This notice has expired. Check the NIH Guide for active opportunities and notices.

EXPIRED


CANCER INTERVENTION AND SURVEILLANCE MODELING NETWORK (CISNET)

RELEASE DATE:  May 14, 2004

RFA:  RFA-CA-05-018

Update: The following update relating to this announcement has been issued:

June 25, 2009 - This RFA has been reissued as (RFA-CA-09-025).

EXPIRATION DATE:  October 15, 2004

Department of Health and Human Services (DHHS)
  
PARTICIPATING ORGANIZATION:  
National Institutes of Health (NIH)
 (http://www.nih.gov)

COMPONENT OF PARTICIPATING ORGANIZATION:  
National Cancer Institute (NCI)
 (http://www.nci.nih.gov/)

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER:  93.393, 93.394
 
LETTER OF INTENT RECEIPT DATE:  September 14, 2004  
APPLICATION RECEIPT DATE:  October 14, 2004 

This RFA is a reissue of RFA-CA-99-013 and RFA-CA-02-010, which were 
published in NIH Guide on August 18, 1999 and July 9, 2001.

THIS RFA CONTAINS THE FOLLOWING INFORMATION

o Purpose of this RFA
o Research Objectives
o Mechanism of Support 
o Funds Available
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirements
o Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations

PURPOSE OF THIS RFA

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 

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).

Prior to the first issuance of CISNET most models of cancer 
interventions had been developed to describe hypothetical cohorts in a 
trial or other limited clinical settings.  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, CA-99-013 funded seven 
grants in breast cancer and one in prostate and one in colorectal 
cancer.  A second round, funded under CA-02-010 in August 2002, funded 
5 grants in lung cancer as well as two additional grants for colorectal 
cancer and one in prostate cancer.  The first round of funding will end 
in September 2004, and the second round in summer/fall  2006.  For a 
summary of currently funded CISNET projects from the first and second 
rounds of funding (which started in FY 2000 and 2002 respectively) 
cancer see http://www.cisnet.cancer.gov.

This reissuance of CISNET will be limited to modeling applications 
focusing on breast, prostate, lung, and colorectal cancer.  While the 
reissuance of CISNET will not be limited to grantees previously or 
currently funded, CISNET will no longer fund models that are either 
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.  Applicants who were funded by either CA-99-013 or CA-
02-010 are eligible to apply for funding, as well as those who have 
never been funded under a CISNET RFA.  

In addition, applications are being solicited for cancer site-specific 
coordinating centers for all four of the cancer sites covered in CISNET 
(i.e. breast, prostate, colorectal and lung cancer).  

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.  The 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 
underway.  

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 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 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.  Prior to CISNET much of the simulation and other modeling 
techniques had 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 NCI because of the 
necessity of understanding if recommended interventions are having 
their expected population impact, and predicting 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 NCI has a longstanding need to provide 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 NCI to bring the most sophisticated tools 
available for evidence-based planning in order to:

1. Be responsive to challenges due to the increasing pace of 
technology, and to provide short-term answers while randomized 
controlled trials (RCT s) are still in progress.  In the future we will 
be increasingly faced with new interventions, biomarkers, 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 products are coming 
on the market, and modeling of their potential impact can benefit the 
FTC and other policy makers.

3. Translate RCT evidence of quantities to the population setting.  

4. Provide estimates of quantities that will never be derived from 
RCT s.  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 for ex-smokers, and the implications for 
future lung cancer trends.  

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 
implications of dramatic changes in national cancer statistics, such as 
patterns of increasing incidence related to screening for breast and 
prostate cancer [2-4], and improving survival due to the dissemination 
of breakthrough treatment approaches in Hodgkin's Disease and 
testicular cancer [5-6].

One of the major accomplishments of CISNET to date has been building an 
infrastructure for the comparative analysis of population-based models 
to answer important policy-based questions.  This infrastructure has 
included the following components:

1. Model Development: Prior to the initiation of CISNET approximately 3 
years ago, there were only a few models that were available to study 
population trends in incidence and mortality as a function of cancer 
control interventions.  Some grantees had existing models that had been 
developed for other purposes, e.g. cost-effectiveness analysis of 
hypothetical cohorts, design of randomized controlled trials, etc.  
These models have been retooled to support multiple cohorts, which 
incorporate the full complement of intervention types (i.e. treatment, 
screening, and prevention). Other models have been built from scratch.  
The development, calibration, and validation of these models has been a 
major infrastructure building activity, and those models funded in the 
first round are now coming  online  to start to address important 
cancer control issues.  In the process of model development, CISNET has 
achieved the stated goal of making outside investigators more aware and 
interested in cancer surveillance and control issues. 

2. CISNET Web Sites: There are three CISNET related web sites:

Model Profiler: One major hindrance to understanding differences 
between disparate model results is the lack of comparable documentation 
on model structure.  The CISNET collaborative group has developed a 
state-of-the-art interactive web site, called the Model Profiler, which 
allows modelers to put components of their models into templates to 
facilitate comparisons of model structure.  Each CISNET team is given a 
private model profile web site on which to maintain their model profile 
information. Since the core documentation format is the same for each 
group, the published profile information is readily comparable among 
models.  After the documentation has matured, each CISNET member group 
can "publish" selected documents on the main CISNET interactive web 
site.  All of the grantees funded in the first round have published at 
least the core documents to the CISNET site.  This site is accessible 
to all CISNET members and allows them to view and compare model profile 
documents over a range of different models.  Talks comparing a 
particular model component across the various grantees are held at the 
CISNET meetings and rely on information from the model profiler.  A 
user will, in the future, be able to "publish" a portion of their model 
profiler so that it is available to the general public and can be used 
as a link to be cited in publications.  Providing such details is 
responsive to suggestions that published models provide enough details 
to allow for better understanding and model comparisons [7].

CISNET Interactive Web Site: This interactive web site is available 
only to CISNET members, and serves as the main  message board .  It 
includes places to post meeting talks and agendas and host discussion 
groups, a home page for each cancer site and grantee and a section on 
data resources. 

CISNET Public Web Site (http://cisnet.cancer.gov/): This is a public 
site that includes a list of the grantees and recent developments 
within the CISNET group. It serves as a place for those outside CISNET 
to learn about the group, and has a contact e-mail address for 
inquiries and for posing policy relevant issues for the CISNET group to 
consider. 

3. Organizational Structure and Meetings: CISNET has instituted an 
organizational structure, which allows for efficient working 
relationships (http://cisnet.cancer.gov/about/orgchart.html).  There 
are four working groups, one for each of the cancer sites, and a 
methodology group. Each group has a rotating Principal Investigator 
(PI) leader and one or more NCI scientific coordinators.  The PI 
leaders for each working group serve on the steering committee along 
with the NCI program director, and the chair of the steering committee 
is chosen from among the PI s. There are two meetings a year.  At the 
annual meeting (in November) approximately one day is devoted to 
general issues with all groups meeting together, one day to 
methodologic issues, and one day to cancer site-specific meetings.  At 
the mid-year meetings (May - June), each cancer site group meets 
separately.  Recently, a computer programmers  support group was formed 
as a forum for discussion of issues of importance to those programming 
statistical simulation models (e.g. random number generation and 
management).     

4. Development of Additional Mechanisms for Scientific Exchange: In 
addition to the web sites and meetings discussed above, the CISNET 
publication policy provides a mechanism for groups to comment on each 
others articles prior to submission.  In addition, a CISNET journal 
club has been instituted, where relevant articles are discussed on 
phone-in conference calls. 

5. Affiliate Member Policy: CISNET allows interested modeling groups 
that share CISNET objectives to apply for affiliate membership, which 
provides access to the web site, the ability to attend meetings and 
participate in discussion groups, etc.  There is no funding associated 
with affiliate membership status.

6. Data Resources: One advantage of the CISNET collaboration is the 
ability to gain access to data resources that otherwise may not have 
been available. This is accomplished through joint requests using the 
imprimatur of the NCI when necessary.  In some cases additional sources 
of funding have been necessary to support both data management and 
scientific staff to assist in utilizing the data.  Requests stress 
collaboration rather than data access.  Each modeling group has posted 
information on data resources to which they have access on the web 
site, and conditions for their use. 

Scientific Questions Being Addressed: CISNET investigators are engaged 
in a wide range of policy-relevant modeling studies including:  

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.  Sometimes widely different results from 
models are often difficult to resolve, and base cases provide a chance 
to reach common 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 non-
cancer causes), and a common set of intermediate and final outputs is 
developed to help understand differences and similarities across 
models.

In breast cancer, all seven grantees are addressing the question  What 
is the Impact of Adjuvant Therapy and Mammography on US Breast Cancer 
Mortality: 1975-2000?"  This is a timely issue, especially given the 
recent controversy, which arose from the publication of meta-analyses 
of randomized controlled trials of mammography screening [8-9].  As 
part of the collaboration, the NCI staff has brought together disparate 
data sources to model the dissemination of adjuvant therapy [10] and 
screening mammography in the US.  The plan is to publish a summary of 
these analyses in high-profile journal article(s), and the Journal of 
the National Cancer Institute (JNCI) Monograph Series has agreed to 
publish a complete authoritative report on this analysis. 

For prostate cancer, the grantees are focusing on the impact of 
Prostate Specific Antigen (PSA) screening on US incidence and mortality 
trends, and then will add the impact of treatment.  Prostate cancer 
poses an interesting contrast to breast cancer because, despite the 
widespread dissemination of PSA screening and various treatment 
modalities, the RCT’s evidence is considerably spottier.  

In colorectal cancer, the group is embarking on a series of base case 
questions, the first of which represents a hypothetical test scenario 
to better understand the implications of how each group is modeling the 
natural history of disease, especially the development of adenomas into 
cancer.  

In lung cancer, the focus will be on modeling the impact of smoking on 
lung cancer mortality from 1975-2000.  While the impact of smoking on 
lung cancer is generally well understood, there are certain aspects of 
this modeling which are still a major challenge, e.g., gaining a better 
understanding of the process of carcinogenesis for those who have quit 
smoking, understanding the role of changing tobacco products on 
population trends, and understanding trends in lung cancer among non-
smokers.

2. Breast Base Case Spin-Off Questions: The breast base case serves as 
a  jumping off  point for each grantee as they vary the basic 
formulation to focus on areas of individual interest.  Spin-off issues 
that are actively being pursued include: modeling the impact of using 
alternative more biologically-based natural disease history 
formulations, especially continuous time tumor growth models which 
include microscopic fatal metastases which are initially undetectable; 
analyses for different racial/ethnic uninsured/underinsured groups; a 
unique Bayesian approach to update its prior estimates of treatment 
efficacy to obtain posterior estimates of community effectiveness of 
adjuvant therapy and mammography which best reproduce national 
mortality trends; geographically based analyses, the role of risk 
factors in breast cancer trends; and the potential impact of optimal 
screening intervals.

3. Prostate Cancer: CISNET researchers have published an analysis of 
trends in the use of the PSA test [11], for modeling prostate cancer 
incidence trends to obtain estimates of overdiagnoses associated with 
PSA screening [12].  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 (SMMR): 
CISNET was invited to sponsor a special issue of SMMR entitled  Uses of 
Stochastic Models for the Early Detection of Cancer,  with articles to 
be submitted in spring 2003.  Articles in the issue include: (1) 
Distribution of Clinical Covariates at Detection of Cancer; Stochastic 
Modeling and Statistical Inference, (2) Planning Public Health Programs 
and Scheduling: Breast Cancer, (3) Planning of Randomized Trials (4) 
The Use of Modeling to Understand the Impact of Screening on US 
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.  Examples 
include:

Immunochemical Fecal Occult Blood Test (iFOBT): The Agency for Health 
Research and Quality (AHRQ) and the Center for Medicare and Medicaid 
Studies (CMS) approached NCI for assistance in studying a reimbursement 
decision related to the immunochemical FOBT test 
(http://cisnet.cancer.gov/reports/medicare.html ).  

Healthy People 2010 Mid-Course Correction Studies: Healthy People 2010 
(HP2010) is the DHHS blueprint for achieving the Nation’s health goals 
to increase quality and years of healthy life, and eliminate health 
disparities.  CISNET modelers have been asked to aid in a mid-course 
(2005) evaluation to help us determine if reaching HP 2010 upstream 
goals for cancer treatment, screening, and prevention will enable us to 
fall short/meet/exceed the downstream 2010 cancer mortality goals, and 
retarget our efforts if necessary.   

Impact of Harm Reduction Tobacco Products: Discussions with the Tobacco 
Control Research Branch, DCCPS, have indicated that modeling the 
potential public health impact of new smokeless tobacco products can 
benefit the FTC and other policy makers.
         
Objectives and Scope    

The objective of this RFA is to take models that have been developed in 
the first rounds of funding or independently and enhance their areas of 
application.  Investigators will apply these models to specific high 
priority, policy-relevant questions in a comparative fashion.  This 
reissue will capitalize and expand upon model development work already 
completed.  While the reissuance of CISNET will not be limited to 
grantees previously funded, it will no longer fund models that are 
either starting from scratch or have not been previously applied to the 
analysis of population trends.  Instead the components of population 
models will be refined and applied.  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 (i.e. basic mathematical and 
statistical relationships necessary for the development of multi-cohort 
population models) and development (i.e. 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 (i.e. 
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 center-piece 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. 
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.

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 etiologic 
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 synergistic impact of multiple 
interventions simultaneously, 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).  However, whenever possible, inference should relate to 
the US as a whole.  Models can be developed for non-US populations, but 
should be justified based on their applicability to understanding US 
cancer trends.  It is not the primary purpose of this RFA to support 
analysis of hypothetical or trial-based cohorts and/or cost 
effectiveness analysis (even though there may be secondary analyses of 
this type), but rather to support analysis based on realistic scenarios 
of population impact.

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.  
Natural History: 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 breast cancer, and what are the implications of these natural 
history models for the overdiagnosis of disease?  

Treatment: What is the contribution of treatment to observed declines 
in prostate cancer mortality, especially the transition from the use of 
androgen deprivation therapy after biochemical failure (i.e. rising PSA 
levels) to use in the adjuvant 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? 

Screening: What is the impact on incidence and mortality of both the 
increased dissemination of currently established screening modalities 
(e.g. FOBT and sigmoidoscopy) and the potential dissemination of new or 
more novel modalities (e.g. screening colonoscopy, advanced imaging 
modalities, immunochemical FOBT, fecal mutagen tests and other 
innovative biomarkers)? As screening trial results for PSA, flexible 
sigmoidoscopy, chest x-ray, and spiral computed tomography (CT) start 
to become available over the next decade; how do these results alter 
our understanding of population trends in incidence and mortality? 

Risk Factors/Prevention: 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 for women with different risk profiles, and what is 
the projected mortality reduction associated with these levels of 
dissemination?  

Resources/Tradeoffs: How would resource requirements be affected by the 
use of risk stratification models (e.g. [14-15]) or biomarkers that 
would allow selective screening and/or selective surveillance 
monitoring of higher risk individuals? What is the national burden of 
iatrogenic morbidity from prostate cancer treatment among screen 
detected men and how do we weigh this against the potential mortality 
gains?

Health Disparities: 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? 

System Modeling: What is the impact of changing Medicare reimbursement 
policies on screening, treatment, and cancer mortality?

Current Events:  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 (NSCLC) increases the 
likelihood that the drug, gefitinib, will show a beneficial response 
[16], the prevention trial which showed that although finasteride 
reduced the risk of developing prostate cancer, those who developed the 
cancer had had higher grade tumors [17], the international clinical 
trial which found that post-menopausal 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 
[18] .

Healthy People 2010, NCI’s 2015 Goals, and Emerging Technologies:  
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 which 
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 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?  

Coordinating Centers

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, i.e., breast, 
prostate, colorectal and lung cancer.  Coordinating centers should be 
site specific because each center needs to be totally conversant 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 PI's, 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 are 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.

Coordinating center grant applications could come from current CISNET 
grantees, current applicants for modeling grants, or other applicants 
with population-based modeling experience. 

Budget

Funds can be allocated towards adapting existing models to address new 
issues and for the development of data sources to inform these models.  
First and early years budgets should be directed at improving the use 
of these models to answer a well-developed list of specified questions.   
Later years should increasingly focus on delivery and synthesis of 
results into formats which are directly usable by policy makers.  Funds 
should also be allocated for making models more accessible for use by 
others.  No funds should be allocated to creating new population based-
models or the basic mathematical structure of new models. 

Modeling groups will be required to attend the following two meetings:  
(1) An annual meeting (approximately 3 days) in which all four cancer 
sites will meet together.  (2) Mid-year meetings (approximately 2 days) 
when each cancer site meets separately.  For purposes of budgeting, 
funds should be requested for up to three persons to travel to each of 
these two 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.  Applicants who were funded 
under CA-02-010 may have a remaining period of funding still available 
when they are funded by this RFA.  In that circumstance, they may be 
asked to terminate their remaining funding under CA-02-010 in order to 
initiate their funding under this RFA.   

It is anticipated that the budgets for the modeling grants will range 
between approximately $100,000 - $250,000 total costs for the first 
year, with only modest changes in funding after that.  We expect the 
average budget to be approximately $200,000 total costs in the first 
year.  The budget for the modeling grants will be limited to a cap of 
$250,000 total cost for the first year, with suggested maximum 
increases of 3 percent for each year after the first year.  If 
increases are larger than 3 percent, strong scientific justification 
must be given.

The budgets for the coordinating centers will be capped at $150,000 
direct costs, excluding third party indirect costs.  In the award, it 
is expected that approximately $50,000 will be restricted for a 
Discretionary Fund used to pay for expertise and programming time to 
gain access to data sources that model specific input components of 
interest to the entire group, and that address timely issues/questions 
that were not anticipated in the original application, etc.  The budget 
for the coordinating center should include substantial involvement of 
the PI (suggested minimum of at least 15% time however a larger 
commitment is preferable) to provide leadership and coordinate 
questions to be addressed and synthesis of results.  Additional 
personnel could include statisticians, programmers, administrative 
assistants, and others with multi-disciplinary expertise as needed.  
Coordinating centers should include funds to send up to four persons to 
both the mid-year and annual meetings.  If a grantee has a coordinating 
center and a modeling grant, travel funds should be reduced to 
eliminate overlap.    

Budgets for both the modeling grants and the coordinating center should 
not be in modular format. 

MECHANISM OF SUPPORT

This RFA will use the NIH (U01) is a cooperative agreement award 
mechanism.  As an applicant, you will be primarily responsible for 
planning, directing, and executing the proposed project.  This RFA is a 
one-time solicitation. Future unsolicited, competing-continuation 
applications based on this project will compete with all investigator-
initiated applications and will be reviewed according to the customary 
peer review procedures.  The anticipated award date is July 2005.

This RFA uses just-in-time concepts.  It also uses the non-modular 
budgeting formats (see 
http://grants.nih.gov/grants/funding/modular/modular.htm).  Follow the 
instructions for non-modular budget research grant applicants.  This 
program does not require cost sharing as defined in the current NIH 
Grants Policy Statement at 
http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part2.htm.

The NIH (U01) is a cooperative agreement award mechanism. In the 
cooperative agreement mechanism, the Principal Investigator 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 "Cooperative Agreement Terms and Conditions of Award

FUNDS AVAILABLE

The NCI intends to commit approximately $1,800,000 in total costs 
(direct and Facilities and Administrative (F&A) costs) in FY 2005 to 
fund 6 to 9 new modeling grants in response to this RFA.  In addition, 
NCI intends to commit approximately $950,000 (direct and Facilities and 
Administrative (F&A) costs) in FY 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.  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. The final awards will reflect the quality of the 
technical aspects and proposed staff of the applications, adherence to 
the spirit of intent of this RFA, and a balance of the number of funded 
applications across the four cancer sites. 

ELIGIBILE INSTITUTIONS 

You may submit (an) application(s) if your institution has any of the 
following characteristics: 

o For-profit or non-profit organizations 
o Public or private institutions, such as universities, colleges, 
hospitals, and laboratories 
o Units of State and local governments
o Eligible agencies of the Federal government  
o Domestic or foreign institutions/organizations 

INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS 
  
Any individual with the skills, knowledge, and resources necessary to 
carry out the proposed research is invited to work with their 
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 programs.   

Since there are many unique aspects specific to each cancer site, each 
modeling grant application is limited to a single cancer site.  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).  

Similarly, each Principal Investigator (PI) is limited to only one 
coordinating center grant application per cancer site, and thus up to 
four applications are possible by one PI.  If a PI, or an institution, 
is submitting a coordinating center applications and a modeling grant 
application or several coordinating center applications they should 
submit any potential areas of overlap between the applications, and 
overlapping funding of activities will be eliminated at the time of 
award.

SPECIAL REQUIREMENTS

Separate applications must be made for modeling grants and coordinating 
centers, even if the same PI is applying for both.  Applications must 
clearly be labeled as either a "Modeling Application" or "Coordinating 
Center Application".

Research Plan

Modeling applications in response to the RFA must address the following 
areas:

Specific Aims and Significance: The application must clearly state the 
surveillance/cancer control research questions which this application 
is designed to address and the importance of these issues for 
understanding current or future trends in incidence or mortality trends 
and/or cancer control strategies in the US.  The plan should 
demonstrate a general understanding of the various factors influencing 
observed trends before investigating secondary goals of future trends 
and optimal cancer controls strategies.  If the application includes 
the modeling of trends outside of the US or in subpopulations of the 
US, justification must be given as to what special insights or 
understanding this will yield.  Applicants should demonstrate the 
flexibility of their model to estimate the potential population impact 
of emerging cancer control technologies.   

Methods: For each research question the applicant should specify data 
sources for model building, calibration and validation, any additional 
model components that must be built, and the overall approach to the 
problem.  

Background/Work to Date: Applicants should describe in detail work 
completed to date and work in progress for developing and applying 
their model. It should be clear to the reviewers of these applications 
that the models are working population-based surveillance models that 
have been applied in situations beyond that of hypothetical cohorts or 
trial- based situations.  They should describe the model structure, 
substantive questions that have been addressed, data sources used for 
model construction, calibration and validation.  They should describe 
the practical importance of questions that have been addressed, and how 
their results will help advance informed decision making.  In addition 
they should describe the types of collaborations they have engaged in 
with others (either within CISNET or outside of CISNET), and the role 
they have played in these collaborations.  

Synthesis/Coordination/Collaboration: Applicants should describe ideas 
for collaborative projects that could be undertaken.  These joint 
projects could involve  base cases  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, sharing 
of methods and data resources, or synthesis of existing results.  While 
it will be a group decision to actually engage in any particular 
proposed collaborative activities, applicants will be judged on the 
soundness of their ideas and understanding of how joint collaborative 
activities can be conducted in a consortium of this type.  
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.  
Investigators will be asked to post project descriptions and pre-
submission publications on the CISNET grantees web site for comment and 
review by the cooperative group. 

Contractual Arrangements: The application should describe contractual 
arrangements necessary for acquisition and/or consolidation of data 
necessary for parameter estimation.  Any other contractual arrangements 
should also be described. 

Model Sharing: In this reissuance, the NCI requires each applicant to 
propose a concrete plan for making their models more accessible to 
those outside the consortium. Ideally, this plan should endeavor to 
address aspects of   the following four components:  (1) enhancing 
understanding of model structure by requiring at least the basic 
templates of the Model Profiler to be posted on a public website, (2) 
allow those outside CISNET to pose questions or scenarios (possibly 
based on national or regional issues of interest) which would lead to 
specific sets of runs to be conducted by the modelers, (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.  Applicants 
should describe how each of these components will be achieved, and can 
add other components as well.  For some aspects of this plan, it is 
reasonable to assume that interested users may need to provide funding.  

Coordinating centers applications in response to this RFA must address 
the following areas: 

Background and Qualifications: The applicant should describe their 
knowledge of data sources, policy issues, and modeling issues relevant 
to the specific cancer site.  The applicant should have prior modeling 
experience with this cancer site, and should describe how this 
experience is relevant to CISNET activities.  

Cooperation/Coordination with Modeling Grantees and NCI Scientific 
Coordinators: Decisions concerning the scientific priorities of the 
site specific working group, use of discretionary funds, etc. will be 
made through consensus of the coordinating center, NCI program staff, 
and the modeling grantees.  The coordinating center will be responsible 
for building group consensus and moving the agenda forward.  The 
applicant should describe general plans for these types of activities.  

Prioritizing Questions to Be Addressed: The coordinating center should 
lay out a process for identifying and synthesizing: the set of 
questions to be addressed by the site specific working group, the 
timelines for these efforts, which questions are best answered using 
collaborative or single efforts, and any gaps in the set of questions 
and how best to fill those gaps.  In addition, the coordinating center 
should work out a general process for handling outside requests to 
address specific questions/issues including when to seek additional 
funding or to fit the work within existing support of either the 
coordinating center (including the use of discretionary funds) or 
individual grantees.

Cooperation with Model Profiler / CISNET Web Site Contractor: NCI has a 
contract to support the development and use of the model profiler and 
CISNET members  only web site.  One aspect of the contract involves the 
use of the model profiler to develop a comparative synthesis of 
particular aspect of the models (e.g., how they model the improvement 
in survival associated with screen detection).  The applicant should 
indicate a willingness to work cooperatively with the NCI contractor 
who maintains the Model Profiler/CISNET Web Site.  For more information 
on the contract for the Model Profiler/CISNET Web site, please contact 
Dr. Eric Feuer, the NCI Program Director (contact information listed 
below).

Base Cases: The coordinating center will be responsible for managing 
the development and analysis of base cases.  The applicant should 
specify the role of the coordinating center in managing this process, 
as well as specific ideas for future base cases.  The applicant may 
state in what type of situations they feel that base cases are 
appropriate.

Synthesis of Results: As CISNET work moves more into the delivery 
phase, the agenda will shift more to the synthesis of modeling results.  
Synthesis involves resolving differences when possible, or coming to a 
clear understanding, differences which remain.  Often the problem in 
comparing disparate modeling results is that many variables are 
changing simultaneously, which makes isolating differences difficult.  
Synthesis efforts could involve comparing results entirely within 
CISNET (e.g. a base case) or a comparison of results between CISNET and 
outside groups.  Applicants should describe their approach to synthesis 
activities, and ideas for specific issues to be addressed.  
  
Current Events: The coordinating center should 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 the cancer site. The plan should make use of the models, 
if appropriate, to help synthesize population-level results related to 
these controversies and results.  Applicants should develop a plan to 
prioritize analyses related to estimating the population impact of 
emerging cancer control technologies.

Cooperative Agreement 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 as described 
below.

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 provide normal stewardship for the 
U01 grants awarded under this RFA.  

NCI PROJECT SCIENTIST: A project scientist from NCI who will coordinate 
the overall scientific efforts and collaborations within the CISNET 
Network.  The NCI Program Director may also serve as the NCI Project 
Scientist.

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 the modeling grants, 
the designated NCI Scientific Coordinator, and the PI of the 
coordinating center.  The co-chairs of the working groups will be the 
NCI Scientific Coordinator and the PI of the coordinating center.  

METHODOLOGY WORKING GROUP: A group comprised of interested 
methodologists among the extramural scientific investigators and NCI 
Scientific Staff.  The chairs of the methodology working group 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: The steering committee will consist of the four 
PI's of the site-specific coordinating centers, the NCI Project 
Scientist, 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 
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.

Awardees are expected to develop and implement a set of procedures for 
making their models accessible to interested parties.

3.  NCI Staff Responsibilities

The NCI Program Director will provide review progress reports and 
perform other administrative duties related to the normal stewardship 
for the U01 grants awarded under this RFA.  The NCI Program Director 
recommends: reductions to the budget, withholding support, or 
suspending, terminating or curtailing 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.

The NCI Project Scientist 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 Project Scientist will serve as a member of the Steering 
Committee.

The NCI Project Scientist 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.

NCI will provide support for a Model Profiler/CISNET Web Site for the 
CISNET project through a separate contract for use by the awardees.

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 and 
recommendations 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.

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 advice on 
policy relevant surveillance questions.

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 micro simulation 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.

D. The Coordinating Center will:

Coordinate the agendas of the cancer site-specific meetings.

Formulate, prioritize, and coordinate work on base case and other 
questions.

Negotiate common requests for outside data sources. 

Build consensus and coordinate critical evaluation of disparate 
results.  

Prepare inputs and collect and process common outputs for model 
comparisons. 

Coordinate synthesis papers and group responses bringing together 
disparate information to inform policy makers.

Field outside requests and work with the modeling grantees to determine 
priorities.  

Coordinate conference calls and communication within the cancer-site 
specific working groups.

Be required to work cooperatively with the contractor who maintains the 
Model Profiler/Interactive Web Site.

E. Responsibilities of the PI's of the coordinating centers 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.

Serve as a voting member of the Steering Committee, and represent their 
Working Group to the Steering Committee. 

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. 

WHERE TO SEND INQUIRIES

We encourage inquiries concerning this RFA and welcome the opportunity 
to answer questions from potential applicants.  The NCI will be holding 
a series of phone conference calls (probably one for each cancer site 
and one for coordinating centers) 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://cisnet.cancer.gov.  Summaries of the calls and/or tapes will 
be available for those unable to participate directly.  Inquiries may 
fall into three areas: scientific/research, peer review, and financial 
or grants management issues:

o Direct your questions about scientific/research 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
Rockville, MD 20852 (express courier)
Telephone:  (301) 496-5029
Fax: (301) 480-2046
Email: rf41u@nih.gov

o Direct your questions about peer review issues to:

Referral Officer 
Division of Extramural Activities 
National Cancer Institute 
6116 Executive Blvd., Room 8041, MSC-8329
Rockville, MD 20852 (express courier)
Bethesda MD 20892-8329
Telephone (301) 496-3428
Fax: (301) 402-0275
Email: ncirefof@dea.nci.nih.gov

o Direct your questions about financial or grants management matters 
to:

Ms. Crystal Wolfrey  
Grants Administration Branch
National Cancer Institute  
6120 Executive Plaza South, Suite 243 
Bethesda, MD  20892
Rockville, MD 20852 (express courier) 
Telephone: (301) 496-8634 
FAX: (301) 496-8601 
Email: crystal.wolfrey@nih.gov

LETTER OF INTENT

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

o Descriptive title of the proposed research
o Name, address, and telephone number of the Principal Investigator
o Names of other key personnel 
o Participating institutions
o Number and title of this RFA 

Although a letter of intent is not required, is not binding, and does 
not enter into the review of a subsequent application, the information 
that it contains allows IC staff to estimate the potential review 
workload and plan the review.
 
The letter of intent is to be sent by the date listed at the beginning 
of this document.  The letter of intent should be sent 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
Rockville, MD 20852 (express courier)
Telephone:  (301) 496-5029
Fax: (301) 480-2046
Email: rf41u@nih.gov

SUBMITTING AN APPLICATION

Applications must be prepared using the PHS 398 research grant 
application instructions and forms (rev. 5/2001).  Applications must 
have a Dun and Bradstreet (D&B) Data Universal Numbering System (DUNS) 
number as the Universal Identifier when applying for Federal grants or 
cooperative agreements.  The DUNS number can be obtained by calling 
(866) 705-5711 or through the web site 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; 
Telephone (301) 710-0267; Email: GrantsInfo@nih.gov.
  
USING THE RFA LABEL: The RFA label available in the PHS 398 (rev. 
5/2001) 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 RFA 
label is also available at 
http://grants.nih.gov/grants/funding/phs398/labels.pdf.
 
SENDING AN APPLICATION TO THE NIH: 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
Bethesda, MD  20817 (for express/courier service)
 
At the time of submission, two additional copies of the application and 
all five copies of the appendices must be sent to:
 
Referral Officer 
Division of Extramural Activities 
National Cancer Institute 
6116 Executive Blvd., Room 8041, MSC-8329
Rockville, MD 20852 (express courier)
Bethesda MD 20892-8329

Appendices should be comprised of unbound materials, with separators 
between documents.  

APPLICATIONS HAND-DELIVERED BY INDIVIDUALS TO THE NATIONAL CANCER 
INSTITUTE WILL NO LONGER BE ACCEPTED.  This policy does not apply to 
courier deliveries (i.e. FEDEX, UPS, DHL, etc.) 
(http://grants.nih.gov/grants/guide/notice-files/NOT-CA-02-002.html).  
This policy is similar to and consistent with the policy for 
applications addressed to Centers for Scientific Review as published in 
the NIH Guide Notice 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-012.html.

APPLICATION PROCESSING: Applications must be received on or before the 
application receipt date listed in the heading of this RFA.  If an 
application is received after that date, it will be returned to the 
applicant without review. 

Although there is no immediate acknowledgement of the receipt of an 
application, applicants are generally notified of the review and 
funding assignment within 8 weeks.
 
The Center for Scientific Review (CSR) will not accept any application 
in response to this RFA 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 an RFA, it is to be prepared as a NEW 
application.  That is the application for the RFA 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 or the application.

PEER REVIEW PROCESS  
 
Upon receipt, applications will be reviewed for completeness by the CSR 
and responsiveness by the NCI.  Incomplete applications will not 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 
NCI in accordance with the review criteria stated below.  As part of 
the initial merit review, all applications will: 

o 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 and assigned a priority score
o Receive a written critique
o 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.  
In the written comments, reviewers will be asked to evaluate the 
application in order to judge the likelihood that the proposed research 
will have a substantial impact on the pursuit of these goals. The 
scientific review group will address and consider each of these 
criteria in assigning the application’s overall score, weighting them 
as appropriate for each application.  The application does not need to 
be strong in all categories to be judged likely to have major 
scientific impact and thus deserve a high priority score.  For example, 
an investigator may propose to carry out important work that by its 
nature is not innovative but is essential to move a field forward.

Criteria for Modeling Grants

SIGNIFICANCE: Does this study propose to address important population-
based surveillance and cancer control problems, rather than an emphasis 
on new mathematical/statistical derivations? 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 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?

WORK TO DATE: Does the applicant have a working multi-cohort 
population-based model, which can be used to address cancer 
surveillance and control issues? Has the model been employed to address 
important cancer surveillance and control issues, and how successfully 
has the model performed? Is the model appropriate to address practical 
issues associated with the aims of the application?    

APPROACH: Are the nature and characteristics of the model to be 
employed adequate? Is there evidence that the model proposed is 
currently being used for multiple cohort population-based studies?  Are 
the plans for adapting the model to address the specific aims of this 
application adequate (e.g. adding a new module to address prevention 
strategies)? 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?  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 adequately addressed?  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? 
Does the applicant lay out a specific and reasonable plan for making 
the model accessible to others?  

INVESTIGATORS: Do the investigators comprise an interdisciplinary team 
that is adequate to present the results for use by policy makers and 
cancer control planners? Is appropriate interdisciplinary expertise 
included? Is the principal 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? Does the 
applicant’s prior work demonstrate an understanding of the problems 
inherent in working with population-based data?

ENVIRONMENT: Does the scientific environment in which the work will be 
done contribute to the probability of success? Are 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?

COLLABORATION: Do the investigators state their willingness to 
participate in joint meetings, share methods and data resources, and 
embark on collaborative efforts to decide overall research direction?  
Is the research plan flexible enough to accommodate further refinement 
and integration with other efforts? While it will be a group decision 
to actually engage in any particular proposed collaborative activities, 
do the applicants show an understanding of how joint collaborative 
activities can be conducted in a consortium of this type? 

Criteria for Coordinating Centers

RESEARCH TEAM: Does the proposed research team have experience with 
population-based modeling, data sources, and policy issues for the 
specific cancer site? Does the PI indicate a sufficient commitment of 
time (suggested minimum of at least 15%, but more may be necessary) to 
devote the time and energy to help focus the research efforts? Has the 
PI demonstrated leadership abilities? 

PLANS FOR COORDINATION: Does the coordinating center lay out a proposed 
set of plans that are flexible to incorporate group input?  Does the 
coordinating center plan recognize that the activities of the 
coordinating center will be dictated by group consensus? Does the plan 
include creative options for 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 application recognize that coordination with the 
contractor for the Model Profiler/Interactive Web Site will be 
necessary?

DATA SOURCES/MODELING INPUTS: Is the coordinating center knowledgeable 
about data sources, and do they have unique access or knowledge of 
particular data sources? Does the coordinating center have plans for 
gaining access to important data sources as they are released (e.g. 
trial results)? Does the coordinating center have plans and 
capabilities to model specific inputs that are of common interest 
across the models? 

CURRENT EVENTS: 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? Is there a plan to make use of the 
models, if appropriate, to help synthesize population-level results 
related to these controversies and results?  

ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, the 
following items will be considered in the determination of scientific 
merit and the priority score:

PROTECTION OF HUMAN SUBJECTS FROM RESEARCH RISK: The involvement of 
human subjects and protections from research risk relating to their 
participation in the proposed research will be assessed. (See criteria 
included in the section on Federal Citations, below).
 
INCLUSION OF WOMEN, MINORITIES AND CHILDREN IN RESEARCH: The adequacy 
of plans to include subjects from both genders, all racial and ethnic 
groups (and subgroups), and children as appropriate for the scientific 
goals of the research.  Plans for the recruitment and retention of 
subjects will also be evaluated. (See Inclusion Criteria in the 
sections on Federal Citations, below).

CARE AND USE OF VERTEBRATE ANIMALS IN RESEARCH: If vertebrate animals 
are to be used in the project, the five items described under Section f 
of the PHS 398 research grant application instructions (rev. 5/2001) 
will be assessed.  

ADDITIONAL REVIEW CONSIDERATIONS

Sharing Research Data 

Applicants requesting more than $500,000 in direct costs in any year of 
the proposed research must include a data sharing plan in their 
application. The reasonableness of the data sharing plan or the 
rationale for not sharing research data will be assessed by the 
reviewers.  However, reviewers will not factor the proposed data 
sharing plan into the determination of scientific merit or priority 
score.

BUDGET: The reasonableness of the proposed budget and the requested 
period of support in relation to the proposed research.

RECEIPT AND REVIEW SCHEDULE

Letter of Intent Receipt Date: September 14, 2004
Application Receipt Date: October 14, 2004
Peer Review Date: February/March 2005
Council Review: June 2005
Earliest Anticipated Start Date: July 2005

AWARD CRITERIA

Award criteria that will be used to make award decisions include:

o Scientific merit (as determined by peer review)
o Availability of funds
o Programmatic priorities

The final awards will reflect the scientific merit of the applications, 
adherence to the spirit of intent of this RFA, and a balance of the 
number of funded applications across the four cancer sites. 

REQUIRED FEDERAL CITATIONS

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.  See 
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).  The establishment of 
data and safety monitoring boards (DSMBs) is required for multi-site 
clinical trials involving interventions that entail potential risk to 
the participants.  (See the NIH Policy for Data and Safety Monitoring, 
NIH Guide for Grants and Contracts, June 12, 1998 at 
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 
(http://grants.nih.gov/grants/policy/data_sharing) or state why this is 
not possible. Investigators should seek guidance from their 
institutions, on issues related to institutional policies, 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.

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 - Amended, October 2001," published in the NIH Guide 
for Grants and Contracts on October 9, 2001 
(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 RESEARCH INVOLVING HUMAN 
SUBJECTS: The NIH maintains a policy 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 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 that is available at 
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 proposals for 
research involving human subjects.  You will find this policy 
announcement in the NIH Guide for Grants and Contracts Announcement, 
dated June 5, 2000, at 
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 in 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.

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.  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.  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 RFA 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 
or Health Systems Agency review.  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.

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. Siegel, JE, Weinstein MC, Torrance GW: Reporting Cost-Effectiveness 
Studies and Results, Cost-Effectiveness in Heath and Medicine. Gold, 
MR, Siegel JE, Russel LB, Weinstein MC (editors) Ch 9 p276-303, 1996.

8. Olsen O and Gotzsche P. Cochrane review on screening for breast 
cancer with mammography. Lancet 2001 358:1340-2, 2001.

9. Humprey L, Chan BKS, Detlefsen, S, Helfland M, Screening for breast 
cancer, Systematic Evidence Review Number 15, Prepared for Agency for 
Healthcare Research and Quality (ahrq.gov), 2002.

10. Mariotto A., Feuer EJ, Harlan LC, Wun LM, Johnson KA, Abrams J., 
Trends in the use of adjuvant multi-agent chemotheapy and Tamoxifen for 
breast cancer in the United States, 1975-1999, JNCI, 94: 1626-1634, 
2002. 

11. Etzioni R, Berry K, Legler J, Shaw P.  PSA Testing in black and 
white men: An analysis of Medicare claims from 1991-1998.  Urology. 
2002, 59:251-5, 2002. 

12. Etzioni R, Penson DF, Legler JM, di Tommaso D, Boer R, Gann PH, 
Feuer EJ. Overdiagnosis due to prostate-specific antigen screening: 
lessons from U.S. prostate cancer incident trends. JNCI, 94:981-90, 
2002.

13. Levin B, Brooks D, Smith RA, Stone A, Emerging technologies in 
screening for colorectal cancer: CT colonography, immunochemical fecal 
occult blood tests, and stool screening using molecular markers, CA 
Cancer J Clin 53: 44-55, 2003.

14. Gail MH, Brinton LA, Byar DP, Corle DK, Green SB, Schairer C, et 
al.; Projecting individualized probabilities of developing cancer for 
white females who are being examined annually. JNCI, 81: 1879-1886, 
1989.

15. Bach PB, Katton MW, Thornquist MD, Fris MG, Tate RC, Barnett MJ, 
Hseih LJ, Begg CB, Variations in lung cancer risk among smokers., JNCI, 
95: 470-478, 2003.

16. Paez JG, Janne PA, Lee JC, Tracy S, Greulich H, Gabriel S, Herman 
P, Kaye FJ, Lindeman N, Boggon TJ, Naoki K, Sasaki H, Fujii Y, Eck MJ, 
Sellers WR, Johnson, BE, Meyerson M. EGFR Mutations in Lung Cancer: 
Correlation with Clinical Response to Gefitinib Therapy. Science, 
Online publication, April 29, 2004.

17. Thompson IM, Goodman PJ, Tangen CM, Lucia MS, Miller GJ, Ford LG, 
Lieber MM, Cespedes RD, Atkins JN, Lippman SM, Carlin SM, Ryan A, 
Szczepanek CM, Crowley JJ, Coltman CA Jr., The influence of finasteride 
on the development of prostate cancer., N Engl J Med., 349(3):215-24, 
2003.

18. Goss PE, Ingle JN, Martino S, Robert NJ, Muss HB, Piccart MJ, 
Castiglione M, Tu D, Shepherd LE, Pritchard KI, Livingston RB, Davidson 
NE, Norton L, Perez EA, Abrams JS, Therasse P, Palmer MJ, Pater JL. A 
randomized trial of letrozole in postmenopausal women after five years 
of tamoxifen therapy for early-stage breast cancer. Obstet Gynecol 
Surv. Mar;59(3):201-3, 2004.


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