Subject: RFA CA 90-l6 from 7/27/90 NIH Guide
From: Dot Baker <[email-masked]>
To: [email-masked]
Date: Thu, 26 Jul 90 08:59 EST

Paul,
   This is the second item from the NIH Guide of 7/27/90.  Please
post this to the NIH Listerver as: RFACA-90-16.072790.
   Thanks a lot.
                Dottie
 ---------------------------- Text of forwarded message -----------------------
     
REQUEST FOR APPLICATIONS for Research Project (R01) Grants
     
RFA:  CA-90-16
     
P.T. 34; K.W. 0740020, 0715035, 0765010
     
BIOLOGICAL AND CHEMICAL STUDIES OF TAXOL
     
National Cancer Institute
     
LETTER OF INTENT RECEIPT DATE:  September 17, 1990
APPLICATION RECEIPT DATE:  October 24, 1990
     
A. INTRODUCTION
     
The Division of Cancer Treatment (DCT) of the National
Cancer Institute (NCI) invites grant applications from
interested investigators for chemical and/or biological
studies on taxol ultimately leading either to: (1) ways to
increase production of this drug; or, (2) define further its
biological properties for use in improved drug design or in
enhanced clinical utility.
     
Grants are awarded to non-profit and for-profit
organizations and institutions, governments and their
agencies, and occasionally, to individuals.  The Request for
Applications (RFA) is the type of grant solicitation used
when it is desired to encourage investigator-initiated
research projects in areas of special importance to the
National Cancer Program.  Applicants funded under the RFA
are supported through the customary National Institutes of
Health (NIH) grant-in-aid in accordance with Public Health
Service (PHS) policies applicable to research project
grants.  However, the RFA solicitation represents a single
solicitation with specific deadlines for receipt of
applications.  All applications received in response to the
RFA will be reviewed by the same NCI initial review group.
     
The present RFA announcement has
a specified deadline (October 24, 1990) for
receipt of applications.  Applications should be prepared
and submitted in accordance with the aims and requirements
described in the following sections:
     
This program is described in the Catalog of Federal
Domestic Assistance number 13.395.  Cancer Treatment
Research.  Awards will be made under the
authority of the Public Health Service Act, Sections 301,
Public Law 78-410, as amended, 42 U.S.C. 241, as amended by
Public Law 99-158, 42 U.S.C. and 285(a).  This program is
not subject to the intergovernmental review requirements of
Executive Order 12372 or Health Systems Agency review.
     
B.  BACKGROUND INFORMATION
C.  RESEARCH GOALS AND SCOPE
D.  MECHANISM OF SUPPORT
E.  ELIGIBILITY
F.  REVIEW PROCEDURES AND CRITERIA
G.  METHOD OF APPLYING
H.  LETTER OF INTENT
I.  INQUIRIES
     
B.  BACKGROUND INFORMATION
     
Taxol is an antitumor drug isolated from the Western Yew,
Taxus brevifolia, and other Taxus species that has shown
excellent confirmed activity against refractory human
ovarian cancer and preliminary activity at other sites; it
is one of the most promising new drugs in many years.  It
has a wholly novel mechanism of action, binding to
microtubules and stabilizing them against depolymerization.
Investigations of the chemistry, biology, biochemistry, and
pharmacology of taxol have been limited.  Many aspects of
drug action and of drug production in the source plants,
Taxus species, are not well understood.
     
C.  RESEARCH GOALS AND SCOPE
     
The intention of this RFA is to encourage investigators to
propose ideas which will increase our knowledge of the
drug's properties and which are likely, in the long term, to
contribute to large-scale drug supply and to maximally
effective usage of taxol in the clinical setting.  The
following are undeveloped or underdeveloped areas of
interest which merit particular attention:  (1)
biosynthesis and its regulation in Taxus sp.; (2) plant
tissue culture to produce taxol and related compounds; (3)
agronomics and plant genetics of taxol to enhance
production; (4) evaluation of genetic engineering methods to
transfer genes involved in taxol biosythesis to fast growing
plants; (5) identification of the specific taxol binding
site on microtubules and of the amino acid sequences
involved, leading to high-resolution definition of the
binding site and eventually to molecular mimics with simpler
structures; (6) frequency, mechanisms, and circumvention of
resistance; (7) studies of in vitro combinations of taxol
with other cytotoxic agents; (8) metabolism of taxol in human tissue;
(9) measurements and consequences of tissue distribution of
taxol; and (10) in vivo evaluation of combination therapy
using taxol in preclinical models.  These areas are not
meant to be restrictive and investigator-initiated proposals
in all areas of taxol research relevant to the goals of this
RFA, such as total chemical synthesis, are encouraged.  Either
single or multidisciplinary approaches may be proposed as
appropriate to the topic area (see also Section I,
INQUIRIES).
     
The NCI is able to supply limited amounts of taxol for these
investigations (up to 100 mg per award).  Investigators
needing substantial amounts of taxol for proposed studies
should contact the Program Director before preparing an
application (see Section I, INQUIRIES).
     
Studies that use taxol as a reagent to isolate microtubules
or to study microtubule or cycloskeletal function without
therapeutic intent will not be considered responsive to this
RFA.
     
D.  MECHANISM OF SUPPORT
     
This RFA will use the National Institutes of Health (NIH)
grant-in-aid.  Responsibility for the planning, direction,
and execution of the proposed project will be solely that of
the applicant.  Except as otherwise stated in this RFA,
awards will be administered under PHS grants policy as
stated in the Public Health Service Grants Policy Statement,
DHHS Publication No. (OASH) 82-50,000, revised January 1,
1987.
     
This RFA is a one-time solicitation.  Generally, future
unsolicited competing renewal applications will compete with
all investigator-initiated applications and be reviewed by
the Division of Research Grants (DRG).  However, should the
NCI determine that there is a sufficient continuing program
need, NCI may announce a request for renewal applications.
Only recipients of awards under this RFA will be eligible to
apply.
     
Approximately $1,000,000 in total costs per year for five
years will be committed to fund applications
submitted specifically in response to this RFA.  It is
anticipated that five to eight awards will be made.  This
funding level is dependent on the receipt of a sufficient
number of applications of high scientific merit.  Program
balance among various areas of taxol/Taxus research will be
an important funding consideration.  The total project period
for applications submitted in response to the present RFA
should not exceed five years.  Foreign grants are limited to
a three-year project period.  The earliest feasible start
date for the initial awards will be July 1, 1991.  Although
this program is provided for in the financial plans of the
NCI, the award of grants
pursuant to this RFA is also contingent upon the
availability of funds for this purpose.
     
E.  ELIGIBILITY REQUIREMENTS
     
Domestic and foreign non-profit and for-profit institutions
are eligible to apply.  Governments and their agencies are
also eligible.
     
F.  REVIEW PROCEDURES AND CRITERIA
     
REVIEW PROCEDURE
     
Upon receipt, applications will be reviewed initially by the
DRG for completeness.
Incomplete applications will be returned to the applicant
without further consideration.  Evaluation for
responsiveness to the RFA is an NCI program staff function.
Applications will be judged to determine how well they meet
the goals and objectives of the program as described in the
RFA.  Applications judged non-responsive will be returned by
the NCI, but may be submitted as investigator-initiated
research grants at the next receipt date.  Questions
concerning the relevance of proposed research to the RFA
should be directed to program staff as described in the
INQUIRIES section.
     
In cases where the number of applications is large compared
to the number of awards to be made, the NCI may conduct a
preliminary scientific peer review to eliminate those
applications that clearly are not competitive.  The NCI
will remove from competition those applications judged to be
noncompetitive for award and notify the applicant and
institutional business official.
     
Those applications judged to be both competitive and
responsive will be further evaluated according to the review
criteria stated below for scientific and technical merit by
an appropriate peer review group convened by the Division of
Extramural Activities, NCI.  The second level of review
by the National Cancer Advisory Board considers the special
needs of the Institute and the priorities of the National
Cancer Plan.
     
REVIEW CRITERIA
     
The factors considered in evaluating the scientific merit of
each response to this RFA will be:
     
1.  The degree of importance of the research to one of the
following:
     
a. understanding and/or enhancement of taxol production;
     
b. mechanism of activity of taxol as an antitumor agent; and
     
c. potential enhancement of clinical utility of taxol.
     
2.  The originality of the research plan from a scientific
and technical viewpoint.
     
3.  Adequacy, thoroughness, and completeness of the
scientific plan.
     
4.  Experience, training and time commitment of the
Principal Investigator and staff.
     
5.  Adequacy and availability of laboratory space and
equipment required.
     
6.  Clearly demonstrated access to all materials (i.e.,
chemicals, reagents, biological samples, human tissues,
etc.) as are needed for the research.
     
The review group will critically examine the submitted
budget and will recommend an appropriate budget and period
of support for each approved application.
     
G.  METHOD OF APPLYING
     
The regular research grant
application form PHS 398 (Revised 10/88) must be used in
applying for these grants.  These forms are available at
most institutional business offices; from the Office of
Grants Inquiries, Division of Research Grants, National
Institutes of Health, Room 449, Westwood Building, 5333
Westbard Avenue, Bethesda, Maryland 20892; or from the NCI
Program Director named below.
     
The RFA label available in the October 1988 revision of
Application Form PHS 398 must be affixed to the bottom of
the face page.  Failure to use this label could result in
delayed processing of your application such that it may not
reach the review committee in time for review.  In addition,
the RFA number and title should be typed on line 2 of the
face page of the application form.
     
Submit a signed, typewritten original of the application,
including the Checklist, and four (4) signed, exact
photocopies, in one package to the address below.  The
photocopies must be clear and single-sided.
     
DIVISION OF RESEARCH GRANTS
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD  20892**
     
At time of submission, send two (2) additional copies of the
application to:
     
REFERRAL OFFICER
Division of Extramural Activities
National Cancer Institute
Room 838, Westwood Building
5333 Westbard Avenue
Bethesda, Maryland 20892
     
Applications must be received by October 24, 1990.  If an
application is received after that date, it will be
returned.
If the application submitted in response to this RFA is
substantially similar to a research grant application already
submitted to the NIH for review, but has not yet been reviewed,
the applicant will be asked to withdraw either the pending
application or the new one.  Simultaneous submission of identical
applications will not be allowed, nor will essentially identical
applications be reviewed by different review committees.  Therefore,
an application cannot be submitted in response to this RFA which is
essentially identical to one that has already been 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.
     
H.  LETTER OF INTENT
     
Prospective applicants are asked to submit by September 17,
1990, a letter of intent that includes a descriptive title of
the proposed research, the name and address of the principal
investigator, the names of other key personnel, the
participating institutions, the number and title of the RFA
in response to which the application is being submitted.
Since taxol is in very limited supply, for planning purposes, the
NCI requests the applicant to indicate the amount of drug that will
be required to support the proposed studies.
     
Although a letter of intent is not required, is not binding,
and does not enter into the review of subsequent
applications, the information it contains is extremely
helpful in planning for the review of applications.  It
allows NCI staff to estimate the potential review workload
and to avoid possible conflict of interest in the review.
     
The letter of intent should be sent to:
     
BY US POSTAL
     
Dr. Matthew Suffness
Program Director
Grants and Contracts Operations Branch
Division of Cancer Treatment
National Cancer Institute
Executive Plaza North, Suite 832
Bethesda, MD  20892
Telephone:  (301) 496-8783
FAX:  (301) 496-8333
     
BY DIRECT DELIVERY
     
Dr. Matthew Suffness
Program Director
Grants and Contracts Operations Branch
Division of Cancer Treatment
National Cancer Institute
Executive Plaza North, Suite 832
6130 Executive Boulevard
Rockville, MD  20852
Telephone:  (301) 496-8783
FAX:  (301) 496-8333
     
I.  INQUIRIES
     
Written or telephone inquiries concerning the objectives and
scope of this RFA or inquiries about whether or not specific
proposed research would be responsive are encouraged and
should be directed to Dr. Matthew Suffness at the above
address.  The Program Director welcomes the opportunity to
clarify any issues or questions from potential applicants.