INTERDISCIPLINARY RESEARCH TEAMS FOR MOLECULAR TARGET ASSESSMENT

Release Date:  November 10, 1999

RFA:  CA-00-001

National Cancer Institute 							

Letter of Intent Receipt Date:  February 1, 2000
Application Receipt Date:  March 15, 2000

PURPOSE

The purpose of this initiative is to discover, develop and validate the 
research tools that will make mechanism assessment in clinical trials and 
preclinical cancer models a reality.

Preclinical and clinical research with novel agents for cancer treatment and 
prevention requires usable tools to determine that the intended molecular 
target has been affected by the agent.  This initiative's major objective is 
the development of methods to assess the effects of interventions directed at 
specific molecular targets that produce the cancer phenotype or are 
associated with it. We seek molecular assays,  molecular and cellular imaging 
probes, and other tools that provide information on the extent to which 
molecular targets are affected in vivo by interventions in preclinical models 
and in proof-of-principle early clinical trials. 

This Request for Applications (RFA) invites investigators to form 
Interdisciplinary Research Teams. These Teams should include investigators 
with expertise in critical biological processes that encompass high-priority 
targets for cancer treatment or prevention; in chemistry; in molecular and 
cellular imaging science and technology; in invasive and/or non-invasive 
evaluation of the molecular effects of drugs; in preclinical models; and in 
early clinical trials. A Team may have investigators from several 
institutions; these may include the intramural programs of the NIH. Teams may 
focus on more than one target and may utilize agents originating from any 
source (industrial, academic and government).  For whatever targets it 
selects, each Team will advance knowledge of the pertinent biology, defining 
what events are most likely to be informative in the context of this 
initiative's goals, and focus on the development of relevant and practical 
assays, probes, and other tools to assess the effects of drugs on that target 
class in vivo.

These Teams will define the molecular basis for these research tools and 
develop and validate novel biochemical, pathological, pharmacologic, 
immunologic, molecular, or imaging methods and reagents to measure the effect 
of new target-directed drugs in proof-of-principle laboratory models and 
clinical trials. These methods and reagents must, therefore, be suitable for 
in vivo use in animal models and in human beings. Examples of target areas 
include, but are not limited to, angiogenesis, invasion and metastases, and 
other microenvironmental processes; signal transduction; cell-cycle control; 
apoptosis; immune effectors;  antimutagenesis (e.g. reverse mutations at 
specifically mutated gene targets)  and antioxidant response elements. 

Public Briefing Date: November 17, 1999 

An initial informational session for those investigators planning to submit 
applications in response to this RFA will be held on Wednesday, November 17, 
1999 from 7:00 AM to 8:30 AM  at the Washington Hilton, Jefferson West Room, 
Washington DC.  Representatives from the NCI's extramural research programs, 
Grants Administration Branch, and Division of Extramural Activities will be 
available to provide information and to answer questions relevant to 
applications responding to this RFA.  Investigators who are unable to attend 
should request transcripts.  Investigators who want transcripts or plan to 
attend should contact the IDB administrator for the NCI program staff member 
listed under INQUIRIES by November 15, 1999 to confirm their attendance (or 
request a transcript) and to obtain further information regarding the meeting 
site.

HEALTHY PEOPLE 2000

The Public Health Service (PHS) is committed to achieving the health 
promotion and disease prevention objectives of "Healthy People 2000," a PHS-
led national activity for setting priority areas. This RFA, Interdisciplinary 
Research Teams for Molecular Target Assessment, is related to the priority 
area of cancer prevention and treatment. Potential applicants may obtain a 
copy of "Healthy People 2000" at http://odphp.osophs.dhhs.gov/pubs/hp2000. 

ELIGIBILITY REQUIREMENTS

Applications may be submitted by for-profit and non-profit organizations, 
public and private, U.S. and foreign, such as universities, colleges, 
hospitals, laboratories, units of State and local governments, and eligible 
agencies of the Federal government.  Racial/ethnic minority individuals, 
persons with disabilities, and women are encouraged to apply as Principal 
Investigators. 

In order to be considered for review, an application for a U54 must have 
three or more related, interactive research projects that provide an 
interdisciplinary, yet thematic, approach to the problems to be investigated.  
Applications will not be accepted that include research activities focused 
exclusively on clinical research or exclusively on basic research, or that 
include epidemiological or large-scale clinical trials.

MECHANISM OF SUPPORT 

This RFA will use the National Institutes of Health (NIH) cooperative 
specialized center (U54) award mechanism.  The U54 mechanism may support any 
part of a full range of research development from very basic to clinical.   
The U54 is a cooperative agreement, an assistance mechanism (rather than an 
acquisition mechanism) in which substantial NIH scientific and/or 
programmatic involvement with the awardee is anticipated during the 
performance of the activities. Under a cooperative agreement, the NIH's 
purpose is to support and stimulate the recipient's activities by involvement 
in and otherwise working jointly with the award recipient in a partner role. 
NIH staff work cooperatively with the award recipients in a partner role and 
do not assume direction, prime responsibility, or a dominant role in the 
activity. Details of the responsibilities, relationships, and governance of 
the activities to be funded under the cooperative agreements awarded for this 
Program are discussed below under "Terms and Conditions of Award."

The total project period for an application submitted in response to this RFA 
may not exceed five years. The anticipated award date is December 1, 2000.

This RFA is a one-time solicitation.  At this time the NCI has not determined 
whether or how this solicitation will be continued beyond the present RFA.  
If it is determined that there is a continuing program need, the NCI will 
either invite recipients of awards under this RFA to submit competitive 
continuation cooperative agreement applications for review or re-issue the 
RFA for re-competition.  If the NCI does not continue the program, awardees 
will be able to submit grant applications through existing investigator-
initiated grant programs.

FUNDS AVAILABLE

It is anticipated that an estimated total of $6.3 million (including direct 
costs and costs for facilities and administration) will be available for the 
first year of the program, which will support approximately 6-8 Teams, 
although the actual funding plan will depend upon the scientific 
opportunities presented and are contingent upon the availability of funds and 
the receipt of a sufficient number of applications of outstanding scientific 
and technical merit.  An applicant may request a project period of up to five 
years.  Because the nature and scope of the proposed research will vary, it 
is anticipated that the sizes of the awards will also vary.  

RESEARCH OBJECTIVES

Background  

The discovery of putative molecular targets and their exploitation in cancer 
drug discovery present clinical researchers with striking opportunities, as 
well as some difficult challenges.  In brief, how are these targets and 
agents directed at them to be validated?  What does target-based drug 
discovery imply for the clinical trials methodology of the future?  Will it 
change the nature of endpoints for Phase I and Phase II trials or for 
deciding how much drug is enough for individual patients? 

Three basic principles underlie the present initiative: 

1.  Since the purpose of drug discovery is to develop effective and selective 
agents for the prevention and treatment of cancer in people, then ultimate 
validation of a target can occur only in the clinic. 
2.  Clinical trials of agents emanating from a target-based drug discovery 
process should focus on endpoints that assess whether the drug has affected 
its putative target.
3.  To make such trials possible, we must develop informative assays, tools, 
reporter cassettes, probes suitable for molecular and cellular imaging, and 
other tools that will reveal an agent's effect on its target and that are 
practical for use in the clinic.

What is needed is the ability to assess in vivo the molecular and cellular 
pharmacology effects of drug on its target, or on pathways regulated by the 
target, and correlate these observations with the clinical effects of drug 
administration. These correlations, or the absence of them, will have 
important implications for judging the validity of the target and for 
optimizing drug administration regimens. The need to assess target effects is 
made even more urgent by new classes of agents (for example, drugs that 
interfere with metastasis or angiogenesis) that may exert effects on cancer, 
precancer, or high risk tissue that take a long time to become clinically 
apparent.  For such classes of agents, assessment of target effects may 
provide badly needed surrogate endpoints of drug activity. Direct assessment 
of effects on molecular targets and the downstream consequences of drug-
target interaction  may, in fact, be the only practicable methods of deciding 
on appropriate doses and schedules for certain drug classes. Confirming that 
the hoped-for biologic effect is achieved, or assessing reasons for failure 
to achieve it, will be critical in proof-of-principle preclinical and 
clinical trials to avoid the expense and futility of carrying ineffective 
agents into full-scale clinical development.

Thus the discovery, development, and validation of accurate and practical 
methods for assessing whether an agent has affected its target is a matter of 
the highest priority. The impressive progress of target identification and 
drug discovery efforts in academia and industry has clearly outpaced the 
development of practical research tools to provide informative molecular 
endpoints in preclinical and clinical research. The development of clinically 
useful probes for the molecular effects of drug administration, whether these 
are assessed by analyses of body fluids or tissue specimens in the 
laboratory, by non-invasive in vivo imaging, or by other techniques, will 
require interdisciplinary  research teams with broad expertise covering many 
areas of science and technology. This initiative is intended to provide the 
critical translational bridge between drug discovery and clinical trials by 
supporting highly interdisciplinary teams, each oriented toward  biological 
mechanisms that seem highly relevant to cancer biology and currently 
constitute high-priority targets for drug discovery. 

As an example, a number of methods have been proposed for in vivo assessment 
of the effect of angiogenesis inhibitors. These have included 1) dynamic MR 
or Doppler ultrasound imaging studies to measure alterations in blood flow; 
2) biopsy specimens to assay apoptosis in malignant and endothelial cells; 
and 3) bioassays to assess plasma effects in ex vivo models of angiogenesis.  
These have not been studied systematically in the pre-clinical efficacy 
models that are being used to provide evidence supporting the further 
development of agents with a putative anti-angiogenic mechanism. Informative 
and efficient clinical evaluation of this class of agents will surely require 
in vivo measures of the extent to which the agents are affecting their 
putative targets. Moreover, the appropriate endpoint of drug effect may 
depend not only on the class of agent (e.g., angiogenesis inhibitor) but on 
the specific molecular target that the agent interacts with (e.g., VEGF-R). 
Thus the development of research tools suitable for clinical use is likely to 
be scientifically and technically challenging. 

Interdisciplinary Research Teams (Teams) are expected to address directly the 
translational links between target-based drug discovery and mechanism-based 
clinical testing.  They will focus on discovering, assessing, and validating 
clinically usable assays, probes, and other tools to make this connection a 
reality. The intent is to develop research tools that will, directly and 
indirectly, revolutionize all stages of research relating to the development 
of drugs to treat or prevent cancer.  NCI expects that these Teams will serve 
as important resources to other investigators developing new agents.  For 
example, they are likely to collaborate with others by making the results of 
their research - information, reagents, and techniques - available to other 
institutions.  They will also provide training to enable other investigators 
to implement newly developed tools and technologies at their own sites. 

The Teams are expected to have productive interactions with many other groups 
in academia, industry, and government. The expertise in the Teams should make 
them very attractive collaborators for industry and academic researchers 
involved in target discovery and validation and in early clinical trials. 
They will also work closely with the staff of several NCI programs 
(Developmental Therapeutics Program, Cancer Therapy Evaluation Program, 
Diagnostic Imaging Program, Cancer Diagnosis Program and the Chemoprevention 
Program).

Related NCI Initiatives

The following Web sites present detailed information on other related NCI 
initiatives in drug discovery for treatment and prevention of cancer, 
clinical trials, and imaging programs that may interact with a proposed Team:
Molecular Targeted Drug Discovery Grants. The output of this initiative will
be a spectrum of new agents. The preclinical development of these agents will
require suitable assays and probes to assess how targets are affected in pre 
clinical models and in the clinic. The Teams are logical  collaborators with 
drug discovery groups in this endeavor (http://grants.nih.gov/grants/guide)

The National Cooperative Drug Discovery Groups (NCDDG).
(http://grants.nih.gov/grants/guide/rfa-files/RFA-CA-99-010.html).

The Rapid Access to Intervention Development (RAID) program focuses on the 
pre-clinical development of anti-cancer drugs and biologics. Modifications of 
RAID that would provide support for production of diagnostic probes for 
research purposes are under consideration.  (http://dtp.nci.nih.gov)


In vivo Cellular and Molecular Imaging Centers. These centers for functional 
imaging  may provide collaborative resources for Team efforts. 
(http://grants.nih.gov/grants/guide/rfa-files/RFA-CA-99-004.html)

Small-Animal Imaging Resource Program. These may be an important resource for 
Teams funded in this initiative, since they will provide access to 
specialized resources and expertise.

RFA for imaging in therapeutic studies 
(http://grants.nih.gov/grants/guide/rfa-files/RFA-CA-98-023.html)

QuickTrials for Prostate Cancer Therapy (currently pilot testing in prostate 
cancer). (http://grants.nih.gov/grants/guide/pa-files/PA-99-070.html)

Grants submitted to the Clinical Oncology SEP 
(http://www.drg.nih.gov/Review/irgdesc.asp#CONC)

Early Therapeutics Development Cooperative Agreements/Contracts (Phase I and 
Phase II). These contracts will include provisions for the support of 
correlative and mechanistic study components of early clinical trials. 
(http://ctep.cancer.gov)

SPORES.  (http://spores.nci.nih.gov/)

Cancer Diagnosis Program What's New (http://www-cdp.ims.nci.nih.gov)

Related initiatives in cancer prevention include:

Contract-based chemoprevention drug development program 
(http://dcp.nci.nih.gov/CB/#MAA)
Rapid Access to Preventive Intervention Development (RAPID) 
(http://dcp.nci.nih.gov/CB/rapid.htm)
Chemopreventive agent drug discovery grants 
http://www.nci.nih.gov/dcb/cpcb.htm)
Prostate, Lung, Colon and Ovary (PLCO) trial (http://dcp.nci.nih.gov/PLCO/)
Chemoprevention in high risk genetic cohorts 
(http://grants.nih.gov/grants/guide/rfa-files/RFA-CA-98-012.html)
Early Detection Research Network (EDRN) 
(http://dcp.nci.nih.gov/cbrg/edrn.html)
Pivotal Clinical Trials for Chemoprevention Agent Development 
(http://grants.nih.gov/grants/guide/rfa-files/RFA-CA-98-001.html)
EDRN Biomarker validation laboratories
(http://grants.nih.gov/grants/guide/rfa-files/RFA-CA-99-008.html)

Objectives 

The central objective of the Teams supported by this initiative the Teams 
will be to discover, develop, and validate clinically practical tools and 
methodologies for assessing the effect of molecularly targeted agents against 
their putative targets. Some of the essential steps in this process will 
include the following:

1. Selecting one or more cancer-relevant targets or pathways for which agents 
are under development and will be available for evaluation

2. Establishing effective collaborations  to enhance the synergy of the 
proposed Team and leverage other available resources

3. Identifying how agents directed at high-priority targets affect 
molecular/cell biology/cellular pharmacology endpoints and develop practical 
ways of assaying these effects in clinical settings.

Activities that a Team may choose to undertake to achieve the translational 
goals of this research may include, but are not limited to, some or all of 
the following:
   a. Invasive techniques that require acquisition of relevant cells (e.g., 
from cancers, preinvasive neoplastic lesions, or fields at risk for cancer) 
by biopsy, aspiration or plasmapheresis:  this material can then be evaluated 
by a variety of molecular and/or immunohistochemical approaches to determine 
whether the targeted pathway has been affected.
   b. Invasive techniques that require temporary placement of catheters (e.g. 
microdialysis)
   c. Techniques for imaging molecular and cellular processes: examples 
include MRI, positron emission tomography(PET) or other techniques based on 
radiotracers, or ultrasound or optical imaging.
   d. Non-invasive techniques that utilize reporter cassettes for genetic 
manipulations that can provide additional imaging options

4. Evaluating and validating the assays, probes, and other techniques it 
develops in in vivo preclinical models, for assessing such matters as target 
inhibition, inhibition of biochemical processes downstream from the target; 
the effect of pharmacokinetics on pharmacodynamics and the establishment of 
exposure-effect relationships; and the establishment of dose/schedule 
combinations suitable for clinical trials.
 
5. Evaluating and validating the tools and methodologies in proof-of-
principle early clinical trials of molecularly targeted agents in patients 
with malignancies, premalignant conditions, or cancer risk factors (genetic, 
infectious or environmental), as appropriate.  Effective collaboration of 
laboratory and clinical scientists is critical for the success of these 
translational efforts.  Depending on the chosen target/process and the 
availability of agents, clinical trials may not be feasible in the initial 
funding year, but the NCI anticipates that expeditious progress will permit 
Teams to initiate proof-of-principle clinical research by the third year of 
funding.

6. Exploring new scientific insights into drug mechanisms and determinants of 
response

7. Exploring new approaches to early clinical trials methodology; for 
example, the use of alternate trial designs and endpoints, or exploring 
designs based on molecular classifications of tumor rather than histology

8. Willingness to share information via publications, meetings and support of 
training activities and to disseminate new reagents and techniques discovered 
under this initiative to other investigators. When dissemination of 
attractive new reagents to other research groups seems desirable, the NCI 
will facilitate this by providing additional support to the originating 
laboratory. Team investigators are expected to participate in NCI-sponsored 
working groups focused on high-priority targets. Awardees are encouraged to 
file patent applications in a timely manner in order to permit timely 
presentation and publication of results. 

Scope

This RFA invites investigators to form interdisciplinary Teams with expertise 
in the several scientific and technical areas mentioned previously, and 
elaborated upon below, that are critical to the success of this initiative. 
The Principal Investigator may draw innovative expertise from wherever it may 
exist; investigators need not be limited to a single institution. 
Collaborating investigators may be from academic, industrial, or government 
institutions (including NIH intramural scientists and non-US sites). In their 
plans to evaluate novel research tools, investigators may incorporate new 
molecularly targeted agents for treatment or prevention originating from any 
source (in-house, other academic, industry, NCI).  This RFA, however, does 
not provide support/funding for synthesis/production of therapeutic agents, .  
See "Related NCI Initiatives" for a list of available initiatives that 
support agent synthesis/production. 

The following is a list of specific research topic areas relevant to 
treatment or prevention of cancer that are considered to be responsive to 
this RFA.  Additionally, these topics identify areas where research at the 
basic/clinical interface is deemed essential to the potential development of 
new agents:
o Signal transduction 
o Angiogenesis
o Invasion and metastases
o Cell-cycle control
o Apoptosis
o Immune effectors 
o Antimutagenesis at specific mutated genes
o Antioxidation response elements

This list is not meant to be all-inclusive and prospective applicants are 
encouraged to discuss program relevance issues with program staff cited under 
INQUIRIES. 

The specific membership and structure of each Team will be determined by the 
research plans of the applicant. Although the relevant components will be 
determined by the selected target(s),  NCI expects that innovative approaches 
to most target classes may entail inclusion of diverse expertise including 
some or all of the following:
 
o Basic biology pertaining to the target (molecular, cellular, immunologic, 
biochemical expertise related to the selected target/pathways/mechanisms)
o Synthetic chemistry (for congeners, labeled agents or novel vectors) and/or 
radiochemistry (for agents suitable for imaging)
o In vivo models suitable for assessment of the relevant target effects.  The 
capacity to select and carry out this research effectively should be 
supported by the clarity of the plans or the track record as evidenced by 
publications or peer-reviewed recognition (funding) for in vivo 
pharmacodynamic studies or specific studies in therapy or prevention on the 
part of the proposed project/core leader.  
o Pharmacokinetics and pharmacodynamics (expertise in designing sampling 
strategies, assays using appropriate analytic techniques, quality assurance 
and data analysis);
o Early clinical trials of investigational agents with invasive and non-
invasive correlative studies: although it is likely that for most targets, 
clinical research will not be feasible early in the period of support, NCI 
hopes that the Team will make enough progress to initiate clinical research 
by the third year of funding;  experience in the daily management and 
treatment of patients with various malignant tumors; experience with persons 
at risk for invasive cancer; assessment of eligibility/evaluability of these 
subjects in clinical trials; experience in recruiting, obtaining informed 
consent and evaluating subjects receiving investigational agents;  commitment 
to investing intellectual effort with basic science colleagues focused on 
novel molecular targets. Access to a patient care and service facility that 
serves a substantial cancer patient population and, if the facility is not 
part of the parent institution, documentation of a consortium agreement with 
an associated institution that assures adequate access to cancer patients for 
clinical research
o Prevention and treatment: for agents/targets suitable for chemoprevention 
development 
o Molecular and cellular imaging (small animal and human): ability to perform 
investigational imaging (possibly with novel imaging agents) for research 
purposes and to evaluate study results with other measures of drug effect 
and/or treatment outcome 
o Interventional radiology (for identification of suitable patients and 
sample acquisition; ability to obtain tissue and radiologic evaluations for 
research purposes)
o Pathology and molecular analysis of tissues: expertise in a variety of 
techniques for analysis of target relevant alterations in human tissues
o Enhanced topical/endoscopic imaging for preinvasive neoplasia

Organizational Structure

In order to provide the greatest flexibility for organizing research efforts 
in these cooperative agreements, the PI should organize the investigators and 
resources into the following required elements:

1.  Research Projects
 
Each Team application must provide details for at least three Research 
Projects, which together represent experimental approaches to the discovery 
and/or development of assays, probes, and other tools suitable for use in 
preclinical models and clinical research. In addition, Research Projects may 
conduct research on the biologic and pharmacodynamic aspects of target 
interactions, to enable assessment of how agents affect the target. All of 
the Research Projects must be related to one or more specific molecular 
targets for anticancer agents.   Research Projects should not focus on 
developing molecular assessment tools for agents that are already approved 
for clinical use. Teams should plan to continually select the most promising 
research approaches that are likely to have impact on the development of 
clinically useful probes. The flexibility of the Team is intended to promote 
the discontinuance of research projects demonstrating little or no 
translational significance and to promote initiation of new projects with 
greater potential.

2. Core Services

The Team is encouraged to develop and maintain core  resources that are 
essential for the conduct of this research.  Core Services may include 
resources that may already be available at the institution and do not need 
further development/research.  Examples of potential Core Services include 
animal cores, imaging resources, pharmacology, pathology, clinical data 
monitoring services, and statistical support.  An Administrative Core is 
required and is responsible for administrative management and coordination of 
meetings and other activities within the Team and with other potential 
collaborators such as industry and NCI and other funded Teams.  By 
definition, the Principal Investigator of the Team also serves as the 
Principal Investigator of the Administrative Core.  The administrative core 
may encompass the other service cores, or, if they are separately organized, 
each service core must provide resources to at least two Research Projects 
and/or Pilot Projects.

3.  Pilot (Developmental) Projects

Every Team must allocate a significant effort to support pilot projects that 
take maximum advantage of new research opportunities. Such projects may be 
collaborative among scientists within one or more Teams, or with scientists 
outside the Team.   If a clinical trial is not described as one of the 
Research Projects, at least one Pilot Project should outline the general plan 
for a (future) clinical trial that incorporates the methodologies, 
techniques, and probes to be developed in the research projects, along with a 
mechanism-specific novel agent. Each application should propose an 
institutional review process for selecting pilot projects for funding that 
generate feasibility data and have the most promising translational research 
potential.  These funds are intended to remain flexible and to support 
studies of a limited duration, e.g., two years or less. The expectation is 
that successful feasibility studies will replace full projects that are not 
progressing satisfactorily with regard to translational research objectives 
within the Team.  The team of scientists that participates in the Team may, 
therefore, change through the course of the research.

Framing experiments as pilot projects permits maximal flexibility to proceed 
in the directions that seem most scientifically fruitful to the 
investigators.  It is expected that individual pilot projects would have 
small budgets since the majority of the personnel and equipment involved may 
be supported by the Research Projects and Cores and funds would only be 
needed for supplies, animals, etc.  The expectation is that successful 
feasibility studies will allow the new approaches and reagents developed in 
this initiative to become a core function and/or be distributed more widely 
to other investigators studying similar targets.

Further information on the structure and organization of the grant 
application is provided in the Supplemental Application Instructions (see 
URL: http://ctep.info.nih.gov)

The research activities included in these cooperative agreements are 
explicitly translational and are, of necessity, highly interdisciplinary. A 
Team should be able to deal expertly with such matters as cancer biology and 
target selection, chemistry, pharmacokinetics and pharmacodynamics, cellular 
and molecular imaging, in vivo animal models, and early clinical trials that 
are centered on hypothesis validation and proof of principle. A Planning 
Committee with appropriate representation from each Team and from NCI Program 
Staff will be established to help coordinate the activities and exchange 
information and techniques among the Teams (see below).

SPECIAL REQUIREMENTS

Terms and Conditions of Award

Cooperative agreements are assistance mechanisms and are subject to the same 
administrative requirements as grants. The following Terms and Conditions of 
Award are in addition to, and not in lieu of, otherwise applicable OMB 
administrative guidelines, HHS grant administration regulations in 45 CFR 
Part 74 and 92 and administered under the NIH Grants Policy Statement. 

The administrative and funding instrument used for this program is a 
cooperative centers agreement (U54), an "assistance" mechanism (rather than 
an "acquisition" mechanism) in which substantial NIH scientific and 
programmatic involvement with the awardee is anticipated during the grant 
award.  The NIH purpose is to support and stimulate the activity by working 
jointly with the recipient in a partner role, but it is not to assume 
direction, prime responsibility or a dominant role in the activity.  The 
prime responsibility for the research resides with the awardees, although 
some activities may be carried out as a collaboration among the awardees with 
coordination and facilitation by NCI program staff.

1. Awardee responsibilities:

a.  Awardees will have primary responsibility for the project as a whole, 
including research design and conduct, data collection, data quality control, 
data analysis and interpretation and preparation of publications, as well as 
collaborations with other awardees.   Awardees will retain primary rights to 
the data developed under these awards, subject to government rights of access 
consistent with current HHS, PHS, and NIH policies.  However, awardees must 
be committed to making the assays and probes they develop available to the 
cancer research community. 

b.  Awardees agree to participate on common projects identified by the 
Planning Committee on common research interests that address a specific basic 
and/or clinical research problem.

c.b.  Each Team (a Team consists of the investigators in a single grant 
award) should plan regular meetings (no less than monthly) to discuss the 
progress and directions of its research and to insure that the necessary 
interdisciplinary interactions are taking place. For Teams including members 
from other institutions, plans to extend meetings via teleconferencing, 
videoconferencing or web conferencing (for more frequent meetings) as well as 
face-to-face meetings (semiannually or quarterly) should be described.  

dc.  The Principal Investigator and other designated investigators will 
attend an Annual Meeting to be organized by NCI staff in Washington D.C.  In 
addition, the PI will be a voting member of the Planning Committee which 
meets twice a year (one meeting will be coordinated with the Annual Meeting).   
The support for attendance at these meetings will be provided through the 
Team's award.  The Team should request support for attending these meetings 
within their travel budget.

ed.  Each Team will submit biannual progress reports to the NCI that describe 
activities and accomplishments during the previous funding period.

f.   NIH intramural scientists, if any are included in a Team, will not 
receive additional budgeted support from this award mechanism. They should 
arrange support for their participation in this initiative through the usual 
NIH intramural mechanisms. 

ge. Intellectual Property
		
Since the discovery of new and improved  research tools for the evaluation of 
the molecular effects of anticancer treatments is the objective of this 
effort and active involvement by commercial laboratories is facilitated by 
the existence of adequate patent coverage, it is essential that applicants 
provide plans to assure such coverage. In order to encourage timely 
presentation and publication of results, the Awardees are encouraged to file 
patent applications in a timely manner.  The situation may be complicated by 
the involvement of multiple institutions. Each applicant Team must provide a 
detailed description of the approach to be used for obtaining patent coverage 
and for licensing where appropriate, in particular where the invention may 
involve investigators from more than one institution. Procedures must be 
described for resolution of legal problems should they arise. Your attention 
is drawn to P.L. 96-517 as amended by P.L. 98-620 and 37 CFR Part 401. 
Instructions were also published in the NIH Guide for Grants and Contracts 
(NIH Guide, Vol. 19, No. 23, June 22, 1990). 

All Awardees must adhere to the policy for distribution of unique research 
resources produced with PHS funding, published in the NIH Guide for Grants 
and Contracts (NIH Guide, Vol. 25, No. 23, July 12, 1996). The Guide can be 
accessed electronically at http://grants.nih.gov/grants/guide/index.html. 
Procedures must be described, which address how Awardees will approach such 
distribution, including acknowledgment of the terms of any related technology 
licenses or sponsored research agreements which Institution may have.

Awardees shall include the following terms concerning intellectual property 
rights, or provide an alternative plan.  NCI acknowledges that some 
commercial collaborators that are members of applicant Teams, or who provide 
agents to applicant Teams,  may require that Institution agree to grant to 
them certain intellectual property rights, as described by the terms below.  
If Institution voluntarily agrees to the described terms, then they should 
appear in the Institution's Team application. NCI recognizes that 
Institutions' ability to access agents from commercial collaborators for this 
effort may be limited absent such a voluntary agreement, or a substantially 
similar independent agreement between Institution and commercial 
collaborators providing agents.  However, in no event will the award of a 
cooperative agreement be dependent upon the described terms' being part of an 
Institution's Team application. Rather, Institution's Team application may 
provide Institution's own plan for accessing agents from commercial 
collaborators. In no event, however, will an award be made absent 
incorporation of either the terms below, or Institution's own plan.

"Institution agrees to grant to commercial collaborator: (i) a paid-up 
nonexclusive, nontransferable, royalty-free, world-wide license to all 
Institution Inventions for research purposes only; and (ii) a time-
limited first option to negotiate an exclusive, world-wide royalty-
bearing license for all commercial purposes, including the right to 
sub-license, to all Institution Inventions on terms to be negotiated in 
good faith by the collaborator and Institution. The collaborator shall 
notify Institution, in writing, of its interest in obtaining such an 
exclusive license to any Institution Invention within six (6) months of 
the collaborator's receipt of notice of such Institution Invention(s). 
In the event that a collaborator fails to so notify Institution, or 
elects not to obtain an exclusive license, then the collaborator's 
option shall expire with respect to that Institution Invention, and 
Institution will be free to dispose of its interests in such 
Institution Invention in accordance with Institution's policies. If 
Institution and collaborator fail to reach agreement within ninety (90) 
days, (or such additional period as collaborator and Institution may 
agree) on the terms for an exclusive license for a particular 
Institution Invention, then for a period of six (6) months thereafter 
Institution shall not offer to license the Institution Invention to any 
third party on materially better terms than those last offered to 
collaborator without first offering such terms to collaborator, in 
which case collaborator shall have a period of thirty (30) days in 
which to accept or reject the offer.

Institution agrees that notwithstanding anything contained herein to 
the contrary, any inventions, discoveries or innovations, whether 
patentable or not, which are not Subject Inventions as defined in 35 
USC 201(e), arising out of any unauthorized use of the collaborator's 
agent and/or any modifications to the agent, shall be the property of 
the collaborator (hereinafter "Collaborator Inventions"). Institution 
will promptly notify the collaborator in writing of any such 
Collaborator Inventions and, at collaborator's request and expense, 
Institution will cause to be assigned to collaborator all right, title 
and interest in and to any such collaborator inventions and provide 
collaborator with assignment or other documents). Institution may also 
be conducting other  research using the agent under the authority of a 
separate Material transfer Agreement (MTA) with the collaborator. 
Inventions arising thereunder shall be subject to the terms of the MTA, 
and not to this clause."

* 35 USC 
(E) The term "Subject Invention" means any invention of the contractor 
first conceived or first actually reduced to practice in the 
performance of work under a funding agreement. 

h. Protection of Proprietary Data

The ability to publish new results in a timely and intellectually 
unconstrained manner is fundamental to the academic enterprise. This need 
must be balanced with the legitimate requirements of commercial collaborators 
to protect the proprietary or confidential information that they provide 
concerning their proprietary agents. Commercial collaborators also may 
require exclusive access to the raw and primary data generated in studies of 
their agents. Therefore, NCI urges that the following statement also be 
incorporated in Team applications:

"Raw and primary data may be provided exclusively to the NCI, 
industrial collaborators, and the FDA, as appropriate. This provision 
shall not affect the investigators' right to disseminate their research 
findings through publications or presentations."

2. NCI Staff responsibilities:

a. Program Staff consists of the NCI Program Director and additional 
representatives from each of the following Programs: Cancer Therapy 
Evaluation Program,  Chemopreventive Agent Development Program, Developmental 
Therapeutics Program, Diagnostic Imaging Program, and Cancer Diagnosis 
Program. The Program Director will identify specific Program Staff  to 
participate in the roles described below: 
 
a. Three (the Program Director and the Associate Directors of the NCI 
Developmental Therapeutics Program and Cancer Diagnosis Program) will serve 
as voting members of the Planning Committee. 

b. Specified program staff have substantial coordinating scientific roles 
based on their knowledge of other related NIH supported research and resource 
activities. Program staff will work closely as
 Program staff have substantial coordinating scientific roles based on their 
knowledge of other related NIH supported research and resource activities

Program Staff will work closely as research coordinators with individual 
investigators and NIH intramural scientists to facilitate collaborations with 
other NCI-funded research groups to leverage the resources available for this 
effort.  The NCI Program Staff will assist in the coordination of activities 
that involve all the awardees, such as annual meetings and Planning Committee 
meetings. They will also assist the research efforts of the Team by 
facilitating access to fiscal and intellectual resources provided by 
industry, private foundations and NIH intramural scientists. As required, 
when projects are not making headway, Program Staff, through the NCI Program 
Director will help reprogram research efforts within the peer-reviewed scope 
of work, including options to modify or terminate projects, by mutual consent 
between a Team and NCI.

cb. The NCI Program Director will interact with each Team, evaluating the 
progress of that particular Team, coordinate research approaches between 
Teams, and contribute to the adjustment of research projects or approaches as 
warranted. The NCI Program Director will assist and facilitate this process 
and not direct it. The NCI Program Director will also provide assistance in 
reviewing and commenting on all major transitional changes of an individual 
Team's activities prior to implementation to assure consistency with the 
goals of this RFA. 

dc. The NCI Program Director will coordinate this activity with other ongoing 
studies supported by NCI to avoid duplication of effort and to encourage 
sharing and collaboration in the development of new clinically useful 
reagents and methodologies for molecular target assessment. The NCI Program 
Director will coordinate access to other resources from NCI including NCI 
sponsored agents for preclinical and clinical testing, drug screening, 
preclinical toxicology testing, assistance in IND filing, etc.

ed.  CTEP Assistance in Protocol Development: When a proof-of-principle 
clinical trial to be supported by this initiative is planned, a detailed 
protocol mutually acceptable to the Team and to the CTEP Protocol Review 
Committee (PRC) will be prepared. Communication at the various stages of 
protocol development is encouraged to promote protocol development and 
implementation. Protocols utilizing NCI-sponsored agents should be preceded 
by a written Letter of Intent (LOI) from the Team declaring interest in 
conducting a particular study. The LOI mechanism is designed for preliminary 
review and is recommended to expedite protocol development and implementation 
and to facilitate agreement on study priority and design (for further 
discussion of these mechanisms see the DCTD Investigator's Handbook available 
at the CTEP Web page at the following URL: 
(http://ctep.info.nih.gov/handbook/index.html).

fe.  CTEP Review of Proposed Clinical Research.  All Team protocols, 
including protocols utilizing agents not sponsored by NCI, will be reviewed 
by the PRC, which meets weekly and is chaired by the Associate Director, 
CTEP.  Ad hoc reviewers, external to NCI, will be utilized when deemed 
appropriate by the PRC chairperson.  Following the review of the protocol by 
the PRC, the NCI Program Director will provide the Team with a consensus 
review that describes recommended modifications and other suggestions, as 
appropriate (see the Investigator's Handbook for further information 
regarding protocol review at CTEP).  NCI will not provide investigational 
drugs or permit expenditure of NCI funds for a protocol that it has not 
approved.  An Investigational Drug Branch Senior Clinical Investigator will 
serve as the Scientific Coordinator for designated agents for clinical trials 
and  will be available to assist the Team in developing a mutually acceptable 
protocol, consistent with the research interests, abilities and strategic 
plans of the Team and of the NCI.

gf. The NCI Program Director will organize an annual meeting of all funded 
investigators to share progress and research insights that may benefit all of 
the projects.  In addition, he/she will be responsible for organizing 
biannual meetings of the Planning Committee.

hg.  NCI Program Staff will assist, where warranted, in data analyses, 
interpretations, and the dissemination of study findings to the research 
community and health care recipients including co-authorship of the 
publication of results of studies conducted by the Teams, subject to NIH 
publication policies.

3. Collaborative responsibilities:

The Planning Committee will provide overall coordination of the Teams; voting 
members will consist of the Team Principal Investigators, 3 additional non-
NCI scientists selected by the PIs and 3 NCI Program Staff.  Additional 
Program Staff and scientists other than PI's may attend as non-voting members 
of the Planning Committee where additional expertise may be required.  A non-
NIH  An extramural chairperson for the Planning Committee will be chosen by a 
majority vote of the Principal Investigators.  The Planning Committee will 
identify the need for collaborations either within or outside the Teams and 
the need to redirect certain efforts as mandated by establishment of 
sufficient data to reach conclusions, data supporting alternative approaches, 
or experience proving that the proposed research is no longer feasible. Some 
Teams will have common research interests that address a specific basic 
and/or clinical research problem; research focus groups may be formed to 
conduct coordinated research activities identified by the Planning Committee.  
The Planning Committee will make recommendations regarding targets and 
possible research tools.  It will also seek input from the scientific 
research communities and consider how to have an impact on drug development 
in the larger community.  The Team investigators must be willing to consider 
addressing future scientific needs discussed by the Planning Committee.  The 
Planning Committee will apprise NCI program staff on scientific 
opportunities, emerging needs or impediments to progress.  

The Planning Committee will meet twice yearly, once at the annual meeting of 
the entire Team.  The purpose of these meetings is to share scientific 
information, assess scientific progress, identify new research opportunities 
and potential avenues of collaborations such as with industry, private 
foundations and/or NIH intramural scientists, establish priorities that will 
accelerate the translation of preclinical findings into clinical 
applications, reallocate resources and conduct the business of the 
cooperative research program.

4.  Arbitration: When agreement between an awardee and NCI staff cannot be 
reached on scientific/programmatic issues that may arise after the award, an 
arbitration panel will be formed. The panel will consist of one person 
selected by the awardee, one person selected by NCI staff, and a third person 
selected by these two members. The decision of the arbitration panel, by 
majority vote, will be binding. This special arbitration procedure in no way 
affects the right of an awardee to appeal an adverse action in accordance 
with PHS regulations at 42 CFR Part 50, Subpart D, and HHS regulations at 45 
CFR Part 16. 


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 subpopulations must be included in all NIH-supported biomedical and 
behavioral research projects involving human subjects, unless a clear and 
compelling rationale and justification are provided 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 "NIH Guidelines for Inclusion of 
Women and Minorities as Subjects in Clinical Research," which have been 
published in the Federal Register of March 28, 1994 (FR 59 14508-14513) and 
the NIH Guide for Grants and Contracts, Volume 23, Number 11, March 18, 1994, 
available on the web at: 
http://grants.nih.gov/grants/guide/notice-files/not94-100.html.

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 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 was published in the NIH Guide for 
Grants and Contracts, March 6, 1998, and is available on the Web at 
http://grants.nih.gov/grants/guide/notice-files/not98-024.html.  

Investigators also may obtain copies of these policies from the program staff 
listed under INQUIRES.

LETTER OF INTENT 

Prospective applicants are asked to submit a letter of intent that includes: 
a descriptive title of the proposed research and the respective projects; the 
name, address, email address and telephone number of the Principal 
Investigator; the identities of other key personnel and participating 
institutions; and the 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 
subsequent applications, the information that it contains allows NCI staff to 
estimate the potential review workload and to avoid conflict of interest in 
the review. The letter of intent is to be sent to the program staff listed 
under INQUIRIES by February 1, 2000.

APPLICATION PROCEDURES

The research grant application form PHS 398 (rev. 4/98) is to be used in 
applying for these awards. These forms are available at most institutional 
offices of sponsored research and 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.  The 398 kit may also be found at 
http://grants.nih.gov/grants/forms.htm 
 
Additional instructions for preparing a U54 grant application are available 
by FAX from the program staff listed under INQUIRIES and on the Internet at  
http://ctep.info.nih.gov/newpage1.htm.  THESE INSTRUCTIONS MUST BE USED IN 
PREPARING AN APPLICATION IN RESPONSE TO THE RFA.
 				
Submission Procedures

The RFA label available in the PHS 398 (rev. 4/98) application form must be 
affixed to the bottom of the face page of the application.  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.
 
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 Boulevard, Room 8062, MSC 8239 
Rockville, MD 20852 (express service) 
Bethesda, MD 20892-8239

Applications must be received by March 15, 2000. 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 RFA 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 
substantial revisions of applications already reviewed, but such applications 
must include an introduction addressing the previous critique.  Applications 
must meet all eligibility requirements as described above and must address 
all programmatic requirements (see Special Requirements above) in the RFA. 

REVIEW CONSIDERATIONS 

Upon receipt, applications will be reviewed for completeness by CSR and 
responsiveness to the RFA by NCI staff. Incomplete and/or non-responsive 
applications will be returned to the applicant without further consideration. 
Any application that does not meet the minimum application requirements as 
set forth under APPLICATION PROCEDURES will be considered unresponsive to the 
RFA. Responsiveness includes, but is not limited to, the program relevance of 
the proposed research projects and pilot projects being proposed to access 
core facilities, as determined by NCI. 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 NCI in accordance with the 
review criteria stated below. As part of the initial merit review, a process 
may be used by the scientific review group in which all applications receive 
a written critique and only those applications deemed to have the highest 
scientific merit will be discussed, assigned a priority score, and receive a 
second level review by the NCAB.

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 general aspects of the application in 
order to judge the likelihood that the proposed research will have an impact 
on these goals.  Note that the application does not need to be strong in all 
the general categories to be judged likely to have a major scientific impact 
and deserve a high priority score. For example, important work that is 
essential to move a field forward may not be innovative by its nature. 

The factors to be considered in the evaluation of all applications are given 
below. 

A.   Individual Research Projects:


1. Significance: How important are the  selected target(s)/pathway(s)/mechanism(s)?
Are the selected targets considered high priority for the development of
anticancer agents? Will development of the proposed assays, probes, and other
tools improve the clinical development of the agents?  What will be the effect
of these studies on the concepts or methods that drive this field? 

2. Approach:  Are the conceptual framework, design, methods, and analyses 
adequately developed, well-integrated, and appropriate to the aims of the 
project?   How effective is the strategy for selecting assessment tools?  
Have preclinical models been proposed in which the agents demonstrate 
activity? Have the investigators considered the appropriate negative and 
positive controls?  Are there adequate plans to assess the feasibility of the 
probes and assays to be developed, and to correlate their readout with useful 
preventive or therapeutic activity in these models?  Are there plans to 
describe the operating characteristics and quality control procedures for the 
reagents to be developed?  

Will the design of preclinical experiments permit conclusions that will be 
applicable to scheduling of drug administration and timing of effect 
assessment in clinical trials?  Does the investigator identify potential 
limitations in currently available models and possible approaches to 
rectifying them?

3. Innovation: Does the project employ novel concepts, approaches or methods?  
Are the aims original and innovative? Does the project challenge existing 
paradigms or develop new methodologies or technologies? Does the project 
study new factors or parameters that will impact drug development and 
evaluation?

4. Investigator:  Is there understanding of the design of relevant laboratory 
studies?  Does the training, experience, qualifications, accomplishments and 
availability of the proposed Investigators and evidence of ability, 
organizational structure and availability to function as a team demonstrate 
capacity in the following areas as is pertinent to the proposed research (not 
all need to be included):

o  Basic biology pertaining to the target (molecular, cellular, immunologic)
o  Synthetic chemistry and/or radiochemistry
o  In vivo models
o  Pharmacokinetics and pharmacodynamics in preclinical and clinical 
experiments
o  Clinical research incorporating novel biological and/or pharmacodynamic 
endpoints
o  Molecular and cellular imaging (small animal and human)
o  Interventional radiology
o  Pathologic and molecular analysis of tissues
o  Enhanced topical/endoscopic imaging for preinvasive neoplasia

5. Environment: Is there related experience of the organization including 
project descriptions and pertinent efforts for any sponsor (commercial, 
government or non-profit)?  In particular, is there evidence of experience 
with preclinical and clinical evaluation of investigational agents?  Is there 
an explanation of how the organization will provide support and expertise to 
this project and the proposed PI?  Is there prior experience of the 
PI/Organization with multi-institutional research projects, or is there a 
clear plan to organize multi-institutional research projects if they are 
proposed?   Is there experience or well defined plans for completing 
correlative studies in trials of anti-cancer agents, including recruitment of 
patients with accessible tissue, integration/scheduling of imaging resources, 
pathology resources and pharmacology resources proposed in prior studies?

Are there plans for Team members to make intellectual investments in the 
relevant disciplines to permit true multidisciplinary collaborations?  Has 
sufficient effort been committed to permit the clinical researchers to attend 
presentations at the basic science laboratory meetings?  Have the basic 
scientists planned to attend relevant clinical meetings at the institution to 
review the course of trials and imaging experiments?   Does the preparation 
of the projects indicate that experts from different backgrounds communicated 
with each other in writing the grant application?

B. Cores

1. Qualifications, experience and commitment of key personnel in the services 
provided by the core unit, as well as their ability to devote the required 
time and effort in providing services to the Team

2. Appropriateness of the use of the core services by the budgeted projects

3. Adequate plans for charge back and priority management procedures for 
service/technical core units

C. Developmental/Pilot Projects

1. Are the specific plans for developmental funds consistent with the Team's 
overall goals and priorities?  Do the Pilot Projects interact with the 
Research Projects and Cores?

2. Does the quality of the pilot projects proposed by the Team demonstrate 
the effectiveness of the selection process?

D. Overall Program Organization and Capability:

1. Significance: Does the Team address an important target/pathway/mechanism? 
If the aims of the application are achieved, how will scientific knowledge be 
advanced? What will be the effect of these studies on the concepts or methods 
that drive this field? 

2. Approach: 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 methods? 
Are the aims original and innovative? Does the project challenge existing 
paradigms or develop new methodologies or technologies? 

4. Investigators: Are the Principal Investigator and collaborators 
appropriately trained and well suited to carry out this work? Does the 
research experience of the PI demonstrate expertise in the biologic 
target/pathway/mechanism?  Is the work proposed appropriate to the experience 
level of the key investigator and other researchers? Is the Principal 
Investigator committed to devote the required time and effort to the Team? 
Does the PI demonstrate willingness to work and collaborate with other Team 
Programs as appropriate and with NCI assistance in the manner summarized in 
this RFA.

5. Environment: Does the scientific environment in which the work will be 
done contribute to the probability of success? Are resources such as space, 
equipment, preclinical models, technical and clinical capabilities described 
that are needed for the success of the research? Do the proposed experiments 
take advantage of unique features of the scientific environment or employ 
useful collaborative arrangements? Is there evidence of institutional 
support? 

6. In addition, the criteria for reviewing the Team as an integrated effort 
are:

a. Overall strength of the Team in terms of the combined strength of the 
research projects, pilot projects and core units, and the significance of the 
application to the objectives of the Program outlined in this RFA;
b. Leadership ability and scientific stature of the Principal Investigator, 
particularly, but not exclusively in the area of the proposed research, and 
his/her ability to meet the Team's demands of time and effort;
c. An appropriate organizational and administrative structure for effective 
attainment of Team objectives that considers arrangements for internal 
quality control of ongoing research, the allocation of funds, day-to-day 
management, contractual agreements, if applicable, and internal communication 
among investigators; 
d. Demonstrated institutional commitment to the Team and its objectives in 
terms of providing research facilities and management support. 


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

FE. Overall Evaluation and Scoring of Applications

The individual Research Projects will be assigned numerical priority scores 
while the Cores and Pilot Projects will be rated superior, satisfactory, or 
NRFC, without numeric scores.  A single numerical priority score will then be 
assigned to the Team application as a whole after discussing all of the 
review elements listed above.  The score will be based on the overall quality 
of the Research Projects, the Developmental/ Pilot Projects, the overall 
effectiveness and adequacy of shared resources, the overall program 
organization and capability, the plans for interactions with the Team, and 
the potential for validation and integration of research tools into new drug 
development programs. 

AWARD CRITERIA

Applications recommended by the National Cancer Advisory Board will be 
considered for award based on a) scientific and technical merit as determined 
by peer review; b) program balance, including, in this RFA, the need for 
Teams that address different targets/processes;  and c) availability of 
funds.

Schedule 

Letter of Intent Receipt Date:    February 1, 2000
Application Receipt Date:         March 15, 2000
Peer Review:                      June/July 2000
Review by NCAB:                   September 2000
Earliest Anticipated Award Date:  December 1, 2000

INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. 
The opportunity to clarify any issues or questions from potential applicants 
is welcome. Direct inquiries regarding programmatic issues and address the 
letter of intent to: 

Louise Grochow, M.D.
Chief, Investigational Drug Branch, CTEP, DCTD
National Cancer Institute
Executive Plaza North, Room 715
6130 Executive blvd
Rockville, MD 20850
Email: grochowl@ctep.nci.nih.gov
Telephone: (301) 496-1196
FAX: (301) 402 0428 Please FAX requests for supplemental instructions to 
Marylou Macgregor
IDB Administrator: Marylou Macgregor (email: macgregorm@ctep.nci.nih.gov). 

Direct inquiries regarding review issues to:

Ms. Toby Friedberg 
Referral Officer 
Division of Extramural Activities 
National Cancer Institute 
6116 Executive Boulevard, Room 8062, MSC 8239 
Rockville, MD 20852 (express service) 
Bethesda, MD 20892-8239
Telephone (301) 496-3428
Fax: (301) 402-0275
Email: tf12w@nih.gov

Direct inquiries regarding fiscal matters to: 
 
Ms. Carolyn Mason
Grants Administration Branch
National Cancer Institute
6120 Executive Boulevard Room 243
Bethesda, MD  20892-7340
Rockville, MD 20852 (for express/courier service)
Telephone:  (301)496-7800 ext 259 
Fax:(301) 496-8601
Email: cm113g@nih.gov
 
AUTHORITY AND REGULATIONS
  
This program is described in the Catalog of Federal Domestic Assistance No. 
93.394, cancer treatment. 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 Parts 
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 and contract 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.


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices


Office of Extramural Research (OER) - Home Page Office of Extramural
Research (OER)
  National Institutes of Health (NIH) - Home Page National Institutes of Health (NIH)
9000 Rockville Pike
Bethesda, Maryland 20892
  Department of Health and Human Services (HHS) - Home Page Department of Health
and Human Services (HHS)
  USA.gov - Government Made Easy


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