and Human Services (HHS)
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: [email protected]
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: [email protected]
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: [email protected]
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: [email protected]
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: [email protected].
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.
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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
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