Part I Overview Information

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Department of Health and Human Services

Participating Organizations
National Institutes of Health (NIH) (http://www.nih.gov/)

Components of Participating Organizations
National Cancer Institute (NCI) http://www.cancer.gov/

Title: Cancer Intervention and Surveillance Modeling Network (CISNET) (U01)

Announcement Type
This funding announcement is a reissuance of RFA-CA-05-018.

Request For Applications (RFA) Number: RFA-CA-09-025

Catalog of Federal Domestic Assistance Number(s)
93.393, 93.394, 93.395, 93.396, 93.399

Key Dates
Release Date: June 25, 2009
Letters of Intent Receipt Date: October 3, 2009
Application Receipt Date: November 3, 2009
Peer Review Date(s): February/March 2010
Council Review Date: May 2010
Earliest Anticipated Start Date: September 2010
Additional Information To Be Available Date (URL Activation Date): Not Applicable
Expiration Date: November 4, 2009

Due Dates for E.O. 12372

Not Applicable

Pre-application Teleconference

The NCI will hold a pre-application teleconference (via conference call arrangements) open to all interested prospective applicants. NCI program staff members will explain the goals and objectives for the CISNET and will answer questions from the participants. For updated announcements and details on this pre-application informational conference call, see http://cisnet.cancer.gov/foa.html..

Additional Overview Content

Executive Summary

• Purpose. Through this funding opportunity announcement (FOA), the National Cancer Institute (NCI) solicits applications for the Cancer Intervention and Surveillance Modeling Network (CISNET). The goal of CISNET is to use simulation and other modeling techniques (a) to understand the impact of cancer control interventions (i.e., screening, treatment, prevention) on national trends in cancer rates, and (b) to inform national/regional/local decisions on the most efficient utilization of existing and emerging technologies and strategies for the control of cancer. This FOA expands CISNET efforts focused on four cancer sites (prostate, lung, colorectal, breast) and will also cover two additional sites (cervical and esophageal cancer). Expansion into new areas of modeling (identified in the FOA) is also encouraged. This FOA will support collaborative, interactive projects involving groups of researchers that would put forward a program of comparative modeling, as well as to allow coverage across the important cancer control issues and relevant specific focus areas for the selected organ site. Investigators may propose the application, extension, and/or merging of existing models. However, de novo model development will NOT be supported. Because of the requirement of conducting cross-model comparisons (i.e. comparative modeling) and coverage of a broad range of cancer control issues, it is expected that each award will support between approximately 2 and 5 modeling groups working together. This FOA is an open competition for all qualified investigators, irrespective of their previous involvement in the CISNET program.
• Mechanism of Support. This FOA will utilize the NIH U01 cooperative agreement mechanism.
  
• Funds Available and Anticipated Number of Awards. The NCI expects to commit $5.4 million in year 1 and $6.0 million per year in years 2-5 to fund approximately four to six awards.
• Budget and Project Period. An applicant may request a project period of up to 5 years and budget for up to $1.3M total costs for the first year. For more details on the budget restrictions, see Section IV.5 - Funding Restrictions of this FOA.
• Eligible Institutions/Organizations. Institutions/organizations listed in Section III, 1.A. are eligible to apply.
• Eligible Project Directors/Principal Investigators (PDs/PIs). Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their institution/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.
• Number of PDs/PIs. More than one PD/PI (i.e., multiple PDs/PIs) may be designated on the application.
• Number of Applications. Applicants may submit more than one application, provided they are scientifically distinct.
• Resubmissions. Resubmission applications are not permitted in response to this FOA.
• Renewals. Renewal applications are not permitted in response to this FOA. Applications from current CISNET awardees will be considered as new applications.
• Special Date(s). This FOA uses non-standard due dates. See Receipt, Review and Anticipated Start Dates.
• Application Materials. See Section IV.1 for application materials.
• Hearing Impaired. Telecommunications for the hearing impaired are available at: TTY 301-451-5936.

Table of Contents

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Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
1. Research Objectives

Section II. Award Information
1. Mechanism(s) of Support
2. Funds Available

Section III. Eligibility Information
1. Eligible Applicants
A. Eligible Institutions
B. Eligible Individuals
2. Cost Sharing or Matching
3. Other - Special Eligibility Criteria

Section IV. Application and Submission Information
1. Address to Request Application Information
2. Content and Form of Application Submission
3. Submission Dates and Times
A. Receipt, Review and Anticipated Start Dates
1. Letter of Intent
B. Sending an Application to the NIH
C. Application Processing
D. Application Assignment
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements

Section V. Application Review Information
1. Criteria
2. Review and Selection Process
A. Additional Review Criteria
B. Additional Review Considerations
C. Resource Sharing Plan(s)
3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information
1. Award Notices
2. Administrative and National Policy Requirements
A. Cooperative Agreement Terms and Conditions of Award
1. Principal Investigator Rights and Responsibilities
2. NIH Responsibilities
3. Collaborative Responsibilities
4. Arbitration Process
3. Reporting

Section VII. Agency Contact(s)
1. Scientific/Research Contact(s)
2. Peer Review Contact(s)
3. Financial/ Grants Management Contact(s)

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement

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Section I. Funding Opportunity Description

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1. Research Objectives

Purpose

This funding opportunity announcement (FOA) is a continuation of Cancer Intervention and Surveillance Modeling Network (CISNET) program. Through this FOA, the Division of Cancer Control and Population Sciences (DCCPS), National Cancer Institute (NCI), solicits applications for collaborative research projects using simulation and other modeling techniques for specific cancer sites (see below). The proposed research is expected to generate sophisticated, evidence-based decision tools that could inform 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 mathematical and statistical techniques within a logical framework to integrate and synthesize known biological, epidemiological, clinical, behavioral, genetic, and 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. Ultimately, applications of these models should provide effective tools for helping to optimize cancer-relevant decisions.

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. 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.
• Applicability to Public Health Issues. The emphasis of the proposed research must be on applications of modeling approaches to important public health issues.
• Cancer Sites. Each proposed project must be limited to a single eligible cancer site. The eligible six sites include: (a) prostate, colorectal, breast, and lung cancers (i.e., the sites covered by the original CISNET issuance); as well as (b) cervical and esophageal cancers (added for this CISNET re-issuance). Applications focused on other cancer sites are non-responsive to this FOA (and will be returned without review).
• Comprehensive Coverage. 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 (a new requirement for this CISNET re-issuance).
• Areas of Interest. There are nine specific areas of interest (see below) 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 add different areas that are more germane.

To facilitate collaborative, transdisciplinary research, comparative modeling, and coverage across the cancer control spectrum and of the specific area of interest, applicants are encouraged to take advantage of the available multiple principal investigator (multiple PD/PIs) option.

This initiative is an open competition FOA and all qualified investigators are invited to apply, regardless of whether or not they were original CISNET awardees.

Background

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. Obviously, 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.

Phases of CISNET Implementation. Initially (2000-2005), CISNET funded projects focused on breast, colorectal, prostate cancers, lung cancers, and colorectal cancers. Support was provided to develop applicable mathematical and statistical methodologies and incorporate those methodologies into multi-cohort population models. During this initial phase, an infrastructure was put into place to facilitate communication among modelers and cross-model comparisons. This phase involved the development of basic mathematical and statistical methodology that is necessary to build multi-cohort population models. Models were validated using available data and applied to the population setting to answer relevant research questions. These initial CISNET projects focused on understanding the impact of interventions (i.e., prevention, screening, and treatment) on current population trends in incidence and mortality.

The next phase (2005-2010) focused on the application of already developed models to study the population impact of existing or emerging cancer control interventions. CISNET II was an opportunity for new applicants who had working models of one of the CISNET cancer sites to apply for funding to join the CISNET consortium as well as for applicants funded under earlier solicitations to be re-funded. CISNET II also provided the opportunity to establish centers that are dedicated to a specific cancer site for coordinating activities such as joint analyses and synthesis papers, collaborations with outside researchers, and group requests for data resources. The goal of CISNET II was to promote the application and extension of models to answer vital questions related to emerging cancer trends, the impact of interventions on future trends, and the identification of optimal strategies for reducing the cancer burden.

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. This CISNET approach to modeling includes the following components:

Flexible broad-based disease models: CISNET models incorporate a central cancer module, which can be modified by the full range of cancer control interventions (i.e., changing risk factor profiles of the population, new screening modalities, and treatment regimens). Outputs can include the full range of the benefits and harms/costs of the interventions. Flexible models of this type can be easily adapted to incorporate the costs, operating characteristics, and unique logistics of emerging technologies as they are developed. For example, colorectal cancer models were easily modified to take into account the unique features of CT Colonography (i.e. virtual colonoscopy), even though this technology was still in its infancy when most of the colorectal models were first being developed.

Multiple birth-cohort modeling: This type of modeling captures a range of birth cohorts and changing risk factor profiles, screening behaviors, and treatments used by each cohort as it ages, allowing investigators to represent the impact(s) of intervention(s) in the actual U.S. population. There is increasing recognition that modeling a single hypothetical cohort often does not fully capture the entire impact and/or potential cost effectiveness of an intervention as implemented in the U.S. population.

Comparative modeling: Independent modeling efforts often yield disparate results that are difficult to reconcile. A comparative modeling approach explores differences between models 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. Disparate results can help to pinpoint areas for which the knowledge base is insufficient and further research is needed. These advantages of the CISNET comparative approach have been recognized by the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Task Force on Good Modeling Practices.

Transparency in model structure and assumptions: CISNET has developed and implemented standardized model documentation. Model profiles (available online at 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 models address different components of the process. Journal articles seldom contain extensive model descriptions; links from publications to model profiles provide a more complete model description.

Outreach and collaboration: To achieve fully the goals of CISNET, the created modeling capacity/approaches must made available to the research and policy communities through appropriate collaborations. With outreach being one of CISNET’s core values, CISNET initiated a series of webinars to encourage discussions with colleagues in the fields of advocacy, public policy, legislative affairs, cancer control planning, and clinical science on the potential use(s) of CISNET’s decision support tools to guide evidence-based recommendations and cancer control planning. Examples of groups that have collaborated with CISNET include the U.S. Preventive Services Task Force, the Center for Medicare and Medicaid Services, the Division of Cancer Prevention and Control of the Centers for Disease Control and Prevention (CDC), and the American College of Radiology Imaging Network.

Highlights of CISNET Accomplishments: CISNET currently consists of 14 active modeling groups, and 7 affiliate members (who are modeling groups not funded by CISNET but who have joined the collaboration). CISNET investigators have contributed significantly to answering research questions related to modeling the natural history of cancer, performed analyses to synthesize results from both clinical trials and observational studies, and applied their models to answer policy-relevant questions. More information about CISNET accomplishments and the impact of CISNET work can be found at http://cisnet.cancer.gov/ and NIH Publication No. 09-7354 CISNET: The Cancer Intervention and Surveillance Modeling Network Modeling to Guide Public Health Research and Priorities, printed December 2008. Overall, the CISNET program and the resulting collaborations have resulted in numerous publications (over 135 as of May 2009) and created a solid foundation for the use of modeling decision tools for the cancer types covered by the initial focus of the program.

New Challenges for CISNET. There is a continued need for refining CISNET tools and expanding their applicability to synthesize emerging evidence as it becomes becomes available, including such areas as: (a) new cancer control technologies, (b) advances in molecular and biological determinants of cancer risk and prognosis, (c) results from new clinical trials, (d) interesting new trends in cancer incidence, survival, and mortality data (available from sources such as the United States Cancer Statistics (http://apps.nccd.cdc.gov/uscs/) and the NCI’s Cancer Statistics Review (http://seer.cancer.gov/csr/1975_2006/index.html), and (e) other new health-related data. Importantly, the successful testing of CISNET approaches for the initial set of cancer sites, and the maturation of cancer modeling approach, warrants the expansion of the program to cover additional cancer sites.

Specific Objectives, Research Scope, and Requirements for this FOA

All applications submitted in response to this FOA must be focused on the development of cancer control models for one of six selected cancer sites (breast, colorectal, lung, prostate, cervical, or esophageal). To be responsive, each proposed project must be limited to only one of these cancer sites. Applicants should also be aware that the NCI’s general intent is to fund one project per each eligible cancer site.

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) detection (although this is not a requirement for all models). Alternatively models without a natural history component can be included, but the application should describe how they complement the suite of models proposed.

Comprehensive Coverage. To meet the objectives of this FOA, 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. The following specific aspects must be addressed in applications:

• 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.
• The emphasis must be on model applications to important public health issues in the U.S. context. International clinical trials, clinical studies, and health care issues can be included, but applicants should explain how they can serve to inform U.S. policies in related issues.
• 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 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.
• To the extent possible, modeling should include the impact of comorbidities (or life expectancy) on relevant issues.
• 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.
• CISNET 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; and (d) other relevant government agencies.
• 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 Areas of Special Interest: Modeling areas of special interest to this round of CISNET funding include the following:

1) Multi-scale modeling;

2) Incorporating genomic and family history risk profiles;

3) Upstream modeling;

4) Comparative effectiveness and downstream modeling;

5) Evaluation of diagnostic tests;

6) Optimizing biomarker development strategies;

7) Suggesting optimal routes to reducing health disparities;

8) Translation of trial results into clinical guidelines and public health policy; and

9) Interactive policy-level decision making tools.

Details and non-inclusive examples pertaining to these Areas of Special Interests are given below:

(1) Multi-scale modeling: Most CISNET models currently incorporate a tumor growth model, and are intended to project population level results. Applicants to this FOA are encouraged to integrate models developed at the molecular/cellular level into their tumor growth models. Results of multi-scale modeling at this level can help extrapolate the potential impact of basic science discoveries (e.g., mechanistic models of the action of drugs at smaller scales validated against clinical trials). Efforts of this type may help prioritize those basic science developments that show the most promise to have a desirable population impact. Models at these smaller scale levels need not be developed de novo. Rather, when possible, existing models at the molecular/cellular level can be integrated into tumor growth/population level models proposed in response to this FOA. Particularly suitable for these efforts could be models developed under NCI’s Integrative Cancer Biology Program (ICBP) (see http://icbp.nci.nih.gov/) or developed under funding initiatives as part of the Interagency Modeling and Analysis Group (IMAG) (http://www.nibib.nih.gov/Research/MultiScaleModeling/IMAG).

(2) Incorporating genomic and family history risk profiles: Utilizing risk profiles that are based on family history and genomic information has the promise of more effectively targeting prevention, screening, and treatment efforts. Incorporation of information on family history, genomics, and gene environment interactions into cancer models provides a platform for fitting together the pieces of this complex puzzle as it becomes available. Given a rapidly evolving state of knowledge with many gaps, modeling efforts are needed to help make more explicit assumptions about complex phenomena and expose the most important leverage points where knowledge gaps exist. The impact of awareness and appropriate usage of genetic screening tests among both physicians and the general public can also be included in modeling efforts. Examples of efforts of this type of modeling include: Ramsey SD et al., Cancer Epidemiol Biomarkers Prev. (2005); Gorlova OY et al., Hum Hered (2003); and Deng L et al., Int J Cancer (2009).

Some useful resources for this area include the following:

Evaluation of Genomic Applications in Practice and Prevention (EGAPP): an existing evidence-based synthesis and reviews with evidence-based recommendations (http://www.egappreviews.org/). The January 2009 issue of Genetics in Medicine is fully dedicated to EGAPP.

The Human Genome Epidemiology Network (Hu GENet) http://www.cdc.gov/genomics/hugenet/default.htm, and the accompanying informatics/knowledge display tool the Hu GENavigator http://www.hugenavigator.net/ are both very useful in finding genomic associations.

The proceedings of a December 2008 personal genomics workshop at NCI: http://www.cancercontrol.cancer.gov/od/phg/workshop.html

(3) Upstream modeling: Most models proposed in response to this CISNET FOA are expected to start with risk factor trends, screening behavior, and diffusion of new treatment advances. However, the expansion of such models upstream is highly desirable. Upstream modeling can add the social, political, cultural, economic, and individual determinants of risk factor changes, screening behavior, and treatment choices. These determinants put the models a step closer to the specific policies and programs that can help modify these factors in the future, and help evaluate specific programs. Upstream modeling efforts need not be developed de novo, and instead CISNET can integrate existing models or use outputs from other models as input into CISNET models.

(4) Comparative Effectiveness and Downstream Modeling: Comparative effectiveness is a rigorous evaluation of the impact of different options that are available for treating a given medical condition for a particular set of patients. In 2007, the Congressional Budget Office issued a report advocating research on the comparative effectiveness of medical treatments (http://www.cbo.gov/doc.cfm?index=8891). In 2005 AHRQ was authorized to conduct and support research on the outcomes, comparative clinical effectiveness, and appropriateness of health care items and services (including prescription drugs). The idea is to focus on what is known now, ensuring that individual choices and programs benefit from past investments in research and identifying what research gaps are critical to fill. Modeling can assist in extending current evidence from intermediate to long term outcomes, and helping to balance trade-offs (e.g., in prostate cancer treatment radical prostatectomy has been shown to have a survival advantage over watchful waiting, but has tradeoffs in terms of greater urinary and sexual dysfunction). In responding to this FOA, applicants should address the needs of comparative effectiveness research. Modeling groups should consider developing model components that are downstream from the initial diagnosis and staging of disease, including post diagnostic sequalae such as first line treatment, adjuvant therapy, post diagnosis surveillance, treatment at failure of first line therapy or recurrence, side effects of treatment, etc. Modeling can include important issues with respect to choices and quality of care. Examples of studies that can inform this type of modeling include the Prostate Cancer Outcomes Study (PCOS; http://www.cancer.gov/cancertopics/factsheet/pcos) and the Cancer Care Outcomes Research & Surveillance Consortium (CANCORS; http://outcomes.cancer.gov/cancors/).

(5) Evaluation of Diagnostics Tests: Empirical studies of the impact of diagnostic test utilization on patient outcomes are rarely done, because of both methodological and resource considerations. CISNET methods developed in the context of screening could be adapted for use in the diagnostic context and thus provide methods for synthesizing available information from all sources in order to make credible projections about the potential impact of the use of diagnostic tests in clinical practice and to estimate their benefit or cost-benefit profile. Examples of applications could include PET, PET/CT, and MRI for colorectal cancer, MRI and ultrasound for breast cancer, and PET/CT and CT for lung cancer, although this list should just be seen as illustrative. Modeling could be done in the context of technology assessments, when appropriate, as part of National Coverage Determination decisions for the Center for Medicare and Medicaid Services (CMS) (e.g., Decision Memo for Positron Emission Tomography [FDG] for Solid Tumors [CAG-00181R]; go to http://www.cms.hhs.gov/mcd/viewdecisionmemo.asp?from2=viewdecisionmemo.asp&id=218&). A potential partner in these types of modeling issues is the American College of Radiology Imaging Network (ACRIN; go to http://www.acrin.org/).

(6) Optimizing Biomarker Development Strategies: Biomarker development proceeds in five phases: Phase I discovery; Phase II validation; Phase III disease detection in serum from patients in longitudinal cohorts; Phase IV prospective screening studies on biomarker performance in large populations; and Phase V large scale studies to evaluate the role of biomarkers for cancer detection and overall screening impact. Each phase costs significantly more than the prior phase, but yields more information about the operating characteristics and impact of the biomarker. Applicants responding to CISNET FOA may propose efforts to explore how early in the development process reasonable models of the potential cost effectiveness can be developed, thus assisting in decisions of selecting the most promising biomarkers. Potential partners in modeling the potential of biomarkers are researchers in NCI’s Early Detection and Research Network, EDRN ((http://edrn.nci.nih.gov/ ). CISNET models can provide tools for EDRN investigators to project the likely impact of screening tests of given sensitivity on disease-specific deaths, investigate how early in the preclinical period the test needs to become sensitive in order to produce a target benefit in terms of lives saved, given specified test characteristics, project benefits and costs associated with different regimens of screening.

(7) Suggesting optimal routes to reducing health disparities: In response to this FOA, modelers are encouraged to move beyond the standard racial/ethnic characterizations of health disparties, and utilize data sources that will enable modeling as a function of disparities in terms of factors such as income/education, insurance status, and geography. Disparities and their downstream consequences can be studied in terms of smoking rates, obesity, and other risk factors; screening rates; follow-up to abnormal screening; treatment; and quality of care. Modeling efforts can focus on explaining why growing disparities in cancer mortality exist, how disparities can be alleviated in the future, how the mix of cancer control activities which may optimal for the general population can be more appropriately tailored for the needs in specific geographic areas or among population subgroups, or the potential population impact of programs which have shown promise in specific studies. Potential partners for this type of research can be found in programs initiated by the NCI Center to Reduce Cancer Health Disparities (go to http://www.cancer.gov/cancertopics/types/disparities).

(8) Translation of clinical trial results into clinical guidelines and public health policy: The translation of clinical trial results into guidelines and policy recommendations can be facilitated by modeling. In the next several years, the significance of this aspect will likely increase as controlled clinical trial results for PSA screening accrues more follow-up and CT screening for lung cancer in the U.S. and Europe become available. For both prostate and lung cancer screening, overdiagnosis and mortality benefits may coexist, complicating population-level recommendations. Controlled clinical trials in different countries are run under different protocols, and modeling may hold the key to translating results from one trial setting to another and reconciling the impact of putative or actual differences. Guideline setting bodies, such as the U.S. Preventive Services Task Force (USPSTF), contract for evidence reviews to assist in their analysis when specific issues are slated for review. More recently, recognizing that modeling could provide additional useful information by synthesizing information over the course of an entire human lifetime (e.g. different screening scenarios from age 40 to 80) modeling results have also been included in the USPSTF deliberations. One of the goals for this FOA is to promote collaborations that would facilitate the tasks of guideline setting bodies by integrating work from modelers evidence review groups, clinical trials, and ongoing studies of how screening and the follow-up of abnormal results operates in population-based settings. Potential collaborators for this latter type of analysis include groups such as the Breast Cancer Surveillance Consortium (BCSC) that collect population based data on screening utilization and test characteristics linked to cancer outcomes, (go to http://breastscreening.cancer.gov/). Therefore, applicants are encouraged to seek respective collaborations (to be documented by letters of support and evidence of intended working relationships with professional societies and guideline-setting bodies).

(9) Interactive policy-level decision-making tools: Another area of priority is the development of interactive interfaces for models that would allow cancer control planners and policy makers to explore the impact of varying key parameters involved in their decision-making options. These tools must be designed so as to facilitate evidence-based decisions, while ensuring that they are understandable and relevant for the target audiences. For this goal, it may not be necessary to design complete interfaces to models, but rather provide interactive reporting tools to visualize the pre-analyzed results for a specific set of relevant scenario/input conditions An example of an interactive interface to a pre-assembled set of outcome data is the CISNET colorectal cancer projections website(Go to http://cisnet.cancer.gov/projections/colorectal/).

Applicants should balance the tradeoffs of broad coverage across these areas with more focused efforts in a narrow range of areas. They should explain how those tradeoffs decisions were made in terms of the potential public health importance of the areas selected, as well as other considerations used in determining the breadth and depth of areas covered. The list of suggested areas is not binding, i.e. applicants could exclude areas that are less appropriate for a particular cancer site, and add different areas that are more germane.

Organizational Structure of Proposed CISNET Teams

Each applicant team must propose two types of components:

• Modeling Groups (approximately two to five groups per application); and
• A Coordinating Center (one per application).

Modeling Groups: 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 related 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. For example, if a policy level model will incorporate new model subcomponents (e.g., an upstream model or a model developed at the cellular level) then the builders of those subcomponents could be considered part of the same modeling group, even if they are at a different institution.

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. 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 all the modeling groups , 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. Proposed CISNET teams should generally have between two to five 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. (For specific budget guidelines for modeling groups, see Section IV.5 - Funding Restrictions.)

Coordinating Centers: Each proposed CISNET team must include a coordinating center, which must be at the institution submitting the CISNET application in response to this FOA. Generally, the coordinating center can be led by the lead investigator (PI) of the modeling group(s) from the application submitting institution (although separate budgets are required for both components, see Section IV.5 Funding Restrictions). Applicants must plan for and describe in their applications the following coordination activities of the Center (which must include the priorities of the CISNET program and consensus of the leaders of the modeling groups of the applicant team):

• 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 an 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., specific clinical expertise, an actuary, or demographer) might be shared across the group.

Because coordination activities will be somewhat decentralized, the budget for the coordinating center is expected to be relatively modest in Year 1. However, the ability of the coordinating center to direct funds to high priority areas will be enhanced in years 2-5 with the addition of discretionary funds. (See Section IV. 5. Funding Restrictions for budget guidelines for coordinating centers and discretionary funds.)

The coordinating center will be able to allocate discretionary funds for centralized administrative and scientific coordination, but will also be able to utilize these funds to tap outside expertise for particular tasks, pay for access to data sources, and provide 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, as it has in the past.

See Section VIII, Other Information - Required Federal Citations, for policies related to this announcement.

Section II. Award Information

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1. Mechanism of Support

This funding opportunity will use the NIH U01 award mechanism. The Project Director/Principal Investigator (PD/PI) will be solely responsible for planning, directing, and executing the proposed project.

This FOA uses Just-in-Time information concepts. It also uses non-modular budget formats described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html).

This funding opportunity will use a cooperative agreement award mechanism. In the cooperative agreement mechanism, the Project Director/Principal Investigator (PD/PI) retains the primary responsibility and dominant role for planning, directing, and executing the proposed project, with NIH staff being substantially involved as a partner with the Principal Investigator, as described under the Section VI. 2. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award."

2. Funds Available

The estimated amount of funds available for support of approximately 6 projects awarded as a result of this announcement is $5.4 million for fiscal year 2010 and $6.0 million for fiscal years 2011 through 2014, although amounts will depend on annual appropriations.

The NCI’s general intent is to fund not more than one project for the modeling of each of the identified cancer types.

Applicants may request project periods of up to 5 years and budget for up to $1.3M total costs for the first year. For more details on the budget restrictions, see Section IV.5 - Funding Restrictions of this FOA.

Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary.

Although the financial plans of the NCI provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications.

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.

Section III. Eligibility Information

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1. Eligible Applicants

1.A. Eligible Institutions

The following organizations/institutions are eligible to apply:

• Public/State Controlled Institutions of Higher Education
• Private 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)
• Small Businesses
• For-Profit Organizations (Other than Small Businesses)
• State Governments
• U.S. Territory or Possession
• Non-domestic (non-U.S.) Entities (Foreign Organizations)
• Other(s):
  • Eligible Agencies of the Federal Government
  • Units of Local Governments

1.B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research as the PD/PI is invited to work with his/her institution 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.

More than one PD/PI, or multiple PDs/PIs, may be designated on the application for projects that require a team science approach and therefore clearly do not fit the single-PD/PI model. Additional information on the implementation plans, policies and procedures to formally allow more than one PD/PI on individual research projects is available at http://grants.nih.gov/grants/multi_pi. All PDs/PIs must be registered in the NIH eRA Commons prior to the submission of the application (see http://era.nih.gov/ElectronicReceipt/preparing.htm for instructions).

The decision of whether to apply for a grant with a single PD/PI or multiple PDs/PIs is the responsibility of the investigators and applicant organizations, and should be determined by the scientific goals of the project. Applications for grants with multiple PDs/PIs will require additional information, as outlined in the instructions below. The NIH review criteria for approach, investigators, and environment have been modified to accommodate applications involving either a single PD/PI or multiple PDs/PIs. When considering multiple PDs/PIs, please be aware that the structure and governance of the PD/PI leadership team as well as the knowledge, skills and experience of the individual PDs/PIs will be factored into the assessment of the overall scientific merit of the application. Multiple PDs/PIs on a project share the authority and responsibility for leading and directing the project, intellectually and logistically. Each PD/PI is responsible and accountable to the grantee organization, or, as appropriate, to a collaborating organization, for the proper conduct of the project or program, including the submission of required reports. For further information on multiple PDs/PIs, please see http://grants.nih.gov/grants/multi_pi.

2. Cost Sharing or Matching

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

3. Other-Special Eligibility Criteria

Number of Applications. Applicants may submit more than one application, provided each application is scientifically distinct.

Resubmissions. Resubmission applications are not permitted in response to this FOA.

Renewals. Renewal applications are not permitted in response to this FOA. Even applications from current CISNET awardees will be considered as new applications.

Section IV. Application and Submission Information

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1. Address to Request Application Information

The PHS 398 application instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. Applicants must use the currently approved version of the PHS 398. For further assistance, contact GrantsInfo -- Telephone: (301) 710-0267; Email: [email protected].

Telecommunications for the hearing impaired: TTY 301-451-5936.

2. Content and Form of Application Submission

Applications must be prepared using the current PHS 398 research grant application instructions and forms with exceptions defined below. Applications must have a D&B Data Universal Numbering System (DUNS) number as the universal identifier when applying for Federal grants or cooperative agreements. The D&B number can be obtained by calling (866) 705-5711 or through the web site at http://www.dnb.com/us/. The D&B number should be entered on line 11 of the face page of the PHS 398 form.

The title and number of this funding opportunity must be typed in item (box) 2 only of the face page of the application form and the YES box must be checked.

Foreign Organizations (i.e., Non-Domestic [non-U.S.] Entities)

NIH policies concerning grants to Foreign (non-U.S.) organizations can be found in the NIH Grants Policy Statement at http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part12.htm#_Toc54600260.

Applications from foreign organizations must:

• Request budgets in U.S. dollars; and
• Contain detailed budgets (see NOT-OD-06-096).

In addition, for applications from Foreign organizations, the following requirements apply.

• Charge back of customs and import fees is not allowed.
• Every effort should be made to comply with the format specifications, which are based upon a standard U.S. paper size of 8.5 x 11 within each PDF.
• Funds for up to 8% Facilities and Administrative (F&A) costs (excluding equipment) may be requested. See NOT-OD-01-028, March 29, 2001.
• Organizations must comply with Federal/NIH policies on human subjects, animals, and biohazards.
• Organizations must comply with Federal/NIH biosafety and biosecurity regulations. See Section VI.2., Administrative and National Policy Requirements.

Proposed research should provide special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States or that augment existing U.S. resources.

SPECIAL INSTRUCTIONS

Applications with Multiple PDs/PIs

When multiple PD/PIs are proposed, use the Face Page-Continued page to provide items 3a 3h for all PD/PIs. NIH requires one PD/PI be designated as the contact PD/PI for all communications between the PD/PIs and the agency. The contact PD/PI must meet all eligibility requirements for PD/PI status in the same way as other PD/PIs, but has no special roles or responsibilities within the project team beyond those mentioned above. The contact PD/PI may be changed during the project period. The contact PD/PI should be listed in block 3 of Form Page 1 (the Face Page), with all additional PD/PIs listed on Form Page 1-Continued. When inserting the name of the PD/PI in the header of each application page, use the name of the Contact PD/PI, et. al. The contact PD/PI must be from the applicant organization if PD/PIs are from more than one institution.

All individuals designated as PD/PI must be registered in the eRA Commons and must be assigned the PD/PI role in that system (other roles such as SO or IAR will not give the PD/PI the appropriate access to the application records). Each PD/PI must include their respective eRA Commons ID in the eRA Commons User Name field.

All projects proposing Multiple PDs/PIs will be required to include a new section describing the leadership plan approach for the proposed project.

Multiple PD/PI Leadership Plan: For applications designating multiple PDs/PIs, a new section of the research plan, entitled Multiple PD/PI Leadership Plan must be included. A rationale for choosing a multiple PD/PI approach should be described. The governance and organizational structure of the leadership team and the research project should be described, and should include communication plans, process for making decisions on scientific direction, and procedures for resolving conflicts. The roles and administrative, technical, and scientific responsibilities for the project or program should be delineated for the PDs/PIs and other collaborators.

If budget allocation is planned, the distribution of resources to specific components of the project or the individual PDs/PIs should be delineated in the Leadership Plan. In the event of an award, the requested allocations may be reflected in a footnote on the Notice of Award.

Additional information is available in the PHS 398 grant application instructions.

3. Submission Dates and Times

Applications must be received on or before the receipt date described below (Section IV.3.A). Submission times N/A.

3.A. Receipt, Review, and Anticipated Start Dates
Letters of Intent Receipt Date: October 3, 2009
Application Receipt Date: November 3, 2009
Peer Review Date(s): February/March 2010
Council Review Date: May 2010
Earliest Anticipated Start Date: September 2010

3.A.1. Letter of Intent

Prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed research;
• Name(s), address(es), and telephone number(s) of the Principal Investigator(s);
• Names of other key personnel;
• Participating institutions; and
• Number and title of this funding opportunity.

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 NCI staff to estimate the potential review workload and plan the review.

The letter of intent is to be sent by the date listed in Section IV.3.A.

The letter of intent should be sent to:

Eric J. (Rocky) Feuer, Ph.D.
Division of Cancer Control and Population Sciences
National Cancer Institute
Surveillance Research Program
Division of Cancer Control and Population Sciences
National Cancer Institute
6116 Executive Blvd, Room 5041, MSC 8317
Bethesda, MD 20892-8317 (for U.S. Postal Service express and regular mail)
Rockville, MD 20852 (for non-U.S.P.S. delivery)
Phone: 301-496-5029 or 301-435-7739
Fax: 301-480-2046
Email: [email protected]

3.B. Sending an Application to the NIH

Applications must be prepared using the forms found in the PHS 398 instructions for preparing a research grant application. Submit a signed, typewritten original of the application, including the checklist, and three signed photocopies in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for non-U.S.P.S. delivery)

Personal deliveries of applications are no longer permitted (see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-040.html).

At the time of submission, two additional copies of the application and all copies of the appendix material must be sent to:

Referral Officer
Division of Extramural Activities
National Cancer Institute
6116 Executive Boulevard, Room 8041, MSC 8329
Bethesda, MD 20892-8329 (for U.S. Postal Service regular or express mail)
Rockville, MD 20852 (for non-USPS delivery)
Telephone: (301) 496-3428
Fax: (301) 402-0275
Email: [email protected]

3.C. Application Processing

Applications must be received on or before the application receipt date described above (Section IV.3.A.). If an application is received after that date, the application may be delayed in the review process or not reviewed. Upon receipt, applications will be evaluated for completeness by the CSR and for responsiveness by the reviewing Institute Incomplete and/or non-responsive applications will not be reviewed.

The NIH will not accept any application in response to this funding opportunity that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. However, when a previously unfunded application, originally submitted as an investigator-initiated application, is to be submitted in response to a funding opportunity, it is to be prepared as a NEW application. That is, the application for the funding opportunity must not include an Introduction describing the changes and improvements made, and the text must not be marked to indicate the changes from the previous unfunded version of the application.

Information on the status of an application should be checked by the Principal Investigator in the eRA Commons at https://commons.era.nih.gov/commons/.

4. Intergovernmental Review

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

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

Pre-award costs are allowable. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new award if such costs: 1) are necessary to conduct the project; and 2) would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new award.

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project (see the NIH Grants Policy Statement at http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part6.htm).

Specific Funding Restrictions for this FOA. Awards are limited to $1.3 million total costs in year 1. It is anticipated that most applicants will request budgets in the range from $600K to $1.2 million total cost in year 1. Additional justification should be given for a large number of modeling groups and budgets close to the maximum.

The budget of individual modeling groups should generally not exceed $275K in total costs in year 1, with up to 3% annual increases per year in years 2-5. (Budget requests for modeling groups with limited anticipated roles should be substantially smaller.)

The budget of the coordinating centers should generally not exceed $125K in total costs in year 1, with up to 3% annual increases after that. On the top of these costs, discretionary funds are to be budgeted starting in Year 2. Total costs in Year 2 for discretionary funds cannot exceed 11% of the total budget of the entire application in Year 1, and can increase up to 3% annually in Years 3-5. In principle, the discretionary funds should remain unallocated (i.e., listed as Other Expenses in the budgetary requests). However, if necessary and justified, applicants may budget up to 50% of the discretionary funds to supplement specific regular coordination activities.

6. Other Submission Requirements

Modifications to PHS398 Instructions for Application Preparation

Table of Contents (PHS 398 Form Page 3): Modify Form Page 3 of the PHS 398 to replace standard Items 2-5 of the PHS 398 Research Plan with the following new sections:

• Section N1. Overall Objectives, Significance, and Specific Aims
• Section N2. Team Leadership and Coordinating Center
• Section N3. Proposed Models and Previous Model Applications
• Section N4. Proposed Model Extensions, Applications and Comparative Modeling

Budget (PHS 398 Form Pages 4 and 5): Follow the current PHS 398 instructions to provide a detailed budget (direct costs) for the entire application for the first 12-month period (Form page 4) and the entire proposed project period (Form page 5). Include appropriate budget pages for any subcontractual arrangements proposed.

Use additional Form Pages 4 and 5 to provide detailed separate budget information (first year and cumulative budgets for the entire project period) for the following individual application components:

• Separately for each proposed modeling group; and
• Separately for the Coordination Center (include discretionary funds allowable for years 2-5)

RESEARCH PLAN: The standard PHS398 Research Plan (Items 2-5 as per Revision 11/07 of the PHS 398 Table of Contents) is altered as follows:

• Standard Items 2-5 of the PHS 398 Research Plan are replaced by the new Sections N1-N4 (specified below)
• The PHS 398 standard page limit for Items 2-5 is replaced by a new limit of 55 pages to encompass the combination of the new Sections N1-N4.

Note: Within the stated overall page limit, numbers of pages suggested in the text below for individual sections are provided solely as a nonbinding guidance for applicants. Applicants are encouraged to use the minimum number of pages necessary to describe the research plan clearly and succinctly.

Other items of the PHS398 Research Plan remain unmodified.

Section N1. Overall Objectives, Significance, and Specific Aims

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. 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. There can be general aims, with sub-aims if that structure is useful

This section is suggested to comprise approximately two to four pages.

Section N2. Team Leadership and Coordinating Center

This section should describe how the activities across the modeling groups will be integrated and coordinated. It will describe not only the activities of the coordinating center, but also how some of the coordination activities will be shared across the modeling groups. The processes for decision making should be described, all well as plans and processes for spending of discretionary funds should be outlined. Even though some of the discretionary funds should remain unallocated, it is appropriate to assign (in the budget request) the remaining balance of these funds to specific, regular coordination activities that are anticipated.

This section should be approximately 2-4 pages.

Section N3. Proposed Models and Previous Model Applications

This section should give an overview of each model, the accomplishments of each modeling group, and if the group or subgroups have worked together previously, the joint accomplishments. A summary of underling model structures and assumptions must be clearly stated in the application. 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.

The length of this section will vary with the number of modeling groups included in the application.

Section N4. Proposed Model Extensions, Applications and Comparative Modeling

This section is meant to describe models extensions, additional model calibration, or validation, and combining of models (if applicable). It 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. 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 group 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.

Other Budgetary Requirements

Applicants must plan to participate in two consortium meetings per year, including: (1) an annual meeting (approximately 3 days) in which awardees focused on all four cancer sites will meet together; and (2) a mid-year meeting (approximately 2 days) when awardees focused on each cancer site meet separately. For purposes of budgeting, funds should be requested for up to three persons per modeling group to travel to each of these two meetings.

Appendix Materials

All paper PHS 398 applications must provide appendix material on CD only, and include five identical CDs in the same package with the application (see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-031.html).

Do not use the Appendix to circumvent the page limitations of the Research Plan component. An application that does not observe the required page limitations may be delayed in the review process.

Resource Sharing Plan(s)

NIH considers the sharing of unique research resources developed through NIH-sponsored research an important means to enhance the value of, and advance research. When resources have been developed with NIH funds and the associated research findings published or provided to NIH, it is important that they be made readily available for research purposes to qualified individuals within the scientific community. If the final data/resources are not amenable to sharing, this must be explained in Resource Sharing section of the application (see http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm).

(a) Data Sharing Plan: Regardless of the amount requested, investigators are expected to include a brief 1-paragraph description of how final research data will be shared, or explain why data-sharing is not possible. Applicants are encouraged to discuss data-sharing plans with their NIH program contact (see Data-Sharing Policy or http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html).

(b) Sharing Model Organisms: Regardless of the amount requested, all applications where the development of model organisms is anticipated are expected to include a description of a specific plan for sharing and distributing unique model organisms and related resources, or state appropriate reasons why such sharing is restricted or not possible (see Sharing Model Organisms Policy, and NIH Guide NOT-OD-04-042).

(c) Genome-Wide Association Studies (GWAS): Regardless of the amount requested, applicants seeking funding for a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible. A genome-wide association study is defined as any study of genetic variation across the entire genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight) or the presence or absence of a disease or condition. For further information, see Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088, and http://grants.nih.gov/grants/gwas/.

Additional Resource Sharing Requirements

In addition to the stated NIH wide requirements, 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 components: (1) enhancing understanding of model structure by keeping up to date versions of documentation on the Model Profiler; (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. Component (3) above could be addressed in a number of different ways, including development of interactive decision making tools (see area of emphasis #9 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 components would be achieved, and could add other components as well. For some aspects of this plan, it is reasonable to assume that interested users may need to provide funding. Applicants should indicate that they will work toward achieving caBIG compatibility (https://cabig.nci.nih.gov/).

Applicants should also indicate their willingness to abide by any additional software and model release policies developed by the CISNET steering committee.

Specific Instructions for Foreign Applications

All foreign applicants must complete and submit budget requests using the Research & Related Budget component found in the application package for this FOA (see NOT-OD-06-096, August 23, 2006).

Section V. Application Review Information

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1. Criteria

Only the review criteria described below will be considered in the review process.

2. Review and Selection Process

Applications that are complete and responsive to the FOA will be evaluated for scientific and technical merit by an appropriate peer review group convened by the National Cancer Institute and in accordance with NIH peer review procedures (http://grants1.nih.gov/grants/peer/), using the review criteria stated below.

As part of the scientific peer review, all applications will:

• 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 a priority score;
• Receive a written critique; and
• Receive a second level of review by National Cancer Advisory Board.

The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by peer review;
• Availability of funds;
• Coverage across the six cancer sites included in this FOA with priority to the sites with high incidence and mortality;
• Relevance of the proposed project to program priorities;
• Compliance with resource sharing requirements.

The mission of the NIH is to support science in pursuit of knowledge about the biology and behavior of living systems and to apply that knowledge to extend healthy life and reduce the burdens of illness and disability. As part of this mission, applications submitted to the NIH for grants or cooperative agreements to support biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

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

Core Review Criteria. Reviewers will consider each of the five review criteria below in the determination of scientific and technical 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?

In addition, specific to this FOA:

• 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 which have a real chance of being implemented in the population?
• Will the results be packaged in a way that policy makers and cancer control planners can understand?

Investigator(s). Are the PDs/PIs, collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, 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?

In addition, specific to this FOA:

• Do the investigators comprise an interdisciplinary team that is adequate to conduct the proposed modeling, but also to provide an understanding of relevant scientific and technology issues, and to communicate the results of modeling in a way that can have maximum impact?
• Does the PD/PI of the proposed coordinating center have the appropriate qualifications and experience to lead and coordinate a program of this size and complexity?
• Are the backgrounds and expertise of the PDs/PIs and key personnel adequate to conduct the proposed work and show evidence of cooperation?
• Are the commitments of the PDs/PI’s and other senior investigators commensurate with the proposed work plans?

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?

In addition, specific to this FOA:

• What is the potential of approaches proposed to influence a change in standards of medical care practice, cancer control strategies and/or public health policy and guidelines? Will these approaches be helpful in demonstrating the value of new and existing health care technologies?
• 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 clinical research, are the plans for: 1) protection of human subjects from research risks; and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

In addition, specific to this FOA:

• How well does the proposed project balance efforts devoted to the various cancer control issues and special areas of interest appropriate for the selected cancer site?
• 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?
• Are the approaches and data sources proposed for model calibration and validation sufficient to avoid problems of lack of identifiability of key parameters?
• 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?

In addition, specific to 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?
• Are there appropriate interactions/arrangements in place to result in the practical translation of modeling results as a systemic factor considered in policy making decisions?

In addition to the above review criteria, the following criteria will be applied to applications in the determination of scientific merit and the priority score.

Collaboration/Integration/Coordinating Center:

• Will the various components of the proposed program of research be coordinated into one unified effort?
• Do the PDs/PIs state their willingness to participate in joint meetings, share methods and data resources, and embark on collaborative efforts to decide on overall research directions?
• Does the coordinating center lay out a proposed set of plans that are flexible to incorporate group input and decision making by consensus?
• 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?
• Does the coordinating center have plans for conducting base cases, fielding outside inquiries, and other group activities?
• Does the coordinating center have a plan for keeping abreast of current policy related controversies, and the latest research results across the spectrum of treatment, screening, and prevention for their cancer site?
• Does the application lay out a reasonable plan for shared decision making across the project?
• Does the coordinating center propose an adequate plan for the discretionary activities and shared responsibilities?

Additional Review Criteria. As applicable for the project proposed, reviewers will consider the following additional items in the determination of scientific and technical merit, 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.

Inclusion of Women, Minorities, and Children. When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children.

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 American Veterinary Medical Association (AVMA) Guidelines on Euthanasia.

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.

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

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

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).

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.

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 (http://grants.nih/gov/grants/policy/data_sharing/data_sharing_guidance.htm); 2) Sharing Model Organisms (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-042.html); and 3) Genome Wide Association Studies (GWAS) (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html).

3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information

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1. Award Notices

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.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official (designated in item 12 on the Application Face Page). If a grantee is not email enabled, a hard copy of the NoA will be mailed to the business official.

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. See also Section IV.5. Funding Restrictions.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part4.htm) and Part II Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part9.htm).

The following Terms and Conditions will be incorporated into the award statement and will be provided to the Principal Investigator as well as to the appropriate institutional official, at the time of award.

2.A. Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS 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 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.

These Terms and Conditions of Award apply to all individual CISNET U01 awards. All the awardee institution(s), principal investigators (PDs/PIs) and other key personnel must agree to collaborate on the goals of the CISNET.

2. A.1. Awardees and Principal Investigator Rights and Responsibilities

The Principal Investigators will have the primary responsibility and rights for:

• Determining research approaches and procedures, developing and applying their models, and analyzing/interpreting results.
• PIs will have primary authority and responsibilities to define objectives and approaches, and to plan, conduct, analyze, and publish results, interpretations, and conclusions of their studies.
• Within this framework, PD/PIs from participating institutions (if the multiple PD/PI option is used) will be expected to collaborate with their coordinating center and the other PD/PIs on their CISNET award.
• Participating in collaborative modeling activities, sharing information 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 the grant, 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 meeting a year along with key co-investigators and participating in regular conference calls.
• Providing an annual progress report and other information on study progress as might be needed,
• Abiding by the Resource Sharing Plan, as laid out in the grant application, 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.
• Approve 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 PD/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 reports by the individual PD/PIs;
• Coordinating use and allocation of discretionary 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; and
• Overseeing adherence to the Resource Sharing Plan.

2. A.2. NIH Responsibilities

An NCI Program Directors acting as a Project Scientist and Project Coordinators will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards.

Specific activities of substantially involved personnel will include the following:

• The NCI Project Scientist will designate an NCI Scientific Coordinator for each cancer site.
• The NCI Project Scientist and one designated NCI Scientific Coordinator will serve on the Consortium Steering Committee as voting members.
• The NCI Project Scientist and the NCI Scientific Coordinators will provide 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. In addition, 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 provide support for a CISNET web site for the awardees. This web site will be a communications portal for posting papers, base case inputs, data sets, and the developmental Model Profiler through a separate contract. In addition, NCI will maintain a public web site for CISNET. The current public web site is 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 will have access to all modeling results generated under this award consistent with current HHS, PHS, and NIH policies.
• Another NCI representative may occasionally serve as a second or substitute Project Scientist.

Additionally, an NCI Program Director acting as the Program Official will be responsible for the normal scientific and programmatic stewardship of the awards and will be named in the award notice. A Program Official may also have substantial programmatic involvement (as a 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.

2.A.3. Collaborative Responsibilities

The NCI Project Scientist and the Principal Investigators representing each awardee will be responsible for forming a Steering Committee, the main governing board of the program, as defined below.

The Steering Committee will consist of:

• The NCI Project Scientist and one of the NCI Scientific Coordinators, as designated by the NCI Project Scientist (all the NCI representatives will collectively have one vote); and
• Representatives of awardees (i.e., the PD/PIs of the coordinating center for each award or designees) (each awardee representative will have one vote).

The activities of the Steering Committee will include the following:

• Setting overall consortium policies and procedures, and be the ultimate decision making body for CISNET, unless a disagreement is brought to arbitration;
• Determining if the policies and procedures of the cancer site specific 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);
• Setting publication procedures and policies; and
• Coordinating communication between the Working Groups.

The NCI Program Official will participate in the meetings of the Steering Committee as a non-voting member. Other NCI representatives may also be included as non-voting members as deemed appropriate.

2.A.4. Dispute Resolution

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

3. Reporting

Awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and Financial Status Report are required when an award is relinquished when a recipient changes institutions or when an award is terminated.

Section VII. Agency Contacts

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We encourage your inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research issues; peer review issues; and financial or grants management issues.

1. Scientific/Research Contacts:

Eric J. (Rocky) Feuer, Ph.D.
Division of Cancer Control and Population Sciences
National Cancer Institute
Surveillance Research Program
Division of Cancer Control and Population Sciences
National Cancer Institute
6116 Executive Boulevard, Room 5041, MSC 8317
Bethesda, MD 20892-8317 (for U.S. Postal Service regular or express mail)
Rockville, MD 20852 (for non-USPS delivery)
Phone: 301-496-5029 301-435-7739
Fax: 301-480-2046
Email: [email protected]

2. Peer Review Contacts:

Referral Officer
Division of Extramural Activities
National Cancer Institute
6116 Executive Boulevard, Room 8041, MSC 8329
Bethesda, MD 20892-8329 (for U.S. Postal Service regular or express mail)
Rockville, MD 20852 (for non-USPS delivery)
Telephone: (301) 496-3428
FAX: (301) 402-0275
Email: [email protected]

3. Financial or Grants Management Contacts:

Crystal Wolfrey
Office of Grants Administration
National Cancer Institute (NCI)
6120 Executive Boulevard, EPS Suite 243, MSC 7150
Bethesda, MD 20892-7150 (for U.S. Postal Service express or regular mail)
Rockville, MD 20852 (for non-USPS delivery)
Telephone: (301) 496-8634
Fax: (301) 496-8601
Email: [email protected]

Section VIII. Other Information

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Required Federal Citations

Use of Animals in Research:
Recipients of PHS support for activities involving live, vertebrate animals must comply with PHS Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf) as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm) as applicable.

Human Subjects Protection:
Federal regulations (45CFR46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

Data and Safety Monitoring Plan:
Data and safety monitoring is required for all types of clinical trials, including physiologic toxicity and dose-finding studies (phase I); efficacy studies (Phase II); efficacy, effectiveness and comparative trials (Phase III). Monitoring should be commensurate with risk. The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risks to the participants (NIH Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Sharing Research Data:
Investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing).

Investigators should seek guidance from their institutions, on issues related to institutional policies and local IRB rules, as well as local, State and Federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of the scientific merit or the priority score.

Policy for Genome-Wide Association Studies (GWAS):
NIH is interested in advancing genome-wide association studies (GWAS) to identify common genetic factors that influence health and disease through a centralized GWAS data repository. For the purposes of this policy, a genome-wide association study is defined as any study of genetic variation across the entire human genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight), or the presence or absence of a disease or condition. All applications, regardless of the amount requested, proposing a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible. Data repository management (submission and access) is governed by the Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088. For additional information, see http://grants.nih.gov/grants/gwas/

Access to Research Data through the Freedom of Information Act:
The Office of Management and Budget (OMB) Circular A-110 has been revised to provide access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this funding opportunity in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award.

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh Dole Act (see the NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/index.htm). All investigators submitting an NIH application or contract proposal, beginning with the October 1, 2004 receipt date, are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

Inclusion of Women And Minorities in Clinical Research:
It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the new PHS Form 398; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences.

Inclusion of Children as Participants in Clinical Research:
The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them.

All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the inclusion of children as participants in research involving human subjects (http://grants.nih.gov/grants/funding/children/children.htm).

Required Education on the Protection of Human Subject Participants:
NIH policy requires education on the protection of human subject participants for all investigators submitting NIH applications for research involving human subjects and individuals designated as key personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

Human Embryonic Stem Cells (hESC):
Criteria for federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov). It is the responsibility of the applicant to provide in the project description and elsewhere in the application as appropriate, the official NIH identifier(s) for the hESC line(s) to be used in the proposed research.

NIH Public Access Policy Requirement:
In accordance with the NIH Public Access Policy (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html) investigators must submit or have submitted for them their final, peer-reviewed manuscripts that arise from NIH funds and are accepted for publication as of April 7, 2008 to PubMed Central (http://www.pubmedcentral.nih.gov/), to be made publicly available no later than 12 months after publication. As of May 27, 2008, investigators must include the PubMed Central reference number when citing an article in NIH applications, proposals, and progress reports that fall under the policy, and was authored or co-authored by the investigator or arose from the investigator’s NIH award. For more information, see the Public Access webpage at http://publicaccess.nih.gov/.

Standards for Privacy of Individually Identifiable Health Information:
The Department of Health and Human Services (DHHS) issued final modification to the "Standards for Privacy of Individually Identifiable Health Information", the "Privacy Rule", on August 14, 2002. The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the DHHS Office for Civil Rights (OCR).

Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR website (http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on "Am I a covered entity?" Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. For publications listed in the appendix and/or Progress report, internet addresses (URLs) must be used for publicly accessible on-line journal articles. Unless otherwise specified in this solicitation, Internet addresses (URLs) should not be used to provide any other information necessary for the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site.

Healthy People 2010:
The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This FOA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:
This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372. 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 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The NIH Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.

Loan Repayment Programs:
NIH encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue a research career involving clinical, pediatric, contraception, infertility, and health disparities related areas. The LRP is an important component of NIH's efforts to recruit and retain the next generation of researchers by providing the means for developing a research career unfettered by the burden of student loan debt. Note that an NIH grant is not required for eligibility and concurrent career award and LRP applications are encouraged. The periods of career award and LRP award may overlap providing the LRP recipient with the required commitment of time and effort, as LRP awardees must commit at least 50% of their time (at least 20 hours per week based on a 40 hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov.