Subject: RFA CA-9l-01 NIH Guide l0/5/90
From: Dot Baker <[email-masked]>
To: [email-masked]
Date: Wed, 03 Oct 90 15:34 EST

Hello Again,
    This is the second item.  Please post to the NIH Listserver as:
     RFACA-91-01.100590
 Thanks.
        Dottie
 ---------------------------- Text of forwarded message -----------------------
 
REQUEST FOR APPLICATIONS
 
RFA NUMBER:  CA-91-01
 
RFA TITLE:  AIDS-Lymphoma Network
 
P.T. 34; K.W. 0715008, 0715035, 0755015
 
NATIONAL CANCER INSTITUTE
 
Letter of Intent Receipt Date:  December 7, 1990
Application Receipt Date: January 16, 1991
 
TABLE OF CONTENTS
 
I.    Introduction
II.   Purpose
III.  Research Goals and Scope
IV.   Mechanism
V.    Special Requirements
      A.  Requirements of Grantees
      B.  Requirements of the AIDS-Lymphoma Network
VI.   Eligibility Requirements
VII.  Special Instructions for Preparation of Applications
VIII. Review Procedures and Criteria
      A.  Review Procedures
      B.  Review Criteria
      C.  Study Population
IX.   Method of Applying
X.    Letters of Intent
XI.   Inquiries
 
I.  INTRODUCTION
 
The Division of Cancer Treatment (DCT) of the National Cancer
Institute (NCI) invites applications (R01 mechanism) from
interested investigators to participate in an AIDS-Lymphoma
Network.  The AIDS-Lymphoma Network will be composed of those
institutions who successfully compete for funding in this
Request for Applications (RFA) to
perform new therapeutic AIDS-lymphoma clinical trials, or AIDS-
lymphoma clinical trials with correlative laboratory studies.  The
purpose of the AIDS-Lymphoma Network is to foster interchange among
different institutions and to coordinate activities of the
different institutions working towards a common goal.
 
This RFA is designed to promote
collaborations and interactions among researchers from a variety of
basic and clinical disciplines to facilitate better treatment and
management of AIDS-lymphoma patients.  Both adult and pediatric
AIDS-lymphoma studies involving non-Hodgkin's or Hodgkin's disease
are encouraged.  Basic science investigators should collaborate
with AIDS Clinical Trial Centers, Cancer Centers, Cooperative
Groups or their equivalent to obtain AIDS-lymphoma tumor specimens
and set up collaborative interdisciplinary studies.
 
The present RFA announcement is for a single solicitation with one
specified deadline January 16, 1991, for receipt of applications.
Applications should be prepared and submitted in accordance with
the aims and requirements described in the RFA.
 
II.  PURPOSE
 
Adult and pediatric acquired immunodeficiency syndrome (AIDS)
patients are surviving longer due to improved retroviral and
opportunistic infection treatment and care.  As a result, acquired
immunodeficiency syndrome-associated malignancies have become more
prevalent and are now a major concern.  Lymphomas and Kaposi
sarcomas are the malignancies most frequently seen in AIDS
patients.  Both non-Hodgkin's lymphoma (NHL) and Hodgkin's disease
(HD) have been described in these patients.  The etiology of NHL in
AIDS patients remains unclear.  The most prominent clinical
features of NHL in HIV-positive patients are the aggressive nature
and course of the disease and the presence of unusual
extralymphatic disease in sites such as the CNS or bowel.  Results
of treatment using standard intensive multi-agent chemotherapy have
been disappointing, with median survival of less than one year in
treated patients, and difficult because conventional aggressive
combination chemotherapy exacerbates the patient's immunodeficient
state.  The choice of therapy must be based on the nature of the
disease and the overall condition of the patient.  The precise
relationship of HD to the underlying immunodeficient state in
patients with HIV infection also remains unclear.  Clinical
observations suggest that HD in this setting may have a different
natural history and therapeutic outcome when compared with HD in
the general population.  Patients with HIV infection and HD are
likely to have a poor therapeutic outcome and to develop AIDS-
associated opportunistic infections during therapy.
 
The NCI recognizes that research in AIDS-lymphoma is technically
difficult to conduct because of the complexity of this disease and
the relatively limited availability of study subjects at any single
institution.  Thus it is encouraging conduct of research relevant
to this RFA in the context of an AIDS-Lymphoma Network.  The AIDS-
Lymphoma Network will serve as a resource of information and will
work to facilitate patient accrual, obtaining tissue samples, and
exchange of information and materials between involved
investigators.  It is NCI's assessment that such collaboration
between investigators will permit achievement of the goals of this
RFA in the most rapid and efficient manner.
 
The purpose of this RFA and the resultant AIDS-Lymphoma Network is
to foster collaborative interactions between laboratory scientists
and clinicians to more precisely characterize the molecular and
genetic characteristics of AIDS-lymphoma or to devise more
effective treatment of this disease.  Laboratory research efforts
and new therapies ready to be applied in clinical situations are
solicited.  The results obtained from studying AIDS-lymphoma
patients will increase our understanding of the biology of
lymphomas and will assist the development of more effective
treatment in the general population of lymphoma
patients as well as those infected with HIV.
 
III.   RESEARCH GOALS AND SCOPE
 
The major goal of this RFA is to develop more effective management
and therapies for AIDS-lymphoma.  This goal can be accomplished by
supporting (1) the development of AIDS-lymphoma therapeutic
clinical trials or (2) AIDS-lymphoma clinical trials with
correlative laboratory studies.  Applications should be focused on
integrating research areas with clinical goals.  Support will be
provided to institutions with established clinical and/or
laboratory resources.  Both adult and pediatric AIDS-lymphoma
studies involving non-Hodgkin's and Hodgkin's disease are
encouraged.
 
This RFA envisions funding therapeutic clinical trials (pilot,
phase I, or phase II).  These therapeutic clinical trials will
usually involve a patient population ranging between 5-40 patients
with survival, response, and/or quality of life end points.  NCI
does not envision the establishment of multi-institutional
collaborative therapeutic clinical trials by the AIDS-Lymphoma
Network at this time.  Examples of clinical questions worth
considering are the following:  (1) What is the best method of
combining retroviral and antitumor therapies?  (2) What clinical
approach affords the least toxicity with the best therapeutic
index?
 
This RFA has a second research goal of funding clinical trials with
correlative laboratory studies.  Examples of scientific questions
worth considering are the following:  (1)  What is the clinical
significance of the abnormal patterns of distribution of disease
sites?  (2) What factors are involved in the different clinical
responses observed in AIDS-lymphomas?  (3) What are the potentially
exploitable features with respect to etiology and pathogenesis of
AIDS-lymphoma?  (4) What is the clinical significance of the
molecular and cytogenetic alterations specifically associated with
AIDS-lymphoma?  (5) What alterations occur in growth factors or
oncogenes in AIDS-lymphoma patients that may potentially lead to
new therapies?
 
Investigators are not limited to the above categories of potential
studies.  Other scientific approaches may be proposed.  All
institutions must have adequate statistical expertise and be
prepared to serve as a source of tumor specimens for other
institutions in the AIDS-Lymphoma Network.  Where feasible and
appropriate, applications for the proposed clinical studies should
include a suitable representation of minorities and women.  If the
applicant cannot comply, a clear rationale for their exclusion must
be provided.  The laboratory studies must have been demonstrated to
be applicable to tissue samples and/or bodily fluids from human
subjects.  A discussion of statistical methodology and significance
pertaining to laboratory data is essential.
 
IV.   MECHANISM OF SUPPORT
 
Awards will be made as investigator-initiated research grants
through the National Institutes of Health (NIH) grant-in-aid, in
accordance with Public Health Service (PHS) policies applicable to
research project grants.  This mechanism is used when the NCI
wishes to stimulate investigator-initiated research projects in
areas of special interest to the National Cancer Program.
Responsibility for the planning, direction, and execution of the
proposed research will be solely that of the applicant.  Except as
otherwise stated in this RFA, awards will be administered under PHS
grants policy as stated in the Public Health Service Grants Policy
Statement, DHHS Publication No.(OASH) 82-50,000, revised January 1,
1987.
 
This RFA is a one-time solicitation.  Applications received after
the deadline will be returned.  Generally, future unsolicited
competing continuation applications will compete as traditional
research project applications with all other investigator-initiated
applications and be reviewed by the Division of Research Grants
(DRG).  However, should the NCI determine that there is a
sufficient continuing program need, a request for renewal
applications will be announced.  Only recipients of awards under
this RFA will be eligible to apply.
 
Approximately $3,000,000 in total costs per year for three years
will be committed to specifically fund applications which are
submitted in response to this RFA.  It is anticipated that 10 to 15
awards will be made.  This funding level is dependent on the
receipt of a sufficient number of applications of high scientific
merit.  The total project period for applications submitted in
response to the present RFA should not exceed three (3) years.  The
earliest feasible start date for the initial award will be July 16,
1991.  Although this program is provided for in the financial plans
of the NCI, the award of grants pursuant to this RFA is contingent
upon the availability of funds appropriated for fiscal year 1991.
 
V.   SPECIAL REQUIREMENTS
 
It is essential that there be good liaison between basic scientists
and clinicians, as the goal of this RFA is to apply the knowledge
and techniques of basic science to the treatment and management of
AIDS-lymphoma.  NCI representatives will assist the AIDS-Lymphoma
Network by facilitating the coordination of the activities and the
exchange of information among the research groups within the AIDS-
Lymphoma Network.
 
A.  REQUIREMENTS OF GRANTEES
 
The grantees are required to participate in the AIDS-Lymphoma
Network.  Participation in the AIDS-Lymphoma Network is defined as,
but not limited to, attendance at the annual meeting of the AIDS-
Lymphoma Network by the Principal Investigator (PI) or a
representative of each research group and the sharing of
appropriate tumor tissue with other participating research groups
of the AIDS-Lymphoma Network.  Grantees conducting clinical trials
are required to accrue patients into approved clinical protocols.
Grantees and PIs are required to comply with all FDA monitoring and
reporting requirements for investigational agents.  Grantees are
required to meet the requirements for the protection of human
subjects and the protection of investigators working with AIDS
materials/patients.
 
B.   REQUIREMENTS OF THE AIDS-LYMPHOMA NETWORK
 
The AIDS-Lymphoma Network will be composed of those institutions
who successfully compete for funding in this RFA.  The PIs of the
grants will be members of the Network and will elect a chairman to
serve as the Chairman of the AIDS-Lymphoma Network.  The Chairman
will set the agenda for all meetings and coordinate all Network
activities.  The members of the Network will review procedures for
patient accrual, quality control, and study monitoring and
procedures for tissue acquisition, processing, distribution,
storage, and methods of histopathological diagnosis for uniformity
among the institutions.  There will be a meeting shortly after the
award of the grants to organize the AIDS-Lymphoma Network.
Subsequent annual meetings of the AIDS-Lymphoma Network will review
progress, plan future research activities, coordinate tissue
utilization, and establish priorities.  Travel funds for the
organizational meeting and subsequent annual meetings are to be set
aside as a budget line item in each project budget.  Funds for
travel to these meetings will be restricted for this purpose only.
Staff from the NCI and the National Institute of Allergy and
Infectious Diseases may attend these meetings.  NCI staff may serve
in a liaison role whenever possible, however, substantial
programmatic involvement is neither anticipated nor implied.
 
VI.  ELIGIBILITY REQUIREMENTS
 
Applicant organizations should be located in the United States
and Canada.  Non-profit and for-profit organizations and
institutions, and government agencies are eligible to apply.
 
VII.   SPECIAL INSTRUCTIONS FOR PREPARATION OF APPLICATIONS
 
General instructions for the preparation of investigator-initiated
grants are contained in the Grant Application Form PHS 398 (revised
10/88).
 
Because of the Special Requirements discussed in Section V above,
it is critical that each applicant include specific plans for
responding to these requirements.  Investigators proposing new
clinical trials should submit a draft protocol with their
application, and address all issues related to clinical trials.
Investigators utilizing on-going clinical trials should also
include the clinical protocol.  Institutions with correlative
laboratory studies should clarify whether their clinical trials
will provide them with sufficient AIDS-lymphoma tumor specimens or
whether they will be dependent upon the AIDS-Lymphoma Network for
additional specimens.
 
All investigators should address issues in communication,
collaboration, tissue procurement, and how these studies would
contribute toward the development of new therapies or management
strategies for AIDS-lymphoma.  A discussion of statistical
methodology and significance pertaining to laboratory and clinical
studies is essential.
 
VIII.  REVIEW PROCEDURES AND CRITERIA
 
A.   REVIEW PROCEDURES
 
Upon receipt, applications will be reviewed initially by the
Division of Research Grants (DRG)
for completeness.  Evaluation for responsiveness to the RFA is an
NCI program staff function.  Applications will be judged to
determine whether they comply with the goals, scope, and objectives
of the program as described in the RFA (Section III).  Incomplete
and non-responsive applications will be returned to the applicant
without further consideration.  Applications that are non-
responsive will be inactivated administratively, but may be
submitted as regular investigator-initiated research grant
applications at the next grant application receipt date.  Questions
concerning the responsiveness of proposed research to the RFA
should be directed to program staff as described in section XI.
 
In cases where the number of applications is large compared to the
number of awards to be made, the NIH will conduct a preliminary
scientific peer review to eliminate those which are clearly not
competitive.  The NIH will administratively withdraw from
competition those applications judged to be noncompetitive and
notify the applicant 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
application in light of the special needs of the Institute and the
priorities of the National Cancer Program.
 
B.  REVIEW CRITERIA
 
The factors considered in evaluating the scientific merit of each
response to this RFA will be:
 
1.  Extent to which the proposed research addresses the goals of
the RFA.
 
2.  The scientific merit of the proposed approach, including
adequacy and quality of the methodological approach, the research
design, the ability to serve as a source of tumor specimens, and a
discussion of statistical methods.
 
3.  Experience, training, time availability, clinical and research
competence of the investigators involved.
 
4.  Adequacy of plans for effective collaboration and communication
between laboratory, clinical, and statistical investigators within
their research institution.  For new clinical trials, adequacy of
draft protocols.
 
5.  Adequacy of available facilities, statistical collaboration,
and data management resources.
 
6.  Adequacy of patient population and plans for inclusion of women
and minorities in clinical trials.
 
7.  Provision for the adequate protection of human subjects and the
humane treatment of animals.
 
8.  Appropriateness of the budget and period of support for the
scientific effort proposed.
 
C.   STUDY POPULATION
 
NCI requires the applicant to recruit women and minorities into
their study population.  Applicants must address the study
population issue in their application.
 
IX.   METHOD OF APPLYING
 
The USPHS research grant application form PHS-398 (revised 10/88)
must be used in applying for these grants. These forms are
available at most institutional business offices; or from the
Office of Grant Inquiries, Division of Research Grants, National
Institutes of Health, Room 449, Westwood Building, 5333 Westbard
Avenue, Bethesda, MD 20892; or from the NCI Program Director named
below.
 
The RFA label available in the 10/88 revision of Application Form
398 must be affixed to the bottom of the face page.  Failure to use
this label could result in delayed processing of your application
such that it may not reach the review committee in time for review.
In addition, the RFA number and title (to the extent that space
permits) should be typed on line 2 of the face page of the
application form.
 
Submit a signed, typewritten original of the application, including
the Checklist, and four (4) signed, exact photocopies, in one
package to the Division of Research Grants at the address below.
The photocopies must be clear and single sided.
 
DIVISION OF RESEARCH GRANTS
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD 20892**
 
At the time of submission, two (2) additional copies of the
application should also be sent to:
 
REFERRAL OFFICER
Division of Extramural Activities
National Cancer Institute
Westwood Building, Room 838
5333 Westbard Avenue
Bethesda, MD 20892
 
Applications should be received by January 16, 1991.  If an
application is received after the indicated dates, it will be
administratively withdrawn.
If the application submitted in response to this RFA is
substantially similar to a research grant application already
submitted to the NIH for review, but has not yet been reviewed,
the applicant will be asked to withdraw either the pending
application or the new one.  Simultaneous submission of identical
applications will not be allowed, nor will essentially identical
applications be reviewed by different review committees.
Therefore, an application cannot be submitted in response to this
RFA that is essentially identical to one that has already been
reviewed.  This does not preclude the submission of substantial
revisions of applications already reviewed, but such applications
must include an introduction addressing the previous critique.
 
X.   LETTER OF INTENT
 
Prospective applicants are asked to submit by December 7, 1990, a
letter of intent that includes a descriptive title of the proposed
research, the name and address of the principal investigator, the
names of other key personnel, the participating institutions, the
number and title of the RFA in response to which the application is
being submitted.  Although a letter of intent is not required, is
not binding, and does not enter into the review of subsequent
applications, the information which it contains is extremely
helpful in planning for the review of   applications.  It allows
NCI staff to estimate the potential review workload and to avoid
possible conflict of interest in the review.  In follow-up phone
conversations, Program staff may be able to assist applicants as
well as ascertain whether they have understood the objectives of
the RFA and opted for an appropriate funding mechanism. Therefore,
NCI would like to emphasize the benefits to the applicant and to
staff of having a principal investigator submit a letter of intent.
The letter establishes communication between the potential
applicant and program staff initiating the RFA.  Program staff may
be able to assist prospective applicants in several areas such as
scientific content and objectives of the application, and
appropriate use of consultants.
 
The letter of intent should be sent to:
 
BY US POSTAL
 
Dr. Roy S. Wu
Health Scientist Administrator
Cancer Therapy Evaluation Program
Division of Cancer Treatment
National Cancer Institute
Executive Plaza North, Room 734
Bethesda, MD 20892
Telephone: (301) 496-8866
FAX: (301) 496-9384
 
BY DIRECT DELIVERY
 
Dr. Roy S. Wu
Health Scientist Administrator
Cancer Therapy Evaluation Program
Division of Cancer Treatment
National Cancer Institute
Executive Plaza North, Room 734
6130 Executive Blvd.
Rockville, MD 20852
Telephone: (301) 496-8866
FAX: (301) 496-9384
 
XI.   INQUIRIES
 
Written or telephone inquiries concerning the objectives and scope
of this RFA or inquiries about whether or not specific proposed
research would be responsive are encouraged and should be directed
to Dr. Roy S. Wu at the above address.  The program director
welcomes the opportunity to clarify any issues or questions from
potential applicants.
 
This program is described in the Catalog of Federal Domestic
Assistance No. 93.395, (Clinical Treatment Research).  Awards are
under authorization of the Public Health Service Act, Title IV,
Part A (Public Law 78-410 as amended: 42 USC 241) and administered
under PHS Grant Policies and Federal Regulations 42 CFR 52 and 45
CFR Part 74.  This program is not subject to the intergovernmental
review requirements of Executive Order 12372 or Health Systems
Agency review.