Subject: RFA DC-90-02.082490 from the NIH Guide
From: Dot Baker <[email-masked]>
To: [email-masked]
Date: Thu, 23 Aug 90 08:44 EST

Hello,
   This looks like the last one coming down the wire this morning.
I think the first one I sent over to be posted as the NIHGUIDE.082490
is a mistake.  Can you hold off posting it until I can check.
     Please post this one to the NIH Listserver as:
          RFADC-90-02.082490
Thanks.
       Dottie
 ---------------------------- Text of forwarded message -----------------------
 
REQUEST FOR APPLICATIONS FOR COOPERATIVE AGREEMENT
 
RFA:  DC-90-02
 
National Institute on Deafness and Other Communication Disorders
 
P.T. 34; K.W. 0715050, 0745070
 
RECOGNITION AND MANAGEMENT OF PERILYMPHATIC FISTULA
 
Application Receipt Date: 11-16-90
Letter of Intent Receipt Date:  10-08-90
 
INTRODUCTION:
 
The National Institute on Deafness and Other Communication
Disorders (NIDCD) invites applications for assistance awards to
support two-phase studies leading first to the development and
validation of a marker to be used for the intraoperative
diagnosis of perilymphatic fistula (PLF), and subsequently, to
studies of the clinical diagnosis and treatment efficacy of PLF.
These awards will be cooperative agreements in which
substantial involvement with the funded investigators by NIDCD
staff is anticipated during performance of the projects.
 
Awards will be made for total project periods of five years.
$7.5 million total  (direct and indirect) costs is available for
the entire project period of five years.  Phase 1 costs may be
significantly less than those for Phase 2.  Budget increments
after the first year will be limited to approved programmatic
changes or to necessary cost-of-living increases but the
specific amount and the number of awards will depend on the
merit and scope of the applications received.   The NIDCD
anticipates making 3-5 awards.  Although this project is
provided for in the financial plans of the NIDCD, the award of
cooperative agreements pursuant to the Request for
Applications (RFA) is contingent on the
availability of funds appropriated in fiscal year 1991.
 
CONTENTS:
 
A.  Background information
B.  Research Goals and Scope
C.  Mechanism of Support - RFA
D.  Terms of Award:  Cooperative Agreement
E.  Appeals
F.  Patent Coverage
G.  Eligibility Requirements
H.  Special Instructions
I.  Review Procedures and Criteria
J.  Applications
K.  Letter of Intent
L.  Inquiries
 
A.  BACKGROUND INFORMATION:
 
Perilymphatic fistulae (PLFs) are abnormal communications
between the fluid surrounding the membranous labyrinth of the
inner ear and the normally air-filled middle ear space, causing
sudden or progressive hearing loss,  dizziness or vertigo,
nausea, or a feeling of fullness in the ear.   They may occur
spontaneously, recurrently, or as a result of head trauma, ear
surgery, barotrauma, physical exertion, or congenital temporal
bone anomalies.
 
When head trauma,  barotrauma, or coincident physical exertion
is associated with the onset of symptoms, the clinical diagnosis
of perilymphatic fistula often can be established with
reasonable confidence, and a patent fistula in the round and/or
oval window covering may be readily apparent on middle ear
exploration.   Prompt surgical repair of the defect often
produces permanent relief of the symptoms.  In the absence of
such history, the clinical and differential diagnosis of
perilymphatic fistula in children and adults is more
controversial.  There is no generally accepted radiologic,
laboratory, or electrophysiologic test that provides objective,
unequivocal evidence of perilymphatic fistula.    The diagnosis
becomes even more difficult with very young children, who are
unable to provide information concerning the onset or nature of
their symptoms,  which may vary widely,  and who often cannot be
tested with many of the usual clinical tests of auditory and
vestibular function.  At present, surgical exploration of the
middle ear is the only means by which the presence of PLF can be
confirmed.
 
Contributing to the controversy is the subjectivity of the
intraoperative diagnosis. There is no pathologic specimen that
can be subjected to laboratory analysis, and  photographic
documentation has been inadequate, leaving confirmation of the
clinical diagnosis solely to the perception of the surgeon and
his/her criteria for identifying a fistula.  Thus, a potentially
serious anatomic defect lacks adequate diagnostic criteria as
indications for exploratory surgery, and there is no objective
means of documenting the lesion.  As a result, estimates of the
incidence and prevalence of perilymphatic fistula in children
and adults vary widely throughout the United States, although it
is possible that it is a significant and often unrecognized
factor in the sudden onset of, or progression of, hearing loss and
idiopathic, nonspecific dizziness.
 
Three important issues related to the recognition and management
of PLF, then, are:  1) The clinical and differential diagnosis
of PLF and the development of data-based criteria for surgical
intervention; 2) the intra-operative diagnosis of perilymph
and/or cerebrospinal fluid in the middle ear and its
differentiation from other adventitious fluids, such as plasma or
local anesthetic agents; and 3) the relative efficacy of various
surgical and non-surgical treatment options for the alleviation
of the auditory and vestibular symptoms associated with PLF.  Of
these, the development of an objective means of
identifying/verifying the presence of perilymph and/or
cerebrospinal fluid in the middle ear can be viewed as pivotal.
Once that goal is achieved, the sensitivity and specificity of
diagnostic tests can be directly assessed; accurate figures as
to incidence and prevalence of the defect can be generated; and
the efficacy of treatment alternatives can be evaluated relative
to the outcome of the intra-operative test.
 
B.  RESEARCH GOALS AND SCOPE:
 
The goals of this RFA are threefold, encompassed within a
two-phase program.  Phase 1 is intended to assist groups of
investigators in their attempts to develop and validate a marker
substance or procedure to identify and differentiate perilymph
in the middle ear.   The goals for Phase 1 must be met before
proceeding to Phase 2 studies, as described in Section D.1.
Phase 2 has two goals:  first, to conduct clinical studies on
objective diagnostic tests for perilymphatic fistula, leading to
the establishment of clinical criteria for middle ear
exploration; and second, to evaluate the efficacy of surgical
and non-surgical treatments in alleviating symptoms.  All
applicant groups are expected to participate fully in both
phases of the project.
 
Proposed diagnostic efficacy studies may determine the
predictive efficiency of batteries of auditory, vestibular,
psychological, and otologic tests for identifying PLF.
Proposed treatment efficacy studies may involve comparing
nonsurgical treatment options such as bedrest or vestibular
exercises, with conventional methods of surgical intervention.
Other questions that may be addressed by these studies include,
but are not limited to:
 
 o Are there patterns of auditory, vestibular, psychological, and
otologic tests that correlate with the presence of perilymph in
the middle ear?
 
 o What are the mechanisms underlying spontaneous or recurrent
PLF?
 
 o What persons are at risk of developing perilymphatic fistula?
 
 o What is the natural history of spontaneous and traumatic PLF?
 
C.  MECHANISM OF SUPPORT:
 
Awards will be made as cooperative agreements.  These awards
reflect an assistance relationship in which substantial
involvement with the funded investigators by NIDCD staff is
anticipated during performance of the project.   There is no
intent, real or implied, for NIDCD staff to direct research
activities or to limit the freedom of participating
investigators.  Cooperative agreements resulting from this RFA
will be subject to the same administrative requirements
pertaining to all assistance awards of the U.S. Public Health
Service.   Except as might be otherwise stated in the 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 1987.
 
This RFA is a one-time solicitation.  Should the NIDCD determine
that there is a sufficient continuing program need for the
studies initiated under this RFA, with the same parameters as
before, competing continuation applications will be invited from
awardees through individual written communications.  If,
however, there are significant changes in award objectives,
approaches or costs, or if the NIDCD seeks new awardees to add
to or replace current ones,   a new RFA will be issued and
applications will be invited for cooperative agreement
applications that will be  reviewed according to the procedures
described in Section I.
 
NIDCD anticipates making 3-5 awards for project periods of up to
five years.  Up to $7.5 million total (direct and indirect)
costs is available for the entire project period of five years.
Funding in response to this RFA is dependent on the receipt of a
sufficient number of applications of high scientific merit.  The
earliest feasible start date for the initial awards will be
April 1991.
 
D.  TERMS OF AWARD:
 
The Cooperative Agreement will require cooperation between an
NIDCD representative  and the principal investigators  in order
to assure smooth and productive interactions among the
cooperating institutions.  NIDCD will be represented by the
Health Scientist Administrator responsible for hearing and
auditory research in the NIDCD Division of Extramural
Activities, hereinafter referred to as the "NIDCD
representative".  As described more fully in Section D.2, the
designated representative will assist in coordinating the
activities of the research groups and by facilitating exchange
of information.
 
1.  ORGANIZATION AND ROLE OF THE COORDINATING COMMITTEE
 
The NIDCD and the participating research groups will be
responsible for forming a Coordinating Committee as defined
below.  Operating policies governing the conduct and integration
of the studies will be developed by the Coordinating Committee
with the input of the NIDCD representative.  NIDCD will review
the operating policies for compatibility with and facilitation
of progress toward the goals set forth in the RFA.
Recommendations for modification of the operating policies will
be discussed as necessary with the Coordinating Committee.
 
The Coordinating Committee will consist of two members from each
cooperating institution, one of whom is the principal
investigator, and the NIDCD representative.  The Coordinating
Committee will be responsible for electing a chairperson (who
shall not be the NIDCD representative).  This can be a rotating
position.  The Chairperson of the Committee will be responsible
for coordinating the Committee activities, preparing meeting
agendas, and scheduling and chairing meetings.  The NIDCD
representative will attend and participate as a non-voting
member in all meetings of the Coordinating Committee and should
be informed of major inter-group interactions.  The Committee
will meet at least twice a year at the National Institutes of
Health in Bethesda, Maryland.  These meetings are aimed at
coordinating the activities of the participating laboratories
and clinical centers, establishing policies and priorities,
reviewing progress, and monitoring the safety and efficacy of
treatments and procedures conducted within the scope of the
awards.  The first Coordinating Committee meeting, to be held
within six weeks of the Notification of Grant Award, will also
require the presence and participation of   a statistician or
biometrist from each cooperating institution to assist in
developing uniform statistical procedures and methods of data
acquisition and analysis.   Travel funds and per diem expenses
for Coordinating Committee meetings are to be identified as a
budget line item in each project budget.    The Coordinating
Committee will prepare an annual progress report which will
include individual reports from each participating research
group.  Each group is responsible for the timely and complete
preparation of its report.
 
At the end of two years an ad hoc Advisory Committee appointed
by NIDCD will review the progress made by the participating
groups in achieving the goals of Phase 1, i.e. development and
validation of a perilymph marker.  After completing such review,
the Advisory Committee may recommend to NIDCD that:  1) Phase 1
studies should be extended for a specified period of time; or 2)
Phase 2 - diagnostic and treatment efficacy studies using as the
"gold standard" the marker developed in Phase 1  - should
proceed; or 3) the study should be terminated.
 
Additional authorities and responsibilities of the Coordinating
Committee are summarized as follows:
 
 o Review the operating procedures proposed by the individual
research groups to ensure that they are compatible with the
overall goals of the RFA;
 
 o Develop uniform procedures for perilymph sampling and testing;
 
 o Develop uniform methods of gathering patient historical
information, diagnostic test results, and statistical analysis of
data;
 
 o Establish publication guidelines.
 
2.  ROLE OF NIDCD REPRESENTATIVE
 
The NIDCD representative  will assist in coordinating the
programs supported by this cooperative agreement, will attend
and participate in all meetings of the Coordinating Committee,
and will provide liaison between the Coordinating Committee and
participating research groups.  The NIDCD representative will
assist the Coordinating Committee in developing operating
policies, quality control procedures, and consistent policies
for dealing with recurring situations that require coordinated
action.  During performance of the award, the NIDCD
representative may provide appropriate assistance, advice, and
guidance by participating in the design of activities;  advising
in the availability of resources, staff, etc.; coordinating or
participating in analysis of data; advising in management and
technical performance; and participating in the preparation of
manuscripts.  In all cases, the role of NIDCD will be to assist
and facilitate and not to direct activities.
 
To assure consistency and quality, NIDCD must concur in
operating policies and procedures prior to their implementation.
The NIDCD representative will, in concert with the Coordinating
Committee, review the operations of individual laboratories for
compliance with the quality control standards and operating
policies developed by the Coordinating Committee.  The NIDCD
representative may recommend to the  NIDCD Director the
withholding of support, suspension or termination of an award to
any participating group for lack of progress or failure to
adhere to policies established by the Coordinating Committee.
 
3.  RESPONSIBILITIES OF AWARDEES
 
The authorities and responsibilities of the Principal
Investigators of each participating institution are summarized
as follows:
 
 o Development of general concepts for potential studies;
 
 o Development of protocols for clinical studies;
 
 o Conduct of clinical and epidemiological studies;
 
 o Coordination of basic science and clinical aspects of the
projects;
 
 o Monitoring of progress, safety, and efficacy of studies;
 
 o Development of data management and quality assurance systems;
 
 o Ensuring the timely publication of results;
 
 o Providing membership/leadership to the Coordinating Committee
and fulfilling the duties and responsibilities described for
members of that committee in Section D-1.
 
Funded investigators will be expected to provide a focus and
capability for development of uniform marker validation
protocols by consensus among participating investigators and for
conducting the specific validation trials,  diagnostic studies,
and treatment efficacy studies as appropriate.  This will
involve the  estimation of sample size requirements, preparation
of data questionnaires, development of quality assurance and
patient protection programs, and development of data management
and analysis systems.
 
The Government, via the NIDCD representative, will have access
to data generated under this Cooperative Agreement and may
periodically review the data.  However, the awardees will retain
rights to the data, and timely publication of major findings by
the participants is encouraged.  Publication or oral
presentation of work done under this agreement will require
appropriate acknowledgement of NIDCD support.
 
Inclusion of women and minorities on the research teams and as
part of the study population is encouraged.  If they are
excluded, reasons for this exclusion must be included in the
application.  (See NIH Guide for Grants and Contracts, Vol. 18,
No. 21, June 16, 1989 for further information.)
 
Investigators applying for these awards should have demonstrated
or available collaborative expertise in otologic clinical
studies and in cochlear biochemistry and/or pharmacology,
audiology, vestibular function assessment, clinical trials, and
data management/biometry.  Investigators should provide, at a
minimum, general designs for marker development and validation
procedures, clinical diagnostic activities, and plans for
treatment efficacy studies.    Active collaboration with  other
professionals who might be involved in the diagnosis or
treatment of patients with PLF is expected and encouraged.
Recruitment potential for proposed validation studies should be
documented.  Applicants should also document the interest,
capabilities, and commitment of all potential participating
clinics identified; letters from potential participating clinic
investigators should be provided as part of this documentation.
 
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 other
HHS, PHS, and NIH grant administration policies.
 
E.  APPEALS
 
These "Terms of Award" require that the NIDCD representative approve the
following:  changes in the Principal Investigator or Program
Leaders; major changes in protocols; and reports intended for
inclusion in clinical brochures.  Disagreements arising pursuant
to these approvals will be arbitrated by a panel composed of one
Coordinating Committee designee, one NIDCD 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.
 
F.  PATENT COVERAGE
 
Since one of the goals of this effort is the development and
validation of marker materials or methods to identify perilymph,
it is essential that consideration be given to plans to assure
coverage of patents.  Each funded investigator group, therefore,
will be required to provide a detailed description of the
approach to be used for obtaining patent coverage and for
licensing, where appropriate, with particular attention to a
situation in which the invention may involve investigators from
more than one institution.    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, NIDCD, within 60 days following the award.  In
addition,  evidence must be presented that procedures are in
place for resolution of any legal problems that may arise.
 
G.  ELIGIBILITY REQUIREMENTS:
 
Any of the following organizations are eligible to apply:
non-profit institutions of higher education; other non-profit
and for-profit organizations; state and local governments and
their agencies; and authorized federal agencies.  Holding a
currently funded NIH research, training, or center grant does
not impair an organization's eligibility.  Additional
eligibility requirements include those listed under
"Responsibilities of Awardees" in Section D.3.
 
H.  SPECIAL INSTRUCTIONS FOR PREPARATION OF COOPERATIVE
AGREEMENT APPLICATIONS:
 
General instructions for the preparation of the Cooperative
Agreement application parallel those relevant to regular
research grant applications and are contained in the Grant
Application Form PHS 398 (revised 10/88 or 9/89).  Forms are
available at most institutional business offices or offices of
sponsored research.  These forms may also be obtained from:
Office of Grants Inquiries, Division of Research Grants,
National Institutes of Health, Westwood Building, Room 449,
Bethesda, MD 20892.
 
To identify the application as a response to this RFA, check
"Yes" on line 2 of the face page on Form PHS 398 and enter the
following:  "RFA DC-90-02,  Recognition and Management of
Perilymphatic Fistula."
 
Use the conventional format for research project grant
applications, but ensure that the issues identified in "Review
Procedures and Criteria" (Sections I.1 and I.2), are addressed.
 
As specified in Section D.1, travel and per diem funds for
attending the required Coordinating Committee meetings should be
identified in the budget.  Routine patient care costs will not
be supported by these awards.
 
Because the Terms of Award in Section D above will be included
in all awards issued as a result of the RFA, it is critical that
each applicant include specific plans for responding to these
terms.
 
I.  REVIEW PROCEDURES AND CRITERIA:
 
1.  REVIEW PROCEDURES
 
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 NIDCD 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 projects may
be submitted as an investigator-initiated regular research grant
application (R01) at the next receipt date.  The new application
would not be considered an application for a cooperative
agreement, nor would it be considered a response to an RFA.
 
In cases where the number of applications is large compared to
the number of awards to be made, the NIDCD may conduct a
preliminary scientific peer review to eliminate those which are
clearly not competitive for award.  Those applications judged to
be noncompetitive will be withdrawn from further competition, and
the Principal Investigator and institutional business official
will be notified accordingly.
 
Applications judged to be complete, competitive, and responsive
will be further evaluated according to the review criteria
stated below for scientific and technical merit by an
appropriate peer review group convened by the Division of
Extramural Activities, NIDCD.  The second level of review is
conducted by the NIDCD Advisory Council.
 
2.  REVIEW CRITERIA
 
Factors considered to be important for review include
demonstrated expertise in cochlear biochemistry and
pharmacology, otolaryngology, and evaluation of auditory and
vestibular disorders; availability of an appropriate patient
population; good interaction among collaborating institutions,
scientists,  and clinicians; and adequate facilities and
ancillary personnel.
 
Reviewers will be asked to review the grant applications by
considering the following criteria:
 
1)  Appropriateness, originality, feasibility, and relevance of
the proposed project to the overall goals and objectives of the
RFA.
 
2)  Qualifications, experience, and proposed responsibilities of
the principal investigators and key support personnel.
 
3)  Scientific merit and organizational plans for implementing
the proposed program.
 
4)  Demonstration of availability of patient populations having
a variety of auditory and vestibular disorders, including
perilymphatic fistula.
 
5)  Proposed collaborations with surgeons, basic scientists, and
other key personnel within the applicant and collaborating
institutions; adequacy of documented interest, capabilities, and
commitment of all potential participating clinics.
 
6)  Facilities and resources, and their availability for this
project.
 
7)  Adequacy of proposed overall administrative procedures and
collaborative arrangements.
 
8)  Reasonableness of the proposed budget.
 
9)  Plans to protect the rights and welfare of human and animal
subjects.
 
10) Commitment to accept NIDCD assistance in accordance with the
guidelines outlined under Section D, "TERMS OF AWARD."
 
J.  APPLICATION:
 
Complete applications are due no later than November 16, 1990,
and must address all requirements in the RFA.  Applications
received after this date will not be accepted.
 
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.
 
The RFA label (found in the 10/88 revision of application form
PHS 398) must be affixed to the bottom of the face page of the
original copy of the application.  Failure to use this label
could result in delayed processing of your application such that
it will not reach the review committee in time for review.
 
Send the completed and signed original application and four
signed, exact photocopies, in one package to:
 
Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD 20892-4500**
 
The photocopies must be clear and single sided.
 
Send an additional two (2) copies of the application under
separate cover to:  Dr. Marilyn Semmes, Review and Special
Projects Officer, National Institute on Deafness and Other
Communication Disorders, Federal Building, Room 9C-14A, 7550
Wisconsin Avenue, Bethesda, MD 20892.
 
K.  LETTER OF INTENT:
 
Prospective applicants are asked to submit, by October 8, 1990,
a letter of intent that includes a descriptive title of the
proposed project, the name and address of the principal
investigator, the names of other key personnel and
collaborating institutions, and 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
NIDCD would like to emphasize the benefits of a letter of
intent, which allows NIDCD staff to estimate the potential
review workload and to avoid possible conflict of interest in
the review.
 
L.  INQUIRIES:
 
Written or telephone inquiries concerning the objectives and
scope of the RFA, or inquiries about whether or not specific
proposed research would be responsive, are encouraged and should
be directed to Dr. Maureen Hannley at the address shown below.
The program administrator welcomes the opportunity to clarify
any issues or questions from potential applicants.
 
The letter of intent and inquiries should be addressed to:
 
Maureen T. Hannley, Ph.D.
Program Administrator, Hearing
Division of Communication Sciences and Disorders
National Institute on Deafness and Other Communication Disorders
Room 1C-04, Federal Building
7550 Wisconsin Avenue
Bethesda, Maryland 20892
Telephone:  (301) 496-5061
Fax:  (301) 402-0104
 
Awards will be made under the authority of the Public Health
Service Act, Section 301 (42 USC241), and administered under PHS
grant policies and Federal Regulation 42 CFR Part 52, and 45 CFR
Part 74.  This program is not subject to review by a Health
Systems Agency or to the intergovernmental review requirements
of Executive Order 12372.