CANCER INTERVENTION AND SURVEILLANCE MODELING NETWORK (CISNET)
 
Release Date:  July 9, 2001

RFA:  RFA-CA-02-010 (see reissue RFA-CA-05-018)
 
National Cancer Institute
 
Letter of Intent Receipt Date:  October 9, 2001
Application Receipt Date:       November 13, 2001

This RFA is a reissue of RFA-CA-99-013, which was published in NIH Guide on 
August 18, 1999.

PURPOSE

The Division of Cancer Control and Population Sciences (DCCPS), National Cancer 
Institute (NCI), invites applications from domestic and foreign applicants to 
support collaborative research using simulation and other modeling techniques 
to describe the impact of interventions (i.e., primary prevention, screening, 
and treatment) in population-based settings in the United States or in non-US 
settings that will shed light on US population-based trends. It is well known 
that great progress in the war against cancer is possible by the complete use 
and adequate delivery of existing modalities of cancer control. The primary 
goals of this research are:

1) to determine the impact of cancer control interventions on observed trends 
in incidence and/or mortality; and to

2) to determine if recommended interventions are having their expected 
population impact by examining discrepancies between controlled cancer 
intervention study results and the population experience.

Once a general understanding of the various factors influencing current trends 
has been achieved, a number of secondary goals may be addressed.  Applicants 
may propose secondary goals of modeling the potential impact of new 
interventions on future national trends, and/or determining the impact of 
targeted cancer control interventions on population outcome (i.e. evaluating 
optimal cancer control strategies).

In the past most models of cancer interventions have been developed to describe 
hypothetical cohorts in a trial or other limited clinical settings.  It is not 
the purpose of this RFA to support analysis of hypothetical or trial-based 
cohorts and/or cost-effectiveness analyses, but rather to support analyses 
based on realistic scenarios of population impact. Projects will focus on 
models describing the population impact of the observed dissemination of cancer 
control interventions as well as other factors on observed national incidence 
and/or mortality trends. 

This second round of funding for CISNET will be limited to applications 
focusing on prostate, colorectal, and lung cancers.  For a summary of currently 
funded CISNET projects from the first round of funding (which started in FY 
2000) in breast, prostate, and colorectal cancer see 
http://www-dccps.ims.nci.nih.gov/SRAB/cisnet.html. 

To keep applications focused, each will be limited to a single cancer site.  
The cooperative agreement mechanism calls for the development of site-specific 
working groups that will: (1) facilitate comparative analyses, (2) allow 
modeling groups access to a broader array of data resources and 
interdisciplinary expertise and (3) provide a forum for discussions of 
validation and other methodologic issues.  The CISNET will allow for diversity 
and originality of modeling approaches that can be compared using uniform 
criteria.

The Division of Cancer Control and Population Sciences, which fulfills a 
federal-level function to respond to evolving surveillance questions of 
national policy relevance, helps focus research questions and act as a conduit 
to national data resources necessary for parameter estimation, model 
calibration, validation and population trends. An emergent property of this 
collaborative agreement is progress towards a comprehensive understanding of 
the determinants of cancer site-specific trends at the population level and a 
better understanding of the science of modeling.   

RESEARCH OBJECTIVES
 
Background    

Modeling is the use of mathematical and statistical techniques within a logical 
framework to integrate and synthesize known biological, epidemiological, 
clinical, behavioral, genetic and economic information.  Simulation and other 
modeling techniques have been utilized to describe the impact of cancer 
interventions (i.e., primary prevention, screening, and treatment) for 
hypothetical cohorts or in trial and other clinical settings.  The goal of this 
RFA is to promote the application and extension of these models to population-
based settings in order to ascertain determinants of cancer trends.  This 
information is critical to the National Cancer Institute because of the 
necessity of understanding: (1) if recommended interventions are having their 
expected population impact, and (2) to predict the potential impact of new 
interventions on national trends. These studies will often involve 
extrapolation of results of controlled cancer intervention studies to estimates 
of U.S. population and community effectiveness.  This type of modeling 
addresses issues of population-based policies and programs, and is distinct 
from individual level models of risk and models of clinical decision making 
used at the individual patient-physician level. An additional goal of this 
concept is to advance methodology for modeling and to develop more uniform 
criteria for model validation in the population setting.

The National Cancer Institute (NCI) has a longstanding need to provide answers 
to critical research questions that cannot be obtained from direct observation 
because of expense, ethical, or other reasons. For example, a trial is only 
conducted in a limited study population under limited study conditions and 
extrapolation to other settings and conditions may only be feasible through 
modeling.  Lead time, the time which a diagnosis is advanced through screening, 
often may only be estimated through modeling because it is unethical to leave a 
screen detected patient untreated until clinical symptoms develop.  Prior to 
the CISNET, NCI had supported a variety of small efforts in this area through 
in-house work, contracts and grants.  The majority of extramural efforts have 
been directed at the analysis of specified cancer control interventions using a 
variety of modeling approaches applied to a hypothetical cohort or in the 
context of a trial or other limited settings, while the in-house work has 
mainly been directed toward addressing cancer surveillance issues at the 
national level.  There has been growing recognition that much can be gained by 
integration of these two approaches.

Models have increasingly been used in recent years to inform public health 
policy decisions at the national level.  In Europe, the cervical and breast 
cancer screening models have been used to design, monitor and evaluate national 
screening programs in several countries [1].  Models have been used in the 
United States to understand the implication of dramatic changes in national 
cancer statistics, such as patterns of increasing incidence related to 
screening for breast and prostate cancer [2-4], improving survival due to the 
dissemination of breakthrough treatment approaches in Hodgkin's Disease and 
testicular cancer [5-6].

Macro-level models use estimates of standard population-based statistics (i.e., 
birth rates, incidence, stage-distribution, relative survival, and mortality 
from causes other than cancer) as parameter estimates to model the life-process 
in terms of birth, the development of cancer, and death from cancer or other 
causes.  The impact of cancer control interventions aimed at primary 
prevention, screening, and treatment are estimated by changing the model 
parameters.  This approach has proven useful in evaluating the potential costs 
and benefits of specific cancer control strategies, and exploring the impact of 
these interventions on population-based cancer incidence and mortality 
statistics.  For example, CAN*TROL (a computer program developed by Dr. David 
Eddy for cancer control planning for the World Heath Organization and adapted 
for use at the NCI) [7] is a tool which has been used to examine the cost-
effectiveness of various strategies for breast cancer screening, and models of 
this type are currently being used to evaluate the impact of the introduction 
of adjuvant therapy on breast cancer mortality as well as the impact of changes 
in modifiable risk factors on colon cancer incidence. CAN*TROL has proven to be 
an effective tool for responding to policy questions from Congress and other 
sources addressed to the NCI.

Macro-level models have their limitations.  For example, macro-level models do 
not capture individual disease history, especially the pre-clinical phase, nor 
how early detection might alter that history. These dynamics are best captured 
using other types of models such as microsimulation.  While these modeling 
efforts have been invaluable in providing insight into the cost and 
effectiveness of specific intervention strategies, they are not designed to 
directly address the question of how trends in screening dissemination at the 
national level affect trends in cancer incidence, survival, mortality, and 
cost.  Recent efforts have been made to adapt these models to address 
population level surveillance questions.  While in the past these models have 
been utilized to model hypothetical cohorts in an organized screening program, 
the NCI has facilitated efforts to model opportunistic screening for multiple 
cohorts reflecting the varying cancer risk of U.S. population over time.  For 
example, current efforts are underway to model the impact of the dissemination 
of the PSA screening test in the US population on prostate cancer incidence and 
mortality [8].  Validating against current population trends can provide 
further clues concerning lead-time, over diagnosis, and the timing and size of 
potential mortality declines.

In conjunction with the development of these models, there have been various 
methodologic spin-offs that have broad uses in a variety of modeling settings.  
For example, NCI researchers, in collaboration with extramural researchers, 
have investigated the issue of obtaining variability of estimates from 
microsimulations [9], estimation techniques have been developed for the 
incidence of pre-clinical prostate cancer from autopsy prevalence data [10], 
and issues related to model validation have been explored. 

OBJECTIVES AND SCOPE    

The objective of this RFA is to enhance research on the development and use of 
models to evaluate the impact of cancer control interventions on population 
level statistics. Funding consists of two rounds in FY2000 and FY2002. In 
FY2000 applications were restricted to breast, prostate and colorectal cancer.  
These are three major cancer control sites where there is substantial modeling 
experience and, for the most part, interest in the population impact of all 
three modalities of cancer control (screening, treatment, and primary 
prevention). Seven breast applications were funded, as well as one apiece in 
prostate and colorectal cancer.   For the list of currently funded projects and 
their abstracts see:  http://www-dccps.ims.nci.nih.gov/SRAB/cisnet.html.   Also 
listed on the web site will be schedules for phone conference calls to discuss 
the existing CISNET program/work, the scope of the current RFA, and answer 
questions by potential applicants. There will probably be one conference call 
per cancer site (i.e. prostate, colorectal and lung cancer).  Summaries of the 
calls and/or tapes will be available for those unable to participate directly.  

Based on our funding results from the first round, the second round of funding 
will be limited to prostate, colorectal, and lung cancer. To keep applications 
focused, each proposal will be limited to a single cancer site. New 
investigators will be expected to join in the ongoing collaborative activities 
already underway.  

All of the proposals must include a central focus on the modeling the impact of 
cancer control interventions and other factors on observed national trends in 
incidence and/or mortality.  Examples of this type of research include:
  
(A) Model of the population impact of the introduction of new therapies using 
estimates of the impact of these therapies in controlled settings and 
population dissemination patterns (e.g., a model of the impact of adjuvant 
chemotherapy on colon cancer mortality starting in 1989).

(B) Model of the impact of interventions aimed at changing modifiable risk 
factors on population trends in incidence and/or mortality (e.g. model the 
impact of US and regional smoking cessation and smoking reduction patterns on 
lung cancer incidence and/or mortality).

(C) Model of the impact of screening on population incidence and/or mortality 
patterns using a model of disease natural history, the population dissemination 
of screening, and the operating characteristics of these screening modalities 
(e.g. what are the relative roles of screening (i.e., early detection), and 
polyp removal (i.e. prevention) on colorectal cancer incidence trends). 

(D) Use discrepancies between modeled and observed population trends to study 
the community effectiveness of interventions (e.g. study discrepancies between 
model predictions and observed data to better understand how community 
screening practices differ from trials. The sensitivity of screening test may 
be better than in a trial setting because of improved technology developed 
since the trial or worse because of less expert application of technology 
compared to the trial setting).

In addition to a central focus on observed trends in incidence and/or 
mortality, applications may also include applications of models that: 

(1) Predict the impact of new interventions on national trends (e.g., model the 
potential impact of spiral CT screening on lung cancer mortality; model the 
impact of new tobacco products on lung cancer incidence and/or mortality).

(2) Determine the impact of targeted cancer control interventions on population 
outcome (e.g., model the population impact of targeting different age groups, 
risk groups, adherence to initial versus repeat screening guidelines; model the 
impact of programs to encourage smoking reduction versus smoking cessation on 
lung cancer incidence and/or mortality).

The purpose of these efforts is to model the impact of the observed 
dissemination of cancer control interventions in the population, rather than 
using observed population trends to postulate new risk factors.  However, these 
models can include components which model the impact of population changes in 
both modifiable and non-modifiable risk factors.  Models which include the 
impact of multiple interventions simultaneously, e.g., the synergistic effects 
of screening and treatment, are desirable.  Models can be of the entire US 
population, a region of the country, or some specific identified population 
where unique data exists on the implementation of an intervention, or in a 
subpopulation of specific interest (e.g., rural poor).  Models can be developed 
for non-US populations, but should be justified based on their applicability to 
understanding US cancer trends.  Models can focus on one aspect of a disease 
(e.g., polyp development and removal), although justification must be given as 
to how one part of the disease process can be modeled separately, and how this 
model can be integrated into the complete disease picture.  It is not the 
purpose of this RFA to support analysis of hypothetical or trial-based cohorts 
and/or cost effectiveness analysis, but rather to support analysis based on 
realistic scenarios of population impact.

Applications should demonstrate modeling capability, and propose a specific 
research plan.  However, applicants should be flexible enough to accommodate 
further refinement and integration with other efforts.

SPECIAL REQUIREMENTS

Research Plan

Applications in response to the RFA must address the following areas:

Specific Aims/Background and Significance - The application must clearly state 
the surveillance research questions which this application is designed to 
address and the importance of these issues for cancer control in the US.  If 
the proposal includes the modeling of trends outside of the US, justification 
must be given as to what special insights this will give in understanding of US 
trends, how these results will be related to US trends, and why the same models 
could not be applied directly to US data.  All applications must include as a 
primary objective modeling of the impact of cancer control interventions and 
other factors on observed national trends in incidence and/or mortality. 
Applicants should discuss plans to develop, calibrate, and validate these 
models.  A well-calibrated and validated model of observed trends will allow 
possible extensions to secondary objectives, which can include projecting the 
impact of new interventions on future trends, as well as designing optimal 
cancer control strategies.  

Preliminary Studies/Research Design and Methods - Since the application of 
models of cancer interventions to population based trends is a relatively new 
area, applicants should describe in detail their approach to adaptation of 
current models, and demonstrate an understanding of the problems inherent in 
working with population based data. The application must describe the nature 
and characteristics of the model to be employed. Is this a new or existing 
model?  How will the model be adapted to address population-based surveillance 
questions?  The application must describe the proposed data resources for model 
development and validation, a description of areas of potential collaboration 
with other grantees in this cooperative agreement, strategies for identifying 
and characterizing differences between modeled and observed population trends, 
and the overall approach towards developing a comprehensive understanding of 
the determinants of cancer site-specific trends at the population level.

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

In addition, investigators should state their willingness to participate in 
joint meetings, to share methods and data resources, and to embark on 
collaborative efforts to decide overall research direction.  For example, to 
allow for easier model comparisons, applicants may be asked to cooperate on a 
standardized “base case” where common model inputs (e.g. dissemination of 
screening in the US population) and outputs would be mutually agreed upon by 
cancer site working group participants. Investigators will be asked to post 
project descriptions and pre-submission publications for comment and review by 
the cooperative group. 
 
Budget

First year costs may include funds for such activities as model development, 
model validation, acquisition of data for parameter estimation, methods 
development, and/or use or purchase of high-speed computer systems.  Activities 
may involve the acquisition and/or consolidation of data necessary for 
parameter estimation, model calibration, or validation, and subcontracts may be 
employed if necessary to make these efforts possible.  For purposes of 
budgeting, funds should be requested for up to three persons to travel to two 
cancer-site specific working group meetings, and one methodology meeting per 
year for each of the four years of the award.  It is anticipated that an annual 
meeting will be a joint meeting with representatives from all four cancer 
sites, and will include the methodology meeting as well.  The mid-year meetings 
will usually be separate cancer site-specific meetings

If a PI, or an institution wishes to submit several applications which share a 
common structure (e.g., models for breast and prostate cancer which share a 
similar computing framework), funds to develop or enhance that common structure 
should be included separately in each application, and duplication of funding 
activities will be negotiated at the time of award. Likewise, travel funds for 
each application should be considered separately, and overlapping funding will 
be negotiated at the time of award.  Finally, a submission from one institution 
may contain subcontracts for consultation from another institution, which may 
be unnecessary if both institutions are funded under CISNET.  Areas of 
potential duplication of funds across multiple applications should be clearly 
identified.

Terms and Conditions of Award

The following terms and conditions will be incorporated into the award 
statement and provided to the Principal Investigator(s) as well as the 
institutional official at the time of award.

Under this cooperative agreement, a partnership will exist between the 
recipient of the award and the NCI. These special Terms of Award are in 
addition to, and not in lieu of, otherwise applicable OMB administrative 
guidelines, HHS Grant Administration Regulations at 45 CFR Parts 74 and 92, and 
other HHS, and NIH Grant Administration policy statements.

The administrative and funding instrument used for this program is a 
cooperative agreement (U01), an "assistance" mechanism (rather than an 
"acquisition" mechanism) in which substantial NCI scientific and/or 
programmatic involvement with the awardee is anticipated during performance of 
the activity. Under the cooperative agreement, the NCI purpose is to support 
and/or stimulate the recipient's activity by involvement in and otherwise 
working jointly with the award recipient in a partner role, but it is not to 
assume direction, prime responsibility, or a dominant role in the activity.  
Consistent with this concept, the dominant role and prime responsibility for 
the activity resides with the awardee(s) for the project as a whole, although 
specific tasks and activities in carrying out the studies will be shared among 
the awardees and the NCI Scientific Staff.

1.  Definitions:

AWARDEES: Institutions receiving cooperative agreements through this RFA.

NCI PROGRAM DIRECTOR: A scientist administrator from the NCI extramural staff, 
the Program Director, will not only provide normal stewardship for the U01 
grants awarded under this RFA, but will also be involved in the scientific 
coordination and collaboration within the Network and will coordinate 
interaction between the research groups.

PRINCIPAL INVESTIGATOR (PI): The investigator who is designated by the 
applicant organization to direct the project to be supported by the U01 grant.  
The PI will assume the responsibility and accountability to the applicant 
organization officials and to the NCI for the performance and proper conduct of 
the research supported by the U01 mechanism.  Each institution may have more 
than one CISNET PI, and a single person may be the PI for applications for more 
than one cancer site. 

NCI SCIENTIFIC COORDINATORS: Scientists from the NCI extramural staff 
designated by the Program Director to coordinate the activities for one of the 
four cancer sites and the methodology working group.  NCI scientific 
coordinators will have substantial scientific involvement with the working 
groups and will help refine research questions.

NCI SCIENTIFIC STAFF: Scientific staff from NCI's extramural and intramural 
programs called upon to provide their expertise to the CISNET efforts.

EXTRAMURAL SCIENTIFIC INVESTIGATORS: Scientific staff named in the application 
from the participating institutions and their subcontractors.

CANCER-SITE WORKING GROUPS: There will be four cancer site specific working 
groups (breast, prostate, colorectal, and lung cancer).  Voting members of each 
working groups will be the PI's of each site specific grant project, and the 
NCI Scientific Coordinator.  Other project and NCI Scientific Staff will attend 
at the discretion of the voting members. The co-chairs of the working groups 
will be the NCI Scientific Coordinator and one of the PI's (chosen by mutual 
consent of the PI's for that cancer site).  Other subcommittees will be formed 
by the working groups as needed.

METHODOLOGY WORKING GROUP: A group comprised of interested methodologists among 
the extramural scientific investigators and NCI Scientific Staff.  The chairs 
of the methodology working groups will be one Extramural Scientific 
Investigator (chosen by mutual consent of the Extramural Scientific 
Investigators on the Methodology Working Group) and an NCI Scientific 
Coordinator designated by the NCI Program Director. Other subcommittees will be 
formed by the working group as needed.

STEERING COMMITTEE: A committee consisting of the five non-NCI chairs of the 
Working groups (breast, prostate, colorectal, lung, and methodology), the NCI 
Program Director, and one NCI Scientific Coordinator as designated by the NCI 
Program Director.  The Chair of the Steering Committee will be one of the PI's 
as selected by the Steering Committee.  The Steering Committee can admit 
additional non-federal members as they deem necessary.  The Steering Committee 
will provide overall direction for the CISNET project and provide oversight to 
procedures and policies.

2.  Awardee Rights and Responsibilities

The award recipients must join the NCI CISNET project for the purpose of 
planning, developing, and conducting collaborative projects to address high 
priority surveillance research objectives.  Within this framework, awardees 
have primary authorities and responsibilities to define objectives and 
approaches, and to plan, conduct, analyze, and publish results, 
interpretations, and conclusions of their studies.

Awardees will be required to attend working group meetings and are obligated to 
adhere to joint decisions for publication and research direction decided on by 
the Steering Committee and the Working Groups. 

Awardees will be expected to share information about model structure and 
assumptions at working group meetings, as well as strategies and data resources 
for parameter estimation.

Awardees will be expected to engage in efforts coordinated by the Working 
Groups for calibration, validation, and comparison of model results.

Awardees will retain custody of and have primary rights to the models and model 
results developed under these awards, subject to Government rights of access 
consistent with current HHS, PHS, and NIH policies.

3.  NCI Staff Responsibilities

The NCI Program Director and his designees will have substantial scientific-
programmatic involvement during conduct of this activity, through technical 
assistance, advice and coordination above and beyond normal program stewardship 
for grants.

The NCI Program Director will serve as a member of the Steering Committee.

The NCI Program Director will designate an NCI Scientific Coordinator for each 
cancer site and for the methodology group who will serve as a co-chair of the 
Working Groups.

The NCI Scientific Coordinators will provide information about a wide range of 
data resources which will be used for parameter estimation and population 
trends, and will serve as a conduit to the potential utility and access to 
these resources.  In addition, the NCI Scientific Coordinators will call upon 
other NCI Scientific Staff to provide advice on specific scientific and 
technical issues as needed.

The NCI reserves the right to reduce the budget, withhold support, or suspend, 
terminate or curtail a study or an award in the event of substantial lack of 
collaborative participation, failure to make satisfactory progress in 
fulfilling the stated goals of the project, refusal to carry out the 
recommendations of the Working Groups or the Steering Committee, or substantial 
failure to comply with the terms of award.

4.  Collaborative Responsibilities

A. Steering Committee

The Steering Committee will:

Be the ultimate decision making body for CISNET, unless a disagreement is 
brought to arbitration.

Review, approve, and provide comments on the written reports of the Cancer 
Site-Specific Working Groups.  This approval process should ensure that the 
proposed activities are consistent with the objectives and scope as specified 
in the RFA.

Review, approve, comment on, and provide directives for implementation based on 
the written recommendations from the Methodology Working Group.

Set publication procedures and policies.

Coordinate communication between the Working Groups.

Meet at least twice a year, and schedule additional meetings and conference 
calls as needed.

B. Working Groups

Meet at least twice a year.

Refine research questions that are consistent with high priority surveillance 
research needs.

Identify key potential determinants and confounders of population based trends, 
and to identify useful data resources to inform these models. 

Collaborate to identify and select common data resources for conducting 
calibration and independent model validation.

Consider the development of common modules that supply intermediate inputs to 
the central simulation models (e.g., screening histories supplied by a 
dissemination module, survival improvements in a screening model supplied by a 
treatment dissemination module).

Consider the use of common input data for dissemination, costs, and other 
parameters based on the best available national estimates.

Facilitate comparative analyses which will improve the credibility of 
individual models.

Evolve into an expert knowledge base to provide technical advise on policy 
relevant surveillance questions.

Will provide written reports to the Steering Committee after each Working Group 
Meeting summarizing research priorities, directions, and method of 
implementation.

Responsibilities of the chairs of the Working Groups will be to:

Convene working meetings.

Set meeting agendas.

Coordinate communication within the Working Group,

Set (in consultation with the working group) the publication agenda and 
schedule.

The PI Co-Chair of the Working Group will serve as a voting member of the 
Steering Committee, and will represent their Working Group to the Steering 
Committee.

C. The Methodology Working Group will:

Meet once a year, mainly for the purpose of scientific presentation and 
exchange of ideas, and to coordinate research plans where necessary.

Provide a forum for the discussion of methods development associated with the 
application of microsimulation and other models to population-based questions.

At the discretion of the group, provide written recommendations to the steering 
committee for common methodologic approaches and validation strategies and 
development of common model components.

5.  Arbitration

Any disagreement that may arise on scientific/programmatic matters (within the 
scope of the award), between award recipients and the NCI may be brought to 
arbitration.  An arbitration panel will be composed of three members; one 
selected by the recipient group, a second member selected by the NCI, and the 
third member selected by the two prior selected members. This special 
arbitration procedure in no way affects the awardee's right to appeal an 
adverse action that is otherwise appealable in accordance with the PHS 
regulations at 42 CFR Part 50, Subpart D and HHS regulation at 45 CFR Part 16. 

MECHANISM OF SUPPORT

The administrative and funding instrument to be used for this program will be a 
cooperative agreement (U01), an "assistance" mechanism (rather than an 
"acquisition" mechanism), in which substantial NIH scientific and/or 
programmatic involvement with the awardee is anticipated during performance of 
the activity.  Under the cooperative agreement, the NIH purpose is to support 
and/or stimulate the recipient's activity by involvement in and otherwise 
working jointly with the award recipient in a partner role, but it is not to 
assume direction, prime responsibility, or a dominant role in the activity. 
Details of the responsibilities, relationships and governance of the study to 
be funded under cooperative agreement(s) are discussed later in this document 
under the section "Terms and Conditions of Award".

The total project period for applications submitted in response to the present 
RFA may not exceed four years.  Awards and level of support depend on receipt 
of a sufficient number of applications of high scientific merit.  The 
anticipated award date is July 2002.

FUNDS AVAILABLE

The NCI intends to commit approximately $1,250,000 in total costs (direct and 
Facilities and Administrative (F&A) costs) in FY 2002 to fund 4 to 6 new grants 
in response to this RFA.  An applicant may request a project period of up to 
four years.  It is anticipated that the award for each application for modeling 
of a single cancer site will be between $75,000 to a maximum of $250,000 total 
cost for the first year.  It is anticipated that several modeling centers will 
submit applications for more than one cancer site.  Each individual application 
must be limited to one cancer site.  Because the nature and scope of the 
research proposed may vary, it is anticipated that the size of each award will 
also vary.  Applications on the lower end of range (e.g., $75,000 - $125,000) 
are encouraged for smaller more focused efforts, while those at the higher end 
of the range ($125,000-$250,000) are for more comprehensive population-based 
applications which consider the entire spectrum of the disease process and/or 
model multiple interventions simultaneously.  Although the financial plans of 
the NCI provide support for this program, awards pursuant to this RFA are 
contingent upon the availability of funds and the receipt of a sufficient 
number of applications of outstanding scientific and technical merit.

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic and foreign for-profit and non-profit 
organizations, public and private, such as universities, colleges, medical 
centers, units of State and Local governments, and eligible agencies of the 
Federal Government.  Applications from minority individuals, women, and persons 
with disabilities, are encouraged to apply.

Each Principal Investigator (PI) is limited to only one application per cancer 
site, and thus up to three applications are possible by one PI.  If a PI, or an 
institution, is submitting several applications that share a common structure 
(e.g., models for lung and prostate cancer which share a similar computing 
framework), funds to develop or enhance that common structure should be 
included separately in each application, and overlapping funding of activities 
will be considered at the time of award (see Special Requirements - Budget).

INQUIRIES

Written and telephone inquiries concerning this RFA are encouraged.  The 
opportunity to clarify any issues or questions from potential applicants is 
welcome.  The NCI will be holding a series of phone conference calls (probably 
one for each cancer site) for applicants to hear more about the existing CISNET 
work, and to discuss the scope of potential applications.  For more information 
about the schedule for these calls see 
http://www-dccps.ims.nci.nih.gov/SRAB/cisnet.html.  Summaries of the calls 
and/or tapes will be available for those unable to participate directly.  

Direct inquiries regarding programmatic issues to:

Dr. Eric Feuer
Division of Cancer Control and Population Sciences
National Cancer Institute
6116 Executive Boulevard, Room 5041, MSC 8317
Bethesda, MD  20892-8317
Telephone:  (301) 496-5029
Fax: (301) 480-2046
Email: rf41u@nih.gov

Direct inquiries regarding review issues to:

Ms. Toby Friedberg
Division of Extramural Activities
National Cancer Institute
6116 Executive Blvd., Room 8109, MSC 8329
Bethesda, MD  20892-8329
Rockville, MD  20852 (for express/courier service)
Telephone:  (301) 496-3428
Fax: (301) 402-0275
Email: tf12w@nih.gov

Direct inquiries regarding fiscal matters to:

Ms. Crystal Wolfrey
Grants Administration Branch
National Cancer Institute
Executive Plaza South, Room 243
Bethesda, MD  20892-7510
Telephone:  (301) 496-8634
Fax: (301) 496-8601
Email: crystal.wolfrey@nih.gov

LETTER OF INTENT

Prospective applicants are asked to submit, by October 9, 2001 a letter of 
intent that includes a descriptive title of the proposed research, name, 
address, and telephone number of the Principal Investigator, identities of 
other key personnel and participating institutions, and number and title of the 
RFA in response to which the application may be submitted.

Although a letter of intent is not required, is not binding, and does not enter 
into the review of subsequent applications, the information allows NCI staff to 
estimate the potential review workload and to plan the review.

The Letter of Intent is to be sent to the program staff listed under INQUIRES 
by the letter of intent receipt date listed in the heading of this RFA.

SCHEDULE

Letter of Intent Receipt Date:    October 9, 2001
Application Receipt Date:         November 13, 2001
Review by NCAB Advisory Board:    May 2002
Earliest Anticipated Start Date:  July 2002

APPLICATION PROCEDURES

The research grant application form PHS 398 is to be used in applying for these 
grants.  All instructions apply unless otherwise noted. Applications kits are 
available at most institutional offices of sponsored research and may be 
obtained from the Division of Extramural Outreach and Information Resources, 
National Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 
20892-7910, telephone 301/435-0714, E-mail: grantsinfo@nih.gov.  For those 
applicants with internet access, the 398 kit may be found at 
http://grants.nih.gov/grants/funding/phs398/phs398.html

The RFA label available in the PHS 398 application form must be affixed to the 
bottom of the face page of the application. Type the RFA number on the label. 
Failure to use this label could result in delayed processing of the application 
such that it may not reach the review committee in time for review. In 
addition, the RFA title and number must be typed on line 2 of the face page of 
the application form and the YES box must be marked.

The sample RFA label available at: 
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf has been modified to 
allow for this change.  Please note this is in pdf format.

Submit a signed, typewritten original of the application, including the 
Checklist, and three signed photocopies, in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive
Room 1040 - MSC 7710
Bethesda, MD  20892-7710
(20817 for express service)
 
At the time of submission, two additional copies of the application must also 
be sent to:

Ms. Toby Friedberg 
Referral Officer 
Division of Extramural Activities 
National Cancer Institute 
6116 Executive Blvd., Room 8109, MSC-8329 
Rockville, MD 20852 (express courier)
Bethesda, MD 20892-8329

Applications must be received by November 13, 2001.  If an application is 
received after that date, it will be returned to the applicant without review.  
The Center for Scientific Review  (CSR) will not accept any application in 
response to this announcement that is essentially the same as one currently 
pending initial review, unless the applicant withdraws the pending application.  
The CSR will not accept any application that is essentially the same as one 
already reviewed.  This does not preclude the submission of a substantial 
revision of an application already reviewed, but such an application must 
include an introduction addressing the previous critique.

REVIEW CONSIDERATIONS

Applicants are encouraged to submit and describe their own ideas about how best 
to meet the general research goals outlined in this RFA, and are expected to 
address issues identified under SPECIAL REQUIREMENTS of the RFA.

Upon receipt, applications will be reviewed for completeness by CSR and 
responsiveness by the National Cancer Institute.  Incomplete and/or non-
responsive applications will be returned to the applicant without further 
consideration.

Applications that are complete and responsive to the RFA will be evaluated for 
scientific and technical merit by an appropriate peer review group convened by 
the Division of Extramural Activities of the National Cancer Institute in 
accordance with the review criteria stated below.  As part of the initial merit 
review, a process will be used by the initial review group in which 
applications receive a written critique and undergo a process in which only 
those applications deemed to have the highest scientific merit, generally the 
top half of the applications under review, will be discussed assigned a 
priority score, and receive a second level review by the National Cancer 
Advisory Board.

Review Criteria

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  The 
reviewers will comment on the following aspects of the application in their 
written critiques in order to judge the likelihood that the proposed research 
will have a substantial impact on the pursuit of these goals.  Each of these 
criteria will be addressed and considered by the reviewers in assigning the 
overall score weighting them as appropriate for each application.  

1.  Significance.  Does this study address an important population-based 
surveillance problem? If the aims of the application are achieved, how will 
surveillance research and cancer control be advanced?  What will be the 
potential effect of these studies on policy of health care practices that could 
ultimately improve the health of the American public?  Does this application 
address realistic strategies and issues, rather than proposed optimal 
strategies that may have no real chance of ever being implemented in the 
population. 

2.  Approach.  Are the nature and characteristics of the model to be employed 
adequate?  How will the model be adapted to address population-based 
surveillance questions? Does the applicant have a plan for demonstrating a 
general understanding of the various factors influencing observed trends before 
investigating secondary goals of future trends and optimal cancer controls 
strategies?  What are the strategies for identifying and characterizing 
differences between modeled and observed population trends, and general 
approach towards developing a comprehensive understanding of the determinants 
of cancer site-specific trends at the population level?  Are the conceptual 
framework, design, methods, and analyses adequately developed, well integrated, 
and appropriate to the aims of the project?  Does the applicant acknowledge 
potential problem areas and consider alternative tactics?

3.  Innovation.  Does the project employ novel concepts, approaches or method?  
Are the aims original and innovative?   Does the application describe in detail 
their approach to adaptation of current models for population modeling, and 
demonstrate an understanding of the problems inherent in working with 
population based data.

4.  Investigator.  Is the investigator appropriately trained and well suited to 
carry out this work?  Do the investigators have extensive modeling experience? 
Is the work proposed appropriate to the experience level of the principal 
investigator and other researchers (if any)?  Do the investigators comprise an 
interdisciplinary team that is adequate to carry out the proposed work?

5.  Environment.  Does the scientific environment in which the work will be 
done contribute to the probability of success?  Is modeling activities an 
established element of the research environment? Do the proposed modeling 
efforts take advantage of unique features of the scientific environment or 
employ useful collaborative arrangements? Is there evidence of institutional 
support?

6.  Collaboration.  Do the investigators state their willingness to participate 
in joint meetings, be willing to share methods and data resources, and to 
embark on collaborative efforts to decide overall research direction?  Do the 
investigators have a documented history of engaging in collaborative modeling 
research with: (a) colleagues at their own institution, (b) modeling groups at 
other institutions, (c) providers of primary data sources, and (d) policy 
oriented organizations or agencies?  Documentation could include letters of 
support from prior collaborations.

7.  Relevance.  Does the application have as its primary goal modeling observed 
trends in incidence and/or mortality as a function of cancer control 
interventions and other factors?  If the application includes secondary goals 
concerning modeling of future trends and/or optimal cancer control strategies, 
do these modeling efforts reflect realistic scenarios, which could be achieved 
in actual population settings?

The initial review group will also examine: the appropriateness of proposed 
project budget and duration; the adequacy of plans to include both genders, 
minorities and their subgroups, and children as appropriate for the scientific 
goals of the research and plans for the recruitment and retention of subjects; 
the provisions for the protection of human and animal subjects; and the safety 
of the research environment.

AWARD CRITERIA

Applications recommended by the National Cancer Advisory Board will be 
considered for award based upon (a) scientific and technical merit; (b) program 
balance, including in this instance, a reasonable representation of projects 
across all three cancer sites, and sufficient compatibility of features to make 
a successful collaborative program a reasonable likelihood; and (c) 
availability of funds.

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS
 
It is the policy of the NIH that women and members of minority groups and their 
sub- populations must be included in all NIH-supported biomedical and 
behavioral research projects involving human subjects, unless a clear and 
compelling rationale and justification is provided indicating that inclusion is 
inappropriate with respect to the health of the subjects or the purpose of the 
research. This policy results from the NIH Revitalization Act of 1993 (Section 
492B of Public Law 103-43). 

All investigators proposing research involving human subjects should read the 
UPDATED "NIH Guidelines for Inclusion of Women and Minorities as Subjects in 
Clinical Research," published in the NIH Guide for Grants and Contracts on 
August 2, 2000 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-048.html); a complete 
copy of the updated Guidelines is available at 
http://grants.nih.gov/grants/funding/women_min/guidelines_update.htm.  The 
revisions relate to NIH defined Phase III clinical trials and require: a) all 
applications or proposals and/or protocols to provide a description of plans to 
conduct analyses, as appropriate, to address differences by sex/gender and/or 
racial/ethnic groups, including subgroups, if applicable; and b) all 
investigators to report accrual, and to conduct and report analyses, as 
appropriate, by sex/gender and/or racial/ethnic group differences.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS.

It is the policy of NIH that children (i.e., individuals under the age of 21) 
must be included in all human subjects research, conducted or supported by the 
NIH, unless there are clear and compelling scientific and ethical reasons not 
to include them.  This policy applies to all initial (Type 1) applications 
submitted for receipt dates after October 1, 1998.

All investigators proposing research involving human subjects should read the 
"NIH Policy and Guidelines on the Inclusion of Children as Participants in 
Research Involving Human Subjects" that was published in the NIH Guide for 
Grants and Contracts, March 6, 1998, and is available at the following URL 
address:  http://grants.nih.gov/grants/guide/notice-files/not98-024.html.

Investigators may also obtain copies of these policies from the program staff 
listed under INQUIRIES.  Program staff may also provide additional relevant 
information concerning the policy.

REQUIRED EDUCATION IN THE PROTECTION OF HUMAN RESEARCH PARTICIPANTS

All investigators proposing research involving human subjects should read the 
NIH policy on education in the protection of human research participants now 
required for all investigators, which is published in the NIH Guide for Grants 
and Contracts, June 5, 2000 (Revised August 25, 2000), available at the 
following URL address:  
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.  
A continuing education program in the protection of human 
participants in research is now available online at http://cme.nci.nih.gov/.

PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT 

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

URLS IN NIH GRANT APPLICATIONS OR APPENDICES

All applications and proposals for NIH funding must be self-contained within 
specified page limitations.  Unless otherwise specified in an NIH solicitation, 
Internet addresses (URLs) should not be used to provide information necessary 
to the review because reviewers are under no obligation to view the Internet 
sites.  Reviewers are cautioned that their anonymity may be compromised when 
they directly access an Internet site.

HEALTHY PEOPLE 2010

The Public Health Service (PHS) is committed to achieving the health promotion 
and disease prevention objectives of "Healthy People 2010," a PHS-led national 
activity for setting priority areas. This RFA, the Cancer Intervention 
Surveillance Modeling Network (CISNET), is related to the priority area of 
cancer surveillance and data systems.  Potential applicants may obtain a copy 
of "Healthy People 2010" at http://www.health.gov/healthypeople/.
 
AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance No. 
93.399, Awards are made under authorization of Sections 301 and 405 of the 
Public Health Service Act as amended (42 USC 241 and 284) and administered 
under NIH grants policies and Federal Regulations 42 CFR 52 and 45 CFR Parts 74 
and 92. This program is not subject to the intergovernmental review 
requirements of Executive Order 12372 or Health Systems Agency review.

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

REFERENCES

1.  van den Akker-van Marle E, de Koning H, Boer R, van der Maas P. Reduction
in breast cancer mortality due to the introduction of mass screening in the
Netherlands: comparison with the United Kingdom.  J Med Screen 1999;6:30-34.

2.  Feuer, E.J., Wun, L.M. "How Much of the Recent Rise in Breast Cancer
Incidence Can be Explained by Increases in Mammography Utilization:  A Dynamic
Population Approach," American Journal of Epidemiology, 1992; 136, 1423-1436.

3.  Wun, L.M. Feuer, E.J., Miller, B.A. "Are Increases in Mammographic
Screening Still a Valid Explanation for Trends in Breast Cancer Incidence in
the United States?" Cancer Causes and Control, 1995; 6, 135-144.

4.  Legler, J.M., Feuer, E.J., Potosky, A.L., Merrill, R.M., Kramer, B.S.,
"The Role of Prostate-Specific Antigen Testing Patterns in the Recent Prostate
Cancer Incidence Decline," Cancer Causes and Control, 1998; 9, 519-527.

5.  Feuer, E.J., Kessler, L.G., Triolo, H.E., Baker, S.G., Green, D.T.  "The
Impact of Breakthrough Clinical Trials on Survival in Population Based Tumor
Registries," Journal of Clinical Epidemiology, 1991; 44, 141-153.

6.  Weller, E.A., Feuer, E.J., Frey, C.M., Wesley, M.N., "Parametric Relative
Survival Modeling Using Generalized Linear Models with Application to
Hodgkin's Lymphoma,"  Applied Statistics, 1999; 48, 79-89.

7.  Levin DL, Gail MH, Kessler LG, Eddy DM, "A Model for Projecting Cancer
Incidence and Mortality in the Presence of Prevention, Screening, and
Treatment Programs,"  NCI Monographs, 2:83-93, 1986.

8. Etzioni, R, Legler, JM, Feuer, EJ, Merrill, RM, Cronin, KA, Hankey, BF,
"Cancer Surveillance Series: Interpreting Trends in Prostate Cancer - Part
III: Quantifying the Link Between Population Prostate-Specific Antigen Testing
and Recent Declines in Prostate Cancer Mortality," JNCI , 91: 1033-1039, 1999.

9.  Cronin KA, Legler, JM, Etzioni RD, "Assessing Uncertainty in
Microsimulation Modeling with Application to Cancer Screening Applications,"
Statistics in Medicine, 1998; 17:2509-23.

10. Etzioni, R., Cha, R, Feuer, E.J., Davidov, O.  "Asymptomatic Incidence and
Duration in Prostate  Cancer,." American Journal of Epidemiology, 1998; 148,
775-785.


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