From: IN%"[email-masked]" "Ken Yow" 9-MAR-1989 18:02:38.68
To: [email-masked], [email-masked]

Received: from JNET-Daemon by UNCVX1.BITNET; Thu, 9 Mar 89 16:50 EDT
Received: From UNC(MAILER) by UNCVAX1 with Jnet id 2693 for PJONES@UNCVAX1;
 Thu,  9 Mar 89 16:50 EST
Date: Thu, 09 Mar 89 16:43 EST
From: Ken Yow <[email-masked]>
Subject: Latest NIH Guide; save as NIHGUIDE.031089
To: [email-masked], [email-masked]

Paul,
  Hope everything went well at SHARE.  Here's the latest Guide;
please put it on NIH-L as NIHGUIDE.031089.  Thanks.
     
Dottie,
  Here's the latest copy of the Guide.  Enjoy.
Ken
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Vol. 18, No. 8, March 10, 1989

                                   NOTICES

NOTICE OF MEETING - PROGRAMS FOR SUPPORT OF MINORITIES IN
BIOMEDICAL RESEARCH ......................................(84/138)........... 1
National Institutes of Health
Index:  NATIONAL INSTITUTES OF HEALTH

                     DATED ANNOUNCEMENTS (RFPs AND RFAs)

STIMULATING ELECTRODES BASED ON THIN FILM TECHNOLOGY (RFP) ..(144/180)....... 1
National Institute of Neurological Disorders and Stroke
Index:  NEUROLOGICAL DISORDERS, STROKE

IMPROVED METHODS FOR THE EARLY DIAGNOSIS OF HIV-INFECTION IN
NEONATES, INFANTS, AND CHILDREN (RFA) .......................(183/197)....... 2
National Institute of Child Health and Human Development
Index:  CHILD HEALTH, HUMAN DEVELOPMENT

NATIONAL COOPERATIVE DRUG DISCOVERY GROUPS FOR SPECIFIC  (200/337, 724/1778)
DISEASE-ORIENTED ANTICANCER TREATMENT (RFA 89-CA-01)
     
NATIONAL COOPERATIVE DRUG DISCOVERY GROUPS FOR GENERAL   (200/337, 1781/2838)
MECHANISM OF ACTION BASED ANTICANCER TREATMENT (RFA 89-CA-02)
     
NATIONAL COOPERATIVE ANTICANCER MODEL DEVELOPMENT GROUPS
(RFA 89-CA-03) ....................................(200/337, 2841/3916)....... 2
National Cancer Institute
Index:  CANCER

MOLECULAR GENETICS OF HYPERTENSION IN HUMANS AND ANIMALS (RFA) .............. 4
National Heart, Lung, and Blood Institute          (340/391, 3919/4478)
Index:  HEART, LUNG, BLOOD

STUDIES FOR THE DEVELOPMENT AND IMPROVEMENT OF ANALYTICAL
METHODOLOGY FOR ANIMAL DRUG RESIDUES IN TISSUES (RFA) .....(401/493)........ 5
Food and Drug Administration
Index:  FOOD AND DRUG ADMINISTRATION

                        ONGOING PROGRAM ANNOUNCEMENTS

RESEARCH TRAINING RELATED TO ALZHEIMER'S DISEASE AND RELATED
DISORDERS .................................................(499/550)......... 6
National Center for Nursing Research
Index:  NURSING RESEARCH

HAIR CELL REGENERATION ....................................(561/714)......... 7
National Institute on Deafness and Other Communication Disorders
Index:  DEAFNESS, COMMUNICATION DISORDERS

     

     

     

     
     
                                   NOTICES

NOTICE OF MEETING - PROGRAMS FOR SUPPORT OF MINORITIES IN BIOMEDICAL RESEARCH
     
P.T. 42, FF;  K.W. 0710030, 0720005
     
National Institutes of Health
     
Notice is hereby given that the National Institutes of Health (NIH) will hold
the second and third of a series of five regional public meetings to be
conducted under the auspices of the Office of the Director, NIH, on "Programs
for Support of Minorities in Biomedical Research."  The purpose of the
meetings is two-fold:
     
  1. to provide current information concerning the activities of the
     NIH by describing in broad terms existing programs offered by NIH;
     and
     
  2. to solicit through public testimony the views of biomedical
     researchers, university faculty and administrators, students,
     representatives of professional societies, and other interested
     parties regarding the nature and scope of programs to attract and
     support minorities in biomedical research.
     
The second meeting will be held on Thursday, April 20, 1989, from 8:30 a.m. to
4:30 p.m. in Building 31, Conference Room #4 at the National Institutes of
Health in Bethesda, Maryland.  The third meeting will be held at the Morehouse
School of Medicine in Atlanta, Georgia, on May 12.  Subsequent meetings will
be held in Phoenix, Arizona, on September 24 and Anchorage, Alaska, on October
9.
     
Following presentations by senior NIH staff, a panel comprised of NIH program
administrators will spend the remainder of the day receiving testimony from
public witnesses.  Each witness will be limited to a maximum of ten minutes.
Attendance and the number of presentations will be limited to the time and
space available.  Consequently, all individuals wishing to attend or to
present a statement at this public meeting should notify, in writing:
     
William H. Pitlick, Ph.D.
Executive Secretary
National Institutes of Health
Shannon Building, Room 250
Bethesda, Maryland  20892
     
Those planning to make a presentation at Bethesda, Maryland, should file a
one-page summary of their remarks with Dr. Pitlick by March 30, 1989; those
wishing to make a presentation at Atlanta should file a one-page summary by
April 14.  A copy of the full text should be submitted for the record at the
time of the meeting.  Additional information may be obtained by calling:
     
Ms. Loretta Beuchert
Research Training Office
Office of Extramural Research
National Institutes of Health
Shannon Building, Room 250
Bethesda, Maryland  20892
Telephone:  (301) 496-9743

                     DATED ANNOUNCEMENTS (RFPs AND RFAs)

STIMULATING ELECTRODES BASED ON THIN FILM TECHNOLOGY
     
RFP AVAILABLE:  NIH-NINDS-89-18
     
P.T. 34;  K.W. 0745047, 0705055, 0740050, 0706000
     
National Institute of Neurological Disorders and Stroke
     
The National Institute of Neurological Disorders and Stroke (NINDS) has a
requirement to design and fabricate multielectrode stimulating probes capable
of stimulating small populations of neurons within the central nervous system.
     
Offerors must have access to facilities for design and development of thin
film microcircuitry and experience in neurophysiology, biomedical engineering
implant materials and neural histopathology.
     
                   Vol. 18, No. 8, March 10, 1989 - Page 1
This is an announcement of an anticipated Request for Proposals.
RFP-NIH-NINDS-89-18 will be issued on or about March 10, 1989, with a closing
date of May 10, 1989, for receipt of proposals.
     
This requirement represents the recompetition of a current contract with the
University of Michigan and the incumbent is expected to reapply.  It is
anticipated that one contract award will be made.
     
To receive a copy of the RFP, please supply this office with two
self-addressed mailing labels.  All responsible sources may submit a proposal
which will be considered by the agency.  The RFP will be available upon
request to:
     
Contracting Officer
Contracts Management Branch
National Institute of Neurological
Disorders and Stroke, NIH
Federal Building, Room 901
7550 Wisconsin Avenue
Bethesda, Maryland  20892

IMPROVED METHODS FOR THE EARLY DIAGNOSIS OF HIV-INFECTION IN
NEONATES, INFANTS, AND CHILDREN
     
RFA:  89-HD-02
     
P.T. 34, AA;  K.W. 0715008, 0745020, 0403020, 0770005
     
National Institute of Child Health and Human Development
     
Revised Application Receipt Date:  March 22, 1989
     
The availability of this Request for Applications was announced in the NIH
Guide for Grants and Contracts on December 16, 1988, Vol. 17, No. 42.  This
notice is to inform potential applicants that the application receipt date has
been changed from March 8, 1989, to March 22, 1989.

NATIONAL COOPERATIVE DRUG DISCOVERY GROUPS FOR SPECIFIC
DISEASE-ORIENTED ANTICANCER TREATMENT (89-CA-01)
     
NATIONAL COOPERATIVE DRUG DISCOVERY GROUPS FOR GENERAL
MECHANISM OF ACTION BASED ANTICANCER TREATMENT (89-CA-02)
     
NATIONAL COOPERATIVE ANTICANCER MODEL DEVELOPMENT GROUPS (89-CA-03)
     
RFA AVAILABLE:  89-CA-01 89-CA-02 89-CA-03
     
P.T. 34;  K.W. 0715035, 0755020, 0740023, 1003006, 0760020, 0710030
     
National Cancer Institute
     
Letter of Intent Receipt Date:  April 28, 1989
Application Receipt Date:  June 9, 1989
     
In FY 1983 and 1984, the National Cancer Institute (NCI) requested
applications for National Cooperative Drug Discovery Groups (NCDDGs) whose
goals were the discovery of improved cancer treatment on the basis of novel
mechanisms of action.  In 1986, the program requested applications focused on
exploitation of specific and unique characteristics of lung and colon cancer.
The NCDDG approach to modern anticancer treatment discovery was broadened
further in August 1987, by RFAs inviting applications for the creation and
evaluation of both general mechanism of action based and specific
disease-oriented anticancer treatments as well as for the development of
innovative preclinical models for determining antitumor selectivity.  In
September 1988, NCI invited applications for the establishment of "National
Cooperative Natural Products Drug Discovery Groups" to stimulate the search
for new effective anticancer treatments from natural sources.
     
SUMMARY
     
The NCI announces the availability of three complementary RFAs for the
expansion of the NCDDG program for the discovery of new entities, strategies
or models for the treatment and cure of cancer.  Applications for the
disease-oriented NCDDGs should specify a type of cancer and provide a
rationale for its selection as a target (89-CA-01).  The cancer type to be
addressed is at the discretion of the applicant.  Research topics may include,
     
                   Vol. 18, No. 8, March 10, 1989 - Page 2
but are not limited to, new approaches to drug delivery, enhancement of immune
responses to unique antigens, or synthesis of new agents which inhibit a
target enzyme, oncogene expression, or the action of hormones and growth
factors on the proliferation of cancer cells.
     
Applications which propose to exploit differences between normal cells and
cancer cells without implications for a specific cancer type are requested in
the mechanism of action RFA (89-CA-02).
     
Model development may be oriented to a general mechanism likely to affect many
types of cancer or be tailored to a particular disease, such as breast cancer
(89-CA-03).  Areas of research are broad and may include a variety of in vitro
and in vivo models, such as biochemical, metastatic, immunological,
radiomodulator, differentiation, etc.  Applications which propose models
limited to diagnosis and without a rationale for new cancer treatments are not
invited.
     
These cooperative agreements are designed to assist leading investigators in
diverse scientific disciplines to interact as a unit, regardless of their
individual institutional affiliations or prior direct involvement in cancer
related research.  The purpose is to mobilize, with NCI support, the
outstanding talents required for exploitation of leads from fundamental
studies and their extrapolation to improved treatments.  Each NCDDG is
envisioned as being composed of a Principal Investigator and a number of
Program Leaders who will conduct interdependent and synergistic preclinical
laboratory programs to conceptualize, create and evaluate new therapies, or
new preclinical models (e.g., RFA 89-CA-03), in accordance with the
applicant's scientific goals.  An NCDDG may be made up of scientists in
academic, non-profit research, and commercial organizations.  Although the RFA
for Model Development allows a Group to consist of a single laboratory
program, multidisciplinary and/or multi-institutional programs are encouraged.
     
Awards will be made as cooperative agreements.  Assistance via cooperative
agreement differs from the research grant in that the cooperative agreement
funding mechanism anticipates substantial NCI staff participation during
performance.  However, the applying Group must define its objectives in accord
with its own interests and perceptions of approaches to the discovery of new
treatments or models.  The role of NCI as a member of the Group is described
in each RFA.  Essentially, the extramural NCI staff concerned with the
administration of grants and contracts will apply its experiences and
appropriate resources to facilitate and stimulate the realization of Group
objectives.  The active participation of industry is encouraged because it
will allow this segment of the scientific community to contribute its
considerable intellectual and material resources.
     
The Principal Investigator's (PI's) institution will be responsible for the
Group's application.  Awards will be made to the applicant institution on
behalf of the Group as a whole and not to individual laboratory programs
within the Group.  The PI's institution will provide a Central Operations
Office for the Group and will be responsible for the performance of the entire
Group and be accountable for the funds awarded.
     
NCI plans to make multiple awards for project periods of up to five years and
has set aside $2,000,000 for the initial year's funding of each RFA.  Special
programmatic consideration may be given to applications on lung and colon
cancer.  These RFAs are being released as a package based on the realization
that the search for better cancer treatments is a dynamic process dependent on
the availability of new agents and strategies coupled with the development and
use of more predictive models.  An individual investigator may respond to more
than one RFA provided there is no scientific or budgetary overlap or
proprietary conflict in funded activities.
     
The RFA label obtained from the NCI staff person named below or from grant
application Form PHS-398 (Revised 9/86) 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.
     
For further information and a copy of the RFAs for either the disease-oriented
(89-CA-01) or mechanism of action based (89-CA-02) National Cooperative Drug
Discovery Group Programs, contact:

     

     

                   Vol. 18, No. 8, March 10, 1989 - Page 3
George S. Johnson, Ph.D.
Developmental Therapeutics Program
Division of Cancer Treatment
National Cancer Institute
Executive Plaza North, Suite 832
Bethesda, Maryland  20892
Telephone:  (301) 496-8783
     
For further information and a copy of the RFA for National Cooperative
Anticancer Model Development Groups (89-CA-03), contact:
     
Mary K. Wolpert, Ph.D.
Developmental Therapeutics Program
Division of Cancer Treatment
Executive Plaza North, Suite 832
Bethesda, Maryland  20892
Telephone:  (301) 496-8783

MOLECULAR GENETICS OF HYPERTENSION IN HUMANS AND ANIMALS
     
RFA AVAILABLE:  89-HL-02-H
     
P.T. 34;  K.W. 1002058, 0715115, 1002008, 0710030
     
National Heart, Lung, and Blood Institute
     
Application Receipt Date:  December 7, 1989
     
The Hypertension and Kidney Diseases Branch of the Division of Heart and
Vascular Diseases, National Heart, Lung and Blood Institute (NHLBI), announces
the availability of a Request for Applications (RFA) on the above subject.
Copies of the RFA are currently available from staff of the NHLBI.
     
This program will support multidisciplinary research studies that combine
contemporary molecular biological methodologies with the genetics of human and
animal pedigrees in order to identify the location of the genes which play a
significant role in the pathogenesis of hypertension, to characterize these
genes and the mechanisms governing their expression, and to determine the gene
products and their modes of action.  It is expected that the research
applications will encompass a variety of approaches and require expertise from
a wide range of disciplines, including genetics, molecular biology, clinical
medicine, mathematics, and statistics.
     
A letter of intent is requested by September 11, l989, and the deadline for
receipt of applications is December 7, 1989.  The earliest award date for
successful applications will be in July 1990.  Awards will be made to foreign
institutions only for research of very unusual merit, need, and promise.
     
The Division of Heart and Vascular Diseases will sponsor an orientation
meeting in an effort to alert potential applicants to the critical issues and
important experimental strategies for an effective application.  This meeting
is tentatively planned for June 15, 1989, in Bethesda, Maryland.  Although
approximately $1.7 million in total costs for this program is included in the
financial plans for fiscal year 1990, award of grants pursuant to this RFA is
contingent upon receipt of funds for this purpose.  The specific amount to be
funded, however, will depend upon the merit and scope of the applications
received and the availability of funds.
     
Potential applicants should write or phone the individual listed below for the
full RFA document and for information about the orientation meeting:
     
Stephen C. Mockrin, Ph.D.
Deputy Chief
Hypertension and Kidney Diseases Branch
Division of Heart and Vascular Diseases
National Heart, Lung and Blood Institute, NIH
Federal Building, Room 4C10
7550 Wisconsin Avenue
Bethesda, Maryland  20892
Telephone:  (301) 496-1857

     

     

                   Vol. 18, No. 8, March 10, 1989 - Page 4
STUDIES FOR THE DEVELOPMENT AND IMPROVEMENT OF ANALYTICAL METHODOLOGY FOR
ANIMAL DRUG RESIDUES IN TISSUES
     
RFA AVAILABLE:  FDA-CVM-89-1
     
P.T. 34;  K.W. 1003008, 0710040, 0710100
     
Center for Veterinary Medicine
Food and Drug Administration
     
Application Receipt Date:  May 19, 1989
     
The Food and Drug Administration (FDA), Center for Veterinary Medicine (CVM)
is announcing the anticipated availability of approximately $100,000 for
fiscal year 1989 for cooperative agreements to support studies on the
development of analytical methodologies for residues of animal drugs in
tissues.  Appropriated FY 1989 funds are currently available for these
studies.  It is anticipated that one award will be made in FY 1989 and
additional awards, at the same level of funding, may be made from the
subsequent year appropriation, if Federal fiscal year funds become available.
The purpose of these agreements is to provide financial assistance to support
research on new or emerging techniques of analytical chemistry that have not
been applied to any great extent to the analysis of animal drug residues.
Support for this program may be for a period of up to 3 years.
     
BACKGROUND
     
The Code of Federal Regulations (21 CFR 556.1 Subpart B) contains prescribed
tolerances for residues of new animal drugs in red meat, poultry, and milk.
In order to ensure that the established tolerances are not exceeded, FDA
requires analytical methods that can be used to monitor and enforce compliance
with the approved conditions of safe use of drugs in animals intended for
human food.
     
Because the responsibility for providing analytical methods for specific
approved drugs in meat and milk rests primarily with a drug's sponsor, FDA is
interested in funding research on:  (1) multiresidue procedures, i.e., methods
of analysis that can be used to reliably quantitate and confirm the identity
of classes of drug residues; (2) methods for residues of unapproved drugs that
may be used illegally in food-producing animals; and (3) chemical-based
methods of analysis that can be used to confirm analytical results obtained
with presently available antimicrobial screening assays for several approved
classes of antibiotics used in food-producing animals.  Drug classes of
primary interest include beta-lactams, aminoglycosides and related
antibiotics, and nitrobenzamides and their reduced (amino) metabolites.  A
more complete list of drugs of interest is included in the RFA.
     
MECHANISM
     
Support for this program will be in the form of cooperative agreement awards.
These awards will be subject to all policies and requirements that govern the
research grant programs of the Public Health Service.
     
REVIEW PROCEDURES
     
Applications will undergo initial review by experts in the fields of
analytical chemistry, drug chemistry, and bioanalysis.  The experts will
review and evaluate each application based on its scientific merit.  The
applications will be subject to a second level review to evaluate them based
on their relevance to FDA's mission in the regulation of animal drugs.
     
Questions concerning the programmatic aspects of the program should be
addressed to:
     
Dr. David B. Batson
Center for Veterinary Medicine, HFV-500
Food and Drug Administration
5600 Fishers Lane
Rockville, Maryland  20857
Telephone:  (301) 443-6510

     

     

     
                   Vol. 18, No. 8, March 10, 1989 - Page 5
Request for copies of the RFA and application kits are available from:
     
Barbara C. Moy
State Contracts and Assistance Agreements Branch, HFA-520
Park Building, Room 3-20
Food and Drug Administration
5600 Fishers Lane
Rockville, Maryland  20857
Telephone:  (301) 443-6170
     
Applications must be submitted to the Food and Drug Administration using Form
398 (Rev. 9/86).  The outside of the mailing package and line 2 of the
application face page should be labeled "Response to RFA-FDA-CVM-89-1".

                        ONGOING PROGRAM ANNOUNCEMENTS

RESEARCH TRAINING RELATED TO ALZHEIMER'S DISEASE & RELATED DISORDERS
     
P.T. 44;  K.W. 0715180, 0720005, 0785130
     
National Center for Nursing Research
     
Application Receipt Dates:  Jan. 10, May 10, Sept. 10
     
The National Center for Nursing Research (NCNR) has an interest in research
training in areas related to patient care.  NCNR recognizes the importance of
supporting potential nurse researchers in their efforts to develop scientific
expertise in their chosen area of research.
     
One focus of patient care that is rapidly growing with the increased
percentage of elderly persons in the population is that of Alzheimer's Disease
and Related Disorders.  Although some research has been done in both the
prevention of this disease and strategies for care to both patients and their
families, further research is needed.  Nurse researchers who are well prepared
in various aspects of the disease and methodological approaches for research
related to Alzheimer's disease will be able to make a significant contribution
to interdisciplinary research efforts as well as to basic nursing research.
     
The NCNR is interested in supporting pre- and post-doctoral fellowships for
qualified nurses who are willing to undertake research training related to
Alzheimer's disease and related disorders.  Applicants for these fellowships
are encouraged to seek training sponsors and sites that have established
research programs with this focus.  An example of these sites is the
Alzheimer's Disease Research Centers currently funded by the National
Institute on Aging in locations throughout the United States.
     
ELIGIBILITY
     
Applicants must meet the criteria for the National Research Service Award for
Individual predoctoral and postdoctoral Nurse Fellowships.  Further
information on these criteria and currently funded Alzheimer's Disease
Research programs can be obtained by contacting:
     
Division of Extramural Programs
Extramural Programs
National Center for Nursing Research
National Institutes of Health
Building 31, Room 5B13
Bethesda, Maryland 20894
Telephone:  (301) 496-0526
     
This program is described in the Catalog of Federal Domestic Assistance No.
13.361, Nursing Research.  Awards are made under the authority of the PHS Act,
Sections 301, 483, 484, and 487 as amended by Public Law 99-158 and 97-219.
Awards are administered under PHS grant policies and Federal regulations 42
CFR Part 52 and 45 CFR Part 74.  This program is not subject to the
intergovernmental review requirements of Executive Order 12372 or to review by
a Health Systems Agency.

     

     

     
                   Vol. 18, No. 8, March 10, 1989 - Page 6
HAIR CELL REGENERATION
     
P.T. 34; K.W. 0705070, 0775005, 0760015, 0715050
     
National Institute on Deafness and Other Communication Disorders
     
The National Institute on Deafness and Other Communication Disorders (NIDCD)
encourages the submission of individual research grant applications related to
the regeneration of hair cells in the auditory and vestibular epithelia of
animals.
     
BACKGROUND
     
The regenerative capacity of the hair cell epithelia in the mechanoreceptive
lateral line organs of fish and amphibians has been known for decades.  The
hair cell epithelia of some of these vertebrates add new hair cells throughout
life and replace those lost or damaged.  The regenerative capacities of the
lateral line organs after injury have been extensively studied in the tail
stumps of amphibian larvae.  Differential interference optics and flourescent
microscopy methods have revealed that regenerated neuromasts develop from
cells in the surviving neuromasts of the tail stump.  Studies have suggested
that the progeny of supporting cells produce both hair cell and supporting
cells.  Differentiated hair cells have not been observed to divide or to
migrate.  Studies of embryonic development and postembryonic regeneration of
the lateral line system have provided approaches and hypotheses for the study
of regeneration of hair cells in the inner ear.
     
The sensory epithelia in the ears of some fish and amphibians continue to grow
throughout postembryonic life and may have the capacity for regeneration of
hair cells in response to injury.  All the cellular elements of these inner
ear epithelia continue to grow during postembryonic life.  Hair cells increase
in number, the supporting cells proliferate, and the nerve supply grows,
primarily through hypertrophy.  In certain anamniotes the location of
postembryonic proliferation of hair cells has been identified by incorporation
of DNA precursors; a set of ultrastructural characteristics has been developed
to identify newly differentiating hair cells.  The major proliferation site
for the hair cells is the outer edge of the sensory epithelia in at least some
ears.  Labeled supporting cells have been found throughout the epithelium.  As
in the lateral line organs, the supporting cells may play a key role in the
repair of damage to hair cell epithelia in the ear.
     
In contrast to the production of hair cells in fish and amphibians, the
production of hair cells in birds and mammals was thought to cease well before
the time of birth.  It is now known that hair cell regeneration in birds can
occur after either acoustic trauma or aminoglycoside ototoxicity.  For
example, recent studies have demonstrated that hair cells in the mature
cochlea of young chickens and adult quail regenerate after acoustic trauma.
Radioactive thymidine labeling was seen in both hair cells and supporting
cells at the lesioned site.  The precursors of the regenerated hair cells may
be supporting cells or other unidentified latent stem cells.
     
RESEARCH GOALS AND SCOPE
     
Understanding the mechanism of the development, death, and regeneration of
hair cells adds to the knowledge of the underlying mechanisms of hearing,
hearing loss, balance, and balance disorders.  Further, the study of hair cell
regeneration in nonmammalian species may provide rational approaches toward
stimulation of hair cell regeneration in mammals.  For example, if
regeneration of hair cells does not spontaneously occur after trauma in
mammals, it might still be possible to induce regeneration of hair cells with
a mitogenic growth factor.  It is hoped that some day controllable production
of hair cells in humans can be achieved and utilized to restore hearing and
balance function.
     
Areas of interest in the regeneration of hair cells include, but are not
limited to, these:
     
  o  Mechanism by which acoustic, ototoxic, or other kinds of trauma
     cause injury and death of hair cells and their elements, including
     the stereocilia.
     
  o  Mechanisms of activation and deactivation of regeneration.
     
  o  Source, migration, and differentiation of regenerated cells.
     
  o  Ultrastructural and biochemical characteristics that identify newly
     differentiated hair cells.

                   Vol. 18, No. 8, March 10, 1989 - Page 7
  o  Trophic and growth factors involved in regeneration.
     
  o  Gene probes and antibody markers of otic epithelial cells,
     particularly those expressed early in differentiation.
     
  o  Innervation of regenerated hair cells and restoration of
     physiological and behavioral function as a result of hair cell
     regeneration.
     
  o  Changes in cochlear mechanics and hair cell physiology as a
     function of regeneration.
     
  o  Regulation of synthesis and function of neurotransmitters in
     regenerated hair cells.
     
  o  Cellular metabolism at various locations in the hair cell epithelia
     before and after trauma.
     
  o  Role of the extracellular milieu, cell adhesion molecules, and
     intracellular and intercellular interactions in regeneration.
     
  o  Interactions of regeneration with other systemic conditions such as
     age and gender.
     
Applicants should focus their research on studies related to the mechanisms of
hair cell regeneration as opposed to purely descriptive studies.  Advances in
research related to the mechanisms of hair cell regeneration will require the
concepts and methods of many disciplines such as biophysics, biochemistry, and
cellular, molecular, and developmental biology.
     
Applicants are encouraged to use quantitative approaches and to develop and
use modern and refined methods, instrumentation, and procedures that may lead
to identification of the specific mechanisms of hair cell regeneration.  For
example, studies may include the development and use of isolated cells in
vitro, the development of permanent cell lines, and various methods of
cellular and molecular biology.
     
MECHANISM OF SUPPORT
     
Applications may be submitted for individual research project grants (R01) and
the First Independent Research Support and Transition (FIRST) Awards (R29).
     
APPLICATION SUBMISSION AND REVIEW PROCEDURES
     
Use the standard PHS-398 (revised 9/86) research grant application form as
instructed in the application kit.  The kits are available from the business
offices or the offices of sponsored research of most institutions or from the
Division of Research Grants, National Institutes of Health.  Type "HAIR CELL
REGENERATION" in Item #2 of the application face page and place a checkmark in
the "YES" box.  Use the mailing label in the application kit to mail the
original and six exact copies of the application to the Division of Research
Grants.
     
Applications should be submitted in accordance with the receipt dates
specified in the application kit.  The applications will be reviewed by a
Division of Research Grants study section and then by a National Advisory
Council according to the schedule specified in the application kit.  For more
information, call or write:
     
Jack Pearl, Ph.D.
National Institute on Deafness
and Other Communication Disorders
National Institutes of Health
Federal Building, Room lC-14
Bethesda, Maryland  20892
Telephone:  (301) 496-5061
     
This program is described in the Catalog of Federal Domestic Assistance No.
13.853, Clinical Basis Research, NINCDS or 13.854, Biological Basis Research.
Awards will be made under the authority of the Public Health Service Act,
Title IV, Section 301 (Public Law 78-410, as amended; 42 USC 241) and
administered under PHS grant policies and Federal Regulations 42 CFR Part 52
and 45 CFR Part 74.  This program is not subject to Health Systems Agency
Review.

     

                   Vol. 18, No. 8, March 10, 1989 - Page 8
                     FULL TEXT OF RFAs FOR ONLINE ACCESS

REQUEST FOR APPLICATIONS FOR COOPERATIVE AGREEMENT
     
89-CA-01
     
P.T. 34;  K.W. 0715035, 0755025, 0740020, 0755020, 0710030, 0785140
     
NATIONAL COOPERATIVE DRUG DISCOVERY  GROUPS  FOR  SPECIFIC
DISEASE-ORIENTED ANTICANCER TREATMENT
     
NATIONAL CANCER INSTITUTE (NCI)
     
Letter of Intent Date:  April 28, 1989
Application Receipt Date:  June 9, 1989
     
The NCI invites applications for the establishment of
National Cooperative Drug Discovery Groups for Specific
Disease-Oriented Anticancer Treatment.
     
There are no plans to reissue this Request for Applications
at any future time.
     
LETTER OF INTENT
     
Prospective applicants are asked to submit, by April 28,
1989, a short letter of intent that includes a descriptive
title of the proposed research, and if possible, names of
members of the proposed Group and their institutions.  The
letter of intent is requested in order to provide an
indication of the number and scope of applications to be
reviewed.  The letter of intent does not commit the sender
to submit an application, nor is it a requirement for
submission of an application.  Letters of intent should be
sent directly to:
     
George S. Johnson, Ph.D.
Executive Plaza North, Suite 832
Developmental Therapeutics Program
Division of Cancer Treatment
National Cancer Institute
Bethesda, MD 20892
Telephone No.:  (301)-496-8783
     
*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 USC 241, as amended by Public Law 99-158, 42
USC and 285(a), and by Sections 410 and 411, Small Business
Innovation Development Act, Public Law 97-219.  This program
is not subject to the intergovernmental review requirements
of Executive Order 12372 or Health Systems Agency review.
     
CONTENTS
     
SUMMARY
MECHANISM OF SUPPORT
DEFINITIONS
COMPOSITION
RESEARCH GOALS AND SCOPE
PATENT COVERAGE
TERMS OF AWARD
MINIMUM REQUIREMENTS FOR APPLICATION
REVIEW PROCEDURES AND CRITERIA
METHOD OF APPLYING
INQUIRIES
     
SUMMARY
     
Cancer claimed the lives of about 483,000 people in the
United States in 1987 and continues to be a leading cause of
death.  The 5-year patient survival rates associated with
some of the major cancer sites have been progressively
increasing as a result of improved diagnoses and the
initiation of earlier and more effective therapeutic
strategies; however, many types of cancer remain largely
refractory to treatment.  For example, despite extensive
research efforts, in 1987 approximately 136,000 people died
of lung cancer alone.  Thus there remains an urgent need for
better treatment of all forms of cancer especially those of
the solid tumor types.
     
The search for better cancer treatments is a dynamic process
dependent on the availability of new agents and strategies
coupled with the development and use of more predictive
models.  Recent advances in modern biomedical research
provide unprecedented opportunities for the discovery of
novel and highly sophisticated cancer treatments.
Exploitation of these exciting leads for development of more
effective cancer therapy requires the organization of
outstanding scientists from diverse scientific disciplines
such as biochemistry, pharmacology, molecular biology, and
chemistry into highly synergistic research teams regardless
of institutional affiliation.  To realize this objective as
well as to utilize facilitating resources of the NCI's drug
development program within these teams, the NCI established
the National Cooperative Drug Discovery Group (NCDDG)
program as a result of RFAs issued in July 1983 and August
1984 for the exploitation of mechanistically based
differences between normal and cancer cells.  October 1986
reissuances established Groups focused on exploitation of
specific and unique characteristics of lung and colorectal
cancers.  The NCDDG approach to modern drug discovery was
broadened further in August 1987 by RFAs inviting
applications for the creation and evaluation of both general
mechanism of action based and specific disease-oriented
anticancer treatments as well as for the development of
innovative preclinical models for determining antitumor
selectivity.  In September 1988 NCI invited applications for
the establishment of "National Cooperative Natural Products
Drug Discovery Groups" to stimulate the search for new
effective anticancer treatments from natural sources.
     
The present RFA is a reissuance for the purpose of funding
additional NCDDGs with the aim of discovering new therapies
for specific cancers based on unique characteristics of a
designated type of cancer; the cancer type to be addressed
is at the discretion of the applying Group.  The "RESEARCH
GOALS AND SCOPE" of this RFA require that an NCDDG has the
capacity within itself to conceive, create, and evaluate new
entities and strategies for the treatment and cure of a
specific type of cancer.  Subsequent studies required for
development of new treatments to clinical trial (e.g.,
formulation development, classical toxicology, etc.) are
beyond the scope of this RFA.  Within this context,
scientific approaches to realization of these goals are
broad and limited only by the creativity and ability of the
applying Group.  For example, programs essential for the
Group's objectives may include (but are not limited to)
research topics such as new approaches to deliver drugs to
the target area, immunological responses to unique antigens,
synthesis of new chemicals which inhibit a target enzyme in
cancer cells or oncogene expression in tumors, and action of
hormones or growth factors on cellular proliferation.
Applications based on general mechanisms of cancer treatment
without implications for a specific cancer are requested in
an accompanying RFA (89-CA-02).  A complementary RFA
(89-CA-03) requests the establishment of National
Cooperative Anticancer Model Development Groups to stimulate
and facilitate the discovery of models which will more
accurately predict clinical efficacy of a potential therapy.
     
MECHANISM OF SUPPORT
     
Awards will be made as COOPERATIVE AGREEMENTS.  Assistance
via Cooperative Agreement differs from the research grant in
that the Government component (NCI) awarding the Cooperative
Agreement anticipates substantial involvement during
performance of the award.  This partnership relationship
will facilitate technology transfer from Government owned
data bases and the use of appropriate contract resources to
enhance the efficiency and effectiveness of a Group's
efforts.  The nature of NCI staff participation is described
in this RFA under "TERMS OF AWARD."  There is no intent,
real or implied, for NCI staff to direct Group activities or
to limit the freedom of investigators.  A Group is expected
to consist of a single consortium of multidisciplinary
and/or multi-institutional Laboratory Programs from
academic, non-profit, or commercial organizations.  The
interaction of academic and non-profit research institutions
with commercial (including industrial) organizations and
Government will favor the efficient invention of new agents
or treatment strategies for cancer.  It should be mentioned
that all industrial companies are now eligible to apply for
grants and Cooperative Agreements.  (See NIH Guide for
Grants and Contracts, Volume 11, Number 5, April 23, 1982,
page 3.) The active participation of industry is encouraged
because it will allow this segment of the scientific
community to contribute its considerable intellectual and
material resources.  Further, the interaction of academic
and non-profit research institutions with industry and
Government will facilitate subsequent development and
marketing of new therapies, although these latter activities
are not within the scope of this RFA.
     
NCI plans to make multiple awards for project periods up to
five years and has set aside $2,000,000 total costs for the
initial year's funding.  Special programmatic consideration
may be given to applications on lung and colon cancer.
Although this program is provided for in the financial plans
of the National Cancer Institute, awards pursuant to this
RFA are contingent upon continuing availability of funds.
The earliest possible starting date for the initial annual
period will be April 1, 1990.  This RFA is a one-time
solicitation.  Generally, future unsolicited competing
renewal applications will compete as research project
applications with all other investigator-initiated
applications.  However, should the NCI determine that there
is a continuing program need, competing renewal applications
for Cooperative Agreements from the then current awardees
will be invited.
     
(When the applying institution is outside the United States,
awards must be limited to three years; this special
provision does not apply when the applying institution is
within the United States and the application contains
proposed Laboratory Programs in a foreign country.)
     
Each award will be made only to the Principal Investigator's
institution.  All Group activities will be coordinated
through a Central Operations Office located at the Principal
Investigator's institution.
     
Under the Cooperative Agreement, a partner relationship
between the recipient of the award and NCI exists in which
the Group is responsive to the requirements and conditions
set forth in the RFA.  Specifically, the Principal
Investigator defines the details for the project within the
guidelines of the RFA, retains primary responsibility for
the performance of the activity, and agrees to accept close
coordination, cooperation, and assistance of NCI extramural
staff in all aspects of scientific and technical management
of the project in accordance with the terms formally
negotiated and mutually agreed upon prior to the award.
     
All policies and requirements that govern the grant program
of the U.S. Public Health Service apply.
     
DEFINITIONS
     
COOPERATIVE AGREEMENT - An assistance mechanism in which
substantial NIH programmatic involvement with the recipient
during performance of the planned activity is anticipated.
     
NATIONAL COOPERATIVE DRUG DISCOVERY GROUP (NCDDG) - A number
of Laboratory Programs representing diverse scientific
disciplines and organizations which join together under
guidance and direction of a single Principal Investigator
and which function as a unit with a common goal:  the
conceptualization, invention, and evaluation of new entities
and strategies for treatment and cure of cancer.  In this
RFA the terms, National Cooperative Drug Discovery Group,
NCDDG, and "Group" are used synonymously.
     
CENTRAL OPERATIONS OFFICE - An administrative unit located
at the Principal Investigator's institution that coordinates
all Group activities and is legally and fiscally accountable
for the disposition of funds awarded.
     
DRUG - In the context of the NCDDG program, a term used
broadly to encompass synthetic agents, natural and
biological products, as well as novel therapeutic strategies
or inventions designed to treat and cure cancer.  Strategies
also encompass creative methods to maximize antitumor
selectivity.
     
PRINCIPAL INVESTIGATOR - The person who assembles the NCDDG,
submits the single application in response to this RFA and
who is responsible for performance of the Group as a whole
and of each Program Leader.  The Principal Investigator may
lead one of the Laboratory Programs of the Group, and in
addition, coordinate Group activities scientifically and
administratively.
     
PROGRAM LEADER - The Director of one of the scientific
Laboratory Programs of the NCDDG.
     
NCI PROGRAM DIRECTOR - A member of the NCI extramural staff
who provides leadership and guidance for the overall NCDDG
program within the NCI.
     
NCI COORDINATOR - A member of the NCI extramural staff,
appointed by the Program Director, who interacts
scientifically with the Group and facilitates the role of
NCI as partner in the NCDDG.  The Program Director also may
serve as the NCI Coordinator for a Group.
     
PATENTABLE INVENTION - Any new and useful process, machine,
manufacture or composition of matter, or any new and useful
improvements thereof, as defined under the U.S. Patent
Statute (35 USC 101).
     
COMPOSITION
     
The composition of an NCDDG is envisioned as follows:
     
A Principal Investigator.
     
Laboratory Programs, each headed by a Program Leader, in
diverse scientific disciplines, such as molecular biology,
cell biology, immunology, biochemistry, chemistry,
pharmacology, etc., that may be appropriate to realization
of Group objectives.
     
An NCI Coordinator designated from the NCI extramural staff
(to be appointed by the NCI Program Director after award).
     
The Principal Investigator, in addition to providing
scientific and administrative leadership, may contribute a
Laboratory Program.  Laboratory Program Leaders will be
directly responsible to the Principal Investigator.  The
formation of the Group, the application in response to this
RFA, the overall management of the Group, and the allocation
of funds to the various Laboratory Programs will be the
responsibility of the Principal Investigator and the
Principal Investigator's institution in accordance with PHS
policies.
     
The constituency of the Group and its Laboratory Programs
should depend on the talents required to accomplish its
scientific and technical objectives as perceived by the
Principal Investigator and Program Leaders.  The major
consideration in structuring an NCDDG should be the
mobilization of maximum intellectual strength and the
ability to carry out the proposed research.  If an NCDDG
includes more than one Laboratory Program, each should be
capable of contributing high quality, necessary, and
non-overlapping talents.
     
An individual scientist may be proposed as a Principal
Investigator or a Program Leader in more than one
application.  If so, the Principal Investigator must
demonstrate in the application that there is no scientific
or budgetary overlap or proprietary conflict with each
individual's proposed activities.  Likewise, individuals
currently receiving funding via contracts, grants, or
Cooperative Agreements (i.e., National Cooperative Drug
Discovery Groups [NCDDGs]) may be funded under this RFA as
long as there is no scientific or budgetary overlap or
proprietary conflict in funded activities.  Any Program
Leader who proposes to be a Group member must complete an
application form in detail even if no funds are requested.
An NIH intramural scientist may participate in an NCDDG as a
collaborator or consultant, but may not submit a formal
application as a Program Leader or receive funds from this
program.  The intramural scientist must provide a letter of
commitment and current curriculum vitae and obtain
appropriate NIH clearances prior to submission of the
application.  The Principal Investigator must incorporate
into the application, in the usual grant format, a full
description of the collaborative project, including
technical details and methodology.  The participation of an
intramural scientist is independent of and unrelated to the
role of the NCI Program Director and Coordinator as
described in "DEFINITIONS."
     
More than one member of an NCDDG might be derived from a
single institution.  However, the varied talents and
commitment required for effective drug discovery, as
described in this RFA, are not usually present in most
single institutions and it is anticipated that the Program
Leaders within a Group will be derived from several
institutions.
     
No minimum or maximum number of Laboratory Programs per
Group is stipulated.  However, the Principal Investigator
could experience difficulty in providing the desirable level
of guidance, and Program Leaders might communicate and
collaborate less efficiently if the Group were to contain
more than five or six Laboratory Programs.
     
In forming Groups, potential Principal Investigators should
remain cognizant of the need for communication, including
regular meetings of members.  While it is not a requirement
of this RFA, the formation of Groups on a geographically
regional basis may be advantageous.  Applicants from outside
the United States or applicants who propose Laboratory
Programs in foreign countries must specifically address how
effective communication will be maintained.
     
Under the provisions of assistance via Cooperative
Agreement, the NCI Coordinator will participate as a member
of the Group in a manner specified in "TERMS OF AWARD."  The
NCI Program Director will carry out the normal programmatic
and scientific responsibilities required for guidance of the
NCDDG program.  The NCI Program Director and Coordinator
will not conduct Laboratory Programs.
     
RESEARCH GOALS AND SCOPE
     
The goals of the NATIONAL COOPERATIVE DRUG DISCOVERY GROUP
program are:
     
The conceptualization, creation and preclinical evaluation
of new drugs and strategies designed to effectively treat
cancer.
     
The recommendation of presumptively curative treatment
entities and strategies for development to clinical trial.
     
The conduct of biological, biochemical, and pharmacological
studies that will permit the most enlightened subsequent
clinical evaluation supported by the most sophisticated
technology, and which may provide information leading to the
future discovery of even more effective treatments.
     
Applications for funding as an NCDDG should stress creative
approaches to the discovery of effective anticancer
therapies and should emphasize the following:
     
Objectives of the proposed NCDDG.
     
Research approaches to the realization of objectives and the
provision of comprehensive information (including citations)
in support of the rationale(s) for the proposed approaches.
     
Specific pertinence to cancer treatment.
     
The scientific and technical areas of expertise (Program
Leaders) required to attain Group objectives.
     
PATENT COVERAGE
     
Since the discovery of new and improved anticancer
treatments is the objective of this effort and active
involvement by industrial laboratories is facilitated by the
existence of adequate patent coverage, it is essential that
applicants provide plans to assure such coverage.  The
situation could be complicated since multiple institutions
are involved.  Each applicant Group, must therefore, 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. 98-6230 and 37 CFR Part 401.  Note that
non-profit organizations (including universities) and small
business firms retain the rights to any patent resulting
from government contracts, grants, or Cooperative
Agreements.  Your further attention is drawn, however, to a
Presidential memorandum of February 18, 1983 (Attachment 1),
which extends to all business concerns, regardless of size,
the first option to the ownership of rights to inventions as
provided in P.L. 96-517.  As a result of this memorandum,
the relationships among industrial organizations and other
participants are simplified, since all Group members can now
be full partners in the research and in any inventions
resulting therefrom.  The specific patenting arrangements
among the institutions may vary and could include joint
patent ownership, exclusive licensing arrangements, etc.
Applicants are encouraged to develop an arrangement that
best suits their own particular circumstances.
     
The proposed patent plan among the institutions comprising
the Group (including formal collaborators) must be included
as part of the application.  It should be inserted following
the overall Group budget section.  A formal patent agreement
signed and dated by the organizational official authorized
to enter into patent arrangements for each Group member and
member institution must be on file at the Division of
Extramural Activities, NCI prior to peer review.  (See
"MINIMUM REQUIREMENTS FOR APPLICATION".)
     
TERMS OF AWARD
     
Authorities and Responsibilities of Awardees
     
Assistance via Cooperative Agreement differs from that of
research grants in that, in addition to the normal
programmatic and administrative stewardship
responsibilities, the component awarding the Cooperative
Agreement anticipates substantial scientific involvement
during performance of the project.  However, the Group must
define its objectives and its approaches to attain these
objectives in accord with its own interests and perceptions
of novel and exploitable approaches to the discovery of
effective anticancer treatment and must develop the details
of the research design following the guidance given in this
RFA.  It is the primary responsibility of the Principal
Investigator to state clearly the objectives of the Group,
to direct the research stipulated in the proposal and to
ensure that the results obtained are published in a timely
manner.  It is anticipated that decisions in all activities
will be reached by consensus of the Group under the
leadership of the Principal Investigator and that the NCI
Coordinator will have the opportunity to offer input to this
process.
     
The Principal Investigator, Program Leaders, and NCI
Coordinator will meet periodically to review progress, plan
and design research activities, and establish priorities.
The frequency of meetings, but not fewer than two per year,
will be determined by the Principal Investigator who will be
responsible for scheduling the time and place (generally at
one of the performance sites) and for preparing concise
proceedings or minutes which will be delivered to the
members of the Group within 60 days of the meeting.  NCI
staff may not chair Group meetings.  A critical determinant
of Group success will be the degree of communication among
its members.  Therefore, additional informal meetings among
all participants as well as regular telephone and written
communication will be important.
     
In addition to the special reports and stipulations
described below, reporting requirements will be identical to
those currently in existence for awardees of program project
grants.
     
The principal end product of NCDDG activities will be the
discovery of new entities and strategies for development to
clinical trial.  Subsequent developmental work through
private resources is encouraged.  Alternatively, the Group
may recommend that development be sponsored by NCI.  In the
latter case, it will be necessary for the Principal
Investigator and NCI Coordinator to cooperate in the
analysis, summarization, preparation, and presentation of
data to the appropriate NCI staff.
     
NCI will retain the option to cross-file or independently
file an application for investigational clinical trial
(e.g., an Investigational New Drug Application [INDA] to the
United States Food and Drug Administration) of any invention
resulting from these NCI supported Cooperative Agreements.
Reports of data generated by the Group or any of its members
required for inclusion in INDAs and Clinical Brochures and
for cross-filing purposes will be submitted by the Principal
Investigator to the NCI Coordinator upon request.  Such
reports will include background information, methods,
results, and conclusions.  They will be subject to approval
and revision by NCI and may be augmented with test results
from other Government sponsored projects prior to submission
to the appropriate regulatory agency.
     
The Government, via the NCI Coordinator, will have access to
data generated under this Cooperative Agreement and may
periodically review the data.  However, the awardee will
retain rights to the data, and timely publication of major
findings by the Group members is encouraged.  Publication or
oral presentation of work done under this agreement will
require appropriate acknowledgement of NCI support.
Dissemination of information on synthetic or natural
substances supplied to the Group by NCI (e.g., for
comparative testing purposes, as reference material, etc.)
will require clearance by NCI to assure conformity to
existing confidentiality agreements with suppliers.
     
Nature of NCI Staff Participation
     
NCI shall participate as a member of the Group and will be
represented by a Coordinator.  The NCI Coordinator will be
selected from the scientific staff that manages extramural
programs but not from the NCI intramural staff.  During
performance of the award, NCI may provide appropriate
assistance, advice, and guidance by participating in the
design of activities; advising in the selection of sources
for resources, staff, etc.; coordinating or participating in
collection and/or analysis of data; advising in management
and technical performance; and participating in the
preparation of publications.  In all cases, the role of NCI
will be to assist and facilitate and not to direct
activities.
     
The NCI Coordinator, as well as any other Group member, may
assist in research planning; may suggest studies within the
scope of the Group's objectives and research activities; may
present to the Group experimental findings from published
sources or from contract projects in support of these
suggestions; may participate in the design of experiments
agreed to by the Group; and may participate in the analysis
of results.
     
Upon recommendation of the NCI Coordinator, NCI may utilize
its contract based resources in support of Group research
activities when such resources may be required on an
occasional basis.  The following is a list of some resources
that might be supplied if they become desirable during
performance, are not anticipated as a continuing need, and
are readily available:
     
Reference compounds for standardization of test systems, as
analytical standards, and for related purposes.
     
Needed resources such as test materials and information that
may not otherwise be available to the Group.
     
Data from testing conducted in resource contract
laboratories.
     
Laboratory testing capacity, whenever appropriate and
possible, in the current contract based preclinical
therapy-related laboratory testing program.  The Group is
expected to provide sufficient test material for such
testing.
     
Searches of computer files of materials, chemical structures
and biological activity, if requests for such searches are
sufficiently focused to avoid excessive costs.  Information
given to an NCDDG will be restricted by any standard
confidentiality agreements between the Government and
suppliers of test materials to the Government.
     
Experimental animals and cultured cells, if available, to
Groups whose main research activities do not require these
materials on a regular basis.  Groups whose experimental
approach involves studies that require animals on a regular
basis must budget for costs in their application.
     
Computer processing and statistical evaluations if costs are
not excessive.
     
These "TERMS OF AWARD" require that NCI staff approve the
following:  changes in the Principal Investigator or Program
Leaders; reports intended for inclusion in INDAs and
Clinical Brochures; redistribution, outside the NCDDG, of
biological and chemical materials received from the
Government; and dissemination of research findings resulting
from the use of such materials.  Disagreements arising
pursuant to these approvals will be arbitrated by a panel
composed of one Group designee, one NCI designee, and a
third designee with expertise in the relevant area chosen by
the other two.  These special arbitration procedures in no
way affect the awardee's right 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.
     
The special "TERMS OF AWARD" described in this section are
in addition to, and not in lieu of, otherwise applicable OMB
administrative Regulations at 45 CFR Part 74, and other HHS,
PHS, and NIH grant administration policy statements.
     
MINIMUM REQUIREMENTS FOR APPLICATION
     
Applications seeking funding as a NATIONAL COOPERATIVE DRUG
DISCOVERY GROUP must meet the following requirements:
     
Name a SINGLE Principal Investigator who will be responsible
for the application, for Group research activities, and for
the dispersal of funds for the support of Group activities.
     
Identify the Principal Investigator's organization
(institution) that will provide the Central Operations
Office and assume legal and financial responsibility and
accountability for the use and disposition of funds awarded
on the basis of this RFA; show availability of personnel and
facilities capable of performing and supporting the
administrative functions of this NCDDG.
     
Provide a description of the Group's plan for assuring
adequate patent coverage of new inventions that may issue as
a result of Government funding of the proposed work.
     
Note:  A formal statement of Patent Agreement among all
Group members and their institutions as well as a detailed
description of procedures to be followed for resolution of
legal problems which may develop, signed and dated by the
organizational official authorized to enter into patent
arrangements for each Group member and member institution is
preferred with the application.  If this signed agreement is
not included in the application, it must be submitted to the
Executive Secretary prior to peer review.
     
Provide from the Principal Investigator and from each
Program Leader a signed statement of acceptance of the
participation of NCI staff during performance of project as
outlined under "TERMS OF AWARD."
     
Provide a clear, concise plan in narrative and diagrammatic
form that depicts the interrelationships among the members
of the Group and the contribution of each to fulfillment of
Group objectives; provide an organizational chart of the
Group showing the name, organization, and scientific
discipline of the Principal Investigator and Program
Leaders; provide an organizational chart for each Laboratory
Program within the Group showing relationships among the key
personnel.
     
Provide a plan to assure the maintenance of close
collaborative and effective communication among members of
the Group which will include letters of commitment to this
plan by all Program Leaders.
     
Demonstrate that the Principal Investigator and the Program
Leaders possess the outstanding scientific skills and
leadership qualities to conduct the proposed research
successfully; include relevant research programs,
experience, unique competencies, and pertinent publications.
     
Demonstrate the competence of the Principal Investigator to
manage comprehensive research projects and to coordinate and
integrate research activities of diverse Laboratory
Programs.
     
Demonstrate that each component Laboratory Program is
required for the attainment of the Group's objectives and
that each has available the professional and technical
personnel to permit efficient and successful conduct of the
proposed research; show that total personnel of the Group
are sufficient in quality and quantity to assure successful
conduct of the proposed research.
     
Note:  Other activities which are essential to maintaining
or achieving the objectives of the stated research programs
(e.g., routine assays, scale-up of materials, shared
equipment, shared services, animal maintenance, etc.) should
be included under the budget for core resources.
Anticipated payments to third parties for such activities
should be shown as subcontracts under the core budget.
     
Demonstrate for all key personnel the time available for
this project and show for all key professional personnel (1)
title, identifying number, percentage of effort devoted to
the project, direct costs, and project period of all awarded
and pending grants, Cooperative Agreements, contracts, and
industrial commitments regardless of source of funding; (2)
identify and explain areas of potential scientific and/or
budgetary overlap with active and pending grants, contracts,
and Cooperative Agreements and what support would be
relinquished if this Cooperative Agreement award is made.
     
Demonstrate that each component Laboratory Program and the
Group as a whole have available the facilities (including
appropriate biohazard facilities) required for conduct of
the proposed research.  Funds will not be provided for
alteration or renovation of facilities under this
Cooperative Agreement.
     
REVIEW PROCEDURES AND CRITERIA
     
Review Procedure
     
Upon receipt, applications will be reviewed by the Division
of Research Grants for completeness.  Incomplete
applications will be returned to the applicant without
further consideration.  Evaluation for responsiveness to
this 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 which are judged non-responsive will be
administratively withdrawn, and the proposed Principal
Investigator and institutional business official will be
notified.  Should an application be judged non-responsive to
this RFA, any of its constituent Laboratory Programs may be
submitted as an investigator initiated regular research
grant (R01) at the next receipt date.  Alternatively, the
consortium of Laboratory Programs could seek funding as a
program project grant (P01).  In either event, the
application would require modification in accordance with
either the R01 or P01 guidelines.  The new application would
not be considered an application for a Cooperative
Agreement, nor would it be considered a response to an RFA.
Questions concerning the relevance of proposed research to
the RFA should be directed to program staff as described in
"INQUIRIES."
     
In cases where the number of applications is large compared
to the number of awards to be made, the NIH may conduct a
preliminary scientific peer review to eliminate those which
are clearly not competitive for award.  The NIH will
withdraw from further competition those applications judged
to be noncompetitive and notify the Principal Investigator
and institutional business official.
     
Those applications judged to be both competitive and
responsive will be further evaluated, using the review
criteria shown 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 Program.
     
Review Criteria
     
Extent of relevance of applicant's (Group) objectives to the
discovery of NOVEL approaches for developing new anticancer
treatments.
     
Scientific merit and originality of proposed research.
     
Technical merit of proposed methods for producing or
obtaining test materials and for their evaluation.
     
Adequacy of the scientific disciplines and specific
competencies represented by the Principal Investigator and
Program Leaders; research experience, competence,
commitment, and time availability of Principal Investigator,
Program Leaders, and other key personnel.
     
Administrative experience and competence of Principal
Investigator in the development, implementation, and
management of comprehensive research programs.
     
Adequacy of plans for effective intra-Group communication
and for assuring Group cohesiveness.
     
Evidence of approval and commitment of institutions
represented by Group members to Group goals.
     
Evidence of availability and competence of the applying
institution to serve as the Central Operations Office for
the Group.
     
Commitment to accept NCI assistance in accordance with the
guidelines outlined under "TERMS OF AWARD."
     
Adequacy of existing physical facilities and resources of
the Principal Investigator and Program Leaders.
     
The review group will recommend an appropriate budget and
period of support for each approved application.
     
METHOD OF APPLYING
     
Receipt Date
     
The deadline for receipt of applications is June 9, 1989.
APPLICATIONS RECEIVED AFTER THIS DATE WILL BE CONSIDERED AS
NOT RESPONSIVE TO THIS RFA AND WILL BE RETURNED WITHOUT
REVIEW.  Please note, the Division of Research Grants will
not accept any application to this "Request for
Applications" that is the same as one currently being
considered by any other review group or awarding unit of the
National Institutes of Health.
     
General
     
The regular research grant application Form PHS-398 (Rev.
9/86) must be used in applying.  These forms are available
at most institutional business offices or from the Division
of Research Grants, National Institutes of Health, 9000
Rockville Pike, Bethesda, Maryland 20892.  One original and
six (6) copies are requested.
     
Submit a signed, typewritten original of the application,
including a single Checklist, and four (4) signed, exact
single sided photocopies in one package to:
     
The Division of Research Grants
National  Institutes  of  Health
Westwood Building, Room 240
Bethesda, Maryland 20892**
     
Send the remaining two (2) copies of your application
directly to:
     
Mr. Hernon Fox
Referral Officer
National Cancer Institute
Westwood Building, Room 848
Bethesda, MD  20892
Telephone: (301) 496-3428
     
To expedite the review of your application, and to assure
its identification with this RFA:
     
The application form should have "NCI National Cooperative
Drug Discovery Groups - Disease-Oriented (RFA 89-CA-01)" on
line 2 of the face page of the application form;
personalized titles more fitting for your application should
be listed on line 1 and not on line 2.
     
The RFA label available in the 9/86 revision of the
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.
     
Organization of Application and Suggested Modifications of
Form PHS-398 (Revised, 9/86)
     
This RFA requires the submission of a single application for
the proposed NATIONAL COOPERATIVE DRUG DISCOVERY GROUP.
     
Because of the multi-institutional nature of an NCDDG and
the special requirements in this RFA, additional suggestions
regarding format and some modifications seem desirable to
provide a comprehensive yet readily reviewable application.
     
Each application should have an INTRODUCTION SECTION
(described below) and Sections for each of the scientific
Laboratory Programs including the LABORATORY PROGRAM of the
proposed Principal Investigator and that these be identified
as "Laboratory Programs" and be numbered consecutively.  Use
Form PHS-398 for each LABORATORY PROGRAM but omit the face
page for the individual program.  A single face page should
apply to the entire application.  Insert the INTRODUCTION
after the Table of Contents.  It is suggested that the title
"Program Leader" (Retain the title "Principal Investigator"
for the section describing the Laboratory Program of the
Principal Investigator) be substituted for "Principal
Investigator/Program Director" and that the "Description"
(grant application form page 2) for each of the Laboratory
Programs, in addition to describing the work proposed,
provide a statement of relevance to the overall objectives
of the proposed NCDDG.  A single checklist should be
provided for the overall application.  Do not include a
checklist for each Laboratory Program.  The 20 page
limitation stipulated in the PHS-398 kit applies to each of
the individual Laboratory Programs.  The overall
Introductory Section should also be limited to 20 pages.
     
Sections pertaining to Laboratory Programs should provide a
Detailed Budget for the First Twelve Month Budget Period
INCLUDING APPLICABLE INDIRECT COSTS FOR CONSORTIUM
INSTITUTIONS and a Budget for the Entire Proposed Project
Period.  JUSTIFY BUDGET REQUESTS according to the guidelines
in Form PHS-398.
     
Often the various research tasks necessary to reach the
Group's goals may need to be phased in, at least in part, in
sequential fashion.  In such cases, the budgets for the
individual Laboratory Programs should, logically, reflect an
appropriate change in relative emphasis among tasks until an
operational steady state situation is attained.
Justification for phase-in budgets also should be provided.
     
The package containing the proposed research plan of the
Principal Investigator and each Program Leader should be
preceded by an INTRODUCTORY SECTION bearing the title
NATIONAL COOPERATIVE DRUG DISCOVERY GROUP - DISEASE-ORIENTED
and the phrase, "Prepared in Response to RFA No. 89-CA-01."
Form PHS-398 should be used for this INTRODUCTORY SECTION
and should describe the proposed NCDDG as a whole with
respect to goals, objectives, and overall research plan.  In
this Introductory Section, list the Program Leaders as "Key
Personnel Engaged on Project."  Other key personnel should
be listed in the proposed research plan for each individual
Laboratory Program.  It is important to discuss any prior
collaborative efforts among investigators in the Group as
well as advantages expected from the Group effort, e.g., how
the projects are mutually reinforcing, how collectively they
will further the goals of the proposed research, etc.
     
In the Introductory Section, budget sheets should reflect
the consolidated TOTAL DIRECT COSTS of the entire proposed
NCDDG.  This should include the direct and indirect costs at
cooperating institutions.  The Introductory Section should
also provide, from the applying institution, a Detailed
Budget for the First Twelve Month Period and a Budget for
the Entire Proposed Project Period for Direct Costs for each
of the following:
     
The Principal Investigator's Laboratory Program.
     
Management and coordination of Group activities.
     
Maintenance of the Central Operations Office.
     
Inasmuch as the Principal Investigator may also function as
a Program Leader for his/her Laboratory Program, parts of
Form PHS-398 that duplicate information provided in the
section describing the Principal Investigator's laboratory
work need not be included in the Introductory Section.  The
Introductory Section should, however, contain any additional
information about the proposed Principal Investigator or
his/her institution as evidence of capability to carry out
the scientific and administrative duties required in this
RFA and the functions of the Central Operations Office.
     
In addition, Form PHS-398 constituting the Introductory
Section must include the following elements to be considered
responsive to minimum requirements (see "MINIMUM
REQUIREMENTS FOR APPLICATION" of this RFA).
     
The name of a single Principal Investigator in accordance
with "MINIMUM REQUIREMENTS FOR APPLICATION."
     
The name of the Principal Investigator's organization that
will provide and operate the Central Operations Office in
accordance with "MINIMUM REQUIREMENTS FOR APPLICATION."
     
A statement assuring adequate patent coverage of new
inventions that may issue as a result of Government funding
in accordance with "MINIMUM REQUIREMENTS FOR APPLICATION"
and as described in "PATENT COVERAGE."
     
A statement of acceptance of the provisions of
"TERMS OF AWARD" regarding NCI staff participation in
accordance with "MINIMUM REQUIREMENTS FOR APPLICATION."
     
A description of the inter-relationships among members of
the Group and organizational charts in accordance with
"MINIMUM REQUIREMENTS FOR APPLICATION."
     
A plan to assure maintenance of close collaboration and
effective communication among members of the Group in
accordance with "MINIMUM REQUIREMENTS FOR APPLICATION."
     
The application will be reviewed as a whole as well as
project by project; therefore, prepare a detailed Table of
Contents that will enable reviewers to find specific
information readily and number all pages consecutively after
the face page, which is page 1.  Complete all items on the
face page of the application (only one per application) as
in a regular research grant proposal.  Identify projects by
number, title and Program Leader.  Identify cores by letter,
title and Program Leader.
     
If internal or external advisory groups will be used, list
their membership and describe their roles.  Include a signed
letter of agreement from each advisor.
     
List in a separate table all consultants, both paid and
unpaid.  Include a signed letter of agreement from each
consultant.
     
INQUIRIES
     
Inquires may be addressed to:
     
George S. Johnson, Ph.D.
Executive Plaza North, Suite 832
Developmental Therapeutics Program
Division of Cancer Treatment
National Cancer Institute
Bethesda, Maryland 20892
Telephone:  (301)-496-8783
     
RFA - National Cooperative Drug Discovery Groups for
Specific Disease-Oriented Anticancer Treatment
     
ATTACHMENT 1
     
A Presidential memorandum of February 18, 1983 directed a
revision in policy respecting allocation of rights in
inventions that are products of Government-funded research
and development.  The memorandum directs the adoption and
implementation of the same or substantially the same
policies for all federally-funded R&D contracts, grants, or
cooperative agreements as those set forth in PL-96-517 (H.R.
6933, "Patent and Trademark Laws, Amendment", December 12,
1980) for small businesses and non-profit organizations.
Under the new policy, the Government would retain "march-in"
rights and require licensing if the inventing organization
fails to pursue development of the invention.
     
The text of the President's memorandum:
     
[Text] To the extent permitted by law, agency policy with
respect to the disposition of any invention made in the
performance of a federally-funded research and development
contract, grant or cooperative agreement award shall be the
same or substantially the same as applied to small business
firms and nonprofit organizations under Chapter 38 (now
Chapter 18) of Title 35 of the United States Code.
     
In awards not subject to Chapter 38 (now Chapter 18) of
Title 35 of the United States Code, any of the rights of the
Government or obligations of the performer described in 35
U.S.C. 202-204 may be waived or omitted if the agency
determines (1) that the interests of the United States and
the general public will be better served thereby as, for
example, where this is necessary to obtain a uniquely or
highly qualified performer, or (2) that the award involves
cosponsored, cost sharing, or joint venture research and
development, and the performer, cosponsor or joint venturer
is making substantial contribution of funds, facilities or
equipment to the work performed under the award.
     
In addition, agencies should protect the confidentiality of
invention disclosure, patent applications and utilization
reports required in performance or in consequence of awards
to the extent permitted by 35 U.S.C. 205 or other applicable
laws.  [End Text]
     
On the basis of the President's memorandum the General
Services Administration has issued a Temporary Regulation
which prescribes revised guidance regarding the rights of
the Government and recipients of federally-funded R&D
contracts, grants, and cooperative agreements.  (Federal
Register, Vol. 48, No. 74, Friday, April 15, 1983, GSA, 41
CFR Ch.1.  FPR Temporary Regulation 69.) The intended effect
is to extend in principle the current implementation of
Public Law 96-517 beyond small businesses and non-profit
organizations.

REQUEST FOR APPLICATIONS FOR COOPERATIVE AGREEMENT
     
P.T. 34;  K.W. 0715035, 0755025, 0740020, 0755020, 0710030, 0785140
     
89-CA-02
     
NATIONAL COOPERATIVE DRUG  DISCOVERY  GROUPS  FOR  GENERAL
MECHANISM OF ACTION BASED ANTICANCER TREATMENT
     
NATIONAL CANCER INSTITUTE (NCI)
     
Letter of Intent Date : April 28, 1989
Application Receipt Date:  June 9, 1989
     
The NCI invites applications for the establishment of
National Cooperative Drug Discovery Groups for General
Mechanism of Action Based Anticancer Treatment.
     
There are no plans to reissue this Request for Applications
at any future time.
     
LETTER OF INTENT
     
Prospective applicants are asked to submit, by April 28,
1989, a short letter of intent that includes a descriptive
title of the proposed research, and if possible, names of
members of the proposed Group and their institutions.  The
letter of intent is requested in order to provide an
indication of the number and scope of applications to be
reviewed.  The letter of intent does not commit the sender
to submit an application, nor is it a requirement for
submission of an application.  Letters of intent should be
sent directly to:
     
George S. Johnson, Ph.D.
Executive Plaza North, Suite 832
Developmental Therapeutics Program
Division of Treatment
National Cancer Institute
Bethesda, MD 20892
Telephone No.:  (301)-496-8783
     
*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, Section 301, Public Law 78-410,
as amended, 42 USC 241, as amended by Public Law 99-158, 42
USC and 285(a), and by Sections 410 and 411, Small Business
Innovation Development Act, Public Law 97-219.  This program
is not subject to the intergovernmental review requirements
of Executive Order 12372 or Health Systems Agency review.
     
CONTENTS
     
SUMMARY
MECHANISM OF SUPPORT
DEFINITIONS
COMPOSITION
RESEARCH GOALS AND SCOPE
PATENT COVERAGE
TERMS OF AWARD
MINIMUM REQUIREMENTS FOR APPLICATION
REVIEW PROCEDURES AND CRITERIA
METHOD OF APPLYING
INQUIRIES
     
SUMMARY
     
Cancer claimed the lives of about 483,000 people in the
United States in 1987 and continues to be a leading cause of
death.  The 5-year patient survival rates associated with
some of the major cancer sites have been progressively
increasing as a result of improved diagnoses and the
initiation of earlier and more effective therapeutic
strategies; however, many types of cancer remain largely
refractory to treatment.  For example, despite extensive
research efforts, in 1987 approximately 136,000 people died
of lung cancer alone.  Thus there remains an urgent need for
better treatment of all forms of cancer especially those of
the solid tumor types.
     
The search for better cancer treatments is a dynamic process
dependent on the availability of new agents and strategies
coupled with the development and use of more predictive
models.  Recent advances in modern biomedical research
provide unprecedented opportunities for the discovery of
novel and highly sophisticated cancer treatments.
Exploitation of these exciting leads for development of more
effective cancer therapy requires the organization of
outstanding scientists from diverse scientific disciplines
such as biochemistry, pharmacology, molecular biology, and
chemistry into highly synergistic research teams regardless
of institutional affiliation.  To realize this objective as
well as to utilize facilitating resources of the NCI's drug
development program within these teams, the NCI established
the National Cooperative Drug Discovery Group (NCDDG)
program as a result of RFAs issued in July 1983 and August
1984 for the exploitation of mechanistically based
differences between normal and cancer cells.  October 1986
reissuances established Groups focused on exploitation of
specific and unique characteristics of lung and colorectal
cancers.  The NCDDG approach to modern drug discovery was
broadened further in August 1987 by RFAs inviting
applications for the creation and evaluation of both general
mechanism of action based and specific disease-oriented
anticancer treatments as well as for the development of
innovative preclinical models for determining antitumor
selectivity.  In September 1988 NCI invited applications for
the establishment of "National Cooperative Natural Products
Drug Discovery Groups" to stimulate the search for new
effective anticancer treatments from natural sources.
     
The present RFA is a reissuance for the purpose of funding
additional NCDDGs with the aim of discovering new therapies
for cancer based on exploitation of general mechanistic
differences between normal cells and cancer cells without
regard to potential differences between individual cancer
types.  The "RESEARCH GOALS AND SCOPE" of this RFA require
that an NCDDG has the capacity within itself to conceive,
create, and evaluate new entities and strategies for the
treatment and cure of cancer.  Subsequent studies required
for development of new treatments to clinical trial (e.g.,
formulation development, classical toxicology, etc.) are
beyond the scope of this RFA.  Within this context,
scientific approaches to realization of these goals are
broad and limited only by the creativity and ability of the
applying Group.  For example, programs essential for the
Group's objectives may include (but are not limited to)
research topics such as new approaches to deliver drugs to
the target area, immunological responses to unique antigens,
synthesis of new chemicals which inhibit a target enzyme in
cancer cells or oncogene expression in tumors, and action of
hormones or growth factors on cellular proliferation.
Applications based on development of treatments for specific
cancer types based on unique characteristics of these tumors
are requested in an accompanying RFA (89-CA-01).  A
complementary RFA (89-CA-03) requests the establishment of
National Cooperative Anticancer Model Development Groups to
stimulate and facilitate the discovery of models which will
more accurately predict clinical efficacy of a potential
therapy.
     
MECHANISM OF SUPPORT
     
Awards will be made as COOPERATIVE AGREEMENTS.  Assistance
via Cooperative Agreement differs from the research grant in
that the Government component (NCI) awarding the Cooperative
Agreement anticipates substantial involvement during
performance of the award.  This partnership relationship
will facilitate technology transfer from Government owned
data bases and the use of appropriate contract resources to
enhance the efficiency and effectiveness of a Group's
efforts.  The nature of NCI staff participation is described
in this RFA under "TERMS OF AWARD."  There is no intent,
real or implied, for NCI staff to direct Group activities or
to limit the freedom of investigators.  A Group is expected
to consist of a single consortium of multidisciplinary
and/or multi-institutional Laboratory Programs from
academic, non-profit, or commercial organizations.  The
interaction of academic and non-profit research institutions
with commercial (including industrial) organizations and
Government will favor the efficient invention of new agents
or treatment strategies for cancer.  It should be mentioned
that all industrial companies are now eligible to apply for
grants and Cooperative Agreements.  (See NIH Guide for
Grants and Contracts, Volume 11, Number 5, April 23, 1982,
page 3.) The active participation of industry is encouraged
because it will allow this segment of the scientific
community to contribute its considerable intellectual and
material resources.  Further, the interaction of academic
and non-profit research institutions with industry and
Government will facilitate subsequent development and
marketing of new therapies, although these latter activities
are not within the scope of this RFA.
     
NCI plans to make multiple awards for project periods up to
five years and has set aside $2,000,000 total costs for the
initial year's funding.  Although this program is provided
for in the financial plans of the National Cancer Institute,
awards pursuant to this RFA are contingent upon continuing
availability of funds.  The earliest possible starting date
for the initial annual period will be April 1, 1990.  This
RFA is a one-time solicitation.  Generally, future
unsolicited competing renewal applications will compete as
research project applications with all other
investigator-initiated applications.  However, should the
NCI determine that there is a continuing program need,
competing renewal applications for Cooperative Agreements
from the then current awardees will be invited.
     
[When the applying institution is outside the United States,
awards must be limited to three years; this special
provision does not apply when the applying institution is
within the United States and the application contains
proposed Laboratory Programs in a foreign country.]
     
Each award will be made only to the Principal Investigator's
institution.  All Group activities will be coordinated
through a Central Operations Office located at the Principal
Investigator's institution.
     
Under the Cooperative Agreement, a partner relationship
between the recipient of the award and NCI exists in which
the Group is responsive to the requirements and conditions
set forth in the RFA.  Specifically, the Principal
Investigator defines the details for the project within the
guidelines of the RFA, retains primary responsibility for
the performance of the activity, and agrees to accept close
coordination, cooperation, and assistance of NCI extramural
staff in all aspects of scientific and technical management
of the project in accordance with the terms formally
negotiated and mutually agreed upon prior to the award.
     
All policies and requirements that govern the grant program
of the U.S. Public Health Service apply.
     
DEFINITIONS
     
COOPERATIVE AGREEMENT - An assistance mechanism in which
substantial NIH programmatic involvement with the recipient
during performance of the planned activity is anticipated.
     
NATIONAL COOPERATIVE DRUG DISCOVERY GROUP (NCDDG) - A number
of Laboratory Programs representing diverse scientific
disciplines and organizations which join together under
guidance and direction of a single Principal Investigator
and which function as a unit with a common goal:  the
conceptualization, invention, and evaluation of new entities
and strategies for treatment and cure of cancer.  In this
RFA the terms, National Cooperative Drug Discovery Group,
NCDDG, and "Group" are used synonymously.
     
CENTRAL OPERATIONS OFFICE - An administrative unit located
at the Principal Investigator's institution that coordinates
all Group activities and is legally and fiscally accountable
for the disposition of funds awarded.
     
DRUG - In the context of the NCDDG program, a term used
broadly to encompass synthetic agents, natural and
biological products, as well as novel therapeutic strategies
or inventions designed to treat and cure cancer.  Strategies
also encompass creative methods to maximize antitumor
selectivity.
     
PRINCIPAL INVESTIGATOR - The person who assembles the NCDDG,
submits the single application in response to this RFA and
who is responsible for performance of the Group as a whole
and of each Program Leader.  The Principal Investigator may
lead one of the Laboratory Programs of the Group, and in
addition, coordinate Group activities scientifically and
administratively.
     
PROGRAM LEADER - The Director of one of the scientific
Laboratory Programs of the NCDDG.
     
NCI PROGRAM DIRECTOR - A member of the NCI extramural staff
who provides leadership and guidance for the overall NCDDG
program within the NCI.
     
NCI COORDINATOR - A member of the NCI extramural staff,
appointed by the Program Director, who interacts
scientifically with the Group and facilitates the role of
NCI as partner in the NCDDG.  The Program Director also may
serve as the NCI Coordinator for the Group.
     
PATENTABLE INVENTION - Any new and useful process, machine,
manufacture or composition of matter, or any new and useful
improvements thereof, as defined under the U.S. Patent
Statute (35 USC 101).
     
COMPOSITION
     
The composition of an NCDDG is envisioned as follows:
     
A Principal Investigator.
     
Laboratory Programs, each headed by a Program Leader, in
diverse scientific disciplines, such as molecular biology,
cell biology, immunology, biochemistry, chemistry,
pharmacology, etc., that may be appropriate to realization
of Group objectives.
     
An NCI coordinator designated from the NCI extramural staff
(to be appointed by the NCI Program Director after award).
     
The Principal Investigator, in addition to providing
scientific and administrative leadership, may contribute a
Laboratory Program.  Laboratory Program Leaders will be
directly responsible to the Principal Investigator.  The
formation of the Group, the application in response to this
RFA, the overall management of the Group, and the allocation
of funds to the various Laboratory Programs will be the
responsibility of the Principal Investigator and the
Principal Investigator's institution in accordance with PHS
policies.
     
The constituency of the Group and its Laboratory Programs
should depend on the talents required to accomplish its
scientific and technical objectives as perceived by the
Principal Investigator and Program Leaders.  The major
consideration in structuring an NCDDG should be the
mobilization of maximum intellectual strength and the
ability to carry out the proposed research.  If an NCDDG
includes more than one Laboratory Program in a specific
area, each should be capable of contributing high quality,
necessary, and non-overlapping talents.
     
An individual scientist may be proposed as a Principal
Investigator or a Program Leader in more than one
application.  If so, the Principal Investigator must
demonstrate in the application that there is no scientific
or budgetary overlap or proprietary conflict with each
individual's proposed activities.  Likewise, individuals
currently receiving funding via contracts, grants, or
Cooperative Agreements (i.e., National Cooperative Drug
Discovery Groups [NCDDGs]) may be funded under this RFA as
long as there is no scientific or budgetary overlap or
proprietary conflict in funded activities.  Any Program
Leader who proposes to be a Group member must complete an
application form in detail even if no funds are requested.
An NIH intramural scientist may participate in an NCDDG as a
collaborator or consultant, but may not submit a formal
application as a Program Leader or receive funds from this
program.  The intramural scientist must provide a letter of
commitment and current curriculum vitae and obtain
appropriate NIH clearances prior to submission of the
application.  The Principal Investigator must incorporate
into the application, in the usual grant format, a full
description of the collaborative project, including
technical details and methodology.  The participation of an
intramural scientist is independent of and unrelated to the
role of the NCI Program Director and Coordinator as
described in "DEFINITIONS."
     
More than one member of an NCDDG might be derived from a
single institution.  However, the varied talents and
commitment required for effective drug discovery, as
described in this RFA, are not usually present in most
single institutions and it is anticipated that the Program
Leaders within a Group will be derived from several
institutions.
     
No minimum or maximum number of Laboratory Programs per
Group is stipulated.  However, the Principal Investigator
could experience difficulty in providing the desirable level
of guidance, and Program Leaders might communicate and
collaborate less efficiently if the Group were to contain
more than five or six Laboratory Programs.
     
In forming Groups, potential Principal Investigators should
remain cognizant of the need for communication, including
regular meetings of members.  While it is not a requirement
of this RFA, the formation of Groups on a geographically
regional basis may be advantageous.  Applicants from outside
the United States or applicants who propose Laboratory
Programs in foreign countries must specifically address how
effective communication will be maintained.
     
Under the provisions of assistance via Cooperative
Agreement, the NCI Coordinator will participate as a member
of the Group in a manner specified in "TERMS OF AWARD."  The
NCI Program Director will carry out the normal programmatic
and scientific responsibilities required for guidance of the
NCDDG program.  The NCI Program Director and Coordinator
will not conduct Laboratory Programs.
     
RESEARCH GOALS AND SCOPE
     
The goals of the NATIONAL COOPERATIVE DRUG DISCOVERY GROUP
program are:
     
The conceptualization, creation and preclinical evaluation
of new drugs and strategies designed to effectively treat
cancer.
     
The recommendation of presumptively curative treatment
entities and strategies for development to clinical trial.
     
The conduct of biological, biochemical, and pharmacological
studies that will permit the most enlightened subsequent
clinical evaluation supported by the most sophisticated
technology, and which may provide information leading to the
future discovery of even more effective treatments.
     
Applications for funding as an NCDDG should stress creative
approaches to the discovery of effective anticancer
therapies and should emphasize the following:
     
Objectives of the proposed NCDDG.
     
Research approaches to the realization of objectives and the
provision of comprehensive information (including citations)
in support of the rationale(s) for the proposed approaches.
     
Specific pertinence to cancer treatment.
     
The scientific and technical areas of expertise (Program
Leaders) required to attain Group objectives.
     
PATENT COVERAGE
     
Since the discovery of anticancer treatment entities and
strategies is the objective of this effort and active
involvement by industrial laboratories is facilitated by the
existence of adequate patent coverage, it is essential that
applicants provide plans to assure such coverage.  The
situation could be complicated since multiple institutions
are involved.  Each applicant Group must, therefore, 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. 98-6230 and 37 CFR Part 401.  Note that
non-profit organizations (including universities) and small
business firms retain the rights to any patent resulting
from government contracts, grants or Cooperative Agreements.
Your further attention is drawn, however, to a Presidential
memorandum of February 18, 1983 (Attachment 1), which
extends to all business concerns, regardless of size, the
first option to the ownership of rights to inventions as
provided in P.L. 96-517.  As a result of this memorandum,
the relationships among industrial organizations and other
participants are simplified, since all Group members can now
be full partners in the research and in any inventions
resulting therefrom.  The specific patenting arrangements
among the institutions may vary, and could include joint
patent ownership, exclusive licensing arrangements, etc.
Applicants are encouraged to develop an arrangement that
best suits their own particular circumstances.
     
The proposed patent plan among the institutions comprising
the Group (including formal collaborators) must be included
as part of the application.  It should be inserted following
the overall Group budget section.  A formal patent agreement
signed and dated by the organizational official authorized
to enter into patent arrangements for each Group member and
member institution must be on file at the Division of
Extramural Activities, NCI prior to peer review.  (See
"MINIMUM REQUIREMENTS FOR APPLICATION.")
     
TERMS OF AWARD
     
Authorities and Responsibilities of Awardees
     
Assistance via Cooperative Agreement differs from that of
research grants in that, in addition to the normal
programmatic and administrative stewardship
responsibilities, the component awarding the Cooperative
Agreement anticipates substantial scientific involvement
during performance of the project.  However, the Group must
define its objectives and its approaches to attain these
objectives in accord with its own interests and perceptions
of novel and exploitable approaches to the discovery of
effective anticancer treatment and must develop the details
of the research design following the guidance given in this
RFA.  It is the primary responsibility of the Principal
Investigator to state clearly the objectives of the Group,
to direct the research stipulated in the proposal and to
ensure that the results obtained are published in a timely
manner.  It is anticipated that decisions in all activities
will be reached by consensus of the Group under the
leadership of the Principal Investigator and that the NCI
Coordinator will have the opportunity to offer input to this
process.
     
The Principal Investigator, Program Leaders, and NCI
Coordinator will meet periodically to review progress, plan
and design research activities, and establish priorities.
The frequency of meetings, but not fewer than two per year,
will be determined by the Principal Investigator who will be
responsible for scheduling the time and place (generally at
one of the performance sites) and for preparing concise
proceedings or minutes which will be delivered to the
members of the Group within 60 days of the meeting.  NCI
staff may not chair Group meetings.  A critical determinant
of Group success will be the degree of communication among
its members.  Therefore, additional informal meetings among
all participants as well as regular telephone and written
communication will be important.
     
In addition to the special reports and stipulations
described below, reporting requirements will be identical to
those currently in existence for awardees of program project
grants.
     
The principal end product of NCDDG activities will be the
discovery of new entities and strategies for development to
clinical trial.  Subsequent developmental work through
private resources is encouraged.  Alternatively, the Group
may recommend that development be sponsored by NCI.  In the
latter case, it will be necessary for the Principal
Investigator and NCI Coordinator to cooperate in the
analysis, summarization, preparation, and presentation of
data to the appropriate NCI staff.
     
NCI will retain the option to cross-file or independently
file an application for investigational clinical trial
(e.g., an Investigational New Drug Application [INDA] to the
United States Food and Drug Administration) of any invention
resulting from these NCI supported Cooperative Agreements.
Reports of data generated by the Group or any of its members
required for inclusion in INDAs and Clinical Brochures and
for cross-filing purposes will be submitted by the Principal
Investigator to the NCI Coordinator upon request.  Such
reports will include background information, methods,
results, and conclusions.  They will be subject to approval
and revision by NCI and may be augmented with test results
from other Government sponsored projects prior to submission
to the appropriate regulatory agency.
     
The Government, via the NCI Coordinator, will have access to
data generated under this Cooperative Agreement and may
periodically review the data.  However, the awardee will
retain rights to the data, and timely publication of major
findings by the Group members is encouraged.  Publication or
oral presentation of work done under this agreement will
require appropriate acknowledgement of NCI support.
Dissemination of information on synthetic or natural
substances supplied to the Group by NCI (e.g., for
comparative testing purposes, as reference materials, etc.)
will require clearance by NCI to assure conformity to
existing confidentiality agreements with suppliers.
     
Nature of NCI Staff Participation
     
NCI shall participate as a member of the Group and will be
represented by a Coordinator.  The NCI Coordinator will be
selected from the scientific staff that manages extramural
programs but not from the NCI intramural staff.  During
performance of the award, NCI may provide appropriate
assistance, advice, and guidance by participating in the
design of activities; advising in the selection of sources
for resources, staff, etc.; coordinating or participating in
collection and/or analysis of data; advising in management
and technical performance; and participating in the
preparation of publications.  In all cases, the role of NCI
will be to assist and facilitate and not to direct
activities.
     
The NCI Coordinator, as well as any other Group member, may
assist in research planning; may suggest studies within the
scope of the Group's objectives and research activities; may
present to the Group experimental findings from published
sources or from contract projects in support of these
suggestions; may participate in the design of experiments
agreed to by the Group; and may participate in the analysis
of results.
     
Upon recommendation of the NCI Coordinator, NCI may utilize
its contract based resources in support of Group research
activities when such resources may be required on an
occasional basis.  The following is a list of some resources
that might be supplied if they become desirable during
performance, are not anticipated as a continuing need, and
are readily available:
     
Reference compounds for standardization of test systems, as
analytical standards, and for related purposes.
     
Needed resources such as test materials and information that
may not otherwise be available to the Group.
     
Data from testing conducted in resource contract
laboratories.
     
Laboratory testing capacity, whenever appropriate and
possible, in the current contract based preclinical
therapy-related laboratory testing program.  The Group is
expected to provide sufficient test material for such
testing.
     
Searches of computer files of materials, chemical structures
and biological activity, if requests for such searches are
sufficiently focused to avoid excessive costs.  Information
given to an NCDDG will be restricted by any standard
confidentiality agreements between the Government and
suppliers of test materials to the Government.
     
Experimental animals and cultured cells, if available, to
Groups whose main research activities do not require these
materials on a regular basis.  Groups whose experimental
approach involves studies that require animals on a regular
basis must budget for costs in their application.
     
Computer processing and statistical evaluations if costs are
not excessive.
     
These "TERMS OF AWARD" require that NCI staff approve the
following:  changes in the Principal Investigator or Program
Leaders; reports intended for inclusion in INDAs and
Clinical Brochures; redistribution, outside the NCDDG, of
biological and chemical materials received from the
Government; and dissemination of research findings resulting
from the use of such materials.  Disagreements arising
pursuant to these approvals will be arbitrated by a panel
composed of one Group designee, one NCI designee, and a
third designee with expertise in the relevant area chosen by
the other two.  These special arbitration procedures in no
way affect the awardee's right 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.
     
The special "TERMS OF AWARD" described in this section are
in addition to, and not in lieu of, otherwise applicable OMB
administrative guidelines, HHS Grant Administration
Regulations at 45 CFR Part 74, and other HHS, PHS, and NIH
grant administration policy statements.
     
MINIMUM REQUIREMENTS FOR APPLICATION
     
Applications seeking funding as a NATIONAL COOPERATIVE DRUG
DISCOVERY GROUP must meet the following requirements:
     
Name a single Principal Investigator who is an employee of
the applicant institution and who will be responsible for
the application, for Group research activities, and for the
dispersal of funds for the support of Group activities.
     
Identify the Principal Investigator's organization
(institution) that will provide the Central Operations
Office and assume legal and financial responsibility and
accountability for the use and disposition of funds awarded
on the basis of this RFA; show availability of personnel and
facilities capable of performing and supporting the
administrative functions of this NCDDG.
     
Provide a description of the Group's plan for assuring
adequate patent coverage of new inventions that may issue as
a result of Government funding of the proposed work.
     
Note:  A formal statement of Patent Agreement among all
Group members and their institutions as well as a detailed
description of procedures to be followed for resolution of
legal problems which may develop, signed and dated by the
organizational official authorized to enter into patent
arrangements for each Group member and member institution is
preferred with the application.  If this signed agreement is
not included in the application, it must be submitted to the
Executive Secretary prior to peer review.
     
Provide from the Principal Investigator and from each
Program Leader a signed statement of acceptance of the
participation of NCI staff during performance of project as
outlined under "TERMS OF AWARD."
     
Provide a clear, concise plan in narrative and diagrammatic
form that depicts the interrelationships among the members
of the Group and the contribution of each to fulfillment of
Group objectives; provide an organizational chart of the
Group showing the name, organization, and scientific
discipline of the Principal Investigator and Program
Leaders; provide an organizational chart for each Laboratory
Program within the Group showing relationships among the key
personnel.
     
Provide a plan to assure the maintenance of close
collaboration and effective communication among members of
the Group which will include letters of commitment to this
plan by all Program Leaders.
     
Demonstrate that the Principal Investigator and the Program
Leaders possess the outstanding scientific skills and
leadership qualities to conduct the proposed research
successfully; include relevant research programs,
experience, unique competencies, and pertinent publications.
     
Demonstrate the competence of the Principal Investigator to
manage comprehensive research projects and to coordinate and
integrate research activities of diverse Laboratory
Programs.
     
Demonstrate that each component Laboratory Program is
required for the attainment of the Group's objectives and
that each has available the professional and technical
personnel to permit efficient and successful conduct of the
proposed research; show that total personnel of the Group
are sufficient in quality and quantity to assure successful
conduct of the proposed research.
     
Note:  Other activities which are essential to maintaining
or achieving the objectives of the stated research programs
(e.g., routine assays, scale-up of materials, shared
equipment, shared services, animal maintenance, etc.) should
be included as subcontracts under the budget for core
resources.  Anticipated payments to third parties for such
activities should be shown as subcontracts under the core
budget.
     
Demonstrate for all key personnel the time available for
this project and show for all key professional personnel (1)
title, identifying number, percentage of effort devoted to
the project, direct costs, and project period of all awarded
and pending grants, cooperative agreements, contracts, and
industrial commitments regardless of source of funding; (2)
identify and explain areas of potential scientific and/or
budgetary overlap with active and pending grants, contracts,
and Cooperative Agreements and what support would be
relinquished if this cooperative agreement is made.
     
Demonstrate that each component Laboratory Program and the
Group as a whole have available the facilities (including
appropriate biohazard facilities) required for conduct of
the proposed research.  Funds will not be provided for
alteration or renovation of facilities under this
Cooperative Agreement.
     
REVIEW PROCECURES AND CRITERIA
     
Review Procedure
     
Upon receipt, applications will be reviewed by the Division
of Research Grants for completeness.  Incomplete
applications will be returned to the applicant without
further consideration.  Evaluation for responsiveness to
this 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 which are judged non-responsive will be
administratively withdrawn, and the proposed Principal
Investigator and institutional business official will be
notified.  Should an application be judged non-responsive to
this RFA, any of its constituent Laboratory Programs may be
submitted as an investigator initiated regular research
grant (R01) at the next receipt date.  Alternatively, the
consortium of Laboratory Programs could seek funding as a
program project grant (P01).  In either event, the
application would require modification in accordance with
either the R01 or P01 guidelines.  The new application would
not be considered an application for a Cooperative
Agreement, nor would it be considered a response to an RFA.
Questions concerning the relevance of proposed research to
the RFA should be directed to program staff as described in
"INQUIRIES."
     
In cases where the number of applications is large compared
to the number of awards to be made, the NIH may conduct a
preliminary scientific peer review to eliminate those which
are clearly not competitive for award.  The NIH will
withdraw from further competition those applications judged
to be noncompetitive and notify the Principal Investigator
and institutional business official.
     
Those applications judged to be both competitive and
responsive will be further evaluated, using the review
criteria shown 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 Program.
     
Review Criteria
     
Extend of relevance of applicant's (Group) objectives to the
discovery of NOVEL approaches for developing new anticancer
treatments.
     
Scientific merit and originality of proposed research.
     
Technical merit of proposed methods for producing or
obtaining test materials and for their evaluation.
     
Adequacy of the scientific disciplines and specific
competencies represented by the Principal Investigator and
Program Leaders; research experience, competence,
commitment, and time availability of Principal Investigator,
Program Leaders, and other key personnel.
     
Administrative experience and competence of Principal
Investigator in the development, implementation, and
management of comprehensive research programs.
     
Adequacy of plans for effective intra-Group communication
and for assuring Group cohesiveness.
     
Adequacy of existing physical facilities and resources of
the Principal Investigator and Program Leaders.
     
Evidence of approval and commitment of institutions
represented by Group members to Group goals.
     
Evidence of availability and competence of the applying
institution to serve as the Central Operations Office for
the Group.
     
Commitment to accept NCI assistance in accordance with the
guidelines outlined under "TERMS OF AWARD."
     
The review group will recommend an appropriate budget and
period of support for each approved application.
     
J. METHOD OF APPLYING
     
Receipt Date
     
The deadline for receipt of applications is June 9, 1989.
APPLICATIONS RECEIVED AFTER THIS DATE WILL BE CONSIDERED AS
NOT RESPONSIVE TO THIS RFA AND WILL BE RETURNED WITHOUT
REVIEW.  Please note, the Division of Research Grants will
not accept any application to this "Request for
Applications" that is the same as one currently being
considered by any other review group or awarding unit of the
National Institutes of Health.
     
General
     
The regular research grant application Form PHS-398 (Rev.
9/86) must be used in applying.  These forms are available
at most institutional business offices or from the Division
of Research Grants, National Institutes of Health, 9000
Rockville Pike, Bethesda, Maryland 20892.  One original and
six (6) copies are requested.
     
Submit a signed, typewritten original of the application,
including a single Checklist, and four (4) signed, exact
single sided photocopies in one package to:
     
The  Division  of  Research  Grants
National Institutes  of  Health
Westwood Building, Room 240
Bethesda, Maryland 20892**
     
Send the remaining two (2) copies of your application
directly to:
     
Mr. Hernon Fox
Referral Officer
National Cancer Institute
Westwood Building, Room 848
Bethesda, MD 20892
Telephone:  (301) 496-3428
     
To expedite the review of your application, and to assure
its identification with this RFA:
     
The application form should have "NCI National Cooperative
Drug Discovery Groups - General Mechanism (RFA 89-CA-02)" on
line 2 of the face page of the application form;
personalized titles more fitting for your application should
be listed on line 1 and not on line 2.
     
The RFA label available in the 9/86 revision of the
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.
     
Organization of Application and Suggested Modifications of
Form PHS-398 (Revised, 9/86)
     
This RFA requires the submission of a single application for
the proposed NATIONAL COOPERATIVE DRUG DISCOVERY GROUP.
     
Because of the multi-institutional nature of an NCDDG and
the special requirements in this RFA, additional suggestions
regarding format and some modifications seem desirable to
provide a comprehensive yet readily reviewable application.
     
Each application should have an INTRODUCTION SECTION
(described below) and Sections for each of the scientific
Laboratory Programs including the LABORATORY PROGRAM of the
proposed Principal Investigator and that these be identified
as "Laboratory Programs" and be numbered consecutively.  Use
Form PHS-398 for each LABORATORY PROGRAM but omit the face
page for the individual program.  A single face page should
apply to the entire application.  Insert the INTRODUCTION
after the Table of Contents.  It is suggested that the title
"Program Leader" (Retain the title "Principal Investigator"
for the section describing the Laboratory Program of the
Principal Investigator) be substituted for "Principal
Investigator/Program Director" and that the "Description"
(grant application form page 2) for each of the Laboratory
Programs, in addition to describing the work proposed,
provide a statement of relevance to the overall objectives
of the proposed NCDDG.  A single checklist should be
provided for the overall application.  Do not include a
checklist for each Laboratory Program.  The 20 page
limitation stipulated in the PHS-398 kit applies to each of
the individual Laboratory Programs.  The overall
Introductory Section should also be limited to 20 pages.
     
Sections pertaining to Laboratory Programs should provide a
Detailed Budget for the First Twelve Month Budget Period
INCLUDING APPLICABLE INDIRECT COSTS FOR CONSORTIUM
INSTITUTIONS and a Budget for the Entire Proposed Project
Period.  JUSTIFY BUDGET REQUESTS according to the guidelines
in Form PHS-398.
     
Often the various research tasks necessary to reach the
Group's goals may need to be phased in, at least in part, in
sequential fashion.  In such cases, the budgets for the
individual Laboratory Programs should, logically, reflect an
appropriate change in relative emphasis among tasks until an
operational steady state situation is attained.
Justification for phase-in budgets also should be provided.
     
The package containing the proposed research plan of the
Principal Investigator and each Program Leader should be
preceded by an INTRODUCTORY SECTION bearing the title
NATIONAL COOPERATIVE DRUG DISCOVERY GROUP - GENERAL
MECHANISM OF ACTION and the phrase, "Prepared in Response to
RFA No. 89-CA-02."  Form PHS-398 should be used for this
INTRODUCTORY SECTION and should describe the proposed NCDDG
as a whole with respect to goals, objectives, and overall
research plan.  In this Introductory Section, list the
Program Leaders as "Key Personnel Engaged on Project."
Other key personnel should be listed in the proposed
research plan for each individual Laboratory Program.  It is
important to discuss any prior collaborative efforts among
investigators in the Group as well as advantages expected
from the Group effort, e.g., how the projects are mutually
reinforcing, how collectively they will further the goals of
the proposed research, etc.
     
In the Introductory Section, budget sheets should reflect
the consolidated TOTAL DIRECT COSTS of the entire proposed
NCDDG.  This should include the direct and indirect costs at
cooperating institutions.  The Introductory Section should
also provide, from the applicant institution, a Detailed
Budget for the First Twelve Month Period and a Budget for
the Entire Proposed Project Period for Direct Costs for each
of the following:
     
The Principal Investigator's Laboratory Program.
     
Management and coordination of Group activities.
     
Maintenance of the Central Operations Office.
     
Inasmuch as the Principal Investigator may also function as
a Program Leader for his/her Laboratory Program, parts of
Form PHS 398 that duplicate information provided in the
section describing the Principal Investigator's laboratory
work need not be included in the Introductory Section.  The
Introductory Section should, however, contain any additional
information about the proposed Principal Investigator or
his/her institution as evidence of capability to carry out
the scientific and administrative duties required in this
RFA and the functions of the Central Operations Office.
     
In addition, Form PHS 398 constituting the Introductory
Section must include the following elements to be considered
responsive to minimum requirements (See "MINIMUM
REQUIREMENTS FOR APPLICATION" of this RFA).
     
The name of a single Principal Investigator in accordance
with "MINIMUM REQUIREMENTS FOR APPLICATION."
     
The name of the Principal Investigator's organization that
will provide and operate the Central Operations Office in
accordance with "MINIMUM REQUIREMENTS FOR APPLICATION."
     
A statement assuring adequate patent coverage of new
inventions that may issue as a result of Government funding
in accordance with "MINIMUM REQUIREMENTS FOR APPLICATION"
and as described in "PATENT COVERAGE."
     
(4) A statement of acceptance of the provisions of "TERMS OF
AWARD" regarding NCI staff participation in accordance with
"MINIMUM REQUIREMENTS FOR APPLICATION."
     
A description of the inter-relationships among members of
the Group and organizational charts in accordance with
"MINIMUM REQUIREMENTS FOR APPLICATION."
     
A plan to assure maintenance of close collaboration and
effective communication among members of the Group in
accordance with "MINIMUM REQUIREMENTS FOR APPLICATION."
     
The application will be reviewed as a whole as well as
project by project; therefore, prepare a detailed Table of
Contents that will enable reviewers to find specific
information readily and number all pages consecutively after
the face page, which is page 1.  Complete all items on the
face page of the application (only one per application) as
in a regular research grant proposal.  Identify projects by
number, title and Program Leader.  Identify cores by letter,
title and Program Leader.
     
If internal or external advisory groups will be used, list
their membership and describe their roles.  Include a signed
letter of agreement from each advisor.
     
List in a separate table all consultants, both paid and
unpaid.  Include a signed letter of agreement from each
consultant.
     
INQUIRIES
     
Inquires may be addressed to:
     
George S. Johnson, Ph.D.
Executive Plaza North, Suite 832
Developmental Therapeutics Program
Division of Cancer Treatment
National Cancer Institute
Bethesda, Maryland  20892
Telephone:  (301) 496-8783
     
RFA - National Cooperative Drug Discovery Groups for General
Mechanism of Action Based Anticancer Treatment
     
ATTACHMENT 1
     
A Presidential memorandum of February 18, 1983 directed a
revision in policy respecting allocation of rights in
inventions that are products of Government-funded research
and development.  The memorandum directs the adoption and
implementation of the same or substantially the same
policies for all federally-funded R&D contracts, grants, or
cooperative agreements as those set forth in PL-96-517 (H.R.
6933, "Patent and Trademark Laws, Amendment", December 12,
1980) for small businesses and non-profit organizations.
Under the new policy, the Government would retain "march-in"
rights and require licensing if the inventing organization
fails to pursue development of the invention.
     
The text of the President's memorandum:
     
[Text] To the extent permitted by law, agency policy with
respect to the disposition of any invention made in the
performance of a federally-funded research and development
contract, grant or cooperative agreement award shall be the
same or substantially the same as applied to small business
firms and nonprofit organizations under Chapter 38 (now
Chapter 18) of Title 35 of the United States Code.
     
In awards not subject to Chapter 38 (now Chapter 18) of
Title 35 of the United States Code, any of the rights of the
Government or obligations of the performer described in 35
U.S.C. 202-204 may be waived or omitted if the agency
determines (1) that the interests of the United States and
the general public will be better served thereby as, for
example, where this is necessary to obtain a uniquely or
highly qualified performer, or (2) that the award involves
co-sponsored, cost sharing, or joint venture research and
development, and the performer, cosponsor or joint venturer
is making substantial contribution of funds, facilities or
equipment to the work performed under the award.
     
In addition, agencies should protect the confidentiality of
invention disclosure, patent applications and utilization
reports required in performance or in consequence of awards
to the extent permitted by 35 U.S.C. 205 or other applicable
laws.  [End Text]
     
On the basis of the President's memorandum the General
Services Administration has issued a Temporary Regulation
which prescribes revised guidance regarding the rights of
the Government and recipients of federally-funded R&D
contracts, grants, and cooperative agreements.  (Federal
Register, Vol. 48, No. 74, Friday, April 15, 1983, GSA, 41
CFR Ch.1.  FPR Temporary Regulation 69.) The intended effect
is to extend in principle the current implementation of
Public Law 96-517 beyond small businesses and non-profit
organizations.

REQUEST FOR APPLICATIONS FOR COOPERATIVE AGREEMENT
     
P.T. 34;  K.W. 0715035, 0755025, 0740020, 0755020, 0710030, 0785140
     
89-CA-03
     
NATIONAL COOPERATIVE ANTICANCER MODEL DEVELOPMENT
GROUPS
     
NATIONAL CANCER INSTITUTE (NCI)
     
Letter of Intent Date : April 28, 1989
Application Receipt Date:  June 9, 1989
     
The NCI invites applications for the establishment of
National Cooperative Anticancer Model Development Groups.
     
There are no plans to reissue this Request for Applications
at any future time.
     
LETTER OF INTENT
     
Prospective applicants are asked to submit, by April 28,
1989, a short letter of intent that includes a descriptive
title of the proposed research, and if possible, names of
members of the proposed Group and their institutions.  The
letter of intent is requested in order to provide an
indication of the number and scope of applications to be
reviewed.  The letter of intent does not commit the sender
to submit an application, nor is it a requirement for
submission of an application.  Letters of intent should be
sent directly to:
     
Mary K. Wolpert, Ph.D.
Executive Plaza North, Suite 832
Developmental Therapeutics Program
Division of Cancer Treatment
National Cancer Institute
Bethesda, MD 20892
Telephone No.:  (301)-496-8783
     
*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 USC 241, as amended by Public Law 99-158, 42
USC and 285(a), and by Sections 410 and 411, Small Business
Innovation Development Act, Public Law 97-219.  This program
is not subject to the intergovernmental review requirements
of Executive Order 12372 or Health Systems Agency review.
     
CONTENTS
     
SUMMARY
MECHANISM OF SUPPORT
DEFINITIONS
COMPOSITION
RESEARCH GOALS AND SCOPE
PATENT COVERAGE
TERMS OF AWARD
MINIMUM REQUIREMENTS FOR APPLICATION
REVIEW PROCEDURES AND CRITERIA
METHOD OF APPLYING
INQUIRIES
     
SUMMARY
     
Cancer claimed the lives of about 483,000 people in the
United States in 1987 and continues to be a leading cause of
death.  The 5-year patient survival rates associated with
some of the major cancer sites have been progressively
increasing as a result of improved diagnoses and the
initiation of earlier and more effective therapeutic
strategies; however, many types of cancer remain largely
refractory to treatment.  For example, despite extensive
research efforts, in 1987 approximately 136,000 people died
of lung cancer alone.  Thus there remains an urgent need for
better treatment of all forms of cancer especially those of
the solid tumor types.
     
The search for better cancer treatments is a dynamic process
dependent on the availability of new agents and strategies
coupled with the development and use of more predictive
models.  Recent advances in modern biomedical research
provide unprecedented opportunities for the development of
novel and highly sophisticated preclinical assays that might
discriminate for more effective treatments.  This Request
for Applications (RFA) is a reissuance for the purpose of
expanding the National Cooperative Anticancer Model
Development Group (NCAMDG) program to enable talented
scientists to form highly synergistic research teams for the
conception and creation of new models for the discovery of
more effective cancer treatments.  An NCAMDG might consist
of a single laboratory or more typically be composed of a
multidisciplinary and multi-institutional team of scientists
from academia, non-profit research, and commercial
organizations, as many single institutions may not possess
either the critical mass of talents or the ancillary
resources to translate leads from basic studies into new
model development.  The NCAMDG program will complement the
National Cooperative Drug Discovery Group program which was
established by the National Cancer Institute (NCI) in 1983
and is currently being expanded in order to stimulate and
facilitate the discovery of new cancer treatments.
Applications based on general mechanisms of cancer treatment
without implications for a specific cancer are requested in
an accompanying RFA (89-CA-02).  A complementary RFA
(89-CA-01) requests the establishment of National
Cooperative Drug Discovery Groups for Specific
Disease-Oriented Anticancer Treatment.
     
The "RESEARCH GOALS AND SCOPE" of this RFA require that an
NCAMDG has the capacity within itself to conceive, create,
and evaluate new model systems.  Areas of research will be
broad and could include a variety of in vitro and in vivo
models, such as biochemical, metastatic, immunological,
radiomodulator, differentiation, gene transfer, oncogene
probe, etc.  The nature of the models is limited only by the
creativity and ability of the applying Group.  Investigators
who have not been associated with traditional cancer
research programs are especially encouraged to apply because
of the desirability of technology transfer from other
rapidly advancing fields to that of cancer.  Applicants must
provide a rationale and develop a testable hypothesis for
why their model is likely to lead to the discovery of a new
cancer treatment or strategy.  Model development may be
oriented to a general mechanism likely to affect many types
of cancer or be tailored to a particular disease, such as
breast cancer.  Although some models might be useful for
both cancer diagnosis and treatment, applications which
propose models limited to diagnosis and without a rationale
for the discovery of new cancer treatments are not invited.
The emphasis of this RFA is on the development of as yet
unevaluated innovative preclinical models for discovery of
improved treatment.  Proposals which focus solely on
screening or which emphasize scale-up of existing procedures
are outside the scope of this RFA.  It is also possible that
some assays may be useful as predictive assays for selecting
therapy for individual patients.  Such techniques would be
responsive to this RFA as they may lead to improved patient
therapy; however, the emphasis must be on the development
and evaluation of the assay and not on prospective clinical
trials to validate the model.
     
MECHANISM OF SUPPORT
     
Awards will be made as COOPERATIVE AGREEMENTS.  Assistance
via Cooperative Agreement differs from the research grant in
that the Government component (NCI) awarding the Cooperative
Agreement anticipates substantial involvement during
performance of the award.  This partnership relationship
will facilitate technology transfer from Government owned
data bases and the use of appropriate contract resources to
enhance the efficiency and effectiveness of a Group's
efforts.  The nature of NCI staff participation is described
in this RFA under "TERMS OF AWARD."  There is no intent,
real or implied, for NIH staff to direct Group activities or
to limit the freedom of investigators.  A Group may consist
of a single Laboratory Program or preferably a consortium of
multidisciplinary and/or multi-institutional Laboratory
Programs from academic, non-profit, or commercial
organizations.  The interaction of academic and non-profit
research institutions with commercial (including industrial)
organizations and Government is expected to favor the
efficient invention of new model systems and will facilitate
their subsequent use in the discovery of new agents or
treatment strategies for cancer.  It should be mentioned
that all industrial companies are now eligible to apply for
grants and Cooperative Agreements (See NIH Guide for Grants
and Contracts, Volume 11, Number 5, April 23, 1982, page 3).
The active participation of industry is encouraged because
it will allow this segment of the scientific community to
contribute its considerable intellectual and material
resources.  Further, the interaction of academic and
non-profit research institutions with industry and
Government will facilitate subsequent development and
marketing of new models, although these latter activities
are not within the scope of this RFA.
     
NCI plans to make multiple awards for project periods up to
five years and has set aside $2,000,000 total costs for the
initial year's funding.  Although this program is provided
for in the financial plans of the National Cancer Institute,
awards pursuant to this RFA are contingent upon continuing
availability of funds.  The earliest possible starting date
for the initial annual period will be April 1, 1990.  This
RFA is a one-time solicitation.  Generally, future
unsolicited competing renewal applications will compete as
research project applications with all other
investigator-initiated applications.  However, should the
NCI determine that there is a continuing program need,
competing renewal applications for Cooperative Agreements
from the then current awardees will be invited.
     
[When the applicant institution is outside the United
States, awards must be limited to three years; this special
provision does not apply when the applying institution is
within the United States and the application contains
proposed Laboratory Programs in a foreign country.]
     
Each award will be made only to the Principal Investigator's
institution.  All Group activities will be coordinated
through a Central Operations Office located at the Principal
Investigator's institution.
     
Under the Cooperative Agreement, a partner relationship
between the recipient of the award and NCI exists in which
the Group is responsive to the requirements and conditions
set forth in the RFA.  Specifically, the Principal
Investigator defines the details for the project within the
guidelines of the RFA, retains primary responsibility for
the performance of the activity, and agrees to accept close
coordination, cooperation, and assistance of NCI extramural
staff in all aspects of scientific and technical management
of the project in accordance with the terms formally
negotiated and mutually agreed upon prior to the award.
     
All policies and requirements that govern the grant program
of the U.S. Public Health Service apply.
     
DEFINITIONS
     
COOPERATIVE AGREEMENT - An assistance mechanism in which
substantial NIH programmatic involvement with the recipient
during performance of the planned activity is anticipated.
     
NATIONAL COOPERATIVE ANTICANCER MODEL DEVELOPMENT GROUPS
(NCAMDG) - A single Laboratory Program or a number of
Laboratory Programs representing diverse scientific
disciplines and organizations which join together under
guidance and direction of a single Principal Investigator
and which function as a unit with a common goal:  the
development of new preclinical models for the discovery of
new cancer treatments or strategies.  In this RFA the terms
National Co-operative Anticancer Model Development Group,
NCAMDG, and the "Group" are used synonymously.
     
CENTRAL OPERATIONS OFFICE - An administrative unit located
at the Principal Investigator's institution that coordinates
all Group activities and is legally and fiscally accountable
for the disposition of funds awarded.
     
DEVELOPMENT - Systematic use of knowledge and understanding
gained from research which is directed towards creating
useful models to meet the requirements of this RFA.
Development may include design of equipment prototypes and
demonstration of processes but excludes routine production
and testing.
     
DRUG - In the context of the NCAMDG program, a term used
broadly to encompass synthetic agents, natural and
biological products, as well as novel therapeutic strategies
or inventions designed to treat and cure cancer.  Strategies
also encompass creative methods to maximize antitumor
selectivity.
     
MODEL - In the context of the NCAMDG program, a term used
broadly to encompass any preclinical assay to be used in
testing and evaluating the anticancer potential of new
treatments.  A "model" can be proposed for any stage of the
cancer treatment discovery process.
     
METHOD - In the context of the NCAMDG program, the
techniques and procedures needed to use a model.
     
PRINCIPAL INVESTIGATOR - The person who assembles the
NCAMDG, submits the single application in response to this
RFA and who is responsible for performance of the Group as a
whole and of each Program Leader.  The Principal
Investigator may lead one of the Laboratory Programs of the
Group, and in addition, coordinate Group activities
scientifically and administratively.
     
PROGRAM LEADER - The Director of one of the scientific
Laboratory Programs of the NCAMDG.
     
NCI PROGRAM DIRECTOR - A member of the NCI extramural staff
who provides leadership and guidance for the overall NCAMDG
program within the NCI.
     
NCI COORDINATOR - A member of the NCI extramural staff,
appointed by the Program Director, who interacts
scientifically with the Group and facilitates the role of
NCI as partner in the NCAMDG.  The Program Director also may
serve as the NCI Coordinator for a Group.
     
NIH INTRAMURAL RESEARCH SCIENTIST - An NIH scientist engaged
in or responsible for research activities conducted in NIH
facilities.
     
NIH EXTRAMURAL SCIENTIST - An NIH scientist engaged in or
responsible for initiating projects, reviewing of
applications or proposals, or otherwise developing or
administering programs or projects conducted under
extramural awards.
     
PATENTABLE INVENTION - Any new and useful process, machine,
manufacture or composition of matter, or any new and useful
improvements thereof, as defined under the U.S. Patent
Statute (35 USC 101).
     
COMPOSITION
     
The composition of an NCAMDG is envisioned as follows:
     
A Principal Investigator.
     
One or more Laboratory Programs, each headed by a Program
Leader, in one or more diverse scientific disciplines, such
as molecular biology, cell biology, pathology, toxicology,
immunology, biochemistry, chemistry, pharmacology, etc.,
that may be appropriate to realization of Group objectives.
     
An NCI Coordinator designated from the NCI extramural staff
(to be appointed by the NCI Program Director after award).
     
The Principal Investigator, in addition to providing
scientific and administrative leadership, may contribute a
Laboratory Program.  Laboratory Program Leaders will be
directly responsible to the Principal Investigator.  The
formation of the Group, the application in response to this
RFA, the overall management of the Group, and the allocation
of funds to the various Laboratory Programs will be the
responsibility of the Principal Investigator and the
Principal Investigator's institution in accordance with PHS
policies.
     
The constituency of the Group and its Laboratory Programs
should depend on the talents required to accomplish its
scientific and technical objectives as perceived by the
Principal Investigator and Program Leaders.  The major
consideration in structuring an NCAMDG should be the
mobilization of maximum intellectual strength and the
ability to carry out the proposed research.  If an NCAMDG
includes more than one Laboratory Program, each should be
capable of con-tributing high quality, necessary, and
non-overlapping talents.
     
An individual scientist may be proposed as a Principal
Investigator or a Program Leader in more than one
application.  If so, the Principal Investigator must
demonstrate in the application that there is no scientific
or budgetary overlap or proprietary conflict with each
individual's proposed activities.  Likewise, individuals
currently receiving funding via contracts, grants, or
Cooperative Agreements (i.e., National Cooperative Drug
Discovery Groups [NCDDGs]) may be funded under this RFA as
long as there is no scien-tific or budgetary overlap or
proprietary conflict in funded activities.  Any Program
Leader who proposes to be a Group member must complete an
application form in detail even if no funds are requested.
An NIH intramural scientist may participate in an NCAMDG as
a collaborator or consultant, but may not submit a formal
application as a Program Leader or receive funds from this
program.  The intramural scientist must provide a letter of
commitment and current curriculum vitae and obtain
appropriate NIH clearances prior to submission of the
application.  The Principal Investigator must incorporate
into the application, in the usual grant format, a full
description of the collaborative project, including
technical details and methodology.  The participation of an
intramural scientist is independent of and unrelated to the
role of the NCI Program Director and Coordinator as
described in "DEFINITIONS."
     
More than one member of an NCAMDG might be derived from a
single institution.  However, the varied talents and
commitment required for effective model discovery, as
described in this RFA, may not be present in most single
institutions; it is anticipated that the Program Leaders
within a Group will be derived from several institutions.
     
No minimum or maximum number of Laboratory Programs per
Group is stipulated.  However, the Principal Investigator
could experience difficulty in providing the desirable level
of guidance and Program Leaders might communicate and
collaborate less efficiently if the Group were to contain
more than five or six Laboratory Programs.
     
In forming Groups, potential Principal Investigators should
remain cognizant of the need for communication, including
regular meetings of members.  While it is not a requirement
of this RFA, the formation of Groups on a geographically
regional basis may be advantageous.  Applicants from outside
the United States or applicants who propose Laboratory
Programs in foreign countries must specifically address how
effective communication will be maintained.
     
Under the provisions of assistance via Cooperative
Agreement, the NCI Coordinator will participate as a member
of the Group in a manner specified in "TERMS OF AWARD."  The
NCI Program Director will carry out the normal programmatic
and scientific responsibilities required for guidance of the
NCAMDG program.  The NCI Program Director and Coordinator
will not conduct Laboratory Programs.
     
RESEARCH GOALS AND SCOPE
     
The goals of the NATIONAL COOPERATIVE ANTICANCER MODEL
DEVELOPMENT program are:
     
The conceptualization, creation and evaluation of new
PRECLINICAL models designed to discover new entities or
strategies for anticancer treatment.
     
The provision of a rationale for a new model and the conduct
of appropriate studies that will permit evaluation of the
model as an indicator of potentially improved cancer
treatment.
     
Applications for funding as an NCAMDG should stress creative
approaches to the discovery of new models and should
emphasize the following:
     
Objectives of the proposed NCAMDG which include a testable
hypothesis.
     
Research approaches to the realization of objectives and the
provision of comprehensive information (including citations)
in support of the rationale(s) for the proposed approaches.
     
Specific pertinence to cancer treatment.
     
The scientific and technical areas of expertise (Program
Leaders) required to attain Group objectives.
     
PATENT COVERAGE
     
Since the discovery of new models for the discovery of new
anticancer treatment entities and strategies is the
objective of this effort and active involvement by
industrial laboratories is facilitated by the existence of
adequate patent coverage, it is essential that applicants
provide plans to assure such coverage.  The situation could
be complicated if multiple institutions are involved.  Each
applicant Group must, therefore, 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. 98-6230
and 37 CFR Part 401.  Note that non-profit organizations
(including universities) and small business firms retain the
rights to any patent resulting from government contracts,
grants, or Cooperative Agreements.  Your further attention
is drawn, however, to a Presidential memorandum of February
18, 1983 (Attachment 1), which extends to all business
concerns, regardless of size, the first option to the
ownership of rights to inventions as provided in P.L.
96-517.  As a result of this memorandum, the relationships
among industrial organizations and other participants are
simplified, since all Group members can now be full partners
in the research and in any inventions resulting therefrom.
The specific patenting arrangements among the institutions
may vary and could include joint patent ownership, exclusive
licensing arrangements, etc.  Applicants are encouraged to
develop an arrangement that best suits their own particular
circumstances.
     
The proposed patent plan among the institutions comprising
the Group (including formal collaborators) must be included
as part of the application.  It should be inserted following
the overall Group budget section.  A formal patent agreement
signed and dated by the organizational official authorized
to enter into patent arrangements for each Group member and
member institution must be on file at the Division of
Extramural Activities, NCI prior to peer review.  (See
"MINIMUM REQUIREMENTS FOR APPLICATION.)
     
TERMS OF AWARD
     
Authorities and Responsibilities of Awardees
     
Assistance via Cooperative Agreement differs from that of
research grants in that, in addition to the normal
programmatic and administrative stewardship
responsibilities, the component awarding the Cooperative
Agreement anticipates substantial scientific involvement
during performance of the project.  However, the Group must
define its objectives and its approaches to attain these
objectives in accord with its own interests and perceptions
of novel anticancer model development and must develop the
details of the research design following the guidance given
in this RFA.  It is the primary responsibility of the
Principal Investigator to state clearly the objectives of
the Group, to direct the research stipulated in the proposal
and to ensure that the results obtained are published in a
timely manner.  It is anticipated that decisions in all
activities will be reached by consensus of the Group under
the leadership of the Principal Investigator and that the
NCI Coordinator will have the opportunity to offer input to
this process.
     
The Principal Investigator, Program Leaders, and NCI
Coordinator will meet periodically to review progress, plan
and design research activities, and establish priorities.
The frequency of meetings, but not fewer than two per year,
will be determined by the Principal Investigator who will
be responsible for scheduling the time and place (generally
at one of the performance sites) and for preparing concise
proceedings or minutes which will be delivered to the
members of the Group within 60 days of the meeting.  NCI
staff may not chair Group meetings.  A critical determinant
of Group success will be the degree of communication among
its members.  Therefore, additional informal meetings among
all participants as well as regular telephone and written
communication will be important.
     
In addition to the special reports and stipulations
described below, reporting requirements will be identical to
those currently in existence for awardees of program project
grants (or research project grants in the case of a single
laboratory program).
     
The principal end product of NCAMDG activities will be the
creation, and if appropriate, patenting of new anticancer
models to be used in the evaluation of new anticancer
treatments.  Subsequent developmental work, and perhaps
commercialization of the model, is encouraged through
private resources.
     
NCI will retain the option to use data generated on new
agents in the model systems resulting from these NCI
supported Cooperative Agreements to cross-file or
independently file Investigational New Drug Applications
[INDAs] to the United States Food and Drug Administration.
Reports of data generated by the Group or any of its members
required for inclusion in INDAs and Clinical Brochures and
for cross-filing purposes will be submitted by the Principal
Investigator to the NCI Coordinator upon request.  Such
reports will include background information, methods,
results, and conclusions.  They will be subject to approval
and revision by NCI and may be augmented with test results
from other Government sponsored projects prior to submission
to the appropriate regulatory agency.
     
The Government, via the NCI Coordinator, will have access to
data generated under this Cooperative Agreement and may
periodically review the data.  However, the awardee will
retain rights to the data, and timely publication of major
findings by the Group members is encouraged.  Publication or
oral presentation of work done under this agreement will
require appropriate acknowledgement of NCI support.
Dissemination of information on synthetic or natural
substances supplied to the Group by NCI (e.g., for
comparative testing purposes, as reference materials, etc.)
will require clearance by NCI to assure conformity to
existing confidentiality agreements with suppliers.
     
Nature of NCI Staff Participation
     
NCI shall participate as a member of the Group and will be
represented by a Coordinator.  The NCI Coordinator will be
selected from the scientific staff that manages extramural
programs but not from the NCI intramural staff.  During
performance of the award, NCI may provide appropriate
assistance, advice, and guidance by participating in the
design of activities; advising in the selection of sources
for resources, staff, etc.; coordinating or participating in
collection and/or analysis of data; advising in management
and technical performance; and participating in the
preparation of publications.  In all cases, the role of NCI
will be to assist and facilitate and not to direct
activities.
     
The NCI Coordinator, as well as any other Group member, may
assist in research planning; may suggest studies within the
scope of the Group's objectives and research activities; may
present to the Group experimental findings from published
sources or from contract projects in support of these
suggestions; may participate in the design of experiments
agreed to by the Group; and may participate in the analysis
of results.
     
Upon recommendation of the NCI Coordinator, NCI may utilize
its contract based resources in support of Group research
activities when such resources may be required on an
occasional basis.  The following is a list of some resources
that might be supplied if they become desirable during
performance, are not anticipated as a continuing need, and
are readily available:
     
Reference compounds for standardization of test systems, as
analytical standards, and for related purposes.
     
Needed resources such as test materials and information that
may not otherwise be available to the Group.
     
Data from testing conducted in resource contract
laboratories.
     
Searches of computer files of materials, chemical structures
and biological activity, if requests for such searches are
sufficiently focused to avoid excessive costs.  Information
given to an NCAMDG will be restricted by any standard
confidentiality agreements between the Government and
suppliers of test materials to the Government.
     
Experimental animals and cultured cells, if available, to
Groups whose main research activities do not require these
materials on a regular basis.  Groups whose experimental
approach involves studies that require animals on a regular
basis must budget for these costs in their application.
     
Computer processing and statistical evaluations if costs are
not excessive.
     
These "TERMS OF AWARD" require that NCI staff approve the
following:  changes in the Principal Investigator or Program
Leaders; reports intended for inclusion in INDAs and
Clinical Brochures; redistribution, outside the NCAMDG, of
biological and chemical materials received from the
Government; and dissemination of research findings resulting
from the use of such materials.  Disagreements arising
pursuant to these approvals will be arbitrated by a panel
composed of one Group designee, one NCI designee, and a
third designee with expertise in the relevant area chosen by
the other two.  These special arbitration procedures in no
way affect the awardee's right 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.
     
The special "TERMS OF AWARD" described in this section are
in addition to, and not in lieu of, otherwise applicable OMB
administrative guidelines, HHS Grant Administration
Regulations at 45 CFR Part 74, and other HHS, PHS, and NIH
grant administration policy statements.
     
MINIMUM REQUIREMENTS FOR APPLICATION
     
Applications seeking funding as a NATIONAL COOPERATIVE
ANTICANCER MODEL DEVELOPMENT GROUP must meet the following
requirements:
     
Name a SINGLE Principal Investigator who will be responsible
for the application, for Group research activities, and for
the dispersal of funds for the support of Group activities.
     
Identify the Principal Investigator's organization
(institution) that will provide the Central Operations
Office and assume legal and financial responsibility and
accountability for the use and disposition of funds awarded
on the basis of this RFA; show availability of personnel and
facilities capable of performing and supporting the
administrative functions of this NCAMDG.
     
Provide a description of the Group's plan for assuring
adequate patent coverage of new inventions that may issue as
a result of Government funding of the proposed work.
     
Note:  A formal statement of Patent Agreement among all
Group members and their institutions as well as a detailed
description of procedures to be followed for resolution of
legal problems which may develop, signed and dated by the
organizational official authorized to enter into patent
arrangements for each Group member and member institution is
preferred with the application.  If this signed agreement is
not included in the application, it must be submitted to the
Executive Secretary prior to peer review.
     
Provide from each Program Leader a signed statement of
acceptance of the participation of NCI staff during
performance of project as outlined under "TERMS OF AWARD."
     
If more than one Laboratory Program is involved, provide a
clear, concise plan in narrative and diagrammatic form that
depicts the interrelationships among the members of the
Group and the contribution of each to fulfillment of Group
objectives; provide an organizational chart of the Group
showing the name, organization, and scientific discipline of
the Principal Investigator and Program Leaders; provide an
organizational chart for each Laboratory Program within the
Group showing relationships among the key personnel.
     
Provide a plan to assure the maintenance of close
collaboration and effective communication among members of
the Group which will include letters of commitment to this
plan by all Program Leaders.
     
Demonstrate that the Principal Investigator and the Program
Leaders possess the outstanding scientific skills and
leadership qualities to conduct the proposed research
successfully; include relevant research programs,
experience, unique competencies, and pertinent publications.
     
Demonstrate the competence of the Principal Investigator to
manage comprehensive research projects and to coordinate and
integrate research activities of diverse Laboratory
Programs.
     
Demonstrate that each component Laboratory Program is
required for the attainment of the Group's objectives and
that each has available the professional and technical
personnel to permit efficient and successful conduct of the
proposed research; show that total personnel of the Group
are sufficient in quality and quantity to assure successful
conduct of the proposed research.
     
Note:  Other activities which are essential to maintaining
or achieving the objectives of the stated research programs
(e.g., routine assays, scale-up of materials, shared
equipment, shared services, animal maintenance, etc.) should
be included under the budget for core resources.
Anticipated payments to third parties for such activities
should be shown as subcontracts under the core budget.
     
Demonstrate for all key personnel the time available for
this project and show for all key professional personnel (1)
title, identifying number, percentage of effort devoted to
the project, direct costs, and project period of all awarded
and pending grants, contracts, Cooperative Agreements and
industrial commitments regardless of source of funding; (2)
identify and explain areas of potential scientific and/or
budgetary overlap with active and pending grants, contracts,
and Cooperative Agreements and what support would be
relinquished if the NCAMDG is awarded.
     
Demonstrate that each component Laboratory Program and the
Group as a whole have available the facilities (including
appropriate biohazard facilities) required for conduct of
the proposed research.  Funds will not be provided for
alteration or renovation of facilities under this
Cooperative Agreement.
     
REVIEW PROCEDURES AND CRITERIA
     
Review Procedure
     
Upon receipt, applications will be reviewed by the Division
of Research Grants for completeness.  Incomplete
applications will be returned to the applicant without
further consideration.  Evaluation for responsiveness to
this 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 which are judged non-responsive will be
administratively withdrawn, and the proposed Principal
Investigator and institutional business official will be
notified.  Should an application be judged non-responsive to
this RFA, any of its constituent Laboratory Programs may be
submitted as an investigator initiated regular research
grant (R01) at the next receipt date.  Alternatively, the
consortium of Laboratory Programs could seek funding as a
program project grant (P01).  In either event, the
application would require modification in accordance with
either the R01 or P01 guidelines.  The new application would
not be considered an application for a Cooperative
Agreement, nor would it be considered a response to an RFA.
Questions concerning the relevance of proposed research to
the RFA should be directed to program staff as described in
"INQUIRIES."
     
In cases where the number of applications is large compared
to the number of awards to be made, the NIH may conduct a
preliminary scientific peer review to eliminate those which
are clearly not competitive for award.  The NIH will
withdraw from further competition those applications judged
to be noncompetitive and notify the Principal Investigator
and institutional business official.
     
Those applications judged to be both competitive and
responsive will be further evaluated, using the review
criteria shown 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 Program.
     
Review Criteria
     
Extent of relevance of applicant's (Group) objectives to the
discovery of NOVEL MODELS for developing new anticancer
treatments and strategies.
     
Scientific merit and originality of proposed research.
     
Adequacy of the scientific disciplines and specific
competencies represented by the Principal Investigator and
Program Leaders; research experience, competence,
commitment, and time availability of Principal Investigator,
Program Leaders, and other key personnel.
     
Technical merit and sufficiency of proposed methods for
using a new model and for evaluating the model.
     
Administrative experience and competence of Principal
Investigator in the development, implementation, and
management of comprehensive research programs.
     
Adequacy of plans for effective intra-Group communication
and for assuring Group cohesiveness.
     
Evidence of approval and commitment of institutions
represented by Group members to Group goals.
     
Evidence of availability and competence of the applying
institution to serve as the Central Operations Office for
the Group.
     
Commitment to accept NCI assistance in accordance with the
guidelines outlined under "TERMS OF AWARD."
     
Adequacy of existing physical facilities and resources of
the Principal Investigator and Program Leaders.
     
The review group will recommend an appropriate budget and
period of support for each approved application.
     
METHOD OF APPLYING
     
Receipt Date
     
The deadline for receipt of applications is June 9, 1989.
APPLICATIONS RECEIVED AFTER THIS DATE WILL BE CONSIDERED AS
NOT RESPONSIVE TO THIS RFA AND WILL BE RETURNED WITHOUT
REVIEW.  Please note, the Division of Research Grants will
not accept any application to this "Request for
Applications" that is the same as one currently being
considered by any other review group or awarding unit of the
National Institutes of Health.
     
General
     
The regular research grant application Form PHS-398 (Rev.
9/86) must be used in applying.  These forms are available
at most institutional business offices or from the Division
of Research Grants, National Institutes of Health, 9000
Rockville Pike, Bethesda, Maryland 20892.  One original and
six (6) copies are requested.
     
Submit a signed, typewritten original of the application,
including a single Checklist, and four (4) signed, exact
single sided photocopies in one package to:
     
The Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, Maryland 20892**
     
Send the remaining two (2) copies of your application
directly to:
     
Mr. Hernon Fox
Referral Officer
National Cancer Institute
Westwood Building, Room 848
Bethesda, MD 20892
Telephone:  (301)-496-3428
     
To expedite the review of your application, and to assure
its identification with this RFA:
     
The application form should have "NCI National Cooperative
Anticancer Model Development Group (RFA 89-CA-03)" typed in
bold letters on line 2 of the face page of the application
form; personalized titles more fitting for your application
should be listed on line 1 and not on line 2.
     
The RFA label available in the 9/86 revision of the