Cancer Intervention and Surveillance Modeling Network (CISNET).The Division of Cancer Control and Population Sciences (DCCPS DCCPS Division of Cancer Control and Population Sciences (NCI)
DCCPS Department of Crime Control and Public Safety (North Carolina, USA) ) of the National Cancer Institute (NCI See Liberate. ) invites applications from domestic and foreign applicants to support collaborative research using simulation and other modeling techniques to describe the impact of interventions in population-based settings that will shed light on U.S. 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 to determine the impact of cancer control interventions on observed trends in incidence and/or mortality, and 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 evaluating optimal cancer control strategies.
The NCI has a long-standing function of providing answers to critical policy questions, which can only be answered through an indirect synthesis of available information and assumptions. A commitment to modeling of this type will allow the NCI to apply the most sophisticated tools available for evidence-based planning to several areas: 1) Be responsive to challenges due to the increasing pace of technology, and to provide short-term answers while randomized controlled trials (RCTs) are still in progress. In the future we will be increasingly faced with new interventions, biomarkers, and diagnostic and genetic tests that will become widely disseminated prior to rigorous testing in controlled settings, and therefore the evaluation of population impact will become even more important. 2) Address emerging questions while they are still being debated in the policy forum. For example, new smokeless tobacco smokeless tobacco,
n chewing tobacco (leaves) or tobacco powder (snuff) that allows the nicotine to be absorbed through the mucous membrane of the oral cavity or digestive tract. It is related to a high risk of oral cancer. products are coming on the market, and modeling of their potential impact can benefit the Federal Trade Commission and other policy makers. 3) Translate RCT RCT Randomized Controlled Trial
RCT Regimental Combat Team (infantry regiment with their own artillery, engineers, medical and tanks)
RCT Rollercoaster Tycoon
RCT Randomized Clinical Trial
RCT Rhondda Cynon Taff evidence of quantities to the population setting. 4) Provide estimates of quantities that will never be derived from RCTs. For example, half of Americans alive today who ever smoked are ex-smokers. It is important to understand the patterns of quitting, the process of carcinogenesis car·ci·no·gen·e·sis
The production of cancer.
production of cancer.
viruses and some parasites are capable of initiating neoplasia. for ex-smokers, and the implications for future lung cancer lung cancer, cancer that originates in the tissues of the lungs. Lung cancer is the leading cause of cancer death in the United States in both men and women. Like other cancers, lung cancer occurs after repeated insults to the genetic material of the cell. trends.
DCCPS, which fulfills a federal-level function to respond to evolving surveillance questions of national policy relevance, helps focus research questions and acts 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 toward a comprehensive understanding of the determinants of site-specific cancer trends at the population level and a better understanding of the science of modeling.
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. Prior to the Cancer Intervention and Surveillance Modeling Network (CISNET), many of the simulation and other modeling techniques had been utilized to describe the impact of cancer interventions (i.e., primary prevention, screening, treatment) for hypothetical cohorts or in trial and other clinical settings. The goal of this request for applications (RFA RFA right frontoanterior (position of the fetus).
Radiofrequency ablation (RFA)
A procedure in which radiofrequency waves are used to destroy blood vessels and tissues.
Mentioned in: Prenatal Surgery ) 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 NCI because of the necessity of understanding whether recommended interventions are having their expected population impact, and of predicting the potential impact of new interventions on national trends. These studies will often involve extrapolation (mathematics, algorithm) extrapolation - A mathematical procedure which estimates values of a function for certain desired inputs given values for known inputs.
If the desired input is outside the range of the known values this is called extrapolation, if it is inside then of results of controlled cancer intervention studies intervention studies,
n.pl the epidemiologic investigations designed to test a hypothesized cause and effect relation by modifying the supposed causal factor(s) in the study population. 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.
It is not the purpose of this RFA to focus on the 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.
CISNET was originally funded as a cooperative agreement (U01) for two phased-in rounds of funding. In September 2000, RFA CA-99-013 funded seven grants in breast cancer, one in prostate cancer prostate cancer, cancer originating in the prostate gland. Prostate cancer is the leading malignancy in men in the United States and is second only to lung cancer as a cause of cancer death in men. , and one in colorectal cancer colorectal cancer
Malignant tumour of the large intestine (colon) or rectum. Risk factors include age (after age 50), family history of colorectal cancer, chronic inflammatory bowel diseases, benign polyps, physical inactivity, and a diet high in fat. . A second round, funded under RFA CA-02-010 in August 2002, funded five grants in lung cancer as well as two additional grants for colorectal cancer and one in prostate cancer.
CISNET investigators are currently engaged in a wide range of policy-relevant modeling studies including the following:
1) Development of base case questions. A major strength of having a consortium of modelers is the ability to employ a comparative modeling approach. While each modeler has areas of individual focus, whenever possible, common "base" questions have been developed that allow for comparisons across models. The sometimes widely different results from models are often difficult to resolve, and base cases provide a chance to reach consensus on important questions, and to better understand differences between models. In these base case questions, a set of common population inputs is used across all models (e.g., dissemination patterns of screening and treatment, mortality from noncancer causes), and a common set of intermediate and final outputs is developed to help understand differences and similarities across models.
2) Breast base case spin-off questions. The breast base case serves as a jumping-off point Noun 1. jumping-off point - a beginning from which an enterprise is launched; "he uses other people's ideas as a springboard for his own"; "reality provides the jumping-off point for his illusions"; "the point of departure of international comparison cannot be an for each grantee An individual to whom a transfer or conveyance of property is made.
In a case involving the sale of land, the buyer is commonly known as the grantee.
grantee n. as they vary the basic formulation to focus on areas of individual interest. Spin-off issues that are actively being pursued include a) modeling the impact of using alternative, more biologically based natural disease history formulations, especially continuous time tumor growth models (which include microscopic fatal metastases Metastasis (plural, metastases)
A tumor growth or deposit that has spread via lymph or blood to an area of the body remote from the primary tumor.
Mentioned in: Malignant Melanoma that are initially undetectable); b) analyses for different racial, ethnic, and insurance-status groups; c) a unique Bayesian approach to update its prior estimates of treatment efficacy to obtain posterior estimates of community effectiveness of adjuvant therapy Adjuvant therapy
A treatment done when there is no evidence of residual cancer in order to aid the primary treatment. Adjuvant treatments for endometrial cancer are radiation therapy, chemotherapy, and hormone therapy. and mammography mammography, diagnostic procedure that uses low-dose X rays to detect abnormalities in the breasts. The early diagnosis of breast cancer made possible by the routine use of mammography for screening women increases a woman's treatment alternatives and improves her that best reproduce national mortality trends; d) geographically based analyses; e) the role of risk factors in breast cancer trends; and f) the potential impact of optimal screening intervals.
3) Prostate cancer. CISNET researchers have published an analysis of trends in the use of the prostate-specific antigen prostate-specific antigen
n. Abbr. PSA
A protease secreted by the epithelial cells of the prostate gland. Serum levels are elevated in patients with benign prostatic hyperplasia and prostate cancer. (PSA (Professional Services Automation) An information system designed to organize, track and manage all opportunities, work, resources, costs, revenues and invoices to improve the productivity and efficiency of the workforce. ) test for modeling prostate cancer incidence trends to obtain estimates of over-diagnoses associated with PSA screening. In addition, these researchers are investigating the use of modeling to better understand the results of ecologic analyses of the effectiveness of PSA screening.
4) Special issue of Statistical Methods in Medical Research. CISNET was invited to sponsor a special issue of the journal Statistical Methods in Medical Research titled "Uses of Stochastic Models Stochastic models
Liability-matching models that assume that the liability payments and the asset cash flows are uncertain. Related: Deterministic models. for the Early Detection of Cancer," with articles submitted in spring 2003. Articles in the issue include 1) "Distribution of Clinical Covariates at Detection of Cancer: Stochastic Modeling and Statistical Inference Inferential statistics or statistical induction comprises the use of statistics to make inferences concerning some unknown aspect of a population. It is distinguished from descriptive statistics. ," 2) "Planning Public Health Programs and Scheduling: Breast Cancer," 3) "Planning of Randomized ran·dom·ize
tr.v. ran·dom·ized, ran·dom·iz·ing, ran·dom·iz·es
To make random in arrangement, especially in order to control the variables in an experiment. Trials," 4) "The Use of Modeling to Understand the Impact of Screening on U.S. Mortality: Examples from Mammography and PSA Screening," 5) "Parameter Estimation for Stochastic Models via Simulation," and 6) "Diversity of Model Approaches."
5) Linkages with other cancer surveillance and control activities. CISNET has sought linkages to be integrated with and responsive to situations where modeling may play an important role. For example, the Agency for Health Research and Quality and the Center for Medicare and Medicaid Medicare and Medicaid
U.S. government programs in effect since 1966. Medicare covers most people 65 or older and those with long-term disabilities. Part A, a hospital insurance plan, also pays for home health visits and hospice care. Studies approached the NCI for assistance in studying a reimbursement decision related to the immunochemical im·mu·no·chem·is·try
The chemistry of immunologic phenomena, as of antigen-antibody reactions.
im fecal occult blood test Fecal Occult Blood Test Definition
The fecal occult blood test (FOBT) is performed as part of the routine physical examination during the examination of the rectum. (iFOBT) (http://cisnet. cancer.gov/reports/medicare.html). CISNET modelers have also been asked to aid in a midcourse mid·course
1. The part of a missile flight between the end of the launching phase and reentry, during which corrective maneuvers are made.
2. The middle point of a course or of a course of action. (2005) evaluation to help determine whether reaching Healthy People 2010 upstream goals for cancer treatment, screening, and prevention will enable us to fall short of, meet, or exceed the downstream 2010 cancer mortality goals, and to retarget our efforts if necessary.
This reissuance of CISNET will be limited to modeling applications focusing on breast, prostate, lung, and colorectal cancer. Although the reissuance of CISNET will not be limited to grantees previously or currently funded, CISNET will no longer fund models that either are starting from scratch or have not been previously applied to the analysis of population trends. This means that models should have been applied to multiple real birth cohorts representing the actual population experience. Models that have been applied only to hypothetical cohorts, as is sometimes done to model trial data or estimate cost-effectiveness, will not be considered. The emphasis in this reissuance is in the application of already developed models to study the population impact of existing or emerging cancer control interventions. In addition, applications are being solicited for cancer site-specific coordinating centers for breast, prostate, colorectal, and lung cancer.
Areas of application will include more refined analyses of current trends, and a renewed emphasis on future trends and optimal cancer control planning. While the original issuance focused primarily on discovery (basic mathematical and statistical relationships necessary for the development of multi-cohort population models) and development (data sources and realistic scenarios to evaluate past intervention impact in the population setting and project future impact), the reissuance will continue development efforts and will greatly enhance the delivery element (synthesizing relevant scenarios for informing policy decisions and cancer control planning implementation).
While some new mathematical and statistical derivations may be necessary, they should not be the centerpiece of these applications. Instead, the focus of the application should be on identifying important cancer surveillance and control questions, obtaining the data sources and making model modifications as necessary to run the model, and producing results that are meaningful and packaged in a way that policy makers and cancer control planners can understand. Inclusion of interdisciplinary expertise will be essential in this phase of CISNET. Applicants 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.
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 postulate: see axiom. new etiologic factors. However, these models can include components that model the impact of population changes in both modifiable and nonmodifiable risk factors nonmodifiable risk factor Medtalk Any risk factor–eg, heredity, for a particular condition–eg, breast CA, which cannot be modified . Models that include the synergistic impact of multiple interventions simultaneously are desirable. Models can be of the entire U.S. population, a region of the country, some specific identified population where unique data exist on the implementation of an intervention, or in a subpopulation sub·pop·u·la·tion
A part or subdivision of a population, especially one originating from some other population: microbial subpopulations.
Noun 1. of specific interest (e.g., the rural poor). However, whenever possible, inference should relate to the United States as a whole. Models can be developed for non-U.S. populations, but should be justified based on their applicability to understanding U.S. cancer trends.
Examples of areas of interest and types of questions are given below. Note that these are examples only, and applicants should not feel constrained to choose areas of application from this list only. 1) What new quantifiable statements can be made concerning estimates and uncertainty in the adenoma-colorectal cancer sequence? What is the range of natural history models associated with in situ In place. When something is "in situ," it is in its original location. breast cancer, and what are the implications of these natural history models for the overdiagnosis of disease?
2) What is the contribution of treatment to observed declines in prostate cancer mortality, especially the transition from the use of androgen androgen (ăn`drəjən): see testosterone.
Any of a group of hormones that mainly influence the development of the male reproductive system. deprivation therapy after biochemical failure (i.e., rising PSA levels) to use in the adjuvant adjuvant /ad·ju·vant/ (aj?dbobr-vant) (a-joo´vant)
1. assisting or aiding.
2. a substance that aids another, such as an auxiliary remedy.
3. setting? How can future improvements in the quality of care and the general health status of older individuals result in increased use and responsiveness to treatment?
3) What is the impact on incidence and mortality of both the increased dissemination of currently established screening modalities (e.g., iFOBT, sigmoidoscopy Sigmoidoscopy Definition
Sigmoidoscopy is a procedure by which a doctor inserts either a short and rigid or slightly longer and flexible fiber-optic tube into the rectum to examine the lower portion of the large intestine (or bowel). ) and the potential dissemination of new or more novel modalities (e.g., screening colonoscopy screening colonoscopy GI disease The use of flexible colonoscopy to detect malignant or premalignant colorectal lesions; SC is most cost effective ≥ age 50. See Colonoscopy. , advanced imaging modalities, iFOBT, fecal mutagen mutagen: see mutation.
Any agent capable of altering a cell's genetic makeup by changing the structure of the hereditary material, DNA. Many forms of electromagnetic radiation (e.g. tests, other innovative biomarkers)? As screening trial results for PSA, flexible sigmoidoscopy, chest X ray, and spiral computed tomography spiral computed tomography Helical scanning Imaging CT imaging based on 'slip-ring' technology, in which a large image volume is acquired by continuous rotation of the detector. See Computed tomography, Cf High-resolution computed tomography. start to become available over the next decade, how do these results alter our understanding of population trends in incidence and mortality?
4) Given that obesity is a major problem that is getting worse, what are the implications for projections of breast and colorectal cancer mortality? What is the expected dissemination of the use of tamoxifen tamoxifen (təmŏk`sĭfĕn'), synthetic hormone used in the treatment of breast cancer. Introduced in 1978, tamoxifen is used to prevent recurrences of cancer in women who have already undergone surgery to remove their tumors. for women with different risk profiles, and what is the projected mortality reduction associated with these levels of dissemination?
5) How would resource requirements be affected by the use of risk stratification risk stratification Medical decision-making The constellation of activities–eg, lab and clinical testing used to determine a person's risk for suffering a particular condition and need–or lack thereof–for preventive intervention models or biomarkers that would allow selective screening and/or selective surveillance monitoring of higher-risk individuals? What is the national burden of iatrogenic iatrogenic /iat·ro·gen·ic/ (i-a´tro-jen´ik) resulting from the activity of physicians; said of any adverse condition in a patient resulting from treatment by a physician or surgeon. morbidity from prostate cancer treatment among screen-detected men, and how do we weigh this against the potential mortality gains?
6) Can we use population trends to better understand differences in the natural history of prostate cancer between white and black men, and how can we use this information to better target interventions? How do racial disparities in obesity impact future trends? What is the impact of racial, economic, and insurance-status disparities in the use of adjuvant therapy and mammography on breast cancer mortality?
7) What is the impact of changing Medicare reimbursement policies on screening, treatment, and cancer mortality?
8) CISNET models should be able to help translate (in a timely manner) the impact of specific emergent results from epidemiologic, genetic, treatment, prevention, and screening studies to the population setting. Recent examples include how the mutation of a gene involved in non-small cell lung cancer Lung Cancer, Non-Small Cell Definition
Non-small cell lung cancer (NSCLC) is a disease in which the cells of the lung tissues grow uncontrollably and form tumors.
There are two kinds of lung cancers, primary and secondary. increases the likelihood that the drug gefitinib will show a beneficial response; how a prevention trial showed that although finasteride Finasteride Definition
Finasteride is a drug that belongs to the class of androgen inhibitors, which means that it blocks the production of male sex hormones. It is sold in the United States and Canada under the brand names Proscar and Propecia. reduced the risk of developing prostate cancer, those who developed the cancer had higher-grade tumors; and how an international clinical trial found that postmenopausal post·men·o·paus·al
Of or occurring in the time following menopause.
postmenopausal Change of life Gynecology adjective Referring to the time in ♀ when menstrual periods stop for ≥ 1 yr survivors of early-stage breast cancer who took the drug letrozole after completing an initial five years of tamoxifen therapy had a significantly reduced risk of cancer.
9) CISNET models can help translate the relationship between upstream (e.g., screening, modifiable risk factors) and downstream (e.g., mortality) goals. It can also help target the upstream Factors that have the most potential for influencing mortality. In addition, CISNET models can help target what types of emerging technologies have the largest potential to help us reach the NCI's 2015 goal of eliminating suffering from cancer. Is enough known about these technologies to have confidence in these projections? Can modeling point to the most important studies that could be conducted to gain more confidence with respect to their operating characteristics?
In the first issuance of CISNET no funds were specifically allocated for coordination activities. In this reissuance we have set aside funds for coordinating centers for all four cancer sites: breast, prostate, colorectal, and lung cancer. Coordinating centers should be site-specific because each center needs to be totally conversant CONVERSANT. One who is in the habit of being in a particular place, is said to be conversant there. Barnes, 162. with the data sources, modeling issues, and policy questions specific to that cancer site. Coordination activities, under the general direction and consensus of the NCI and principal investigators, will include 1) formulating, prioritizing, and coordinating work on base case and other questions (including outside requests); 2) negotiating common requests for outside data sources; 3) consensus building and coordinating critical evaluation of disparate results; 4) preparing inputs, and collecting and processing common outputs for model comparisons; and 5) coordinating synthesis papers and group responses, bringing together disparate information to inform policy makers. 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 surveillance questions. Because all of the expertise necessary to accomplish these goals is not likely to exist in one place, the coordinating center would have discretionary funds to tap outside expertise for particular tasks, pay for access to data sources, and provide funds to modeling groups to mount intensive efforts to provide technical advice while issues are still relevant in the policy area. Even though one group would be tasked with being the coordinating center, CISNET would be run through consensus, as it has in the past.
To keep applications focused, each will be limited to a single cancer site. The CISNET project requirements call 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. CISNET will allow for diversity and originality of modeling approaches that can be compared using uniform criteria. New investigators will be expected to join in the ongoing collaborative activities already under way.
The NCI intends to commit approximately $1.8 million in total costs (direct and facilities and administrative [F&A] costs) in fiscal year 2005 to fund 6-9 new modeling grants in response to this RFA. In addition, the NCI intends to commit approximately $950,000 (direct and F&A costs) in fiscal year 2005 to fund 4 coordinating centers (one each in breast, prostate, colorectal, and lung cancer). An applicant may request a project period of up to five years. Although an applicant can submit applications for more than one cancer site (either for modeling grants or coordinating centers), each individual application must be limited to one cancer site. Coordinating center grants must be submitted separately from modeling grants, even if one applicant submits both.
Applications must be prepared using the PHS (Personal Handyphone System) A TDMA-based cellular phone system introduced in Japan in mid-1995. Operating in the 1880-1930 MHz band, PHS uses microcells that cover an area only 100 to 500 meters in diameter, resulting in lower equipment costs but requiring more base 398 research grant application instructions and forms (rev. 5/2001). Applications must have a Dun and Bradstreet Data Universal Numbering System The Data Universal Numbering System, abbreviated as DUNS or D-U-N-S is a system developed and regulated by Dun & Bradstreet (D&B) which assigns a unique numeric identifier to a single business entity. This numeric identifier is then referred to as a DUNS number. (DUNS) number as the Universal Identifier when applying for federal grants or cooperative agreements. The DUNS number can be obtained by calling 1-866-705-5711 or through the website at http://www. dunandbradstreet.com/. The DUNS number should be entered on line 11 of the face page of the PHS 398 form. The PHS 398 document is available at http://grants.nih.gov/grants/funding/phs398/phs398. html in an interactive format. For further assistance, contact GrantsInfo by calling 301-435-0714 or e-mailing GrantsInfo@nih.gov.
Letters of intent must be received by 14 September 2004. Applications must be received by 14 October 2004. The anticipated award date is July 2005.
Contact: Eric Feuer, DCCPS, NCI, 6116 Executive Blvd, Rm 5041, MSC (1) (MSC.Software Corporation, Santa Ana, CA, www.mscsoftware.com) Founded in 1963 by Richard H. MacNeal and Robert G. Schwendler, MSC is the world's largest provider of mechanical computer aided engineering (MCAE) strategies, simulation software and services. 8317, Bethesda, M D 20892-8317 USA, 301-496-5029, fax: 301-480-2046, e-mail: firstname.lastname@example.org. Reference: RFA No. RFA-CA-05-018