiliate membership, where outside modelers or others with special expertise can join the collaborative activities.

Applicants are strongly encouraged to form appropriate collaborations, for example, with: (a) investigators who are involved with cancer-relevant clinical prevention, treatment, or screening trials and/or epidemiologic or observational studies; (b) investigators involved in other cancer-relevant programs; (c) policy and/or guideline setting organizations/entities; (d) professional societies; (e) other relevant government agencies and (f) patient, caregiver, and other relevant stakeholder organizations. In addition to the extension of models and their application, it is essential that the proposed activities emphasize the communication and transfer of modeling results to policy makers and members of other organizations who could utilize the results for decision-making.

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

Area 1) Exploring the Evolving Potential of Stratification based on Polygenic Risk for Cancer Screening and Genomic Tumor Profiles for Treatment;

Area 2) State, Local, and International Cancer Control Planning;

Area 3) Understanding How Screening and Treatment Work in Real-World Settings and Determining the Best Routes to Optimize the Processes;

Area 4) Assisting in the Development of Decision Support Tools;

Area 5) Evaluating Natural Experiments Generated as a Result of the Affordable Care Act (ACA);

Area 6) Value of Information Analyses;

Area 7) Pan-Cancer and Pan-Disease Modeling;

Area 8) Suggesting Optimal Routes to Reduce Health Disparities; and

Area 9) Cancer-Specific Opportunities.

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

Area 1) Exploring the Evolving Potential of Stratification based on Polygenic Risk for Cancer Screening and Genomic Tumor Profiles for Treatment

Polygenic risk is based on the additive effects of many genetic variants and their association with disease risk. To date, the discriminatory ability of polygenic risk models has not been sufficient to utilize for risk stratification in population screening. Modeling can help determine the discriminatory thresholds these polygenic models must reach to become clinically useful. CISNET models can also assist in transforming this knowledge into practical population-based screening guidelines. For example, while behavioral risk factors and family history evolve over one's lifetime, polygenic risk has the ability to be at least partially established at birth, raising questions as to the age when genetic testing might occur, and how genetic and non-genetic factors should be combined in models. Polygenic risk stratification has the potential of identifying both high and low risk individuals. The U.S. is plagued by overuse of screening in certain segments and underuse in others, and identifying low risk individuals could help partially alleviate this problem by targeting individuals for less intense screening regimens. In this context, modeling could help determine cut-points for low risk individuals, and evaluate alternative screening schedules. Modeling can also help address the balance of benefits and harms of risk stratified screening. Finally, to be effective, screening needs to identify cancers in the mid-range of aggressiveness rather than cancers that are so indolent that they would never produce clinical symptoms during one’s lifetime, or cancers that are so aggressive that early detection would be unlikely to make any difference. Traditional GWAS studies only discriminate between cases and controls; however, more recent studies consider factors such as aggressive prostate cancer, ER+/- breast cancer and colorectal adenomas. CISNET models would use information from these studies to more fully exploit links between specific polygenic risk profiles and the natural history of disease to determine optimal screening regimens. Work in this area is being piloted by the CISNET colorectal group in support of the Evaluation of Genomic Applications in Practice and Prevention (EGAPP) working group. The pilot project is working to include familial and polygenic risk in their natural history models and to evaluate potential risk stratified screening strategies. Collaborations with genetic epidemiologists should be considered in advancing this area.

Efforts, such as The Cancer Genome Atlas (TCGA), have improved our knowledge of the genomic characterization of cancers. Further, there have been recent examples where treatment of cancer is informed by the tumor’s molecular subtype, which may lead to advances in precision medicine. Modeling can inform the future directions of this research by tying specific subtypes to explicit models of the natural history of disease. As researchers explore candidates for novel therapies based on their tumor profile, CISNET models can integrate evidence on the prevalence of target profiles and the potential benefit of these therapies, to understand the impact of these therapies on population mortality. As treatment stratification becomes more refined, the cost of these therapies climbs, and competing therapies are developed, modeling could become a key to evaluating the comparative effectiveness of different treatment strategies in real world settings.

Area 2) State, Local, and International Cancer Control Planning

While a major thrust of CISNET efforts has been cancer control planning at the national level, CDC supplements have supported selected efforts to assist state and local cancer control planners. For example, CISNET investigators worked with cancer control planners from South Carolina to assist in determining the best program that could be developed for a fixed budget to provide colorectal cancer screening for uninsured individuals aged 50-64. In another supplemental study, CISNET investigators worked with planners in Northeastern Pennsylvania to determine the best frequency of colorectal cancer screening based on that populations 25% elevated risk of colorectal cancer relative to the U.S. population. In all cases, state estimates from national surveys or local data were utilized to customize the models to the local area. From these pilot projects, modelers now understand how to tailor model inputs developed for national analyses based on more limited data at the state- or local level. Based on these experiences, the emphasis should be on developing state and local models that could be customized with less intensive efforts than those undertaken in these pilot programs and/or interfaces with limited sets of parameters that could be customized to state or local conditions.

A stated NCI priority is to advance global cancer research to address worldwide challenges in cancer. The NCI Center for Global Health will serve as a liaison in establishing linkages between consortia of cancer planners in various countries and modelers, with a focus on middle-income countries. Cancer control planning in middle-income countries represents an opportunity for CISNET to make an impact on planning efforts in these countries. Much like state and local cancer control planning, international cancer control planning requires customization of models to the target countries disease and health care characteristics. International collaborations bring up many unique issues with respect to different health care systems, cultural barriers to screening and care, access to health care, and the data infrastructure necessary to support modeling. Challenges with respect to the data infrastructure necessary to support modeling efforts should be taken into consideration.

Area 3) Understanding How Screening and Treatment Work 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 considerably attenuated when screening is implemented in routine clinical practice. For example, USPSTF’s recent draft lung cancer screening recommendations are based on a 20 percent reduction in lung cancer mortality in the low-dose CT screening arm of the NLST trial, which was conducted at specialized screening centers. However, screening of lower-risk individuals who would not have met the eligibility requirements of NLST, interpretation of CT examinations by community radiologists, and variable protocols to follow up suspicious nodules could lead to substantially smaller benefits than observed in the trial setting. CISNET investigators could help optimize the translation of clinical trial results to practice in population settings. A prerequisite is to develop new partnerships, and leverage existing ones, with investigators collecting cancer screening process data in community settings. For example, PROSPR (Population-based Research Optimizing Screening through Personalized Regimens) is an NCI-sponsored program that recognizes that screening is not a singular event, but rather a process (recruitment, screening, positive screen evaluation, diagnosis, referral for treatment), and that all parts of the process must be optimally completed in order to maximize the benefits of screening. PROSPR collects data on all phases of the process in various health care settings for breast, colorectal, and cervical cancers. Modeling can quantitate the reduction in screening effectiveness that occurs with breakdowns at various stages in the screening process and identify the most important leverage points to improve efficiency. PROSPR includes modelers (including CISNET modelers), but formal CISNET-PROSPR collaborations could foster comparative modeling to help bring additional credibility and consensus to complicated cancer control issues. Modeling also could estimate the costs and/or effects of strategies to intervene at those breakdowns. Other research could also result in beneficial collaborations. For example, CISNET investigators have had a long term collaborative relationship with the Breast Cancer Surveillance Consortium. The Cancer Research Network, an NCI-funded consortium of 9 nonprofit research centers based in integrated health care delivery systems, represents another resource where additional partnerships could be developed. Similar modeling efforts can be conducted in the area of optimizing treatment using other data sources.

Area 4) Assisting in the Development of Decision Support Tools

It is widely believed that preference-sensitive screening and treatment decisions should be shared between the patient and his or her physician. For example, the USPSTF stated The decision to start regular, biennial screening mammography before the age of 50 years should be an individual one and take patient context into account, including the patient's values regarding specific benefits and harms. Additional assistance can come from decision support tools that inform patients and physicians about the potential harms and benefits of screening and treatment options and allow them to make decisions based on their 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 processes. Models can also estimate quantities, such as over-diagnosis and over-treatment, which are not directly observable in trials. Since modeling results can provide key elements for input into decisions, CISNET modelers could team with established decision analysts to support the development of tools that could be used directly by the public, by health care professionals to guide shared decision making, or by physicians to aid in making decisions, e.g. assisting radiologists in making decisions about call backs. In addition to directly supporting the development of tools, CISNET models could be used to evaluate the benefits versus costs and associated burdens (especially the time costs for health care providers) of specific models of shared decision making and the resultant choices and their long term outcomes; CISNET models could also be used to consider approaches to implementing shared decision making in clinical practice and consequences of that implementation at patient, provider, and practice levels.

Area 5) Evaluating Natural Experiments Generated as a Result of the Affordable Care Act (ACA)

As the ACA is implemented across the country (in some cases differently in different health care settings and geographic areas), there will be opportunities to explore the differential impact on health care outcomes. For example, while the ACA requires that all health insurance plans eliminate cost-sharing for high value preventive services, it exempts existing employer sponsored (group) plans from these policies if they do not make major changes in their benefits or policies. This sets up a natural experiment on how the elimination of cost sharing affects usage. However, these natural experiments are often difficult to interpret. Simulation modeling is an ideal way to explore these relationships, and allows for control of confounding factors, time lags between policy changes and their impact, and statistical variation. Opportunities include modeling of the potential attenuation in health disparities as a result of improved access to care, the impact of access to BRCA and other genetic counseling for women at higher risk, and the elimination of cost sharing for mammography and colonoscopy. Part of the ACA includes enhancement of surveys to support research on the impact of the ACA, including enhancements to BRFSS, NHIS, the National Ambulatory Care Surveys, and MEPS, and these surveys can be used to supply vital model inputs.

Area 6) Value of Information Analyses

Value of Information (VOI) analysis is an area of decision science that quantifies how much answering a question allows a decision-maker to improve the decision, or the potential economic losses associated with choosing suboptimal policies, when that decision is made with uncertain information. Historically, one limitation of the development of VOI analyses has been the effort necessary to build appropriate models and informing the models with appropriate data. CISNET models are ideally structured to incorporate VOI analyses, since they can take advantage of much of the existing model structure and data already accumulated and incorporated into the models. VOI analyses can evaluate the impact of individual decisions (e.g. the decision to get an additional scans or tests prior to starting therapy, the impact of which can be aggregated up to the population level), or the Value of Research (VOR) (e.g., the decision to conduct additional laboratory studies to better understand a mechanism of action prior to launching a large expensive cancer prevention study). VOI analyses can help identify which of the uncertain parameters have the largest leverage in the final outcome, and thus can pinpoint the topics that are most important in making policy. The VOI methodology and its application in health care have recently been attracting more attention (e.g., http://grants.nih.gov/grants/funding/SBIRContract/PHS2014-1.pdf and http://www.pcori.org/assets/Value-of-Information-and-Research-Prioritization2.pdf ).

Area 7) Pan-Cancer and Pan-Disease Modeling

While each application focuses on a single cancer site, it has become increasingly apparent that cross-cancer or cross-disease work has tremendous potential. Risk factors like smoking and obesity affect more than just the single cancer under study. A number of single nucleotide polymorphisms have been identified with pleiotropic effects that affect the risk of multiple cancers. Additionally, comprehensive characterization is redefining how cancers are classified, and commonalities in somatic alterations across cancer sites may lead to discoveries of treatments that are effective across cancers. Diseases like chronic obstructive pulmonary disease (COPD) interact in complex ways with lung cancer. While still keeping the single cancer site as the focus, applicants may propose modeling studies which relate that cancer to other diseases. Collaborative opportunities may emerge with the other cancer sites funded under this FOA, and applicants may describe how they will utilize rapid response funds to capitalize on these opportunities.

Area 8) Suggesting Optimal Routes to Reduce Health Disparities

Applicants are encouraged to explore both the source of disparities and the best leverage points to reduce them. Modelers are encouraged to move beyond the standard racial/ethnic characterizations of health disparities and utilize data sources that will enable modeling as a function of disparities in terms of income/education, insurance status, geography, and access to health care. 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 9) Cancer-Specific Opportunities

In addition to the theme areas listed above that cut across cancer sites, there are many opportunities specific to each cancer site to be leveraged in the next round of CISNET. For example, in breast cancer, there is increasing discussion of possible trials of active surveillance of low-risk DCIS (especially in the UK), and follow-up information from trials of this type coupled with genomic characterization should give us a better understanding of which tumors are most likely to progress and which ones are relatively indolent. The new information on the natural history of DCIS can be synthesized by the models to develop new and more effective breast cancer control strategies. The results of the UK Aspirin and Esomeprazole Chemoprevention in Barrett's Metaplasia (AspECT) Trial, studying the benefits of acid suppression with low or high dose esomeprazole, with or without aspirin, in reducing the risk of cancer in Barrett’s esophagus, will be completed in 3-4 years, and should allow the esophageal models to be calibrated to individual level patient data and then used to provide recommendations regarding aspirin chemoprevention. In lung cancer, The Dutch-Belgian Randomized Lung Cancer Screening Trial (Dutch acronym: NELSON study) should provide mortality results in the next few years. This trial, which includes over 5,000 individuals aged 50-75, compares CT screening to a no-screening arm and is sufficiently large to show a 25% lung cancer mortality reduction at 10-years follow-up. The trial should shed further light on nodule management, since it is the first large lung cancer screening trial in which the nodule management protocol is based on volumetric nodule assessment and the presence or absence of growth. In prostate cancer, a growing understanding of the mechanisms behind the development of castrate-resistant disease is giving rise to a host of new treatments that are extremely costly. Work to guide polices regarding the administration of these treatments, and in general who and when to treat recurrent disease will be needed. In colorectal cancer, three RCT’s comparing flexible sigmoidoscopy to usual care (i.e. the UK Flexiscope trial, Italian Score trial, and U.S. PLCO trial), which provided the first randomized evidence of an endoscopic effect for colorectal cancer mortality reductions, should provide new insights into the growth rate of adenomas (a critical model input).

Organizational Structure and Coordination of Proposed CISNET Teams

Each applicant team must propose the elements:

• Modeling Groups (approximately three to six groups per application);
• a Coordinating Center (one per application); and
• a plan to facilitate the training and experiences of Junior Modelers.

Further details can be found in Section IV.2 Research Strategy.

CISNET Governance

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

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

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

• State Governments
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

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

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

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

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

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

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

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

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

To facilitate collaborative, transdisciplinary research, comparative modeling, and coverage across the cancer control spectrum and of the specific area of interest, applicants are required designate multiple PDs/PIs. A PD/PI may be designated for each proposed Modeling Group and the Coordinating Center.

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

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

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

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

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

In addition, the NIH will not accept a resubmission (A1) application that is submitted later than 37 months after submission of the new (A0) application that it follows. The NIH will accept submission:

• To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
• Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
• Of an application with a changed grant activity code.

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

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

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

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.
Telephone: 240-276-6772
Fax: 240-276-7908
Email: [email protected]

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

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

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

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

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

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

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

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

It is anticipated that requested budgets will vary, depending on the scale of work and, in particular, the number of modelling groups proposed. It is anticipated that the budget request (total cost) for the entire application per year will not exceed $1.2M, $1.5M, $1.8M, and $2M for 3, 4, 5, and 6 (or more) modeling groups, respectively.

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

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

• The coordinating center;
• The rapid response funds; and
• Each modeling group.

The budget allocation for the Coordinating Center should generally not exceed $90K in direct costs per year (including all costs for the required Patient and Stakeholder Advisory Group, see Research Strategy below).

The budget allocations for individual modeling groups should generally not exceed $160K in direct costs per year. Budget allocations for modeling groups with specialized focus and/or limited anticipated roles should be substantially smaller. This amount would include special expertise needed to address some of the priority areas (local, state, or international cancer control planners, genetic epidemiologists, developers of decision aids), and junior modelers. Persons with specialized expertise in one modeling group would generally be expected to be shared across the groups as needed.

Rapid response funds should generally not exceed $100K in direct costs per year.

Other Budgetary Requirements: Applicants must plan to participate in two consortium meetings per year, including: (1) an annual meeting (approximately 2 days for a cancer site specific meeting, with an additional half day for a cross-cancer site plenary session) and (2) a mid-year meeting with individual cancer site specific meetings of approximately 2 days. The mid-year meeting is at one of the modeling groups home institutions, selected on a rotating basis, and that group is expected to host the meeting providing administrative support and on-campus meeting rooms. For purposes of budgeting, funds should be requested for up to three persons per modeling group to travel to each of these two meetings. Since the mid-year meetings all held at a common location to facilitate modelers who are part of more than one cancer site, each application should budget to host one meeting during the five year award period.

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

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

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

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

Sub-section A. Overview

Sub-section B. Team Leadership and Coordinating Center

Sub-section C. Models and Their Prior Applications

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

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

Sub-section A. Overall Objectives and Significance

Briefly sketch the background leading to the present application, critically evaluate existing knowledge, and specifically identify the gaps that the project is intended to fill. 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 in both in terms of the modeling work that needs to be done, but also in terms of the broader objective of the modeling exercise.

A rationale for determining which of the priority areas will be addressed should be included in this section. A separate subsection highlighting patient-centered modeling work to be conducted should be included.

Sub-Section B. Team Leadership and Coordination, Advisory Groups, and Training

This section should describe how the activities across the modeling groups will be integrated and coordinated. This section should have three subheadings:

B.1 Team Leadership and Coordination - Each proposed CISNET team must include a Coordinating Center and a Coordinating Center PD/PI. Applicants must plan for and describe in their applications the following coordination activities of the Unit: formulating, prioritizing, and coordinating work on base case and other questions (including outside requests with new funding opportunities); negotiating common requests for outside data sources; consensus building and coordinating critical evaluation of disparate results; preparing inputs and collecting and processing common outputs for model comparisons; coordinating synthesis papers and group responses bringing together disparate information to inform policy makers; 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.

Outline plans and processes for the use of the rapid response funds, listing examples of anticipated activities. These activities may include expertise for particular tasks, gaining access to data sources, and providing funds to modeling groups to mount important efforts not originally anticipated. 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, CISNET would be run through consensus. Decisions about the use of discretionary funds will be coordinated through the Coordinating Center via a consensus process.

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.

B.2 Training - Senior CISNET researchers have a responsibility to train the next generation of population modelers and an appropriate plan for this training needs to be included here. While this is not a formal training program, it should describe a plan for providing an enriched experience for those joining modeling groups at the doctoral, post-doctoral, or junior faculty level. The modelers could work with one of the modeling groups, could rotate among the groups, or could (to foster independence) work on a model component of their own. Rather than duplicating other modeling efforts, they could build a unique model component, which can be attached to another model or even all the other models for that cancer site. The junior modelers could take a novel and somewhat experimental approach to modeling some aspect of the disease process. If a junior modeler has an existing model, they may be brought in as their own modeling group, perhaps focusing on a specialized area (see section on Proposed Models and Previous Model Applications).

Sub-Section C. Proposed Models and Previous Model Applications

Multiple modeling groups are needed to meet the requirements of comparative modeling as well as to allow coverage across the important cancer control issues and relevant specific focus areas for the selected cancer site. For the purpose of this FOA, a modeling group is defined as a group of researchers using a single model or a set of interrelated components of models that are applicable to cancer control and/or policy related issues. A modeling group may include investigators from a single institution or multiple institutions. To the extent possible, the proposed modeling groups should come from institutions where modeling activities are an established element of the research environment.

Applicants should carefully consider how many modeling groups to include, as this element will be an important consideration in the evaluation of applications. Too few groups may make it difficult to conduct comparative modeling, and to provide adequate coverage of the range of relevant topics for that cancer site. Too many groups may make collaboration, communications, and consensus difficult. Proposed CISNET teams should generally have between three to a maximum of six modeling groups. Within this general guideline, applicants are expected to present a coherent and well thought-out plan that will permit group work to proceed efficiently. Thus, applicants need to show how the type and number of modeling groups proposed can provide reasonable coverage (as defined above). In addition, these groups should be sufficient to provide enough diversity to conduct useful comparative analyses, but should not duplicate efforts. Not all modeling groups need to play an equal role in the work of the group. Comprehensive, "full-fledged" modeling groups are well suited to participate in full range of work across the cancer control spectrum. Conversely, narrowly specialized modeling groups may be needed only for a limited range of activities.

This section should give an overview of each model, the accomplishments of each modeling group, and if the group have worked together previously, their joint accomplishments. A summary of underlying model structures and assumptions must be clearly stated in the application. Most models should include a natural history component, modeling the initiation, growth, and metastatic spread of the tumor, relevant precursor lesions, and biomarkers prior to (and possibly after). If models without a natural history component are included, justify how they complement the suite of models proposed. This section should also give a synthesis of why these models complement each other in terms of providing implementations of different modeling perspectives, or different ways of synthesizing available evidence. Additional pages can be devoted to cross model summaries. It may be useful to consecutively place all the model descriptions together, followed by all the model applications. Each of these subsections (i.e., model description and model applications) should be concluded with summary comments on the breadth and depth of prior work. A table summarizing key modeling differences and similarities, and another table summarizing areas of model applications could be useful in providing a summary at a glance.

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

Provide a coordinated plan of reasonably comprehensive coverage of the cancer control issues amenable to modeling for the cancer site of focus. This section is meant to describe models extensions, additional model calibration, or validation, and combining of models (if applicable). Investigators responding to this FOA may propose the application, extension, refinement and/or merging of existing models. If well justified, an existing model can be reformulated using a more robust statistical/mathematical framework. This FOA will NOT support the development of models de novo. This section is also meant to describe model applications, development of user interfaces, web sites, and plans to disseminate and effectively communicate the results of modeling to planners and policy makers. New modeling methodology should be justified in the service of 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. Beyond currently recognized issues that warrant modeling efforts, proposed projects are expected to address (and cover) 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). Consideration should also be given to the ability to scale up to take on new projects when additional funding opportunities arise. Comprehensive coverage stipulates that proposed projects should, if possible, include in the modeling all the main aspects of 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. Modeling efforts can focus on interpreting past trends and evolving trends in incidence and mortality, future trends, and informing cancer control and policy related issues. To summarize the efforts and demonstrate coverage, applicants are encouraged to provide a table with the rows indicating projects, and the columns including items such as the project title, areas of coverage (e.g., prevention/screening/ treatment and/or which of the nine special target areas it represents), modeling groups included, timeline, coordinator, etc. The applicant team will need to jointly decide which areas are important and central enough to warrant full bases 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. Collaborations with outside groups for specific applications should be described.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modification:

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

In addition to the stated NIH data sharing policies, applicants responding to this FOA are expected to work consistently towards achieving the programmatic goals of CISNET. The NCI is committed to the transparency of models, and dissemination of modeling results, model runs and software whenever possible to the scientific community. It is recognized, however, that there are no standards for the release of complex microsimulation models, but that the development of policies, methods and standards for model sharing are critically important for CISNET.

All applicants should provide a plan for the dissemination of models and modeling results. This plan should address the following four goals: (1) enhancing understanding of model structure by keeping up to date versions of documentation on the Model Profiler, but expanding the development of "higher level" documentation necessary to make the models and their assumptions accessible to those without specialized training in population modeling; (2) active solicitation of inquiries from those outside of CISNET to pose questions or scenarios (possibly based on national or regional issues of interest) amenable to modeling; (3) enhancing the ability of others to run the models directly by developing public versions of executable programs of model or model subcomponents when feasible; and (4) enhancing access to source code by releasing code in the context of collaborations or other specified scenarios. Goal (3) above could be addressed in a number of different ways, including development of interactive decision making tools (see priority area#4 in Section I.1 Research Objectives Specific Objectives, Research Scope, and Requirements), possibly with access to a limited set of parameters or a set of pre-determined set of runs for which the results have already been assembled. Applicants should describe how each of these goals would be achieved, and could add other goals as well. For some aspects of this plan, it is reasonable to assume that interested users may need to provide funding.

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

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

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

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.

Part I. Overview Information contains information about Key Dates. 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.

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. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically.

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 by the Center for Scientific Review and responsiveness by the NCI, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

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

For this particular announcement, note the following: Applicants must put forward a plan of research that addresses the major cancer control issues where there is an opportunity to make a public health impact for their cancer site, and present an approach using comparative modeling to address these issues.

Note that in addition to the standard 5 scored review criteria, one additional custom review criterion will receive numerical score: "Coordinating Center and Program Integration".

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

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

Significance

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

Specific for this FOA: How well does the proposed project balance efforts devoted to the various priority areas and cancer control issues and special areas of interest appropriate for the selected cancer 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? Does the application address realistic strategies and issues that have a real potential for being implemented in the population? How adequate are the proposed steps after the publication of study results in terms of ensuring that the published findings are efficiently disseminated, including their clarity to policy makers and cancer control planners?

Investigator(s)

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

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

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

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? 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?

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

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

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 are an established element of the research environment? Are the planned collaborative arrangements with appropriate clinical trial and clinical study groups adequate to ensure timely access to new data for incorporation in the models?

Coordinating Center and Program Integration

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

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

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Children

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

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. 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

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) Genome Wide Association Studies (GWAS).

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.

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:

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

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

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the 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.
• It is anticipated that there will be one award per cancer site.

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.

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

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

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

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

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

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

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), 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 NIH involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

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

• Determining research approaches and procedures, developing and applying their models, and analyzing/interpreting results.
• Defining objectives and approaches, and to plan, conduct, analyze, and publish results, interpretations, and conclusions of their studies.
• Collaborating with their Coordinating Center and the other PDs/PIs on their CISNET award (if the multiple PD(s)/PI(s) option is used).
• Participating in collaborative modeling activities, sharing information, as appropriate, about model structure and assumptions at working groups meetings, as well as strategies and data resources for parameter estimation and calibration.
• Ensuring that up-to-date detailed descriptions of models will be made publically available in a timely manner through the model profile portion of the CISNET website (http://cisnet.cancer.gov/profiles/).
• Abiding by policies and procedures developed by the Coordinating Center for their award, as well as policies and procedures as developed for the entire Consortium by the CISNET steering committee to the extent the decisions are consistent with the terms and conditions of the grant award and applicable grant regulations. Awardees are expected to harmonize procedures at their Coordinating Centers with those established by the Steering Committee.
• Attending two meetings a year along with key co-investigators and participating in regular conference calls. One meeting will be in the Washington DC area, and the second meeting at one of the PI/PD's home institutions. If their institution is selected, that PI/PD is expected to assist in hosting the meeting by helping to find on campus meeting space and providing administrative assistance to help the NCI organize the meeting and to provide support during the meeting.
• Providing an annual progress report and other information on study progress as might be needed.
• Abiding by the Resource Sharing Plan, as appropriate, as well as specific procedures to be developed for the entire Consortium by the CISNET Steering Committee.
• Working cooperatively with the contractor who maintains the Model Profiler/Interactive Web Site.
• 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 HHS, PHS, and NIH policies.
• Approving affiliate members (groups funded elsewhere but whose are interested in joining the collaboration). Affiliate membership will be approved by the PD/PIs in the applicable cancer site.

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;
• 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 critical evaluation of disparate results;
• Preparing inputs and collecting and processing common outputs for model comparisons;
• Coordinating synthesis papers and group responses bringing together disparate information to inform policy makers;
• 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 and mid-year reports by the individual PD/PIs;
• Coordinating use and allocation of rapid response funds;
• Maintaining a set of policies and procedures within the cancer site-specific group that are in compliance with the procedures and policies of the CISNET steering committee;
• Following to the extent consistent with Grant Regulations the overall Consortium policies and procedures established by Steering Committee.

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

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

Designated NCI Program staff members serving as Project Scientists/Coordinators will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below.

• An NCI Program staff member will be designated as the NCI Project Scientist for CISNET.
• The NCI will also designate NCI Scientific Coordinators for each of the cancer organ sites.
• The NCI Project Scientist will serve as a voting member on the Consortium Steering Committee.
• The NCI Project Scientist and the NCI Scientific Coordinators will share with awardees information about a wide range of data resources, which will be used for parameter estimation and population trends, and will serve as a conduit to the potential utility and access to these resources.
• The NCI Scientific Coordinators will serve as liaisons to other NCI Scientific Staff to provide advice on specific scientific and technical issues as needed.
• NCI will maintain a web site for the internal use by CISNET investigators. This web site will be a communications portal for posting papers, base case inputs, data sets, and model documentation. In addition, NCI will maintain a public web site for CISNET (http://cisnet.cancer.gov/).
• The NCI Project Scientist and the NCI Scientific Coordinators will provide advice on specific scientific and technical issues as needed to the Consortium.
• The NCI Project Scientist and NCI Scientific Coordinators will contribute scientifically to the process of model applications and will have opportunities to participate in analyses of joint model results and publication efforts of the Consortium.
• The NCI Project Scientist, NCI Scientific Coordinators, and NCI Program Director will have access to all modeling results generated under this award consistent with current HHS, PHS, and NIH policies.
• NCI, in consultation with the Coordinating Center PI/PD's, will set the location of the two annual meetings, and will coordinate the organization of these meetings.

The NCI reserves the right to adjust, withhold, suspend, or terminate the funding to underperforming awardee institutions.

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

Additionally, an NCI Program staff member acting as a Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. A Program Official may also have substantial programmatic involvement (as Project Scientist/Coordinator). In that case, the individual involved will not attend peer review meetings of renewal (competing continuation) and/or supplemental applications or will seek NCI waiver as stated above.

Areas of Joint Responsibility include:

The NCI Project Scientist and the PDs/PIs representing each awardee will be responsible for forming a Steering Committee. Steering Committee will serve as the CISNET main governing board as defined below.

The Steering Committee will consist of the following voting members: the Coordinating Center PD/PI's from each award and the NCI Project Scientist.

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

The activities of the Steering Committee will include the following:

• Setting overall consortium policies and procedures and being the ultimate decision making body for overall CISNET matters;
• Determining if the policies and procedures of the cancer site specific Working Groups are in adherence with those of the Steering Committee (this approval process should ensure that the proposed activities are consistent with the objectives and scope as specified in the FOA);
• Coordinating communication between the Working Groups.
• Setting publication procedures and policies.
• Setting the timing and location of the two annual CISNET investigators meetings coordinating the organization of these meetings. Organization of the meeting will be a joint responsibility of NCI, the coordinating center PI/PDs, and the PD/PI at the host site of the meeting (for meetings outside the Washington DC area).

Steering Committee will meet 3 times per year (in person or by teleconference), or more frequently if needed.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipient and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. The Dispute Resolution Panel will have three members: two designees of the Steering Committee chosen without NIH representatives voting; and one NIH designee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

When multiple years are involved, awardees will be required to submit the annual Non-Competing Progress Report (PHS 2590 or RPPR) and financial statements as required in the NIH Grants Policy Statement.

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

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

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

eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
Finding Help Online: http://grants.nih.gov/support/index.html
Email: [email protected]

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone: 301-710-0267
Email: [email protected]

Eric J. (Rocky) Feuer
National Cancer Institute (NCI)
Telephone: 240-276-6772
Email: [email protected]

Referral Officer
National Cancer Institute (NCI)
Telephone: 240-276-6390
Email: [email protected]

Esther Young
National Cancer Institute (NCI)
Telephone: 240-276-6325
Email: [email protected]

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

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.