Full Text CA-94-003

TISSUE AND BIOLOGICAL FLUIDS BANKS OF HIV-RELATED MALIGNANCIES

NIH GUIDE, Volume 23, Number 2, January 14, 1994

RFA:  CA-94-003

P.T. 34

Keywords: 
  AIDS 
  Cancer/Carcinogenesis 
  Biological Resources 


National Cancer Institute

Letter of Intent Receipt Date:  April 15, 1994
Application Receipt Date:  May 17, 1994

PURPOSE

The Cancer Therapy Evaluation Program (CTEP) of the Division of
Cancer Treatment (DCT), National Cancer Institute (NCI) invites
applications from consortia of institutions for cooperative
agreements to design and develop banks of tissue and biological
fluids and clinical data from patients with HIV-associated
malignancies.  The purpose of the proposed awards is to stimulate
cooperative efforts to identify and improve access to tumor tissue,
biological specimens, and associated clinical outcome data that could
then be utilized for research by the research community at-large on
the pathogenesis of HIV-associated malignancies and development of
more effective therapies.  Seed money can be requested (as described
below) for proposed pilot studies utilizing these materials.

HEALTHY PEOPLE 2000

The Public Health Service (PHS) is committed to achieving the health
promotion and disease prevention objectives of "Healthy People 2000,"
a PHS-led national activity for setting priority areas.  This Request
for Applications (RFA), Tissue and Biological Fluids Banks of
HIV-Related Malignancies, is related to the priority area of cancer
and AIDS.  Potential applicants may obtain a copy of "Healthy People
2000" (Full Report:  Stock No. 017-001-00474-0) or "Healthy People
2000" (Summary Report:  Stock No.  017-001--00473-1) through the
Superintendent of Documents, Government Printing Office, Washington,
DC 20402-9325 (telephone 202-783-3238).

ELIGIBILITY REQUIREMENTS

Domestic and Canadian for-profit and non-profit organizations, public
and private such as universities, colleges, hospitals, laboratories,
units of State and local governments, and eligible agencies of the
Federal government are eligible to apply.  Foreign institutions other
than Canadian are not eligible to apply or be a collaborating
institution.  Canadian institutions are included because many of them
are members of the NCI-Sponsored Clinical Trials Cooperative Groups
and the NIAID-sponsored AIDS Clinical Treatment Units.  Applications
must be from a consortium of no less than two institutions, which can
include, but are not limited to, the NCI-Sponsored Clinical Trials
Cooperative Groups, the NIAID-Sponsored AIDS Clinical Treatment
Units, or a coalition of Cancer Centers.  New and experienced
investigators are encouraged to apply.  Applications from minority
individuals and women are encouraged.

MECHANISM OF SUPPORT

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

Awards and level of support depend on receipt of a sufficient number
of applications of high scientific merit.  Because of the variation
in numbers of patients to be accrued, and specimens to be accessed,
it is anticipated that the size of awards will vary also.  The total
project period for applications submitted in response to the RFA may
not exceed four years.  The anticipated award date is September 30,
1994.  Although this program is provided for in the financial plans
of the NCI, awards pursuant to this RFA are contingent upon the
availability of funds for this purpose.

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

FUNDS AVAILABLE

Approximately $2,000,000 in total costs per year for four years will
be committed to fund applications submitted in response to this RFA.
It is anticipated that three to four awards for the Tissue and
Biological Fluids Banks of HIV-Related Malignancies will be made.  Up
to ten percent of the total costs, or $50,000 per year for three
years (whichever number is smaller, and to start in year two of the
cooperative agreement) can be requested for pilot studies.

RESEARCH OBJECTIVES

Background

Congenital and acquired states of immunodeficiency increase the
incidence of high-grade B cell non-Hodgkin's lymphoma (NHL), Kaposi's
sarcoma, and certain types of epithelial malignancies.  Individuals
infected with human immunodeficiency virus (HIV) have a marked
increase in the appearance of intermediate and high-grade B cell NHL
and Kaposi's sarcoma, and show trends for an increased incidence for
Hodgkin's disease, anogenital dysplasia and cancer, and basal cell
carcinoma, compared to age-matched controls.  The tumors in
HIV-infected individuals are generally aggressive and insufficiently
sensitive to conventional therapy.

The need to obtain tumor tissue for research was discussed at the
conference on AIDS-Lymphoma convened in May 1992 by the Cancer
Immunology Branch, Division of Cancer Biology, Diagnosis, and Centers
(DCBDC), NCI.  The request for tissue was made both by investigators
participating in clinical trials research, as well as those
laboratory investigators without ready access to clinical specimens.
The conference also resulted in the development of the currently
available RFA for studies on the basic biology of AIDS lymphoma (RFA:
CA-93-40), issued by the Cancer Immunology Branch of DCBDC.

The CTEP, DCT has been investigating methods to develop and utilize
tissue and clinical data banks.  Tumor tissue collected during
clinical trials would permit research on the pathogenesis of
HIV-associated malignancies and on the development of effective
therapies.  It was concluded that the most efficient method to obtain
tumor specimens and bodily fluids would take advantage of the
meticulous follow-up and monitoring of patients in the context of
clinical trials in the institutions involved in the care of patients
with HIV-associated malignancies.

Objectives and Scope

The purpose of the proposed awards is to stimulate cooperative
efforts to design and develop Tissue and Biological Fluids Banks of
HIV-associated malignancies with associated clinical and outcome
data.  The Banks would provide critical resources to the research
community at-large for research studies to gain insight into the
pathogenesis of the malignancies that arise in HIV-infected
individuals.

Formation of a consortium of institutions is encouraged to maximize
specimen accession.  All applicants must provide evidence of
availability and access to patient specimens, and each Consortium
(made up of a minimum of two institutions) must have an Operations
Office that is capable of providing the necessary coordination of
specimen collection, data management, and storage of specimens at a
central location.  Banked specimens may consist of fixed or frozen
tumor tissue and biological fluids.  Investigators must address
coordination of quality control among collaborating institutions and
consortia with regard to collection, shipment and storage of
specimens.

The awardees will provide to the research community at-large tissue
and biological fluids of high quality from patients with
HIV-associated malignancies for high priority research studies.  This
task will be accomplished through the workings of two committees, the
Steering Committee and the Research Evaluation and Decision Panel
(REDP).  The duties of these two committees are described below under
SPECIAL REQUIREMENTS.

Of the funds provided by this RFA, at least 90 percent of the total
costs proposed in each application must be directed to the actual
banking (accession of tissues and biological fluids, facilities,
laboratory personnel, clinical data collection and linkage to
specimens) and up to 10 percent of the total costs, or $50,000 per
year for three years (whichever number is smaller, to start in year 2
of the cooperative agreement) can be requested for pilot studies.
Pilot studies should be designed to obtain sufficient data to form
the foundation for future R01 research grant applications.  The pilot
studies should also help identify new research areas where additional
investigations should be pursued.  Examples of such studies could
include, but are not limited to, the following:  prospectively
comparing the response to therapy in patients with different
molecular characteristics, determining the cytokine expression that
might be etiologically involved in the development of the
malignancies seen in HIV infection and the effect on such expression
by therapy; evaluating the interaction of other factors with HIV in
malignancies and the effects of therapy on those factors; assessing
the impact of therapy on both viral burden and tumor response, and
designing assays for in vitro or in vivo animal models for testing of
pharmacologic compounds in HIV-associated malignancies that could be
tested in the context of a clinical trial.

SPECIAL REQUIREMENTS

Definitions

CONSORTIUM - A consortium must include a minimum of two institutions,
which join together under the guidance and direction of a single
Principal Investigator.  Each consortium must have clinical
laboratory, and pathology components representing diverse scientific
disciplines.

AWARDEE - The organization to which a cooperative agreement is
awarded and which is responsible and accountable to NCI for the use
of funds provided and for performance of the cooperative
agreement-supported project.

PRINCIPAL INVESTIGATOR (PI) - The single individual at the awardee
institution designated by the awardee in the cooperative agreement
application, who is responsible for the scientific and technical
direction of the project.

OPERATIONS OFFICE - The central office at the Applicant/Awardee
Institution that handles all the clinical data and the tissue and
biological fluids repository data.  All specimens and clinical data
from the Applicant/Awardee Institution will be coordinated and
located at one central location.  The Principal Investigator serves
as the Head of the Operations Office.

NCI PROGRAM DIRECTOR - The CTEP extramural grants Program Director,
who will be coordinating DCT's interactions and administering and
providing guidance for the overall program within the NCI.  He/she is
available for consultation during preparation of applications as well
as the duration of research conducted through this cooperative
agreement.  He/she serves in a back-up role for the NCI Coordinator.

NCI COORDINATOR - The Senior Investigator, Medicine Section, Clinical
Investigations Branch, CTEP, DCT, who interacts scientifically with
the Applicant/Awardee Institutions.

STEERING COMMITTEE -  a single Committee whose membership includes
the NCI Coordinator, the PI and one other investigator from each
awarded cooperative agreement, and one research scientist with
expertise in the field of HIV-associated malignancies who is not
affiliated with any of the Awardee Institutions/Consortia.  This
research scientist on the Steering Committee will be appointed by
mutual agreement of the NCI Coordinator and the PIs.  The Steering
Committee will serve as the governing board of the Tissue and
Biological Fluids Banks of HIV-Related Malignancies (see under "Terms
and Conditions of Award" for function of Steering Committee).

REVIEW AND EVALUATION DECISION PANEL (REDP) - A panel composed of the
NCI Program Director and six to eight scientists with clinical/basic
research expertise in the field of HIV-associated malignancies.  The
members of the panel will evaluate all research (those of the
awardees as well as proposals from the research community at-large)
proposing to utilize the specimen and data Banks according to the
evaluation and review criteria provided by the Steering Committee.
The panel will provide a recommendation to the Steering Committee
regarding the priority of the proposed research.  The membership of
the REDP may vary, depending on the scientific areas of the proposed
research to be reviewed and evaluated.  All members will be selected
by the Steering Committee (see under "Terms and Conditions of Award"
for function of REDP).

Study Organization and Function

The overall structure of the Tissue and Biological Fluids Banks of
HIV-Related Malignancies is envisioned to consist of three or four
funded Consortia that are governed and coordinated through the
Steering Committee.  Each Bank or funded Consortium is composed as
follows: two or more member institutions of the Consortium who are
responsible for contributing specimens, biological fluids and
clinical data; an Operations Office at the awardee institution; and
one PI who is responsible for providing the scientific and
administrative leadership for the Consortium and serves as the Head
of the Operations Office.

The overall function of the Tissue and Biological Fluids Banks of
HIV-Related Malignancies is to serve as a national resource to the
research community at-large.  The Tissue and Biological Fluids Banks
of HIV-Related Malignancies will provide tissue specimens and
clinical outcome data after the requests for such specimens and data
have been reviewed and prioritized by the REDP and approved by the
Steering Committee.  Requests for specimens and data from the
awardees and their collaborators will be reviewed, prioritized by the
REDP and approved by the Steering Committee along with all other
requests from investigators in the research community at-large.

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

Terms and Conditions of Award

These special Terms of Award are in addition to, and not in lieu of,
otherwise applicable OMB administrative guidelines, HHS Grant
Administration Regulations at 45 CFR part 74 and 92, and other HHS,
PHS, and NIH Grant Administration policy statements.

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

1.  Awardee Rights and Responsibilities

The Awardee will have primary and lead responsibilities for the
project as a whole, including the following:

The Awardee will establish a bank, collect specimens and clinical
data.

The Awardee Principal Investigator, and one other investigator from
the Consortium, will serve on the Steering Committee.

The Awardee will work together with the other Awardees through the
Steering Committee to establish uniform collection methods and
policies, and to assure quality control of specimens and data.  The
Awardee will be required to accept and implement the common policies
and procedures approved by the Steering Committee.

The awardee agrees to provide access to specimens and data to
investigators both within and outside of the awardees' institutions
based on the prioritization of research proposals set by the REDP and
final approval by the Steering Committee.  The awardee will abide by
the decisions of the Steering Committee based on recommendations from
the REDP.

The Awardee will retain custody of and have primary rights to the
data developed under these awards, subject to Government rights of
access consistent with current HHS, PHS, and NIH policies.

The Awardee will ensure that all cooperating institutions must have
an approved assurance of compliance for the protection of human
subjects on file with the Office for Protection from Research Risks
NIH and that necessary IRB reviews are conducted by the IRBs of the
appropriate institutions in accordance with 45 CFR part 46 prior to
the involvement of human subjects.

The Awardee must provide an annual progress report in its continuing
application to CTEP, NCI, and a copy to the chairperson of the
Steering Committee, in a format that is standardized and compatible
with the annual progress reports from the other Awardees.
Information on the operations of the bank as well as performance and
progress on pilot studies are to be included.

2.  National Cancer Institute Staff Responsibilities

The NCI Coordinator and the NCI Program Director will have
substantial scientific-programmatic involvement during conduct of
this activity through participation in the Steering Committee and the
REDP, respectively.  They will provide technical assistance, advice
and coordination, assure that the Steering Committee and the REDP
follow the NIH guidelines on conflict of interest issues and play
critical roles in promoting the availability and use of the Banks.
The roles of the NCI Coordinator and the NCI Program Director are to
assist and facilitate, but not to direct activities of the Tissue and
Fluids Banks of HIV-related Malignancies.

The NCI Coordinator will serve as a voting member on the Steering
Committee, may attend meetings of the REDP as an observer and will
serve as an information resource on the relevant NCI extramural
awardees likely to require the resources of the proposed banks.  The
NCI Program Director will serve as the non-voting executive secretary
of the REDP.  He/she will advise the ad hoc REDP members on the
Steering Committee's algorithm for reviewing the proposals requesting
biological specimens and clinical data and will provide information
on other relevant on-going NCI activities and help answer any
programmatic issues.  Both NCI staff will serve on subcommittees of
the Steering Committee and the REDP as required.  If the NCI
Coordinator is not able to attend a meeting of the Steering
Committee, the NCI Program Director will attend that meeting.  The
NCI Program Director attending such Steering Committee meeting will
not vote on any proposals reviewed by the REDP, but will vote on
other issues.

The National Cancer Institute reserves the right to reduce the
budget, to withhold support, and to suspend, terminate or curtail a
study or an award in the event of substantial shortfall in specimen
accrual, data reporting, inadequate quality control in specimens or
clinical data collection, non-adherence to biohazard precautions,
refusal to carry out the recommendations of the REDP and Steering
Committee, or substantial failure to comply with the terms of award.

3.  Collaborative Responsibilities

a.  Steering Committee

The Steering Committee will serve as the governing board of the
Tissue and Biological Fluids Banks of HIV-Related Malignancies.  The
Steering Committee is composed of the NCI Coordinator, the PI and one
other investigator from each awarded Consortium, and one research
scientist with expertise in the field of HIV-associated malignancies
who is not affiliated with any of the Awardee Institutions/Consortia.
This research scientist on the Steering Committee will be appointed
by mutual agreement of the NCI Coordinator and the PIs.

The Steering Committee has primary responsibility for developing and
evaluating policies for quality control of the specimens, and
uniformity of procedures across institutions; for promoting the
availability and the uses of the specimen bank; and for developing an
algorithm for review and prioritization of research proposals, to be
used by the REDP, utilizing the banked specimens and clinical data
(e.g., based on scientific merit with high priority awarded to
investigators with funded grants).  The NCI Coordinator will assist
the other members of the Steering Committee in all these tasks.
Furthermore, the NCI Coordinator will serve as the scientific liaison
between the awardees and other program staff of NCI who have previous
experience in the establishment of tumor banks.  Each member of the
Steering Committee will have one vote.  One Chairperson will be
selected by the Steering Committee, and be someone other than the NCI
Coordinator.  The Chairperson is responsible for coordinating the
Steering Committee's activities, for preparing meeting agendas and
for scheduling and chairing meetings.  The Chairperson must prepare
an annual progress report which will include individual reports from
each awardee.  Each awardee is responsible for timely preparation of
this report.  The NCI Coordinator will prepare the minutes of all
meetings.

The Steering Committee is responsible for providing documentation as
to the availability and accessibility of specimens and data for
scientific investigations (e.g., the Chairperson of the Steering
Committee will send the principal investigator of an REDP reviewed
high priority proposal a letter as to the availability of the
specimens, with a final letter to be sent stating that specimens
and/or data will be made available as requested when funding for the
REDP reviewed high priority proposal is documented.  If the proposal
is already funded at the time it is submitted to the REDP and
reviewed as high priority, then the Chairperson of the Steering
Committee will send the final letter at that time).  The only
occurrence in which the Steering Committee can overturn the
recommendations of the REDP is when specimens and/or data are not
available.

Subcommittees will be established by the Steering Committee as it
deems appropriate.  The NCI Coordinator will serve on subcommittees
as appropriate.

The Steering Committee will meet at a minimum of twice per year in
conjunction with the NCI Coordinator, to map strategies to fulfill
the objectives of their function, to develop operating procedures and
to evaluate progress.  The initial meeting will occur immediately
after funding.  The Steering Committee will also meet with the REDP
once per year.  The NCI Program Director will attend the joint
meeting of the Steering Committee and REDP as a non-voting member.

The Steering Committee will select members of the REDP.  The Steering
Committee in the conduct of all business matters will pay particular
attention to conflict of interest issues, especially in actions
regarding recommended prioritizations of the REDP.

b.  Research Evaluation and Decision Panel

The REDP will serve the Steering Committee by reviewing and
evaluating all research submitted by the research community at-large
as well as by the awardees proposing to utilize the specimen and
clinical data Banks   A recommendation in terms of priority of the
proposed research would be provided to the Steering Committee.  The
only occurrence in which the Steering Committee can overturn the
recommendations of the REDP is the unavailability of the requested
specimens and/or clinical data.  The REDP will meet with the Steering
Committee at least once yearly, at one of the two scheduled Steering
Committee meetings.

The REDP will be composed of the NCI Program Director and six to
eight scientists with clinical/basic research expertise in the field
of HIV-associated malignancies.  The members of the panel will
evaluate all research (those of the awardees as well as proposals
from the research community at-large) proposing to utilize the
specimen and data Banks according to the evaluation and review
criteria provided by the Steering Committee.  The panel will provide
a recommendation to the Steering Committee as to the priority of the
proposed research. The membership of the REDP may vary, depending on
the scientific areas of the proposed research to be reviewed and
evaluated.  All members will be selected by the Steering Committee.
The Chairperson of the REDP will always be someone other than the NCI
Program Director.

The review of proposals can be conducted either in person, by
conference call or by mail at a minimum of twice per year.  All
reviews will be conducted according to rules pertaining to conduct of
reviewers for NIH grants, contracts, and cooperative agreements,
paying special attention to issues of conflict of interest, whether
real or apparent.  The NCI Program Director will serve as the
executive secretary (non-voting role) for the review and will forward
the final recommendation to the Steering Committee.  The NCI Program
Director in the role of executive secretary of review will inform and
advise the ad hoc REDP members on the Steering Committee's algorithm
for review and prioritization of proposals; will provide information
to the ad hoc REDP members on the studies that have already been
approved and on other relevant on-going NCI activities so that
redundant studies are not performed; and will help answer any
programmatic issues.  The NCI Program Director also plays an
important role in the whole review process by lending a degree of
continuity with the Steering Committee, as the ad hoc REDP
composition may change depending on the expertise required to review
the submitted research proposals.

4.  Arbitration

Any disagreement that may arise on scientific/programmatic matters
(within the scope of the award), between award recipients and the NCI
may be brought to arbitration.  An arbitration panel will be composed
of three members -- one selected by the Steering Committee (with the
NCI member not voting) or by the individual awardee in the event of
an individual disagreement, a second member selected by the NCI, and
the third member selected by the two prior selected members.  This
special arbitration procedure in no way affects the awardee's right
to appeal an adverse action that is otherwise appealable in
accordance with the PHS regulations at 42 CFR part 50, subpart D and
HHS regulation at 45 CFR part 16.

STUDY POPULATIONS

SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH
POLICIES CONCERNING INCLUSION OF FEMALES AND MINORITIES IN CLINICAL
RESEARCH STUDY POPULATIONS

NIH policy is that applicants for NIH clinical research grants and
cooperative agreements are required to include minorities and females
in study populations so that research findings can be of benefit to
all persons at risk of the disease, disorder or condition under
study; special emphasis must be placed on the need for inclusion of
minorities and females in studies of diseases, disorders and
conditions which disproportionately affect them.  This policy is
intended to apply to males and females of all ages.  If females or
minorities are excluded or inadequately represented in clinical
research, particularly in proposed population-based studies, a clear
compelling rationale must be provided. As Kaposi's sarcoma occurs
predominantly in men, the lack of female participation should be
rationally explained.

The composition of the proposed study population must be described in
terms of gender and racial/ethnic group.  In addition, gender and
racial/ethnic issues should be addressed in developing a research
design and sample size appropriate for the scientific objectives of
the study.  This information should be included in the form PHS 398
in Sections 1-4 of the Research Plan, AND summarized in Section 5,
Human Subjects.  Applicants are urged to assess carefully the
feasibility of including the broadest possible representation of
minority groups.  However, NIH recognizes that it may not be feasible
or appropriate in all research projects to include representation of
the full array of United States racial/ethnic minority populations
(i.e., Native Americans including American Indians or Alaskan
Natives, Asian/Pacific Islanders, Blacks, Hispanics).  The rationale
for studies on single minority population groups must be provided.

For the purpose of this policy, clinical research is defined as human
biomedical and behavioral studies of etiology, epidemiology,
prevention (and preventive strategies), diagnosis, or treatment of
diseases, disorders or conditions, including but not limited to
clinical trials.

The usual NIH policies concerning research on human subjects also
apply.  Basic research or clinical studies in which human tissues
cannot be identified or linked to individuals are excluded.  However,
every effort should be made to include human tissues from females and
racial/ethnic minorities when it is important to apply the results of
the study broadly, and this should be addressed by applicants.

For foreign awards, the policy on inclusion of females applies fully;
since the definition of minority differs in other countries, the
applicant must discuss the relevance of research involving foreign
population groups to the United States' populations, including
minorities.

If the required information is not contained within the application,
the application will be returned.

Peer reviewers will address specifically whether the research plan in
the application conforms to these policies.  If the representation of
females or minorities in a study design is inadequate to answer the
scientific question(s) addressed AND the justification for the
selected study population is inadequate, it will be considered a
scientific weakness or deficiency in the study design and will be
reflected in assigning the priority score to the applications.

All applications for clinical research submitted to NIH are required
to address these policies.  NIH funding components will not award
grants or cooperative agreements that do not comply with these
policies.

Note:  In addition to the requested information about the composition
of proposed study populations involving human subjects, peer review
groups need similar information about the clinical or regional
populations from which the samples are drawn in order to evaluate the
extent of participation by women and minorities.  To avoid delays in
review of such applications, the NCI advises that, as a minimum, the
application should provide gender/minority information on hospital
admissions, accruals to trials, and patient catchment areas.  Studies
involving non-hospital populations, such as community-based studies
should provide similar data abut populations in the area or region
from which the study subjects will be drawn.  In the absence of
current data, historical demographic information and/or previous
recruitment data for similar studies from the proposed study sites
should be provided.  Further, any specific plans for increasing
gender/minority representation in studies should also be included in
the application to facilitate review.

LETTER OF INTENT

Prospective applicants are asked to submit, by April 15, 1994, a
letter of intent that includes a descriptive title of the proposed
research, name, address, and telephone number of the Principal
Investigator, identities of other key personnel and participating
institutions, and the number and title of the RFA in response to
which the application may be submitted.

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

The letter of intent is to be sent to:

Dr. Roy S. Wu
Division of Cancer Treatment
National Cancer Institute
Executive Plaza North, Room 734
6130 Executive Boulevard
Bethesda, MD  20892
Telephone:  (301) 496-8866
FAX:  (301) 480-4663

APPLICATION PROCEDURES

The research grant application form PHS 398 (rev. 9/91) is to be used
in applying for these awards.  These forms are available at most
institutional offices of sponsored research; from the Office of
Grants Information, Division of Research Grants, National Institutes
of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892,
telephone 301/584-7248; and from the NIH program administrator named
below.

It is critical that applicants clearly describe plans to accommodate
stated criteria and staff involvement as listed in the Terms and
Conditions of Award, and in the Review Criteria section.

The applicant should form a Consortium composed of no less than two
institutions to design and develop a specimen bank and document their
access to and numbers of HIV infected oncology patients in clinical
trials.  Details on the mechanism for tissue accession and storage
and procedures for clinical data collection and storage need to be
provided.  Investigators also should address quality control issues
for the specimens and clinical data collected.  The investigators
need to address the types of specimens (frozen and fixed tumor
tissue, biological fluids) planned for inclusion in the bank.
Tissues and fluids to be collected should come from groups of
patients that are treated uniformly on standard therapeutic regimens
or clinical trials where clinical and outcome data are available.
Examples of pathology and clinical data forms that will be used
should be provided in the appendix of the application.  Investigators
should propose an approach to setting up a common database for the
Banks.

Applicants should clearly describe the Operations Office, the
facilities for banking and data collection, the investigators'
experience and expertise in banking and the applicants' ability to
obtain tumor tissue and biological specimens from HIV-infected
patients with malignancies.  The applicants must provide details on
the appropriate facilities and biohazard precautions and comply with
all applicable Federal, State and Local regulations, laws and
ordinances in the operation of the Banks.

The applicants must state a willingness to cooperate with other
awardees in developing policies for quality control and to share data
with other awardees.

The applicants must state a willingness and should discuss their
approach to cooperate with the Steering Committee and the REDP in
evaluating research proposals utilizing specimens obtained in their
bank(s) and to abide by the decisions of the REDP in prioritizing
such proposals, after final approval by the Steering Committee based
on specimen availability.

Each applicant should provide the name and qualifications for the
second investigator from the consortium on the Steering Committee.
Each applicant should also provide the name and qualifications of one
scientist not affiliated with its institution/consortium as a
potential member of the Steering Committee.  In addition, each
applicant should provide the names and qualifications of two
scientists not affiliated with its institution/consortium  as
potential members of the REDP.  Travel funds for two investigators to
attend two Steering Committee meetings per year should be included in
the budget.  Furthermore, each awardee should include travel funds
for two REDP members in the budget for one yearly meeting with the
Steering Committee.  A conference call budget should be included for
two members of the REDP to review research proposals.

All costs required for the proposed Banks must be included in the
application and must be fully justified.  These costs include the
collection and storage of specimens, quality assurance, data
management and analysis, and travel.  An estimate and explanation
based on cost per specimen is required.

Applicants seeking up to 10 percent of the total cost, or up to
$50,000 per year for three years (whichever is the smaller number,
and to start in year two of the Cooperative Agreement), for pilot
studies utilizing the clinical specimen Bank should document the
ability to conduct research with HIV-malignancies and any ongoing
work in this area.  The research hypothesis, background and rationale
and design of the pilot studies should be described as part of the
research plan (keep within the allowed page limits).  The Steering
Committee and REDP will review the pilot studies proposed in the
application in response to this RFA, even if the studies received
approval under peer review.  Moneys for pilot studies will be
restricted until the REDP give these pilot studies high priority
ratings and the requested specimens and/or data are available and
have been released by the Steering Committee.  Furthermore, the
review of these pilot studies will occur along with the review and
prioritization of other requests submitted by investigators in the
research community at-large.  The pilot studies will begin no sooner
than year two of the Cooperative Agreement.  If the REDP does not
rank the pilot project as high priority, a new pilot study that is
rated as a high priority by the REDP could be substituted.

The RFA label available in the research grant application form PHS
398 (rev. 9/91) must be affixed to the bottom of the face page.
Failure to use this label could result in delayed processing of the
application such that it may not reach the review committee in time
for review. In addition, the RFA number and title must be typed on
line 2a of the face page of the application form.

Submit a signed, typewritten original of the application, including
the Checklist, and three signed, exact, clear, and single-sided
photocopies, in one package to:

Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD  20892**

At the time of submission, send two additional copies of the
application directly to:

Ms. Toby Friedberg
Division of Extramural Activities
National Cancer Institute
6130 Executive Boulevard
Executive Plaza North, Room 636
Bethesda, MD  20892

Applications must be received by May 17, 1994.  If an application is
received after that date, it will be returned.  If the application
submitted in response to this RFA is substantially similar to a
research grant application already submitted to the NIH for review,
but has not yet been reviewed, the applicant will be asked to
withdraw either the pending application or the new one.  Simultaneous
submission of identical applications will not be allowed, nor will
essentially identical applications be reviewed by different review
committees.  Therefore, an application cannot be submitted in
response to this RFA 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.

REVIEW CONSIDERATIONS

General Considerations

All applications will be judged on the basis of the scientific merit
of the proposed project and the documented ability of the
investigators to meet the RESEARCH OBJECTIVES of the RFA.  Although
the technical merit of the proposed protocol is important, it will
not be the sole criterion for selection of a study.  Other
considerations, such as the importance and timeliness of the proposed
study or clinical trials, access to patients, and multidisciplinary
nature of the studies, will be part of the evaluation criteria.

Review Method

Upon receipt, applications will be reviewed for completeness by the
DRG and responsiveness by the NCI.  Incomplete applications will be
returned to the applicant without further consideration.  If the
application is not responsive to the RFA, NCI staff will return the
application to the applicant.  If the number of applications
submitted is large compared to the number of awards to be made, the
NCI may conduct a preliminary scientific peer review (triage) to
determine their relative competitiveness by an NCI peer review group.
The NCI will withdraw from further competition those applications
judged to be non-competitive for award and notify the applicant
Principal Investigator and institutional official.  Those
applications that are complete and responsive, and judged to be
competitive in triage (if triage is used), will undergo further
scientific merit review in accordance with the criteria stated below
for scientific/technical merit by an appropriate peer review group
convened by the NCI.  The second level of review will be provided by
the National Cancer Advisory Board.

Review Criteria

Reviewers will be asked to review the grant applications according to
the following criteria:

o  extent to which the application address the goals and objectives
of the RFA;

o  adequacy of applicant's plans for addressing the special
scientific and technical program requirements presented in the RFA;

o  merit of the proposed activities and organizational plans for
implementing the proposed Tissue and Biological Fluids Banks of
HIV-Related Malignancies;

o  demonstration of the numbers of patients with HIV-associated
malignancies accessible to the investigators for clinical data and
specimen collection;

o  qualifications and experience of the Principal Investigator and
staff, particularly, but not exclusively, in the area of the banking
facilities and procedures and clinical data collection;

o  adequacy of existing physical facilities and resources of the
organization;

o  adequacy of plans for effective cooperation and coordination among
participating awardees, the NCI Program Director and the NCI
Coordinator, as per Special Requirements of the RFA;

o  evidence that appropriate steps have been taken to insure the
protection of human subjects;

o  the scientific, technical or medical significance and originality
of the proposed pilot studies.  Note that since not more than 10
percent of the money, or up to $50,000 per year for three years
(whichever number is smaller, and not to begin until year two of the
Cooperative Agreement) may be requested for these studies, the review
of this aspect of the grant application will be given much less
importance than the banking facilities, procedures and the clinical
data base;

o  evidence that the applicant is in compliance with NIH policies
regarding the inclusion of women and minorities in clinical research
study populations;

The review group will critically examine the submitted budget and
will recommend an appropriate budget and period of support for each
application.  If a pilot study has been proposed, the budget for the
pilot study will be reviewed separately from the budget for the
banking proposal.

AWARD CRITERIA

Applications recommended by the National Cancer Advisory Board will
be considered for award based upon (a) technical merit of the
application as reflected in the priority score, (b) availability of
resources, and study population, and (c) availability of funds.
Furthermore, the applicant organization must indicate a commitment to
accept provisions outlined under the SPECIAL REQUIREMENTS section,
Terms and Conditions of Award.  The anticipated date of award is
September 30, 1994.

Letter of Intent Receipt Date:   April 15, 1994
Application Receipt Date:        May 17, 1994
Review by NCI Advisory Council:  September 1994
Anticipated Award Date:          September 30, 1994

INQUIRIES

Written and telephone inquiries concerning this RFA are encouraged.
The opportunity to clarify any issues or questions from potential
applicants is welcome.

Direct inquiries regarding scientific issues to:

Ellen Feigal, M.D.
Division of Cancer Treatment
National Cancer Institute
6130 Executive Boulevard
Executive Plaza North, Suite 741
Bethesda, MD 20892
Telephone:  (301) 496-2522
FAX:  (301) 402-0557

Direct inquiries regarding fiscal matters to:

Ms. Carolyn Mason
Grants Management Branch
National Cancer Institute
6120 Executive Boulevard
Executive Plaza South, Room 242
Bethesda, MD 20892
Telephone:  (301) 496-7800, ext. 59
FAX:  (301) 496-8601

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic
Assistance No. 93.395, Cancer Treatment Research.  Awards are made
under the authorization of the Public Health Service Act, Title IV
Sections 301, 410, and 411, Part A (Public Law 78-410, 42 USC 241 as
amended, Public Law 99-158, 42 USC 285a) and administered under PHS
grants policies and Federal Regulations at 42 CFR Part 52, 45 CFR
Part 74 and 45 CRF Part 92.  This program is not subject to the
intergovernmental review requirements of Executive Order 12372 or
Health Systems agency review.

.

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