and Human Services (HHS)
EXPIRED
CANCER INTERVENTION AND SURVEILLANCE MODELING NETWORK (CISNET) Release Date: July 9, 2001 RFA: RFA-CA-02-010 (see reissue RFA-CA-05-018) National Cancer Institute Letter of Intent Receipt Date: October 9, 2001 Application Receipt Date: November 13, 2001 This RFA is a reissue of RFA-CA-99-013, which was published in NIH Guide on August 18, 1999. PURPOSE The Division of Cancer Control and Population Sciences (DCCPS), National Cancer Institute (NCI), invites applications from domestic and foreign applicants to support collaborative research using simulation and other modeling techniques to describe the impact of interventions (i.e., primary prevention, screening, and treatment) in population-based settings in the United States or in non-US settings that will shed light on US population-based trends. It is well known that great progress in the war against cancer is possible by the complete use and adequate delivery of existing modalities of cancer control. The primary goals of this research are: 1) to determine the impact of cancer control interventions on observed trends in incidence and/or mortality, and to 2) to determine if recommended interventions are having their expected population impact by examining discrepancies between controlled cancer intervention study results and the population experience. Once a general understanding of the various factors influencing current trends has been achieved, a number of secondary goals may be addressed. Applicants may propose secondary goals of modeling the potential impact of new interventions on future national trends, and/or determining the impact of targeted cancer control interventions on population outcome (i.e. evaluating optimal cancer control strategies). In the past most models of cancer interventions have been developed to describe hypothetical cohorts in a trial or other limited clinical settings. It is not the purpose of this RFA to support analysis of hypothetical or trial-based cohorts and/or cost-effectiveness analyses, but rather to support analyses based on realistic scenarios of population impact. Projects will focus on models describing the population impact of the observed dissemination of cancer control interventions as well as other factors on observed national incidence and/or mortality trends. This second round of funding for CISNET will be limited to applications focusing on prostate, colorectal, and lung cancers. For a summary of currently funded CISNET projects from the first round of funding (which started in FY 2000) in breast, prostate, and colorectal cancer see http://www-dccps.ims.nci.nih.gov/SRAB/cisnet.html. To keep applications focused, each will be limited to a single cancer site. The cooperative agreement mechanism calls for the development of site-specific working groups that will: (1) facilitate comparative analyses, (2) allow modeling groups access to a broader array of data resources and interdisciplinary expertise and (3) provide a forum for discussions of validation and other methodologic issues. The CISNET will allow for diversity and originality of modeling approaches that can be compared using uniform criteria. The Division of Cancer Control and Population Sciences, which fulfills a federal-level function to respond to evolving surveillance questions of national policy relevance, helps focus research questions and act as a conduit to national data resources necessary for parameter estimation, model calibration, validation and population trends. An emergent property of this collaborative agreement is progress towards a comprehensive understanding of the determinants of cancer site-specific trends at the population level and a better understanding of the science of modeling. RESEARCH OBJECTIVES Background Modeling is the use of mathematical and statistical techniques within a logical framework to integrate and synthesize known biological, epidemiological, clinical, behavioral, genetic and economic information. Simulation and other modeling techniques have been utilized to describe the impact of cancer interventions (i.e., primary prevention, screening, and treatment) for hypothetical cohorts or in trial and other clinical settings. The goal of this RFA is to promote the application and extension of these models to population- based settings in order to ascertain determinants of cancer trends. This information is critical to the National Cancer Institute because of the necessity of understanding: (1) if recommended interventions are having their expected population impact, and (2) to predict the potential impact of new interventions on national trends. These studies will often involve extrapolation of results of controlled cancer intervention studies to estimates of U.S. population and community effectiveness. This type of modeling addresses issues of population-based policies and programs, and is distinct from individual level models of risk and models of clinical decision making used at the individual patient-physician level. An additional goal of this concept is to advance methodology for modeling and to develop more uniform criteria for model validation in the population setting. The National Cancer Institute (NCI) has a longstanding need to provide answers to critical research questions that cannot be obtained from direct observation because of expense, ethical, or other reasons. For example, a trial is only conducted in a limited study population under limited study conditions and extrapolation to other settings and conditions may only be feasible through modeling. Lead time, the time which a diagnosis is advanced through screening, often may only be estimated through modeling because it is unethical to leave a screen detected patient untreated until clinical symptoms develop. Prior to the CISNET, NCI had supported a variety of small efforts in this area through in-house work, contracts and grants. The majority of extramural efforts have been directed at the analysis of specified cancer control interventions using a variety of modeling approaches applied to a hypothetical cohort or in the context of a trial or other limited settings, while the in-house work has mainly been directed toward addressing cancer surveillance issues at the national level. There has been growing recognition that much can be gained by integration of these two approaches. Models have increasingly been used in recent years to inform public health policy decisions at the national level. In Europe, the cervical and breast cancer screening models have been used to design, monitor and evaluate national screening programs in several countries [1]. Models have been used in the United States to understand the implication of dramatic changes in national cancer statistics, such as patterns of increasing incidence related to screening for breast and prostate cancer [2-4], improving survival due to the dissemination of breakthrough treatment approaches in Hodgkin"s Disease and testicular cancer [5-6]. Macro-level models use estimates of standard population-based statistics (i.e., birth rates, incidence, stage-distribution, relative survival, and mortality from causes other than cancer) as parameter estimates to model the life-process in terms of birth, the development of cancer, and death from cancer or other causes. The impact of cancer control interventions aimed at primary prevention, screening, and treatment are estimated by changing the model parameters. This approach has proven useful in evaluating the potential costs and benefits of specific cancer control strategies, and exploring the impact of these interventions on population-based cancer incidence and mortality statistics. For example, CAN*TROL (a computer program developed by Dr. David Eddy for cancer control planning for the World Heath Organization and adapted for use at the NCI) [7] is a tool which has been used to examine the cost- effectiveness of various strategies for breast cancer screening, and models of this type are currently being used to evaluate the impact of the introduction of adjuvant therapy on breast cancer mortality as well as the impact of changes in modifiable risk factors on colon cancer incidence. CAN*TROL has proven to be an effective tool for responding to policy questions from Congress and other sources addressed to the NCI. Macro-level models have their limitations. For example, macro-level models do not capture individual disease history, especially the pre-clinical phase, nor how early detection might alter that history. These dynamics are best captured using other types of models such as microsimulation. While these modeling efforts have been invaluable in providing insight into the cost and effectiveness of specific intervention strategies, they are not designed to directly address the question of how trends in screening dissemination at the national level affect trends in cancer incidence, survival, mortality, and cost. Recent efforts have been made to adapt these models to address population level surveillance questions. While in the past these models have been utilized to model hypothetical cohorts in an organized screening program, the NCI has facilitated efforts to model opportunistic screening for multiple cohorts reflecting the varying cancer risk of U.S. population over time. For example, current efforts are underway to model the impact of the dissemination of the PSA screening test in the US population on prostate cancer incidence and mortality [8]. Validating against current population trends can provide further clues concerning lead-time, over diagnosis, and the timing and size of potential mortality declines. In conjunction with the development of these models, there have been various methodologic spin-offs that have broad uses in a variety of modeling settings. For example, NCI researchers, in collaboration with extramural researchers, have investigated the issue of obtaining variability of estimates from microsimulations [9], estimation techniques have been developed for the incidence of pre-clinical prostate cancer from autopsy prevalence data [10], and issues related to model validation have been explored. OBJECTIVES AND SCOPE The objective of this RFA is to enhance research on the development and use of models to evaluate the impact of cancer control interventions on population level statistics. Funding consists of two rounds in FY2000 and FY2002. In FY2000 applications were restricted to breast, prostate and colorectal cancer. These are three major cancer control sites where there is substantial modeling experience and, for the most part, interest in the population impact of all three modalities of cancer control (screening, treatment, and primary prevention). Seven breast applications were funded, as well as one apiece in prostate and colorectal cancer. For the list of currently funded projects and their abstracts see: http://www-dccps.ims.nci.nih.gov/SRAB/cisnet.html. Also listed on the web site will be schedules for phone conference calls to discuss the existing CISNET program/work, the scope of the current RFA, and answer questions by potential applicants. There will probably be one conference call per cancer site (i.e. prostate, colorectal and lung cancer). Summaries of the calls and/or tapes will be available for those unable to participate directly. Based on our funding results from the first round, the second round of funding will be limited to prostate, colorectal, and lung cancer. To keep applications focused, each proposal will be limited to a single cancer site. New investigators will be expected to join in the ongoing collaborative activities already underway. All of the proposals must include a central focus on the modeling the impact of cancer control interventions and other factors on observed national trends in incidence and/or mortality. Examples of this type of research include: (A) Model of the population impact of the introduction of new therapies using estimates of the impact of these therapies in controlled settings and population dissemination patterns (e.g., a model of the impact of adjuvant chemotherapy on colon cancer mortality starting in 1989). (B) Model of the impact of interventions aimed at changing modifiable risk factors on population trends in incidence and/or mortality (e.g. model the impact of US and regional smoking cessation and smoking reduction patterns on lung cancer incidence and/or mortality). (C) Model of the impact of screening on population incidence and/or mortality patterns using a model of disease natural history, the population dissemination of screening, and the operating characteristics of these screening modalities (e.g. what are the relative roles of screening (i.e., early detection), and polyp removal (i.e. prevention) on colorectal cancer incidence trends). (D) Use discrepancies between modeled and observed population trends to study the community effectiveness of interventions (e.g. study discrepancies between model predictions and observed data to better understand how community screening practices differ from trials. The sensitivity of screening test may be better than in a trial setting because of improved technology developed since the trial or worse because of less expert application of technology compared to the trial setting). In addition to a central focus on observed trends in incidence and/or mortality, applications may also include applications of models that: (1) Predict the impact of new interventions on national trends (e.g., model the potential impact of spiral CT screening on lung cancer mortality, model the impact of new tobacco products on lung cancer incidence and/or mortality). (2) Determine the impact of targeted cancer control interventions on population outcome (e.g., model the population impact of targeting different age groups, risk groups, adherence to initial versus repeat screening guidelines, model the impact of programs to encourage smoking reduction versus smoking cessation on lung cancer incidence and/or mortality). The purpose of these efforts is to model the impact of the observed dissemination of cancer control interventions in the population, rather than using observed population trends to postulate new risk factors. However, these models can include components which model the impact of population changes in both modifiable and non-modifiable risk factors. Models which include the impact of multiple interventions simultaneously, e.g., the synergistic effects of screening and treatment, are desirable. Models can be of the entire US population, a region of the country, or some specific identified population where unique data exists on the implementation of an intervention, or in a subpopulation of specific interest (e.g., rural poor). Models can be developed for non-US populations, but should be justified based on their applicability to understanding US cancer trends. Models can focus on one aspect of a disease (e.g., polyp development and removal), although justification must be given as to how one part of the disease process can be modeled separately, and how this model can be integrated into the complete disease picture. It is not the purpose of this RFA to support analysis of hypothetical or trial-based cohorts and/or cost effectiveness analysis, but rather to support analysis based on realistic scenarios of population impact. Applications should demonstrate modeling capability, and propose a specific research plan. However, applicants should be flexible enough to accommodate further refinement and integration with other efforts. SPECIAL REQUIREMENTS Research Plan Applications in response to the RFA must address the following areas: Specific Aims/Background and Significance - The application must clearly state the surveillance research questions which this application is designed to address and the importance of these issues for cancer control in the US. If the proposal includes the modeling of trends outside of the US, justification must be given as to what special insights this will give in understanding of US trends, how these results will be related to US trends, and why the same models could not be applied directly to US data. All applications must include as a primary objective modeling of the impact of cancer control interventions and other factors on observed national trends in incidence and/or mortality. Applicants should discuss plans to develop, calibrate, and validate these models. A well-calibrated and validated model of observed trends will allow possible extensions to secondary objectives, which can include projecting the impact of new interventions on future trends, as well as designing optimal cancer control strategies. Preliminary Studies/Research Design and Methods - Since the application of models of cancer interventions to population based trends is a relatively new area, applicants should describe in detail their approach to adaptation of current models, and demonstrate an understanding of the problems inherent in working with population based data. The application must describe the nature and characteristics of the model to be employed. Is this a new or existing model? How will the model be adapted to address population-based surveillance questions? The application must describe the proposed data resources for model development and validation, a description of areas of potential collaboration with other grantees in this cooperative agreement, strategies for identifying and characterizing differences between modeled and observed population trends, and the overall approach towards developing a comprehensive understanding of the determinants of cancer site-specific trends at the population level. Contractual Arrangements The application should describe contractual arrangement necessary for acquisition and/or consolidation of data necessary for parameter estimation. Any other contractual arrangements should also be described. In addition, investigators should state their willingness to participate in joint meetings, to share methods and data resources, and to embark on collaborative efforts to decide overall research direction. For example, to allow for easier model comparisons, applicants may be asked to cooperate on a standardized base case where common model inputs (e.g. dissemination of screening in the US population) and outputs would be mutually agreed upon by cancer site working group participants. Investigators will be asked to post project descriptions and pre-submission publications for comment and review by the cooperative group. Budget First year costs may include funds for such activities as model development, model validation, acquisition of data for parameter estimation, methods development, and/or use or purchase of high-speed computer systems. Activities may involve the acquisition and/or consolidation of data necessary for parameter estimation, model calibration, or validation, and subcontracts may be employed if necessary to make these efforts possible. For purposes of budgeting, funds should be requested for up to three persons to travel to two cancer-site specific working group meetings, and one methodology meeting per year for each of the four years of the award. It is anticipated that an annual meeting will be a joint meeting with representatives from all four cancer sites, and will include the methodology meeting as well. The mid-year meetings will usually be separate cancer site-specific meetings If a PI, or an institution wishes to submit several applications which share a common structure (e.g., models for breast and prostate cancer which share a similar computing framework), funds to develop or enhance that common structure should be included separately in each application, and duplication of funding activities will be negotiated at the time of award. Likewise, travel funds for each application should be considered separately, and overlapping funding will be negotiated at the time of award. Finally, a submission from one institution may contain subcontracts for consultation from another institution, which may be unnecessary if both institutions are funded under CISNET. Areas of potential duplication of funds across multiple applications should be clearly identified. Terms and Conditions of Award The following terms and conditions will be incorporated into the award statement and provided to the Principal Investigator(s) as well as the institutional official at the time of award. Under this cooperative agreement, a partnership will exist between the recipient of the award and the NCI. These 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, and other HHS, and NIH Grant Administration policy statements. The administrative and funding instrument used for this program is a cooperative agreement (U01), an "assistance" mechanism (rather than an "acquisition" mechanism) in which substantial NCI scientific and/or programmatic involvement with the awardee is anticipated during performance of the activity. Under the cooperative agreement, the NCI purpose is to support and/or stimulate the recipient"s activity by involvement in and otherwise working jointly with the award recipient in a partner role, but it is not to assume direction, prime responsibility, or a dominant role in the activity. Consistent with this concept, the dominant role and prime responsibility for the activity resides with the awardee(s) for the project as a whole, although specific tasks and activities in carrying out the studies will be shared among the awardees and the NCI Scientific Staff. 1. Definitions: AWARDEES: Institutions receiving cooperative agreements through this RFA. NCI PROGRAM DIRECTOR: A scientist administrator from the NCI extramural staff, the Program Director, will not only provide normal stewardship for the U01 grants awarded under this RFA, but will also be involved in the scientific coordination and collaboration within the Network and will coordinate interaction between the research groups. PRINCIPAL INVESTIGATOR (PI): The investigator who is designated by the applicant organization to direct the project to be supported by the U01 grant. The PI will assume the responsibility and accountability to the applicant organization officials and to the NCI for the performance and proper conduct of the research supported by the U01 mechanism. Each institution may have more than one CISNET PI, and a single person may be the PI for applications for more than one cancer site. NCI SCIENTIFIC COORDINATORS: Scientists from the NCI extramural staff designated by the Program Director to coordinate the activities for one of the four cancer sites and the methodology working group. NCI scientific coordinators will have substantial scientific involvement with the working groups and will help refine research questions. NCI SCIENTIFIC STAFF: Scientific staff from NCI"s extramural and intramural programs called upon to provide their expertise to the CISNET efforts. EXTRAMURAL SCIENTIFIC INVESTIGATORS: Scientific staff named in the application from the participating institutions and their subcontractors. CANCER-SITE WORKING GROUPS: There will be four cancer site specific working groups (breast, prostate, colorectal, and lung cancer). Voting members of each working groups will be the PI"s of each site specific grant project, and the NCI Scientific Coordinator. Other project and NCI Scientific Staff will attend at the discretion of the voting members. The co-chairs of the working groups will be the NCI Scientific Coordinator and one of the PI"s (chosen by mutual consent of the PI"s for that cancer site). Other subcommittees will be formed by the working groups as needed. METHODOLOGY WORKING GROUP: A group comprised of interested methodologists among the extramural scientific investigators and NCI Scientific Staff. The chairs of the methodology working groups will be one Extramural Scientific Investigator (chosen by mutual consent of the Extramural Scientific Investigators on the Methodology Working Group) and an NCI Scientific Coordinator designated by the NCI Program Director. Other subcommittees will be formed by the working group as needed. STEERING COMMITTEE: A committee consisting of the five non-NCI chairs of the Working groups (breast, prostate, colorectal, lung, and methodology), the NCI Program Director, and one NCI Scientific Coordinator as designated by the NCI Program Director. The Chair of the Steering Committee will be one of the PI"s as selected by the Steering Committee. The Steering Committee can admit additional non-federal members as they deem necessary. The Steering Committee will provide overall direction for the CISNET project and provide oversight to procedures and policies. 2. Awardee Rights and Responsibilities The award recipients must join the NCI CISNET project for the purpose of planning, developing, and conducting collaborative projects to address high priority surveillance research objectives. Within this framework, awardees have primary authorities and responsibilities to define objectives and approaches, and to plan, conduct, analyze, and publish results, interpretations, and conclusions of their studies. Awardees will be required to attend working group meetings and are obligated to adhere to joint decisions for publication and research direction decided on by the Steering Committee and the Working Groups. Awardees will be expected to share information about model structure and assumptions at working group meetings, as well as strategies and data resources for parameter estimation. Awardees will be expected to engage in efforts coordinated by the Working Groups for calibration, validation, and comparison of model results. Awardees will retain custody of and have primary rights to the models and model results developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies. 3. NCI Staff Responsibilities The NCI Program Director and his designees will have substantial scientific- programmatic involvement during conduct of this activity, through technical assistance, advice and coordination above and beyond normal program stewardship for grants. The NCI Program Director will serve as a member of the Steering Committee. The NCI Program Director will designate an NCI Scientific Coordinator for each cancer site and for the methodology group who will serve as a co-chair of the Working Groups. 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 call upon other NCI Scientific Staff to provide advice on specific scientific and technical issues as needed. The NCI reserves the right to reduce the budget, withhold support, or suspend, terminate or curtail a study or an award in the event of substantial lack of collaborative participation, failure to make satisfactory progress in fulfilling the stated goals of the project, refusal to carry out the recommendations of the Working Groups or the Steering Committee, or substantial failure to comply with the terms of award. 4. Collaborative Responsibilities A. Steering Committee The Steering Committee will: Be the ultimate decision making body for CISNET, unless a disagreement is brought to arbitration. Review, approve, and provide comments on the written reports of the Cancer Site-Specific Working Groups. This approval process should ensure that the proposed activities are consistent with the objectives and scope as specified in the RFA. Review, approve, comment on, and provide directives for implementation based on the written recommendations from the Methodology Working Group. Set publication procedures and policies. Coordinate communication between the Working Groups. Meet at least twice a year, and schedule additional meetings and conference calls as needed. B. Working Groups Meet at least twice a year. Refine research questions that are consistent with high priority surveillance research needs. Identify key potential determinants and confounders of population based trends, and to identify useful data resources to inform these models. Collaborate to identify and select common data resources for conducting calibration and independent model validation. Consider the development of common modules that supply intermediate inputs to the central simulation models (e.g., screening histories supplied by a dissemination module, survival improvements in a screening model supplied by a treatment dissemination module). Consider the use of common input data for dissemination, costs, and other parameters based on the best available national estimates. Facilitate comparative analyses which will improve the credibility of individual models. Evolve into an expert knowledge base to provide technical advise on policy relevant surveillance questions. Will provide written reports to the Steering Committee after each Working Group Meeting summarizing research priorities, directions, and method of implementation. Responsibilities of the chairs of the Working Groups will be to: Convene working meetings. Set meeting agendas. Coordinate communication within the Working Group, Set (in consultation with the working group) the publication agenda and schedule. The PI Co-Chair of the Working Group will serve as a voting member of the Steering Committee, and will represent their Working Group to the Steering Committee. C. The Methodology Working Group will: Meet once a year, mainly for the purpose of scientific presentation and exchange of ideas, and to coordinate research plans where necessary. Provide a forum for the discussion of methods development associated with the application of microsimulation and other models to population-based questions. At the discretion of the group, provide written recommendations to the steering committee for common methodologic approaches and validation strategies and development of common model components. 5. Arbitration Any disagreement that may arise on scientific/programmatic matters (within the scope of the award), between award recipients and the NCI may be brought to arbitration. An arbitration panel will be composed of three members, one selected by the recipient group, a second member selected by the NCI, and the third member selected by the two prior selected members. This special arbitration procedure in no way affects the awardee"s right to appeal an adverse action that is otherwise appealable in accordance with the PHS regulations at 42 CFR Part 50, Subpart D and HHS regulation at 45 CFR Part 16. MECHANISM OF SUPPORT The administrative and funding instrument to be used for this program will be a cooperative agreement (U01), an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH scientific and/or programmatic involvement with the awardee is anticipated during performance of the activity. Under the cooperative agreement, the NIH purpose is to support and/or stimulate the recipient"s activity by involvement in and otherwise working jointly with the award recipient in a partner role, but it is not to assume direction, prime responsibility, or a dominant role in the activity. Details of the responsibilities, relationships and governance of the study to be funded under cooperative agreement(s) are discussed later in this document under the section "Terms and Conditions of Award". The total project period for applications submitted in response to the present RFA may not exceed four years. Awards and level of support depend on receipt of a sufficient number of applications of high scientific merit. The anticipated award date is July 2002. FUNDS AVAILABLE The NCI intends to commit approximately $1,250,000 in total costs (direct and Facilities and Administrative (F&A) costs) in FY 2002 to fund 4 to 6 new grants in response to this RFA. An applicant may request a project period of up to four years. It is anticipated that the award for each application for modeling of a single cancer site will be between $75,000 to a maximum of $250,000 total cost for the first year. It is anticipated that several modeling centers will submit applications for more than one cancer site. Each individual application must be limited to one cancer site. Because the nature and scope of the research proposed may vary, it is anticipated that the size of each award will also vary. Applications on the lower end of range (e.g., $75,000 - $125,000) are encouraged for smaller more focused efforts, while those at the higher end of the range ($125,000-$250,000) are for more comprehensive population-based applications which consider the entire spectrum of the disease process and/or model multiple interventions simultaneously. Although the financial plans of the NCI provide support for this program, awards pursuant to this RFA are contingent upon the availability of funds and the receipt of a sufficient number of applications of outstanding scientific and technical merit. ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign for-profit and non-profit organizations, public and private, such as universities, colleges, medical centers, units of State and Local governments, and eligible agencies of the Federal Government. Applications from minority individuals, women, and persons with disabilities, are encouraged to apply. Each Principal Investigator (PI) is limited to only one application per cancer site, and thus up to three applications are possible by one PI. If a PI, or an institution, is submitting several applications that share a common structure (e.g., models for lung and prostate cancer which share a similar computing framework), funds to develop or enhance that common structure should be included separately in each application, and overlapping funding of activities will be considered at the time of award (see Special Requirements - Budget). INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. The NCI will be holding a series of phone conference calls (probably one for each cancer site) for applicants to hear more about the existing CISNET work, and to discuss the scope of potential applications. For more information about the schedule for these calls see http://www-dccps.ims.nci.nih.gov/SRAB/cisnet.html. Summaries of the calls and/or tapes will be available for those unable to participate directly. Direct inquiries regarding programmatic issues to: Dr. Eric Feuer Division of Cancer Control and Population Sciences National Cancer Institute 6116 Executive Boulevard, Room 5041, MSC 8317 Bethesda, MD 20892-8317 Telephone: (301) 496-5029 Fax: (301) 480-2046 Email: [email protected] Direct inquiries regarding review issues to: Ms. Toby Friedberg Division of Extramural Activities National Cancer Institute 6116 Executive Blvd., Room 8109, MSC 8329 Bethesda, MD 20892-8329 Rockville, MD 20852 (for express/courier service) Telephone: (301) 496-3428 Fax: (301) 402-0275 Email: [email protected] Direct inquiries regarding fiscal matters to: Ms. Crystal Wolfrey Grants Administration Branch National Cancer Institute Executive Plaza South, Room 243 Bethesda, MD 20892-7510 Telephone: (301) 496-8634 Fax: (301) 496-8601 Email: [email protected] LETTER OF INTENT Prospective applicants are asked to submit, by October 9, 2001 a letter of intent that includes a descriptive title of the proposed research, name, address, and telephone number of the Principal Investigator, identities of other key personnel and participating institutions, and number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information allows NCI staff to estimate the potential review workload and to plan the review. The Letter of Intent is to be sent to the program staff listed under INQUIRES by the letter of intent receipt date listed in the heading of this RFA. SCHEDULE Letter of Intent Receipt Date: October 9, 2001 Application Receipt Date: November 13, 2001 Review by NCAB Advisory Board: May 2002 Earliest Anticipated Start Date: July 2002 APPLICATION PROCEDURES The research grant application form PHS 398 is to be used in applying for these grants. All instructions apply unless otherwise noted. Applications kits are available at most institutional offices of sponsored research and may be obtained from the Division of Extramural Outreach and Information Resources, National Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 301/710-0267, E-mail: [email protected]. For those applicants with internet access, the 398 kit may be found at http://grants.nih.gov/grants/funding/phs398/phs398.html The RFA label available in the PHS 398 application form must be affixed to the bottom of the face page of the application. Type the RFA number on the label. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2 of the face page of the application form and the YES box must be marked. The sample RFA label available at: http://grants.nih.gov/grants/funding/phs398/label-bk.pdf has been modified to allow for this change. Please note this is in pdf format. 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 (20817 for express service) At the time of submission, two additional copies of the application must also be sent to: Ms. Toby Friedberg Referral Officer Division of Extramural Activities National Cancer Institute 6116 Executive Blvd., Room 8109, MSC-8329 Rockville, MD 20852 (express courier) Bethesda, MD 20892-8329 Applications must be received by November 13, 2001. If an application is received after that date, it will be returned to the applicant without review. The Center for Scientific Review (CSR) will not accept any application in response to this announcement that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. The CSR will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of a substantial revision of an application already reviewed, but such an application must include an introduction addressing the previous critique. REVIEW CONSIDERATIONS Applicants are encouraged to submit and describe their own ideas about how best to meet the general research goals outlined in this RFA, and are expected to address issues identified under SPECIAL REQUIREMENTS of the RFA. Upon receipt, applications will be reviewed for completeness by CSR and responsiveness by the National Cancer Institute. Incomplete and/or non- responsive applications will be returned to the applicant without further consideration. Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by the Division of Extramural Activities of the National Cancer Institute in accordance with the review criteria stated below. As part of the initial merit review, a process will be used by the initial review group in which applications receive a written critique and undergo a process in which only those applications deemed to have the highest scientific merit, generally the top half of the applications under review, will be discussed assigned a priority score, and receive a second level review by the National Cancer Advisory Board. Review Criteria The goals of NIH-supported research are to advance our understanding of biological systems, improve the control of disease, and enhance health. The reviewers will comment on the following aspects of the application in their written critiques in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered by the reviewers in assigning the overall score weighting them as appropriate for each application. 1. Significance. Does this study address an important population-based surveillance problem? If the aims of the application are achieved, how will surveillance research and cancer control be advanced? What will be the potential effect of these studies on policy of health care practices that could ultimately improve the health of the American public? Does this application address realistic strategies and issues, rather than proposed optimal strategies that may have no real chance of ever being implemented in the population. 2. Approach. Are the nature and characteristics of the model to be employed adequate? How will the model be adapted to address population-based surveillance questions? Does the applicant have a plan for demonstrating a general understanding of the various factors influencing observed trends before investigating secondary goals of future trends and optimal cancer controls strategies? What are the strategies for identifying and characterizing differences between modeled and observed population trends, and general approach towards developing a comprehensive understanding of the determinants of cancer site-specific trends at the population level? Are the conceptual framework, design, methods, and analyses adequately developed, well integrated, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics? 3. Innovation. Does the project employ novel concepts, approaches or method? Are the aims original and innovative? Does the application describe in detail their approach to adaptation of current models for population modeling, and demonstrate an understanding of the problems inherent in working with population based data. 4. Investigator. Is the investigator appropriately trained and well suited to carry out this work? Do the investigators have extensive modeling experience? Is the work proposed appropriate to the experience level of the principal investigator and other researchers (if any)? Do the investigators comprise an interdisciplinary team that is adequate to carry out the proposed work? 5. Environment. Does the scientific environment in which the work will be done contribute to the probability of success? Is modeling activities an established element of the research environment? Do the proposed modeling efforts take advantage of unique features of the scientific environment or employ useful collaborative arrangements? Is there evidence of institutional support? 6. Collaboration. Do the investigators state their willingness to participate in joint meetings, be willing to share methods and data resources, and to embark on collaborative efforts to decide overall research direction? Do the investigators have a documented history of engaging in collaborative modeling research with: (a) colleagues at their own institution, (b) modeling groups at other institutions, (c) providers of primary data sources, and (d) policy oriented organizations or agencies? Documentation could include letters of support from prior collaborations. 7. Relevance. Does the application have as its primary goal modeling observed trends in incidence and/or mortality as a function of cancer control interventions and other factors? If the application includes secondary goals concerning modeling of future trends and/or optimal cancer control strategies, do these modeling efforts reflect realistic scenarios, which could be achieved in actual population settings? The initial review group will also examine: the appropriateness of proposed project budget and duration, the adequacy of plans to include both genders, minorities and their subgroups, and children as appropriate for the scientific goals of the research and plans for the recruitment and retention of subjects, the provisions for the protection of human and animal subjects, and the safety of the research environment. AWARD CRITERIA Applications recommended by the National Cancer Advisory Board will be considered for award based upon (a) scientific and technical merit, (b) program balance, including in this instance, a reasonable representation of projects across all three cancer sites, and sufficient compatibility of features to make a successful collaborative program a reasonable likelihood, and (c) availability of funds. INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS 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 biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and 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 research involving human subjects should read the UPDATED "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research," published in the NIH Guide for Grants and Contracts on August 2, 2000 (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-048.html), a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_update.htm. The revisions relate to NIH defined Phase III clinical trials and require: a) all applications or proposals and/or protocols to 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) all investigators to report accrual, and to conduct and report analyses, as appropriate, by sex/gender and/or racial/ethnic group differences. INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS. It is the policy of NIH that children (i.e., individuals under the age of 21) must be included in all human subjects research, conducted or supported by the NIH, unless there are clear and compelling scientific and ethical reasons not to include them. This policy applies to all initial (Type 1) applications submitted for receipt dates after October 1, 1998. 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" that was published in the NIH Guide for Grants and Contracts, March 6, 1998, and is available at the following URL address: http://grants.nih.gov/grants/guide/notice-files/not98-024.html. Investigators may also obtain copies of these policies from the program staff listed under INQUIRIES. Program staff may also provide additional relevant information concerning the policy. REQUIRED EDUCATION IN THE PROTECTION OF HUMAN RESEARCH PARTICIPANTS All investigators proposing research involving human subjects should read the NIH policy on education in the protection of human research participants now required for all investigators, which is published in the NIH Guide for Grants and Contracts, June 5, 2000 (Revised August 25, 2000), available at the following URL address: http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html. A continuing education program in the protection of human participants in research is now available online at http://cme.nci.nih.gov/. PUBLIC 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 public 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 RFA 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. URLS IN NIH GRANT APPLICATIONS OR APPENDICES All applications and proposals for NIH funding must be self-contained within specified page limitations. Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) should not be used to provide information necessary to the review because reviewers are under no obligation to view the Internet sites. Reviewers are cautioned 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 RFA, the Cancer Intervention Surveillance Modeling Network (CISNET), is related to the priority area of cancer surveillance and data systems. 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 No. 93.399, Awards are made under authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and administered under NIH grants policies and Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. The PHS strongly encourages all grant recipients to provide a smoke-free workplace and promote the non-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. REFERENCES 1. van den Akker-van Marle E, de Koning H, Boer R, van der Maas P. Reduction in breast cancer mortality due to the introduction of mass screening in the Netherlands: comparison with the United Kingdom. J Med Screen 1999,6:30-34. 2. Feuer, E.J., Wun, L.M. "How Much of the Recent Rise in Breast Cancer Incidence Can be Explained by Increases in Mammography Utilization: A Dynamic Population Approach," American Journal of Epidemiology, 1992, 136, 1423-1436. 3. Wun, L.M. Feuer, E.J., Miller, B.A. "Are Increases in Mammographic Screening Still a Valid Explanation for Trends in Breast Cancer Incidence in the United States?" Cancer Causes and Control, 1995, 6, 135-144. 4. Legler, J.M., Feuer, E.J., Potosky, A.L., Merrill, R.M., Kramer, B.S., "The Role of Prostate-Specific Antigen Testing Patterns in the Recent Prostate Cancer Incidence Decline," Cancer Causes and Control, 1998, 9, 519-527. 5. Feuer, E.J., Kessler, L.G., Triolo, H.E., Baker, S.G., Green, D.T. "The Impact of Breakthrough Clinical Trials on Survival in Population Based Tumor Registries," Journal of Clinical Epidemiology, 1991, 44, 141-153. 6. Weller, E.A., Feuer, E.J., Frey, C.M., Wesley, M.N., "Parametric Relative Survival Modeling Using Generalized Linear Models with Application to Hodgkin"s Lymphoma," Applied Statistics, 1999, 48, 79-89. 7. Levin DL, Gail MH, Kessler LG, Eddy DM, "A Model for Projecting Cancer Incidence and Mortality in the Presence of Prevention, Screening, and Treatment Programs," NCI Monographs, 2:83-93, 1986. 8. Etzioni, R, Legler, JM, Feuer, EJ, Merrill, RM, Cronin, KA, Hankey, BF, "Cancer Surveillance Series: Interpreting Trends in Prostate Cancer - Part III: Quantifying the Link Between Population Prostate-Specific Antigen Testing and Recent Declines in Prostate Cancer Mortality," JNCI , 91: 1033-1039, 1999. 9. Cronin KA, Legler, JM, Etzioni RD, "Assessing Uncertainty in Microsimulation Modeling with Application to Cancer Screening Applications," Statistics in Medicine, 1998, 17:2509-23. 10. Etzioni, R., Cha, R, Feuer, E.J., Davidov, O. "Asymptomatic Incidence and Duration in Prostate Cancer,." American Journal of Epidemiology, 1998, 148, 775-785.
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